Copper-Induced Supramolecular Peptide Assemblies for Multi-Pathway Cell Death and Tumor Inhibition.

Although self-assembly has emerged as an effective tool for fabricating biomaterials, achieving precise control over the morphologies and functionalities of the resultant assemblies remains an ongoing challenge. Inspired by the copper peptide naturally present in human plasma, in this study, we designed a synthetic precursor, FcGH. FcGH can self-assemble via two distinct pathways: spontaneous and Cu2+-induced. These two assembly pathways enabled the formation of assemblies with tunable morphologies by adjusting the amount of added Cu2+. We found that the nanoparticles formed by Cu2+-induced self-assembly exhibited a significantly higher cellular uptake efficiency than the wormlike fibers formed spontaneously. Moreover, this Cu2+-induced assembly process occurred spontaneously at a 1 : 1 molar ratio of Cu2+ to FcGH, avoiding the excessive use of Cu2+ and a tedious preparation procedure. By co-assembling with 10-hydroxycamptothecin (HCPT)-conjugated FcGH, Cu2+-induced supramolecular nanodrugs elicited multiple cell death modalities in cancer cells with elevated immunogenicity, enhancing the therapeutic effect compared to free HCPT. This study highlights Cu2+-induced self-assembly as an efficient tool for directing the assembly of nanodrugs and for synergistic tumor therapy.

Recent Achievements for Flexible Encapsulation Films Based on Atomic/Molecular Layer Deposition.

The purpose of this paper is to review the research progress in the realization of the organic-inorganic hybrid thin-film packaging of flexible organic electroluminescent devices using the PEALD (plasma-enhanced atomic layer deposition) and MLD (molecular layer deposition) techniques. Firstly, the importance and application prospect of organic electroluminescent devices in the field of flexible electronics are introduced. Subsequently, the principles, characteristics and applications of PEALD and MLD technologies in device packaging are described in detail. Then, the methods and process optimization strategies for the preparation of organic-inorganic hybrid thin-film encapsulation layers using PEALD and MLD technologies are reviewed. Further, the research results on the encapsulation effect, stability and reliability of organic-inorganic hybrid thin-film encapsulation layers in flexible organic electroluminescent devices are discussed. Finally, the current research progress is summarized, and the future research directions and development trends are prospected.

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes for Monitoring Mitochondrial Viscosity in Living Cells.

Viscosity, at the subcellular level, plays a crucial role as a physicochemical factor affecting microenvironment homeostasis. Abnormal changes in mitochondrial viscosity often lead to various diseases in the organism. Based on the twisted intramolecular charge transfer mechanism, four hemicyanine dye fluorescent probes (HT-SA, HT-SA-S, HT-Bzh, and HT-NA) were designed and synthesized for viscosity response. The single bond between the nitrogen-containing heterocycle and the carbon-carbon double in the structure of the probe bond served as the viscosity response site. Finally, the probe HT-Bzh was screened as the optimal mitochondrial viscosity probe according to its responsiveness, targeting, and interference resistance. The fluorescence intensity of the probe HT-Bzh increased 22-fold when the viscosity was increased from 13.75 to 811.2 cP. In summary, all four viscosity probes we have developed can be used in different applications depending on the external environment, providing a valuable reference for the design of potential tools to address viscosity monitoring in biological systems.

A ThT Derivative as Zn2+ Sensor Based on DNA G-quadruplex.

In this report, we developed a sensing strategy based on ThT-E (a ThT derivative) and DNA G-quadruplex for the label-free detection of Zn2+. In the absence of Zn2+, there was a fluorescence enhancement of ThT-E by interaction with human telomere sequence. On the addition of Zn2+, Zn2+ induced a more compact antiparallel G-quadruplex to release ThT-E, resulting in fluorescence quenching. The detection limit was 0.6996 µM, and the fluorescence intensity showed a good linear relationship with the concentration of Zn2+ in the range of 0-10 µM. This sensing strategy which only needs to mix two kinds of materials has the characteristics of label-feel, simple operation, short response time, economical and efficient.

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes to Sensitively Respond to HSO3- in Living Cells.

