Reversible Regulation of Long-Distance Charge Transport in DNA Nanowires by Dynamically Controlling Steric Conformation.

Understanding of DNA-mediated charge transport (CT) is significant for exploring circuits at the molecular scale. However, the fabrication of robust DNA wires remains challenging due to the persistence length and natural flexibility of DNA molecules. Moreover, CT regulation in DNA wires often relies on predesigned sequences, which limit their application and scalability. Here, we addressed these issues by preparing self-assembled DNA nanowires with lengths of 30-120 nm using structural DNA nanotechnology. We employed these nanowires to plug individual gold nanoparticles into a circuit and measured the transport current in nanowires with an optical imaging technique. Contrary to the reported cases with shallow or no length dependence, a fair current attenuation was observed with increasing nanowire length, which experimentally confirmed the prediction of the incoherent hopping model. We also reported a mechanism for the reversible CT regulation in DNA nanowires, which involves dynamic transitions in the steric conformation.

Antibacterial Carbon Dots-Based Composites.

The emergence and global spread of bacterial resistance to conventionally used antibiotics have highlighted the urgent need for new antimicrobial agents that might replace antibiotics. Currently, nanomaterials hold considerable promise as antimicrobial agents in anti-inflammatory therapy. Due to their distinctive functional physicochemical characteristics and exceptional biocompatibility, carbon dots (CDs)-based composites have attracted a lot of attention in the context of these antimicrobial nanomaterials. Here, a thorough assessment of current developments in the field of antimicrobial CDs-based composites is provided, starting with a brief explanation of the general synthesis procedures, categorization, and physicochemical characteristics of CDs-based composites. The many processes driving the antibacterial action of these composites are then thoroughly described, including physical destruction, oxidative stress, and the incorporation of antimicrobial agents. Finally, the obstacles that CDs-based composites now suffer in combating infectious diseases are outlined and investigated, along with the potential applications of antimicrobial CDs-based composites.

A Telomerase-Assisted Strategy for Regeneration of DNA Nanomachines in Living Cells.

DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.

Multistage Photoactivatable Zinc-Responsive Nanodevices for Monitoring and Regulating Dysfunctional Islet ß-Cells.

The dysfunctional islet ß-cell triggered by excessive deposition of Zn2+ constituted a striking indicator of the occurrence of diabetic disease. However, it remained a formidable challenge to reflect the real-time function of ß-cell by monitoring the Zn2+ content. Herein, multistage photoactivatable Zn2+-responsive nanodevice (denoted as AD2@USD1) was presented for sensing, regulating, and evaluating Zn2+ levels in dysfunctional islet ß-cells. The photoactivated signatures on the satellite shell layer of the nanodevices and the internally loaded chelating factors effectively identified and intervened in the real-time concentration of Zn2+, the photothermal feedback component decorated on the inner core permitted the assessment of the post-intervention Zn2+ levels, achieving an integrated intervention and prognostic assessment in response to the abnormal islet ß-cell function induced by Zn2+ deposition. In this way, one strategy for sensing and regulating islet ß-cell function-oriented to Zn2+ was established. Our study introduced AD2@USD1 as a tool for effectively sensing, adjusting, and assessing the Zn2+ level in islet ß-cells with abnormalities, gaining a potential breakthrough in the treatment of diabetes.

Damage-Free and Time-Saving Platform Integrated by a Flow Membrane Separation Device and a Dual-Target Biofuel Cell-Based Biosensor for Continuous Sorting and Detection of Exosomes and Host Cells in Human Serum.

