Search Results (3,400)

Figure 1
<p>Morphological and transcriptomic differences of callus cultured by sucrose, glucose, and maltose. (<b>A</b>) Morphology of samples including callus cultured by sucrose, glucose, and maltose; the bar represents 1.0 cm. The white arrow indicates an adventitious bud and a hairy root. (<b>B</b>) Cell micromorphology of callus, bar = 100 μm. (<b>C</b>) Correlation analysis among samples; the horizontal axis represents the sample clusters, and colors from blue to red indicate the correlation index from low to high. (<b>D</b>) Venn diagram of DEGs among three compared pairs, including Suc/Mal, Suc/Glu, and Glu/Mal. The red arrows indicate upregulation, and the green arrows indicate downregulation. (<b>E</b>) KEGG pathway enrichment of the comparison of Suc/Glu. The bubble size represents the number of members detected in the KEGG pathway, and the color of the bubble represents the <span class="html-italic">p</span>-value, the same as below. (<b>F</b>) KEGG pathway enrichment of the comparison of Suc/Mal. (<b>G</b>) KEGG pathway enrichment of the comparison of Glu/Mal.</p> Full article ">Figure 2
<p>Hierarchical clustering analyses of DEGs among samples of sucrose, glucose, maltose, and IEC. (<b>A</b>) Hierarchical clustering analyses of DEGs between samples including Suc, Glu, Mal, and IEC. (<b>B</b>) Hierarchical clustering analyses of DEGs in subcluster 1. (<b>C</b>) Hierarchical clustering analyses of DEGs in subcluster 2. (<b>D</b>) Hierarchical clustering analyses of DEGs in subcluster 3. (<b>E</b>) Hierarchical clustering analyses of DEGs in subcluster 4.</p> Full article ">Figure 3
<p>Differential analyses of plant hormone signal transduction and metabolism. (<b>A</b>) Analyses of the contents and enzymatic activity of plant hormones. The data are means, <span class="html-italic">n</span> = 3. Means marked by the same letter in the column are not significantly different according to Duncan’s multiple range test at <span class="html-italic">p</span> &lt; 0.05. Table marked in red, yellow, and green indicating high, middle, and low values with different carbon source treatments. (<b>B</b>) DEGs with higher expression levels with sucrose. (<b>C</b>) DEGs with lower expression levels with sucrose. (<b>D</b>) Hierarchical clustering analyses of DEGs. (<b>E</b>) Size of callus treated by PIC, <span class="html-italic">n</span> = 3. Means marked by the same letter on the bar are not significantly different according to Duncan’s multiple range test at <span class="html-italic">p</span> &lt; 0.05, and the same hereinafter. (<b>F</b>) Size of callus treated by GA₄. (<b>G</b>) Size of callus treated by homobrassinolide (HBL). (<b>H</b>) Size of callus treated by ABA. Abbreviations: BIN2: brassinosteroid insensitive2; TGA: TGACG binding TFs; IAA: auxin/indole-3-acetic acid; PP2C: type 2C protein phosphatases; JAZ: jasmonate ZIM domain protein; SAUR: small auxin-up RNA; ARR-A: type-A authentic response regulator; ARR-B: type-B authentic response regulator; NPR1: nonexpressor of pathogenesis-related genes 1; BZR1_2: brassinosteroid-resistant 1/2; AHP: histidine-containing phosphotransfer protein; PIF3: phytochrome-interacting factor 3; SNRK2: sucrose nonfermenting 1-related protein kinase 2; EIN3: ethylene-insensitive protein 3; TIR1: transport inhibitor response 1; TCH4: xyloglucan: xyloglucosyl transferase TOUCH4; BSK: BR-signaling kinase; PIF4: phytochrome-interacting factor 4; GH3: Gretchen Hagen 3; AHK2_3_4: Arabidopsis histidine kinase 2/3/4 (cytokinin receptor); PR1: pathogenesis-related protein 1; DELLA: DELLA transcriptional regulatory proteins; ABF: ABA responsive element binding factor; CTR1: constitutive triple response1; AUX1, LAX: auxin influx carrier (AUX1/LAX family); ARF: auxin response factor; CYCD3: cyclin D3; PYL: pyrabactin resistance 1-like protein; GID1: gibberellin insensitive dwarf1; MPK6: mitogen-activated protein kinase 6; BRI1: brassinosteroid insensitive 1.</p> Full article ">Figure 4
<p>Differential analyses of starch and sucrose metabolism. (<b>A</b>) Analyses of the contents of starch and soluble sugars. The data are means, <span class="html-italic">n</span> = 3. Means marked by the same letter in the column are not significantly different according to Duncan’s multiple range test at <span class="html-italic">p</span> &lt; 0.05. Table marked in red, yellow, and green indicates high, middle, and low values with different carbon source treatments. (<b>B</b>) DEGs with higher expression levels in Suc/Glu and Suc/Mal. (<b>C</b>) DEGs with lower expression levels in Suc/Glu and higher expression levels in Glu/Mal. (<b>D</b>) DEGs with lower expression levels in Suc/Glu and higher expression levels in Glu/Mal. (<b>E</b>) Hierarchical clustering analyses of DEGs involved in starch and sucrose metabolism. (<b>F</b>) DEGs with lower expression levels in Suc/Glu and Suc/Mal. (<b>G</b>) Size of callus treated by different concentrations of sucrose, <span class="html-italic">n</span> = 3. Means marked by the same letter on the bar are not significantly different according to Duncan’s multiple range test at <span class="html-italic">p</span> &lt; 0.05, and the same hereinafter. (<b>H</b>) Size of callus treated by the combination of sucrose and glucose. (<b>I</b>) Size of callus treated by the combination of sucrose and fructose. (<b>J</b>) Size of callus treated by the combination of sucrose and maltose. Abbreviations: GBE1, glgB: 1,4-alpha-glucan branching enzyme; SUS: sucrose synthase; glgC: glucose-1-phosphate adenylyltransferase; INV, sacA: beta-fructofuranosidase; PYG, glgP: glycogen phosphorylase; scrK: fructokinase; malZ: alpha-glucosidase; TREH, treA, treF: alpha-trehalase; TPS: trehalose 6-phosphate synthase/phosphatase; ISA, treX: isoamylase; otsB: trehalose 6-phosphate phosphatase; GPl, pgi: glucose-6-phosphate isomerase; ENPP1_3, CD203: ectonucleotide pyrophosphatase/phosphodiesterase family member 1/3; malQ: 4-alpha-glucanotransferase; UGP2, galU, galF: UTP--glucose-1-phosphate uridylyltransferase; SPP: sucrose-6-phosphatase; HK: hexokinase; NV, sacA: beta-fructofuranosidase; TREH, treA, treF: alpha,alpha-trehalase.</p> Full article ">Figure 5
