Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole ...derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound
exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against
,
,
,
,
,
,
and
(MICs: 8-32 µg/mL). Compound
also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including
f. sp.
and
(MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.
Improving heteroatomic interactions via alloying or forming heterogeneous catalysts is of importance to the enhancement in terms of electrocatalytic activity and stability. In this work, a simple ...galvanic replacement reaction was utilized to synthesize low Pt-based quaternary nanotubes (NTs). It is easy to obtain PtPdRuTe NTs with different composition and controlled shape using ultrathin Te nanowires (NWs) as sacrificial templates for its high activity. The NT wall thickness and formed NPs on the surface are closely related with the composition, especially Pd content. The optimized incorporation of Pd atoms into ternary PtRuTe NTs formed a uniform protecting PtPd surface and modified the Pt electronic structure to improve the methanol oxidation reaction (MOR) performance. X-ray photoelectron spectroscopy (XPS) reveals a larger extent of electron transfer from neighboring atoms to Pt on PtPdRuTe, consequently leading to a weaker bonding of the intermediate on Pt. As a result, the quaternary PtPdRuTe NTs exhibit enhanced activity and stability toward efficient MOR.
Direct methanol fuel cells (DMFCs) as candidates for dominant energy conversion devices based on the higher energy densities of liquid methanol show unique advantages over hydrogen-based fuel cells, ...such as cheapness and ease of storage and transportation. However, the fundamental challenges for electrochemical oxidation of methanol are the sluggish electro-oxidation kinetics and recovery of Pt surfaces to lower costs. Here, we report a mixed solvent strategy to prepare a highly active and durable class of electrocatalysts with connected single crystalline nanoparticles (NPs), forming an open architecture. Each single crystalline NP along PtCu nanotubes (NTs) can be considered as a highly active unit with specific facet and assembles along one-dimensional (1D) direction. The Pt 1 Cu 1 –AA NTs achieve a factor of 5.5 and 10.3 enhancement in mass activity (2252 mA mg −1 ) and specific activity (6.09 mA cm −2 ) for methanol oxidation reaction (MOR) relative to Pt/C catalysts, respectively. Moreover, after long-term stability tests, the activity of the NTs could be recovered via a simple potential cycling process (reactivation process) to the initial value or better. Thus this kind of catalysts would limit the costs to the initial investment and recovery and show potential possibility in real DMFC devices.
This article reports a novel scalable method to prepare ultrathin and uniform Pd@Pt nanowires (NWs) with controllable composition and shell thickness, high aspect ratio, and smooth surface, triggered ...by bromide ions via a galvanic replacement reaction between PtCl6 2– and Pd NWs. It was found that bromide ions played a vital role in initiating and promoting the galvanic reaction. The bromide ions served as capping and oxidized etching agents, counterbalancing the Pt deposition and Pd etching on the surface to give final Pd@Pt core–shell nanostructures. Such a counterbalance and the formation PtBr6 2– with lower redox potential could lower the reaction rate and be responsible for full coverage of a smooth Pt shell. The full coverage of Pt deposited on Pd NWs is important for the enhancement of the activity and stability, which depend strongly on the Pt content and Pt shell thickness. Significantly, the Pd@Pt NWs with Pt content of 21.2% (atomic ratio) exhibited the highest mass activity (810 mA mg–1 Pt) and specific activity (0.4 mA cm–2). Interestingly, the mass activity (1560 mA mg–1 Pt) and specific activity (0.98 mA cm–2) of Pd@Pt (21.2%) NWs increased to 2.45 and 1.95 times the initial values after 60k cycles tests, 8.5 and 9.0 times greater than those of Pt/C catalysts. In addition, these ultrathin NW electrocatalysts with large aspect ratio are easy to form into a freestanding film, which improves the mass transport, electrical conductivity, and structure stability.
