Concentration-Dependent Enrichment Identifies Primary Protein Targets of Multitarget Bioactive Molecules

Multitarget bioactive molecules (MBMs) are of increasing importance in drug discovery as they could produce high efficacy and a low chance of resistance. Several advanced approaches of quantitative proteomics were developed to accurately identify the protein targets of MBMs, but little study has been carried out in a sequential manner to identify primary protein targets (PPTs) of MBMs. This set of proteins will first interact with MBMs in the temporal order and play an important role in the mode of action of MBMs, especially when MBMs are at low concentrations. Herein, we describe a valuable observation that the result of the enrichment process is highly dependent on concentrations of the probe and the proteome. Interestingly, high concentrations of probe and low concentrations of incubated proteome will readily miss the hyper-reactive protein targets and thereby increase the probability of rendering PPTs with false-negative results, while low concentrations of probe and high concentrations of incubated proteome more than likely will capture the PPTs. Based on this enlightening observation, we developed a proof-of-concept approach to identify the PPTs of iodoacetamide, a thiol-reactive MBM. This study will deepen our understanding of the enrichment process and improve the accuracy of pull-down-guided target identification

Concentration-Dependent Enrichment Identifies Primary Protein Targets of Multitarget Bioactive Molecules

Multitarget bioactive molecules (MBMs) are of increasing importance in drug discovery as they could produce high efficacy and a low chance of resistance. Several advanced approaches of quantitative proteomics were developed to accurately identify the protein targets of MBMs, but little study has been carried out in a sequential manner to identify primary protein targets (PPTs) of MBMs. This set of proteins will first interact with MBMs in the temporal order and play an important role in the mode of action of MBMs, especially when MBMs are at low concentrations. Herein, we describe a valuable observation that the result of the enrichment process is highly dependent on concentrations of the probe and the proteome. Interestingly, high concentrations of probe and low concentrations of incubated proteome will readily miss the hyper-reactive protein targets and thereby increase the probability of rendering PPTs with false-negative results, while low concentrations of probe and high concentrations of incubated proteome more than likely will capture the PPTs. Based on this enlightening observation, we developed a proof-of-concept approach to identify the PPTs of iodoacetamide, a thiol-reactive MBM. This study will deepen our understanding of the enrichment process and improve the accuracy of pull-down-guided target identification

Reduced Graphene Oxide/O-MWCNT Hybrids Functionalized with p‑Phenylenediamine as High-Performance MoS₂ Electrocatalyst Support for Hydrogen Evolution Reaction

Efficient hydrogen evolution through water splitting at low overpotentials is crucial to develop renewable energy technology, which depends on the design of efficient and durable electrocatalysts composed of earth-abundant elements. Herein, a highly and stable electrocatalyst for hydrogen evolution reaction (HER) has been developed on the basis of MoS₂ on p-phenylenediamine (PPD)-functionalized reduced graphene oxide/O-containing carbon nanotubes (rGO/O-MWCNT) hybrids via facile and green hydrothermal process. Among the prepared catalysts, the optimized MoS₂/rGO/PPD/O-MWCNT with nanosized and highly dispersed MoS₂ sheets provides a large amount of available edge sites and the improved electron transfer in 3D conductive networks. It exhibits excellent HER activity with a low overpotential of 90 mV and large current density of 47.6 mA·cm^–2 at 200 mV, as well as excellent stability in an acidic medium. The Tafel slope of 48 mV·dec^–1 reveals the Volmer–Heyrovsky mechanism for HER. Thus, this work paves a potential pathway for designing efficient MoS₂-based electrocatalysts for HER by functionalized conductive substrates

The Impact of Bisphenol A on the Anaerobic Sulfur Transformation: Promoting Sulfur Flow and Toxic H₂S Production