<p>Differential analyses of MAPK signaling pathway. (<b>A</b>) Analyses of the contents and enzymatic activity involved in ROS metabolism. The data are means, <span class="html-italic">n</span> = 3. Means marked by the same letter in the column are not significantly different according to Duncan’s multiple range test at <span class="html-italic">p</span> &lt; 0.05. Table marked in red, yellow, and green indicates high, middle, and low values with different carbon source treatments. (<b>B</b>) DEGs with higher expression levels in Suc/Glu and Suc/Mal. (<b>C</b>) DEGs with higher expression levels in Suc/Glu and lower expression levels in Glu/Mal. (<b>D</b>) DEGs with lower expression levels in Suc/Glu and higher expression levels in Glu/Mal. (<b>E</b>) DEGs with lower expression levels in Suc/Glu and Suc/Mal. (<b>F</b>) Size of callus treated by H₂O₂, <span class="html-italic">n</span> = 3. Means marked by the same letter on the bar are not significantly different according to Duncan’s multiple range test at <span class="html-italic">p</span> &lt; 0.05, and the same hereinafter. (<b>G</b>) Size of callus treated by 2, 4-D. (<b>H</b>) Size of callus treated by PEG 6000. (<b>I</b>) Size of callus treated by Ac-DEVD-CHO (CHO) and carbonyl cyanide m-chlorophenylhydrazone (CCCP). Abbreviations: MAPK7: mitogen-activated protein kinase 7; RBOH: respiratory burst oxidase; IRAK1: interleukin-1 receptor-associated kinase 1; CALM: calmodulin; WRKY33: WRKY DNA-binding protein 33; CTSL: cathepsin L; IDH1, IDH2, icd: isocitrate dehydrogenase; CYC: cytochrome c; PR1: pathogenesis-related protein 1; ACsL, fadD: long-chain acyl-CoA synthetase; CTSH: cathepsin H; PEX12, PAF3: peroxin-12; HAO: (S)-2-hydroxy-acid oxidase; VIP1: transcription factor VIP1; ACAA1: acetyl-CoA acyltransferase 1; PXMP2, PMP22: peroxisomal membrane protein 2; PEX10: peroxin-10; FLS2: LRR receptor-like serine/threonine-protein kinase FLS2; EIN3: ethylene-insensitive protein 3; FBXL2_20: F-box and leucine-rich repeat protein 2/20; PP2C: type 2C protein phosphatases; PYL: abscisic acid receptor PYR/PYL family; NRK2: sucrose nonfermenting 1-related protein kinase 2; ANP1: mannan polymerase II complex ANP1 subunit; copA, ATP7: P-type Cu+ transporter; katE, CAT, catB, srpA: catalase; MKK9: mitogen-activated protein kinase kinase 9; PARP: poly (ADP-ribose) polymerases; ATF4, CREB2: cyclic AMP-dependent transcription factor ATF-4; EIF2S1: translation initiation factor 2 subunit 1.</p> Full article ">Figure 6
<p>Analyses of the effects of carbon source combination on the proliferation and differentiation of callus. (<b>A</b>) Morphological differences of callus treated by the combination of sucrose and the hydrolysate of sucrose (glucose and fructose). The bars in the morphology and micromorphology represent 1.0 cm and 100 μm, respectively, and the same hereinafter. (<b>B</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of sucrose and hydrolysate of sucrose. Data on the bars marked without the same lowercase letter indicate significant differences at <span class="html-italic">p</span> &lt; 0.05, <span class="html-italic">n</span> = 3, and the same hereinafter. (<b>C</b>) Morphological differences of callus treated by the combination of sucrose and glucose. (<b>D</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of sucrose and glucose. (<b>E</b>) Morphological differences of callus treated by the combination of sucrose and fructose. (<b>F</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of sucrose and fructose. (<b>G</b>) Morphological differences of callus treated by the combination of hydrolysate of sucrose and glucose. (<b>H</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of hydrolysate of sucrose and glucose. (<b>I</b>) Morphological differences of callus treated by the combination of hydrolysate of sucrose and fructose. (<b>J</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of hydrolysate of sucrose and fructose. (<b>K</b>) Morphological differences of callus treated by the combination of hydrolysate of sucrose and maltose. (<b>L</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of hydrolysate of sucrose and maltose.</p> Full article ">Figure 7
<p>Analyses of the effects of osmotic regulatory substance (ORS) on the proliferation and differentiation of callus. (<b>A</b>) Morphological differences of callus treated by the combination of sucrose and PEG. The bars in the morphology and micromorphology represent 1.0 cm and 100 μm, respectively, and the same hereinafter. (<b>B</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of sucrose and PEG. Data on the bars marked without the same lowercase letter indicate significant differences at <span class="html-italic">p</span> &lt; 0.05, <span class="html-italic">n</span> = 3, and the same hereinafter. (<b>C</b>) Morphological differences of callus treated by the combination of glucose and PEG. (<b>D</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of glucose and PEG. (<b>E</b>) Morphological differences of callus treated by the combination of fructose and PEG. (<b>F</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of fructose and PEG. (<b>G</b>) Morphological differences of callus treated by the combination of glucose, fructose, and PEG. (<b>H</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of glucose, fructose, and PEG. (<b>I</b>) Morphological differences of callus treated by the combination of sucrose, glucose, and PEG. (<b>J</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of sucrose, glucose, and PEG. (<b>K</b>) Morphological differences of callus treated by the combination of sucrose, fructose, and PEG. (<b>L</b>) Size of callus (left Y-axis) and single cell (right Y-axis) treated by the combination of sucrose, fructose, and PEG.</p> Full article ">Figure 8
<p>Hypothesized model diagram of the acquisition of regenerative potential induced by carbon sources in <span class="html-italic">A. praecox</span>. (<b>A</b>) Carbon sources affected the proliferation and differentiation of callus, and the intensity of ROS determined the cell fate of callus. (<b>B</b>) Schematic diagram about the influence of carbon sources on hormone metabolism, sugar content, ROS, and protective enzymes. Since maltose treatment usually results in moderate levels of physiological indicators, maltose is used as a control. The short horizontal line indicate control, the red arrows indicate a significant increase, and the green arrows a indicate significant decrease.</p> Full article ">

Graphical abstract
Full article ">Figure 1
<p>PCA of the NTs and their metabolites in the serum of METH abusers and healthy controls. (<b>A</b>) Nonsupervised PCA score plot. (<b>B</b>) PLS-DA score plot. (<b>C</b>) OPLS-DA score plot. Red triangles represent the METH abusers’ serum metabolomes; blue dots represent the healthy controls’ serum metabolomes. (<b>D</b>) Permutation test. It verifies the prediction ability of the OPLS-DA model. <span class="html-italic">p</span> values of &lt;0.05 were considered statistically significant. The permutation number was set to 100. (<b>E</b>) VIP plot of the serum metabolomes. VIP &gt; 0.8. (<b>F</b>) Volcano plot. Red dots: upregulated metabolites; blue dots: downregulated metabolites; gray dots: no obviously affected metabolites.</p> Full article ">Figure 2
