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1.
ACS Nano ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38723039

RESUMEN

Transition metal oxides are promising catalysts for catalytic oxidation reactions but are hampered by low room-temperature activities. Such low activities are normally caused by sparse reactive sites and insufficient capacity for molecular oxygen (O2) activation. Here, we present a dual-stimulation strategy to tackle these two issues. Specifically, we import highly dispersed nickel (Ni) atoms onto MnO2 to enrich its oxygen vacancies (reactive sites). Then, we use molecular ozone (O3) with a lower activation energy as an oxidant instead of molecular O2. With such dual stimulations, the constructed O3-Ni/MnO2 catalytic system shows boosted room-temperature activity for toluene oxidation with a toluene conversion of up to 98%, compared with the O3-MnO2 (Ni-free) system with only 50% conversion and the inactive O2-Ni/MnO2 (O3-free) system. This leap realizes efficient room-temperature catalytic oxidation of transition metal oxides, which is constantly pursued but has always been difficult to truly achieve.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38723979
3.
Nat Commun ; 15(1): 3854, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38719830

RESUMEN

Phasing down fossil fuels is crucial for climate mitigation. Even though 80-90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China's respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China's emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

4.
Plant Physiol Biochem ; 211: 108697, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705045

RESUMEN

Dunaliella salina, a microalga that thrives under high-saline conditions, is notable for its high ß-carotene content and the absence of a polysaccharide cell wall. These unique characteristics render it a prime candidate as a cellular platform for astaxanthin production. In this study, our initial tests in an E. coli revealed that ß-ring-4-dehydrogenase (CBFD) and 4-hydroxy-ß-ring-4-dehydrogenase (HBFD) genes from Adonis aestivalis outperformed ß-carotene hydroxylase (BCH) and ß-carotene ketolase (BKT) from Haematococcus pluvialis counterparts by two-fold in terms of astaxanthin biosynthesis efficiency. Subsequently, we utilized electroporation to integrate either the BKT gene or the CBFD and HBFD genes into the genome of D. salina. In comparison to wild-type D. salina, strains transformed with BKT or CBFD and HBFD exhibited inhibited growth, underwent color changes to shades of red and yellow, and saw a nearly 50% decline in cell density. HPLC analysis confirmed astaxanthin synthesis in engineered D. salina strains, with CBFD + HBFD-D. salina yielding 134.88 ± 9.12 µg/g of dry cell weight (DCW), significantly higher than BKT-D. salina (83.58 ± 2.40 µg/g). This represents the largest amount of astaxanthin extracted from transgenic D. salina, as reported to date. These findings have significant implications, opening up new avenues for the development of specialized D. salina-based microcell factories for efficient astaxanthin production.

5.
Exp Clin Transplant ; 22(3): 229-238, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38695592

RESUMEN

OBJECTIVES: The eradication of leukemia cells while sparing hematopoietic stem cells in the graft before autologous hematopoietic stem cell transplant is critical to prevention of leukemia relapse. Proliferating cells have been shown to be more prone to apoptosis than differentiated cells in response to ultraviolet radiation; however, whether leukemia cells are more sensitive to ultraviolet LED radiation than hematopoietic stem cells remains unclear. MATERIALS AND METHODS: We compared the in vitro responses between murine leukemia L1210 cells and murine hematopoietic stem cells to 280-nm ultraviolet LED radiation. We also investigated the effects of ultraviolet LED radiation on the tumorigenic and metastatic capacity of L1210 cells and hematopoietic stem cell hematopoiesis in a mouse model of hematopoietic stem cell transplant. RESULTS: L1210 cells were more sensitive to ultraviolet LED radiation than hematopoietic stem cells in vitro, as evidenced by significantly reduced colony formation rates and cell proliferation rates, along with remarkably increased apoptosis rates in L1210 cells. Compared with corresponding unirradiated cells, ultraviolet LED-irradiated L1210 cells failed to generate palpable tumors in mice, whereas ultraviolet LED-irradiated bone marrow cells restored hematopoiesis in vivo. Furthermore, transplant with an irradiated mixture of L1210 cells and bone marrow cells showed later onset of leukemia, milder leukemic infiltration, and prolonged survival in mice, compared with unirradiated cell transplant. CONCLUSIONS: Our results suggest that ultraviolet LED radiation can suppress the proliferative and tumorigenic abilities of leukemia cells without reducing the hematopoietic reconstitution capacity of hematopoietic stem cells, serving as a promising approach to kill leukemia cells in autograft before autologous hematopoietic stem cell transplant.


