FraHMT: A Fragment-Oriented Heterogeneous Graph Molecular Generation Model for Target Proteins.

The molecular generation task stands as a pivotal step in the domains of computational chemistry and drug discovery, aiming to computationally generate molecular structures for specific properties. In contrast to previous models that focused primarily on SMILES strings or molecular graphs, our model placed a special emphasis on the substructure information on molecules, enabling the model to learn richer chemical rules and structure features from fragments and chemical reaction information on molecules. To accomplish this, we fragmented the molecules to construct heterogeneous graph representations based on atom and fragment information. Then our model mapped the heterogeneous graph data into a latent vector space by using an encoder and employed a self-regressive generative model as a decoder for molecular generation. Additionally, we performed transfer learning on the model using a small set of ligand molecules known to be active against the target protein to generate molecules that bind better to the target protein. Experimental results demonstrate that our model is highly competitive with state-of-the-art models. It can generate valid and diverse molecules with favorable physicochemical properties and drug-likeness. Importantly, they produce novel molecules with high docking scores against the target proteins.

Domain-limited thermal transformation preparation of novel graphitized carbon-supported layered double oxides for efficient tetracycline degradation.

The resource utilization of industrial lignin to construct high-performance catalysts for wastewater treatment field is pioneering research. Herein, the novel graphitized carbon-supported CuCoAl-layered double oxides (LDOs-GC) were successfully designed by the domain-limited thermal transformation technology using sodium lignosulfonate (LS) self-assembled CuCoAl-layered double hydroxides as the precursor. The optimized LDOs-GC catalyst owned the excellent tetracycline (TC) degradation of 98.0% within 15 min by activated peroxymonosulfate (PMS) under optimal conditions (20 mg/L catalyst, 1.5 mM PMS, 30 mg/L TC). The density of metal ions in the catalyst and the synergistic interaction between graphitized carbon (GC) and metal ions played a major role in TC degradation. Based on a comprehensive analysis, the TC degradation in LDOs-GC/PMS system was proved to be accomplished by a combination of free radicals (SO4·- and HO·) and non-radicals (1O2). Meanwhile, the possible degradation pathways of TC were proposed by the analysis of TC degradation intermediates and a comprehensive analysis of the rational reaction mechanism for TC degradation by LDOs-GC/PMS system was also performed. This work provides a new strategy for developing novel high-performance catalysts from industrial waste, while offering a green, cheap and sustainable approach to antibiotic degradation.

Virtual screening of natural products targeting ubiquitin-specific protease 7.

Ubiquitin-specific protease 7 (USP7) is a promising prognostic and druggable target for cancer therapy. Inhibition of USP7 can activate the MDM2-P53 signaling pathway, thereby promoting cancer cell apoptosis. This study based on watvina molecular docking of virtual screening method and biological evaluation found the new USP7 inhibitors targeting catalytic active site. Three hits were screened from 3760 natural products and validated as USP7 inhibitors by enzymatic and kinetic assays. The IC50 values of scutellarein (Scu), semethylzeylastera (DML) and salvianolic acid C (SAC) were 3.017, 6.865 and 8.495 µM, respectively. Further, we reported that the hits could downregulate MDM2 and activate p53 signal pathway in HCT116 cells. Molecular dynamics simulation was used to investigate the binding mechanism of USP7 to Scu, the compound with the best performance, which formed stable contact with Val296, Gln297, Phe409, Tyr465 and Tyr514. These interactions are essential for maintaining the biological activity of Scu. Three natural products are suitable as lead compounds for the development of novel USP7 inhibitors, especially anti-colon cancer drugs.Communicated by Ramaswamy H. Sarma.

Novel Engineered Carbon Cloth-Based Self-Cleaning Membrane for High-Efficiency Oil-Water Separation.

A novel engineered carbon cloth (CC)-based self-cleaning membrane containing a Cu:TiO2 and Ag coating has been created via hydrothermal and light deposition methods. The engineered membrane with chrysanthemum morphology has superhydrophilic and underwater superoleophilic performance. The cooperativity strategy of Cu doping and Ag coating to the TiO2 is found to be critical for engineering the separation efficiency and self-cleaning skill of the CC-based membrane under visible light due to the modulated bandgap structure and surface plasmon resonance. The CC-based membrane has excellent oil-water separation performance when Cu is fixed at 2.5 wt% and the Ag coating reaches a certain amount of 0.003 mol/L AgNO3. The contact angle of underwater oil and the separation efficiency are 156° and 99.76%, respectively. Furthermore, the membrane has such an outstanding self-cleaning ability that the above performance can be nearly completely restored after 30 min of visible light irradiation, and the separation efficiency can still reach 99.65% after 100 cycles. Notably, the membrane with exceptional wear resistance and durability can work in various oil-water mixtures and harsh environments, indicating its potential as a new platform of the industrial-level available membrane in dealing with oily wastewater.

A co-precipitation route for the preparation of eco-friendly Cu-Al-layered double hydroxides with efficient tetracycline degradation.

The construction of novel efficient catalysts for the treatment of organic pollutants in the aqueous environment is essential. The lamellar-like Cu-Al layered double hydroxides (CuAl-LDHs) with various mole ratios were synthesized by a simple route of co-precipitation, and the corresponding degradation characteristic was tested for the removal of tetracycline (TC) using PMS activation. The degradation efficiency of TC over CuAl-LDHs increased up to 93% within 10 min for the Cu/Al mole ratio of 3:1 and almost not changed at a higher mole ratio. For further calcining the optimal catalyst at 300 ℃, the degradation efficiency of TC was found to be increased to 96%. Sulfuric radicals and singlet oxygen were analyzed to be the main reason for the change in degradation characteristics, which was proved by radical quenching experiments and electron paramagnetic resonance technique. The parameters including PMS concentration, catalyst dosage, and reaction temperature on the TC degradation as well as the degradation mechanism for PMS activation were elaborated. The best proportion of CuAl-LDHs owned splendid stability and catalytic activity after reusing, which showed enormous potential in practical application.