New S in town: Sulfonyl hydrazides smoothly undergo sulfenylation with indoles in the presence of 10 mol % I2 to give structurally diverse indole thioethers in moderate to excellent yields with ...extremely high regioselectivity. This study paves the way for the use of sulfonyl hydrazides as unique sulfur electrophiles in chemical synthesis.
The identification of interactions between compounds and proteins plays an important role in network pharmacology and drug discovery. However, experimentally identifying compound-protein interactions ...(CPIs) is generally expensive and time-consuming, computational approaches are thus introduced. Among these, machine-learning based methods have achieved a considerable success. However, due to the nonlinear and imbalanced nature of biological data, many machine learning approaches have their own limitations. Recently, deep learning techniques show advantages over many state-of-the-art machine learning methods in some applications. In this study, we aim at improving the performance of CPI prediction based on deep learning, and propose a method called DL-CPI (the abbreviation of Deep Learning for Compound-Protein Interactions prediction), which employs deep neural network (DNN) to effectively learn the representations of compound-protein pairs. Extensive experiments show that DL-CPI can learn useful features of compound-protein pairs by a layerwise abstraction, and thus achieves better prediction performance than existing methods on both balanced and imbalanced datasets.
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•The state-of-the art strategies for constructing highly repetitive genes.•The versatile host systems for the biosynthesis of recombinant protein polymers.•The host engineering ...strategies for optimizing the expression of protein polymers.•Representative protein polymers for fabricating delivery vehicles.
Vehicles derived from genetically engineered protein polymers have gained momentum in the field of biomedical engineering due to their unique designability, remarkable biocompatibility and excellent biodegradability. However, the design and production of these protein polymers with on-demand sequences and supramolecular architectures remain underexplored, particularly from a synthetic biology perspective. In this review, we summarize the state-of-the art strategies for constructing the highly repetitive genes encoding the protein polymers, and highlight the advanced approaches for metabolically engineering expression hosts towards high-level biosynthesis of the target protein polymers. Finally, we showcase the typical protein polymers utilized to fabricate delivery vehicles.
Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in ...the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9‐associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR‐185‐5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia‐induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR‐185‐5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT‐PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR‐185‐5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR‐185‐5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.
Although face‐centered cubic (fcc), body‐centered cubic (bcc), hexagonal close‐packed (hcp), and other structured gold nanoclusters have been reported, it was unclear whether gold nanoclusters with ...mix‐packed (fcc and non‐fcc) kernels exist, and the correlation between kernel packing and the properties of gold nanoclusters is unknown. A Au49(2,4‐DMBT)27 nanocluster with a shell electron count of 22 has now been been synthesized and structurally resolved by single‐crystal X‐ray crystallography, which revealed that Au49(2,4‐DMBT)27 contains a unique Au34 kernel consisting of one quasi‐fcc‐structured Au21 and one non‐fcc‐structured Au13 unit (where 2,4‐DMBTH=2,4‐dimethylbenzenethiol). Further experiments revealed that the kernel packing greatly influences the electrochemical gap (EG) and the fcc structure has a larger EG than the investigated non‐fcc structure.
Gold in the shell: A gold nanocluster with a shell electron count of 22 was synthesized and structurally resolved by X‐ray crystallography. The nanocluster contains a unique Au34 kernel with one quasi face‐centered‐cubic structured Au21 and one non‐fcc structured Au13 unit. The kernel packing greatly influences the electrochemical gap (EG), and the quasi‐fcc structure has a larger EG than the investigated non‐fcc structure.