The growth relationship between exosomes (EXOs) and the host cells is highly desired for tumor evaluations, which puts forward high demand on the accurate and convenient acquisition of their individual quantitative information. However, the tedious and destructive separation process and the requirement of dual-channel detection make it become an extremely challenging task. Herein, we integrated an enzymatic biofuel cell (EBFC)-powered biosensor with a flow cell-supported membrane separation device (FMSC) to develop a continuous separation and detection platform for EXOs and host cancer cells in human serum. The FMSC equipped with an aluminum oxide membrane served as a size-dependent sorting unit to nondestructively extract EXOs from human serum within 5 min, representing a 99.3% reduction in isolating time compared to ultracentrifugation. The EBFC-powered biosensors modified with different aptamers on anodes and cathodes were used as a dual-channel sensing unit. By regulating the controlling valves of different fluid passages, the extracted EXOs and residual host cells could be successively inputted into EBFC-powered biosensors, which generated a segmental degradation in output performance due to the EXO-and host cell-caused increase in the steric hindrance of anodes and cathodes, respectively. Based on these degradations, we obtained the quantitative information of EXOs and host cells with a record-breaking sensitivity (EXOs: 5.59 × 103 particles/mL and host cells: 25 cells/mL). Moreover, the growth relationship between EXOs and host cells was also built, which would be beneficial for the disclosure of the growth state or even more detailed biology information of tumor.

CRISPR System-Linked Self-Assembling Nanoplatforms for Inspection and Screening of Gastric Cancer Stem Cells.

Cancer stem cells (CSCs) possess a high degree of plasticity, constituting a formidable challenge to identify and screen CSCs in situ with outstanding specificity and sensitivity. To overcome this limitation, a self-assembled heterodimer consisting of clustered regularly interspaced short palindromic repeats/Cas12a (named A-CCA) linkage is designed for in situ identification and screening of gastric CSCs (GCSCs) from gastric cancer cells (GCCs). In this system, the editable character of crRNA performs recognition of dual-targets in GCSCs, effectively boosting the specificity of identification, while the enzymatic reaction of Cas12a contributes meaningfully to the sensitivity of sensing, enabling in situ examination and screening of GCSCs. Specifically, the A-CCA nanoplatforms hybridized with ABCG 2 and ABCB 1 overexpress in GCSCs, which can generate heterodimers and simultaneously restore the function of trans-cleavage. At this time, the asymmetry of the heterodimer causes a circular dichroism signal, which together with the recovered fluorescence signal form a dual-signals output system that can further ensure the precision of screening GCSC. Therefore, fluorescence-enhanced GCSCs can be sorted out from GCCs by flow cytometry. Furthermore, GCSCs screened by this assay possess extremely aggressive tumorigenic efficiency, providing a fundamental research object for further developing CSC targeted drugs in vivo.

Nanomaterials Facilitating Conversion Efficiency Strategies for Microbial CO2 Reduction.

Microbial electro- and photoelectrochemical CO2 reduction represents an opportunity to tackle the environmental demand for sustainable fuel production. Nanomaterials critically impact the electricity- and solar-driven microbial CO2 reduction processes. This minireview comprehensively summarizes the recent developments in the configuration and design of nanomaterials for enhancement of the bacterial adhesion and extracellular electron transfer (EET) processes, based on the modification technologies of improving chemical stability, electrochemical conductivity, biocompatibility, and surface area. Furthermore, the investigation of incorporating non-photosynthetic microorganisms using advanced light-harvesting nanostructured photoelectrodes for solar-to-chemical conversion, as well as the current understanding of EET mechanisms occurring at photosynthetic semiconductor nanomaterials-bacteria biohybrid interface is detailed. The crucial factors influencing the performance of microbial CO2 reduction systems and future perspectives are discussed to provide guidance for the realization of their large-scale application.

Self-assembled nanomaterials for biosensing and therapeutics: recent advances and challenges.

Self-assembled nanomaterials (SANs) exhibit designable biofunctions owing to their tunable nanostructures and modifiable surface. Various constituent units and multi-dimensional structures of SANs provide unlimited possibilities for numerous applications. This review emphasizes the recent development of SANs in the fields of biosensing, bioimaging, and nano-drug engineering. The unit type, design concepts, material advantages, assembly driving force, nanostructure effects, drug loading performance, etc. are discussed and summarized. Finally, we briefly summarize how to assemble unique nanomaterials and point out the key challenges in this field.

Bioapplications of DNA nanotechnology at the solid-liquid interface.