<p>The changed serum NTs and the dynamic metabolism of the TRP–kynurenic pathway in METH abusers. (<b>A</b>) Pathway schematic of TRP–kynurenic metabolism. Black arrows show the host pathway; blue arrows show the microbial pathway. Host enzymes with genomic evidence are marked in red; microbial enzymes with genomic evidence are marked in green. (<b>B</b>) Differences in absolute concentrations (ng/mL) of TRP–kynurenic metabolites and the statistically significant ratios in the TRP–kynurenic pathway. C, healthy controls. M, METH abusers. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 3
<p>The changed serum NTs and the dynamic metabolism of the TRP–serotonergic pathway in METH abusers. (<b>A</b>) Pathway schematic of TRP–serotonergic metabolism. Black arrows indicate the host degradation pathway; host enzymes with genomic evidence are marked in red. (<b>B</b>) Differences in absolute concentrations (ng/mL) of TRP–serotonergic metabolites and the statistically significant ratios in the TRP–serotonergic pathway. C, healthy controls. M, METH abusers. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 4
<p>The changed serum NTs and the dynamic metabolism of the TRP–microbial metabolic pathway in METH abusers. (<b>A</b>) Pathway schematic of TRP–microbial metabolism. Black arrows show the host pathway; blue arrows show the microbial pathway. Host enzymes with genomic evidence are marked in red; microbial enzymes with genomic evidence are marked in green. (<b>B</b>) Differences in absolute concentrations (ng/mL) of TRP–microbial metabolism and the statistically significant ratios in the TRP–microbial metabolic pathway. C, healthy controls. M, METH abusers. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 5
<p>The changed serum NTs and the dynamic metabolism of the TYR–dopamine pathway in METH abusers. (<b>A</b>) Pathway schematic of TYR–dopamine metabolism. Black arrows indicate the host degradation pathway; host enzymes with genomic evidence are marked in red. (<b>B,C</b>) Differences in absolute concentrations (ng/mL) of TYR–dopamine metabolism, other amino acid NTs, and the statistically significant ratios. C, healthy controls. M, METH abusers. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01.</p> Full article ">Figure 6
<p>ROC curves distinguishing the controls and the METH abusers. Model 1 contained the TRP–microbial metabolic pathway. Model 2 contained the TRP–kynurenic pathway. Model 3 contained the TRP–serotonergic pathway.</p> Full article ">Figure 7
<p>Alterations in NTs and neuroactive metabolites from the <span class="html-italic">t</span>-test in METH abusers of different genders. (<b>A,B</b>) Heatmaps of statistically significant metabolites from the <span class="html-italic">t</span>-test in male and female METH abusers. C, healthy controls. M, METH abusers. hrM, METH abusers of higher exposure. hM, METH abusers of high exposure. mM, METH abusers of medium exposure. lM, METH abusers of low exposure. (<b>C</b>) Venn plot that illustrates differences in serum metabolites between male and female METH abusers, with overlapping areas indicating shared changes caused by METH use in both genders.</p> Full article ">

Figure 1
<p>Microbial metabolite receptor (MMR) expression in the Cancer Cell Line Encyclopedia (CCLE) dataset. (<b>A</b>) MMR with the highest expression per tissue-specific cell line. (<b>B</b>) MMRs summarized by their ligand, showing which tissue-specific cell line they are highly expressed in.</p> Full article ">Figure 2
<p>Differential expression of microbial metabolite receptors (MMRs) in a pan-cancer setting. (<b>A</b>) Each MMR’s dysregulation versus control samples per studied cancer type. (<b>B</b>) MMR expression dysregulation summarized by ligand type per studied cancer type. Red color signifies upregulation and blue downregulation.</p> Full article ">Figure 3
<p>Top dysregulated microbial metabolite receptors (MMRs) per studied cancer type. X-axis represents log2FoldChange values, while the dashed red lines signify log₂FoldChange of ±1.</p> Full article ">Figure 4
<p>Spearman Correlation Heatmap showcasing the relationship between cancer types based on MMR expression profiles. Red indicates a positive correlation, while blue highlights inverse correlations. (* <span class="html-italic">p</span>-value &lt; 0.05; ** <span class="html-italic">p</span>-value &lt; 0.01; *** <span class="html-italic">p</span>-value &lt; 0.001).</p> Full article ">Figure 5
<p>(<b>A</b>) Pairwise Spearman correlation of cancer hallmark genes (CHGs) and microbial metabolite receptors (MMRs) based on their expression. All correlations exhibit Spearman’s rho lower than −0.8 or higher than 0.8 and <span class="html-italic">p</span>-values lower than 10⁻¹⁰. (<b>B</b>) Pairwise Spearman correlation of MMRs when the CHGs are aggregated into cancer hallmark pathways (CHPs) (<b>C</b>) Summary of the strongest correlations between MMRs and CHPs.</p> Full article ">

Figure 1
<p>Hypothesized model.</p> Full article ">Figure 2
<p>Standardized coefficients for the hypothesized model revised. Note. All relationships were significant at <span class="html-italic">p</span> ≤ 0.001.</p> Full article ">Figure 3
<p>Standardized coefficients for the alternative model revised.</p> Full article ">

Figure 1
<p>The LC-MS detection of extracts produced by <span class="html-italic">H. anguillulae</span> YMF1.01751 in five media. (<b>A</b>) Principal component analysis of the metabolites from <span class="html-italic">H. anguillulae</span> YMF1.01751 in different media. (<b>B</b>) LC-MS profiles of metabolites extracted from <span class="html-italic">H. anguillulae</span> YMF1.01751 in total ion chromatography.</p> Full article ">Figure 2
<p>The COSY and key HMBC correlations of <b>1</b>.</p> Full article ">Figure 3
<p>The metabolites isolated from <span class="html-italic">H. anguillulae</span> YMF1.01751.</p> Full article ">Figure 4
<p>The nematicidal activity of compounds against <span class="html-italic">M. incognita</span>. In the same time period of data, two way-ANOVA statistical analysis indicates significant differences (* <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.005; *** <span class="html-italic">p</span> &lt; 0.003; **** <span class="html-italic">p</span> &lt; 0.001) compared with the control.</p> Full article ">Figure 5
<p>The chemotactic activity of compounds towards <span class="html-italic">M. incognita</span>. (<b>A</b>) Schematic diagram of chemotactic activity. (<b>B</b>) The chemotactic activity of compounds. In the same time period of data, two way-ANOVA statistical analysis indicates significant differences (* <span class="html-italic">p</span> &lt; 0.05) compared with the control.</p> Full article ">

Graphical abstract
