A 12-Vertex Metallacarborane of Silver(I).

The discovery of ferrocene in 1951 was a significant landmark in the field of organometallic chemistry, and since then, numerous sandwich- or half-sandwich metallic complexes have been reported. However, silver stands as an intriguing exception in this regard, and knowledge of its bonding situation has remained undisclosed. Herein, unprecedented 12-vertex metallacarboranes of Ag(I) (2a and 2b) were synthesized through the reaction of sodium hexamethyldisilazide (NaHMDS) with the mixture of nido-C2B9 carborane anion-supported N-heterocyclic carbene precursors (1a and 1b) and [Ag(PPh3)Cl]4. The X-ray structural analysis of the resulting metallacarboranes revealed a unique "slipped" half-sandwich structure, which is a rarity among cyclopentadienyl analogues. DFT calculations provided insights into the asymmetric π-interactions between the pentagonal C2B3 face and the silver ion.

Rational Engineering of a Multifunctional DNA Assembly for Enhanced Antibacterial Efficacy and Accelerated Wound Healing.

DNA-based assemblies hold immense prospects for antibacterial application, yet are constrained by their poor specificity and deficient antibacterial delivery. Herein, the fabrication of a versatile rolling circle amplification (RCA)-sustained DNA assembly is reported, encoding simultaneously with multivalent aptamers and tandem antibacterial agents, for target-specific and efficient antibacterial application. In the compact RCA-sustained antibacterial platform, the facilely organized multivalent aptamers guarantee the target bacteria-specific delivery of sufficient antibacterial agents which is assembled through DNA-stabilizing silver nanostructures. It is shown that the biocompatible DNA system could enhance bacteria elimination and simultaneously facilitate wound healing in vivo. By virtue of the programmable RCA assembly, the present RCA-sustained system provides a highly modular and scalable approach to design versatile multifunctional therapeutic systems.

Intelligent Electrochemical Point-of-Care Test Method with Interface Control Based on DNA Pyramids: Aflatoxin B1 Detection in Food and the Environment.

Sensitive, intelligent point-of-care test (iPOCT) methods for small molecules like aflatoxin B1 (AFB1) are urgently needed for food and the environment. The challenge remains of surface control in iPOCT. Herein, we developed an electrochemical sensor based on the DNA pyramid (DNP), combining a smartphone, app, and mobile electrochemical workstations to detect AFB1. The DNP's structure can reduce local overcrowding and entanglement between neighboring probes, control the density and orientation of recognition probes (antibodies), produce uniform and orientational surface assemblies, and improve antigen-antibody-specific recognition and binding efficiency. Simultaneously, the hollow structure of the DNP enhances the electron transfer capacity and increases the sensitivity of electrochemical detection. In this work, the biosensor based on DNP was first combined with electrochemical (Ec) iPOCT to simultaneously achieve ordered interface modulation of recognition probes and intelligent detection of AFB1. Under optimal conditions, we found a detection limit of 3 pg/mL and a linear range of 0.006-30 ng/mL (R2 = 0.995). Further, using peanut, soybean, corn, and lake water as complex matrices, it recorded recoveries of 82.15-100.53%, excellent selectivity, acceptable stability, and good reproducibility. Finally, this Ec iPOCT provides consistent results compared to the high-performance liquid chromatography-tandem mass spectrometry method.

Light-Up Aptameric Sensor of Serotonin for Point-of-Care Use.