SO2, a gas signaling molecule, can be produced endogenously in mitochondria. Its hydrolysate, HSO3-, plays a key role in food preservation, cardiovascular relaxation, and other fields, suggesting that it is important to achieve its detection. Here, based on the Michael addition mechanism, four hemicyanine dye fluorescent probes (ETN, ETB, STB, and EIB) were designed and synthesized for responding to HSO3-. We evaluated the reaction ability of different probes with HSO3- and tried to explain the reasons for the significantly different response effects between probes and HSO3- according to the structure-activity relationship. The influence of different substituents of probes on the properties of mitochondria-targeting was also discussed. Finally, we screened out ETN as the optimal HSO3- probe due to its high sensitivity, rapid reactivity, and good mitochondria-targeting, and it could sensitively respond to HSO3- in living cells. The LODs of ETN for HSO3- were calculated by both absorption and fluorescence methods, respectively, which were 2.727 and 0.823 µM. Our work provided valuable references for designing strategies and potential tools for response to SO2 derivatives in biosystems.

"One stone, two birds": a mitochondria-targeted fluorescent probe for the detection of viscosity and HSO3- in living cells.

The material transport and physiological events of mitochondria need to be supported by a suitable microenvironment. For example, high viscosity will seriously hinder material exchange, and SO2, as the precursor of HSO3-, is an endogenous signal molecule that plays a key role in information transmission. It is very important to detect viscosity and HSO3- in mitochondria. Here, we developed a dual-responsive fluorescent probe (named Hcy-NT) to image the changes in mitochondrial viscosity and HSO3- in a "killing two birds with one stone" manner. Hcy-NT showed an OFF-ON fluorescence signal for the increase in cell viscosity induced by nystatin, while an ON-OFF fluorescence signal for intracellular and endogenous HSO3-. Its limits of detection for HSO3- were calculated by both absorption and fluorescence methods, which were 1.200 and 1.291 µM, respectively. This work provides a valuable tool for the study of viscosity and HSO3- related physiological processes and the diagnosis of potential diseases.

High-Efficiency CsPbBr3 Light-Emitting Diodes using One-Step Spin-Coating In Situ Dynamic Thermal Crystallization.

All-inorganic perovskite materials (such as CsPbBr3) have received widespread attention because of their better stability than hybrid counterparts, but their poor film morphology and crystalline quality limit their application in perovskite light-emitting devices (PeLEDs). Some previous studies have attempted to improve the morphology and crystalline quality of perovskite films by heating the substrate, but there are still some problems such as inaccurate temperature control, excessive temperature is not conducive to flexible applications, and the mechanism of action is not clear. In this work, we used a one-step spin-coating, low-temperature in situ thermally assisted crystallization process, in which the temperature was accurately monitored using a thermocouple in the range of 23-80 °C, and explored the effect of the in situ thermally assisted crystallization temperature on the crystallization of the all-inorganic perovskite material CsPbBr3 and the performance of PeLEDs. In addition, we focused on the influence mechanism for the in situ thermally assisted crystallization process on the surface morphology and phase composition of the perovskite films and promote its possible application in inkjet printing and scratch coating methods.

Cy3 Cyanine Dye with Strong Fluorescence Enhancement for AGRO100 and Its Derivative.

Nucleic acids, as important substances for biological inheritance, have attracted extensive attention in the biomedical field. More and more cyanine dyes are emerging as one of the probe tools for nucleic acid detection due to their excellent photophysical properties. Here, we discovered that the insertion of the AGRO100 sequence can specifically disrupt the twisted intramolecular charge transfer (TICT) mechanism of the trimethine cyanine dye (TCy3), resulting in a clear "turn-on" response. Moreover, the fluorescence enhancement of TCy3 combined with the T-rich AGRO100 derivative is more obvious. One explanation for the interaction between dT (deoxythymidine) and positively charged TCy3 may be that its outer layer carries the most negative charge. This study provides a theoretical basis for the use of TCy3 as a DNA probe, which has promising applications in the DNA detection of biological samples. It also provides the basis for the following construction of probes with specific ability for recognition.

