Mechanism of skin whitening through San-Bai decoction-induced tyrosinase inhibition and discovery of natural products targeting tyrosinase.

Melanin deposition is the main cause of skin darkening, which can lead to severe physical and psychological distress, necessitating the development of approaches for preserving skin health and fairness. Tyrosinase (TYR) is the rate-limiting enzyme in melanin synthesis, and its activity directly determines the degree of melanin accumulation in the skin, which in turn affects skin color. Currently, TYR inhibitors derived from natural products are widely used for skin whitening. San-Bai decoction (SBD) is effective for skin whitening and softening, but its mechanism of action, efficacy and high efficiency TYR inhibitors for skin whitening remain poorly understood. Here, we employed systems biology and network pharmacology to analyze the active compounds and targets of SBD, using the follow databases: TCMIP, TCMID, and BATMAN-TCM. Construct a molecular network centered on the regulation of TYR by SBD in skin whitening, using STRING database and cytoscape. Enrichment analysis using KOBAS database and ClusterProfiler. Virtual screening of candidate TYR inhibitors using Molecular Operating Environment software and Amber 18 software. SBD may act through tyrosine metabolism, melanogenesis, and other signaling pathways to regulate TYR activity and inhibit melanogenesis. We identified TYR and ESR1 as possible key targets for the whitening effect of SBD and screened out pentagalloylglucose, 1,3,6-tri-O-galloyl-beta-D-glucose, 1,2,4,6-tetragalloylglucose, and liquiritigenin 4',7-diglucoside as inhibitors of TYR, in addition to glycyrrhizic acid, pachymic acid methyl ester, nicotiflorin, gamma-sitosterol, and isoliensinine as inhibitors of ESR1. We also performed virtual drug screening of a library of natural small-molecule compounds (19,505 in total) and screened out lycopsamine, 2-phenylethyl b-D-glucopyranoside, and 6-beta-hydroxyhyoscyamine as inhibitors of TYR. We identified natural compounds with the potential for skin whitening through inhibition of TYR, thus advancing research on SBD and its applications.

Cultivation-dependent and cultivation-independent investigation of O-methylated pollutant-producing bacteria in three drinking water treatment plants.

O-methylated pollutants (OMPs) are emerging contaminants in drinking water and mainly produced through bacterial O-methylation. However, the information of OMP-producing bacteria (OMPPB) in drinking water treatment plant (DWTP) is largely unknown so far. In this study, the OMPPB in water samples from three DWTPs (XL, JX and NX) were investigated by using cultivation-dependent and cultivation-independent technologies. Four OMPs were detected and their odor and toxicity risks were assessed. Formation potentials (FPs) of 2,4,6-trichloanisole, 2,3,6-trichloanisole, 2,4,6-tribromoanisole, pentachloroanisole and diclofenac methyl ester were determined in water samples and their values shifted significantly among DWTPs. A most probable number (MPN) method was established to quantify OMPPB numbers and the relationships between total haloanisole FPs (HAFPs) (y) and OMPPB numbers (x) in three DWTPs could be described by the following functions: y = 0.496×0.373 (XL), y = 0.041×0.465 (JX) and y = 0.218×0.237 (NX). Several genera like Bacillus, Ralstonia, Brevundimonas, etc. were newly found OMPPB among the cultivable bacteria, and their OMP products were evaluated in terms of quantity and environment risks (odor, toxicity and bioaccumulation). High-throughput sequencing revealed treatment process was the main driving factor to shape the OMPPB community structures and Mantel test showed HAFP profile was significantly influenced by Mycobacterium and Pelomonas. PICURSt2 analysis discovered four phenolic O-methyltransferases (OMTs) and four carboxylic OMTs which might be responsible for OMP formation. Several strategies were recommended to assess risk and control contamination brought by OMPPB in DWTPs.

Mycobacterial PPE13 activates inflammasome by interacting with the NATCH and LRR domains of NLRP3.

Pathogenic mycobacteria, such as Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium marinum, can trigger NLRP3 inflammasome activation leading to maturation and secretion of interleukin 1ß (IL-1ß). However, the mycobacterial factors involved in the activation of NLRP3 inflammasome are not fully understood. Here, we identified that the PPE family protein PPE13 was responsible for the induction of IL-1ß secretion in a NLRP3 inflammasome-dependent manner. We found that the recombinant Mycobacterium smegmatis expressing PPE13 activates NLRP3 inflammasome, thereby inducing caspase-1 cleavage and IL-1ß secretion in J774A.1, BMDMs, and THP-1 macrophages. To examine whether this inflammasome activation was triggered by PPE13 rather than components of M. smegmatis, PPE13 was introduced into the aforementioned macrophages by lentivirus as a delivery vector. Similarly, this led to the activation of NLRP3 inflammasome, indicating that PPE13 is a direct activator of NLRP3 cascade. We further demonstrated that the NLRP3 complex activated the inflammasome cascade, and the assembly of this complex was facilitated by PPE13 through interacting with the LRR and NATCH domains of NLRP3. Finally, we found that all PPE13 proteins isolated from M. tuberculosis, M. bovis, and M. marinum can activate NLRP3 inflammasome through binding to NLRP3, which requires C-terminal repetitive MPTR domain of PPE13. Thus, we, for the first time, revealed that PPE13 triggers the inflammasome-response by interacting with the MPTR domain of PPE13 and the LRR and NATCH domains of NLRP3. These findings provide a novel perspective on the function of PPE proteins in the immune system during mycobacteria invasion.

Direct Z-scheme La1-xCexMnO3 catalyst for photothermal degradation of toluene.

A series of Ce-doped LaMnO3 (La1-xCexMnO3) were prepared and were tested for gaseous toluene oxidation in order to investigate the effect of cerium doping in LaMnO3 on activity under photothermal conditions. It was found that the activity and CO2 yield of the catalyst can be effectively increased when x = 0.25. A group of characterization is used to characterize the morphology, composition, and physical properties of the as-prepared catalysts. Results show that the Ce-doped LaMnO3 can form coexistence of La1-xCexMnO3 and CeO2, the reaction of CeO2/La1-xCexMnO3 under photothermal conditions follows the Mars-van Krevelen redox cycle mechanism, and the prepared CeO2/La1-xCexMnO3 can form a highly efficient Z-scheme heterojunction, which can enhance the electrons transfer speed of the catalyst. Moreover, in the photothermal catalytic degradation, lattice oxygen is the most important active substance, a small amount of cerium doping can increase the lattice oxygen content of perovskite and increase the activity of the reaction.