Serotonin is a vital neurotransmitter for regulating organism functions, and its abnormal level indicates multiple diseases. Aptamer has emerged as an innovative tool for serotonin analysis very recently; however, the current aptameric sensing platform lacks design flexibility and portability. Here, we introduce a light-up aptameric sensor using designer DNA molecules with tunable affinity and dynamic response and achieve mobile phone-based detection for point-of-care use. We develop a type of allosteric DNA sensor through flanking the serotonin recognition domain with split fluorogenic sequences, where both linker lengths and split sites of the aptamer affect its function. In addition, we design a series of molecular constructs that contain nucleotide mutations and systematically investigate the structure folding and ligand binding of the aptameric molecules. The results show distinct effects of variant mutation sites on conformation change and sensing responses. Notably, the variable aptameric molecules allow affinity and dynamic response regulation, which are adaptable to diverse sensing applications that require different threshold levels. Furthermore, we demonstrate a simple surface-based assay that can use smartphone imaging to visualize results for diagnosis. In a portable and simple manner, highly sensitive and selective serotonin assay is achieved in different biofluids, with detection limits in the low nanomolar range. This study offers an alternative approach for serotonin assay using engineered aptameric molecular probes. We expect that the practical utility may make the method promising in resource-limited settings.

Fe-N-C single-atom nanozyme for ultrasensitive, on-site and multiplex detection of mycotoxins using lateral flow immunoassay.

Sensitive, on-site and multiple detection of mycotoxins is a vital early-warning tool to minimize food losses and protect human health and the environment. Although paper-based lateral flow immunoassay (LFIA) has been extensively applied in mycotoxins monitoring, low-cost, portable, ultrasensitive and quantitative detection is still a formidable challenge. Herein, a series of Fe-N-C single-atom nanozymes (SAzymes) were synthesized and systematic characterized. The optimal Fe-N-C SAzyme with highly efficient catalytic performance was successfully used as both label and catalyst in lateral flow immunoassays for mycotoxin detection. By taking advantage of the catalytic amplified system, the qualitative and quantitative detection can be easily and flexibly done via observing the test lines by naked eyes or a smartphone, with the limit of detections (LODs) of 2.8 and 13.9 pg mL-1 for AFB1 and FB1, which were respectively over 700- and 71,000-fold lower than the maximum limit set by the European Union. Besides, underlying catalytic mechanisms and the active sites of the Fe-N-C SAzyme are also investigated by DFT simulation. This work not only provides a promising detection strategy for the application of advanced SAzymes but also offers experimental and theoretical guidelines to understand the active centers of Fe-N-C SAzymes and the catalytic process.

A versatile nanozyme integrated colorimetric and photothermal lateral flow immunoassay for highly sensitive and reliable Aspergillus flavus detection.

Visual lateral flow immunoassays (LFA) have been recognized as the attractive point-of-care testing (POCT) for bioanalysis; however, they have been constrained by insufficient sensitivity and limited reliability. Herein, combining the catalytic sites of Cu nanoparticles with an inherent photothermal polydopamine (PDA) scaffold via a one-step process, a compact Cu-anchored PDA (PCu) was engineered as the efficient signal element for the multimodal LFA (mLFA). The robust PCu with peroxidase-mimics and photothermal properties, could simultaneously provide triple signal readouts for colorimetric, amplified colorimetric and photothermal detection toward Aspergillus flavus (A. flavus). Attractively, the multiple guaranteed detection of PCu-based mLFA enabled the accurate and sensitive detection of A. flavus mycelium biomass, down to 0.45 and 0.22 ng mL-1, which was 19- and 40-fold improvements compared to traditional colorimetry. Besides, mLFA was successfully applied to actual samples with satisfactory recoveries from 89.9 to 109%, indicating the highly reliable analytical performance. This work paved a prospective way for the construction of efficient peroxidase-mimics and superior photothermal multifunctional nanomaterials, providing a potential versatile visual POCT platform for analytical events.

Nanozyme-strip based on MnO2 nanosheets as a catalytic label for multi-scale detection of aflatoxin B1 with an ultrabroad working range.

