Colorimetric aptasensor based on magnetic beads and gold nanoparticles for detecting mucin 1.

In this work, a colorimetric aptasensor based on magnetic beads (MBs), gold nanoparticles (AuNPs) and Horseradish Peroxidase (HRP) was prepared for the detection of mucin 1 (MUC1). Complementary DNA of the MUC1 aptamer (Apt) immobilized on the MBs was combined with the prepared AuNPs-Apt-HRP complex (AuNPs@Apt-HRP). In the presence of MUC1, it specifically bound to Apt, resulting in the detachment of gold nanoparticles from the MBs. After magnetic separation, AuNPs@Apt-HRP was separated into the supernatant and reacted with 3,3',5,5'-Tetramethylbenzidine (TMB) to produce color reaction from colorless to blue. The linear range of MUC1 was from 75 to 500 µg/mL (R2 = 0.9878), and the detection limit was 41.95 µg/mL. The recovery rate of MUC1 in human serum was 99.18 %∼101.15 %. This method is simple and convenient. Moreover, it does not require complex and expensive equipment for detection of MUC1. It provides value for the development of MUC1 colorimetric sensors and a promising strategy for the determination of MUC1 in clinical diagnosis.

Corrigendum: A Novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma.

[This corrects the article DOI: 10.3389/fgene.2022.1068837.].

Regio- and stereoselective syntheses of chiral α-quaternary (Z)-trisubstituted allylic amino acids via synergistic Pd/Cu catalysis.

Synergistic palladium/copper catalysis for asymmetric allylic alkylation of vinylethylene carbonates with aldimine esters has been developed for the synthesis of α-quaternary (Z)-trisubstituted allylic amino acids under mild conditions. This methodology features broad substrate compatibilities in yields of up to 87% and up to 94% ee. A facile scale-up and straightforward conversion to 1,2,3,5-tetrasubstituted pyrrole and 1,2,5,6-tetrahydropyridine bearing chiral quaternary carbon centers verifies the synthetic utility of this method.

An electrochemical biosensor for the detection of aflatoxin B1 based on the specific aptamer and HCR biological magnification.

Aflatoxin B1 (AFB1) is a highly toxic mycotoxin, which causes severe acute or cumulative poisoning. Therefore, it is important to develop sensitive and selective detection methods for AFB1 for the safety of food and medicinal herbs. Herein, we have developed a "signal-on" electrochemical aptasensor based on the high specificity of the aptamer and hybridization chain reaction (HCR) biological amplification for AFB1 detection. In this work, thiol-modified complementary DNA (cDNA) immobilized on the surface of a gold electrode (GE) served as an initiator DNA. When AFB1 was present, it competed with the cDNA for binding to the aptamers, which resulted in the detaching of aptamers from the cDNA-aptamer duplexes. Then, the single-stranded cDNA acted as an initiator to trigger the HCR signal amplification. Therefore, long double-stranded DNA (dsDNA) products were produced, which could load large amounts of methylene blue (MB) molecules to generate a distinct electrochemical signal. Under the optimized conditions, the proposed electrochemical aptasensor achieved the ultrasensitive detection of AFB1 with a linear detection range of 0.01-100 pg mL-1, and a limit of detection (LOD) down to 2.84 fg mL-1. Furthermore, the electrochemical aptasensor was successfully applied for detecting AFB1 in corn and two kinds of traditional Chinese medicine samples, indicating the potential value for AFB1 detection in practical samples.

A fluorescent aptasensor based on gold nanoparticles quenching the fluorescence of rhodamine B to detect acetamiprid.

Pesticide residue detection is one of the main safety issues in the utilization of medicinal plants. In this work, a highly selective and sensitive aptasensor for acetamiprid determination was designed. The mechanism of the proposed method is based on the fluorescence resonance energy transfer (FRET) between gold nanoparticles (AuNPs) and rhodamine B (RB). Aptamers protect AuNPs from salt-induced aggregation, which causes fluorescence quenching of RB by the AuNPs via surface energy transfer. In the absence of acetamiprid, AuNPs were coated with aptamers on the surface and dispersed in NaCl solution. At this time, the dispersed AuNPs could perfectly quench the fluorescence intensity of RB. In contrast, in the presence of acetamiprid, aptamers specifically combine with acetamiprid to form a complex. With a high salt concentration, AuNPs would be aggregated without aptamer protection, weakening the RB quenching effect. Therefore, the concentration of acetamiprid could be obtained from the change in fluorescence intensity in the system. A fluorescent sensing method was established with a linear range from 0.1 to 3 µg mL-1, and the LOD was 0.0285 µg mL-1. The recoveries of acetamiprid in traditional Chinese medicine (TCM) samples were 96.23-105.75%. This method has great application value for the detection of acetamiprid in a complex sample matrix.

