Dual-Aptamer Recognition of DNA Logic Gate Sensor-Based Specific Exosomal Proteins for Ovarian Cancer Diagnosis.

Clinical diagnosis of ovarian cancer lacks high accuracy due to the weak selection of specific biomarkers along with the circumstance biomarkers localization. Clustering analysis of proteins transported on exosomes enables a more precise screening of effective biomarkers. Herein, through bioinformatics analysis of ovarian cancer and exosome proteomes, two coexpressed proteins, EpCAM and CD24, specifically enriched, were identified, together with the development of an as-derived dual-aptamer targeted exosome-based strategy for ovarian cancer screening. In brief, a DNA ternary polymer with aptamers targeting EpCAM and CD24 was designed to present a logic gate reaction upon recognizing ovarian cancer exosomes, triggering a rolling circle amplification chemiluminescent signal. A dynamic detection range of 6 orders of magnitude was achieved by quantifying exosomes. Moreover, for clinical samples, this strategy could accurately differentiate exosomes from healthy persons, other cancer patients, and ovarian cancer patients, enabling promising in situ detection. By accurately selecting biomarkers and constructing a dual-targeted exosomal protein detection strategy, the limitation of insufficient specificity of traditional protein markers was circumvented. This work contributed to the development of exosome-based prognosis monitoring in ovarian cancer through the identification of disease-specific exosome protein markers.

Metal-organic framework-based ratiometric point-of-care testing for quantitative visual detection of nitrite.

Nitrite (NO2-) is categorized as a carcinogenic substance and is subjected to severe limitations in water and food. To safeguard the public's health, developing fast and convenient methods for determination of NO2- is of significance. Point-of-care testing (POCT) affords demotic measurement of NO2- and shows huge potential in future technology beyond those possible with traditional methods. Here, a novel ratiometric fluorescent nanoprobe (Ru@MOF-NH2) is developed by integrating UiO-66-NH2 with tris(2,2'-bipyridyl)ruthenium(II) ([Ru(bpy)3]2+) through a one-pot approach. The special diazo-reaction between the amino group of UiO-66-NH2 and NO2- is responsible for the report signal (blue emission) with high selectivity and the red emission from [Ru(bpy)3]2+ offers the reference signal. The proposed probe shows obviously distinguishable color change from blue to red towards NO2- via naked-eye. Moreover, using a smartphone as the detection device to read color hue, ultra-sensitive quantitative detection of NO2- is achieved with a low limit of detection at 0.6 µΜ. The accuracy and repeatability determined in spiked samples through quantitative visualization is in the range of 105 to 117% with a coefficient of variation below 4.3%. This POCT sensing platform presents a promising strategy for detecting NO2- and expands the potential applications for on-site monitoring in food and environment safety assessment.

An ATMND/SGI based three-way junction ratiometric fluorescent probe for rapid and sensitive detection of bleomycin.

In this work, we developed a rapid and sensitive label-free ratiometric fluorescent (FL) probe for the detection of bleomycin (BLM). The probe consists of a DNA sequence (D6) and two fluorophore groups, 2-amino-5,6,7-trimethyl-1,8-naphthalene (ATMND) and SYBR Green I (SGI). The D6 sequence could be folded into a three-way junction structure containing a C-C mismatch position in the junction pocket. The unique "Y" structure not only could entrap ATMND in the mismatch pocket with high affinity, leading to FL quenching at 408 nm, but also embed SGI in the grooves of the double-stranded portion, resulting in FL enhancement at 530 nm. In the presence of BLM-Fe(II), the "Y" structure of D6 was destroyed due to the specific cleavage of the BLM recognition site, the 5'-GT-3' site in D6. This caused the release of ATMND and SGI and thus the ratiometric signal change of FL enhancement by ATMND and FL quenching by SGI. Under optimal conditions, the ratiometric probe exhibited a linear correlation between the intensity ratio of F408/F530 and the concentration of BLM in the range of 0.5-1000 nM, with a detection limit of 0.2 nM. In addition, the probe was applied to detect BLM in human serum samples with satisfactory results, indicating its good clinical application potential.

Study on Reaction Mechanism and Process Safety for Epoxidation.