DNA nanotechnology engineered at the solid-liquid interface has advanced our fundamental understanding of DNA hybridization kinetics and facilitated the design of improved biosensing, bioimaging and therapeutic platforms. Three research branches of DNA nanotechnology exist: (i) structural DNA nanotechnology for the construction of various nanoscale patterns; (ii) dynamic DNA nanotechnology for the operation of nanodevices; and (iii) functional DNA nanotechnology for the exploration of new DNA functions. Although the initial stages of DNA nanotechnology research began in aqueous solution, current research efforts have shifted to solid-liquid interfaces. Based on shape and component features, these interfaces can be classified as flat interfaces, nanoparticle interfaces, and soft interfaces of DNA origami and cell membranes. This review briefly discusses the development of DNA nanotechnology. We then highlight the important roles of structural DNA nanotechnology in tailoring the properties of flat interfaces and modifications of nanoparticle interfaces, and extensively review their successful bioapplications. In addition, engineering advances in DNA nanodevices at interfaces for improved biosensing both in vitro and in vivo are presented. The use of DNA nanotechnology as a tool to engineer cell membranes to reveal protein levels and cell behavior is also discussed. Finally, we present challenges and an outlook for this emerging field.

An Improved Strategy for High-Quality Cesium Bismuth Bromine Perovskite Quantum Dots with Remarkable Electrochemiluminescence Activities.

Low-toxic trivalent bismuth, with an isoelectronic structure (6s26p0) and a similar ionic radius to divalent lead, represents a promising candidate for constructing lead-free perovskites. Herein, cesium bismuth halide perovskite quantum dots (Cs3Bi2Br9 QDs) were synthesized via a comprehensively improved ligand-assisted reprecipitation method with the addition of γ-butyrolactone, trace distilled water, and tetrabutylammonium bromide, as well as the aid of ultrasonic technology. The as-prepared QDs displayed remarkable monodispersity, outstanding stability, and highly passivated surfaces with a near-single-component PL decay, thus affording superb optical properties with a photoluminescence quantum yield up to 37%, outperforming all the reported bismuth-based perovskites. Furthermore, Cs3Bi2Br9 QDs were first attempted for electrochemiluminescence (ECL) and exhibited a stable and efficient ECL response following either an annihilation or a coreaction ECL mechanism. Not only were the optical properties and stability of Cs3Bi2Br9 QDs greatly improved in this work, but their electrochemical behaviors and ECL natures were also investigated systematically for the first time, demonstrating the significant potential to extend this environmentally friendly bismuth-based perovskite into the ECL domain.

Dexmedetomidine Attenuates Lung Injury by Promoting Mitochondrial Fission and Oxygen Consumption.

BACKGROUND Sepsis is among the major antecedents of lung injury characterized by mitochondrial dysfunction. The functional integrity of the cell is influenced by mitochondrial dynamics. The present investigation evaluated the protective effects of dexmedetomidine against lung injury and speculates on the possible mechanism underlying its effects on mitochondrial function. MATERIAL AND METHODS Lung injury was induced by cecal ligation and puncture (CLP) in mice treated with 0.1, 0.3, or 0.5 mg/kg intravenous dexmedetomidine after a 30-minute surgery. The effects of dexmedetomidine were determined by the oxygenation index and the wet/dry weight ratio of the lung. The expression of mitochondrial protein was assessed by western blot analyses and real-time polymerase chain reaction, to determine the effects of dexmedetomidine on mitochondrial dynamics. The histopathology of the lung tissue was determined by hematoxylin and eosin staining, and TUNEL-positive cells were counted in TUNEL assays. Activity of caspase-3, caspase-8, and caspase-9 enzymes were determined by colorimetric assay. RESULTS Treatment with dexmedetomidine significantly attenuated changes in the oxygenation index and the wet/dry weight ratio in mice with CLP-induced lung injury. There was a significant decrease in pro-inflammatory mediators and markers of oxidative stress in the lung tissue of the dexmedetomidine-treated group compared to the negative control group. Moreover, treatment with dexmedetomidine attenuated the altered gene expression caused by mitochondrial fusion and fission in the lung tissue of mice with CLP-induced lung injury. The number of TUNEL-positive cells was significantly reduced in the dexmedetomidine-treated group compared to the negative control group. Moreover, dexmedetomidine ameliorated the altered activity of caspase-3, caspase-8, and caspase-9 enzyme in the lung tissues of CLP-induced lung injure mice. CONCLUSIONS Dexmedetomidine protected mice against CLP-induced lung injury by attenuating changes in mitochondrial fusion and fission.