Advances in the Functional Nucleic Acid Biosensors for Detection of Lead Ions.

Lead ions (Pb2+) are destructive to the natural environment and public health, so the efficient detection of Pb2+ is particularly important. Although the instrumental analysis methods have high accuracy, they require high cost and precise operation, which limits their wide application. Therefore, many strategies have been extensively studied for detecting Pb2+ by biosensors. Functional nucleic acids have become an efficient tool in this field. This review focuses on the recent biosensors of detecting Pb2+ based on functional nucleic acids from 2010 to 2020, in which DNAzyme, DNA G-quadruplex and aptamer will be introduced. The biosensors are divided into three categories that colorimetric, fluorometric and electrochemical biosensors according to the different reported signals. The action mechanism and detection effect of each biosensor are explained. Finally, the present situation of nucleic acid biosensor for the detection of Pb2+ is summarized and the future research direction is prospected.

Recent advances in bioprobes and biolabels based on cyanine dyes.

As a functional dye, cyanine dye promotes the widespread application of bioprobes in the fields of medicine, genetics and environment, owing to its advantages of good photophysical properties, excellent biocompatibility and low toxicity to biological systems. Nowadays, it is mainly used in the fields of life sciences such as fluorescent labeling of biological macromolecules, disease diagnosis, immunoassay and DNA detection, all of which lie at the core of this review. First, we briefly introduced the characteristics and principles of the cyanine dye bioprobe. Afterward, we paid attention to the recent progress of cyanine dye bioprobes widely used in the 10 years from 2010 to 2020. The application of cyanine dyes as bioprobes with different identification elements, including enzymes, organelles, immunity and DNAs, was mainly summarized. Finally, this review gave an outlook on the future development trend of cyanine dye bioprobes. This facilitates the construction of a new type of multifunctional fluorescent probe and promotes its clinical application.

A cysteine and Hg2+ detection method based on transformation supramolecular assembly of cyanine dye by AGRO100.

ETC (3,3'-di(3-sulfopropyl)-4,5,4',5'-dibenzo-9-ethylthiacarbocyanine triethylammonium salt), as a derivative of thiazole, is capable of forming various aggregates by the short-range noncovalent interaction forces under specific conditions, accompanying with significant absorbance and fluorescence characteristics. In this work, a label-free probe (ETC) for the detection of Cys (Cysteine) and Hg2+ was developed based on transformation between monomers and J-aggregations by AGRO100. AGRO100 can transform between single-stranded DNA and G-quadruplex to realize recognition of Cys and Hg2+ in dual-channel mode. These recognitional signals can be captured by UV-visible absorption spectra and fluorescence spectroscopy. ETC exhibits high sensitivity and selectivity with the detection limit of 0.197 nM in a wide range of 0-15 µM, which can apply of Cys and Hg2+ detection in human serum.

Analysis of the Effect of Graphene, Metal, and Metal Oxide Transparent Electrodes on the Performance of Organic Optoelectronic Devices.

Transparent electrodes (TEs) are important components in organic optoelectronic devices. ITO is the mostly applied TE material, which is costly and inferior in mechanical performance, and could not satisfy the versatile need for the next generation of transparent optoelectronic devices. Recently, many new TE materials emerged to try to overcome the deficiency of ITO, including graphene, ultrathin metal, and oxide-metal-oxide structure. By finely control of the fabrication techniques, the main properties of conductivity, transmittance, and mechanical stability, have been studied in the literatures, and their applicability in the potential optoelectronic devices has been reported. Herein, in this work, we summarized the recent progress of the TE materials applied in optoelectronic devices by focusing on the fabrication, properties, such as Graphene, ultra-thin metal film, and metal oxide and performance. The advantages and insufficiencies of these materials as TEs have been summarized and the future development aspects have been pointed out to guide the design and fabrication TE materials in the next generation of transparent optoelectronic devices.

Evaluation of analytic and clinical performance of two immunoassays for detecting thyroid-stimulating receptor antibody in the diagnosis of Graves' disease.

