Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 3.025
Filter
1.
Heliyon ; 10(9): e29845, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38707354

ABSTRACT

Objectives: To develop and validate a risk prediction model by identifying the preoperative factors associated with an increased risk of pneumonia after spinal surgery. Methods: This study included patients with spinal disease from two hospitals between January 2021 and June 2023. The patients were divided into the training and validation sets, which were categorized as postoperative pneumonia (POP) or non-POP, respectively. This study identified the independent risk variables for POP using a multivariate logistic regression analysis. A nomogram prediction model was developed and validated using risk factors, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) to assess predictive performance. Results: Following exclusion, 2223 patients from Changzheng Hospital were enrolled in the training set and 357 patients from the No. 905 Hospital of PLA Navy were enrolled in the validation set. Univariate and multivariate logistic regression analyses revealed that operation time, American Society of Anesthesiologists (ASA) grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, chronic obstructive pulmonary disease (COPD), underlying diseases, and spinal section were risk factors for POP development in patients with spinal diseases. The area under the ROC curve of the training set was 0.950, whereas that of the validation set was 0.879. The model calibration curves demonstrated good agreement, and the DCA indicated a high expected net benefit value. Conclusion: The POP risk prediction model has high accuracy and efficiency in predicting POP in patients with spinal diseases. POP development is influenced by factors such as operation length, ASA grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, COPD, underlying diseases, and lumbar surgery.

2.
Cardiovasc Diagn Ther ; 14(2): 229-239, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38716319

ABSTRACT

Background: Arterial remodeling is a compensatory mechanism of the vessel wall in response to atherosclerotic plaque growth. However, the clinical significance of vascular remodeling of carotid lesions remains unclear. Through this study, we aimed to evaluate the association between vascular remodeling and ischemic symptoms in patients with an internal carotid artery (ICA) stenosis degree ≥50%, considering the differences in plaque calcification patterns. Methods: This retrospective cross-sectional study included adult patients with moderate-to-severe proximal ICA stenosis associated with atherosclerotic plaques admitted to the Zhejiang Hospital between September 2018 and March 2023. Parameters such as lumen diameter, plaque calcification types, calcium scores, and calcification thickness were assessed using non-contrast and contrast-enhanced computed tomography angiography (CTA). The remodeling ratio (RR) was calculated by dividing the maximum distance of the proximal ICA between the inner border of the arterial lumen at the plaque site and the outer borders of the plaque by the luminal diameter. Atherosclerosis risk factors and medications were recorded. The Mann-Whitney U test or chi-square test was used to compare the differences between groups. Correlations were measured using Pearson's correlation coefficient. Predictors of ischemic symptoms were assessed using multivariable logistic regression analysis, with results expressed as odds ratio (ORs) with 95% confidence intervals (CIs). A P value less than 0.05 (two-sided) was considered to indicate statistical significance The differences in RR among plaque calcification types and the association between vascular remodeling and clinical symptoms were analyzed. Results: A total of 242 ICAs in 196 patients were included in this study, and 84 were symptomatic and 158 were asymptomatic. The RR in symptomatic ICA [median, 1.31 (interquartile range, 1.17-1.68)] was significantly greater than that in asymptomatic group [median, 1.20 (interquartile range, 1.05-1.45)], P=0.006). Significant differences in RR existed among plaque calcification types, among which type 5 and 6 plaques had the highest RR. About 71.5% (173/242) of all ICAs showed positive remodeling. Significant correlations were observed between RR and ischemic symptoms and between positive remodeling and calcification thickness (P<0.05 for all variables). On multivariable logistic regression analysis, calcification thickness remained significantly associated with positive remodeling of carotid arteries (OR 2.30; 95% CI: 1.06-5.01; P=0.036). Conclusions: Arterial remodeling exists in the ICA. A significant association between arterial positive remodeling and plaque calcification thickness was established. RR helps predict ischemic symptoms. The results of our study suggest that arterial remodeling serves as a novel measure to help ascertain the risk stratification of ischemic events in carotid atherosclerotic disease.

3.
Mol Cancer Res ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38718076

ABSTRACT

Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long non-coding RNAs (lncRNAs) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, a lncRNA which we referring to a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. We found that MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrantly expression of MSL3P1. Mechanistically, due to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway, and promote tumor invasion and metastasis. Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes the metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.

