Discovery of Topsentin Alkaloids and Their Derivatives as Novel Antiviral and Anti-phytopathogenic Fungus Agents

Topsentin alkaloids and their derivatives were designed, synthesized, and characterized on the basis of NMR and mass spectroscopy. The antiviral activities against tobacco mosaic virus (TMV) and anti-phytopathogenic fungus activities of these alkaloids were evaluated for the first time. Alkaloids <b>1c</b>, <b>1e</b>, <b>2b</b>, and <b>2d</b> displayed significantly higher antiviral activities against TMV than Ribavirin, emerging as new lead compounds for anti-TMV research. Further fungicidal activity tests against 14 kinds of phytopathogenic fungi revealed that these alkaloids displayed broad-spectrum fungicidal activities. Topsentin derivative <b>2d</b> with 4–5 mg/kg EC₅₀ values against Sclerotinia sclerotiorum (Lib.), Rhizoctonia solani (Kuhn), and Botrytis cinerea (Pers.) emerged as a new lead compound for fungicidal research. Current studies provide support for the application of topsentin alkaloids as novel agrochemicals

Marine-Natural-Product Development: First Discovery of Nortopsentin Alkaloids as Novel Antiviral, Anti-phytopathogenic-Fungus, and Insecticidal Agents

Nortopsentin alkaloids were found to have potent antiviral, anti-phytopathogenic-fungus, and insecticidal activities for the first time. Antiviral-activity tests revealed that these compounds were very sensitive to substituents, so a series of nortopsentin derivatives were designed, synthesized, and systematically evaluated for their antiviral activities against TMV, their fungicidal activities, and their insecticidal activities on the basis of a structural-diversity-derivation strategy. Compounds <b>2e</b> (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 50, 59, and 56%, respectively, at 500 μg/mL) and <b>2k</b> (in vivo inactivation-, curative-, and protective-activity inhibitory rates of 60, 58, and 52%, respectively, at 500 μg/mL), with excellent antiviral activities and good physicochemical properties, emerged as new lead compounds for novel-antiviral-agent development. Further fungicidal-activity tests revealed that these alkaloids displayed broad-spectrum fungicidal activities. Compounds <b>2f</b>, <b>2h</b>, and <b>2j</b> emerged as new lead compounds for antifungal-activity research. Additionally, all the compounds displayed good insecticidal activities against five kinds of insects, including <i>Mythimna separate</i>, <i>Helicoverpa armigera</i>, <i>Ostrinia nubilalis</i>, <i>Plutella xylostella</i>, and <i>Culex pipiens pallens</i>

Green-Solvent-Processable Low-Cost Fluorinated Hole Contacts with Optimized Buried Interface for Highly Efficient Perovskite Solar Cells

Solution-processed hole contact materials, as an indispensable component in perovskite solar cells (PSCs), have been widely studied with consistent progress achieved. One bottleneck for the commercialization of PSCs is the lack of hole contact materials with high performance, cost-effective preparation, and green-solvent processability. Therefore, the development of versatile hole contact materials is of great significance. Herein, we report two novel donor–acceptor (D–A)-type hole contact molecules (FMPA–BT-CA and 2FMPA–BT-CA) with low cost and alcohol-based processability by utilizing a fluorination strategy. We showed that the fluorine atoms lead to the lowered highest occupied molecular orbital (HOMO) energy levels and larger dipole moments for FMPA–BT-CA and 2FMPA–BT-CA. Moreover, fluorination also improves the buried interfacial interaction between hole contacts and perovskite. As a result, a remarkable power conversion efficiency (PCE) of 22.37% along with good light stability could be achieved for green-solvent-processed FMPA–BT-CA-based inverted PSC devices, demonstrating the great potential of environmentally compatible hole contacts for highly efficient PSCs

Dimensional Regulation from 1D/3D to 2D/3D of Perovskite Interfaces for Stable Inverted Perovskite Solar Cells