The reaction mechanism and process safety for epoxidation were investigated in this study. 1-(2-Chlorophenyl)-2-(4-fluorophenyl)-3-(1,2,4-triazole) propene (triazolene), a typical representative of high steric olefinic compounds, was chosen as the raw material. In addition, hydrogen peroxide was chosen as the oxygen source in the reaction. Online Raman spectroscopy combined with high-performance liquid chromatography (HPLC) was used for the process monitoring analysis. The results of this study indicated that the epoxidation process is exothermic, and the apparent reaction heat was 1340.0 kJ·kg-1 (measured by the mass of triazolene). The heat conversion rate was 39.7% immediately after hydrogen peroxide dosing to a triazolene and maleic anhydride mixture solution in chloroform. This result indicated that a considerable amount of heat is accumulated during the epoxidation reaction, which leads to a potential high safety concern. The study of the reaction mechanism showed that maleic anhydride reacts with hydrogen peroxide quickly to form maleic acid peroxide, which is controlled by hydrogen peroxide feeding, and the formed maleic acid peroxide further reacts with triazolenes slowly, which is a kinetically controlled reaction. Decomposition kinetics studies revealed that the temperatures corresponding to the time of maximum reaction rate for 8 and 24 h are TD24 = 89.9 °C and TD8 = 104.1 °C, respectively.

Ratiometric fluorescence determination of alkaline phosphatase activity based on carbon dots and Ce3+-crosslinked copper nanoclusters.

A new ratiometric fluorescent probe for efficient determination of ALP was developed. The probe was constructed by combining Ce3+-crosslinked copper nanoclusters (Ce3+-CuNCs) which exhibit the aggregation-induced emission (AIE) feature with carbon dots (CDs). The introduction of phosphate (Pi) induced the generation of CePO4 precipitation, resulting in significant decrease of fluorescence emission of CuNCs at 634 nm. At the same time, the fluorescence of CDs at 455 nm was obviously enhanced, thus generating ratiometric fluorescence response. Based on the fact that the hydrolysis of pyrophosphate (PPi) by ALP can produce Pi, the CD/Ce3+-CuNCs ratiometric probe was successfully used to determine ALP. A good linear relationship between the ratiometric value of F455/F634 and ALP concentrations ranging from 0.2 to 80 U·L- 1 was obtained, with a low detection limit of 0.1 U·L- 1. The ratiometric responses of the probe resulted in the visible fluorescence color change from orange red to blue with the increase of ALP concentration. The smartphone-based RGB recognition of the fluorescent sample images was used for ALP quantitative determination. A novel ratiometric fluorescent system based on Ce3+-CuNCs with AIE feature and CDs were constructed for efficient detection of ALP.

Responsive calcium-derived nanoassemblies induce mitochondrial disorder to promote tumor calcification.

Physiological calcification of the treated tumor area is considered to be a predictor of good prognosis. Promoting tumor calcification by inducing mitochondrial metabolic disorder and destroying calcium equilibrium has a potential inhibitory effect on tumor proliferation. Here, by promoting calcification by inducing mitochondrial dysfunction combined with triggering a surge of reactive oxygen species, we construct a bioresponsive calcification initiator, termed CaP-AA, using CaHPO4 covalently doped l-ascorbic acid. CaHPO4 releases Ca2+ within the cytoplasm of tumor cells to trigger calcium overload. Meanwhile, exogenous l-ascorbic acid indirectly enhances metabolic balance disruption via pro-oxidant effects. Such Ca2+ overload increases the likelihood of tumor calcification in vivo for tumor inhibition by perturbing mitochondrial homeostasis. The introduction of responsive calcium sources that would, in turn, trigger intratumoral calcification mediated by perturbing mitochondrial homeostasis would be an effective regulatory strategy for tumor therapy.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold CmiR-21 > CmiR-892b, the CAR-CHA-HCR circuit performs a compute-and-release operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.

Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.

Entanglement Purification for Logic-Qubit of Photon System Based on Parity Check Measurement Gate.

It has been found that logic-qubit entanglement has great potential for applications in quantum communication and quantum networks in recent years. However, along with the effects of noise and decoherence, the fidelity of the communication transmission can be greatly reduced. In this paper, we investigate the entanglement purification of logic bit-flip error and phase-flip error in polarization logic-qubit entanglement based on the parity-check measurement (PCM) gate, which is constructed by the cross-Kerr nonlinearity and used to distinguish the parity information of two-photon polarization states. The probability of entanglement purification is higher than the scheme using the linear optical method. Moreover, the quality of logic-qubit entangled states can be improved by a cyclic purification process. This entanglement purification protocol will be useful in the future when faced with long-distance communication with logic-qubit entanglement states.

Promoting sensitive colorimetric detection of hydroquinone and Hg2+ via ZIF-8 dispersion enhanced oxidase-mimicking activity of MnO2 nanozyme.

