Aggregation-Induced Near-Infrared Emission and Electrochemiluminescence of an Iridium(III) Complex for Ampicillin Sodium Sensing.

A new iridium(III) complex was synthesized and characterized. Its photophysical properties and aggregation-induced emission and electrochemiluminescence in the near-infrared range were studied. The large conjugated cyclometallic ligand 1,2-phenylbenzoquinoline (pbq) was selected to form the Ir-C bond with the metal iridium(III) center and provide near-infrared emission of the complex. The auxiliary ligand 4,4'-diamino-2,2'-bipyridine (dabpy) can form hydrogen bonds, which was beneficial for the generation of aggregation-induced emission. The complex was aggregated into small spherical nanoparticles in 80% water and fascinating nanorings in 90% water. The sensing of ampicillin sodium (AMP) antibiotic by the iridium(III) complex were also investigated by photoluminescent and electrochemiluminescent methods. The complex showed a good selectivity toward AMP antibiotic compared to sodium phenylacetate and other eight antibiotics. The detection limits for AMP antibiotic was 0.76 µg/mL. This work provided a new strategy for the design of iridium(III) complex-based aggregation-induced emission and electrochemiluminescence probes for the sensing application.

FeNC nanozyme-based electrochemical immunoassay for sensitive detection of human epidermal growth factor receptor 2.

The proof-of-concept of sensitive electrochemical immunoassay for the quantitative monitoring of human epidermal growth factor receptor 2 (HER2) is reported. The assay is carried out on iron nitrogen-doped carbon (FeNC) nanozyme-modified screen-printed carbon electrode using chronoamperometry. Introduction of target HER2 can induce the sandwiched immunoreaction between anti-HER2 monoclonal antibody-coated microplate and biotinylated anti-HER2 polyclonal antibody. Thereafter, streptavidin-glucose oxidase (GOx) conjugate is bonded to the detection antibody. Upon addition of glucose, 3,3',5,5'-tetramethylbenzidine (TMB) is oxidized through the produced H2O2 with the assistance of GOx and FeNC nanozyme. The oxidized TMB is determined via chronoamperometry. Experimental results revealed that electrochemical immunosensing system exhibited good amperometric response, and allowed the detection of target HER2 as low as 4.5 pg/mL. High specificity and long-term stability are acquired with FeNC nanozyme-based sensing strategy. Importantly, our system provides a new opportunity for protein diagnostics.

Parental Psychological Control, the Parent-Adolescent Relationship, and Non-suicidal Self-Injury Among Chinese Adolescents: The Moderating Effect of the Oxytocin Receptor Gene rs53576 Polymorphism.

Parental psychological control (PPC) is associated with adolescent non-suicidal self-injury (NSSI); however, its underlying mechanisms have not been extensively investigated. Considering that genetic and environmental factors interactively influence adolescent development, this study examined whether the parent-adolescent relationship mediated the link between PPC and adolescent NSSI, and whether this mediating process was moderated by the oxytocin receptor gene rs53576 polymorphism (OXTR rs53576). Participants comprised 673 adolescents (Meanage = 12.81 years, SD = 0.48 years) who completed questionnaires regarding PPC, the parent-adolescent relationship, and NSSI. DNA was extracted from each participant's saliva samples. The results indicated that the positive association between PPC and adolescent NSSI was mediated by the parent-adolescent relationship. Moreover, this indirect link was stronger for adolescents with AA homozygotes of OXTR rs53576 than for those with the GG or AG genotype. These findings extend our understanding of the association between PPC and adolescent NSSI and suggest that a simultaneous focus on PPC, the parent-adolescent relationship, and OXTR rs53576 may favor NSSI interventions.

Tunable Competitive Absorption-Induced Signal-On Photoelectrochemical Immunoassay for Cardiac Troponin I Based on Z-Scheme Metal-Organic Framework Heterojunctions.

