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1.
Artigo em Inglês | MEDLINE | ID: mdl-38775170

RESUMO

NiFe layered double hydroxide (LDH) with abundant heterostructures represents a state-of-the-art electrocatalyst for the alkaline oxygen evolution reaction (OER). Herein, NiFe LDH/Fe2O3 nanosheet arrays have been fabricated by facile combustion of corrosion-engineered NiFe foam (NFF). The in situ grown, self-supported electrocatalyst exhibited a low overpotential of 248 mV for the OER at 50 mA cm-2, a small Tafel slope of 31 mV dec-1, and excellent durability over 100 h under the industrial benchmarking 500 mA cm-2 current density. A balanced Ni and Fe composition under optimal corrosion and combustion contributed to the desirable electrochemical properties. Comprehensive ex-situ analyses and operando characterizations including Fourier-transformed alternating current voltammetry (FTACV) and in situ Raman demonstrate the beneficial role of modulated interfacial electron transfer, dynamic atomic structural transformation to NiOOH, and the high-valence active metal sites. This study provides a low-cost and easy-to-expand way to synthesize efficient and durable electrocatalysts.

2.
Br J Radiol ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724228

RESUMO

OBJECTIVE: To methodically analyze the swirl sign and construct a scoring system to predict the risk of hematoma expansion (HE) after spontaneous intracerebral hemorrhage (sICH). METHODS: We analysed 231 of 683 sICH patients with swirl signs on baseline noncontrast computed tomography (NCCT) images. The characteristics of the swirl sign were analyzed, including the number, maximum diameter, shape, boundary, minimum CT value of the swirl sign and the minimum distance from the swirl sign to the edge of the hematoma. In the development cohort, univariate and multivariate analyses were used to identify independent predictors of HE, and logistic regression analysis was used to construct the swirl sign score system. The swirl sign score system was verified in the validation cohort. RESULTS: The number and the minimum CT value of the swirl sign were independent predictors of HE. The swirl sign score system was constructed (2 points for the number of swirl signs > 1 and 1 point for the minimum CT value ≤ 41 Hounsfield units). The area under the curve of the swirl sign score system in predicting HE was 0.773 and 0.770 in the development and validation groups, respectively. CONCLUSIONS: The swirl sign score system is an easy-to-use radiological grading scale that requires only baseline NCCT images to effectively identify subjects at high risk of HE. ADVANCES IN KNOWLEDGE: Our newly developed semi-quantitative swirl sign score system greatly improves the ability of swirl sign to predict HE.

3.
Food Funct ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727519

RESUMO

In order to explore the in vivo anti-food allergy activity of Lactobacillus sakei subsp. sakei-fermented Eucheuma spinosum polysaccharides F1-ESP-3, an ovalbumin (OVA)-induced food allergy mouse model was established by ascites immunization and gavage. The weight, temperature, incidence of diarrhea, levels of allergic mediators and inflammatory factors in the serum of mice were analyzed. We analyzed the differentiation of mouse spleen lymphocytes and the proportion of sensitized mast cells by flow cytometry. The intestinal barrier status of mice was analyzed by intestinal pathological tissue sections and microbiota sequencing. The results showed that F1-ESP-3 could alleviate the food allergy symptoms of mice, such as hypothermia and loose stool; levels of OVA-specific immunoglobulin E, mast cell protease and histamine in the serum of sensitized mice and the proportion of dendritic cells and mast cells in mouse spleen were significantly reduced; in addition, F1-ESP-3 may protect the intestinal barrier and further improve the intestinal microenvironment of food-allergic mice by regulating the abundance of Bacteroidetes and Firmicutes. F1-ESP-3 can further improve the intestinal microenvironment of food-allergic mice by upregulating the levels of Lachnospiraceae, and may affect the signal pathways such as NOD-like receptor, MAPK, I kappa B and antigen processing and presentation.