Full article ">Figure 1
<p>Material applications of indole and bisindole compounds with medicinal properties reported in the literature [<a href="#B24-antibiotics-13-01212" class="html-bibr">24</a>,<a href="#B25-antibiotics-13-01212" class="html-bibr">25</a>,<a href="#B26-antibiotics-13-01212" class="html-bibr">26</a>,<a href="#B27-antibiotics-13-01212" class="html-bibr">27</a>,<a href="#B28-antibiotics-13-01212" class="html-bibr">28</a>,<a href="#B29-antibiotics-13-01212" class="html-bibr">29</a>,<a href="#B30-antibiotics-13-01212" class="html-bibr">30</a>,<a href="#B31-antibiotics-13-01212" class="html-bibr">31</a>,<a href="#B32-antibiotics-13-01212" class="html-bibr">32</a>,<a href="#B33-antibiotics-13-01212" class="html-bibr">33</a>,<a href="#B34-antibiotics-13-01212" class="html-bibr">34</a>,<a href="#B35-antibiotics-13-01212" class="html-bibr">35</a>,<a href="#B36-antibiotics-13-01212" class="html-bibr">36</a>,<a href="#B37-antibiotics-13-01212" class="html-bibr">37</a>,<a href="#B38-antibiotics-13-01212" class="html-bibr">38</a>].</p> Full article ">Figure 2
<p>Natural bisindolic compounds with various therapeutic properties.</p> Full article ">Figure 3
<p>Medicinal properties of bisindolic compounds.</p> Full article ">Figure 4
<p>The structures of <span class="html-italic">bis</span>(indolyl)methanes <b>62</b>–<b>67</b> with antimicrobial properties.</p> Full article ">Figure 5
<p>The structures of <span class="html-italic">bis</span>(indolyl)methanes <b>68</b>–<b>70</b> with antimicrobial properties.</p> Full article ">Figure 6
<p>The structures of bisindoles <b>76</b>–<b>84</b> with antimicrobial properties.</p> Full article ">Figure 7
<p>The structures of bisindoles <b>86</b>–<b>87</b> with antimicrobial properties.</p> Full article ">Figure 8
<p>The structures of bisindole compounds <b>94</b>–<b>98</b> with antimicrobial properties.</p> Full article ">Figure 9
<p>Binding mode of compound <b>100e</b> and active site residue in isoform 1 of Bcl-2. Adapted from [<a href="#B149-antibiotics-13-01212" class="html-bibr">149</a>].</p> Full article ">Figure 10
<p>The structures of bisindole compounds <b>102</b>–<b>105</b> with antitubercular properties.</p> Full article ">Figure 11
<p>The structures of bisindole compounds <b>106</b>–<b>111</b> with antimalarial properties.</p> Full article ">Figure 12
<p>The structures of bisindole compounds <b>112</b>–1<b>38</b> with antileishmanial properties.</p> Full article ">Figure 13
<p>(<b>a</b>) Binding mode of the most active compounds in pteridine reductase active site. (<b>b</b>) Binding mode of compound <b>119</b> (green color) in comparison with pentamidine (blue color). Adapted from [<a href="#B161-antibiotics-13-01212" class="html-bibr">161</a>].</p> Full article ">Figure 14
<p>Bisindoles with antiviral properties.</p> Full article ">Figure 15
<p>Docked pose of <b>142</b> in the hydrophobic pocket of gp41 (PDB 2xra), allowing movement of side chains of Gln 575 and Trp 571. A salt bridge from one carbonyl oxygen on the ligand to Lys574-εNH₂ is shown as an orange dotted line, and a hydrogen bond is predicted from the second carbonyl oxygen to the lysine eNH₂. Adapted from [<a href="#B167-antibiotics-13-01212" class="html-bibr">167</a>].</p> Full article ">Figure 16
<p>Bisindoles with anticancer properties.</p> Full article ">Figure 17
<p>Possible binding mode of the most potent compounds and target proteins. Binding modes of the cocrystallized ligand Ibrutinib (orange), compound <b>152</b> (green), and <b>153</b> (magenta) against the anticancer target EGFR (PDB ID: 5YU9). Adapted from [<a href="#B178-antibiotics-13-01212" class="html-bibr">178</a>].</p> Full article ">Figure 18
<p>Dock pose of indole derivatives <b>154</b> and <b>155</b> with Bcr-Abl and GSK-3β proteins. Adapted from [<a href="#B179-antibiotics-13-01212" class="html-bibr">179</a>].</p> Full article ">Figure 19
<p>Bisindoles <b>157</b>–<b>162</b> with anticancer properties.</p> Full article ">Figure 20
<p>Molecular orbital energy-generated 2D interaction plot of bisindoles (<b>a</b>) <b>161</b>; (<b>b</b>) <b>162</b>. Adapted from [<a href="#B160-antibiotics-13-01212" class="html-bibr">160</a>].</p> Full article ">Figure 21
<p>Bisindoles <b>168</b>–<b>179</b> as MARK4 inhibitors.</p> Full article ">Figure 22
<p>Bisindoles <b>182</b>–<b>193</b> with anti-inflammatory properties.</p> Full article ">Figure 23
<p>Bisindoles <b>194</b>–<b>197</b> with anti-inflammatory activity.</p> Full article ">Figure 24
<p>Bisindoles <b>200</b>–<b>197</b> with anti-Alzheimer properties.</p> Full article ">Figure 25
<p>(<b>a</b>) A 2D interaction diagram of compound <b>205</b> within the binding site of MAO-A (PDB ID = 2Z5X); (<b>b</b>) 2D interaction diagram of compound <b>205</b> within the binding site of MAO-B (PDB ID = 2V5Z). Adapted from [<a href="#B195-antibiotics-13-01212" class="html-bibr">195</a>].</p> Full article ">Figure 26
<p>Bisindole <b>209</b> with antioxidant properties.</p> Full article ">Figure 27
<p>Bisindoles <b>212</b>–<b>219</b> with antidiabetic properties.</p> Full article ">Figure 28
<p>Bisindoles <b>221a</b> and <b>221b</b> as carbonic anhydrase II inhibitors.</p> Full article ">Scheme 1
<p>Synthesis of bis(indolyl)methanes <b>3</b> using different catalysts.</p> Full article ">Scheme 2
<p>Synthesis of bis(indolyl)methanes <b>6</b> by LiO<span class="html-italic">t</span>-Bu-promoted alkylation of indoles <b>4</b>.</p> Full article ">Scheme 3
<p>Synthesis of bis(indolyl)methane phosphonates <b>9</b> using In(OTf)₃ as catalyst.</p> Full article ">Scheme 4
<p>Synthesis of 3,3-bis(indol-3-yl)propanoates <b>12</b> FeCl₃/AgOTf as catalyst.</p> Full article ">Scheme 5
<p>Synthesis of bis(indolyl)methanes <b>14</b> from indole <b>1</b> and ketones [<a href="#B107-antibiotics-13-01212" class="html-bibr">107</a>,<a href="#B108-antibiotics-13-01212" class="html-bibr">108</a>,<a href="#B109-antibiotics-13-01212" class="html-bibr">109</a>].</p> Full article ">Scheme 6
<p>Synthesis of bis(indolyl)methanes <b>16</b> from indole <b>1</b> and electron-deficient alkenes <b>15</b>.</p> Full article ">Scheme 7
<p>Synthesis of bis(indolyl)methanes <b>19</b> using a domino reaction.</p> Full article ">Scheme 8
<p>Synthesis of <span class="html-italic">homo</span>-bisindolylmethanes <b>22</b> using RMgX <b>21</b> as reactant.</p> Full article ">Scheme 9
<p>Synthesis of <span class="html-italic">homo</span>-bis(indolyl)methanes <b>25</b> using RLi <b>24</b> as reactant.</p> Full article ">Scheme 10
<p>Synthesis of <span class="html-italic">homo</span>-bis(indolylmethanes) <b>28</b> using alkynyl lithium reagents <b>27</b> as reactants.</p> Full article ">Scheme 11
<p>Synthesis of bis(indolyl) oximes <b>31</b> via hetero-Diels-Alder reaction.</p> Full article ">Scheme 12