Lateral flow immunoassay (LFIA) is the most effective real-time detection method for aflatoxin B1 (AFB1). Here, we constructed a nanozyme-strip based on MnO2 nanosheets (MnO2 NSs) as a catalytic label for detection of AFB1. By taking advantage of the MnO2-TMB catalytic amplified system, the new test achieves rapid detection with high sensitivity and ultrawide range. The limit of detection of the assay was 15 pg mL-1, which was over 100-fold lower than the maximum limit set by the European Union (EU) of AFB1 in foods. In addition, the strip test could offer 7 dynamic detection ranges, spanning 4 orders of magnitude, which could cater to the varieties of limits on AFB1 residues in foods and feeds set by different countries. The estimated recoveries were in the range of 85.67%-106.38% with coefficients of variations (CVs) less than 9.68%. Overall, the developed approach is a rapid, reliable, sensitive and widely available tool for on-site detection of AFB1.

Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients With Crohn's Disease: A Pilot Study.

BACKGROUND: Early changes in bowel behavior during anti-tumor necrosis factor (anti-TNF) induction therapy in Crohn's disease (CD) are relatively unknown. We determined (1) the onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound and (2) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. METHODS: Consecutive ileal or ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. RESULTS: Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the nonresponse group (P = .003 and P = .011, respectively). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P < .001, P < .001, and P = .003, respectively) in the response group. Baseline SWE values (21.3 ± 8.7 kPa vs 15.3 ± 4.7 kPa; P = .022) and bowel wall thickness (8.5 ± 2.3 mm vs 6.9 ± 1.5 mm; P = .027) in the nonresponse group were significantly higher than in the response group. CONCLUSIONS: This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as 2 weeks after anti-tumor necrosis factor therapy in patients with Crohn's disease. Bowel ultrasound together with elasticity imaging could predict early response to anti-tumor necrosis factor therapy.

A direct competitive nanozyme-linked immunosorbent assay based on MnO2 nanosheets as a catalytic label for the determination of fumonisin B1.

A direct competitive nanozyme-linked immunosorbent assay (dcNLISA) based on MnO2 nanosheets (MnO2 NSs) as a nanozyme label was developed for the highly sensitive determination of fumonisin B1 (FB1). MnO2 NS-labeled fumonisin B1-bovine serum albumin was easily synthesized as a competing antigen for the dcNLISA. And color changes derived from the MnO2-3,3',5,5'-tetramethylbenzidine (TMB) system were exploited as the output signals of the dcNLISA. Several experimental parameters including the concentrations of the coating antibody, pH values, ionic strength and methanol concentration were optimized. Under the optimal conditions, the proposed method demonstrated a linear range (1.17-20.74 ng mL-1) with a reliable correlation coefficient (R2 = 0.9989), a satisfactory limit of detection (0.63 ng mL-1) and high selectivity for the detection of FB1. The recoveries of FB1 in spiked corn and wheat samples were in the range of 85.31-108.16% with coefficients of variation (CVs) ranging from 6.14% to 9.23%. Meanwhile, the testing results showed good consistency (R2 = 0.9892) between the developed dcNLISA and the reference method, liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) method. The proposed method was proven to be simple, sensitive, cost-effective and reliable for the screening of FB1 in cereals.

Engineering Inorganic Nanoflares with Elaborate Enzymatic Specificity and Efficiency for Versatile Biofilm Eradication.

Nanozyme has emerged as a versatile nanocatalyst yet is constrained with limited catalytic efficiency and specificity for various biomedical applications. Herein, by elaborately integrating the recognition/transduction carbon dots (CDs) with platinum nanoparticles (PtNPs), an exquisite CDs@PtNPs (CPP) nanoflare is engineered as an efficient and substrate-specific peroxidase-mimicking nanozyme for high-performance biosensing and antibacterial applications. The intelligent CPP-catalyzed hydrogen peroxide (H2 O2 )-generated reactive oxygen species realize the sensitive diagnosis-guided enhanced disinfection of pathogens. Significantly, the CPP nanozyme shows the prominent biofilm eradication and wound healing in vivo by virtue of endogenous H2 O2 in acidic infection tissues, which can substantially preclude the annoying antibiotics resistance. A fundamental understanding on the present CPP nanoflare would not only facilitate the advancement of various prospective biocatalysts, but also establish a multifunctional means for versatile biosensing and smart diagnostic applications.