Recently emerged Z-scheme heterostructure-based immunoassays have presented new opportunities for photoelectrochemical (PEC) biosensing development. Here, we described a tunable signal-on PEC biosensor for the detection of cardiac troponin I (cTnI), which exploited a competitive absorption effect between Cu(II) ions and a Zr metal-organic framework (Zr-MOF) constructed on TiO2 nanorods (Cu2+@Zr-MOF@TiO2 NRs). Water-stable Zr-MOF was coated onto TiO2 NRs on fluorine-doped tin oxide to form a Z-scheme heterostructure substrate (Zr-MOF@TiO2 NRs), which exhibited a high photoelectric response. Cu2+@Zr-MOF@TiO2 NRs, constructed by loading Cu(II) ions onto the architecture of Zr-MOF by electrostatic interaction, demonstrated a low background signal. After sandwich immunorecognition within a 96-well plate, H2S, generated by confined alkaline phosphatase on zeolitic imidazolate framework-8, was directed to react with Cu(II) ions to form CuS. This resulted in an in situ change in the photoelectrode and an enhanced photoelectric signal. The developed PEC biosensing platform exhibited high sensitivity and selectivity for the cTnI immunoassay with a detection limit of 8.6 pg/mL. The Z-scheme-based competition absorption modulation of photoelectrochemistry provides a new strategy for general PEC biosensing development.

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

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

The Genome Copy Number of the Thermophilic Cyanobacterium Thermosynechococcus elongatus E542 Is Controlled by Growth Phase and Nutrient Availability.

The recently isolated thermophilic cyanobacterium Thermosynechococcus elongatus PKUAC-SCTE542 (here Thermosynechococcus E542) is a promising strain for fundamental and applied research. Here, we used several improved ploidy estimation approaches, which include quantitative PCR (qPCR), spectrofluorometry, and flow cytometry, to precisely determine the ploidy level in Thermosynechococcus E542 across different growth stages and nutritional and stress conditions. The distribution of genome copies per cell among the populations of Thermosynechococcus E542 was also analyzed. The strain tends to maintain 3 or 4 genome copies per cell in lag phase, early growth phase, or stationary phase under standard conditions. Increased ploidy (5.5 ± 0.3) was observed in exponential phase; hence, the ploidy level is growth phase regulated. Nearly no monoploid cells were detected in all growth phases, and prolonged stationary phase could not yield ploidy levels lower than 3 under standard conditions. During the late growth phase, a significantly higher ploidy level was observed in the presence of bicarbonate (7.6 ± 0.7) and high phosphate (6.9 ± 0.2) at the expense of reduced percentages of di- and triploid cells. Meanwhile, the reduction in phosphates decreased the average ploidy level by increasing the percentages of mono- and diploid cells. In contrast, temperature and antibiotic stresses reduced the percentages of mono-, di-, and triploid cells yet maintained average ploidy. The results indicate a possible causality between growth rate, stress, and genome copy number across the conditions tested, but the exact mechanism is yet to be elucidated. Furthermore, the spectrofluorometric approach presented here is a quick and straightforward ploidy estimation method with reasonable accuracy.IMPORTANCE The present study revealed that the genome copy number (ploidy) status in the thermophilic cyanobacterium Thermosynechococcus E542 is regulated by growth phase and various environmental parameters to give us a window into understanding the role of polyploidy. An increased ploidy level is found to be associated with higher metabolic activity and increased vigor by acting as backup genetic information to compensate for damage to the other chromosomal copies. Several improved ploidy estimation approaches that may upgrade the ploidy estimation procedure for cyanobacteria in the future are presented in this work. Furthermore, the new spectrofluorometric method presented here is a rapid and straightforward method of ploidy estimation with reasonable accuracy compared to other laborious methods.

Ultrasensitive photoelectrochemical immunoassay for prostate-specific antigen based on silver nanoparticle-triggered ion-exchange reaction with ZnO/CdS nanorods.