4.
Org Lett ; 2024 May 26.
Article in English | MEDLINE | ID: mdl-38796776

ABSTRACT

Reported herein is a novel radical decarboxylation-initiated SH2' reaction of ß,ß-difluoroenol sulfonates. This transformation is characterized by mild reaction conditions, a broad substrate scope, and late-stage modification of drug molecules, providing general and mechanistically distinct access to bioactive and synthetically versatile α,α-difluoroketones. Preliminary mechanistic studies demonstrate that this reaction proceeds through a succession of silver-mediated decarboxylative radical generation and radical-addition-induced ß-elimination of the sulfonyl radical.

5.
J Hazard Mater ; 473: 134629, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38762987

ABSTRACT

Given the necessity and urgency in removing organic pollutants such as malachite green (MG) from the environment, it is vital to screen high-capacity adsorbents using artificial neural network (ANN) methods quickly and accurately. In this study, a series of ZIF-67 were synthesized, which adsorption properties for organic pollutants, especially MG, were systematically evaluated and determined as 241.720 mg g-1 (25 â„ƒ, 2 h). The adsorption process was more consistent with pseudo-second-order kinetics and Langmuir adsorption isotherm, which correlation coefficients were 0.995 and 0.997, respectively. The chemisorption mechanism was considered to be π-π stacking interaction between imidazole and aromatic ring. Then, a Python-based neural network model using the Limited-memory BFGS algorithm was constructed by collecting the crucial structural parameters of ZIF-67 and the experimental data of batch adsorption. The model, optimized extensively, outperformed similar Matlab-based ANN with a coefficient of determination of 0.9882 and mean square error of 0.0009 in predicting ZIF-67 adsorption of MG. Furthermore, the model demonstrated a good generalization ability in the predictive training of other organic pollutants. In brief, ANN was successfully separated from the Matlab platform, providing a robust framework for high-precision prediction of organic pollutants and guiding the synthesis of adsorbents.

6.
Ecotoxicol Environ Saf ; 279: 116461, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38763051

ABSTRACT

Polystyrene nanoplastics (PS-NPs) have been reported to accumulate in the testes and constitute a new threat to reproductive health. However, the exact effects of PS-NPs exposure on testicular cells and the underlying mechanisms remain largely unknown. The C57BL/6 male mice were orally administered with PS-NPs (80 nm) at different dosages (0, 10, and 40 mg/kg/day) for 60 days, and GC-1 cells were treated with PS-NPs in this study. Enlarged seminiferous tubule lumens and a loose and vacuolated layer of spermatogenic cells were observed in PS-NPs-exposed mice. Spermatogenic cells which may be one of the target cells for this reproductive damage, were decreased in the mice from PS-NPs group. PS-NPs caused spermatogenic cells to undergo senescence, manifested as elevated SA-ß-galactosidase activity and activated senescence-related signaling p53-p21/Rb-p16 pathways, and induced cell cycle arrest. Mechanistically, Gene Ontology (GO) enrichment suggested the key role of reactive oxygen species (ROS) in PS-NPs-induced spermatogenic cell senescence, and this result was confirmed by measuring ROS levels. Moreover, ROS inhibition partially attenuated the senescence phenotype of spermatogenic cells and DNA damage. Using the male health atlas (MHA) database, Sirt1 was filtrated as the critical molecule in the regulation of testicular senescence. PS-NPs induced overexpression of the main ROS generator Nox2, downregulated Sirt1, increased p53 and acetylated p53 in vivo and in vitro, whereas these disturbances were partially restored by pterostilbene. In addition, pterostilbene intervention significantly alleviated the PS-NPs-induced spermatogenic cell senescence and attenuated ROS burst. Collectively, our study reveals that PS-NPs exposure can trigger spermatogenic cell senescence mediated by p53-p21/Rb-p16 signaling by regulating the Sirt1/ROS axis. Importantly, pterostilbene intervention may be a promising strategy to alleviate this damage.

