One-Pot, Metal-Free Synthesis of Allyl Sulfones in Water.

A one-pot dehydration cross-coupling reaction between allyl alcohols and sodium sulfinates that provides allyl sulfones in good to excellent yields is presented. Its broad substrate scope includes symmetrical and asymmetrical α,α-diaryl- and α-aryl-substituted allylic alcohols and aryl and alkyl sodium sulfinates. For asymmetrical allylic substrates, the E isomer predominates with examples of excellent stereoselectivity. Control experiments provide the basis for a proposed radical-mediated mechanism. The metal-free procedure applies cheap and commercially available tetrabutylammonium tribromide as the catalyst and H2O as the solvent. Notable features of this simple, efficient, weakly toxic, and environmentally benign strategy include mild and convenient operating conditions and readily accessible starting materials.

Visible light-driven photocatalytic sulfonative oxidation of benzyl secondary amines.

A method for the α-oxidation and sulfonation of benzyl secondary amines was developed utilizing Ir(III) or Eosin Y as the photocatalyst in the presence of O2 as a green oxidant. Using commercial substrates, 37 products from cyclic and acyclic benzylamines were achieved with good functional group compatibility in 48-87% yields. Furthermore, tetrahydroisoquinoline protected by an Ac or a Boc group was oxidized under standard conditions.

Rolling circle transcription: A new system to produce RNA microspheres for improving RNAi efficiency in an agriculturally important lepidopteran pest (Mythimna separate).

We applied a new RNA interference (RNAi) system using rolling circle transcription (RCT) technology to generate RNA microspheres (RMS) for targeting two key chitin synthetic pathway genes [chitin synthase A (CHSA), chitin synthase B (CHSB)] in the larvae of the oriental armyworm (Mythimna separate), a RNAi-unsusceptible agriculturally important lepidopteran pest. Feeding the third-instar larvae with the RMS-CHSA- or RMS-CHSB-treated corn leaf discs suppressed the expression of CHSA by 81.7% or CHSB by 88.1%, respectively, at 72 h. The silencing of CHSA consequently affected the larval development, including the reduced body weight (54.0%) and length (41.3%), as evaluated on the 7th day, and caused significant larval mortalities (51.1%) as evaluated on the 14th day. Similar results were obtained with the larvae fed RMS-CHSB. We also compared RNAi efficiencies among different strategies: 1) two multi-target RMS [i.e., RMS-(CHSA + CHSB), RMS-CHSA + RMS-CHSB], and 2) multi-target RMS and single-target RMS (i.e., either RMS-CHSA or RMS-CHSB) and found no significant differences in RNAi efficiency. By using Cy3-labeled RMS, we confirmed that RMS can be rapidly internalized into Sf9 cells (<6 h). The rapid cellular uptake of RMS accompanied with significant RNAi efficiency through larval feeding suggests that the RCT-based RNAi system can be readily applied to study the gene functions and further developed as bio-pesticides for insect pest management. Additionally, our new RNAi system takes the advantage of the microRNA (miRNA)-mediated RNAi pathway using miRNA duplexes generated in vivo from the RMS by the target insect. The system can be used for RNAi in a wide range of insect species, including lepidopteran insects which often exhibit extremely low RNAi efficiency using other RNAi approaches.

Comparative Study on the Sensing Kinetics of Carbon and Nitrogen Nutrients in Cancer Tissues and Normal Tissues Based Electrochemical Biosensors.

In this study, an electrochemical sensor was developed by immobilizing colon cancer and the adjacent tissues (peripheral healthy tissues on both sides of the tumor) and was used to investigate the receptor sensing kinetics of glucose, sodium glutamate, disodium inosinate, and sodium lactate. The results showed that the electrical signal triggered by the ligand-receptor interaction presented hyperbolic kinetic characteristics similar to the interaction of an enzyme with its substrate. The results indicated that the activation constant values of the colon cancer tissue and adjacent tissues differed by two orders of magnitude for glucose and sodium glutamate and around one order of magnitude for disodium inosinate. The cancer tissues did not sense sodium lactate, whereas the adjacent tissues could sense sodium lactate. Compared with normal cells, cancer cells have significantly improved nutritional sensing ability, and the improvement of cancer cells' sensing ability mainly depends on the cascade amplification of intracellular signals. However, unlike tumor-adjacent tissues, colon cancer cells lose the ability to sense lactate. This provides key evidence for the Warburg effect of cancer cells. The methods and results in this study are expected to provide a new way for cancer research, treatment, the screening of anticancer drugs, and clinical diagnoses.

Study of the Sensing Kinetics of G Protein-Coupled Estrogen Receptor Sensors for Common Estrogens and Estrogen Analogs.

