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Streptomyces sp. HNA39 is a promising candidate for the production of antineoplastic metabolites screened from a collection of 448 actinomycetes derived from coastal sediments. The complete genome sequence of HNA39 comprises a 7,351,753-bp linear chromosome with a GC content of 71.94%. Whole genome analysis reveals the presence of 29 putative biosynthetic gene clusters (BGCs) encoding secondary metabolites. Among them, a type I PKS BGC shows an 82% similarity with the cyclizidine (CLD) BGC identified from Streptomyces NCIB 11649. LC-MS profiles further supported the production of new CLD congeners. Bafilomycins were also found produced in abundance, corresponding to another type I PKS BGC highly homologous to that of bafilomycin B1 from S. lohii. CLDs are indolizidine alkaloids consisting a fused five- and six-membered ring system with an intriguing cyclopropane terminal linked by a trans-dienic chain. The cyclization mechanism of the cylopropyl ring, one of its pharmacophores, is still unknown. Genome sequencing of the new CLD producer and subsequent comparative analysis of their gene clusters would further our understanding of the chemistry behind cyclopropane formation., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polychlorinated biphenyls (PCBs) and microplastics (MPs) commonly co-exist in various environments. MPs inevitably start aging once they enter environment. In this study, the effect of photo-aged polystyrene MPs on microbial PCB dechlorination was investigated. After a UV aging treatment, the proportion of oxygen-containing groups in MPs increased. Photo-aging promoted the inhibitory effect of MPs on microbial reductive dechlorination of PCBs, mainly attributed to the inhibition of meta-chlorine removal. The inhibitory effects on hydrogenase and adenosine triphosphatase activity by MPs increased with increasing aging degree, which may be attributed to electron transfer chain inhibition. PERMANOVA showed significant differences in microbial community structure between culturing systems with and without MPs (p < 0.05). Co-occurrence network showed a simpler structure and higher proportion of negative correlation in the presence of MPs, especially for biofilms, resulting in increased potential for competition among bacteria. MP addition altered microbial community diversity, structure, interactions, and assembly processes, which was more deterministic in biofilms than in suspension cultures, especially regarding the bins of Dehalococcoides. This study sheds light on the microbial reductive dechlorination metabolisms and mechanisms where PCBs and MPs co-exist and provides theoretical guidance for in situ application of PCB bioremediation technology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The latent reservoir of HIV-1 in resting memory CD4 + T cells serves as a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 is proposed as a promising strategy for the clearance of the viral reservoirs. Because of the limitations of current latency reversal agents (LRAs), identification of new LRAs is urgently required. Here, we analyzed Euphorbia kansui extracts and obtained three ingenol derivative compounds named EK-1A, EK-5A and EK-15A. We found that ingenol derivatives can effectively reactivate latent HIV-1 at very low (nanomolar) concentrations in HIV latency model in vitro. Furthermore, ingenol derivatives exhibited synergy with other LRAs in reactivating latent HIV-1. We verified that EK-15A can promote latent HIV-1 reactivation in the ex vivo resting CD4 + T cells isolated from the peripheral blood of HIV-infected individuals on suppressive antiretroviral therapy. In addition, ingenol derivatives down-regulated the expression of cell surface HIV co-receptors CCR5 and CXCR4, therefore potentially preventing new infection of HIV-1. Our results indicated that the ingenol derivatives extracted from Euphorbia kansui have dual functions: reactivation of latent HIV-1 and inhibition of HIV-1 infection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Unlabelled: Glycoproteomics is greatly developed in recent years and big data of N-glycoproteome in mammalian tissues and cells were already established. However, the glycoproteomic studies on plant, fungus and bacteria are far left behind. In this study, we comprehensively mapped and quantified the N-glycosylation of Fusarium graminearum by combining stable isotope dimethyl labeling, hydrophilic interaction chromatography (HILIC) and high-resolution mass spectrometry. The N-glycosylation changes in Fusarium graminearum after fungicide treatment were extensively studied. Altogether we identified 927 N-glycopeptides, corresponding to 406 proteins and 774 sites and the glycosylation level was found to be largely down-regulated upon fungicide treatment. With the help of advanced bioinformatics, it was found that the N-glycoproteome changes were highly enriched in cell wall, membrane and extracellular regions. Moreover, the fungal metabolism, protein and glycosylation synthesis, and protease and glycosyl-transferase activity were all closely related with the down-regulated proteins, indicates that fungicide may affect fungal development in these aspects. These results will be useful for future studies on fungal biology. The established system for N-glycoproteome quantification has comparative or better performance compared with previous strategies and will be helpful in N-glycoproteomics of fungus and other species., Significance: We developed a robust HILIC-based system for N-glycoproteome quantification in fungus and established the largest quantitative N-glycosylation dataset in fungus, showing the high performance of the new system. The identified N-glycoproteins were proved to be high confident due to the high percentage of proteins in extracellular region and plasma. The