DNA Framework-Based Programmable Atom-Like Nanoparticles for Non-Coding RNA Recognition and Differentiation of Cancer Cells.

The cooperative diagnosis of non-coding RNAs (ncRNAs) can accurately reflect the state of cell differentiation and classification, laying the foundation of precision medicine. However, there are still challenges in simultaneous analyses of multiple ncRNAs and the integration of biomarker data for cell typing. In this study, DNA framework-based programmable atom-like nanoparticles (PANs) are designed to develop molecular classifiers for intra-cellular imaging of multiple ncRNAs associated with cell differentiation. The PANs-based molecular classifier facilitates signal amplification through the catalytic hairpin assembly. The interaction between PAN reporters and ncRNAs enables high-fidelity conversion of ncRNAs expression level into binding events, and the assessment of in situ ncRNAs levels via measurement of the fluorescent signal changes of PAN reporters. Compared to non-amplified methods, the detection limits of PANs are reduced by four orders of magnitude. Using human gastric cancer cell lines as a model system, the PANs-based molecular classifier demonstrates its capacity to measure multiple ncRNAs in living cells and assesses the degree of cell differentiation. This approach can serve as a universal strategy for the classification of cancer cells during malignant transformation and tumor progression.

Antidiabetic Close Loop Based on Wearable DNA-Hydrogel Glucometer and Implantable Optogenetic Cells.

Diabetes mellitus and its associated secondary complications have become a pressing global healthcare issue. The current integrated theranostic plan involves a glucometer-tandem pump. However, external condition-responsive insulin delivery systems utilizing rigid glucose sensors pose challenges in on-demand, long-term insulin administration. To overcome these challenges, we present a novel model of antidiabetic management based on printable metallo-nucleotide hydrogels and optogenetic engineering. The conductive hydrogels were self-assembled by bioorthogonal chemistry using oligonucleotides, carbon nanotubes, and glucose oxidase, enabling continuous glucose monitoring in a broad range (0.5-40 mM). The optogenetically engineered cells were enabled glucose regulation in type I diabetic mice via a far-red light-induced transgenic expression of insulin with a month-long avidity. Combining with a microchip-integrated microneedle patch, a prototyped close-loop system was constructed. The glucose levels detected by the sensor were received and converted by a wireless controller to modulate far-infrared light, thereby achieving on-demand insulin expression for several weeks. This study sheds new light on developing next-generation diagnostic and therapy systems for personalized and digitalized precision medicine.

Amplification of an Electrochemiluminescence-Emissive Aptamer into DNA Nanotags for Sensitive Fecal Calprotectin Determination.

The precision additive manufacturing and tessellated multitasking out of the structural DNA nanotechnology enable a configurable expression of densified electrochemiluminescent (ECL) complexes, which would streamline the bioconjugation while multiplying signals. Herein, a completely DNA-scaffold ECL "polyploid" was replicated out via the living course of rolling circle amplification. The amplicon carried the aptameric sequences of ZnPPIX/TSPP porphyrin as photoreactive centers that rallied at periodical intervals of the persistent extension into a close-packed nanoflower, ZnPDFI/II. Both microscopies and electrophoresis proved the robust nesting of guests at their deployed gene loci, while multispectral comparisons among cofactor substituents pinpointed the pivotal roles of singlet seclusion and Zn2+-chelation for the sake of intensive ECL irradiation. The adversity-resilient hydrogel texture made lipoidal filmogens as porphyrinic ECL prerequisites to be of no need at all, thus not only simplifying assay flows but also inspiring an in situ labeling plan. Upon bioprocessing optimization, an enriched probe ZnPDFIII was further derived that interpolated the binding motif related to calprotectin as validated by molecular docking and affinity titration. With it being a strongly indicative marker of inflammatory bowel disease (IBD), a competitive ECL aptasensing strategy was contrived, managing a signal-on and sensitive detection in mild conditions with a subnanogram-per-milliliter limit of detection by 2 orders of magnitude lower than the standard method as well as a comparable accuracy in clinical stool sample testing. Distinct from those conventional chemophysical rebuilding routes, this de novo biosynthetic fusion demonstrated a promising alternative toward ECL-source bioengineering, which may intrigue vibrant explorations of other ECL-shedding fabrics and, accordingly, a new bioanalytic mode downstream.

programmably engineered FRET-nanoflare for ratiometric live-cell ATP imaging with anti-interference capability.

Herein, we present a poly-adenine (polyA)-mediated programmably engineered FRET-nanoflare for ratiometric intracellular ATP imaging with anti-interference capability. The programmable polyA attachment is advantageous in enhancing the signal response for ATP. Moreover, the FRET-based nanoflare is capable of avoiding false-positive signals due to probe degradation in a complex environment, which has great potential for clinical diagnosis.