<p>Synthesis of bis(indolyl) hydrazones <b>34</b> via hetero-Diels-Alder reaction.</p> Full article ">Scheme 13
<p>Synthesis of bisindoles <b>37</b> using a multicomponent reaction.</p> Full article ">Scheme 14
<p>Synthesis of 3,3-bis(1<span class="html-italic">H</span>-indol-3-yl)indolin-2-ones <b>40</b>.</p> Full article ">Scheme 15
<p>Synthesis of isatin bisindoles <b>43</b>.</p> Full article ">Scheme 16
<p>Synthesis of acenaphthene bisindoles <b>46</b>.</p> Full article ">Scheme 17
<p>Synthesis of acenaphthene bisindoles <b>48</b>.</p> Full article ">Scheme 18
<p>Synthesis of acenaphthene bisindoles <b>51</b>.</p> Full article ">Scheme 19
<p>Synthesis of amide bisindoles <b>54</b>, <b>55</b>, and <b>57</b>.</p> Full article ">Scheme 20
<p>Synthesis of O,O′-dimethyl scalaridine A <b>62</b>.</p> Full article ">Scheme 21
<p>Synthesis of bisindoles <b>74</b> and <b>75</b>.</p> Full article ">Scheme 22
<p>Synthesis of antimicrobial bisindoles <b>93</b>.</p> Full article ">Scheme 23
<p>Synthesis of antileishmanial bisindoles <b>112</b>–<b>138</b>.</p> Full article ">Scheme 24
<p>Synthesis of antileishmanial seleno-bisindole <b>139</b>.</p> Full article ">Scheme 25
<p>Synthesis of anti-HIV-1 bisindoles <b>140a</b>–<b>140m</b>.</p> Full article ">Scheme 26
<p>Synthesis of anticancer bisindoles <b>148</b> and <b>149</b>.</p> Full article ">Scheme 27
<p>Synthesis of anticancer bisindoles <b>154</b>–<b>156</b>.</p> Full article ">Scheme 28
<p>Synthesis of anticancer bisindoles <b>180</b>–<b>181</b>.</p> Full article ">Scheme 29
<p>Synthesis of anti-Alzheimer bisindole <b>204</b>.</p> Full article ">Scheme 30
<p>Synthesis of antioxidant bisindole <b>210</b>.</p> Full article ">Scheme 31
<p>Synthesis of antidiabetic bisindole <b>211</b>.</p> Full article ">Scheme 32
<p>Synthesis of antidiabetic bisindole <b>213</b>.</p> Full article ">Scheme 33
<p>Synthesis of analgesic bisindoles <b>220a</b> and <b>220b</b>.</p> Full article ">

Figure 1
<p>Pathogen-free in vitro seedling preparation from Cheungsam seeds. (<b>A</b>) Enhanced germination rates of Cheungsam seeds germinated in different volumes of 1% H₂O₂. (<b>B</b>) Reduced contamination rates of seedlings germinated in different volumes of 1% H₂O₂. Contamination rates were assessed 2 weeks after transferring the sterilized seedlings to MS medium. (<b>C</b>) Reduced contamination rates of seedlings additionally sterilized with different volumes of 1% H₂O₂ after removing the seed coat. (<b>D</b>) Reduced contamination rates of seedlings with removed seed coat, additionally sterilized with 3% H₂O₂ for different durations (1, 2, 3, and 4 h). (<b>E</b>) Representative images of seedlings with removed seed coat sterilized with 3% H₂O₂ for different durations (1, 2, 3, and 4 h). Pictures were taken 2 weeks after transferring the sterilized seedlings to MS medium. CON: water control (Scale bar in all panels = 2 cm). Different letters above the bars indicate a statistically significant difference at <span class="html-italic">p</span> &lt; 0.05 according to the Tukey HSD test.</p> Full article ">Figure 2
<p>Callus formation and de novo organogenesis of the excised leaf of Cheungsam plants. (<b>A</b>) Pathogen-free seedlings germinated in H₂O₂ solution as a liquid germination medium and grown on MS medium. Red circle: Leaf tissue used for callus formation. Scale bar = 0.2 cm. (<b>B</b>–<b>D</b>) Callus induced from leaf explants. Scale bar = 0.2 cm. Initial swelling and formation of callus from leaf explants (4-week-old, (<b>B</b>)). Green nodular photosynthetic and friable callus (red arrows, 5-week-old, (<b>C</b>)). The initial stage of shoot regeneration from photosynthetic callus (red arrow, 6-week-old). (<b>D</b>). Scale bar = 0.2 cm. (<b>E</b>,<b>F</b>) De Novo shoot morphogenesis from leaf-induced callus on shoot induction medium (SIM) containing 0.5 mg/L TDZ. Scale bar = 0.2 cm. (<b>G</b>) De Novo root morphogenesis from leaf-induced callus on root induction medium (RIM) containing 2.5 mg/L IBA. Scale bar = 1 cm. Regenerated roots are indicated by the red arrow.</p> Full article ">Figure 3
<p>Callus formation and de novo organogenesis of excised cotyledon tissues from Cheungsam plants. (<b>A</b>) Pathogen-free seedlings germinated in H₂O₂ solution as a liquid germination medium and grown on MS medium. Red circle: Cotyledon tissue used for callus formation. Scale bar = 0.2 cm. (<b>B</b>) Callus induced from the cotyledon explants 7 days after incubation on CIM. Initial swelling and formation of callus from cotyledon explant. Green nodular photosynthetic and friable calli are indicated by red arrows. Scale bar = 0.2 cm. (<b>C</b>,<b>D</b>). De Novo shoot morphogenesis from cotyledon-induced callus on SIM containing 0.5 mg/L TDZ. Scale bar = 0.2 cm. (<b>E</b>) De Novo root morphogenesis from cotyledon-induced callus on RIM containing 2.5 mg/L IBA. Regenerated roots are indicated by the red arrow. Scale bar = 1 cm.</p> Full article ">Figure 4
<p>GC–MS total ion chromatogram (TIC) obtained from the analyses of ethanol extract of Cheungsam callus. TIC was generated from the analysis of ethanol extract of one-month-old Cheungsam leaf callus.</p> Full article ">

Figure 1
<p>Structure and function of MetAP2 in ribosomal interaction and catalytic mechanism. (<b>A</b>) 3D structure of MetAP2. The structure of human MetAP2 (composed of 478 amino acids) features a central β-sheet core surrounded by α-helices (α1–α7), providing structural stability necessary for its catalytic function. The conserved “pita bread” fold within the C-terminal domain forms a deep cleft that houses the active site. The 3D structure of MetAP2 was obtained from the Protein Data Bank (PDB ID: 1BOA, <a href="https://www.rcsb.org/structure/1BOA" target="_blank">https://www.rcsb.org/structure/1BOA</a>, accessed on 11 November 2024). (<b>B</b>) Active site and catalytic mechanism of MetAP2. The active site, located within the deep pocket of the pita bread fold, binds two metal ions, typically cobalt but potentially manganese under physiological conditions. These metal ions are stabilized by conserved residues, including Asp251, Asp262, His331, Glu364, and Glu459. Asp262 and Glu459 act as bidentate ligands, coordinating both metal ions, while Asp251, Glu364, and His331 each coordinate one of the metal ions individually. The metal ions activate a bridging water molecule (H₂O), converting it into a nucleophilic hydroxide ion (OH⁻) through deprotonation. This hydroxide ion then attacks the carbonyl carbon of the N-terminal methionine peptide bond, leading to peptide bond cleavage and the removal of the initiator methionine from the nascent polypeptide. (<b>C</b>) MetAP2 binds to the large ribosomal subunit at the tunnel exit, where it specifically interacts with the expansion segment ES27L of the rRNA. This interaction positions MetAP2 to efficiently engage with the emerging nascent polypeptide, allowing it to cleave the N-terminal methionine as the polypeptide exits the ribosome. The figure illustrates MetAP2’s location relative to the mRNA and tRNA during translation, with ES27L providing an anchor point that stabilizes MetAP2 at the ribosome. This precise positioning enables MetAP2 to facilitate the maturation of newly synthesized proteins by selectively removing the initiator methionine from nascent polypeptides.</p> Full article ">Figure 2