Reducing the agglomeration and improving the dispersibility in water of two-dimensional (2D) nanozymes is one of the effective ways to improve their enzyme-like activity. In this work, we propose a method by constructing zeolitic imidazolate framework-8 (ZIF-8)-dispersed 2D manganese-based nanozymes to achieve the specific regulated improvement of oxidase-mimicking activity. By in-situ growth of manganese oxides nanosheets of MnO2(1), MnO2(2) and Mn3O4 on the surface of ZIF-8, the corresponding nanocomposites of ZIF-8 @MnO2(1), ZIF-8 @MnO2(2), and ZIF-8 @Mn3O4 were prepared at room temperature. The Michaelis-Menton constant measurements indicated that ZIF-8 @MnO2(1) exhibits best substrate affinity and fastest reaction rate for 3,3',5,5'-tetramethylbenzidine (TMB). The ZIF-8 @MnO2(1)-TMB system was exploited to detection of trace hydroquinone (HQ) based on the reducibility of phenolic hydroxyl groups. In addition, by employing the fact that the cysteine (Cys) with the excellent antioxidant capacity can bind the Hg2+ based on the formation of "S-Hg2+" bonds, the ZIF-8 @MnO2(1)-TMB-Cys system was applied to detection of Hg2+ with high sensitivity and selectivity. Our findings not only provide a better understanding of the relationship between dispersion of nanozyme and enzyme-like activity, but also provide a general method for the detection of environmental pollutants using nanozymes.

Dual trace gas detection using a compact two-channel multipass cell with dense and line spot patterns.

A highly sensitive dual-gas sensor based on a two-channel multipass cell (MPC) was designed and developed for simultaneous detection of atmospheric methane (CH4) and carbon dioxide (CO2) by using two distributed feedback lasers emitting at 1653 nm and 2004 nm. The nondominated sorting genetic algorithm was applied to intelligently optimize the MPC configuration and accelerate the dual-gas sensor design process. A compact and novel two-channel MPC was used to achieve two optical path lengths of 27.6 m and 2.1 m in a small volume of 233 cm3. Simultaneous measurements of CH4 and CO2 in the atmosphere were performed to demonstrate the stability and robustness of the gas sensor. According to the Allan deviation analysis, the optimal detection precision for CH4 and CO2 was 4.4 ppb at an integration time of 76 s and 437.8 ppb at an integration time of 271 s, respectively. The newly developed dual-gas sensor exhibits superior characteristics of high sensitivity and stability, cost-effectiveness and simple structure, which make it well-suited for multiple trace gas sensing in various applications, including environmental monitoring, safety inspections and clinical diagnosis.

Optical design of Lissajous pattern multipass cells with multiple spherical mirrors based on particle swarm optimization.

We propose a method to intelligently design and optimize a multiple-spherical-mirror-based multipass cell (MPC) with Lissajous patterns. The MPC consists of at least three spherical mirrors, which are placed in a rotationally symmetric arrangement. Particle swarm optimization (PSO) is performed to optimize the parameters of the MPC configurations and accelerate the design process. Two Lissajous patterned MPCs with three and five mirrors are built and tested experimentally. We further develop an open-path gas sensor based on a five-mirror-based MPC to detect methane concentrations in ambient laboratory air, and a detection precision of 1.1 ppb with a 123 s averaging time is realized. The PSO algorithm is efficient for optimizing the proposed MPC, which has superior proprieties of symmetry configuration, cost-effectiveness and high detection sensitivity and is well suited for trace gas sensing applications.

Silver ion-regulated ratiometric fluorescence assay for alkaline phosphatase detection based on carbon dots and o-phenylenediamine.

In this work, a novel silver ion (Ag+)-regulated ratiometric fluorescence method for the effective and sensitive determination of alkaline phosphatase (ALP) was established based on carbon dots (CDs) and o-phenylenediamine (OPD). OPD can be oxidized by Ag+ to generate fluorescent 2, 3-diaminophenazine (DAP). Thus, based on inner-filter effect (IFE) or/and fluorescence resonance energy transfer (FRET) between CDs and DAP, the CDs-Ag+-OPD system can generate dual-emission at 454 nm and 570 nm respectively when excited at 360 nm. The introduction of ascorbic acid (AA) can react with Ag+ to produce dehydroascorbic acid (DHAA), which inhibits the generation of DAP, resulting in the fluorescence decrease at 570 nm and fluorescence recovery of CDs at 454 nm. Meanwhile, DHAA can react with OPD to generate quoxaline (QX), which emits strong blue fluorescence at 440 nm, further inhibiting the IFE or/and FRET between CDs and DAP. An obvious ratiometric fluorescence response was observed with the increase of the concentration of AA introduced. Due to the fact that AA can be generated by the enzyme catalysis reaction between ALP and 2-phospho-l-ascorbic acid (AAP), the CDs-Ag+-OPD ratiometric system was applied to the determination of ALP successfully. The ratiometric fluorescence value of F454/F570 increases with increasing ALP concentration, with a linear range of 0.2 to 40 U/L and detection limit of 0.1 U/L. In addition, the CDs-Ag+-OPD ratiometric system was successfully applied to the detection of ALP in human serum samples.