Silver-Laden Black Phosphorus Nanosheets for an Efficient In Vivo Antimicrobial Application.

Nanobactericides represent one of the most efficient and promising strategies for eliminating bacterial infection considering the increasing resistance threats of conventional antibiotics. Black phosphorus (BP) is the most exciting postgraphene layered 2D nanomaterial with convincing physiochemical properties, yet the study of BP-based antibiotics is still in its infancy. Here, a compact silver nanoparticle (AgNP)-doped black phosphorus nanosheet (BPN) is constructed to synergistically enhance solar disinfection through the promoted reactive oxygen species (ROS) photogeneration, which is attributed to the improved electron-hole separation and recombination of BPNs as revealed from the systematic experimental studies. An in-depth density functional theory (DFT) calculation confirms that the integrated AgNPs provide a preferred site for facilitating the adsorption and activation of O2 , thus promoting the more efficient and robust ROS generation on BPN-AgNP nanohybrids. Besides the enhanced photoinduced ROS, the anchored AgNPs simultaneously lead to a dramatically increased affinity toward bacteria, which facilitates a synergetic pathogen inactivation. Significantly, the convincing antimicrobial BPN-AgNP contributes to the prominent wound healing and antimicrobial ability in vivo with minimized biological burden. This sophisticated design of new 2D nanohybrids opens a new avenue for further exploiting BP-based nanohybrids in portable bandage and broad-spectrum disinfection applications.

Facile Assembly of Multifunctional Antibacterial Nanoplatform Leveraging Synergistic Sensitization between Silver Nanostructure and Vancomycin.

The emergence of antibiotic-resistant bacterial strains renders the conventional antibiotic therapy less efficient. The integration of two distinct bactericides into one compact platform provides a promising strategy to realize a combinational antimicrobial therapy. In this work, an efficient chemo-Ag nanohybrid antibacterial platform was facilely developed based on the integration of vancomycin-carrying polydopamine with silver nanoparticles (PDA@Van-Ag). The as-synthesized antibacterial nanohybrid inherited the intrinsic properties of both bactericides to achieve a synergistic antibacterial performance against both Staphylococcus aureus and Escherichia coli strains by attacking bacteria from two distinct fronts. Through this combinational therapy, the efficiency of antibiotic against S. aureus was significantly improved by reducing drug dosage with less opportunity for imparting drug resistance. In addition, this antibacterial nanohybrid, with innate photothermal properties, could achieve auxiliary hyperthermia-assisted bacterial inactivation in the meantime. Furthermore, the outstanding in vivo bacteria-killing activity and wound-healing acceleration were demonstrated in a S. aureus-infected mouse skin defect model. Taken together, this bactericidal nanohybrid could achieve sustained antibiotic release and wipe out bacteria more effectively in a synergistic way, thus reducing the emergence of antibiotic resistance. This work holds great potential to advance the development of novel antibacterial agents and combinational strategies as a promising supplement of antibiotics in the near future.

A DNAzyme-amplified DNA circuit for highly accurate microRNA detection and intracellular imaging.

Biomolecular self-assembly circuits have been well developed for high-performance biosensing and bioengineering applications. Here we designed an isothermal concatenated nucleic acid amplification system which is composed of a lead-in catalyzed hairpin assembly (CHA), intermediate hybridization chain reaction (HCR) and ultimate DNAzyme amplifier units. The analyte initiates the self-assembly of hairpin reactants into dsDNA products in CHA, which generates numerous trigger sequences for activating the subsequent HCR-assembled long tandem DNAzyme nanowires. The as-acquired DNAzyme catalyzed the successive cleavage of its substrates, leading to an amplified fluorescence readout. The sophisticated design of our CHA-HCR-DNAzyme scheme was systematically investigated in vitro and showed dramatically enhanced detection performance. As a general sensing strategy, this CHA-HCR-DNAzyme method enables the amplified analysis of miRNA and its accurate intracellular imaging in living cells, originating from their synergistic signal amplifications. This method shows great potential for analyzing trace amounts of biomarkers in various clinical research studies.