quantification results were also accuracy and reproducible in two replicates. By the help of advanced bioinformatic tools, the obtained data was systematically analyzed. It was found that the N-glycosylation level was largely changed in cell wall, membrane and extracellular regions. Moreover, the cell metabolism, protein synthesis, and protease activity were also greatly deceased after fungicide treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the present study, the EtOAc extract of the persistent calyx of Physalis angulata L. var. villosa Bonati (PA) was tested for its potential quinone reductase (QR) inducing activity with glutathione (GSH) as the substrate using an UPLC-ESI-MS method. The result revealed that the PA had electrophiles that could induce quinone reductase (QR) activity, which might be attributed to the modification of the highly reactive cysteine residues in Keap1. Herein, three new withanolides, compounds 3, 6 and 7, together with four known withanolides, compounds 1, 2, 4 and 5 were isolated from PA extract. Their structures were determined by spectroscopic techniques, including (1)H-, (13)C NMR (DEPT), and 2D-NMR (HMBC, HMQC, (1)H, (1)H-COSY, NOESY) experiments, as well as by HR-MS. All the seven compounds were tested for their QR induction activities towards mouse hepa 1c1c7 cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A new prenylated chalcone xanthohumol M (1), a novel prenylated bichalcone humulusol (2) and six known chalcones (3-8) were found from Humulus lupulus. Their structures were determined by spectroscopic methods. All the chalcones' electrophilic abilities were assessed by GSH (glutathione) rapid screening, and their QR (quinone reductase) induction activities were evaluated using hepa 1c1c7 cells. The results of electrophilic assay and QR induction activity assay were quite well. New compounds 1 and 2, along with some known prenylated chalcones, displayed certain QR induction activity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the present study, it was demonstrated that the dichloromethane extract of Physalis pubescens L. (DEPP) had weak potential quinone reductase (QR) inducing activity, but an UPLC-ESI-MS method with glutathione (GSH) as the substrate revealed that the DEPP had electrophiles (with an α,β-unsaturated ketone moiety). These electrophiles could induce quinone reductase (QR) activity, which might be attributed to the modification of the highly reactive cysteine residues in Keap1. Herein, four withanolides, including three new compounds physapubescin B (2), physapubescin C (3), physapubescin D (4), together with one known steroidal compound physapubescin (1) were isolated. Structures of these compounds were determined by spectroscopic analysis and that of physapubescin C (3) was confirmed by a combination of molecular modeling and quantum chemical DFT-GIAO calculations. Evaluation of the QR inducing activities of all withanolides indicated potent activities of compounds 1 and 2, which had a common α,β-unsaturated ketone moiety., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In the present study, it was demonstrated that the petroleum extract of Andrographis paniculata (AP) had quinone reductase (QR) inducing activity, which might be attributed to the modification of key cysteine residues in Keap1 by Michael addition acceptors (MAAs) in it. To screen MAAs in AP, glutathione (GSH) was employed, and a LC/MS/MS method was implied. Three compounds, andrographoside, andrographolide, 14-deoxy-14,15-dehydroandrographolide were revealed could well conjugated with GSH. Then, andrographolide along with 4 new and 14 known compounds were isolated to conduct QR induction evaluation, and the CD (the concentration required to double the activity of QR) value of andrographolide is 1.43μM. The QR induce activity of andrographolide might be attributed to its targeting multiple cysteine residues in Keap1, therefore, the alkylation of Keap1 by andrographolide was further studied and the result showed that four cysteine residues: Cys77, Cys151, Cys273 and Cys368 were alkylated, which indicated that Keap1 is a potential target for the QR induce activity of andrographolide., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Michael reaction acceptors (MRAs) are a class of active molecules that are directly or indirectly involved in various cellular processes, including the regulation of many signaling pathways. In this study, the inducible nitric oxide synthase (iNOS) assay was used to demonstrate that the dichloromethane extract of Physalis alkekengi var. franchetii (DCEP) possesses anti-inflammatory activity that might be attributed to the modification of key cysteine residues in IKKβ by the MRAs in DCEP. To isolate these MRAs, glutathione (GSH) was employed, and a simple ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) screening method was developed to investigate the GSH conjugates with potential MRAs. Five physalins, including one new compound isophysalin A (2), together with four known steroidal compounds, physalin A (1), physalin O (3), physalin L (4) and physalin G (5), were isolated to evaluate the GSH conjugating abilities, and it was indicated that compounds 1, 2 and 3, which had a common α,β-unsaturated ketone moiety, exhibited conjugating abilities with GSH and also showed significant nitric oxide (NO) production inhibiting activities. The anti-inflammatory activities of compounds 1, 2 and 3 might be attributed to their targeting multiple cysteine residues on IKKβ; therefore, the alkylation of IKKβ by compound 1 was further studied by micrOTOF-MS. The result showed that six cysteine residues (C(59), C(179), C(299), C(370), C(412), and C(618)) were alkylated, which indicated that IKKβ is a potential target for the anti-inflammatory activity of physalin A., (Copyright © 2011 Elsevier Inc. All rights reserved.)