Highly diastereo- and enantioselective synthesis of multisubstituted allylic amino acid derivatives by allylic alkylation of a chiral glycine-based nickel complex and vinylethylene carbonates.

The asymmetric synthesis of multisubstituted allylic amino acid derivatives was accomplished by the allylic alkylation of a chiral glycine-based nickel complex with vinylethylene carbonates. High enantioselectivities and diastereoselectivities were obtained under mild reaction conditions. The gram-scale synthesis was carried out with a good yield and high enantioselectivity, indicating that the method is a highly efficient route to chiral multisubstituted allylic amino acid derivatives.

Palladium-Catalyzed Asymmetric [3 + 2] Annulation of Vinylethylene Carbonates with Alkenes Installed on Cyclic N-Sulfonyl Imines: Highly Enantio- and Diastereoselective Construction of Chiral Tetrahydrofuran Scaffolds Bearing Three Vicinal and Quaternary Stereocenters.

A multisubstituted tetrahydrofuran building block bearing three vicinal chiral carbon centers widely exists in a broad spectrum of bioactive natural products, and the development of efficient and convenient methods to establish this skeleton remains a challenging task. Herein, we have developed an efficient method for the construction of significant tetrahydrofuran scaffolds bearing three vicinal and α-quaternary chiral carbon stereocenters through Pd-catalyzed asymmetric [3 + 2] annulation of vinylethylene carbonates with alkenes installed on cyclic N-sulfonyl imines. A series of multisubstituted tetrahydrofuran derivatives are obtained in high efficiencies with excellent enantioselectivities and diastereoselectivities. Density functional theory (DFT) studies are accomplished to rationalize the stereocontrol of the annulation process and disclose that methanol could be applied to stabilize the reactive zwitterionic π-allylpalladium via the H-bond interaction.

Visual detection of aflatoxin B1 based on specific aptamer recognition combining with triple amplification strategy.

A highly sensitive and specific visual detection method for aflatoxin B1 (AFB1) based on the target specificity of aptamer, rolling circle amplification (RCA) and enzyme catalysis biological amplification effect has been established. In this work, AFB1 aptamer immobilized on the surface of magnetic beads (MB) serves as a molecular recognition probe. In the absence of AFB1, the aptamer and auxiliary linking probe (LP) maintain a double stranded state due to partial base pair complementarities. By contrast, in the presence of AFB1, the aptamer preferentially binds to AFB1 specifically, and the LP later restores to a single stranded state. Subsequently, the RCA reaction is triggered by above-mentioned single stranded LP to generate long DNA strands, which are employed to capture amounts of signal probes (SP) and horse radish peroxidases (HRP). Finally, amounts of HRP catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 and leads to a dramatic color change of the solution from colorlessness to deep blue as a signal indicator, obtaining a high sensitivity, high specificity and visual detection of AFB1. Under optimal conditions, a good linear detection range (0.5-40 pg·mL-1) was achieved, and the limit of detection (LOD) was 0.13 pg·mL-1. Besides, the proposed aptasensor showed excellent specificity for AFB1 compared with five other mycotoxins. More than that, all reactions occur on the surface of the magnetic beads, which not only facilitates the detection operation process including the efficient isolation and collection of AFB1 from sample matrix, but also gets better selectivity and stronger resistibility to target analyte in complex sample matrix, adequately indicating its potential application in AFB1 practical detection.

A novel transcription factor-based signature to predict prognosis and therapeutic response of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive malignancies with increasing incidence worldwide. The oncogenic roles of transcription factors (TFs) were increasingly recognized in various cancers. This study aimed to develop a predicting signature based on TFs for the prognosis and treatment of HCC. Methods: Differentially expressed TFs were screened from data in the TCGA-LIHC and ICGC-LIRI-JP cohorts. Univariate and multivariate Cox regression analyses were applied to establish a TF-based prognostic signature. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the signature. Subsequently, correlations of the risk model with clinical features and treatment response in HCC were also analyzed. The TF target genes underwent Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, followed by protein-protein-interaction (PPI) analysis. Results: A total of 25 differentially expressed TFs were screened, 16 of which were related to the prognosis of HCC in the TCGA-LIHC cohort. A 2-TF risk signature, comprising high mobility group AT-hook protein 1 (HMGA1) and MAF BZIP transcription factor G (MAFG), was constructed and validated to negatively related to the overall survival (OS) of HCC. The ROC curve showed good predictive efficiencies of the risk score regarding 1-year, 2-year and 3-year OS (mostly AUC >0.60). Additionally, the risk score independently predicted OS for HCC patients both in the training cohort of TCGA-LIHC dataset (HR = 2.498, p = 0.007) and in the testing cohort of ICGC-LIRI-JP dataset (HR = 5.411, p < 0.001). The risk score was also positively correlated to progressive characteristics regarding tumor grade, TNM stage and tumor invasion. Patients with a high-risk score were more resistant to transarterial chemoembolization (TACE) treatment and agents of lapatinib and erlotinib, but sensitive to chemotherapeutics. Further enrichment and PPI analyses demonstrated that the 2-TF signature distinguished tumors into 2 clusters with proliferative and metabolic features, with the hub genes belonging to the former cluster. Conclusion: Our study identified a 2-TF prognostic signature that indicated tumor heterogeneity with different clinical features and treatment preference, which help optimal therapeutic strategy and improved survival for HCC patients.