<p>A model of MetAP2-dependent N-myristoylation and its role in T2DM. (<b>A</b>) Adipocyte: The model illustrates the effects of MetAP2-dependent N-myristoylation on cAMP signaling and lipid metabolism within adipocytes. The myristoylation of Gαi enables its membrane localization, where it suppresses adenylate cyclase activity, reducing cAMP levels. MetAP2 inhibition prevents Gαi membrane anchoring, resulting in elevated cAMP levels. This activates PKA, which phosphorylates hormone-sensitive lipase (HSL), promoting triglyceride breakdown into glycerol and free fatty acids. Concurrently, cAMP activates CREB, enhancing the transcription of thermogenic genes, such as UCP1, to increase mitochondrial thermogenesis and energy expenditure, reducing fat accumulation and aiding in obesity management. (<b>B</b>) Hepatocyte: The panel highlights the role of myristoylated PKCε in promoting hepatic insulin resistance. Elevated fatty acid levels increase diacylglycerol (DAG) accumulation, activating PKCε, which is stabilized on the membrane through myristoylation. Activated PKCε inhibits IRS-1/IRS-2 phosphorylation, impairing PI3K/AKT signaling, reducing glycogen synthesis, and increasing gluconeogenesis. MetAP2 inhibition could modulate PKCε activity by preventing its myristoylation, offering potential therapeutic effects against lipid-induced hepatic insulin resistance. (<b>C</b>) Macrophage and skeletal muscle cell: The model illustrates the importance of TRAM’s N-myristoylation in TLR4-mediated inflammatory signaling. Upon LPS binding, TLR4 dimerizes, and myristoylated TRAM colocalizes with TLR4 on the membrane. PKCε phosphorylates TRAM at Ser-16, causing its dissociation from the membrane to interact with TRIF. This activates NF-κB and IRF3 pathways, inducing TNF-alpha expression. Secreted TNF-alpha exacerbates insulin resistance by activating JNK, which disrupts insulin signaling in skeletal muscle cells. TNF-alpha activates JNK, which inhibits IRS-1 phosphorylation and downstream PI3K/AKT signaling. This impairs GLUT4 translocation to the plasma membrane, reducing glucose uptake and contributing to insulin resistance.</p> Full article ">Figure 3
<p>Docking results of Fumagillin, TNP-470, and Beloranib with MetAP2. The docking results of fumagillin (<b>A</b>), TNP-470 (<b>B</b>), and beloranib (<b>C</b>) with MetAP2, performed using CB-Dock2 (<a href="https://cadd.labshare.cn/cb-dock2/" target="_blank">https://cadd.labshare.cn/cb-dock2/</a>, accessed on 14 November 2024) and visualized with the Biovia Discovery Studio Visualizer (version 21.1.0.20298), are presented. The MetAP2 structure (PDB ID: 1BOA) was obtained from the Protein Data Bank, and ligand structures (SDF files) were downloaded from PubChem. The docking process was conducted using CB-Dock2, which predicted binding poses and calculated binding scores (in kcal/mol). The binding scores for fumagillin, TNP-470, and beloranib were −6.7, −6.8, and −6.2 kcal/mol, respectively. Key contact residues involved in hydrogen bonding and hydrophobic interactions are displayed in the 2D interaction diagrams, including His231, Tyr444, Leu447, and His382. These residues are critical for stabilizing the inhibitors within the MetAP2 active site. The docking study highlights the covalent and hydrophobic interactions, particularly with His231, which is essential for MetAP2 inhibition.</p> Full article ">Figure 4
<p>Docking results of ZGN-1061, Indazole, and Pyrazolo[4,3-b]indole with MetAP2. The docking results of ZGN-1061 (<b>A</b>), indazole (<b>B</b>), and pyrazolo[4,3-b]indole (<b>C</b>) with MetAP2 were obtained using CB-Dock2 (<a href="https://cadd.labshare.cn/cb-dock2/" target="_blank">https://cadd.labshare.cn/cb-dock2/</a>, accessed on 14 November 2024) and visualized with the Biovia Discovery Studio Visualizer (version 21.1.0.20298). The MetAP2 structure (PDB ID: 1BOA) was obtained from the Protein Data Bank, and ligand structures (SDF files) were retrieved from PubChem. CB-Dock2 was employed to predict the binding sites and calculate binding scores (in kcal/mol), which were −7.2, −8.3, and −8.1 kcal/mol for ZGN-1061, indazole, and pyrazolo[4,3-b]indole, respectively. The 2D interaction diagrams depict the binding interactions with key residues such as His231, His339, Tyr444, and Leu447. Both indazole and pyrazolo[4,3-b]indole formed strong non-covalent interactions with the active site metal ions, while ZGN-1061 demonstrated a balanced binding profile with hydrophobic contacts in the adjacent pocket. The results emphasize the importance of nitrogen-containing warheads and hydrophobic substituents at the 6- and 7-positions for maximizing the binding affinity and stability.</p> Full article ">

Figure 1
<p>Maize was grown in plastic containers in a climate chamber. (<b>a</b>) Aerial view of the container; (<b>b</b>,<b>c</b>) side view of the container in a climate chamber.</p> Full article ">Figure 2
<p>Effects of GA-IAA-BL WP on the germination rate at different temperatures. The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. The A, B, and C lettering indicates differences between temperatures under the same treatment (<span class="html-italic">p</span> &lt; 0.05). Lowercase letters (a and b) indicate significant differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 3
<p>Effect of GA-IAA-BL WP on maize seedling growth at different temperatures.</p> Full article ">Figure 4
<p>Effect of GA-IAA-BL WP on maize seedling shoot (<b>a</b>) and root (<b>b</b>) growth at different temperatures. The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. The A, B, and C lettering indicates differences between temperatures under the same treatment (<span class="html-italic">p</span> &lt; 0.05). Lowercase letters (a, b, c, and d) indicate significant differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 5
<p>Effect of temperature and GA-IAA-BL WP seed dressing on the root–shoot ratio of maize seedlings. The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. The A, B, and C lettering indicates differences between temperatures under the same treatment (<span class="html-italic">p</span> &lt; 0.05). Lowercase letters (a, b, and c) indicate differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 6