Rheumatoid arthritis (RA) is a progressive autoimmune disease. Due to local infiltration and damage to the joints, activated CD4
T cells play a crucial role in the progression of RA. However, the ...exact regulatory mechanisms are perplexing, which makes the effective management of RA frustrating. This study aimed to investigate the effect of mitochondria fission on the polarization and migration of CD4
T cells as well as the regulatory mechanism of NAR, so as to provide enlightenment on therapeutic targets and novel strategies for the treatment of RA. In this study, a collagen-induced arthritis (CIA) model was established, and rats were randomly given saline or naringenin (NAR, 10 mg/kg, 20 mg/kg, 50 mg/kg, i.p.) once a day, before being euthanized on the 42nd day of primary immunization. The pain-like behavior, articular index scores, account of synovial-infiltrated CD4
T cells, and inflammatory factors were investigated in each group. In vitro, spleen CD4
T lymphocytes were derived from each group. In addition, mitochondrial division inhibitor 1 (Mdivi-1) or NAR was added to the cell medium containing C-X-C motif chemokine ligand 12 (CXCL12) in order to induce CD4
T lymphocytes, respectively. The polarization capacity of CD4
T cells was evaluated through the immunofluorescence intensity of the F-actin and myosin light chain phosphorylated at Ser19 (pMLC S19), and the mitochondrial distribution was determined by co-localization analysis of the translocase of outer mitochondrial membrane 20 (TOM20, the mitochondrial marker) and intercellular adhesion molecule 1 (ICAM1, the uropod marker). The mitochondrial fission was investigated by detecting dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) using Western blot and immunofluorescence. This study revealed that high-dose NAR (50 mg/kg, i.p.) alleviated pain-like behavior and articular index scores, reduced the serum level of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and accounted for CD4
T lymphocytes that infiltrated into the synovial membrane of the CIA group. Meanwhile, NAR (50 mg/kg, i.p.) suppressed the polarization of spleen CD4
T lymphocytes, reduced the redistribution of mitochondria in the uropod, and inhibited the expression of Drp1 and Fis1 in the CIA model. Furthermore, the in vitro experiments confirmed that NAR reduced mitochondrial fission, which in turn inhibited the CXCL12-induced polarization and migration of CD4
T lymphocytes. Our results demonstrated that the flavonoid NAR was a promising drug for the treatment of RA, which could effectively interfere with mitochondrial fission, thus inhibiting the polarization and migration of CD4
T cells in the synovial membrane.
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A series of 18-Ar-spirotryprostatin A analogs were synthesized stereoselectively from isatin via a five-step reaction sequence involving Wittig reaction, 1,3-dipolar cycloaddition, ...amidated ring closure reaction, hydrolyze and decarboxylation. The two one-pot reactions employed in the synthetic route resulted in high yields. The 1,3-dipolar cycloaddition reaction exhibited a diastereomeric ratio (dr) exceeding 20:1 and an enantiomeric ratio (er) reaching 90:10. Additionally, the amidated ring closure reaction achieved yields of up to 93%.
Abstract
COVID-19 vaccines from multiple manufacturers are needed to cope with the problem of insufficient supply. We did two single-center, randomised, double-blind, placebo-controlled phase 1 and ...phase 2 trials to assess the safety, tolerability and immunogenicity of a recombinant COVID-19 vaccine (Sf9 cells) in healthy population aged 18 years or older in China. Eligible participants were enrolled, the ratio of candidate vaccine and placebo within each dose group was 3:1 (phase 1) or 5:1 (phase 2). From August 28, 2020, 168 participants were sequentially enrolled and randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 28 days or 0, 14, 28 days in phase 1 trial. From November 18, 2020, 960 participants were randomly assigned to receive the low dose vaccine, high dose vaccine or placebo with the schedule of 0, 21 days or 0, 14, 28 days in phase 2 trial. The most common solicited injection site adverse reaction within 7 days in both trials was pain. The most common solicited systematic adverse reactions within 7 days were fatigue, cough, sore throat, fever and headache. ELISA antibodies and neutralising antibodies increased at 14 days, and peaked at 28 days (phase 1) or 30 days (phase 2) after the last dose vaccination. The GMTs of neutralising antibody against live SARS-CoV-2 at 28 days or 30 days after the last dose vaccination were highest in the adult high dose group (0, 14, 28 days), with 102.9 (95% CI 61.9–171.2) and 102.6 (95% CI 75.2–140.1) in phase 1 and phase 2 trials, respectively. Specific T-cell response peaked at 14 days after the last dose vaccination in phase 1 trial. This vaccine is safe, and induced significant immune responses after three doses of vaccination.