Constructing low-dimensional/three-dimensional (LD/3D) perovskite solar cells can improve efficiency and stability. However, the design and selection of LD perovskite capping materials are incredibly scarce for inverted perovskite solar cells (PSCs) because LD perovskite capping layers often favor hole extraction and impede electron extraction. Here, we develop a facile and effective strategy to modify the perovskite surface by passivating the surface defects and modulating surface electrical properties by incorporating morpholine hydriodide (MORI) and thiomorpholine hydriodide (SMORI) on the perovskite surface. Compared with the PI treatment that we previously developed, the one-dimensional (1D) perovskite capping layer derived from PI is transformed into a two-dimensional (2D) perovskite capping layer (with MORI or SMORI), achieving dimension regulation. It is shown that the 2D SMORI perovskite capping layer induces more robust surface passivation and stronger n–N homotype 2D/3D heterojunctions, achieving a p–i–n inverted solar cell with an efficiency of 24.55%, which retains 87.6% of its initial efficiency after 1500 h of operation at the maximum power point (MPP). Furthermore, 5 × 5 cm2 perovskite mini-modules are presented, achieving an active-area efficiency of 22.28%. In addition, the quantum well structure in the 2D perovskite capping layer increases the moisture resistance, suppresses ion migration, and improves PSCs’ structural and environmental stability

Estrogen Receptor (ER)-α36 Is Involved in Estrogen- and Tamoxifen-Induced Neuroprotective Effects in Ischemic Stroke Models

<div><p>The neuroprotection by estrogen (E2) and tamoxifen is well documented in experimental stroke models; however, the exact mechanism is unclear. A membrane-based estrogen receptor, ER-α36, has been identified. Postmenopausal-levels of E2 act through ER-α36 to induce osteoclast apoptosis due to a prolonged activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) signaling. We hypothesized that ER-α36 may play a role in the neuroprotective activities of estrogen and tamoxifen. Here, we studied ER-α36 expression in the brain, as well as its neuroprotective effects against oxygen and glucose deprivation (OGD) in PC12 cells. We found that ER-α36 was expressed in both rat and human brain. In addition, OGD-induced cell death was prevented by l nmol/L 17β-estradiol (E2β). E2β activates the MAPK/ERK signaling pathway in PC12 cells under basal and OGD conditions by interacting with ER-α36 and also induces ER-α36 expression. Low-dose of tamoxifen up-regulated ER-α36 expression and enhanced neuronal survival in an ovariectomized ischemic stroke model. Furthermore, low-dose of tamoxifen enhanced neuroprotective effects by modulating activates or suppress ER-α36. Our results thus demonstrated that ER-α36 is involved in neuroprotective activities mediated by both estrogen and tamoxifen.</p></div

Expression of ER-α36 and caveolin-1 protein in the human cerebral cortex.

<p>Immunocytochemical staining of ER-α36 (green), caveolin-1 (red), and nuclei (blue) in brain slices at different magnifications. Scale bars = 75 μm/10 μm.</p

ER-α36 mediates the ability of estradiol 17β (E2β) to protect against oxygen and glucose deprivation (OGD).

<p>(<b>A</b>) OGD reduced PC12 cell viability after 6 h. (<b>B</b>) Different IC162 concentrations increased the protection against OGD in PC12 cells. (<b>C</b>) Decreased expression of ER-α36 after knockdown. ER-α36 knockdown promoted apoptosis in PC12 cells exposed to 6-h OGD, and weakened the neuroprotective effect of E2β. The results represent a percentage of the control values (no exposure to OGD), expressed as mean ± standard deviation (<i>s</i>.<i>d</i>.; <i>n</i> = 3). *<i>p</i> < 0.05, ** <i>p</i> < 0.01 vs. control; ^#<i>p</i> < 0.05, ^##<i>p</i> < 0.01 vs. vehicle-treated cells.</p

The ischemic brain of the MCAO model.

<p>Ischemia-reperfusion produced infarcts in the rat hippocampus, cortex and striatum. Red arrows show that ATP activity was decreased in the injured hippocampal CA1 region, as revealed by ATPase staining.</p

ER-α36 is involved in mitogen-activated protein kinase (MAPK) signaling pathway activation.

<p>(<b>A</b>) Low-dose E2β-induced activation of MAPK in PC12 cells under non-injury conditions. (B) Low-dose E2β induced activation of the ER-α36 promoter. The results represent a percentage of the control values (no exposure to OGD), expressed as mean ± standard deviation (<i>s</i>.<i>d</i>.; n = 3). *<i>p</i> < 0.05 vs. control.</p

Estrogen receptor (ER)-α36 expression in the rat hippocampus.

<p>(<b>A</b>) Hyperfluorescence of ER-α36 expressed in the CA1 and CA3 regions of the rat hippocampus, and co-staining of ER-α36 with the neuronal marker, NeuN. (<b>B</b>) Nissl staining of the hippocampus. (<b>C</b>) Statistical analysis of ER-α36 expression. Scale bar = 200 μm (200×), <i>n</i> = 3. *<i>p</i> < 0.05, **<i>p</i> < 0.01.</p