4.
Small ; : e2402265, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757418

RESUMO

The emerging applications of thermally conductive elastomer composites in modern electronic devices for heat dissipation require them to maintain both high toughness and resilience under thermomechanical stresses. However, such a combination of thermal conductivity and desired mechanical characteristics is extremely challenging to achieve in elastomer composites. Here this long-standing mismatch is resolved via regulating interfacial structure and dynamics response. This regulation is realized both by tuning the molecular weight of the dangling chains in the polymer networks and by silane grafting of the fillers, thereby creating a broad dynamic-gradient interfacial region comprising of entanglements. These entanglements can provide the slipping topological constraint that allows for tension equalization between and along the chains, while also tightening into rigid knots to prevent chain disentanglement upon stretching. Combined with ultrahigh loading of aluminum-fillers (90 wt%), this design provides a low Young's modulus (350.0 kPa), high fracture toughness (831.5 J m-2), excellent resilience (79%) and enhanced thermal conductivity (3.20 W m-1 k-1). This work presents a generalizable preparation strategy toward engineering soft, tough, and resilient high-filled elastomer composites, suitable for complex environments, such as automotive electronics, and wearable devices.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38758128

RESUMO

Mouse models of congenital aortic valve malformations are useful for studying disease pathobiology, but most models have incomplete penetrance (e.g., ~2 to 77% prevalence of bicuspid aortic valves (BAVs) across multiple models). For longitudinal studies of pathologies associated with BAVs and other congenital valve malformations, which manifest over months in mice, it is operationally inefficient, economically burdensome, and ethically challenging to enroll large numbers of mice in studies without first identifying those with valvular abnormalities. To address this need, we established and validated a novel in vivo high frequency (30 MHz) ultrasound imaging protocol capable of detecting aortic valvular malformations in juvenile mice. Fifty natriuretic peptide receptor 2 heterozygous mice on a low density lipoprotein receptor deficient background (Npr2+/-;Ldlr-/-; 32 male, 18 female) were imaged at 4- and 8-weeks of age. Fourteen percent of the Npr2+/-;Ldlr-/- mice exhibited features associated with aortic valve malformations, including: i) abnormal trans-aortic flow patterns on color Doppler (recirculation and regurgitation); ii) peak systolic flow velocities distal to the aortic valves reaching or surpassing ~1250 mm/s by pulsed wave Doppler; and iii) putative fusion of cusps along commissures and abnormal movement elucidated by 2D imaging with ultra-high temporal resolution. Valves with these features were confirmed by ex vivo gross anatomy and histological visualization to have thickened cusps, partial fusions, or Sievers type 0 bicuspid valves. This ultrasound imaging protocol will enable efficient, cost-effective and humane implementation of studies of congenital aortic valvular abnormalities and associated pathologies in a wide range of mouse models.

6.
ACS Omega ; 9(18): 20410-20424, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737081

RESUMO

The droplet-to-iron electrochemical reaction is common in nature and industrial production, and it causes damage to the economy, safety, and the environment. The electrochemical reaction of droplet-to-iron is a coupling process of wetting and corrosion. Presently, investigations into electrochemical reactions mainly focus on the corrosions caused by a solution, and wetting is rarely considered. However, for the droplet-to-iron electrochemical reaction, the mechanism of charge transfer in the process is still unclear. In this paper, a reactive molecular dynamics simulation model for the droplet-to-iron electrochemical reaction is developed for the first time. The electrochemical reaction of droplet-to-iron is studied, and the interaction between droplet wetting and corrosion on iron is investigated. The effects of temperature, electric field strength, and salt concentration on the electrochemical reaction are explored. Results show that droplet wetting on the iron surface and the formation of a single-molecular-layer ordered structure are prerequisites for corrosion. The hydroxyl radicals that penetrate the ordered structure acquire electrons from iron atoms on the substrate surface under the action of Coulomb forces and form iron-containing oxides with these iron atoms. The corrosion products and craters lead to a reduced droplet height, which promotes droplet wetting on iron and further intensifies the droplet-to-iron electrochemical reaction.