Light-Driven Nano-oscillators for Label-Free Single-Molecule Monitoring of MicroRNA.

Here, we present a mapping tool based on individual light-driven nano-oscillators for label-free single-molecule monitoring of microRNA. This design uses microRNA as a single-molecule damper for nano-oscillators by forming a rigid dual-strand structure in the gap between nano-oscillators and the immobilized surface. The ultrasensitive detection is attributed to comparable dimensions of the gap and microRNA. A developed surface plasmon-coupled scattering imaging technology enables us to directly measure the real-time gap distance vibration of multiple nano-oscillators with high accuracy and fast dynamics. High-level and low-level states of the oscillation amplitude indicate melting and hybridization statuses of microRNA. Lifetimes of two states reveal that the hybridization rate of microRNA is determined by the three-dimensional diffusion. This imaging technique contributes application potentials in a single-molecule detection and nanomechanics study.

Prediction of Both Electrical and Mechanical Reverse Remodeling on Acute Electrocardiogram Changes After Cardiac Resynchronization Therapy.

BACKGROUND: The development of both electrical reverse remodeling and mechanical reverse remodeling (ERR+MRR) after cardiac resynchronization therapy (CRT) implantation could reduce the incidence of lethal arrhythmia, hence the prediction of ERR+MRR is clinically important.Methods and Results:Eighty-three patients (54 male; 67±12 years old) with CRT >6 months were enrolled. ERR was defined as baseline intrinsic QRS duration (iQRSd) shortening ≥10 ms in lead II on ECG after CRT, and MRR as improvement in LVEF ≥25% on echocardiography after CRT. Acute ECG changes were measured by comparing the pre-implant and immediate post-implant ECG. Ventricular arrhythmia episodes, including ventricular tachycardia and ventricular fibrillation, detected by the implanted device were recorded. Patients were classified as ERR only (n=12), MRR only (n=23), ERR+MRR (n=26), or non-responder (ERR- & MRR-, n=22). On multivariate regression analysis, difference between baseline intrinsic QRS and paced QRS duration (∆QRSd) >35 ms was a significant predictor of ERR+MRR (sensitivity, 68%; specificity, 64%; AUC, 0.7; P=0.003), and paced QTc >443 ms was a negative predictor of ERR+MRR (sensitivity, 78%; specificity, 60%; AUC, 0.7; P=0.002). On Cox proportional hazard modeling, ERR+MRR may reduce risk of ventricular arrhythma around 70% compared with non-responder (HR, 0.29; 95% CI: 0.13-0.65). CONCLUSIONS: Acute ECG changes after CRT were useful predictors of ERR+MRR. ERR+MRR was also a protective factor for ventricular arrhythmia.

Near-Infrared Photothermally Activated DNAzyme-Gold Nanoshells for Imaging Metal Ions in Living Cells.

DNAzymes have enjoyed success as metal ion sensors outside cells. Their susceptibility to metal-dependent cleavage during delivery into cells has limited their intracellular applications. To overcome this limitation, a near-infrared (NIR) photothermal activation method is presented for controlling DNAzyme activity in living cells. The system consists of a three-stranded DNAzyme precursor (TSDP), the hybridization of which prevents the DNAzyme from being active. After conjugating the TSDP onto gold nanoshells and upon NIR illumination, the increased temperature dehybridizes the TSDP to release the active DNAzyme, which then carries out metal-ion-dependent cleavage, resulting in releasing the cleaved product containing a fluorophore. Using this construct, detecting Zn2+ in living HeLa cells is demonstrated. This method has expanded the DNAzyme versatility for detecting metal ions in biological systems under NIR light that exhibits lower phototoxicity and higher tissue penetration ability.

