Supporting Information from Copper-catalysed regioselective sulfenylation of indoles with sodium sulfinates

A copper-catalysed sulfenylation of indoles with sodium sulfinates to afford 3-sulfenylindoles in good-to-excellent yields in DMF is described. In the process, DMF is not only used as a solvent, but also as a reductant. This transformation features easy operation, mild reaction conditions and good functional group tolerance

Multimodal Model to Predict Tissue-to-Blood Partition Coefficients of Chemicals in Mammals and Fish

Tissue-to-blood partition coefficients (Ptb) are key parameters for assessing toxicokinetics of xenobiotics in organisms, yet their experimental data were lacking. Experimental methods for measuring Ptb values are inefficient, underscoring the urgent need for prediction models. However, most existing models failed to fully exploit Ptb data from diverse sources, and their applicability domain (AD) was limited. The current study developed a multimodal model capable of processing and integrating textual (categorical features) and numerical information (molecular descriptors/fingerprints) to simultaneously predict Ptb values across various species, tissues, blood matrices, and measurement methods. Artificial neural network algorithms with embedding layers were used for the multimodal modeling. The corresponding unimodal models were developed for comparison. Results showed that the multimodal model outperformed unimodal models. To enhance the reliability of the model, a method considering categorical features, weighted molecular similarity density, and weighted inconsistency in molecular activities of structure–activity landscapes was used to characterize the AD. The model constrained by the AD exhibited better prediction accuracy for the validation set, with the determination coefficient, root mean-square error, and mean absolute error being 0.843, 0.276, and 0.213 log units, respectively. The multimodal model coupled with the AD characterization can serve as an efficient tool for internal exposure assessment of chemicals

Multimodal Model to Predict Tissue-to-Blood Partition Coefficients of Chemicals in Mammals and Fish

Tissue-to-blood partition coefficients (Ptb) are key parameters for assessing toxicokinetics of xenobiotics in organisms, yet their experimental data were lacking. Experimental methods for measuring Ptb values are inefficient, underscoring the urgent need for prediction models. However, most existing models failed to fully exploit Ptb data from diverse sources, and their applicability domain (AD) was limited. The current study developed a multimodal model capable of processing and integrating textual (categorical features) and numerical information (molecular descriptors/fingerprints) to simultaneously predict Ptb values across various species, tissues, blood matrices, and measurement methods. Artificial neural network algorithms with embedding layers were used for the multimodal modeling. The corresponding unimodal models were developed for comparison. Results showed that the multimodal model outperformed unimodal models. To enhance the reliability of the model, a method considering categorical features, weighted molecular similarity density, and weighted inconsistency in molecular activities of structure–activity landscapes was used to characterize the AD. The model constrained by the AD exhibited better prediction accuracy for the validation set, with the determination coefficient, root mean-square error, and mean absolute error being 0.843, 0.276, and 0.213 log units, respectively. The multimodal model coupled with the AD characterization can serve as an efficient tool for internal exposure assessment of chemicals

Alteration of Diastereoisomeric and Enantiomeric Profiles of Hexabromocyclododecanes (HBCDs) in Adult Chicken Tissues, Eggs, and Hatchling Chickens

The concentrations and enantiomer fractions (EFs) of α-, β-, and γ-hexabromocyclododecanes (HBCDs) were measured in chicken diet sources (soil and chicken feed), home-raised adult chicken (<i>Gallus domesticus</i>) tissues, eggs during incubation, and hatchling chicken tissues. HBCD concentrations were not detected–0.69 ng/g dry weight (dw) and 25.6–48.4 ng/g dw in chicken feed and soil, respectively. HBCDs were detected in all adult chicken tissues, except the brain, at median levels of 13.1–44.0 ng/g lipid weight (lw). The proportions of α-HBCD in total HBCDs increased from 51% in soil to more than 87% in adult chicken tissues. The accumulation ratios (ARs) of α-HBCD from diet to adult chicken tissues were 4.27 for liver, 11.2 for fat, and 7.64–12.9 for other tissues, respectively. The AR and carry-over rate (COR) of α-HBCD from diet to eggs were 22.4 and 0.226, respectively. The concentrations of α-HBCD in hatchling chicken liver (median: 35.4 ng/g lw) were significantly lower than those in hatchling chicken pectoral muscle (median: 130 ng/g lw). The EFs of α-HBCD decreased from soil to adult chicken tissues and from eggs to hatchling chicken liver. Meanwhile, the EFs of γ-HBCD increased from soil to adult chicken tissues. These results indicate the preferential enrichment of (−)-α-HBCD and (+)-γ-HBCD in chickens. The alteration of diastereoisomeric and enantiomeric patterns of HBCDs might be influenced by the different absorption and elimination rates of the six HBCD enantiomers as well as variations in HBCD metabolism in chickens

Additional file 2: Figure S2. of CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma

Specific inhibitor of miR-15a was used to inhibit the expression of miR-15a in shCDK4-2 and shCDK4-3 NPC 5–8 F cells. (TIFF 383 kb

Additional file 1: Figure S1. of CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in nasopharyngeal carcinoma

Lentivirus-mediated miR-15a expression in NPC 5–8 F and HONE1 cells. (TIFF 342 kb