Asunto(s)
Apoptosis , Proliferación Celular , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas , Animales , Células Madre Hematopoyéticas/efectos de la radiación , Células Madre Hematopoyéticas/patología , Células Madre Hematopoyéticas/metabolismo , Apoptosis/efectos de la radiación , Hematopoyesis/efectos de la radiación , Proliferación Celular/efectos de la radiación , Línea Celular Tumoral , Rayos Ultravioleta/efectos adversos , Ratones , Ratones Endogámicos C57BL , Factores de Tiempo , Terapia Ultravioleta
6.
Adv Sci (Weinh) ; : e2401210, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38751126

RESUMEN

The molecular structures of surfactants play a pivotal role in influencing their self-assembly behaviors. In this work, using simulations and experiments, an unconventional hierarchically layered structure in the didodecyldimethylammonium bromide (DDAB)/water binary system: lamellae-in-lamellae is revealed, a new self-assembly structure in surfactant system. This self-assembly structure refers to a lamellar structure with a shorter periodic length (inner lamellae) embedded in a lamellar phase with a longer periodic length (outer lamellae). The normal vectors of these two lamellar regions orient perpendicularly. In addition, it is observed that this lamellar-in-lamellar phase disappears when the two tails of the cationic surfactants become longer. The formation of the lamellar-in-lamellar architecture arises from multiple interacting factors. The key element is that the short tails of the DDAB surfactants enhance hydrophilicity and rigidity, which facilitates the formation of the inner lamellae. Moreover, the lateral monolayer of the inner lamellae provides shielding from the water and prompts the formation of the outer lamellae. These findings indicate that molecular structures and flexibility can profoundly redirect the hierarchical self-assembly behaviors in amphiphilic systems. More broadly, this work presents a new strategy to deliberately program hierarchical nanomaterials by designing specific surfactant molecules to act as tunable scaffolds, reactors, and carriers.

7.
Appl Opt ; 63(8): 1971-1981, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38568637

RESUMEN

The extraction of phase information is crucial in moiré tomography for achieving accurate results. In this paper, a method for extracting phase information of moiré fringes based on the Morlet continuous wavelet transform is introduced. A detailed exposition of the theoretical deduction and algorithmic procedure of this method is provided. And then, to validate the feasibility and applicability of this approach, four flow fields are conducted as test objects for experiments. Based on that, the phase results provided by the Morlet continuous wavelet transform are compared with those obtained by the reported techniques such as Fourier transform and Gabor wavelet transform. It is evident that Morlet continuous wavelet transform demonstrates superior accuracy and smoothness, which proves the reliability of this method. In summary, the method presented in this study probably offers an effective method with broad applications.

8.
Opt Express ; 32(6): 9904-9919, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571215

RESUMEN

Scattering caused by suspended particles in the water severely reduces the radiance of the scene. This paper proposes an unsupervised underwater restoration method based on binocular estimation and polarization. Based on the correlation between the underwater transmission process and depth, this method combines the depth information and polarization information in the scene, uses the neural network to perform global optimization and the depth information is recalculated and updated in the network during the optimization process, and reduces the error generated by using the polarization image to calculate parameters, so that detailed parts of the image are restored. Furthermore, the method reduces the requirement for rigorous pairing of data compared to previous approaches for underwater imaging using neural networks. Experimental results show that this method can effectively reduce the noise in the original image and effectively preserve the detailed information in the scene.

9.
BMC Genomics ; 25(1): 352, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594623

RESUMEN

BACKGROUND: Posterior capsular opacification (PCO) is the main reason affecting the long-term postoperative result of cataract patient, and it is well accepted that fibrotic PCO is driven by transforming growth factor beta (TGFß) signaling. Ferroptosis, closely related to various ocular diseases, but has not been explored in PCO. METHODS: RNA sequencing (RNA-seq) was performed on both TGF-ß2 treated and untreated primary lens epithelial cells (pLECs). Differentially expressed genes (DEGs) associated with ferroptosis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate their biological function. Additionally, protein-to-protein interactions among selected ferroptosis-related genes by PPI network and the top 10 genes with the highest score (MCC algorithm) were selected as the hub genes. The top 20 genes with significant fold change values were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our analysis revealed 1253 DEGs between TGF-ß2 treated and untreated pLECs, uncovering 38 ferroptosis-related genes between two groups. Among these 38 ferroptosis-related genes,the most prominent GO enrichment analysis process involved in the response to oxidative stress (BPs), apical part of cell (CCs),antioxidant activity (MFs). KEGG were mainly concentrated in fluid shear stress and atherosclerosis, IL-17 and TNF signaling pathways, and validation of top 20 genes with significant fold change value were consistent with RNA-seq. CONCLUSIONS: Our RNA-Seq data identified 38 ferroptosis-related genes in TGF-ß2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-ß2 stimulation.


