Design, Synthesis, and Structure-Activity Relationship of Novel Pyridazinone-Based PARP7/HDACs Dual Inhibitors for Elucidating the Relationship between Antitumor Immunity and HDACs Inhibition.

Histone deacetylases (HDACs) inhibitors such as vorinostat (SAHA) has been used to treat hematologic malignancies (rather than solid tumors) and have been found to suppress the JAK/STAT, a critical signal pathway for antitumor immunity, while PARP7 inhibitor RBN-2397 could activate the type I interferons (IFN-I) pathway, facilitating downstream effects such as STAT1 phosphorylation and immune activation. To elucidate whether simultaneous inhibition of these two targets could interfere with these two signal pathways, a series of pyridazinone-based PARP7/HDACs dual inhibitors have been designed, synthesized, and evaluated in vitro and in vivo experiments. Compound 9l was identified as a potent and balanced dual inhibitor for the first time, exhibiting excellent antitumor capabilities both in vitro and in vivo. This suggests that 9l can be used as a valuable tool molecule for investigating the relationship between anticancer immunity and HDAC inhibition.

Convolution Neural Network-Assisted Smart Fluorescent-Tongue Based on Lanthanide Ion-Induced Forming MOF/HOF Composite for Differentiation of Flavor Compounds and Wine Identification.

Wine flavor is a vital quality characteristic in wine, influenced by those flavor components with low sensory thresholds. It is crucial to recognize and classify the wine components related to their flavor contribution. The integration of fluorescent sensors and artificial intelligence shows huge potential in flavor recognition by emulation of the gustatory perception system. Meanwhile, achieving information identification of wine based on multiple information barcodes has hopeful applications in anticounterfeiting. In this study, we present a simple method in which organic linkers are weaved into a hydrogen-bonded organic framework (HOF) for the available transformation of a metal-bonded organic framework (MOF) induced by lanthanide ions (Ln3+). The fluorescent Ln-MOF/HOF composite exhibits high sensitivity, rapid response, and good recyclability for detecting seven flavor compounds in wine, including tannic acid, ionone, vanillin, anethole, anisaldehyde, hydroxybenzaldehyde, and 4-hydroxy-2-methylacetophenone. Depending on its satisfactory detectability, a novel strategy is provided in which a fluorescent sensor is able to function as a smart fluorescent-tongue (F-tongue) by the aid of convolutional neural network to differentiate these seven flavor compounds. In addition, the Ln-MOF/HOF composite has been used to prepare multiple information barcodes for wine information identification on the basis of dynamic fluorescence response toward tannic acid. The mimetic gustatory perception system developed in this study may offer a promising strategy for flavor recognition in food and further food anticounterfeiting.

Nickel-Catalyzed Enantioconvergent Transformation of Anisole Derivatives via Cleavage of C-OMe Bond.

Herein, a protocol for enantioconvergent transformation of anisole derivatives is disclosed via nickel-catalyzed dynamic kinetic asymmetric cross-coupling of the C(Ar)-OMe bond. Versatile axially chiral heterobiaryls are successfully assembled. Synthetic transformations demonstrate the application potential of this method. Mechanistic studies indicate that the enantioconvergence of this transformation might be accessed through a chiral ligand-controlled epimerization of diastereomeric 5-membered aza-nickelacycle species rather than a conventional dynamic kinetic resolution.

Electrochemical Biosensors for Whole Blood Analysis: Recent Progress, Challenges, and Future Perspectives.

Whole blood, as one of the most significant biological fluids, provides critical information for health management and disease monitoring. Over the past 10 years, advances in nanotechnology, microfluidics, and biomarker research have spurred the development of powerful miniaturized diagnostic systems for whole blood testing toward the goal of disease monitoring and treatment. Among the techniques employed for whole-blood diagnostics, electrochemical biosensors, as known to be rapid, sensitive, capable of miniaturization, reagentless and washing free, become a class of emerging technology to achieve the target detection specifically and directly in complex media, e.g., whole blood or even in the living body. Here we are aiming to provide a comprehensive review to summarize advances over the past decade in the development of electrochemical sensors for whole blood analysis. Further, we address the remaining challenges and opportunities to integrate electrochemical sensing platforms.