Conductive Polymer Nanocomposites for Stretchable Electronics: Material Selection, Design, and Applications.

Stretchable electronics that can elongate elastically as well as flex are crucial to a wide range of emerging technologies, such as wearable medical devices, electronic skin, and soft robotics. Critical to stretchable electronics is their ability to withstand large mechanical strain without failure while retaining their electrical conduction properties, a feat significantly beyond traditional metals and silicon-based semiconductors. Herein, we present a review of the recent advances in stretchable conductive polymer nanocomposites with exceptional stretchability and electrical properties, which have the potential to transform a wide range of applications, including wearable sensors for biophysical signals, stretchable conductors and electrodes, and deformable energy-harvesting and -storage devices. Critical to achieving these stretching properties are the judicious selection and hybridization of nanomaterials, novel microstructure designs, and facile fabrication processes, which are the focus of this Review. To highlight the potentials of conductive nanocomposites, a summary of some recent important applications is presented, including COVID-19 remote monitoring, connected health, electronic skin for augmented intelligence, and soft robotics. Finally, perspectives on future challenges and new research opportunities are also presented and discussed.

Impact of portal hypertension on short- and long-term outcomes after liver resection for intrahepatic cholangiocarcinoma: A propensity score matching analysis.

OBJECTIVE: We explored the impact of clinically significant portal hypertension (CSPH) on short- and long-term outcomes of intrahepatic cholangiocarcinoma (ICC) after liver resection (LR). METHODS: Data of 352 ICC patients with cirrhosis who underwent LR were extracted from the Primary Liver Cancer Big Data (PLCBD) between 2005 and 2015 and reviewed. A nomogram based on logistic analyses was developed to illustrate the influencing factors of post-hepatectomy liver failure (PHLF). The impact of CSPH on long-term survival was explored through propensity score matching (PSM) analysis, log-rank test, Cox proportional hazards model, and Kaplan-Meier curves. RESULTS: A total of 106 patients had CSPH, and 246 patients did not. A nomogram established based on GGT level, CSPH, intraoperative blood loss, and multiple tumors had an area under the receiver operating characteristic curve of 0.721 (95% confidence interval [CI] = 0.630-0.812), which displayed a better PHLF predictive value than the MELD score (0.639, 95% CI = 0.532-0.747) and Child-Pugh score (0.612, 95% CI = 0.506-0.719). Moreover, the patients with CSPH had worse overall survival (OS) rates than the patients without CSPH in the whole cohort (p = 0.011) and PSM cohort (p = 0.017). After PSM, multivariable Cox analyses identified that CSPH was an independent risk factor for OS (hazard ratio = 1.585, 95% CI = 1.107-2.269; p = 0.012). CONCLUSION: CSPH is a significant risk factor for PHLF and OS in ICC patients with cirrhosis after surgery. Selecting the proper patients before operation can effectively avoid PHLF and improve the prognosis of ICC.

Wearable Temperature Sensors with Enhanced Sensitivity by Engineering Microcrack Morphology in PEDOT:PSS-PDMS Sensors.

Wearable temperature sensors with high sensitivity, linearity, and flexibility are required to meet the increasing demands for unobtrusive monitoring of temperature changes indicative of the onset of infections and diseases. Herein, we present a new method for engineering highly sensitive and flexible temperature sensors made by sandwiching a poly(3,4-ethylenedioxythiophene):polystyrene (PEDOT:PSS) sensing film between two poly(dimethylsiloxane) (PDMS) substrates. Pre-stretching the sensor to a certain strain can create stable microcracks in the sensing layer that bestow high senstivity and linearity. The average length and density of the microcracks, which dictate the sensor's temperature sensitivity, can be engineered by controlling three key processing parameters, incuding (a) pre-stretching strain, (b) sulfuric acid treatment time, and (c) surface roughness of the substrate. For a given acid treatment time and surface roughness condition, the density and average length of the microcracks increase pre-stretching strain. A smooth PDMS substrate tends to yield long and straight cracks in the PEDOT:PSS film, compared to shorter microcracks with higher density on rough surfaces. Crack density can be further increased via sulfuric acid treatment with an optimum duration of approximately 3 h. Prolonged treatment would result in weak adhesion between the PEDOT:PSS film and the PDMS substrate, which in turn reduces the microcrack density but increases the crack length. By optimizing the three design parameters we have designed a high performance PEDOT:PSS-PDMS sensor that provides a combined high temperature sensitivity of 0.042 °C-1 with an excellent linearity of 0.998 (from 30 to 55 °C), better than the highest temperature sensitivity of PEDOT:PSS based sensors reported in the literature. With a good optical transparency, high temperature sensitivity, excellent linearity, and high flexibility, this microcrack-based sensor is a very promising wearable temperature-sensing solution.