Asunto(s)
Opacificación Capsular , Ferroptosis , Humanos , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/farmacología , Transcriptoma , Transición Epitelial-Mesenquimal/genética , Ferroptosis/genética , Western Blotting , Opacificación Capsular/genética , Opacificación Capsular/metabolismo , Células Epiteliales/metabolismo
10.
J Appl Toxicol ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639436

RESUMEN

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first-line drugs for regulating blood lipids and treating hyperlipidemia-related cardiovascular diseases. However, ATV-associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 µM) and demonstrated the effects of BBR (10, 50, and 100 µM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish. BBR was found to reduce brain inflammation and locomotion injury in ICH-zebrafish. Mechanism research showed that ATV increased the levels of VE-cadherin and occludin proteins but disturbed their localization at the cell membrane by abnormal phosphorylation, which decreased the number of intercellular junctions between vascular endothelial cells (VECs), disrupting the integrity of vascular walls. BBR reversed the effects of ATV by promoting autophagic degradation of phosphorylated VE-cadherin and occludin in ATV-induced VECs examined by co-immunoprecipitation (co-IP). These findings provide crucial insights into understanding the BBR mechanisms involved in the maintenance of vascular integrity and in mitigating adverse reactions to ATV.

11.
Sci Bull (Beijing) ; 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38641514

RESUMEN

Topological band theory has conventionally been concerned with the topology of bands around a single gap. Only recently non-Abelian topologies that thrive on involving multiple gaps were studied, unveiling a new horizon in topological physics beyond the conventional paradigm. Here, we report on the first experimental realization of a topological Euler insulator phase with unique meronic characterization in an acoustic metamaterial. We demonstrate that this topological phase has several nontrivial features: First, the system cannot be described by conventional topological band theory, but has a nontrivial Euler class that captures the unconventional geometry of the Bloch bands in the Brillouin zone. Second, we uncover in theory and probe in experiments a meronic configuration of the bulk Bloch states for the first time. Third, using a detailed symmetry analysis, we show that the topological Euler insulator evolves from a non-Abelian topological semimetal phase via. the annihilation of Dirac points in pairs in one of the band gaps. With these nontrivial properties, we establish concretely an unconventional bulk-edge correspondence which is confirmed by directly measuring the edge states via. pump-probe techniques. Our work thus unveils a nontrivial topological Euler insulator phase with a unique meronic pattern and paves the way as a platform for non-Abelian topological phenomena.

12.
Acta Radiol ; : 2841851241242653, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38644751

RESUMEN

BACKGROUND: The grading of adult isocitrate dehydrogenase (IDH)-mutant astrocytomas is a crucial prognostic factor. PURPOSE: To investigate the value of conventional magnetic resonance imaging (MRI) features and apparent diffusion coefficient (ADC) in the grading of adult IDH-mutant astrocytomas, and to analyze the correlation between ADC and the Ki-67 proliferation index. MATERIAL AND METHODS: The clinical and MRI data of 82 patients with adult IDH-mutant astrocytoma who underwent surgical resection and molecular genetic testing with IDH and 1p/19q were retrospectively analyzed. The conventional MRI features, ADCmin, ADCmean, and nADC of the tumors were compared using the Kruskal-Wallis single factor ANOVA and chi-square tests. Receiver operating characteristic (ROC) curves were drawn to evaluate conventional MRI and ADC accuracy in differentiating tumor grades. Pearson correlation analysis was performed to determine the correlation between ADC and the Ki-67 proliferation index. RESULTS: The difference in enhancement, ADCmin, ADCmean, and nADC among WHO grade 2, 3, and 4 tumors was statistically significant (all P <0.05). ADCmin showed the preferable diagnostic accuracy for grading WHO grade 2 and 3 tumors (AUC=0.724, sensitivity=63.4%, specificity=80%, positive predictive value (PPV)=62.0%; negative predictive value (NPV)=82.5%), and distinguishing grade 3 from grade 4 tumors (AUC=0.764, sensitivity=70%, specificity=76.2%, PPV=75.0%, NPV=71.4%). Enhancement + ADC model showed an optimal predictive accuracy (grade 2 vs. 3: AUC = 0.759; grade 3 vs. 4: AUC = 0.799). The Ki-67 proliferation index was negatively correlated with ADCmin, ADCmean, and nADC (all P <0.05), and positively correlated with tumor grade. CONCLUSION: Conventional MRI features and ADC are valuable to predict pathological grading of adult IDH-mutant astrocytomas.