Prostate-specific antigen (PSA), a glycoprotein that is most likely to cause prostate cancer, has attracted widespread attention in recent years due to its increasing threat to people's lives and health. Herein, we developed a new signal-amplified photoelectrochemical (PEC) immunosensing method for quantitative monitoring of the target PSA based on the ion-exchange reaction for the in situ formation of ZnO/CdS/Ag2S nanohybrids triggered by the as-released silver ions (Ag+) from silver nanolabels. Initially, the introduction of a target PSA caused the formation of a sandwich immunocomplex in an anti-PSA capture antibody (cAb)-coated microplate with the help of a silver nanoparticle-labeled detection antibody (AgNPs-dAb). Thereafter, the introduced AgNPs were dissolved with acid to release numerous silver ions. In this regard, an ion-exchange reaction occurred between the silver ions and ZnO/CdS nanorods on the photosensitive electrode, thus producing ZnO/CdS/Ag2S nanohybrids to generate a relatively strong photocurrent. Under optimal conditions, the ion-exchange reaction-based PEC immunoassay exhibited a good linear range of 0.05-50 ng mL-1 and allowed the detection of the target PSA at a concentration as low as 0.018 ng mL-1. In addition, the PEC immunoassay displayed satisfactory repeatability, high specificity, and acceptable method accuracy. Importantly, the ion-exchange reaction-based PEC immunoassay provides a new perspective for the detection of other disease-related biomarkers by controlling the corresponding antibodies.

Ultrasensitive fluorometric biosensor based on Ti3C2 MXenes with Hg2+-triggered exonuclease III-assisted recycling amplification.

Herein a rapid and sensitive fluorometric bioanalysis platform for mercury(ii) (Hg2+) detection was innovatively developed using ultrathin two-dimensional MXenes (Ti3C2) as fluorescence quencher and Hg2+-induced exonuclease III (Exo III)-assisted target recycling strategy for efficient signal amplification. Initially, fluorophore-labeled single-stranded DNA (FAM-labeled probe) can be easily adsorbed onto the surface of ultrathin Ti3C2 nanosheets by hydrogen bonding and metal chelating interaction, and the fluorescence signal emitted by the FAM-labeled probe is quenched strongly owing to the fluorescence resonance energy transfer between the FAM and ultrathin Ti3C2 nanosheets. Upon sensing the target Hg2+, the protruding DNA fragment at the 3' end of hairpin will hybridize with primer (hairpin-Hg2+-primer), and then further digested by Exo III to produce a probe (nicker). The released target Hg2+ and primer continue to participate in the next recycling, resulting in more hairpin probes becoming nickers. The combination of a large number of nickers and FAM-probe resulted in a significant increase in the fluorescence signal of the system, which was attributed to the fact that the double helix DNA was more rigid and separated from the surface of the ultrathin Ti3C2 nanosheets. The obvious fluorescence signal change of the Ti3C2-based Exo III-assisted target recycling can be accurately monitored by fluorescence spectrometry, which is also proportional to the concentration of Hg2+. Under optimum operating conditions, the peak intensity (520 nm wavelength) of fluorescence increased with increasing Hg2+ within a wide dynamic working range from 0.05 nM to 50 nM (R2 = 0.9913) with a limit of detection down to 42.5 pM. The proposed strategy uses ultrathin MXenes as a platform for binding nucleic acids, which contributes to its potential in nucleic acid hybridization-based biosensing and/or nucleic acid signal amplification bio-applications.

The role of claudin-4 in the development of gastric cancer.

Gastric cancer is one of most challenging cancers and a significant cause of death worldwide. Gastric cancer is, associated with a high incidence and recurrence rate of metastatic disease and poor survival for those with metastatic disease. Claudin-4 is a transmembrane protein that plays an important role in tight junctions. Increasing experimental research has demonstrated that claudin-4 plays an important role in the progression of gastric cancer, including the occurrence of epithelial to mesenchymal transition, intestinal metaplasia, and gastric cancer. In addition, claudin-4 regulates cell proliferation, invasion, migration and apoptosis. Claudin-4 may represent a potential biomarker for gastric cancer patient prognosis and is useful in the classification of gastric cancer. Therefore, in this review, we summarize current information on claudin-4 and gastric cancer, describing the role of claudin-4 in gastric cancer progression and its application in clinical treatment to provide a basis for further research and promote the claudin-4 gene as a potential target to diagnose and treat gastric cancer.

