* HPPD is one of the most promising targets for new herbicides. * A family of novel HPPD inhibitors based on the triketone-quinoxaline scaffold was designed and synthesized. * One particular product ...(7d) gave the highest inhibition of HPPD of the newly synthesized derivatives. * Triketone-quinoxaline derivatives provide a useful molecular scaffold for the discovery of novel HPPD-inhibiting herbicides.
p-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) belongs to the family of Fe(II)-dependent non-heme oxygenases that occur in the majority of aerobic organisms. HPPD has proved to be a promising target in herbicide research and development. A battery of novel triketone-quinoxaline compounds has been designed using a structure-based drug design strategy and then prepared. Enzyme inhibition assays show that these synthesized derivatives possess favorable inhibition capability against Arabidopsis thaliana HPPD with IC 50 values ranging from 0.317 to 0.891 μmol·L − 1. Subsequently, the molecular docking results indicate that two adjacent carbonyls of the triketone moiety of the representative compound 2-(2,3-dimethyl-8-(o-tolyl)quinoxaline-6-carbonyl)-3-hydroxycyclohex-2-en-1-one (7d) engage in chelation with the ferrous ion of A. thaliana HPPD in a bidentate pose, and its quinoxaline scaffold forms two sets of parallel π-stacking interaction between two phenylalanine residues (Phe424 and Phe381). In addition, the extended phenyl group also interacts with Phe392 in a π-π stacking way. This study indicates that triketone-quinoxaline is a promising scaffold for discovering HPPD inhibitors with substantially increased potency, providing insight into the molecular design of new herbicides.
Despite increasing awareness of the biological impacts of long‐chain fatty acyl‐CoA esters (LCACoAs), our knowledge about the subcellular distribution and regulatory functions of these acyl‐CoA ...molecules is limited by a lack of methods for detecting LCACoAs in living cells. Here, we report development of a genetically encoded fluorescent sensor that enables ratiometric quantification of LCACoAs in living cells and subcellular compartments. We demonstrate how this FadR‐cpYFP fusion “LACSer sensor” undergoes LCACoA‐induced conformational changes reflected in easily detectable fluorescence responses, and show proof‐of‐concept for real‐time monitoring of LCACoAs in human cells. Subsequently, we applied LACSer in scientific studies investigating how disruption of ACSL enzymes differentially reduces cytosolic and mitochondrial LCACoA levels, and show how genetic disruption of an acyl‐CoA binding protein (ACBP) alters mitochondrial accumulation of LCACoAs.
LACSer, a genetically encoded long‐chain acyl‐CoA fluorescence sensor, generates a specific fluorescence response to long‐chain acyl‐CoA, and can be used for the ratiometric quantification of long‐chain acyl‐CoA in cells and subcellular structures. The effects of ACSL and ACBP on the biosynthesis, transport, and downstream metabolism of long‐chain acyl‐CoA can be studied.
As a disease with high incidence, mutilation, and fatality rates, diabetic ulcers (DUs) have become a difficult and complicated disease of widely concern in recent years due to the unclear healing ...mechanism. The main reason for the delayed healing in DU patients is the unduly long chronic inflammation window, and the polarization state of macrophages plays a key role in this process. Since autophagy is believed to be closely related to the polarization trend of macrophages, recent studies have shown that autophagy is closely related to the healing of DU. To this end, a lysosome-targeting polarity-sensitive probe, XZTU-VIS, was developed to monitor the changes in lysosomal polarity, thereby assessing the autophagy of macrophages in mice suffering from DU. The experimental results showed that under two-photon fluorescence microscopy, the green channel fluorescence signal of XZTU-VIS decreased significantly during autophagy. In the meantime, DU models established using BV-2 cells and mice showed a process that could cause inflammation and the release of ROS, thereby inducing autophagy.
As a disease with high incidence, mutilation, and fatality rates, diabetic ulcers (DUs) have become a difficult and complicated disease of widely concern in recent years due to the unclear healing ...mechanism. The main reason for the delayed healing in DU patients is the unduly long chronic inflammation window, and the polarization state of macrophages plays a key role in this process. Since autophagy is believed to be closely related to the polarization trend of macrophages, recent studies have shown that autophagy is closely related to the healing of DU. To this end, a lysosome-targeting polarity-sensitive probe, XZTU-VIS, was developed to monitor the changes in lysosomal polarity, thereby assessing the autophagy of macrophages in mice suffering from DU. The experimental results showed that under two-photon fluorescence microscopy, the green channel fluorescence signal of XZTU-VIS decreased significantly during autophagy. In the meantime, DU models established using BV-2 cells and mice showed a process that could cause inflammation and the release of ROS, thereby inducing autophagy.
A polarity-dependent two-photon fluorescent probe for evaluation of autophagy in the process of diabetic mouse skin ulcer-induced inflammation was constructed.