13.
Arch Oral Biol ; 163: 105982, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38678878

RESUMEN

OBJECTIVES: To investigate the importance of fatty acid oxidation (FAO)-related genes in predicting the progression and prognosis of head and neck squamous cell carcinoma (HNSCC). METHODS: The FAO-related gene prognostic model was established employing Cox regression analyses, during which accuracy and sensitivity of the gene model were evaluated in The Cancer Genome Atlas (TCGA) internal testing and Gene Expression Omnibus (GEO) external validation cohorts. Ultimately, hub genes were identified among 13 model genes using STRING and Cytoscape, with preliminary validation carried out through immunohistochemistry. RESULTS: The model, which comprised 13 genes (ABCD2, ACAA1, ACACB, AKT1, CNR1, CPT1C, CROT, ECHDC2, ETFA, HADHB, IRS2, LONP2, and SLC25A17), was established. On the basis of the median risk score, the two cohorts were grouped into low-and high-risk groups in the subsequent test and validation, and the former exhibited significantly higher survival rates than the latter. Nomograms were established based on prognostic factors, including stage and risk score, and individualized for the prediction of HNSCC patients. Ultimately, immunohistochemical staining showed that ACAA1 and HADHB were significantly under-expressed in HNSCC, with a favorable prognosis associated with low HADHB and high ACAA1. CONCLUSIONS: The gene prognostic model has illustrated promising capability in predicting the prognosis, and ACAA1 and HADHB might serve as potential therapeutic biomarkers for HNSCC patients.


Asunto(s)
Biomarcadores de Tumor , Ácidos Grasos , Neoplasias de Cabeza y Cuello , Nomogramas , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estudios Retrospectivos , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Masculino , Ácidos Grasos/metabolismo , Femenino , Persona de Mediana Edad , Oxidación-Reducción , Inmunohistoquímica , Anciano , Regulación Neoplásica de la Expresión Génica
14.
J Chem Phys ; 160(16)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38661200

RESUMEN

In extreme and nanoconfinement conditions, the tetrahedral arrangement of water molecules is challenged, resulting in a rich and new phase behavior unseen in bulk phases. The unique phase behavior of water confined in hydrophobic nanoslits has been previously observed, such as the formation of a variety of two-dimensional (2D) ices below the freezing temperature. The primary identified 2D ice phase, termed square tube ice (STI), represents a unique arrangement of water molecules in 2D ice, which can be viewed as an array of 1D ice nanotubes stacked in the direction parallel to the confinement plane. In this study, we report the molecular dynamics (MD) simulations evidence of a novel 2D ice phase, namely, helical square tube ice (H-STI). H-STI is characterized by the stacking of helical ice nanotubes in the direction parallel to the confinement plane. Its structural specificity is evident in the presence of helical square ice nanotubes, a configuration unseen in both STI and single-walled ice nanotubes. A detailed analysis of the hydrogen bonding strength showed that H-STI is a 2D ice phase diverging from the Bernal-Fowler-Pauling ice rules by forming only two strong hydrogen bonds between adjacent molecules along its helical ice chain. This arrangement of strong hydrogen bonds along ice nanotube and weak bonds between the ice nanotube shows a similarity to quasi-one-dimensional van der Waals materials. Ab initio molecular dynamics simulations (over a 30 ps) were employed to further verify H-STI's stability at 1 GPa and temperature up to 200 K.