7.
Front Immunol ; 15: 1369892, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707897

RESUMO

Background: The transcription factor, SOX13 is part of the SOX family. SOX proteins are crucial in the progression of many cancers, and some correlate with carcinogenesis. Nonetheless, the biological and clinical implications of SOX13 in human breast cancer (BC) remain rarely known. Methods: We evaluated the survival and expression data of SOX13 in BC patients via the UNLCAL, GEPIA, TIMER, and Kaplan-Meier plotter databases. Immunohistochemistry (IHC) was used to verify clinical specimens. The gene alteration rates of SOX13 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between SOX13 mRNA expression and copy number alterations (CNA) and methylation was determined. LinkedOmics was used to identify the genes that co-expressed with SOX13 and the regulators. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuCellAI and TIMER2.0 databases. SOX13 correlated drug resistance analysis was performed using the GDSC2 database. Results: Higher SOX13 expression was discovered in BC tissues in comparison to normal tissues. Moreover, increased gene mutation and amplification of SOX13 were found in BC. Patients with increased SOX13 expression levels showed worse overall survival (OS). Cox analysis showed that SOX13 independently served as a prognostic indicator for poor survival in BC. Further, the expression of SOX13 was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells. In terms of drug sensitivity analysis, we found higher expression level of SOX13 predicts a high IC50 value for most of 198 drugs which predicts drug resistance. Conclusion: The present findings demonstrated that high expression of SOX13 negatively relates to prognosis and SOX13 plays an important role in cancer immunity. Therefore, SOX13 may potentially be adopted as a biomarker for predicting BC prognosis and infiltration of immune cells.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Microambiente Tumoral , Humanos , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Feminino , Biomarcadores Tumorais/genética , Prognóstico , Microambiente Tumoral/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Estimativa de Kaplan-Meier
8.
Artigo em Inglês | MEDLINE | ID: mdl-38710844

RESUMO

Streamflow time series data typically exhibit nonlinear and nonstationary characteristics that complicate precise estimation. Recently, multifactorial machine learning (ML) models have been developed to enhance the performance of streamflow predictions. However, the lack of interpretability within these ML models raises concerns about their inner workings and reliability. This paper introduces an innovative hybrid architecture, the TCN-LSTM-Multihead-Attention model, which combines two layers of temporal convolutional networks (TCN) followed by one layer of long short-term memory (LSTM) units, integrated with a Multihead-Attention mechanism for predicting streamflow with streamflow causation-driven prediction samples (RCDP), employing local and global interpretability studies through Shapley values and partial dependency analysis. The find_peaks method was used to identify peak flow events in the test dataset, validating the model's generality and uncovering the physical causative patterns of streamflow. The results show that (1) compared to the LSTM model with the same hyperparameter settings, the proposed TCN-LSTM-Multihead-Attention hybrid model increased the R2 by 52.9%, 2.5%, 43.1%, and 10.7% respectively at four stations in the test set predictions using RCDP samples. Moreover, comparing the prediction results of the hybrid model under different samples in Hengshan station, the R2 for RCDP increased by 5.06% and 1.22% compared to streamflow autoregressive prediction samples (RAP) and meteorological-soil volumetric water content coupled autoregressive prediction samples (MCSAP) respectively. (2) Historical streamflow data from the preceding 3 days predominantly influences predictions due to strong autocorrelation, with flow quantity (Q) typically emerging as the most significant feature alongside precipitation (P), surface soil moisture (SSM), and adjacent station flow data. (3) During periods of low and normal flow, historical data remains the most crucial factor; however, during flood periods, the roles of upstream inflow and precipitation become significantly more pronounced. This model facilitates the identification and quantification of various hydrodynamic impacts on flow predictions, including upstream flood propagation, precipitation, and soil moisture conditions. It also elucidates the model's nonlinear relationships and threshold responses, thereby enhancing the interpretability and reliability of streamflow predictions.

9.
Sci Robot ; 9(90): eadi8666, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748782

RESUMO

Garnering inspiration from biological compound eyes, artificial vision systems boasting a vivid range of diverse visual functional traits have come to the fore recently. However, most of these artificial systems rely on transformable electronics, which suffer from the complexity and constrained geometry of global deformation, as well as potential mismatches between optical and detector units. Here, we present a unique pinhole compound eye that combines a three-dimensionally printed honeycomb optical structure with a hemispherical, all-solid-state, high-density perovskite nanowire photodetector array. The lens-free pinhole structure can be designed and fabricated with an arbitrary layout to match the underlying image sensor. Optical simulations and imaging results matched well with each other and substantiated the key characteristics and capabilities of our system, which include an ultrawide field of view, accurate target positioning, and motion tracking function. We further demonstrate the potential of our unique compound eye for advanced robotic vision by successfully completing a moving target tracking mission.