Developing efficient and stable non‐noble electrocatalysts for the oxygen evolution reaction (OER) remains challenging for practical applications. While nickel–iron layered double hydroxides ...(NiFe‐LDH) are emerging as prominent candidates with promising OER activity, their catalytic performance is still restricted by the limited active sites, poor conductivity and durability. Herein, hierarchical nickel–iron–cobalt LDH nanosheets/carbon fibers (NiFeCo‐LDH/CF) are synthesized through solvent‐thermal treatment of ZIF‐67/CF. Extended X‐ray adsorption fine structure analyses reveal that the Co substitution can stabilize the Fe local coordination environment and facilitate the π‐symmetry bonding orbital in NiFeCo‐LDH/CF, thus modifying the electronic structures. Coupling with the structural advantages, including the largely exposed active surface sites and facilitated charge transfer pathway ensured by CF, the resultant NiFeCo‐LDH/CF exhibits excellent OER activity with an overpotential of 249 mV at 10 mA cm−1 as well as robust stability over 20 h.
Hierarchical nanostructures fabricated from edge‐rich nickel–iron–cobalt layered double hydroxides (NiFeCo‐LDH) nanosheets and carbon fiber are synthesized by solvent‐thermal treatment of ZIF‐67/CF. Owing to the synergistic interaction between the three metal ions, largely exposed active surface sites and tunable electronic structure in LDH materials, NiFeCo‐LDH/CF displays superior oxygen evolution reaction performance and robust stability.
The charge‐accelerated aza‐Claisen rearrangement of ammonium salts serves as a key step in the construction of complex nitrogen‐containing molecules. However, much less attention has been paid to the ...aromatic aza‐Claisen rearrangement than to the aliphatic one. Herein, we report an unprecedented aromatic aza‐Claisen rearrangement of arylpropargylammonium salts, generated in situ from arynes and tertiary propargylamines, delivering structurally diverse 2‐propargylanilines in moderate to good yields with high regioselectivity. This rearrangement proceeds in the absence of strong bases or transition metals, is compatible with moisture and air, tolerates a wide variety of functional groups, and is amenable to forming 11‐ to 13‐membered heterocycles with a triple bond. The 2‐propargylaniline products were treated with aluminum chloride in ethanol to afford multisubstituted indoles in moderate to excellent yields. Finally, a series of deuterium‐labeling experiments was performed to elucidate the reaction mechanism.
An unprecedented aromatic aza‐Claisen rearrangement of arylpropargylammonium salts, generated in situ from arynes and tertiary propargylamines, has been established, delivering structurally diverse 2‐propargylanilines. These further cyclize in the presence of aluminum chloride to afford multisubstituted indoles.
A useful source: Arylsulfonyl hydrazides have been identified as synthetically useful aryl sources for the Pd(OAc)2 catalyzed oxidative Mizoroki–Heck‐type reaction under molecular oxygen to provide a ...convenient access to polysubstituted alkenes in a highly regio‐ and stereoselective manner (see scheme). The reaction well tolerates various functional groups such as alkoxy, halo, alcohol, carboxylic acid, ester, amide, sulfonamide, and sulfone.
The NH2 group serves as an effective leaving group in the palladium‐catalyzed regioselective and stereospecific title reaction (see scheme). The reaction works well with aryl‐ and alkenylboronic ...acids and aryl‐, alkenyl‐, allyl‐, and benzylboronates, and complete transfer of chirality has been achieved when using α‐chiral primary allylic amines as the allylic electrophiles.
A highly regioselective halogenation reaction of symmetrical and unsymmetrical aromatic azo compounds has been developed at room temperature or at 50 °C. In the presence of 5 mol% palladium diacetate ...and 0.5 equiv. of p‐toluenesulfonic acid, a range of symmetrical aromatic azo compounds smoothly undergo monobromination with N‐bromosuccinimide to give the corresponding unsymmetrical aromatic azo compounds in good to excellent yields with >99:1 ortho‐selectivity. This chemistry has been successfully extended to unsymmetrical aromatic azo compounds, whose electron‐richer aryl groups prefer to be monobrominated. Moreover, replacing N‐bromosuccinimide with N‐iodosuccinimide in the reaction allows the synthesis of monoiodinated aromatic azo compounds with >99:1 regioselectivity.