<p>Effect of temperature and GA-IAA-BL WP seed dressing on dry and fresh weights of maize seedling shoots (<b>a</b>,<b>c</b>,<b>e</b>,<b>g</b>,<b>i</b>,<b>k</b>) and roots (<b>b</b>,<b>d</b>,<b>f</b>,<b>h</b>,<b>j</b>,<b>l</b>). The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. Lowercase letters (a, b, c, and d) indicate differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 7
<p>Effect of temperature and GA-IAA-BL WP on enzymes. Superoxide dismutase (SOD) (<b>a</b>–<b>c</b>), catalase (CAT) (<b>d</b>–<b>f</b>), and peroxidase (POD) (<b>g</b>–<b>i</b>) activity in maize seedling shoots and roots. The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. Lowercase letters (a, b, c, and d) indicate differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05). A0–A4 indicate the GA-IAA-BL WP concentration: 0, 50, 100, 150, and 200 mg mL⁻¹, respectively.</p> Full article ">Figure 8
<p>Effect of temperature and GA-IAA-BL WP on proline (Pro) (<b>a</b>–<b>c</b>) and malondialdehyde (MDA) (<b>d</b>–<b>f</b>) in maize seedling shoots and roots. The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. Lowercase letters (a, b, c, and d) indicate differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05). A0–A4 indicate the GA-IAA-BL WP concentration: 0, 50, 100, 150, and 200 mg mL⁻¹, respectively.</p> Full article ">Figure 9
<p>Effect of temperature and GA-IAA-BL WP on root soluble sugar concentration (<b>a</b>), root soluble protein concentration (<b>b</b>), and root vigor (TTC) (<b>c</b>) of maize seedlings. The bars represent the mean ± SE, <span class="html-italic">n</span> = 50 replicates. The A, B, and C lettering indicates differences between temperatures under the same treatment (<span class="html-italic">p</span> &lt; 0.05). Lowercase letters (a, b, c, and d) indicate differences between GA-IAA-BL WP treatments at the same temperature (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 10
<p>Structural equation modeling (SEM) of the effect of GA-IAA-BL WP and temperature on maize seed germination and seedling growth. Blue arrows indicate negative correlations, and red arrows indicate positive correlations between variables (* <span class="html-italic">p</span> &lt; 0.05). The black dotted line indicates no significant correlation (<span class="html-italic">p</span> &gt; 0.05). A1–A4 indicate the GA-IAA-BL WP concentration: 50, 100, 150, and 200 mg mL⁻¹, respectively. Organic matter accumulation includes the dry and fresh weights of maize seedling shoots and roots. Antioxidant enzyme activity includes catalase, superoxide dismutase, and peroxidase.</p> Full article ">

Figure 1
<p>The chemical structural formula of CY1-4.</p> Full article ">Figure 2
<p>In vitro release of CY1-4 from MSNM@CY1-4 in (<b>a</b>) artificial gastric fluid (pH 1.2) and (<b>b</b>) artificial intestinal fluid (pH 6.8).</p> Full article ">Figure 3
<p>In vivo plasma concentration–time curve of CY1-4 after oral administration of MSNM@CY1-4.</p> Full article ">Figure 4
<p>In vivo anti-tumor study of MSNM@CY1-4 in B16F10 tumor-bearing C57BL/6 mice. (<b>a</b>) Schematic graph of the experimental design. (<b>b</b>) Tumor volume curves of tumor-bearing mice received different treatments. (<b>c</b>) Body weight changes of the tumor-bearing mice. (<b>d</b>) Survival curve of tumor-bearing mice received different treatments. Data are shown as mean ± SD, n = 6 (** <span class="html-italic">p</span> &lt; 0.01 vs. control; <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01 vs. 50 mg/kg CY1-4 suspension; # <span class="html-italic">p</span> &lt; 0.05 vs. 10 mg/kg MSNM@CY1-4).</p> Full article ">Figure 5
<p>In vivo IDO inhibition study of MSNM@CY1-4 in B16F10 tumor-bearing C57BL/6 mice. (<b>a</b>) Schematic graph of the experimental design. (<b>b</b>) The Kyn/Trp ratio in (<b>b₁</b>) blood and (<b>b₂</b>) tumor following various treatments. (<b>c</b>) The photograph images (<b>c₁</b>) and weight (<b>c₂</b>) of tumors collected from mice on the 14th day after tumor inoculation. Data are shown as mean ± SD, n = 3 (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. control; <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01 vs. CY1-4 suspension).</p> Full article ">Figure 5 Cont.
<p>In vivo IDO inhibition study of MSNM@CY1-4 in B16F10 tumor-bearing C57BL/6 mice. (<b>a</b>) Schematic graph of the experimental design. (<b>b</b>) The Kyn/Trp ratio in (<b>b₁</b>) blood and (<b>b₂</b>) tumor following various treatments. (<b>c</b>) The photograph images (<b>c₁</b>) and weight (<b>c₂</b>) of tumors collected from mice on the 14th day after tumor inoculation. Data are shown as mean ± SD, n = 3 (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. control; <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.01 vs. CY1-4 suspension).</p> Full article ">Figure 6
<p>In vivo anti-tumor immunity response of MSNM@CY1-4 in B16F10 tumor-bearing C57BL/6 mice. (<b>a</b>) Schematic illustration of the experimental design. (<b>b</b>) Infiltration of (<b>b₁</b>) Tregs, (<b>b₂</b>) CD4⁺ T cells, and (<b>b₃</b>) CD8⁺ T cells in tumors through the flow cytometric examination. (<b>c</b>) Tumor-draining lymph node infiltration of (<b>c₁</b>) Tregs, (<b>c₂</b>) CD4⁺ T cells, and (<b>c₃</b>) CD8⁺ T cells through flow cytometric examination. Data are shown as mean ± SD, n = 3 (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 vs. control).</p> Full article ">

Figure 1
<p>Chemical structure of the (<span class="html-italic">S</span>,<span class="html-italic">R</span>)-diastereoisomers of alkyl (((3-oxo-1,3-diphenylpropyl)thio)carbonothioyl)-ʟ-tryptophanates previously analyzed [<a href="#B15-organics-05-00031" class="html-bibr">15</a>].</p> Full article ">Figure 2
<p>Chromatographic profiles for the crude reaction mixtures obtained after the synthesis of compounds <b>1a</b>–<b>d</b>. Lowercase numbers for each signal assignment (i.e., <b>1a₁</b>–<b>d₁</b> and <b>1a₂</b>–<b>d₂</b>) indicate the discrimination of two diastereoisomers ((<span class="html-italic">S</span>,<span class="html-italic">S</span>) or (<span class="html-italic">S</span>,<span class="html-italic">R</span>)). Each plot pinpointed to a specific diastereoisomer corresponds to its respective mass spectrum, which displays <span class="html-italic">m</span>/<span class="html-italic">z</span> signals for the ESI-MS adducts [M + H]⁺ (the more intense MS signal) and [M + MeOH + H]⁺ (lesser intense, final MS signal).</p> Full article ">Figure 3