10.
Front Neurosci ; 18: 1394795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745941

RESUMO

Background: The relationship between early perihematomal edema (PHE) and hematoma expansion (HE) is unclear. We investigated this relationship in patients with acute spontaneous intracerebral hemorrhage (ICH), using radiomics. Methods: In this multicenter retrospective study, we analyzed 490 patients with spontaneous ICH who underwent non-contrast computed tomography within 6 h of symptom onset, with follow-up imaging at 24 h. We performed HE and PHE image segmentation, and feature extraction and selection to identify HE-associated optimal radiomics features. We calculated radiomics scores of hematoma (Radscores_HEA) and PHE (Radscores_PHE) and constructed a combined model (Radscore_HEA_PHE). Relationships of the PHE radiomics features or Radscores_PHE with clinical variables, hematoma imaging signs, Radscores_HEA, and HE were assessed by univariate, correlation, and multivariate analyses. We compared predictive performances in the training (n = 296) and validation (n = 194) cohorts. Results: Shape_VoxelVolume and Shape_MinorAxisLength of PHE were identified as optimal radiomics features associated with HE. Radscore_PHE (odds ratio = 1.039, p = 0.032) was an independent HE risk factor after adjusting for the ICH onset time, Glasgow Coma Scale score, baseline hematoma volume, hematoma shape, hematoma density, midline shift, and Radscore_HEA. The areas under the receiver operating characteristic curve of Radscore_PHE in the training and validation cohorts were 0.808 and 0.739, respectively. After incorporating Radscore_PHE, the integrated discrimination improvements of Radscore_HEA_PHE in the training and validation cohorts were 0.009 (p = 0.086) and -0.011 (p < 0.001), respectively. Conclusion: Radscore_PHE, based on Shape_VoxelVolume and Shape_MinorAxisLength of PHE, independently predicts HE, while Radscore_PHE did not add significant incremental value to Radscore_HEA.

11.
Int Immunopharmacol ; 134: 112076, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733818

RESUMO

BACKGROUND: The research on the S100 family has garnered significant attention; however, there remains a dearth of understanding regarding the precise role of S100A16 in the tumor microenvironment of liver cancer. METHOD: Comprehensive analysis was conducted on the expression of S100A16 in tumor tissues and its correlation with hypoxia genes. Furthermore, an investigation was carried out to examine the association between S100A16 and infiltration of immune cells in tumors as well as immunotherapy. Relevant findings were derived from the analysis of single cell sequencing data, focusing on the involvement of S100A16 in both cellular differentiation and intercellular communication. Finally, we validated the expression of S100A16 in liver cancer by Wuhan cohort and multiplexed immunofluorescence to investigate the correlation between S100A16 and hypoxia. RESULT: Tumor tissues displayed a notable increase in the expression of S100A16. A significant correlation was observed between S100A16 and genes associated with hypoxic genes. Examination of immune cell infiltration revealed an inverse association between T cell infiltration and the level of S100A16 expression. The high expression group of S100A16 exhibited a decrease in the expression of genes related to immune cell function. Single-cell sequencing data analysis revealed that non-immune cells predominantly expressed S100A16, and its expression levels increased along with the trajectory of cell differentiation. Additionally, there were significant variations observed in hypoxia genes as cells underwent differentiation. Cellular communication identified non-immune cells interacting with immune cells through multiple signaling pathways. The Wuhan cohort verified that S100A16 expression was increased in liver cancer. The expression of S100A16 and HIF was simultaneously elevated in endothelial cells. CONCLUSION: The strong association between S100A16 and immune cell infiltration is observed in the context of hypoxia, indicating its regulatory role in shaping the hypoxic tumor microenvironment in liver cancer.

12.
Int Immunopharmacol ; 134: 112173, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38728884

RESUMO

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is characterized by a high incidence and mortality rate, highlighting the need for biomarkers to detect ILD early in RA patients. Previous studies have shown the protective effects of Interleukin-22 (IL-22) in pulmonary fibrosis using mouse models. This study aims to assess IL-22 expression in RA-ILD to validate foundational experiments and explore its diagnostic value. The study included 66 newly diagnosed RA patients (33 with ILD, 33 without ILD) and 14 healthy controls (HC). ELISA was utilized to measure IL-22 levels and perform intergroup comparisons. The correlation between IL-22 levels and the severity of RA-ILD was examined. Logistic regression analysis was employed to screen potential predictive factors for RA-ILD risk and establish a predictive nomogram. The diagnostic value of IL-22 in RA-ILD was assessed using ROC. Subsequently, the data were subjected to 30-fold cross-validation. IL-22 levels in the RA-ILD group were lower than in the RA-No-ILD group and were inversely correlated with the severity of RA-ILD. Logistic regression analysis identified IL-22, age, smoking history, anti-mutated citrullinated vimentin antibody (MCV-Ab), and mean corpuscular hemoglobin concentration (MCHC) as independent factors for distinguishing between the groups. The diagnostic value of IL-22 in RA-ILD was moderate (AUC = 0.75) and improved when combined with age, smoking history, MCV-Ab and MCHC (AUC = 0.97). After 30-fold cross-validation, the average AUC was 0.886. IL-22 expression is dysregulated in the pathogenesis of RA-ILD. This study highlights the potential of IL-22, along with other factors, as a valuable biomarker for assessing RA-ILD occurrence and progression.