7.
Nat Metab ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38777856

ABSTRACT

Nutrient handling is an essential function of the gastrointestinal tract. Hormonal responses of small intestinal enteroendocrine cells (EECs) have been extensively studied but much less is known about the role of colonic EECs in metabolic regulation. To address this core question, we investigated a mouse model deficient in colonic EECs. Here we show that colonic EEC deficiency leads to hyperphagia and obesity. Furthermore, colonic EEC deficiency results in altered microbiota composition and metabolism, which we found through antibiotic treatment, germ-free rederivation and transfer to germ-free recipients, to be both necessary and sufficient for the development of obesity. Moreover, studying stool and blood metabolomes, we show that differential glutamate production by intestinal microbiota corresponds to increased appetite and that colonic glutamate administration can directly increase food intake. These observations shed light on an unanticipated host-microbiota axis in the colon, part of a larger gut-brain axis, that regulates host metabolism and body weight.

9.
World J Clin Oncol ; 15(4): 531-539, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38689626

ABSTRACT

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

10.
Glob Health Med ; 6(2): 132-140, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38690130

ABSTRACT

This study aimed to explore the brain network characteristics in elderly patients with Parkinson's disease (PD) with depressive symptoms. Thirty elderly PD patients with depressive symptoms (PD-D) and 26 matched PD patients without depressive symptoms (PD-NOD) were recruited based on HAMD-24 with a cut-off of 7. The resting-state functional connectivity (RSFC) was conducted by 53-channel functional near-infrared spectroscopy (fNIRS). There were no statistically significant differences in MMSE scores, disease duration, Hoehn-Yahr stage, daily levodopa equivalent dose, and MDS-UPDRS III between the two groups. However, compared to the PD-NOD group, the PD-D group showed significantly higher MDS-UPDRS II, HAMA-14, and HAMD-24. The interhemispheric FC strength and the FC strength between the left dorsolateral prefrontal cortex (DLPFC-L) and the left frontal polar area (FPA-L) was significantly lower in the PD-D group (FDR p < 0.05). As for graph theoretic metrics, the PD-D group had significantly lower degree centrality (aDc) and node efficiency (aNe) in the DLPFC-L and the FPA-L (FDR, p < 0.05), as well as decreased global efficiency (aEg). Pearson correlation analysis indicated moderate negative correlations between HAMD-24 scores and the interhemispheric FC strength, FC between DLPFC-L and FPA-L, aEg, aDc in FPA-L, aNe in DLPFC-L and FPA-L. In conclusion, PD-D patients show decreased integration and efficiency in their brain networks. Furthermore, RSFC between DLPFC-L and FPA-L regions is negatively correlated with depressive symptoms. These findings propose that targeting DLPFC-L and FPA-L regions via non-invasive brain stimulation may be a potential intervention for alleviating depressive symptoms in elderly PD patients.

11.
J Environ Manage ; 360: 121167, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38749136

ABSTRACT

Organic amendment substitutes mineral fertilizers has been proven to increase the organic matter content of soils, which in turn may induce phosphorus (P) mobilization by triggering the redox reaction. However, under flooded conditions according to local agricultural practices, as one of the factors restricting the decomposition of organic matter, the role ammonium plays in P transformation and leaching from soils with different organic matter remains unclear. To address the knowledge gap, the calcareous soils were collected from a long-term field trial (>13 years) containing two treatments with equal P inputs: a long-term mineral fertilization and a long-term organic amendment. Both long-term mineral fertilized soil and long-term organic amended soil were split into ammonium applications or no ammonium applications. A series of column devices were deployed to create flooded conditions and monitor the P leaching from the collected soils. The K-edge X-ray absorption near-edge structure and sequential extraction method were employed jointly to detect soil P fractions and speciation, and the P sorption/desorption characteristics of soil were evaluated by Langmuir fitting. The results showed a reduction of cumulative leached P from soils by 33.2%-43.3% after ammonium addition, regardless of previous long-term mineral fertilization or organic amendment history. A significant enhancement of soil labile P pool (indicated by the H2O-P fraction and NaHCO3-P fraction) after ammonium addition results in the reduction in soil P leaching. The reduced P sorption capacity coupled with the transformation from hydroxyapatite to ß-tricalcium phosphate indicated that the phosphate retention is attributed to the precipitation formation rather than phosphate sorption by soil. The present study highlights that the ammonium addition could affect the phosphate precipitation transformation. This may be attributed to the effect of ammonium addition on the calcium and magnesium ion content and molar ratio in this soil, thereby regulating the form of soil phosphate precipitation. The mechanisms revealed in this study can support developing optimized agricultural management practices to alleviate soil P loss.