The relationship between canopy microclimate, fruit and seed yield, and quality in Xanthoceras sorbifolium.

Xanthoceras sorbifolium has high oil content and important biomass energy value, but its development is limited by the problem of low yield. This study investigated the relationship between the canopy microclimate, fruit yield, and fruit quality of Xanthoceras sorbifolium. Difference between the distributions of canopy microclimate factors as well as fruit and seed parameters in the inner and outer canopies of the lower layer, as well as between the inner and outer canopies of the upper layer, were investigated for a period of one year. Canopy structure induced significant differences between canopy microclimate factors during various periods of the year. Light intensity and temperature of the outer and upper canopies were higher than those of inner and lower canopies. However, relative humidity showed an opposing trend. Light intensity was significantly and positively correlated with fruit set percentage, fruit yield, and seed yield. Temperature was significantly and positively correlated with fruit yield and seed yield, but significantly negatively correlated with the oil concentration of seed kernels. Fruit and seed yields significantly decreased from the outer to the inner canopy and from the upper to the lower canopy. Fruit set percentage in the outer canopy was also significantly higher than that in the inner canopy. However, oil concentrations in the seed kernels of the lower layer were significantly higher than those of the upper layer. Additionally, regression analysis was used to construct evaluation models for microclimate, fruit, and seed parameters. Regression equations corresponding to the association between single microclimatic factors during different periods and the fruit and seed parameters may provide a reference for canopy pruning and help develop an optimal regression model that may be used to predict and estimate fruit and seed parameters.

A pH-independent electrochemical aptamer-based biosensor supports quantitative, real-time measurement in vivo.

The development of biosensors capable of achieving accurate and precise molecular measurements in the living body in pH-variable biological environments (e.g. subcellular organelles, biological fluids and organs) plays a significant role in personalized medicine. Because they recapitulate the conformation-linked signaling mechanisms, electrochemical aptamer-based (E-AB) sensors are good candidates to fill this role. However, this class of sensors suffers from a lack of a stable and pH-independent redox reporter to support their utility under pH-variable conditions. Here, in response, we demonstrate the efficiency of an electron donor π-extended tetrathiafulvalene (exTTF) as an excellent candidate (due to its good electrochemical stability and no proton participation in its redox reaction) of pH-independent redox reporters. Its use has allowed improvement of E-AB sensing performance in biological fluids under different pH conditions, achieving high-frequency, real-time molecular measurements in biological samples both in vitro and in the bladders of living rats.

Incorporating Hydrophobic Moieties into Self-Assembled Monolayers to Enable Electrochemical Aptamer-Based Sensors Deployed Directly in a Complex Matrix.

Continuous real-time measurement of specific targets in complex biological samples is of great significance for early diagnosis and treatment of diseases and thus enables achievement of personalized medicine. Electrochemical aptamer-based (E-AB) sensors are good candidates to fill this role due to their high specificity, sensitivity, rapid detection, and simple preparation. However, this sensor class suffers from severe baseline drift in the complex matrix probably due to the nonspecific adsorption of components. Here, we introduce a series of self-assembled monolayers with a variety of hydrophobic functional groups into an E-AB sensor platform, achieving enhancement of the antifouling performance and thus the detection performance (e.g., stability, sensitivity, and specificity). We reveal that the antifouling performance enhanced by such hydrophobic SAMs is probably due to its instant adsorption of components onto the surface, rather than the repelling of these components by hydrophilic SAMs in previous reports.

Enantioselective alkylative cross-coupling of unactivated aromatic C-O electrophiles.