Decomposition-based multiobjective optimization for multipass cell design aided by particle swarm optimization and the K-means algorithm.

We proposed a method to intelligently design two-spherical-mirror-based multipass cells (MPCs) and optimize multiple objectives simultaneously. By integrating the K-means algorithm into the particle swarm optimization (PSO) algorithm, an efficient method is developed to optimize MPC configurations possessing characteristics of both long optical path lengths (OPLs) and circle patterns. We built and tested an MPC with four concentric circle patterns, which achieved an OPL of 54.1 m in a volume of 273.1 cm3. We demonstrated the stability and detection precision of the developed gas sensor. Continuous measurement of methane in ambient laboratory air was realized, with a detection precision of 8 ppb and an averaging time of 13 s. The combination of K-means and PSO algorithms is effective in optimizing MPCs with multiple objectives, which makes it suitable for designing versatile MPCs satisfying various requirements of field applications, including pollution and greenhouse gas emission monitoring and high-sensitivity measurements of other trace gases.

Long-wavelength emission carbon dots as self-ratiometric fluorescent nanoprobe for sensitive determination of Zn2.

A novel ratiometric fluorescence nanoprobe based on long-wavelength emission carbon dots (CDs) was designed for high sensitive and selective detection of Zn2+. The CDs were conveniently prepared by a one-step solvothermal treatment of formamide and glutathione (GSH). Under single excitation wavelength (420 nm), the obtained CDs exhibit three emission peaks at 470, 650, and 685 nm, respectively. For the long-wavelength emission region of the CDs, the fluorescence at 685 nm can be quenched with different levels upon the addition of most metal ions. However, the presence of Zn2+ not only results in the fluorescence quenching at 685 nm effectively but also enhances at 650 nm remarkably, which may be due to the formation of CD-Zn2+ chelate complex inducing the dispersion of CDs aggregates and changes in the group distribution on the surface of CDs. Taking the advantage of the unique fluorescence response induced by Zn2+, the prepared CDs were successfully employed as nanoprobe for self-ratiometric fluorescence determination of Zn2+ with F650/F685 as signal output. A good linear relationship in the concentration range 0.01 to 2 µM, and a detection limit as low as 5.1 nM has been obtained. The ratiometric nanoprobe was successfully applied to  Zn2+ determination  in human serum samples.

Subjective and objective risk perceptions and the willingness to pay for agricultural insurance: evidence from an in-the-field choice experiment in rural China.

We conducted in-the-field choice experiments in China to investigate farmers' willingness to pay for crop insurance and to determine how objective and subjective beliefs affect Willingness to Pay (WTP). We deploy three variants of the choice experiment using a priming mechanism on objective and subjective beliefs plus a control. We find that the cuing frame matters in that there are differences in WTP within five attributes and across variants. In terms of practical policy, our results suggest that farmers' frame of reference toward objective and subjective risks can affect insurance demand.

Combination of pipette tip solid phase extraction and high performance liquid chromatography for determination of plant growth regulators in food samples based on the electrospun covalent organic framework/polyacrylonitrile nanofiber as highly efficient sorbent.

Facile and sensitive determination of plant growth regulators (PGRs) in food samples is important but still remains great challenge. Herein, a pipette tip solid phase extraction (PT-SPE) method was developed for fast and sensitively detecting PGRs. The PT-SPE adsorbent was prepared by integrating a novel covalent organic framework (COF) of schiff base network 3 (SNW-3) and polyacrylonitrile (PAN) through electrospinning. The SNW-3 can easily adsorb PGRs with high special affinity through electrovalent bands between the ammonium ions of SNW-3 and the carboxy groups of PGRs. The polymer of PAN acts as scaffold material for SNW-3, which can lower seepage pressure hence accelerates adsorption/desorption kinetics. By combination with HPLC-DAD, a satisfactory method was successfully developed for simultaneous determination of ten PGRs in watermelon. Good analytical performances were achieved with this proposed method, including good linearity (5-500 ng/mL) with high correlation coefficients (R ≥ 0.9981), low limits of detection (S/N = 3, 0.24-3.19 ng/mL) and limits of quantification (S/N = 10, 1.65-5.72 ng/mL), satisfactory precision (intra-day RSDs ≤ 2.7%, inter-day RSDs ≤ 3.7%), and high accuracy (recovery: 82.8-113.0%). The method developed in this study shows high potential for design of high target-affinity adsorbents for food sample preparing.

