Advancing the Boundary of Pre-trained Models for Drug Discovery: Interpretable Fine-Tuning Empowered by Molecular Physicochemical Properties.

In the field of drug discovery, a proliferation of pre-trained models has surfaced, exhibiting exceptional performance across a variety of tasks. However, the extensive size of these models, coupled with the limited interpretative capabilities of current fine-tuning methods, impedes the integration of pre-trained models into the drug discovery process. This paper pushes the boundaries of pre-trained models in drug discovery by designing a novel fine-tuning paradigm known as the Head Feature Parallel Adapter (HFPA), which is highly interpretable, high-performing, and has fewer parameters than other widely used methods. Specifically, this approach enables the model to consider diverse information across representation subspaces concurrently by strategically using Adapters, which can operate directly within the model's feature space. Our tactic freezes the backbone model and forces various small-size Adapters' corresponding subspaces to focus on exploring different atomic and chemical bond knowledge, thus maintaining a small number of trainable parameters and enhancing the interpretability of the model. Moreover, we furnish a comprehensive interpretability analysis, imparting valuable insights into the chemical area. HFPA outperforms over seven physiology and toxicity tasks and achieves state-of-the-art results in three physical chemistry tasks. We also test ten additional molecular datasets, demonstrating the robustness and broad applicability of HFPA.

New natural furfural derivatives from the leaves and stems of Pogostemon cablin.

A new furfural derivative, pogoscafuran A (1), a new natural product, HMF levulinate (2), together with four known compounds (3-6) were isolated from an extract of the leaves and stems of Pogostemon cablin (Blanco) Benth. Their structures were elucidated on the basis of extensive spectroscopic analyses and single-crystal X-ray crystallography. Compound 1 was the first example of natural furfural derivative with a unique C5-C1' linkage between a molecule of furfural and 3-methyl-2-cyclopentenone moiety. The plausible biogenetic pathway for the new compound 1 was proposed. All these isolated compounds were tested for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and only compound 1 exhibited weak inhibitory activity.

N-doped biochar-catalyzed dechlorination of carbon tetrachloride in sulfide-containing aqueous solutions: Performances, mechanisms and pathways.

Nitrogen-doped biochar (N-BC) has been widely concerned in the field of environmental protection. This study verified the alfalfa-based N-BC pyrolyzed at different temperatures is able to catalyze carbon tetrachloride (CT) dechlorination in sulfide-containing aqueous solutions under normal environmental pH range (6.3 ∼ 8.3) effectively, with Cl-, trichloromethane (CF), CS2 and HCO3- as predominated products. Higher pyrolysis temperature resulted in larger specific surface area, more pores and better catalytic capacity. The N-BC had a good tolerance to water matrix in catalyzing CT dechlorination by sulfide, while the higher pH value or higher dosage of sulfide or N-BC was beneficial to catalytic CT dechlorination. The generation of CS2 was the major CT dechlorination pathway, attributing to the SN2 nucleophilic substitution by newborn C-SS- structure generating from the interaction between pyridine-N and sulfide. Besides, generation of CF via hydrogenolysis process was the minor CT dechlorination pathway, owing to the enhanced electron transfer by pyrrole-N, graphitic-N and quinones on surface of N-BC. It was the first time that N-BC was found to be effective in catalyzing the hydrogenolysis process of CT dechlorination. This study emphasized the importance of N-BC in restoring chlorinated hydrocarbons polluted aquatic environment containing sulfide, such as sediments.

0D/3D NiCo2O4/defected UiO-66 catalysts for enhanced degradation of tetracycline in peroxymonosulfate/simulated sunlight systems: Degradation mechanisms and pathways.

Developing synergistic systems and taking environmental risks into account are two necessary aspects of being considered to remove persistent organic pollutants efficiently. Thus, a combined catalytic system uniting the Fenton-like process and simulated solar-light photocatalysis has been constructed. Moreover, a series of NiCo2O4/HP-UiO-66 catalysts (yNiCo-DUx) were also fabricated to improve tetracycline (TC) removal efficiency. The NiCo2O4 nanoparticles (NPs) and hierarchically porous metal-organic frameworks (HP-MOFs) were synthesised using one-step calcination. The Z-scheme structure of the catalysts was confirmed by ESR, XPS, DRS, time-resolved PL (TR-PL) spectra and the quenching experiments. The NiCo2O4 nanoparticles could be embedded and fixed into the defects of the MOF structure, and the leaching of toxic metals was also significantly suppressed. In the optimal reaction condition with 15NiCo-DU50, sunlight, and peroxymonosulfate (PMS), the total removal efficiency of TC could reach 98.5% within 8 min of irradiation, and the highest % RSE could reach 11.2%. Moreover, the corresponding reaction rate was 28.7, 3.6 and 1.3-10.2 times higher than photocatalysis, Fenton-like processes and other catalysts. Furthermore, the possible degradation mechanism, generation of reactive species and PMS excitation pathways were also investigated in depth. The present study sheds light on the fabrication of HP-MOFs based catalysts and the combination of various methods to eliminate organic pollutants.

Hexachloroethane dechlorination in sulfide-containing aqueous solutions catalyzed by nitrogen-doped carbon materials.