12.
Phytochem Anal ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750654

ABSTRACT

INTRODUCTION: Polygala fallax Hemsl (PFH) is a widely used herbal medicine in Guangxi, China. At present, research on PFH mainly focuses on extraction technology and cultivation, lacking quality control standards for systematic evaluation. OBJECTIVES: The study aimed to assess the quality of PFH from different sources and to predict markers that would help assess quality. METHODS: Fingerprinting of 15 batches of PFH samples was performed by ultra-high performance liquid chromatography (UPLC) and similarity was assessed using hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares discrimination (OPLS-DA). Differential components were screened by mathematical analysis, and a "component-target-pathway" network map was constructed in combination with network pharmacology, quality markers (Q-markers) of PFH were predicted, and quantitative analysis was performed. RESULTS: Fifteen batches were fingerprinted for PFH, with 11 common peaks, and peak 5 was identified as 4-hydroxybenzoic acid, which was generally consistent with the results of HCA, PCA, and OPLS-DA. Network pharmacology screened 18 potential compounds, 45 core targets, and 20 key pathways, integrating fingerprinting, pattern recognition, and network pharmacology methods. One of the potential Q-markers that can identify the principle of testability, efficacy, and specificity is 4-hydroxybenzoic acid, whose content ranges from 0.0188 to 1.4517 mg/g. CONCLUSION: The potential Q-markers of PFH were predicted by integrating fingerprinting, pattern recognition, and network pharmacological analysis, which provided a scientific basis for the overall control and evaluation of the quality of PFH and a theoretical reference for the study of the quality standard of multi-base traditional Chinese medicine.

13.
Ann Med ; 56(1): 2329259, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38738380

ABSTRACT

Opioids are the most prescribed drugs for the alleviation of pain. Both clinical and preclinical studies have reported strong evidence for sex-related divergence regarding opioid analgesia. There is an increasing amount of evidence indicating that gonadal hormones regulate the analgesic efficacy of opioids. This review presents an overview of the importance of gonadal steroids in modulating opioid analgesic responsiveness and focuses on elaborating what is currently known regarding the underlyingmechanism. We sought to identify the link between gonadal hormones and the effect of oipiod antinociception.


Gonadal hormones contribute to the sexual dimorphism of opioid antinociception.Generally, oestradiol is a negative modulator of opioid analgesia via both non-genomic and genomic effects.Testosterone facilitates opioid analgesia mainly through the transcriptional activities of androgen receptors.Under normal physiological conditions, progestin and oestrogen exist in parallel and have a combined effect. However, progestin alone could promote opioid analgesia by increasing the expression of opioid receptors.


Subject(s)
Analgesics, Opioid , Gonadal Hormones , Pain , Analgesics, Opioid/pharmacology , Humans , Animals , Gonadal Hormones/metabolism , Male , Pain/drug therapy , Pain/metabolism , Female
14.
Gut Microbes ; 16(1): 2353394, 2024.
Article in English | MEDLINE | ID: mdl-38743047

ABSTRACT

Exposing C-section infants to the maternal vaginal microbiome, coined "vaginal seeding", partially restores microbial colonization. However, whether vaginal seeding decreases metabolic disease risk is unknown. Therefore, we assessed the effect of vaginal seeding of human infants on adiposity in a murine model. Germ-free mice were colonized with transitional stool from human infants who received vaginal seeding or control (placebo) seeding in a double-blind randomized trial. There was a reduction in intraabdominal adipose tissue (IAAT) volume in male mice that received stool from vaginally seeded infants compared to control infants. Higher levels of isoleucine and lower levels of nucleic acid metabolites were observed in controls and correlated with increased IAAT. This suggests that early changes in the gut microbiome and metabolome caused by vaginal seeding have a positive impact on metabolic health.