Lighting Up Fluorescent Silver Clusters via Target-Catalyzed Hairpin Assembly for Amplified Biosensing.

Isothermal enzyme-free nucleic acid circuits have been developed for carrying out diverse functions ranging from dictate biocomputing to amplified biosensing. Catalytic hairpin assembly (CHA), the catalyzed cross-opening of two hairpin substrates by an initiator, has attracted increasing attention because of its facile design and high amplification capacity. The complex labeling and frequent photobleaching of a conventional fluorescent CHA biosensor still remains a challenge that needs to be solved. Herein, we constructed a new label-free and enzyme-free isothermal CHA lighting up AgNCs strategy for amplified nucleic acid assay by integrating the interfacially and spatially sensitive feature of DNA-templated fluorescent silver nanoclusters (DNA-AgNCs) and the high signal amplification capability of the CHA circuit. In this strategy, one polyguanine-grafted hairpin and the other AgNCs-capturing hairpin were engineered as assembly constitutes, which were kinetically impeded from cross-hybridizations without target. However, in the presence of target, the CHA-catalyzed assembly of two functional hairpins was successively progressed and concomitantly accompanied by an efficient accommodation of AgNCs to the polyguanine-elongated dsDNA product, leading to highly efficient AgNCs-lighting up and to the generation of an amplified fluorescence signal. As a simple mix-and-detect strategy, the isothermal enzyme-free CHA-mediated lighting up AgNCs (CHA-AgNCs) system provided a facile visualization way for amplified detection of DNA with a detection limit of 20 pM, which was comparable to or even better than some enzyme-involved amplification methods. The homogeneous CHA-AgNCs system can be used as a general sensing platform and be easily adapted for analyzing other biologically important analytes, for example, microRNA (miRNA), by introducing the sensing module consisting of an auxiliary hairpin through an easy-to-integrate procedure. By taking advantage of the signal amplification features of CHA and the robust AgNCs-lighting up procedure, we anticipate that the CHA-lighting up AgNCs system can provide an important tool for biomedicine and bioimaging applications and thus should hold great promise in clinical diagnoses and treatment fields.

Development of functional black phosphorus nanosheets with remarkable catalytic and antibacterial performance.

Highly dispersed 2D-nanostructured ultrathin black phosphorus nanosheets (BPNs)-integrated Au nanoparticles (AuNPs) hybrids were constructed in situ through a facile and environmentally friendly strategy. No additional reductants, surfactants, or polymer templates were introduced during this green and convenient synthesis process. The resulting AuNPs/BPNs nanohybrids were characterized by UV-vis, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The content of BPNs plays an essential role in modulating the morphologies and chemical states of AuNPs/BPNs hybrids, which have been investigated systematically and are discussed in detail. As high-density ultrasmall AuNPs are properly stabilized and accommodated without passivation by the surrounding ultrathin BPNs, the resulting AuNPs/BPNs hybrids exhibit excellent catalytic/antibacterial properties and long-term stabilities, benefiting from a possible synergistic enhancement effect between AuNPs and BPNs constructs. This simple, mild and environmentally benign strategy could be generalized to the preparation of other metal- or metal oxide-doped complexes and holds great promise for potential catalytic, bioanalytical and biomedical applications.

One-step synthesis of nitrogen, boron co-doped fluorescent carbon nanoparticles for glucose detection.