Exploring the Emissive States of Heteroatom-Doped Graphene Quantum Dots

The photoluminescence (PL) emission states of heteroatom-doped graphene quantum dots (GQDs) remain unknown, particularly the assignment of the low-energy excitation band (more than 330 nm). To address these issues, this work synthesized three different types of GQDs: undoped GQDs (UGQDs), nitrogen-doped GQDs (NGQDs), and boron-doped GQDs (BGQDs), with similar sizes, chemical compositions (types and compositions of surface functional groups), and defects using a constant potential electrolysis method. The PL emissive states in these GQDs and the effects of the dopant heteroatom on the PL were revealed based on the combination of spectroscopic methods and theoretical calculations. The results indicated that the GQDs exhibit multiemissive centers for the PL emission mechanism. An excitation-independent PL emission band (band I) results from a high-energy transition originating from the quantum confinement of the carbon core (carbon π–π* transitions in sp² domain), and an excitation-dependent PL emission band (band II) originates from a low-energy edge band transition, which is attributed to radiative recombination associated with both the n−π* transition of N/O/B-containing groups and the π–π* charge transfer between the carbon core and the edge of the GQDs. Moreover, the PL emission maxima (both bands I and II) for NGQDs and BGQDs show a blue shift and a red shift, respectively, relative to UGQDs because of the doping that led to the alteration in the electronic structure and the distribution of molecular orbitals in the GQDs. These results clarify previous inconsistencies regarding the PL emission mechanism and the electronic properties of GQDs and can thus provide a foundation for the application of doped GQDs in electronics, photonics, and biology

Design, Synthesis, and Evaluation of Diazeniumdiolate-Based DNA Cross-Linking Agents Activatable by Glutathione S‑Transferase

A novel class of <i>O</i>²-(2,4-dinitrophenyl)-1-[<i>N</i>,<i>N</i>-bis­(2-substituted ethyl)­amino]­diazen-1-ium-1,2-diolates <b>4</b>–<b>6</b> were designed, synthesized, and biologically evaluated. The most active compound <b>6</b> caused significant DNA damage by releasing <i>N,N</i>-bis­(2-TsO ethyl)­amine and two molecules of nitric oxide (NO) after activation by GST/GSH in cancer cells, being more cytotoxic against three cancer cell lines than a well-known diazeniumdiolate-based anticancer agent JS-K, suggesting that the strategy has potential to extend to other <i>O</i>²-derived diazeniumdiolates to improve anticancer activity

Additional file 3: of Isoliquiritigenin suppresses human melanoma growth by targeting miR-301b/LRIG1 signaling

Figure S1. ISL inhibits cell proliferation and induces cell apoptosis in melanoma cells in vitro. (A) MEWO cells were treated with ISL (0, 10, 20, 40, 80 μM) for 24 h, and cell viability was analyzed by CCK-8 assay. (B) MEWO cells were treated with 20 μM ISL, cell proliferation at indicated time (24, 48, 72 h) was measured by CCK-8 assay. (C, D) Flow cytometry analysis of apoptosis of MEWO cells after being treated with ISL (0, 10, 20 μM) for 24 h. (E, F) Representative images and quantification of colony formation of MEWO cells after being treated with ISL (0, 5, 10 Μm). (G, H)Western blot analysis of the protein level of apoptosis associated proteins(bcl-2, bax, parp, cleaved-caspase-3) in ISL treated A375 and A2058 cells. *P < 0.05, **P < 0.01, ***P < 0.001 vs ISL(0 μM) treated group. n = 3. (TIF 25527 kb

Additional file 4: of Isoliquiritigenin suppresses human melanoma growth by targeting miR-301b/LRIG1 signaling

Figure S3. (A)RT-qPCR analysis of the mRNA level alteration of 7 common target genes of miR301b in A375 and A2058 cells after being transfected with miR301b mimic/NC or treated with miR301b inhibitor/NC. *P < 0.05 vs NC. (B)Design of luciferase reporters with the WT Akt3 3’UTR (Akt3–3’UTR WT) or the site-directed mutant Akt3 3’UTR (Akt3–3’UTR MUT). (C)RT-qPCR analysis of miR301b level in A375 and A2058 cells after being transfected with miR301b mimic/NC or treated with miR301b inhibitor/NC. **P < 0.01 vs NC. (D)RT-qPCR analysis of the mRNA level of LRIG1 in A375 and A2058 cells after being transfected with miR301b mimic/NC or treated with miR301b inhibitor/NC. **P < 0.01 vs NC.*P < 0.05 vs NC. (E, F)Western blot analysis of the protein level of apoptosis associated proteins(LRIG1, c-PARP, Bax, cleaved-caspase-3) in ISL treated A375 and A2058 cells which were transfected with si-LRIG1 or control(NC). *P < 0.05, **P < 0.01 vs PBS Treated in si-NC groups. #P < 0.05, ##P < 0.01 vs PBS Treated in si-LRIG1 groups. (G)Flow cytometry analysis of cell apoptosis in ISL treated A375 and A2058 cells which were transfected with si-LRIG1 or si-NC.*P < 0.05, **P < 0.01 vs PBS + si-NC. (H)Quantification of TUNEL positive cells in ISL treated A375 and A2058 cells which were transfected with si-LRIG1 or si-NC.*P < 0.05, **P < 0.01 vs PBS + si-NC. (TIF 25520 kb