This study demonstrated that nitrogen-doped carbon materials (NCMs) could effectively catalyze the chlorine elimination process in hexachloroethane (HCA) declorination in sulfide-containing environments for the first time. The kobs values of HCA dechlorination by sulfide in the presence of 10 mg/L NCMs were higher than that of no mediator at pH 7.3 by one or two orders of magnitude. The catalytic capabilities of NCMs on HCA dechlorination were evident in common ranges of natural pH (5.3-8.9) and it could be accelerated by the increase of pH but be suppressed by the presence of dissolved humic acid. Moreover, NCMs exhibited much better catalytic capability on HCA dechlorination compared to the carbon materials, mainly owing to the combined contributions of pyridine N, including enhanced nucleophilic attack to HCA molecule by generating newborn C-S-S and activation of HCA molecule by elongating C-Cl bonds. The functions of pyridine N in micron-sized NCMs with mesopores were better than in nano-sized NCMs on HCA dechlorination. These findings displayed the potential of NCMs, when released into sulfide-containing environments, may significantly increase the dechlorination of chlorinated aliphatic hydrocarbons.

Nitrogen-Doped Carbon Materials as Metal-Free Catalyst for the Dechlorination of Trichloroethylene by Sulfide.

A new method for trichloroethylene (TCE) dechlorination is proposed using sulfide (HS- and S2-) as reductant under the mediation of nitrogen-doped carbon materials (NCMs). About 99% of the TCE was converted to acetylene after 200 h using this method. Dechlorination of TCE in the NCMs-sulfide system (NCSS) followed pseudo-first-order kinetics. Pyridinic N (N6) on surface of the NCMs appeared to play a critical role in NCSS as shown by the good linear relationship between the surface content of N6 and kobs. Nucleophilic substitution was suggested as the first step in TCE dechlorination, and the nucleophilic reagent was identified as a sulfur intermediate with C-S-S-H as the functional group. The generation of C-S-S-H could be ascribed to the interaction between positively charged carbon atoms in N6 and negative charged sulfide. This work is the first to demonstrate that sulfide combined with NCMs can produce active substances that are effective in TCE dechlorination and the findings will assist in the development of strategies that use natural sulfide as reductant for detoxicating organic chloroethene contaminants.

Stable carbon isotope fractionation of chlorinated ethenes by a microbial consortium containing multiple dechlorinating genes.

The study aimed to determine the possible contribution of specific growth conditions and community structures to variable carbon enrichment factors (Ɛ-carbon) values for the degradation of chlorinated ethenes (CEs) by a bacterial consortium with multiple dechlorinating genes. Ɛ-carbon values for trichloroethylene, cis-1,2-dichloroethylene, and vinyl chloride were -7.24% ±â€¯0.59%, -14.6% ±â€¯1.71%, and -21.1% ±â€¯1.14%, respectively, during their degradation by a microbial consortium containing multiple dechlorinating genes including tceA and vcrA. The Ɛ-carbon values of all CEs were not greatly affected by changes in growth conditions and community structures, which directly or indirectly affected reductive dechlorination of CEs by this consortium. Stability analysis provided evidence that the presence of multiple dechlorinating genes within a microbial consortium had little effect on carbon isotope fractionation, as long as the genes have definite, non-overlapping functions.

Oxygen exposure effects on the dechlorinating activities of a trichloroethene-dechlorination microbial consortium.

The aim of this work was to study the effects of the presence of oxygen on the dechlorination of trichloroethene by a microbial consortium containing D. mccartyi. The 16S rRNA and reductive dechlorination genes of the functional bacteria and the non-dechlorinators were monitored. Exposing the consortium to oxygen altered the overall biotransformation rate of the dechlorination process, biotransformation processes prolonged with oxygen concentrations changing from 0 to 7.2mg/L, however, trichloroethylene was eventually dechlorinated to ethene. The qPCR analyses revealed that the D. mccartyi strains containing the tceA gene were less sensitive to exposure to oxygen than were the D. mccartyi strains containing the vcrA gene. High-throughput sequencing by Illumina MiSeq indicated that the non-dechlorinating organisms were probably crucial to scavenge the oxygen to protect D. mccartyi from being damaged.

N-doped nanoporous carbon as efficient catalyst for nitrobenzene reduction in sulfide-containing aqueous solutions.

Metal-free N-doped porous carbon (NC) materials have been demonstrated to be promising catalysts in contaminated environment remediation. Two NC materials (NC-1 and NC-2) were prepared by sol-gel routes. Their catalytic properties were investigated for the reduction of nitrobenzene (NB) in sulfide-containing aqueous solution. Both NC-1 and NC-2 can efficiently catalyze the reduction of NB to aniline (AN) under ambient conditions, but also can be reused for more than 5 times. The reaction fits excellently to the pseudo-first-order kinetic. Compared with NC-1 material, NC-2 shows much higher removal efficiency (rate constant kobs: 0.283h-1vs. 2.50h-1). The important features of NC material, including high specific surface area, suitable surface functional groups (especially nitrogen-containing groups), and enhanced electron transfer ability, should be mainly factors for its excellent catalytic activity. This work demonstrates that N-doped carbon materials have great potential for degradation of NB to AN in the natural aquatic environment.