Subject(s)
Adiposity , Fecal Microbiota Transplantation , Feces , Gastrointestinal Microbiome , Vagina , Animals , Humans , Female , Mice , Male , Vagina/microbiology , Feces/microbiology , Feces/chemistry , Double-Blind Method , Intra-Abdominal Fat/metabolism , Infant , Infant, Newborn
15.
Molecules ; 29(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38731600

ABSTRACT

Rosa roxburghii Tratt pomace is rich in insoluble dietary fiber (IDF). This study aimed to investigate the influence of three modification methods on Rosa roxburghii Tratt pomace insoluble dietary fiber (RIDF). The three modified RIDFs, named U-RIDF, C-RIDF, and UC-RIDF, were prepared using ultrasound, cellulase, and a combination of ultrasound and cellulase methods, respectively. The structure, physicochemical characteristics, and functional properties of the raw RIDF and modified RIDF were comparatively analyzed. The results showed that all three modification methods, especially the ultrasound-cellulase combination treatment, increased the soluble dietary fiber (SDF) content of RIDF, while also causing a transition in surface morphology from smooth and dense to wrinkled and loose structures. Compared with the raw RIDF, the modified RIDF, particularly UC-RIDF, displayed significantly improved water-holding capacity (WHC), oil-binding capacity (OHC), and swelling capacity (SC), with increases of 12.0%, 84.7%, and 91.3%, respectively. Additionally, UC-RIDF demonstrated the highest nitrite ion adsorption capacity (NIAC), cholesterol adsorption capacity (CAC), and bile salt adsorption capacity (BSAC). In summary, the combination of ultrasound and cellulase treatment proved to be an efficient approach for modifying IDF from RRTP, with the potential for developing a functional food ingredient.


Subject(s)
Dietary Fiber , Rosa , Dietary Fiber/analysis , Rosa/chemistry , Solubility , Cellulase/metabolism , Cellulase/chemistry , Adsorption
16.
Front Psychiatry ; 15: 1398669, 2024.
Article in English | MEDLINE | ID: mdl-38736623

ABSTRACT

Objective: This study used latent profile analysis to explore the level of depression among US adults with obstructive sleep apnea hypopnea syndrome (OSAHS) symptoms and to identify different latent categories of depression to gain insight into the characteristic differences between these categories. Methods: The data of this study were obtained from the National Health and Nutrition Examination Survey (NHANES) database, and the subjects with OSAHS symptoms were aged 18 years and older. The latent profile analysis (LPA) method was used to fit the latent depression categories in subjects with OSAHS symptoms. The chi-square test, rank sum test, and binary logistic regression were used to analyze the influencing factors of depression subgroups in subjects with OSAHS symptoms. Results: Three latent profiles were identified: low-level (83.7%), moderate-level (14.5%) and high-level (1.8%) depression. The scores of 9 items in the high-level depression group were higher than those in the other two groups. Among them, item 4 "feeling tired or lack of energy" had the highest score in all categories. Conclusion: Depression in subjects with OSAHS symptoms can be divided into low-level, moderate-level and high-level depression. There are significant differences among different levels of depression in gender, marital status, PIR, BMI, smoking, general health condition, sleep duration and OSAHS symptom severity.

17.
Front Public Health ; 12: 1352983, 2024.
Article in English | MEDLINE | ID: mdl-38694990

ABSTRACT

Background: Levels of self-awareness may affect the decision-making ability of clinical nurses and may also be related to mental health. Therefore, it is crucial to develop tools to identify nurses' level of self-awareness. The purpose of this study was to investigate the reliability and validity of a short scale among Chinese nurses and to explore the factors associated with nurses' self-awareness. Methods: A total of 957 participants were recruited, 549 participants were used for reliability tests and 408 subjects were used for impact factor studies. They completed the General Information Questionnaire, the Self-Awareness Scale for Nurses, and the Psychological Distress Scale. Exploratory factor analysis, confirmatory factor analysis, Cronbach's alpha, and retest reliability were used to investigate the psychometric properties of the Self-Awareness Scale for Nurses. Multiple regression analyses were used in this study to investigate the relationship between nurses' self-awareness and the independent variables. Results: A 4-factor model of the Chinese version of the Self-Awareness Scale for Nurses was validated. The overall Cronbach's alpha value for the Chinese version of the Self-Awareness Scale for Nurses was 0.873. Cronbach's alpha values for each subscale ranged from 0.808 to 0.979. Significant predictors of each dimension of the Self-awareness and the total score of the scale were age and work experience. Conclusion: The Chinese version of the Self-Awareness Scale for Nurses is a valid and reliable scale.