Bisphenol A (BPA), as a typical leachable additive from microplastics and one of the most productive bulk chemicals, is widely distributed in sediments, sewers, and wastewater treatment plants, where active sulfur cycling takes place. However, the effect of BPA on sulfur transformation, particularly toxic H2S production, has been previously overlooked. This work found that BPA at environmentally relevant levels (i.e., 50–200 mg/kg total suspended solids, TSS) promoted the release of soluble sulfur compounds and increased H2S gas production by 14.3–31.9%. The tryptophan-like proteins of microbe extracellular polymeric substances (EPSs) can spontaneously adsorb BPA, which is an enthalpy-driven reaction (ΔH = −513.5 kJ mol–1, ΔS = −1.60 kJ mol–1K –1, and ΔG = −19.52 kJ mol–1 at 35 °C). This binding changed the composition and structure of EPSs, which improved the direct electron transfer capacity of EPSs, thereby promoting the bioprocesses of organic sulfur hydrolysis and sulfate reduction. In addition, BPA presence enriched the functional microbes (e.g., Desulfovibrio and Desulfuromonas) responsible for organic sulfur mineralization and inorganic sulfate reduction and increased the abundance of related genes involved in ATP-binding cassette transporters and sulfur metabolism (e.g., Sat and AspB), which promoted anaerobic sulfur transformation. This work deepens our understanding of the interaction between BPA and sulfur transformation occurring in anaerobic environments

Improving the Resolution of Flexible Large-Area Tactile Sensors through Machine-Learning Perception

Industrial robots are the main piece of equipment of intelligent manufacturing, and array-type tactile sensors are considered to be the core devices for their active sensing and understanding of the production environment. A great challenge for existing array-type tactile sensors is the wiring of sensing units in a limited area, the contradiction between a small number of sensing units and high resolution, and the deviation of the overall output pattern due to the difference in the performance of each sensing unit itself. Inspired by the human somatosensory processing hierarchy, we combine tactile sensors with artificial intelligence algorithms to simplify the sensor architecture while achieving tactile resolution capabilities far greater than the number of signal channels. The prepared 8-electrode carbon-based conductive network achieves high-precision identification of 32 regions with 97% classification accuracy assisted by a quadratic discriminant analysis algorithm. Notably, the output of the sensor remains unchanged after 13,000 cycles at 60 kPa, indicating its excellent durability performance. Moreover, the large-area skin-like continuous conductive network is simple to fabricate, cost-effective, and can be easily scaled up/down depending on the application. This work may address the increasing need for simple fabrication, rapid integration, and adaptable geometry tactile sensors for use in industrial robots

Different Performances of BF₃, BCl₃, and BBr₃ in Hypervalent Iodine-Catalyzed Halogenations

Herein, hypervalent iodine-catalyzed halogenation of aryl-activated alkenes using BX3 (X = Cl, Br) as the halogen source and activating reagents was reported. Various halogenated 1,3-oxazine/2-oxazoline derivatives were obtained in good-to-high yields. Using BF3 resulted in different substitute sites from BBr3 and BCl3 of the products, indicating different reactive intermediates and reaction pathways. The reaction underwent a “ligand coupling/oxidative addition/intermolecular nucleophilic attack/1,2-aryl migration/reductive elimination/intramolecular nucleophilic attack” cascade when BF3 was applied as the halogen source, while 1,2-aryl migration has “disappeared” when the halogen source was BBr3 or BCl3. Possible catalytic cycles were proposed, and DFT calculations were conducted to demonstrate the differences among BX3 (X = F, Cl, Br) in the hypervalent iodine-catalyzed halogenations

Improving the Resolution of Flexible Large-Area Tactile Sensors through Machine-Learning Perception

Industrial robots are the main piece of equipment of intelligent manufacturing, and array-type tactile sensors are considered to be the core devices for their active sensing and understanding of the production environment. A great challenge for existing array-type tactile sensors is the wiring of sensing units in a limited area, the contradiction between a small number of sensing units and high resolution, and the deviation of the overall output pattern due to the difference in the performance of each sensing unit itself. Inspired by the human somatosensory processing hierarchy, we combine tactile sensors with artificial intelligence algorithms to simplify the sensor architecture while achieving tactile resolution capabilities far greater than the number of signal channels. The prepared 8-electrode carbon-based conductive network achieves high-precision identification of 32 regions with 97% classification accuracy assisted by a quadratic discriminant analysis algorithm. Notably, the output of the sensor remains unchanged after 13,000 cycles at 60 kPa, indicating its excellent durability performance. Moreover, the large-area skin-like continuous conductive network is simple to fabricate, cost-effective, and can be easily scaled up/down depending on the application. This work may address the increasing need for simple fabrication, rapid integration, and adaptable geometry tactile sensors for use in industrial robots