Vibration Characteristics and Experimental Research of Combined Beam Tri-Stable Piezoelectric Energy Harvester.

Vibration energy harvesting technology is expected to solve the power supply and endurance problems of wireless sensor systems, realize the self-power supply of wireless sensor systems in coal mines, and promote the intelligent development of coal mine equipment. A combined beam tri-stable piezoelectric energy harvester (CTPEH) is designed by introducing magnetic force into the combined beam structure. In order to explore the vibration characteristics of CTPEH, a nonlinear magnetic model is obtained based on the magnetic dipole theory, and the dynamic equation of the system is established using the Lagrange theorem and Rayleigh-Ritz theory. The influence of the different magnet distances and excitation conditions on the static bifurcation characteristics and dynamic response characteristics of the system are analyzed by numerical simulation, and the simulation results are validated by the experiments. The research results show that the motion state of the CTPEH system has four transition forms from mono-stable to tri-stable with the change in magnet distance. The tri-stable system has three potential energy curves with different characteristic shapes. The appropriate starting excitation position and excitation frequency can make it easier for the system to realize a large-amplitude response state, thereby improving the output performance of the system. This research provides new ideas and methods for optimizing the performance of the combined beam piezoelectric energy harvester.

A Linear-Arc Composite Beam Piezoelectric Energy Harvester Modeling and Finite Element Analysis.

To improve the output performance of the piezoelectric energy harvester, this paper proposed the design of a linear-arc composite beam piezoelectric energy harvester (PEH-C). First the nonlinear restoring force model of a composite beam was obtained by the numerical simulation method. Afterwards, the corresponding coupled governing equations were derived by using the generalized Hamilton principle, laying the foundation for subsequent in-depth research. After this, a finite element simulation was performed in the COMSOL software to simulate the output voltage, stress distribution, and resonance frequency of the PEH-C under different curvatures. In this way, the effect of curvature change on the PEH-C was analyzed. Finally, the PEH-C with a curvature of 40 m−1 was prepared, and an experimental platform was built to verify the correctness of the relevant analysis. The results showed that the resonant frequency of the PEH-C can be changed by changing the curvature, and that the stress on the composite beam will increase after the arc segment is introduced. When the curvature of the PEH-C was 40 m−1, the open-circuit output voltage was 44.3% higher than that of the straight beam.

Dynamic Characteristics and Experimental Research of Linear-Arch Bi-Stable Piezoelectric Energy Harvester.

Collecting vibration energy in the environment is expected to solve the problem of the self-power supply of wireless monitoring nodes in underground coal mines. By introducing nonlinear factors, a linear-arch bi-stable piezoelectric energy harvester (LBPEH) is designed. In order to reveal the influence of system parameters on the dynamic characteristics of LBPEH, the magnetic force model is established by the magnetizing current method, and the restoring force model is acquired through experimental measurement. The electromechanical coupling dynamics model of the system is established based on the Lagrange equation and Kirchhoff's law. The influence of excitation amplitude and excitation frequency on the dynamic characteristics of the piezoelectric energy harvester is simulated and analyzed. Moreover, experiments are designed to verify the results of the simulation. The results reveal that the restoring force of the linear-arch beam is nonlinear, and the LBPEH constructed by the linear-arch beam has an asymmetric potential well. Changing the excitation frequency or excitation amplitude can make the system in the well chaotic and achieve a large periodic motion state. With the increase of excitation amplitude, it is beneficial for the system to realize large periodic motion. The research provides theoretical guidance for the design of piezoelectric energy harvesters for different excitation conditions.

A Method for Parameter Identification of Composite Beam Piezoelectric Energy Harvester.

This paper proposes a parameter identification method for the multiparameter identification study of the linear-arch composite beam piezoelectric energy harvester. According to the voltage response characteristics of the system under short-circuit conditions, the mechanical equation is solved by transient excitation, combined with the backbone curve theory and logarithmic attenuation method, to obtain the system's linear damping, linear stiffness, and nonlinear stiffness. According to the voltage response characteristics of the system under open-circuit conditions, combined with the electrical equations, the system electromechanical coupling coefficient and equivalent capacitance coefficient are obtained; numerical simulation results show that the identification parameters have good accuracy. Finally, an experimental platform was built for verification, and the results show that the method has high accuracy and practicability.

Time-Domain Dynamic Characteristics Analysis and Experimental Research of Tri-Stable Piezoelectric Energy Harvester.