Generalized optical design and optimization of multipass cells with independent circle patterns based on the Monte Carlo and Nelder-Mead simplex algorithms.

In this paper, we propose an automatic approach to optimize the multipass cell (MPC) design with independent circle patterns. First, the Monte Carlo algorithm is performed to globally search for the characteristic values of the distance between two mirrors. Second, the Nelder-Mead simplex (NM) algorithm is applied to locally optimize the re-entry condition. In addition, we utilize the clustering method to select the independent circle patterns automatically. Three optimal MPCs with five, seven and nine independent circles are built and tested experimentally. We analyze the stability of the final point for the MPCs and optimize the quality of the output beam based on multi-ray tracing. This type of MPC shows the superior characteristics of compactness, high detection sensitivity, and affordability, has various applications, and can promote the development of portable gas sensors. The proposed approach is effective and efficient for automatically optimizing MPC design and can be further extended to versatile optical designs.

A novel ratiometric fluorescence nanoprobe for sensitive determination of uric acid based on CD@ZIF-CuNC nanocomposites.

A novel ratiometric fluorescence nanoprobe based on carbon dots (CDs) and Cu nanoclusters (CuNCs) was designed for the label-free determination of uric acid (UA). The metal-organic framework (MOF) encapsulated CuNCs (ZIF-CuNC), and nitrogen-doped CDs can self-assemble into well-defined spherical nanocomposites (CD@ZIF-CuNC) due to physical adsorption. Under the excitation wavelength of 360 nm, the CD@ZIF-CuNC nanocomposites exhibit two evident intrinsic emissions peaked at 460 nm (CDs) and 620 nm (ZIF-CuNC), respectively. In the presence of H2O2, the fluorescence of CD@ZIF-CuNC at 620 nm is quenched remarkably within 1 min, while little effect on the emission at 460 nm is observed. Therefore, taking the fluorescence at 620 nm as the report signal and 460 nm as the reference signal, ratiometric quantitative determination of H2O2 was achieved with a linear range of 1-100 µM and a detection limit of 0.30 µM. The CD@ZIF-CuNC nanoprobe was successfully applied to the determination of UA that is catalyzed by uricase to produce H2O2, obtaining the linear range of 1-30 µM and the detection limit of 0.33 µM. Eventually, this strategy has been successfully applied to the determination of UA in human urine samples. A novel and convenient CDs@ZIF-CuNCs-based nanoplatform was constructed for sensitive ratiometric fluorescence determination of UA.

Bioenergy consumption, carbon emissions, and agricultural bioeconomic growth: A systematic approach to carbon neutrality in China.

China is the world's largest fossil fuel consumer and carbon emitter country. In September 2020, China pledged to reduce carbon emissions, and achieve carbon neutrality by 2060. Therefore, this study aimed to contribute to the literature and show the pictorial nexus of bioenergy and fossil fuel consumption, carbon emission, and agricultural bioeconomic growth, a new pathway towards carbon neutrality. For this study, time-series data from 1971 to 2019 were used to analyze the autoregressive distributed lag (ARDL) bound testing and novel dynamic autoregressive distributed lag (DYNARDL) simulation models. Initially, the unit root tests results showed that all variables were stationarity at the level and first difference. The presence of cointegration between selected variables was confirmed by the results from ARDL bound test. In addition, the results of long-run and short-run nexus show an increase in bioenergy consumption that caused an increase in agricultural bioeconomic growth both in the long and short-run nexus. A decrease in fossil fuel consumption was shown to result in increased agricultural bioeconomic growth with respect to both long- and short-term effects. Furthermore, the results of the novel dynamic ARDL simulation model demonstrated that a 10% positive shock from bioenergy consumption caused an increase in agricultural bioeconomic growth, while at the same time, a 10% negative shock in bioenergy consumption led to a decrease. A 10% negative shock from fossil fuels caused an increase in agricultural bioeconomic growth, whereas a 10% positive shock from fossil fuels led to a decrease. Therefore, this study suggests that China needs to switch from fossil fuel and other non-renewable energy consumption to sources of bioenergy and other renewable energy consumption to achieve carbon neutrality by 2060.