Living and Conducting: Coating Individual Bacterial Cells with In†Situ Formed Polypyrrole.

Coating individual bacterial cells with conjugated polymers to endow them with more functionalities is highly desirable. Here, we developed an in situ polymerization method to coat polypyrrole on the surface of individual Shewanella oneidensis MR-1, Escherichia coli, Ochrobacterium anthropic or Streptococcus thermophilus. All of these as-coated cells from different bacterial species displayed enhanced conductivities without affecting viability, suggesting the generality of our coating method. Because of their excellent conductivity, we employed polypyrrole-coated Shewanella oneidensis MR-1 as an anode in microbial fuel cells (MFCs) and found that not only direct contact-based extracellular electron transfer is dramatically enhanced, but also the viability of bacterial cells in MFCs is improved. Our results indicate that coating individual bacteria with conjugated polymers could be a promising strategy to enhance their performance or enrich them with more functionalities.

Cathode Photoelectrochemical Immunosensing Platform Integrating Photocathode with Photoanode.

Generally, photoanode-based photoelectrochemical immunoassay possesses obvious photocurrent response and lower detection limit for ideal sample detection, but it has the inherent imperfection of poor anti-interference capability for real sample detection. Photocathode-based immunoassay can well avoid the intrinsic drawback of photoanode-based immunoassay, but it has low photocurrent response resulting in less good sensitivity. Herein, a promising new cathode photoelectrochemical immunosensing platform integrating photocathode with photoanode was reported for accurate and sensitive detection of biomarkers. In this proposal, prostate-specific antigen (PSA, Ag) was chosen as a model of target analyte to exhibit the analytical performances of this platform. TiO2/CdS:Mn hybrid structure modified indium-tin oxide (ITO) electrode served as photoanode, whereas CuInS2 microflowers modified ITO electrode was selected as photocathode. The transducer elements of PSA antibody (Ab) were modified on photocathode to fabricate a label-free cathode immunosensing electrode. The proposed immunosensing platform possesses two distinct advantages simultaneously. First, it has good anti-interference capability for the detection of real biological samples, since the biorecognition events occurred on photocathode. Second, the photoelectrochemical system owns evident photocurrent response and low detection limit for target Ag detection thanks to the introduction of the photoanode. Moreover, the proposed immunosensing platform also exhibits good specificity, reproducibility, and stability, and meanwhile it opens up a new horizon to construct other kinds of photoelectrochemical biosensors.

Enhanced Photoelectrochemical Immunosensing Platform Based on CdSeTe@CdS:Mn Core-Shell Quantum Dots-Sensitized TiO2 Amplified by CuS Nanocrystals Conjugated Signal Antibodies.

A new, ultrasensitive photoelectrochemical immunosensing platform was established on the basis of CdSeTe@CdS:Mn core-shell quantum dots-sensitized TiO2 coupled with signal amplification of CuS nanocrystals conjugated signal antibodies. In this proposal, carcinoembryonic antigen (CEA, Ag) was selected as an example of target analyte to show the analytical performances of the platform. Specifically, TiO2-modified electrode was first assembled with CdSeTe alloyed quantum dots (AQDs) via electrostatic adsorption assisted by oppositely charged polyelectrolyte, and then further deposited with CdS:Mn shells on the surface of CdSeTe AQDs via successive ionic layer adsorption and reaction strategy, forming TiO2/CdSeTe@CdS:Mn sensitization structure, which was used as photoelectrochemical matrix to immobilize capture CEA antibodies (Ab1); signal CEA antibodies (Ab2) were labeled with CuS nanocrystals (NCs) to form Ab2-CuS conjugates, which were employed as signal amplification elements when specific immunoreaction occurred. The ultrahigh sensitivity of this immunoassay resulted from the following two aspects. Before detection of target Ag, the TiO2/CdSeTe@CdS:Mn sensitization structure could adequately harvest the exciting light with different bands, evidently expedite the electron transfer, and effectively depress the charge recombination, resulting in noticeably increased photocurrent. When target Ag existed, the Ab2-CuS conjugates could dramatically decrease the photocurrent due to competitive absorption of exciting light and consumption of electron donor for CuS NCs coupled with steric hindrance of Ab2 molecules. The fabricated photoelectrochemical immunosensor showed a low limit of detection of 0.16 pg/mL and a wide linear range from 0.5 pg/mL to 100 ng/mL for CEA detection, and it also exhibited good specificity, reproducibility, and stability.