Sluggish kinetics of anodic hydrogen oxidation reaction (HOR) in alkaline media, which arises from the two orders of magnitude lower HOR activity in alkali than that in acid media for platinum group ...metals, hinders the commercial implementation of anion exchange membrane fuel cells (AEMFCs). Consequently, the development of platinum-based catalysts combined with high efficiency and durability is urgently required. Herein, we report a facile route for the synthesis of ternary PtRuTe alloy nanofibers with Pt atomic ratio of only 11%
via
a simple galvanic replacement reaction. We optimize the adsorption strength of platinum and ruthenium towards hydrogen and hydroxyl species by regulating the electron donation from tellurium to platinum and ruthenium. Hence, the obtained trimetallic alloy catalyst exhibits an impressive kinetic current density of 30.6 mA cm
−2
geo
at 50 mV and an exchange current density of 0.426 mA cm
−2
metal
, which shows 3.0- and 2.5-fold enhancement compared with the commercial Pt/C in alkaline electrolyte, respectively. Moreover, the catalyst also demonstrates excellent stability with merely 5% activity attenuation after 2000 potential cycles. This work offers new pathways to boost alkaline HOR by rationally designing multicomponent alloys.
Hepatocellular carcinoma (HCC) is an aggressive tumor with limited treatment options, and it is the third leading cause of cancer-related deaths. Hence, novel therapeutic strategies are required to ...treat HCC. Eupatorium chinense L. is a traditional Chinese medicine (TCM) that can effectively neutralize heat and smoothen the flow of “Qi” through the liver. However, the anti-HCC effects of Eupatorium chinense L. remain unknown.
The present study investigated the anti-HCC effects and the underlying mechanisms of the electrophilic sesquiterpenes isolated from E. chinense L. (EChLESs) in the regulation of ferroptosis and apoptosis in HCC cells.
Cell viability was assessed by the MTT assay. Cell apoptosis was confirmed by flow cytometry and western blotting assay. Ferroptosis was assessed by flow cytometry, transmission electron microscopy, and western blotting assay. Ferritinophagy was detected by acridine orange staining and western blotting assay. Small interfering RNA of nuclear receptor coactivator 4 (NCOA4) was used to confirm the role of ferritinophagy in the therapeutic effect of EChLESs on HCC cells. A mouse xenograft model was constructed to determine the inhibitory effect of EChLESs on HCC in vivo.
EChLESs induced apoptosis by disrupting mitochondrial membrane potential depolarization and mitochondrial reactive oxygen species. EChLESs induced ferroptosis as noted by a significant increase in mitochondrial disruption, lipid peroxidation, and intracellular iron level and decreased glutathione level. The apoptosis inhibitor Z-VAD-FMK and lipid reactive oxygen species scavenger ferrostatin 1 attenuated EChLESs-induced cell death. NCOA4-mediated ferritinophagy through autophagic flux was the crucial pathway for ferroptosis induced by EChLESs. NCOA4 knockdown alleviated EChLESs-induced cell death. EChLESs controlled the expression of NCOA4 at the transcriptional and post-transcriptional levels. In the in vivo experiment, EChLESs suppressed HCC growth in the xenograft tumor mouse model.
EChLESs enhances cell apoptosis through mitochondrial dysfunction and ferroptosis through NCOA4-mediated ferritinophagy. Thus, Eupatorium chinense L. could be a potential TCM for treating HCC.
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Hantaan virus (HTNV) is asymptomatically carried by rodents, yet causes lethal hemorrhagic fever with renal syndrome in humans, the underlying mechanisms of which remain to be elucidated. Here, we ...show that differential macrophage responses may determine disparate infection outcomes. In mice, late-phase inactivation of inflammatory macrophage prevents cytokine storm syndrome that usually occurs in HTNV-infected patients. This is attained by elaborate crosstalk between Notch and NF-κB pathways. Mechanistically, Notch receptors activated by HTNV enhance NF-κB signaling by recruiting IKKβ and p65, promoting inflammatory macrophage polarization in both species. However, in mice rather than humans, Notch-mediated inflammation is timely restrained by a series of murine-specific long noncoding RNAs transcribed by the Notch pathway in a negative feedback manner. Among them, the lnc-ip65 detaches p65 from the Notch receptor and inhibits p65 phosphorylation, rewiring macrophages from the pro-inflammation to the pro-resolution phenotype. Genetic ablation of lnc-ip65 leads to destructive HTNV infection in mice. Thus, our findings reveal an immune-braking function of murine noncoding RNAs, offering a special therapeutic strategy for HTNV infection.
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