Nonpolar alkyl moieties, especially methyl group, are frequently used to modify bioactive molecules during lead optimization in medicinal chemistry. Thus transition-metal catalyzed alkylative cross-coupling reactions by using readily available and environmentally benign C-O electrophiles have been established as powerful tools to install alkyl groups, however, the C(sp3)-C(sp2) cross-coupling via asymmetric activation of aromatic C-O bond for the synthesis of alkylated chiral compounds remains elusive. Here, we unlock a C(sp3)-C(sp2) cross-coupling via enantioselective activation of aromatic C-O bond for the efficient synthesis of versatile axially chiral 2-alkyl-2'-hydroxyl-biaryl compounds. By employing a unique chiral N-heterocyclic carbene ligand, this transformation is accomplished via nickel catalysis with good enantiocontrol. Mechanistic studies indicate that bis-ligated nickel complexes might be formed as catalytically active species in the enantioselective alkylative cross-coupling. Moreover, further derivation experiments suggest this developed methodology holds great promise for complex molecule synthesis and asymmetric catalysis.

Nickel-Catalyzed Enantioselective Arylative Activation of Aromatic C-O Bond.

The pioneering nickel-catalyzed cross-coupling of C-O electrophiles was unlocked by Wenkert in the 1970s; however, the transition-metal-catalyzed asymmetric activation of aromatic C-O bonds has never been reported. Herein the first enantioselective activation of an aromatic C-O bond is demonstrated via the catalytic arylative ring-opening cross-coupling of diarylfurans. This transformation is facilitated via nickel catalysis in the presence of chiral N-heterocyclic carbene ligands, and chiral 2-aryl-2'-hydroxy-1,1'-binaphthyl (ArOBIN) skeletons are delivered axially in high yields with high ee. Moreover, this versatile skeleton can be transformed into various synthetic useful intermediates, chiral catalysts, and ligands by using the CH- and OH-based modifiable sites. This chemistry features mild conditions and good atom economy.

Exploring End-Group Effect of Alkanethiol Self-Assembled Monolayers on Electrochemical Aptamer-Based Sensors in Biological Fluids.

The continuous, real-time monitoring of specific analytes in situ in biological fluids would provide personalized, high-precision pharmacokinetic information for the goal of precision medicine. Due to their conformationally linked signaling mechanism, electrochemical aptamer-based (E-AB) sensors are promising candidates for accurate measurements in such complex media. They suffer, however, from severe baseline drift when interrogated continuously and in real-time manner. In response, here, we investigate a couple of self-assembled monolayers in the application of E-AB sensors, achieving the improvement of their baseline stability and simultaneous modulation of sensor performance, e.g., target affinity and specificity.

Application of a sorbent trap system to gas-phase elemental and oxidized mercury analysis.

A sorbent trap that utilizes activated carbon (AC) as the solid trapping medium is a new technology for measuring total mercury (Hg) emissions from combustion facilities. In this study, sorbent trap technology was further developed, improved and evaluated at the laboratory scale. AC was impregnated with 5% aqua regia to enhance its Hg adsorption capacity. Sorbent traps spiked with an Hg standard solution were found to be reproducibly prepared and highly stable. The effect of the Hg concentration on the spiking efficiency was further investigated. The adsorption of elemental and oxidized Hg by the sorbent trap was studied under various experimental conditions (temperature, flow rate and inlet Hg concentration). The Hg concentration of the flue gas effluent from the sorbent trap was measured. In addition, the concentration of Hg adsorbed on the AC was determined by digesting the used AC with an acid according to US EPA method 3052 and then analyzing it with cold vapor atomic absorption spectrometry. Furthermore, the gas-phase Hg emissions from a combustion source were measured using the sorbent trap according to US EPA method 30B. The results showed that the sorbent trap could be used for Hg concentrations between 10.0 and 40.0 µg m(-3) and flow rates between 0.5 and 1.0 lpm with adsorption efficiencies greater than 90%.