An abietane diterpenoid, triptobenzene Y and six sesquiterpene polyol esters, wilforsinines C-H, together with 14 known compounds, have been isolated from the roots of Tripterygium wilfordii. The structures of the compounds were elucidated on the basis of spectroscopic analyses. The quinone reductase (QR) induction assay indicated that two compounds showed moderate QR-inducing activities at concentrations of 25 μM and 50 μM, respectively., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Keap1-Nrf2 pathway has emerged as a regulator for the endogenous antioxidant response, which is critical in defending cells against carcinogenesis. Herein, we demonstrated that depleting the cellular level of glutathione (GSH) by a novel electrophilic agent 2-(pro-1-ynyl)-5-(5,6-dihydroxypenta-1,3-diynyl) thiophene (PYDDT) could activate Keap1-Nrf2 pathway. In above process, it was found that Keap1 was modified by S-glutathionylation, an important post-translational modification of protein cysteines with critical roles in oxidative stress and signal transduction. We concluded from our findings that conjugation with intracellular GSH by PYDDT might lead to Keap1 S-glutathionylation and was a key event involved in its Nrf2 inducing activity., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

A new secoiridoid named chinensisol (1) along with twenty known compounds were isolated from the 95% ethanol extract of Cortex fraxini. Their structures were elucidated on the basis of NMR, MS, IR and UV spectral evidences. The quinone reductase (QR) inducing activities of the compounds were evaluated and the results showed that compounds 1, 9 and 14 had moderate QR inducing activities with CD values (concentration required to double the specific activity of QR) of 72.4 ± 7.7, 34.3 ± 3.3 and 42.0 ± 0.4 μM respectively., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Four compounds, including one new lignan cavaol H (1), one new coumarinolignoid 5'-hydroxycleomiscosin B (4) and two known lignans (2-3) were isolated from the 95% ethanol extract of the twigs of Eurycorymbus cavaleriei. Their structures were established on the basis of various spectroscopic analyses including 1D-(1H, 13C, and DEPT) and 2D-NMR (COSY, HMQC, and HMBC). The absolute stereochemistry of the two known lignans was firstly reported in this article by 1H NMR studies on Mosher's ester derivatives. In the present study, quinone reductase induction activities of compounds 1-4 were assayed, compound 4 showed moderate quinone reductase induction with concentration to double the enzyme activity (CD) of 10.5 +/- 0.8 microg/mL. Then we established LC-MS-MS analysis of glutathione (GSH) incubation with compound 4 to explain whether compound 4 induced quinone reductase through alkylating of the sulfhydryl groups of Keap1. Reconstructed selected ion chromatogram (SIC) of m/z 706 after compound 4 incubation with GSH was different from that with Tris-HCl buffer solution, which meant the quinone reductase induction activity of compound 4 attributed to alkylating the sulfhydryl groups of Keap1.

In the present study, we examined the potential chemopreventive activity of dichloromethane extract of Eurycorymbus cavaleriei by investigating the change of constitutions after incubation with glutathione (GSH). The major constitutions in the dichloromethane extract of E. cavaleriei were cumarin compounds and their cleavage pattern was examined by LC-MS-MS and the characteristic product ions at m/z 206 and 207 were helpful to determine the substitutions of coumarinolignoid compounds. The mechanism of conjugations of 5'-demethylaquillochin and its isomer with GSH was discussed and validated through analysis of the conjugations of reference compound 6-hydroxy-7-methoxycoumarin with GSH by LC-MS-MS and NMR spectrum. The relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1) of nine coumarin compounds was tested which also showed 5'-demethylaquillochin exhibited the most potential chemopreventive ability. These observations suggest that 5'-demethylaquillochin and its isomer from the dichloromethane extract of E. cavaleriei have potential as chemopreventive agents through induction of detoxification enzymes.