<p>(<b>a</b>) DFT-derived models for diastereomers of compounds <b>1c</b>–<b>d</b>; (<b>b</b>) ¹H and ¹³C calculated chemical shift for the diastereoisomers (<span class="html-italic">S</span>,<span class="html-italic">R</span>)-<b>1c</b>, (<span class="html-italic">S</span>,<span class="html-italic">S</span>)-<b>1c</b>, (<span class="html-italic">S</span>,<span class="html-italic">R</span>)-<b>1d</b>, and (<span class="html-italic">S</span>,<span class="html-italic">S</span>)-<b>1d</b>.</p> Full article ">Figure 4
<p>Two-dimensional NMR experiments for compound <b>1d</b>. (<b>a</b>) HMQC, (<b>b</b>) HMBC, (<b>c</b>) COSY, and (<b>d</b>) NOESY.</p> Full article ">Scheme 1
<p>Synthesis of compounds <b>1a</b>–<b>d</b> from ʟ-tryptophan and 4-substituted (<span class="html-italic">E</span>)-chalcones <b>3a</b>–<b>b</b>.</p> Full article ">

Figure 1
<p>Volcano plot showing the magnitude of associations (odds ratio [OR]) and statistical significance (−log10 <span class="html-italic">p</span> values) for plasma metabolites and overall prostate cancer risk in the nested case–control within the EPIC cohort. Significant associations (above the dotted horizontal line) were set at −log10 <span class="html-italic">p</span>-values ≥ −1.30 (<span class="html-italic">p</span> ≤ 0.05).</p> Full article ">Figure 2
<p>Volcano forest plot showing odds ratios and 95% CI for the associations between plasma metabolites and five relevant clinical tumor subtypes of prostate cancer in the nested case–control study within the EPIC cohort. Only significant associations at <span class="html-italic">p</span> &lt; 0.05 (not FDR adjusted) are shown. Abbreviations: 3-MPPAG = 3-(3′-methoxyphenyl)propanoic acid-4′-glucuronide; 3-MPPAS = 3-(3′-methoxyphenyl)propanoic acid-4′-sulfate; 4-HHPPA = (R/S)-2-hydroxy-3-(4′-hydroxyphenyl)propanoic acid; 6-AMMU = 6-amino-5-(N-methylformylamino)-1-methyluracil; CMPF = 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; DHPPA = 3-(3′,4′-dihydroxyphenyl)propanoic acid; DHSBA = 3,5-dihydroxy-4-(sulfooxy)benzoic acid; HPAA sulfate = N-(2-hydroxyphenyl)-acetamide sulfate; TMAO = trimethylamine N-oxide.</p> Full article ">Figure 3
<p>Heatmap showing significant (<span class="html-italic">p</span> &lt; 0.05) Spearman’s correlations between plasma concentrations of 31 metabolites and the habitual intake of selected foods and food groups in the nested prostate cancer case–control study within the EPIC cohort. Full data on rho coefficients and statistical significance for each pair of correlations are shown in <a href="#app1-cancers-16-04116" class="html-app">Supplementary Table S2</a>. Abbreviations: 3-MPPAG = 3-(3′-methoxyphenyl)propanoic acid-4′-glucuronide; 3-MPPAS = 3-(3′-methoxyphenyl)propanoic acid-4′-sulfate; 4-HHPPA = (R/S)-2-hydroxy-3-(4′-hydroxyphenyl)propanoic acid; 6-AMMU = 6-amino-5-(N-methylformylamino)-1-methyluracil; CMPF = 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; DHPPA = 3-(3′,4′-dihydroxyphenyl)propanoic acid; DHSBA = 3,5-dihydroxy-4-(sulfooxy)benzoic acid; HPAA sulfate = N-(2-hydroxyphenyl)-acetamide sulfate; TMAO = trimethylamine N-oxide.</p> Full article ">

Figure 1
<p>Low-molecular-weight organic acid treatment promotes the rooting of persimmon rootstock L938. (<b>A</b>). The morphological changes in adventitious roots of L938 cuttings under different treatments. (<b>B</b>). Rooting rate (% of cuttings that developed at least one root). (<b>C</b>). Survival rate (% of live cuttings). There were 33 plants per treatment and three replications. Values are the means of three replicates and the error bars represent the standard error. Asterisks indicate a significant difference between the CK and the organic acid treatment in the rooting rate and the survival rate (*** means <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">Figure 2
<p>Histological observations of pre-adventitious root initiation stages of L938 cutting under 4000 mg/L malic acid treatment. (<b>A</b>). 0 d. (<b>B</b>). 10 d. (<b>C</b>). 20 d. (<b>D</b>). 30 d. (<b>E</b>). 40 d. (<b>F</b>). 50 d. Rp: root primordium; Ar: adventitious root; Pe: epidermis; Co: cortex; Ph: phloem; ve: vessel; Xy: xylem; Vc: vascular cambium; Pi: pith; Ra: pith ray. Scale bar: 100 μm.</p> Full article ">Figure 3
<p>Histological observations of pre-adventitious root initiation stages of L938 cuttings under 4000 mg/L tartaric acid treatments. (<b>A</b>). 0 d. (<b>B</b>). 10 d. (<b>C</b>). 20 d. (<b>D</b>). 30 d. (<b>E</b>). 40 d. (<b>F</b>). 50 d. Rp: root primordium; Ar: adventitious root; Pe: epidermis; Co: cortex; Ph: phloem; Ve: vessel; Xy: xylem; Vc: vascular cambium; Pi: pith; Ra: pith ray. Scale bar: 100 μm.</p> Full article ">Figure 4
<p>Histological observations of pre-adventitious root initiation stages of L938 cutting under water condition (CK). (<b>A</b>). 0 d. (<b>B</b>). 10 d. (<b>C</b>). 20 d. (<b>D</b>). 30 d. (<b>E</b>). 40 d. (<b>F</b>). 50 d. Rp: root primordium; Ar: adventitious root; Pe: epidermis; Co: cortex; Ph: phloem; Ve: vessel; Xy: xylem; Vc: vascular cambium; Pi: pith; Ra: pith ray. Scale bar: 100 μm.</p> Full article ">Figure 5
<p>Dynamic changes in the contents of soluble sugar (<b>A</b>), starch (<b>B</b>), and soluble protein (<b>C</b>) during the rooting process of cuttings. Values are means of three replicates, and the error bars represent the standard error. Asterisks indicate significant difference between CK and organic acid treatments (* means <span class="html-italic">p</span> &lt; 0.05, ** means <span class="html-italic">p</span> &lt; 0.01, *** means <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">Figure 6
<p>Dynamic changes in the contents of four endogenous hormones during the rooting process of cuttings. (<b>A</b>). ZT content. (<b>B</b>). ABA content. (<b>C</b>). IAA content. (<b>D</b>). GA₃ content. Values are means of three replicates, and the error bars represent standard errors. Asterisks indicate significant differences between CK and organic acid treatments (* means <span class="html-italic">p</span> &lt; 0.05, ** means <span class="html-italic">p</span> &lt; 0.01, *** means <span class="html-italic">p</span> &lt; 0.001).</p> Full article ">Figure 7
<p>Cutting process of date plum L938. (<b>A</b>). Date plum L938 plants used for cutting. (<b>B</b>). The substrate was sprayed with 1000 × carbendazim for disinfection. (<b>C</b>,<b>D</b>). The planted cuttings of date plum L938 placed in the full-light misty seedbed.</p> Full article ">

Scheme 1
<p>Possible modes of cyclization in anilides of <span class="html-italic">N</span>-protected 3-oxo-4-phenylaminobutyric acid.</p> Full article ">Scheme 2
<p>Products obtained from anilides of <span class="html-italic">N</span>-protected 3-oxo-4-phenylaminobutyric acid under Knorr conditions.</p> Full article ">Scheme 3
<p>Alternative pathways to the spirocyclic product <b>4a</b>.</p> Full article ">Scheme 4
<p>Protonation of quinolones <b>3</b>.</p> Full article ">