Endogenous and exogenous estrogens are widely present in food and food packaging, and high levels of natural estrogens and the misuse or illegal use of synthetic estrogens can lead to endocrine disorders and even cancer in humans. Therefore, it is consequently important to accurately evaluate the presence of food-functional ingredients or toxins with estrogen-like effects. In this study, an electrochemical sensor based on G protein-coupled estrogen receptors (GPERs) was fabricated by self-assembly, modified by double-layered gold nanoparticles, and used to measure the sensing kinetics for five GPER ligands. The interconnected allosteric constants (Ka) of the sensor for 17ß-estradiol, resveratrol, G-1, G-15, and bisphenol A were 8.90 × 10-17, 8.35 × 10-16, 8.00 × 10-15, 5.01 × 10-15, and 6.65 × 10-16 mol/L, respectively. The sensitivity of the sensor for the five ligands followed the order of 17ß-estradiol > bisphenol A > resveratrol > G-15 > G-1. The receptor sensor also demonstrated higher sensor sensitivity for natural estrogens than exogenous estrogens. The results of molecular simulation docking showed that the residues Arg, Glu, His, and Asn of GPER mainly formed hydrogen bonds with -OH, C-O-C, or -NH-. In this study, simulating the intracellular receptor signaling cascade with an electrochemical signal amplification system enabled us to directly measure GPER-ligand interactions and explore the kinetics after the self-assembly of GPERs on a biosensor. This study also provides a novel platform for the accurate functional evaluation of food-functional components and toxins.

Enhanced Shielding Performance of Layered Carbon Fiber Composites Filled with Carbonyl Iron and Carbon Nanotubes in the Koch Curve Fractal Method.

Layered carbon fiber composites (CFC) with enhanced shielding effectiveness (SE) were prepared with mixed fillers of carbon nanotubes (CNTs) and carbonyl iron powders (CIPs) in the form of a Koch curve fractal. In the layered composite structure, glass fiber (GF) cloth was used in the wave-transmissive layer (WTL), and the carbon fiber (CF) cloth was used in the supporting layer (SL). Between WTL and SL, CNTs and CIPs were distributed in epoxy resin in the form of a Koch curve fractal to act as an absorbing layer (AL), and copper foil was used as a reflective layer (RL) and bonded at the bottom of the whole composites. The layered structure design and excellent interlayer interface integration obviously improved the SE performance of the CFC. The SE of different samples was investigated, and the results show that, with the increase in the number (n) of Koch curve fractals, the SE of the samples enhanced in the low frequency scope (1-5 GHz). The sample with n = 2 has the highest SE value of 73.8 dB at 2.3 GHz. The shielding performance of the fractal sample filled by CNTs and CIPs simultaneously has a comprehensive improvement in the whole scope of 1-18 GHz, especially for the sample with n = 2. The cumulative bandwidth value of the SE exceeding 55 dB is about 14.3 GHz, accounting for 85% of the whole frequency scope, indicating the composite fabricated in this paper is an electromagnetic shielding material with great prospect.

Recent Advances in the Quantitative Determination of Protein Receptor-Ligand Interaction Kinetics.

Receptor-ligand binding, which is crucial to a variety of biomedical and biochemical processes, immune responses, and signal transduction, forms the basis for many biotechnological applications. The specific binding between a receptor and a ligand is the beginning of the biological function of the receptor or ligand molecule. Therefore, a summary study of methods for quantitative determination of receptor-ligand interaction kinetics is necessary. In this review, the kinetic parameters that traditionally describe the pattern of receptor-ligand interactions are first introduced. We then summarize and analyze methods for quantitative determination of receptor-ligand interaction kinetics, including direct kinetic measurements, cytology-based measurements, computational chemistry-based measurements, and single-molecule force spectrometry technique measurements of receptor-ligand interactions. Direct measurements of the kinetics of receptor-ligand interactions are further described in methods based on surface plasmon resonance, surface-enhanced Raman spectroscopy, photoelectrochemistry, mass spectrometry binding analyses, nuclear magnetic resonance technology, and electrochemical methods. This review provides a comprehensive and accurate description of the kinetic studies of protein receptor-ligand interactions.

Studying allosteric regulation of chemokines and antagonists using a nanoscale hCCR3 receptor sensor.