Coupling coumarin to gold nanoparticles by DNA chains for sensitive detection of DNase I.

A kind of coumarin-modified gold nanoparticle by the bridge of dsDNA chains was designed and synthesized for sensitive detection of DNase I. The fluorescence of coumarin 343 at emission wavelengths of 491 nm excited at 440 nm was quenched by the gold nanoparticles due to the energy transfer process after the coumarin 343 was connected on the gold nanoparticles by DNA chains. When dsDNA chains were cut off by DNase I, the coumarin 343 molecules were released from gold nanoparticles and the fluorescence of coumarin 343 would be restored. The DNase I activity could be detected by this fluorescence assay with a high sensitivity based on the change of the energy transfer efficiency. The intensity of restored fluorescence is linearly related to the quantity of DNase I in the range from 1.0 to 40 mU/mL with a detection limit of 0.22 mU/mL. This design idea could render a useful way to develop similar molecular or enzyme sensor in analytical or biological fields.

Barbituric acid-modified graphitic carbon nitride nanosheets for ratiometric fluorescent detection of Cu2.

In this work, barbituric acid-modified graphitic carbon nitride (BCN) nanosheets with blue-green fluorescence were prepared by a copolymerization of dicyandiamide with barbituric acid and then by a chemical oxidation process. A ratiometric fluorescent sensor for Cu2+ was designed by using BCN nanosheets as the report probe and Ru(bpy)3Cl2 as the reference probe. In the presence of different concentrations of Cu2+, the blue-green fluorescence of BCN nanosheets was drastically quenched, while the red fluorescence of Ru(bpy)3Cl2 remained constant. The color of the sensor changed from blue-green to red, resulting in ratiometric and visual detection of Cu2+ ions. The detection limit for Cu2+ was estimated to be 70 nM, and as low as 5 µM Cu2+ was distinguished with the naked eye. Additionally, this sensor was also applied for the detection of Cu2+ in tap water samples.

Sensitive determination of lysozyme by using a luminescent and colorimetric probe based on the aggregation of gold nanoparticles induced by an anionic ruthenate(II) complex.

The negatively charged ruthenate(II) complex [Ru(bpy)(PPh3)(CN)3]- and gold nanoparticles (AuNPs) were used for detecting lysozyme (LYS). The luminescence of the ruthenate(II) complex is quenched by AuNPs, and this induces the aggregation of AuNPs and a color change from red to blue. After addition of lysozyme, the positively charged lysozyme and the negatively charged ruthenate(II) complex bind each other by electrostatic interaction firstly. This prevents AuNPs from aggregation and quenches the emission of the ruthenate(II) complex. Its luminescence and the degree of aggregation of the AuNPs can be used to quantify LYS. The fluorometric calibration plot is linear in the 0.01 to 0.20 µM LYS concentration range, and the calibration plot is linear between 0.02 and 0.20 µM of LYS. The color of the solution can be easily distinguished by bare eyes at 0.08 µM or higher concentration of LYS. The applicability of the method was verified by the correct analysis of LYS in chicken egg white. Graphical abstract Schematic of a luminometric and colorimetric probe based on the induced aggregation of gold nanoparticles by an anionic luminescent ruthenate(II) complex or sensitive lysozyme detection.

A luminescent and colorimetric probe based on the functionalization of gold nanoparticles by ruthenium(ii) complexes for heparin detection.