13.
Cancer Med ; 13(10): e7227, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38770632

RESUMO

BACKGROUND: To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. METHODS: A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis-related genes and establish a predictive model for stratifying patients with LUAD. RESULTS: In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK-RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic-Related Genes (CCRGs) were found to closely related to the clinical high-risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM-low group showed significantly better overall survival (OS) compared to the MPGM-high group (p < 0.0001, area under the curve (AUC) = 0.754). The robust performance was validated in 55 LUAD patients from the DPH cohort and another LUAD dataset. Immune characteristics analysis revealed a higher proportion of primarily DCs and mononuclear cells in the MPGM-low risk group, while the MPGM-high risk group showed lower immune cells and higher tumor cell infiltration. CONCLUSION: This study provides a comprehensive genomic landscape of Chinese LUAD patients and develops an MPGM risk model for LUAD prognosis stratification. Further follow-up will be performed for the patients in the DPH cohort consistently to explore the resistance and prognosis genetic features.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Mutação , Humanos , Masculino , Feminino , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Prognóstico , Pessoa de Meia-Idade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Idoso , Estudos Retrospectivos , Receptores ErbB/genética , Biomarcadores Tumorais/genética , China/epidemiologia , Adulto , Relevância Clínica , População do Leste Asiático , Receptores de LDL , Proteína Supressora de Tumor p53 , Proteínas Proto-Oncogênicas p21(ras) , Proteínas de Ligação a RNA
15.
Curr Opin Plant Biol ; 80: 102552, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38776571

RESUMO

The precise targeted gene regulation in plants is essential for improving plant traits and gaining a comprehensive understanding of gene functions. The regulation of gene expression in eukaryotes can be achieved through transcriptional and epigenetic mechanisms. Over the last decade, advancements in gene-targeting technologies, along with an expanded understanding of epigenetic gene regulation mechanisms, have significantly contributed to the development of programmable gene regulation tools. In this review, we will discuss the recent progress in targeted plant gene regulation through epigenome editing, emphasizing the role of effector proteins in modulating target gene expression via diverse mechanisms, including DNA methylation, histone modifications, and chromatin remodeling. Additionally, we will also briefly review targeted gene regulation by transcriptional regulation and mRNA modifications in plants.

16.
Meat Sci ; 215: 109541, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38776591

RESUMO

The impact of basic amino acids (Lysine, Arginine, Histidine) on the formation of total heterocyclic amines (HAs) was investigated in fried beef patties at 1% NaCl level. Different levels of basic amino acids (0.1%, 0.5%, 1%) significantly inhibited the formation of the total and individual HAs at 1% NaCl, and the inhibitory effect was more effective than 3% NaCl (6.19 ng/g, 26.93% inhibition) (P < 0.05). Lys at 1% reduced total HAs the most (2.46 ng/g, 70.88% inhibition), followed by 1% His (2.79 ng/g, 67.03% inhibition) and 1% Arg (3.43 ng/g, 59.51% inhibition). Compared to the 3% NaCl, the quality characteristics (moisture content, frying loss, texture profile, and color) of the fried beef patties were significantly improved when basic amino acids were added at 1% NaCl (P < 0.05). The lipid oxidation of fried beef patties was significantly inhibited by 1% Arg and 1% Lys at 1% NaCl level (P < 0.05). The results indicated that basic amino acids could inhibit the formation of total HAs while maintaining the quality of meat products at low NaCl condition.