OBJECTIVE: To evaluate the analytical and clinical performance of two immunoassays for diagnosis of Graves' disease (GD), the Immulite thyroid-stimulating immunoglobulin (TSI), and Elecsys Anti-TSH receptor (TSHR) assay. METHODS: Precision and analytical measurement range were assessed using pooled samples of patients. The comparison between the two methods was evaluated using 579 clinical samples, and receiver operating characteristic (ROC) curves were drawn using the final diagnosis as reference. Clinical sensitivity and specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the two tests. RESULTS: The repeatability and intermediate imprecision coefficient of variation (CV%) of the TSI assay were 3.8% and 4.1% at 0.95 IU/L, and 3.5% and3.6% at 19.5 IU/L, respectively. The assays were linear over a range 0.27-38.5 IU/L. There was a high correlation between the quantitative results of the two methods (correlation coefficient r = 0.930). The cut-off value obtained by ROC analysis for TSI assay was 0.7 IU/L with sensitivity of 93.7% and specificity of 85.1%. An overall qualitative agreement of 91.5% between two methods was observed. Among 44 patients with discordant qualitative results, the TSI assay provided more satisfactory results consistent with clinical diagnoses. CONCLUSION: The TSI assay showed excellent analytical performance and provided a high PPV for GD.

Establishment of reference intervals of monomeric prolactin to identify macroprolactinemia in Chinese patients with increased total prolactin.

BACKGROUND: Macroprolactin is responsible for pseudohyperprolactinemia and is a common pitfall of the prolactin immunoassay. We aimed to determine the frequency of macroprolactinemia in Chinese hyperprolactinemic patients using monomeric prolactin discriminated by precipitation with polyethylene glycol (PEG). METHODS: Post-PEG monomeric prolactin gender-specific reference intervals were established for the Elecsys immunoassay method (Roche Diagnostics) using sera from healthy female (n = 120) and male (n = 120) donors. The reference intervals were validated using 20 macroprolactinemic (as assessed by gel filtration chromatography (GFC)) sera samples, and presence of monomeric prolactin was discriminated by GFC. Patients with high total prolactin were then screened by PEG precipitation to analyze macroprolactin. The demographic and biochemical details of patients with true hyperprolactinemia and macroprolactinemia were compared. RESULTS: Reference intervals for monomeric prolactin in females and males were 3.4-18.5 and 2.7-13.1 ng/mL, respectively. Among 1140 hyperprolactinemic patients, macroprolactinemia was identified in 261 (22.9 %) patients while the other 879 (77.1 %) patients were diagnosed with true hyperprolactinemia. Menstrual disturbances were the most common clinical feature in both groups. Galactorrhea, amenorrhea, and visual disturbances occurred more frequently in true hyperprolactinemic patients (P < 0.05). CONCLUSIONS: The prevalence of macroprolactin in Chinese patients with hyperprolactinemia was described for the first time. Monomeric prolactin concentration, along with a reference interval screening with PEG precipitation, provides a diagnostic approach for hyperprolactinemia with improved accuracy.

Adaptive bilateral filter for sharpness enhancement and noise removal.

In this paper, we present the adaptive bilateral filter (ABF) for sharpness enhancement and noise removal. The ABF sharpens an image by increasing the slope of the edges without producing overshoot or undershoot. It is an approach to sharpness enhancement that is fundamentally different from the unsharp mask (USM). This new approach to slope restoration also differs significantly from previous slope restoration algorithms in that the ABF does not involve detection of edges or their orientation, or extraction of edge profiles. In the ABF, the edge slope is enhanced by transforming the histogram via a range filter with adaptive offset and width. The ABF is able to smooth the noise, while enhancing edges and textures in the image. The parameters of the ABF are optimized with a training procedure. ABF restored images are significantly sharper than those restored by the bilateral filter. Compared with an USM based sharpening method-the optimal unsharp mask (OUM), ABF restored edges are as sharp as those rendered by the OUM, but without the halo artifacts that appear in the OUM restored image. In terms of noise removal, ABF also outperforms the bilateral filter and the OUM. We demonstrate that ABF works well for both natural images and text images.