Subject(s)
Nurses , Psychometrics , Humans , Female , Male , Adult , Reproducibility of Results , Surveys and Questionnaires , China , Nurses/psychology , Middle Aged , Factor Analysis, Statistical , Awareness , Translations
18.
J Agric Food Chem ; 72(20): 11321-11330, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38714361

ABSTRACT

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial target enzyme in albino herbicides. The inhibition of HPPD activity interferes with the synthesis of carotenoids, blocking photosynthesis and resulting in bleaching and necrosis. To develop herbicides with excellent activity, a series of 3-hydroxy-2-(6-substituted phenoxynicotinoyl)-2-cyclohexen-1-one derivatives were designed via active substructure combination. The title compounds were characterized via infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies, and high-resolution mass spectrometry. The structure of compound III-17 was confirmed via single-crystal X-ray diffraction. Preliminary tests demonstrated that some compounds had good herbicidal activity. Crop safety tests revealed that compound III-29 was safer than the commercial herbicide mesotrione in wheat and peanuts. Moreover, the compound exhibited the highest inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD), with a half-maximal inhibitory concentration of 0.19 µM, demonstrating superior activity compared with mesotrione (0.28 µM) in vitro. A three-dimensional quantitative structure-activity relationship study revealed that the introduction of smaller groups to the 5-position of cyclohexanedione and negative charges to the 3-position of the benzene ring enhanced the herbicidal activity. A molecular structure comparison demonstrated that compound III-29 was beneficial to plant absorption and conduction. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound III-29 and AtHPPD. Thus, this study may provide insights into the development of green and efficient herbicides.


Subject(s)
4-Hydroxyphenylpyruvate Dioxygenase , Arabidopsis , Drug Design , Enzyme Inhibitors , Herbicides , Molecular Docking Simulation , Herbicides/chemistry , Herbicides/pharmacology , Herbicides/chemical synthesis , 4-Hydroxyphenylpyruvate Dioxygenase/antagonists & inhibitors , 4-Hydroxyphenylpyruvate Dioxygenase/chemistry , 4-Hydroxyphenylpyruvate Dioxygenase/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Arabidopsis/drug effects , Arabidopsis/growth & development , Structure-Activity Relationship , Molecular Structure , Ketones/chemistry , Ketones/pharmacology , Ketones/chemical synthesis , Cyclohexanones/chemistry , Cyclohexanones/pharmacology , Cyclohexanones/chemical synthesis , Triticum/chemistry , Arabidopsis Proteins/antagonists & inhibitors , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/metabolism
19.
SLAS Discov ; 29(4): 100159, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723666

ABSTRACT

To confirm target engagement of hits from our high-throughput screening efforts, we ran biophysical assays on several hundreds of hits from 15 different high-throughput screening campaigns. Analyzing the biophysical assay results from these screening campaigns led us to conclude that we could be more strategic in our biophysical analysis of hits by first confirming activity in a thermal shift assay (TSA) and then confirming activity in either a surface plasmon resonance (SPR) assay or a temperature-related intensity change (TRIC) assay. To understand how this new workflow shapes the quality of the final hits, we compared TSA/SPR or TSA/TRIC confirmed and unconfirmed hits to one another using four measures of compound quality: quantitative estimate of drug-likeness (QED), Pan-Assay Interference Compounds (PAINS), promiscuity, and aqueous solubility. In general, we found that the biophysically confirmed hits performed better in the compound quality metrics than the unconfirmed hits, demonstrating that our workflow not only confirmed target engagement of the hits but also enriched for higher quality hits.

20.
Article in English | MEDLINE | ID: mdl-38709405

ABSTRACT

The environmental pollution caused by petroleum hydrocarbons has received considerable attention in recent years. Microbial remediation has emerged as the preferred method for the degradation of petroleum hydrocarbons, which is experiencing rapid development driven by advancements in molecular biology. Herein, the capacity of different microorganisms used for crude oil bioremediation was reviewed. Moreover, factors influencing the effectiveness of microbial remediation were discussed. Microbial remediation methods, such as bioaugmentation, biostimulation, and bioventilation, are summarized in this review. Aerobic and anaerobic degradation mechanisms were reviewed to elucidate the metabolic pathways involved. The impacts of petroleum hydrocarbons on microorganisms and the environment were also revealed. A brief overview of synthetic biology and a unique perspective of technique combinations were presented to provide insight into research trends. The challenges and future outlook were also presented to stimulate contemplation of the mechanisms involved and the development of innovative techniques.

SELECTION OF CITATIONS
SEARCH DETAIL
...