Multimodal Capacitive and Piezoresistive Sensor for Simultaneous Measurement of Multiple Forces.

Quantitative information on the magnitudes and directions of multiple contacting forces is crucial for a wide range of applications including human-robot interaction, prosthetics, and bionic hands. Herein we report a highly stretchable sensor integrating capacitive and piezoresistive mechanisms that can simultaneously determine multiple forces. The sensor consists of three layers in a sandwich design. The two facesheets serve as both piezoresistive sensors and electrodes for the capacitive sensor, with the core being a porous structure made by using a simple sugar particle template technique to give them high stretchability. The two facesheets contain segregated conductive networks of silver nanowires (AgNWs) and carbon nanofibers (CNFs). By measuring the changes in the electrical resistance of the facesheets and the capacitance between the facesheets, three separate mechanical stimuli can be determined, including normal pressure, in-plane stretch, and transverse shear force. The newly developed multidirectional sensor offers a significant opportunity for the next generation of wearable sensors for human health monitoring and bionic skin for robots.

ATP-Triggered, Allosteric Self-Assembly of DNA Nanostructures.

Responsive self-assembly is a general process in biological systems and is highly desired in engineered systems. DNA nanostructures provide a versatile molecular platform for studying such responsive self-assembly. Various triggers have been explored for DNA nanostructures. However, each trigger requires a unique mechanism for its response. This situation brings a great challenge to engineer the responsiveness. Herein, we propose an aptamer-based, allosteric mechanism for responsive DNA self-assembly. The aptamer-ligand binding causes the DNA motif to change its conformation and thus influences the motif assembly. With a model of an ATP aptamer, we have demonstrated the responsive assembly. Such responsive behavior, we believe, will be an important element for molecular machines, bioimaging/biosensing, and drug delivery.

Nanoparticle based bio-bar code technology for trace analysis of aflatoxin B1 in Chinese herbs.

A novel and sensitive assay for aflatoxin B1 (AFB1) detection has been developed by using bio-bar code assay (BCA). The method that relies on polyclonal antibodies encoded with DNA modified gold nanoparticle (NP) and monoclonal antibodies modified magnetic microparticle (MMP), and subsequent detection of amplified target in the form of bio-bar code using a fluorescent quantitative polymerase chain reaction (FQ-PCR) detection method. First, NP probes encoded with DNA that was unique to AFB1, MMP probes with monoclonal antibodies that bind AFB1 specifically were prepared. Then, the MMP-AFB1-NP sandwich compounds were acquired, dehybridization of the oligonucleotides on the nanoparticle surface allows the determination of the presence of AFB1 by identifying the oligonucleotide sequence released from the NP through FQ-PCR detection. The bio-bar code techniques system for detecting AFB1 was established, and the sensitivity limit was about 10-8 ng/mL, comparable ELISA assays for detecting the same target, it showed that we can detect AFB1 at low attomolar levels with the bio-bar-code amplification approach. This is also the first demonstration of a bio-bar code type assay for the detection of AFB1 in Chinese herbs.

Time-dependent aggregation-induced enhanced emission, absorption spectral broadening, and aggregation morphology of a novel perylene derivative with a large D-π-A structure.

Strong aggregation-caused quenching of perylene diimides (PDI) is changed successfully by simple chemical modification with two quinoline moieties through C=C at the bay positions to obtain aggregation-induced enhanced emission (AIEE) of a perylene derivative (Cya-PDI) with a large π-conjugation system. Cya-PDI is weakly luminescent in the well-dispersed CH(3)CN or THF solutions and exhibits an evident time-dependent AIEE and absorption spectra broadening in the aggregated state. In addition, morphological inspection demonstrates that the morphology of the aggregated form of Cya-PDI molecules changed from plate-shaped to rod-like aggregates under the co-effects of time and water. An edge-to-face arrangement of aggregation was proposed and discussed. The fact that the Cya-PDI aggregates show a broad absorption covering the whole visible-light range and strong intermolecular interaction through π-π stacking in the solid state makes them promising materials for optoelectric applications.