Virtual database screening allows for millions of chemical compounds to be computationally selected based on structural complimentary to known inhibitors or to a target binding site on a biological macromolecule. Compound selection in virtual database screening when targeting a biological macromolecule is typically based on the interaction energy between the chemical compound and the target macromolecule. In the present study it is shown that this approach is biased toward the selection of high molecular weight compounds due to the contribution of the compound size to the energy score. To account for molecular weight during energy based screening, we propose normalization strategies based on the total number of heavy atoms in the chemical compounds being screened. This approach is computationally efficient and produces molecular weight distributions of selected compounds that can be selected to be (1) lower than that of the original database used in the virtual screening, which may be desirable for selection of leadlike compounds or (2) similar to that of the original database, which may be desirable for the selection of drug-like compounds. By eliminating the bias in target-based database screening toward higher molecular weight compounds it is anticipated that the proposed procedure will enhance the success rate of computer-aided drug design.

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Background: The black soldier fly (Hermetia illucens) is gaining attention as an efficient decomposer of food waste. However, recalcitrant compounds such as plastics mixed into food waste may have negative effects on its growth and survival. Moreover, its efficiency of food waste degradation may also be affected by plastics. In addition, salt (NaCl) can also be present in high concentrations, which also reduces the efficiency of H. illucens-mediated food waste treatment. In this study, we assessed the growth of black soldier fly larvae (BSFL) reared on food waste containing polyethylene (PE) and polystyrene (PS) and NaCl. The weight of BSFL was measured every 2-4 days. Survival and substrate reduction rates and pupation ratio were determined at the end of the experiment. Results: The total larval weight of Hermetia illucens reared on food waste containing PS was greater than that of the control on days 20 and 24. However, the survival rate was lower in the group treated with 5% PS, as was substrate reduction in all PS-treated groups. The weight of BSFL reared on food waste containing PE was lower than that of the control on day 6. PE in food waste did not affect the survival rate, but the pupation ratio increased and substrate consumption decreased with increasing PE concentrations. Regardless of the plastic type, the addition of NaCl resulted in decreased larval weight and pupation ratio. Conclusions: Larval growth of black soldier fly was inhibited not by plastics but by substrate salinity. Additional safety assessments of larvae reared on food waste containing impurities are needed to enable wider application of BSFL in vermicomposting.

Significance Statement Understanding the mechanisms underlying adaptive and maladaptive renal repair after AKI and their long-term consequences is critical to kidney health. The authors used lineage tracing of cycling cells and single-nucleus multiomics (profiling transcriptome and chromatin accessibility) after AKI. They demonstrated that AKI triggers a cell-cycle response in most epithelial and nonepithelial kidney cell types. They also showed that maladaptive proinflammatory proximal tubule cells (PTCs) persist until 6 months post-AKI, although they decreased in abundance over time, in part, through cell death. Single-nucleus multiomics of lineage-traced cells revealed regulatory features of adaptive and maladaptive repair. These included activation of cell state–specific transcription factors and cis-regulatory elements, and effects in PTCs even after adaptive repair, weeks after the injury event. Background AKI triggers a proliferative response as part of an intrinsic cellular repair program, which can lead to adaptive renal repair, restoring kidney structure and function, or maladaptive repair with the persistence of injured proximal tubule cells (PTCs) and an altered kidney structure. However, the cellular and molecular understanding of these repair programs is limited. Methods To examine chromatin and transcriptional responses in the same cell upon ischemia-reperfusion injury (IRI), we combined genetic fate mapping of cycling (Ki67 +) cells labeled early after IRI with single-nucleus multiomics—profiling transcriptome and chromatin accessibility in the same nucleus—and generated a dataset of 83,315 nuclei. Results AKI triggered a broad cell cycle response preceded by cell type–specific and global transcriptional changes in the nephron, the collecting and vascular systems, and stromal and immune cell types. We observed a heterogeneous population of maladaptive PTCs throughout proximal tubule segments 6 months post-AKI, with a marked loss of maladaptive cells from 4 weeks to 6 months. Gene expression and chromatin accessibility profiling in the same nuclei highlighted differences between adaptive and maladaptive PTCs in the activity of cis-regulatory elements and transcription factors, accompanied by corresponding changes in target gene expression. Adaptive repair was associated with reduced expression of genes encoding transmembrane transport proteins essential to kidney function. Conclusions Analysis of genome organization and gene activity with single-cell resolution using lineage tracing and single-nucleus multiomics offers new insight into the regulation of renal injury repair. Weeks to months after mild-to-moderate IRI, maladaptive PTCs persist with an aberrant epigenetic landscape, and PTCs exhibit an altered transcriptional profile even following adaptive repair.