15.
Pain ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38598349

RESUMEN

ABSTRACT: Tendon injury produces intractable pain and disability in movement, but the medications for analgesia and restoring functional integrity of tendon are still limited. In this study, we report that proteinase-activated receptor 2 (PAR2) activation in dorsal root ganglion (DRG) neurons contributes to chronic pain and tendon histopathological changes produced by Achilles tendon partial transection injury (TTI). Tendon partial transection injury increases the expression of PAR2 protein in both somata of DRG neurons and their peripheral terminals within the injured Achilles tendon. Activation of PAR2 promotes the primary sensory neuron plasticity by activating downstream cAMP-PKA pathway, phosphorylation of PKC, CaMKII, and CREB. Blocking PAR2 signaling by PAR2 small-interference RNA or antagonistic peptide PIP delays the onset of TTI-induced pain, reverses the ongoing pain, as well as inhibits sensory nerve sprouting, and promotes structural remodeling of the injured tendon. Vitamin B complex (VBC), containing thiamine (B1), pyridoxine (B6), and cyanocobalamin (B12), is effective to ameliorate TTI-induced pain, inhibit ectopic nerve sprouting, and accelerate tendon repair, through suppressing PAR2 activation. These findings reveal a critical role of PAR2 signaling in the development of chronic pain and histopathological alterations of injured tendon following Achilles tendon injury. This study suggests that the pharmaceuticals targeting PAR2, such as VBC, may be an effective approach for the treatment of tendon injury-induced pain and promoting tendon repair.

16.
Exp Biol Med (Maywood) ; 249: 10040, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577707

RESUMEN

Regulatory T cells (Tregs) constitute a specialized subset of T cells with dual immunoregulatory and modulatory functions. Recent studies have reported that Tregs mediate immune responses and regulate the development and repair processes in non-lymphoid tissues, including bone and cardiac muscle. Additionally, Tregs facilitate the repair and regeneration of damaged lung tissues. However, limited studies have examined the role of Tregs in pulmonary development. This study aimed to evaluate the role of Tregs in pulmonary development by investigating the dynamic alterations in Tregs and their hallmark cellular factor Forkhead box P3 (Foxp3) at various stages of murine lung development and establishing a murine model of anti-CD25 antibody-induced Treg depletion. During the early stages of murine lung development, especially the canalicular and saccular stages, the levels of Treg abundance and expression of Foxp3 and transforming growth factor-ß (TGF-ß) were upregulated. This coincided with the proliferation period of alveolar epithelial cells and vascular endothelial cells, indicating an adaptation to the dynamic lung developmental processes. Furthermore, the depletion of Tregs disrupted lung tissue morphology and downregulated lung development-related factors, such as surfactant protein C (SFTPC), vascular endothelial growth factor A (VEGFA) and platelet endothelial cell adhesion molecule-1 (PECAM1/CD31). These findings suggest that Tregs promote murine lung development.


Asunto(s)
Linfocitos T Reguladores , Factor A de Crecimiento Endotelial Vascular , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular/metabolismo , Células Endoteliales/metabolismo , Pulmón/metabolismo , Factores de Transcripción Forkhead/metabolismo
17.
Toxicology ; 505: 153814, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38677583

RESUMEN

The field of chemical toxicity testing is undergoing a transition to overcome the limitations of in vivo experiments. This evolution involves implementing innovative non-animal approaches to improve predictability and provide a more precise understanding of toxicity mechanisms. Adverse outcome pathway (AOP) networks are pivotal in organizing existing mechanistic knowledge related to toxicological processes. However, these AOP networks are dynamic and require regular updates to incorporate the latest data. Regulatory challenges also persist due to concerns about the reliability of the information they offer. This study introduces a generic Weight-of-Evidence (WoE) scoring method, aligned with the tailored Bradford-Hill criteria, to quantitatively assess the confidence levels in key event relationships (KERs) within AOP networks. We use the previously published AOP network on chemical-induced liver steatosis, a prevalent form of human liver injury, as a case study. Initially, the existing AOP network is optimized with the latest scientific information extracted from PubMed using the free SysRev platform for artificial intelligence (AI)-based abstract inclusion and standardized data collection. The resulting optimized AOP network, constructed using Cytoscape, visually represents confidence levels through node size (key event, KE) and edge thickness (KERs). Additionally, a Shiny application is developed to facilitate user interaction with the dataset, promoting future updates. Our analysis of 173 research papers yielded 100 unique KEs and 221 KERs among which 72 KEs and 170 KERs, respectively, have not been previously documented in the prior AOP network or AOP-wiki. Notably, modifications in de novo lipogenesis, fatty acid uptake and mitochondrial beta-oxidation, leading to lipid accumulation and liver steatosis, garnered the highest KER confidence scores. In conclusion, our study delivers a generic methodology for developing and assessing AOP networks. The quantitative WoE scoring method facilitates in determining the level of support for KERs within the optimized AOP network, offering valuable insights into its utility in both scientific research and regulatory contexts. KERs supported by robust evidence represent promising candidates for inclusion in an in vitro test battery for reliably predicting chemical-induced liver steatosis within regulatory frameworks.