17.
Chem Sci ; 15(20): 7502-7514, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38784726

RESUMO

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

18.
J Neurochem ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690718

RESUMO

Positron emission tomography (PET) imaging studies in laboratory animals are almost always performed under isoflurane anesthesia to ensure that the subject stays still during the image acquisition. Isoflurane is effective, safe, and easy to use, and it is generally assumed to not have an impact on the imaging results. Motivated by marked differences observed in the brain uptake and metabolism of the PET tracer 3-[18F]fluoro-4-aminopyridine [(18F]3F4AP) between human and nonhuman primate studies, this study investigates the possible effect of isoflurane on this process. Mice received [18F]3F4AP injection while awake or under anesthesia and the tracer brain uptake and metabolism was compared between groups. A separate group of mice received the known cytochrome P450 2E1 inhibitor disulfiram prior to tracer administration. Isoflurane was found to largely abolish tracer metabolism in mice (74.8 ± 1.6 vs. 17.7 ± 1.7% plasma parent fraction, % PF) resulting in a 4.0-fold higher brain uptake in anesthetized mice at 35 min post-radiotracer administration. Similar to anesthetized mice, animals that received disulfiram showed reduced metabolism (50.0 ± 6.9% PF) and a 2.2-fold higher brain signal than control mice. The higher brain uptake and lower metabolism of [18F]3F4AP observed in anesthetized mice compared to awake mice are attributed to isoflurane's interference in the CYP2E1-mediated breakdown of the tracer, which was confirmed by reproducing the effect upon treatment with the known CYP2E1 inhibitor disulfiram. These findings underscore the critical need to examine the effect of isoflurane in PET imaging studies before translating tracers to humans that will be scanned without anesthesia.

19.
Biotechnol Adv ; 73: 108374, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729229

RESUMO

Indigo is a natural dye extensively used in the global textile industry. However, the conventional synthesis of indigo using toxic compounds like aniline, formaldehyde, and hydrogen cyanide has led to environmental pollution and health risks for workers. This method also faces growing economic, sustainability, and environmental challenges. To address these issues, the concept of bio-indigo or indigo biosynthesis has been proposed as an alternative to aniline-based indigo synthesis. Among various enzymes, Flavin-containing Monooxygenases (FMOs) have shown promise in achieving a high yield of bio-indigo. However, the industrialization of indigo biosynthesis still encounters several challenges. This review focuses on the historical development of indigo biosynthesis mediated by FMOs. It highlights several factors that have hindered industrialization, including the use of unsuitable chassis (Escherichia coli), the toxicity of indole, the high cost of the substrate L-tryptophan, the water-insolubility of the product indigo, the requirement of reducing reagents such as sodium dithionite, and the relatively low yield and high cost compared to chemical synthesis. Additionally, this paper summarizes various strategies to enhance the yield of indigo synthesized by FMOs, including redundant sequence deletion, semi-rational design, cheap precursor research, NADPH regeneration, large-scale fermentation, and enhancement of water solubility of indigo.

20.
Int J Biol Macromol ; 269(Pt 2): 132215, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38729482

RESUMO

Food allergy has a significant impact on the health and well-being of individuals, affecting both their physical and mental states. Research on natural bioactive compounds, such as polysaccharides extracted from seaweeds, holds great promise in the treatment of food allergies. In this study, fermented Gracilaria lemaneiformis polysaccharides (F-GLSP) were prepared using probiotic fermentation. Probiotic fermentation of Gracilaria lemaneiformis reduces the particle size of polysaccharides. To compare the anti-allergic activity of F-GLSP with unfermented Gracilaria lemaneiformis polysaccharides (UF-GLSP), an OVA-induced mouse food allergy model was established. F-GLSP exhibited a significant reduction in OVA-specific IgE and mMCP levels in allergic mice. Moreover, it significantly inhibited Th2 differentiation and IL-4 production and significantly promoted Treg differentiation and IL-10 production in allergic mice. In contrast, UF-GLSP only reduced OVA-specific IgE and mMCP in the serum of allergic mice. Furthermore, F-GLSP demonstrated a more pronounced regulation of intestinal flora abundance compared to UF-GLSP, significantly influencing the populations of Firmicutes, Bacteroidetes, Lactobacillus, and Clostridiales in the intestines of mice with food allergy. These findings suggest that F-GLSP may regulate food allergies in mice through multiple pathways. In summary, this study has promoted further development of functional foods with anti-allergic properties based on red algae polysaccharides.

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