A sensitive assay was demonstrated for the colorimetric and luminescent detection of heparin. Positively charged [Ru(phen)2np]2+ (np: naphtho[2,3-f][1,10]phenanthroline) can interact with negatively charged AuNPs through electrostatic interaction, leading to the luminescence quenching of [Ru(phen)2np]2+via energy transfer as well as the aggregation of AuNPs together with a color change in solution from red to blue. Upon the addition of negatively charged heparin to gold nanoparticles functionalized by ruthenium(ii) complexes, the emission of [Ru(phen)2np]2+ recovered due to the competitive adsorption of [Ru(phen)2np]2+ to heparin and AuNPs. A linear calibration curve was obtained in the 0.4 µM to 100 µM range and 0.1 µM to 6 µM with a low detection limit of 0.22 µM and 0.024 µM based on 3σ/s for heparin quantification in buffer solution and in 1% fetal bovine serum (FBS), respectively. Interestingly, the naked eye alone can judge the presence of 0.02 µM heparin without the aid of any advanced instruments by color change. Thus a convenient and visual method to detect heparin was established.

Gold Nanoparticle-Based Probe for Colorimetric Detection of Copper Ions.

A new ligand 10-mercaptodecyl-1-iminodiacetic acid (MDIA) was synthesized and used to modify gold nanoparticles to provide a simple assay to repeatedly sense Cu²âº in the solution at room temperature. This functionalized gold nanosensor was applied for the detection of Cu²âº in water samples with sensitivity and simplicity. The chelation/aggregation process is reversible via addition of a strong metal ion chelator such as EDTA. This simple and fast colorimetric sensor is important in the application of copper ion detection in water quality during the emergency and early warning monitoring.

Dual-channel luminescent Ir(III) complex for detection of GSH and Hcy/Cys in cells.

Glutathione (GSH), homocysteine (Hcy) and cysteine (Cys) play important roles in many physiological processes. However, due to their structural and functional similarities, it is still a challenge to develop a probe that can differentiate between GSH and Hcy/Cys simultaneously. In this work, a luminescent probe Ir-NBD was designed and synthesized, which emit weakly due to the presence of photo induced electron transfer (PET) interaction. When it reacted with the three biothiols, NBD dissociated and luminescence of Ir-OH was enhanced in the near-infrared (NIR) region due to the disappearance of the PET effect. On the other hand, the products obtained from the reaction of GSH with NBD were hardly luminescent, but the products from the reaction of Hcy/Cys with NBD could undergo an intramolecular rearrangement, resulting in an enhanced luminescence of the solution in the visible region. Ir-NBD enabled highly selective and sensitive detection of GSH and Cys/Hcy in a relatively short time (15 min). The two luminescent colors were clearly differentiated without spectral interference and the detection limit reached 1.32 µM (GSH), 0.42 µM (Hcy) and 0.51 µM (Cys), respectively. Ir-NBD also had low cytotoxicity, it realized the simultaneous detection of GSH and Hcy/Cys by dual-channel luminescence, and also provided ideas for the design of multifunctional luminescent probes.

Mitochondria-targeted ruthenium(II) complexes for photodynamic therapy and GSH detection in living cells.

Photodynamic therapy is an emerging tumor therapy that kills tumor cells by activating reactive oxygen species (ROS) produced by photosensitizers. Mitochondria, as an important organelle, are the main generator of cellular ROS. Therefore, the development of photosensitizers capable of targeting mitochondria could significantly enhance the efficacy of photodynamic therapy. In this study, two novel ruthenium(II) complexes, Ru-1 and Ru-2, were designed and synthesized, both of which were functionalized with α,ß-unsaturated ketones for sensing of glutathione (GSH). The crystal structures of the two complexes were determined and they exhibited good recognition of GSH by off-on luminescence signals. The complex Ru-2 containing aromatic naphthalene can enter the cells and react with GSH to generate a strong luminescence signal that can be used to monitor intracellular GSH levels through imaging. Ru-2 also has an excellent mitochondrial localization ability with a Pearson's coefficient of 0.95, which demonstrates that it can efficiently target the mitochondria of tumor cells to enhance the effectiveness of photodynamic therapy as a photosensitizer.

Synthesis, characterization, and DNA binding of a novel ligand and its Cu (II) complex.