In order to explore the dynamic characteristics of the linear-arch beam tri-stable piezoelectric energy harvester (TPEH), a magnetic force model was established by the magnetic dipole method, and the linear-arch composite beam nonlinear restoring force model was obtained through experiments. Based on the Euler-Bernoulli beam theory, a system dynamic model is established, and the influence of the horizontal distance, vertical distance and excitation acceleration of magnets on the dynamic characteristics of the system is simulated and analyzed. Moreover, the correctness of the theoretical results is verified by experiments. The results show that the system can be mono-stable, bi-stable and tri-stable by adjusting the horizontal or vertical spacing of the magnets under proper excitation. The potential well of the system in the tri-stable state is shallow, and it is easier to achieve a large-amplitude response. Increasing the excitation level is beneficial for the large-amplitude response of the system. This study provides theoretical guidance for the design of linear-arch beam TPEH.

A Curve-Shaped Beam Bistable Piezoelectric Energy Harvester with Variable Potential Well: Modeling and Numerical Simulation.

To improve the energy harvesting performance of an energy harvester, a novel bistable piezoelectric energy harvester with variable potential well (BPEH-V) is proposed by introducing a spring to the external magnet from a curve-shaped beam bistable harvester (CBH-C). First, finite element simulation was performed in COMSOL software to validate that the curved beam configuration was superior to the straight beam in power generation performance, which benefits energy harvesting. Moreover, the nonlinear magnetic model was obtained by using the magnetic dipoles method, and the nonlinear restoring force model of the curve-shaped beam was acquired based on fitting the experimental data. The corresponding coupled governing equations were derived by using generalized Hamilton's principle, the dynamic responses were obtained by solving the coupling equations with the ode45 method. Finally, the numerical simulations showed that the proposed harvester can make interwell oscillations easier due to the spring being efficiently introduced to pull down the potential barrier compared with the conventional bistable harvester. Spring stiffness has a great impact on characteristics of the system, and a suitable stiffness contributes to realize large-amplitude interwell oscillations over a wide range of excitation, especially in the low excitation condition.

Controllable design of a nano-bio aptasensing interface based on tetrahedral framework nucleic acids in an integrated microfluidic platform.

The limited reaction time and sample volume in the confined space of microfluidic devices give considerable importance to the development of more effective biosensing interfaces. Herein, the self-assembling of tetrahedral framework nucleic acids (FNAs) with controllable size on the interface of the microfluidic microchannels is studied. Compared with macroscopic turbulence control on traditional micro-structured microfluidic surface, the novel FNA-engineered microfluidic interface successfully constructs a 3D reaction space at nanoscale by raising DNA probes away from the surface. This FNA interface dramatically improves the reaction kinetics during molecular recognition due to extremely ordered orientation, configuration and density of DNA probes on the surface. Finally, the FNA-engineered interface is applied in a novel multi-functional microfluidic platform, towards a "one-stop" assay of Escherichia coli O157: H7 (E. coli O157: H7), integrating capture, release, enrichment, cell culture and antimicrobial susceptibility testing (AST). With the FNA-aptamer probe, we achieved an enhanced bacterial detecting efficiency (10 CFU/mL) plus excellent selectivity and precision. The appicability was strongly demonstrated when the biosensor was successfully applied in real samples, including the analysis of antibiotic susceptibility and minimum inhibitory concentration (MIC) of E. coli O157: H7 among different antibiotics. The application of FNA interface will open a wide avenue for the development of microfluidic biosensors for other pathogenic microorganisms or circulating tumor cells (CTC) simply by changing the aptamers.

Terminal-conjugated non-aggregated constraints of gold nanoparticles on lateral flow strips for mobile phone readouts of enrofloxacin.

Antibiotics abuse now poses a global threat to public health. Monitoring their residual levels as well as metabolites are of great importance, still challenges remain in in situ tracing during the circulation. Herein, taking the typical antibacterial Enrofloxacin (ENR) as a subject, a paper-based aptasensor was tailored by manipulating a duo of aptameric moieties to "sandwich" the target in a lateral-flow regime. To visualize the tight-binding sandwich motif more vividly, an irregular yet robust DNA-bridged gold nanoparticles (AuNPs) proximity strategy was developed with recourse to terminal deoxynucleotidyl transferase, of which the nonaggregate constraining feature was unveiled via optical absorption and scanning probe topography. This complex performed exceptionally better in the test strip context than single-particle tags, leading to an enhanced on-chip focusing. Rather than qualitative color developing, further efforts were taken to visualize the readouts in a quantitative manner by exploiting the smartphone camera for pattern recognition along with data processing in a professional App. Overall, this prototyped contraption realized a rapid and ultrasensitive quantification of ENR down to 0.1 µg/L along with a broad linear range over 5 orders of magnitude, plus excellent selectivity and precision even for real samples. Such innovative fusion across DNA-structured nanomanufacturing and intelligent perception provides a prospective and invigorating solution to point-of-care inspection.