Improving the Resolution of Flexible Large-Area Tactile Sensors through Machine-Learning Perception

Industrial robots are the main piece of equipment of intelligent manufacturing, and array-type tactile sensors are considered to be the core devices for their active sensing and understanding of the production environment. A great challenge for existing array-type tactile sensors is the wiring of sensing units in a limited area, the contradiction between a small number of sensing units and high resolution, and the deviation of the overall output pattern due to the difference in the performance of each sensing unit itself. Inspired by the human somatosensory processing hierarchy, we combine tactile sensors with artificial intelligence algorithms to simplify the sensor architecture while achieving tactile resolution capabilities far greater than the number of signal channels. The prepared 8-electrode carbon-based conductive network achieves high-precision identification of 32 regions with 97% classification accuracy assisted by a quadratic discriminant analysis algorithm. Notably, the output of the sensor remains unchanged after 13,000 cycles at 60 kPa, indicating its excellent durability performance. Moreover, the large-area skin-like continuous conductive network is simple to fabricate, cost-effective, and can be easily scaled up/down depending on the application. This work may address the increasing need for simple fabrication, rapid integration, and adaptable geometry tactile sensors for use in industrial robots

Morphology Design of IRMOF‑3 Crystal by Coordination Modulation

A one-pot synthesis design on shape-controlled growth of Zn-based isoreticular metal–organic framework (i.e., IRMOF-3) was carried out in this work with the controllable crystal morphological evolution from simple cubes to several complex shapes. A new synthetic protocol was devised where poly­(vinylpyrrolidone) (PVP), noble metal source (AgNO₃), mixed solvents (<i>N</i>,<i>N</i>-dimethylformamide (DMF)–ethanol mixture) and tetramethylammonium bromide (TMAB) were mutually introduced to the reaction medium as surfactant, adjuvant, accelerator, and structure-directing agent (SDA), respectively. Meanwhile, the crystallization process was investigated by a series of time-dependent experiments. Indeed, the added modulators and crystallization time were able to regulate the growth and thus the morphology of the final products. The resulting homogeneous IRMOF-3-Ag-<i><b>n</b></i> materials with unique and novel crystal morphologies were characterized via scanning electron microscopy (SEM), X-ray powder diffraction (XRD), thermogravimetric and differential thermal analyses (TG-DTA), transmission electron microscopy (TEM), infrared spectrum (IR), and optical microscope characterizations. Various shapes of IRMOF-3-Ag-<i><b>n</b></i> crystals as sorbents for capturing dibenzothiophene (DBT) were evaluated. Among all the morphology-controlled samples, IRMOF-3-Ag-<b>5</b> with hollow sphere morphology was demonstrated to show the highest DBT capture capacity due to its unique morphology

Energy-Transfer-Powered Sultine Synthesis

Molecules with precise sultine structures are particularly sought after since the function of a molecule depends on this interesting structure. Despite the positive pivotal significance of the sultines in synthesis, medicine, and materials science, the sultines’ chemistry long remains unexplored due to their inaccessibility; only very limited protocols have been developed. Here, we report an energy-transfer-powered intramolecular radical–radical cross-coupling cyclization for the practical and atom-economical assembly of otherwise challenging-to-access sultines under mild and operationally simple conditions using an inexpensive organic photocatalyst. Importantly, this work presents a practical method of trifluoromethyl radical generation from alkyl trifluoromethanesulfinate, and the obtained sultines were confirmed as promising electrolyte additives for high-voltage lithium batteries employing LiNi0.5Mn1.5O4 cathodes and carbonate electrolytes. Sultines were applied to build highly valuable sultones, mercaptoalkanols, and disulfides. Mechanistic studies and density functional theory calculations supported that the reaction likely proceeds through an energy-transfer-powered radical–radical cross-coupling cyclization process