A novel naphthalene-2,3-diamine-2-salicylaldehyde (NS) ligand and its mononuclear copper(II) complex (CuNS) have been synthesized and structurally characterized. The UV­vis absorption and emission spectra of NS showed obvious changes on addition of Cu2+ solution. The interaction of the compounds with calf thymus DNA and G-quadruplex DNA were investigated by spectroscopic methods and thermal melting assay. The nucleolytic cleavage activity of the compounds was investigated on double-stranded circular pBR322 plasmid DNA and G-quadruplex DNA by electrophoretic mobility shift assay. The results show that CuNS has a greater ability to stabilize G-quadruplex DNA over calf-thymus DNA. The cytotoxicity of the compounds toward HpeG2 cancer cells was also studied, and they showed significant potential for antineoplastic effects.

Coupling gold nanoparticles to silica nanoparticles through disulfide bonds for glutathione detection.

Advances in the controlled assembly of nanoscale building blocks have resulted in functional devices which can find applications in electronics, biomedical imaging, drug delivery etc. In this study, novel covalent nanohybrid materials based upon [Ru(bpy)3](2+)-doped silica nanoparticles (SiNPs) and gold nanoparticles (AuNPs), which could be conditioned as OFF-ON probes for glutathione (GSH) detection, were designed and assembled in sequence, with the disulfide bonds as the bridging elements. The structural and optical properties of the nanohybrid architectures were characterized using transmission electron microscopy, UV-vis spectroscopy and fluorescence spectroscopy, respectively. Zeta potential measurements, x-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy were employed to monitor the reaction processes of the SiNPs-S-S-COOH and SiNPs-S-S-AuNPs synthesis. It was found that the covalent nanohybrid architectures were fluorescently dark (OFF state), indicating that SiNPs were effectively quenched by AuNPs. The fluorescence of the OFF-ON probe was resumed (ON state) when the bridge of the disulfide bond was cleaved by reducing reagents such as GSH. This work provides a new platform and strategy for GSH detection using covalent nanohybrid materials.

Ultrathin mesoporous BiOCl nanosheets-mediated liposomes for photoelectrochemical immunoassay with in-situ signal amplification.

Designing new biochemical sensors and achieving selectivity and high-sensitivity analysis is one of main research directions for immunoassays. Herein, a liposome-amplification photoelectrochemical (PEC) immunoassay was developed using ultrathin mesoporous bismuth chloride oxide nanosheets (BiOCl MSCN) for the highly selective and sensitive detection of carcinoembryonic antigen (CEA). Based on good photocurrent response of BiOCl MSCN toward dopamine, a liposome-conjugated secondary antibody loaded with dopamine was added for specific recognition in the presence of CEA. After the lysis treatment, the liberated dopamine was injected into the three-electrode electrolytic cell to enhance the photocurrent of BiOCl MSCN. Under the optimized conditions, the constructed liposome-mediated PEC immunoassay showed high sensitivity against CEA, with a dynamic response in the linear range of 0.05 ng mL-1 to 100 ng mL-1 and a detection limit of 35 pg mL-1. The present study proposes a new approach to the liposome-mediated PEC immunoassay constructed on ultrathin mesoporous BiOCl nanosheets, which can be used to target further the study of the sensing mechanism.

Two near-infrared phosphorescent iridium(III) complexes for the detection of GSH and photodynamic therapy.

GSH is one of the most important reducing agents in biological systems. The depletion of GSH in the human body is linked to many diseases. Therefore, it is necessary to develop suitable and efficient probes for detecting GSH concentrations in real samples. In this work, we designed and synthesized two near-infrared emitting iridium(III) complex probes containing a novel ligand functionalized with an α,ß-unsaturated ketone for the rapid and sensitive detection of GSH. The molecular structure of Ir2 was determined by X-ray crystallography. Due to their large Stokes shift, long luminescence lifetime and NIR emission, these probes were successfully applied in the imaging of GSH in living cells. In addition, two iridium(III) complexes have strong singlet oxygen generation ability which can be used for photodynamic therapy (PDT) upon visible light irradiation. On the basis of these findings, our iridium(III) complexes may serve as GSH probes for HeLa cell imaging and as photosensitizers for PDT.