18.
J Agric Food Chem ; 72(17): 10005-10013, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38626461

RESUMEN

Dunaliella bardawil is a marine unicellular green algal that produces large amounts of ß-carotene and is a model organism for studying the carotenoid synthesis pathway. However, there are still many mysteries about the enzymes of the D. bardawil lycopene synthesis pathway that have not been revealed. Here, we have identified a CruP-like lycopene isomerase, named DbLyISO, and successfully cloned its gene from D. bardawil. DbLyISO showed a high homology with CruPs. We constructed a 3D model of DbLyISO and performed molecular docking with lycopene, as well as molecular dynamics testing, to identify the functional characteristics of DbLyISO. Functional activity of DbLyISO was also performed by overexpressing gene in both E. coli and D. bardawil. Results revealed that DbLyISO acted at the C-5 and C-13 positions of lycopene, catalyzing its cis-trans isomerization to produce a more stable trans structure. These results provide new ideas for the development of a carotenoid series from engineered bacteria, algae, and plants.


Asunto(s)
Chlorophyceae , Liasas Intramoleculares , Licopeno , cis-trans-Isomerasas , Proteínas Algáceas/genética , Proteínas Algáceas/metabolismo , Proteínas Algáceas/química , Secuencia de Aminoácidos , Carotenoides/metabolismo , Carotenoides/química , Chlorophyceae/enzimología , Chlorophyceae/genética , Chlorophyceae/química , Chlorophyceae/metabolismo , Chlorophyta/enzimología , Chlorophyta/genética , Chlorophyta/química , Chlorophyta/metabolismo , cis-trans-Isomerasas/genética , cis-trans-Isomerasas/metabolismo , cis-trans-Isomerasas/química , Escherichia coli/genética , Escherichia coli/metabolismo , Licopeno/metabolismo , Licopeno/química , Simulación del Acoplamiento Molecular , Alineación de Secuencia
19.
Physiol Plant ; 176(2): e14296, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650503

RESUMEN

In Dunaliella tertiolecta, a microalga renowned for its extraordinary tolerance to high salinity levels up to 4.5 M NaCl, the mechanisms underlying its stress response have largely remained a mystery. In a groundbreaking discovery, this study identifies a choline dehydrogenase enzyme, termed DtCHDH, capable of converting choline to betaine aldehyde. Remarkably, this is the first identification of such an enzyme not just in D. tertiolecta but across the entire Chlorophyta. A 3D model of DtCHDH was constructed, and molecular docking with choline was performed, revealing a potential binding site for the substrate. The enzyme was heterologously expressed in E. coli Rosetta (DE3) and subsequently purified, achieving enzyme activity of 672.2 U/mg. To elucidate the role of DtCHDH in the salt tolerance of D. tertiolecta, RNAi was employed to knock down DtCHDH gene expression. The results indicated that the Ri-12 strain exhibited compromised growth under both high and low salt conditions, along with consistent levels of DtCHDH gene expression and betaine content. Additionally, fatty acid analysis indicated that DtCHDH might also be a FAPs enzyme, catalyzing reactions with decarboxylase activity. This study not only illuminates the role of choline metabolism in D. tertiolecta's adaptation to high salinity but also identifies a novel target for enhancing the NaCl tolerance of microalgae in biotechnological applications.


Asunto(s)
Betaína , Colina-Deshidrogenasa , Tolerancia a la Sal , Betaína/metabolismo , Tolerancia a la Sal/genética , Colina-Deshidrogenasa/metabolismo , Colina-Deshidrogenasa/genética , Colina/metabolismo , Chlorophyceae/genética , Chlorophyceae/fisiología , Chlorophyceae/enzimología , Chlorophyceae/metabolismo , Microalgas/genética , Microalgas/enzimología , Microalgas/metabolismo , Simulación del Acoplamiento Molecular , Cloruro de Sodio/farmacología
20.
Phytochemistry ; 222: 114094, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38604325

RESUMEN

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 µM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.


Asunto(s)
Carthamus tinctorius , Glicósidos , Oxidación-Reducción , Glicósidos/química , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Animales , Carthamus tinctorius/química , Ratas , Estructura Molecular , Neuronas/efectos de los fármacos , Relación Estructura-Actividad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Corteza Cerebral/efectos de los fármacos , Chalconas/farmacología , Chalconas/química , Chalconas/aislamiento & purificación
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