Decarboxylation-promoted Pd-catalyzed asymmetric propargylic [3 + 2] annulation for the enantioselective construction of a quaternary stereocenter in 2,3-dihydrofurans.

The enantioselective construction of a quaternary stereocenter in 2,3-dihydrofuran frameworks has been realized via the palladium-catalyzed asymmetric [3 + 2] cycloaddition of tertiary propargylic carbonates with ß-ketoesters enabled by a chiral ferrocene/benzimidazole-based bidentate P,N-ligand. The reaction was significantly promoted by loss of CO2 to irreversibly form π-propargylpalladium or allenylpalladium intermediates. This protocol features a good tolerance of functional groups in both tertiary propargylic carbonates and ß-ketoesters, thereby delivering a variety of highly functionalized chiral 2,3-dihydrofurans bearing a quaternary stereocenter at the 2-position and an exocyclic double bond at the 3-position in good chemical yields and high enantioselectivities (up to 98% ee).

Chiral Ferrocenyl P,N-Ligands for Palladium-Catalyzed Asymmetric Formal [3 + 2] Cycloaddition of Propargylic Esters with ß-Ketoesters: Access to Functionalized Chiral 2,3-Dihydrofurans.

A highly enantioselective palladium-catalyzed [3 + 2] cycloaddition of propargylic esters with ß-ketoesters has been realized by employing a newly developed chiral ferrocene/benzimidazole-based P,N-ligand. This protocol features a good tolerance of functional groups in both propargylic esters and ß-ketoesters, thereby delivering a variety of highly functionalized chiral 2,3-dihydrofurans bearing an exocyclic double bond at the 3-position in good yields and with high enantioselectivities (up to 98% ee).

Enantioselective Copper-Catalyzed Formal [4 + 2] Cycloaddition of o-Aminophenol Derivatives with Propargylic Esters for Synthesis of Optically Active 3,4-Dihydro-2H-1,4-benzoxazines.

The first copper-catalyzed asymmetric formal [4 + 2] cycloaddition of o-aminophenol derivatives with propargylic esters as the bis-electrophilic C2 synthons for the stereoselective construction of chiral 2,3,4-trisubstituted 2H-1,4-benzoxazines bearing an exocyclic double bond has been developed. By using a structurally modified chiral ketimine P,N,N-ligand, a wide range of optically active 2H-1,4-benzoxazines were prepared in high yields and with excellent enantioselectivities (up to 97% ee).

Highly diastereo- and enantioselective copper-catalyzed propargylic alkylation of acyclic ketone enamines for the construction of two vicinal stereocenters.

The first highly diastereo- and enantioselective propargylic alkylation of acyclic ketone enamines to form vicinal tertiary stereocenters has been reported by employing copper catalysis in combination with a bulky and structurally rigid tridentate ketimine P,N,N-ligand.

Enantioselective synthesis of highly functionalized dihydrofurans through copper-catalyzed asymmetric formal [3+2] cycloaddition of ß-ketoesters with propargylic esters.

An enantioselective synthesis of highly functionalized dihydrofurans through a copper-catalyzed asymmetric [3+2] cycloaddition of ß-ketoesters with propargylic esters has been developed. With a combination of Cu(OTf)2 and a chiral tridentate P,N,N ligand as the catalyst, a variety of 2,3-dihydrofurans bearing an exocyclic double bond at the 2 position were obtained in good chemical yields and with good to high enantioselectivities. The exocyclic double bond can be hydrogenated in a highly diastereoselective fashion to give unusual cis-2,3-dihydrofuran derivatives, thus further enhancing the scope of this transformation.

Enantioselective copper-catalyzed decarboxylative propargylic alkylation of propargyl ß-ketoesters with a chiral ketimine P,N,N-ligand.

The first enantioselective copper-catalyzed decarboxylative propargylic alkylation has been developed. Treatment of propargyl ß-ketoesters with a catalyst, prepared in situ from [Cu(CH3 CN)4 BF4 ] and a newly developed chiral tridentate ketimine P,N,N-ligand under mild reaction conditions, generates ß-ethynyl ketones in good yields and with high enantioselectivities without requiring the pregeneration of ketone enolates. This new process provides facile access to a range of chiral ß-ethynyl ketones in a highly enantioenriched form.

Highly enantioselective copper-catalyzed propargylic substitution of propargylic acetates with 1,3-dicarbonyl compounds.

A chiral tridentate ketimine P,N,N-ligand has been successfully applied in the copper-catalyzed enantioselective propargylic substitution of propargylic acetates with a variety of ß-dicarbonyl compounds, in which excellent enantioselectivities (up to >99% ee) and high yields have been obtained.