CC chemokine receptor-3 (hCCR3), a G protein-coupled receptor (GPCR) expressed predominantly on eosinophils, is an important drug target. However, it was unclear how chemokine ligands, activators and antagonists recognize hCCR3, and quantitative measurements of hCCR3 inhibition or activation were rare. This study constructed a nanogold receptor sensor using hCCR3 as the molecular recognition element and horseradish peroxidase as the signal amplifier. We quantified the kinetic antagonism between chemokines and hCCR3 before and after adding hCCR3 antagonists. A molecular docking study was carried out to investigate how hCCR3 and its ligands work. The study results indicate chemokines interact with hCCR3 at low concentrations, and reversible hCCR3 inhibitors solely inhibit hCCR3, not CCLs. Moreover, a quantitative evaluation of hCCR3 chemokine activators and their antagonists was carried out using a directed weighted network. This offers a novel approach to quantitatively evaluate chemokine-receptor activation and antagonism together. This research could potentially offer new insights into the mechanisms of action of chemokines and drug screening.

Kinetics of Drug Molecule Interactions with a Newly Developed Nano-Gold-Modified Spike Protein Electrochemical Receptor Sensor.

In March 2020, the World Health Organization (WHO) declared COVID-19 a pandemic, and the spike protein has been reported to be an important drug target for anti-COVID-19 treatment. As such, in this study, we successfully developed a novel electrochemical receptor biosensor by immobilizing the SARS-CoV-2 spike protein and using AuNPs-HRP as an electrochemical signal amplification system. Moreover, the time-current method was used to quantify seven antiviral drug compounds, such as arbidol and chloroquine diphosphate. The results show that the spike protein and the drugs are linearly correlated within a certain concentration range and that the detection sensitivity of the sensor is extremely high. In the low concentration range of linear response, the kinetics of receptor-ligand interactions are similar to that of an enzymatic reaction. Among the investigated drug molecules, bromhexine exhibits the smallest Ka value, and thus, is most sensitively detected by the sensor. Hydroxychloroquine exhibits the largest Ka value. Molecular docking simulations of the spike protein with six small-molecule drugs show that residues of this protein, such as Asp, Trp, Asn, and Gln, form hydrogen bonds with the -OH or -NH2 groups on the branched chains of small-molecule drugs. The electrochemical receptor biosensor can directly quantify the interaction between the spike protein and drugs such as abidor and hydroxychloroquine and perform kinetic studies with a limit of detection 3.3 × 10-20 mol/L, which provides a new research method and idea for receptor-ligand interactions and pharmacodynamic evaluation.

Electrochemical Signal Amplification Strategies and Their Use in Olfactory and Taste Evaluation.

Biosensors are powerful analytical tools used to identify and detect target molecules. Electrochemical biosensors, which combine biosensing with electrochemical analysis techniques, are efficient analytical instruments that translate concentration signals into electrical signals, enabling the quantitative and qualitative analysis of target molecules. Electrochemical biosensors have been widely used in various fields of detection and analysis due to their high sensitivity, superior selectivity, quick reaction time, and inexpensive cost. However, the signal changes caused by interactions between a biological probe and a target molecule are very weak and difficult to capture directly by using detection instruments. Therefore, various signal amplification strategies have been proposed and developed to increase the accuracy and sensitivity of detection systems. This review serves as a reference for biosensor and detector research, as it introduces the research progress of electrochemical signal amplification strategies in olfactory and taste evaluation. It also discusses the latest signal amplification strategies currently being employed in electrochemical biosensors for nanomaterial development, enzyme labeling, and nucleic acid amplification techniques, and highlights the most recent work in using cell tissues as biosensitive elements.

Distorted 1T-ReS2 Nanosheets Anchored on Porous TiO2 Nanofibers for Highly Enhanced Photocatalytic Hydrogen Production.

Recently, loading TiO2 with transition-metal disulfides (TMDs) to construct dual functional heterostructures has been widely researched as an effective strategy to improve the photocatalytic performance of a TiO2 photocatalyst. For the TMD cocatalysts, the 2H-MoS2 and 1T-MoS2 have been widely studied and researched. However, they suffer from poor catalytic activity sites/low charge transfer ability and an unstable structure. In this regard, distorted 1T-phase TMDs with a stable structure are greatly fit for the cocatalyst due to their high charge transfer ability and rich catalytic sites on both the edge and basal plane. Therefore, it is highly desirable to develop distorted 1T-phase TMD/TiO2 heterostructures with well-identified interfaces for highly enhanced photocatalytic performance. Herein, we first introduce distorted 1T-ReS2 anchored on porous TiO2 nanofibers as a promising photocatalyst for achieving an excellent photocatalytic hydrogen production. The excellent performance is attributed to the strong chemical interaction of the Ti-O-Re bond between TiO2 and ReS2, the excellent electron mobility of distorted 1T-ReS2, and the abundant catalytic activity sites on both the plane and edge of the ReS2 cocatalyst.