Despite increasing awareness of the biological impacts of long‐chain fatty acyl‐CoA esters (LCACoAs), our knowledge about the subcellular distribution and regulatory functions of these acyl‐CoA ...molecules is limited by a lack of methods for detecting LCACoAs in living cells. Here, we report development of a genetically encoded fluorescent sensor that enables ratiometric quantification of LCACoAs in living cells and subcellular compartments. We demonstrate how this FadR‐cpYFP fusion “LACSer sensor” undergoes LCACoA‐induced conformational changes reflected in easily detectable fluorescence responses, and show proof‐of‐concept for real‐time monitoring of LCACoAs in human cells. Subsequently, we applied LACSer in scientific studies investigating how disruption of ACSL enzymes differentially reduces cytosolic and mitochondrial LCACoA levels, and show how genetic disruption of an acyl‐CoA binding protein (ACBP) alters mitochondrial accumulation of LCACoAs.
LACSer, a genetically encoded long‐chain acyl‐CoA fluorescence sensor, generates a specific fluorescence response to long‐chain acyl‐CoA, and can be used for the ratiometric quantification of long‐chain acyl‐CoA in cells and subcellular structures. The effects of ACSL and ACBP on the biosynthesis, transport, and downstream metabolism of long‐chain acyl‐CoA can be studied.
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•Ni2P/NF electrode can directly oxidize ammonia without active chlorine mediation.•Ni2P/NF exhibits a much higher activity than Ni(OH)2/NF without phosphorization.•Ni2P/NF electrode ...has an excellent stability for ammonia oxidation.•In-situ formed Ni oxyhydroxides on the Ni2P/NF surface is the real active catalyst.•A possible degradation mechanism of ammonia catalyzed by Ni2P/NF was proposed.
Converting ammonia in wastewater into harmless nitrogen is a green strategy and electrochemical advanced oxidation processes (EAOP) based on electron transfer are the important means to realize this strategy. As a typical EAOP, ammonia oxidation catalyzed by high-valence transition metal anodes is one of the most effective and greenest conversion measures. Hence, in this study we constructed an electrocatalytic ammonia oxidation system using a nickel phosphide anode (Ni2P/NF). When the initial concentration of ammonia was 1000 mg l−1, and the current was 10 mA, the Faraday efficiency of Ni2P/NF in ammonia oxidation catalysis reached 52.8%. In addition, the Ni2P/NF anode could stabilize the electrolysis of ammonia for up to 24 h. When the voltage was higher than 1.44 V vs. RHE, two peaks appeared at 479 cm−1 and 558 cm−1 in the in situ Raman spectrum and the corresponding current on the CV curve increased rapidly, which revealed that Ni oxyhydroxides formed on the reconstructed surface of Ni2P/NF were the real active sites for catalyzing the ammonia decomposition. The generated intermediates nitrate and nitrite were detected based on the in situ FTIR and spectrophotometric analysis. According to the experimental findings, we proposed a possible pathway for ammonia removal based on the participation of the Ni(II)/Ni(III) redox couple. This study enriched the in-depth understanding of ammonia oxidation and provided a very promising way to treat ammonia containing wastewater.
Autism spectrum disorder (ASD) is a multifaceted developmental condition that commonly appears during early childhood. The etiology of ASD remains multifactorial and not yet fully understood. The ...identification of biomarkers may provide insights into the underlying mechanisms and pathophysiology of the disorder. The present study aimed to explore the causes of ASD by investigating the key biomedical markers, trace elements, and microbiota factors between children with autism spectrum disorder (ASD) and control subjects.
Medline, PubMed, ProQuest, EMBASE, Cochrane Library, PsycINFO, Web of Science, and EMBSCO databases have been searched for publications from 2012 to 2023 with no language restrictions using the population, intervention, control, and outcome (PICO) approach. Keywords including "autism spectrum disorder," "oxytocin," "GABA," "Serotonin," "CRP," "IL-6," "Fe," "Zn," "Cu," and "gut microbiota" were used for the search. The Joanna Briggs Institute (JBI) critical appraisal checklist was used to assess the article quality, and a random model was used to assess the mean difference and standardized difference between ASD and the control group in all biomedical markers, trace elements, and microbiota factors.
From 76,217 records, 43 studies met the inclusion and exclusion criteria and were included in this meta-analysis. The pooled analyses showed that children with ASD had significantly lower levels of oxytocin (mean differences, MD = -45.691, 95% confidence interval, CI: -61.667, -29.717), iron (MD = -3.203, 95% CI: -4.891, -1.514), and zinc (MD = -6.707, 95% CI: -12.691, -0.722), lower relative abundance of
(MD = -1.321, 95% CI: -2.403, -0.238) and
(MD = -0.081, 95% CI: -0.148, -0.013), higher levels of c-reactive protein, CRP (MD = 0.401, 95% CI: 0.036, 0.772), and GABA (MD = 0.115, 95% CI: 0.045, 0.186), and higher relative abundance of
(MD = 1.386, 95% CI: 0.717, 2.055) and
(MD = 0.281, 95% CI: 0.035, 0.526) when compared with controls. The results of the overall analyses were stable after performing the sensitivity analyses. Additionally, no substantial publication bias was observed among the studies.
Children with ASD have significantly higher levels of CRP and GABA, lower levels of oxytocin, iron, and zinc, lower relative abundance of
and
, and higher relative abundance of
,
and
when compared with controls. These results suggest that these indicators may be a potential biomarker panel for the diagnosis or determining therapeutic targets of ASD. Furthermore, large, sample-based, and randomized controlled trials are needed to confirm these results.
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