Supersensitive and selective detection of picric acid explosive by fluorescent Ag nanoclusters.

Picric acid (PA) explosive is a hazard to public safety and health, so the sensitive and selective detection of PA is very important. In the present work, polyethyleneimine stabilized Ag nanoclusters were successfully used for the sensitive and selective quantification of PA on the basis of fluorescence quenching. The quenching efficiency of Ag nanoclusters is proportional to the concentration of PA and the logarithm of PA concentration over two different concentration ranges (1.0 nM-1 µM for the former and 0.25-20 µM for the latter), thus the proposed quantitative strategy for PA provides a wide linear range of 1.0 nM-20 µM. The detection limit based on 3σ/K is 0.1 nM. The quenching mechanism of Ag nanoclusters by PA is discussed in detail. The results indicate that the selective detection of PA over other nitroaromatics including 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), p-nitrotoluene (p-NT), m-dinitrobenzene (m-DNB), and nitrobenzene (NB), is due to the electron transfer and energy transfer between PA and polyethyleneimine-capped Ag nanoclusters. In addition, the experimental data obtained for the analysis of artificial samples show that the proposed PA sensor is potentially applicable in the determination of trace PA explosive in real samples.

Sensitive electrochemical detection of telomerase activity using spherical nucleic acids gold nanoparticles triggered mimic-hybridization chain reaction enzyme-free dual signal amplification.

We report an electrochemical sensor for telomerase activity detection based on spherical nucleic acids gold nanoparticles (SNAs AuNPs) triggered mimic-hybridization chain reaction (mimic-HCR) enzyme-free dual signal amplification. In the detection strategy, SNAs AuNPs and two hairpin probes were employed. SNAs AuNPs as the primary amplification element, not only hybridized with the telomeric repeats on the electrode to amplify signal but also initiated the subsequent secondary amplification, mimic-hybridization chain reaction of two hairpin probes. If the cells' extracts were positive for telomerase activity, SNAs AuNPs could be captured on the electrode. The carried initiators could trigger an alternative hybridization reaction of two hairpin probes that yielded nicked double helices. The signal was further amplified enzyme-free by numerous hexaammineruthenium(III) chloride ([Ru(NH3)6](3+), RuHex) inserting into double-helix DNA long chain by electrostatic interaction, each of which could generate an electrochemical signal at appropriate potential. With this method, a detection limit of down to 2 HeLa cells and a dynamic range of 10-10,000 cells were achieved. Telomerase activities of different cell lines were also successfully evaluated.

"Signal-on" photoelectrochemical biosensor for sensitive detection of human T-Cell lymphotropic virus type II DNA: dual signal amplification strategy integrating enzymatic amplification with terminal deoxynucleotidyl transferase-mediated extension.

A novel "signal-on" photoelectrochemical (PEC) biosensor for sensitive detection of human T-cell lymphotropic virus type II (HTLV-II) DNA was developed on the basis of enzymatic amplification coupled with terminal deoxynucleotidyl transferase (TdT)-mediated extension strategy. The intensity of the photocurrent signal was proportional to the concentration of the HTLV-II DNA-target DNA (tDNA) by dual signal amplification. In this protocol, GR-CdS:Mn/ZnS nanocomposites were used as photoelectric conversion material, while pDNA was used as the tDNA recognizing unit. Moreover, the TdT-mediated extension and the enzymatic signal amplification technique were used to enhance the sensitivity of detection. Using this novel dual signal amplification strategy, the prototype of PEC DNA sensor can detect as low as ∼0.033 fM of HTLV-II DNA with a linear range of 0.1-5000 fM, with excellent differentiation ability even for single-base mismatches. This PEC DNA assay opens a promising platform to detect various DNA targets at ultralow levels for early diagnoses of different diseases.