Heteroatom-doped carbon nanoparticles (CNPs) have attracted considerable attention due to an effective improvement in their intrinsic properties. Here, a facile and simple synthesis of nitrogen, boron co-doped carbon nanoparticles (NB-CNPs) from a sole precursor, 3-aminophenylboronic acid, was performed via a one-step solid-phase approach. Because of the presence of boronic acid, NB-CNPs can be used directly as a fluorescent probe for glucose. Based on a boronic acid-triggered specific reaction, we developed a simple NB-CNP probe without surface modification for the detection of glucose. When glucose was introduced, the fluorescence of NB-CNPs was suppressed through a surface-quenching states mechanism. Obvious fluorescence quenching allowed the highly sensitive determination of glucose with a limit of detection of 1.8 µM. Moreover, the proposed method has been successfully used to detect glucose in urine from people with diabetes, suggesting potential application in sensing glucose.

"Switch-On" Fluorescent Sensing of Ascorbic Acid in Food Samples Based on Carbon Quantum Dots-MnO2 Probe.

This work describes a "switch-on" fluorescence approach for sensing of ascorbic acid (AA) in food samples. In the present method, the fluorescence intensity (FL) of carbon quantum dots (CQDs) was first quenched by addition of MnO2 nanosheets through an inner filter effect to form a CQDs-MnO2 probe. When reductive AA was introduced into the quenched CQDs solution, the added MnO2 was destroyed due to the redox reaction between AA and MnO2 nanosheets, and the FL of the system was recovered. Under the optimal conditions, the limit of detection for AA was 42 nM, with a wide concentration linear range of 0.18-90 µM. Furthermore, the as-fabricated fluorescent sensing system was successfully applied to the analysis of AA in fresh fruits, vegetables, and commercial fruit juices samples with satisfactory results.

Fluorescence resonance energy transfer-based ratiometric fluorescent assay for highly sensitive and selective determination of sulfide anions.

A novel and effective ratiometric fluorescence strategy was developed for rapidly, sensitively and selectively probing sulfide anions (S(2-)). A dual-emission nanosensor was prepared by covalently attaching fluorescent carbon nanoparticles (CNPs) to gold nanoclusters (Au NCs), triggering the sensing mechanism of fluorescence resonance energy transfer (FRET) from CNPs (donor) to Au NCs (acceptor). Once S(2-) was added, considerable fluorescence recovery of CNPs and quenching of Au NCs were observed due to the inhibition of FRET progress via the formation of Au2S. The ratiometric probe showed good, specific S(2-) sensing behavior and high sensitivity with a detection limit of 18 nM. Significantly, the assay was successfully employed to determine the S(2-) content in biological and water samples, presenting immense promise in the biological and environmental fields.

Solid-phase synthesis of highly fluorescent nitrogen-doped carbon dots for sensitive and selective probing ferric ions in living cells.

Carbon quantum dots (C-Dots) have drawn extensive attention in recent years due to their stable physicochemical and photochemical properties. However, the development of nitrogen-doped carbon quantum dots (N-doped C-Dots) is still on its early stage. In this paper, a facile and high-output solid-phase synthesis approach was proposed for the fabrication of N-doped, highly fluorescent carbon quantum dots. The obtained N-doped C-Dots exhibited a strong blue emission with an absolute quantum yield (QY) of up to 31%, owing to fluorescence enhancement effect of introduced N atoms into carbon dots. The strong coordination of oxygen-rich groups on N-doped C-Dots to Fe(3+) caused fluorescence quenching via nonradiative electron-transfer, leading to the quantitative detection of Fe(3+). The probe exhibited a wide linear response concentration range (0.01-500 µM) to Fe(3+) with a detection limit of 2.5 nM. Significantly, the N-doped C-Dots possess negligible cytotoxicity, excellent biocompatibility, and high photostability. All these features are favorable for label-free monitoring of Fe(3+) in complex biological samples. It was then successfully applied for the fluorescence imaging of intracellular Fe(3+). As an efficient chemosensor, the N-doped C-Dots hold great promise to broaden applications in biological systems.