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1.
Abdom Radiol (NY) ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38977489

ABSTRACT

BACKGROUND: Although systemic therapies are recommended for hepatocellular carcinoma (HCC) patients with main portal vein (MPV) invasion and preserved liver function, the outcome is limited. In the real-world, chemoembolization is a commonly used local treatment for advanced HCC. PURPOSE: To evaluate whether the additional chemoembolization treatment yields survival benefits compared to systemic therapy for HCC patients with MPV invasion and preserved liver function (Child-Pugh score ≤ B7) in a real-world study from multiple centers. PATIENTS AND METHODS: Between January 2020 and December 2022, 91 consecutive HCC patients with MPV invasion who received either systemic medical therapy (i.e., tyrosine kinase inhibitors (TKIs) plus anti-PD-1 immunotherapy, S group, n = 43) or in combination with chemoembolization treatment (S-T group, n = 48) from five centers were enrolled in the study. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and treatment response. Adverse events (AEs) related to treatment were also recorded. Survival curves were constructed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: The baseline characteristics were comparable between the two groups. The mean number of chemoembolization sessions per patient was 2.1 (range 1-3). The median OS was 10.0 months and 8.0 months in the S-T group and S group, respectively (P = 0.254). The median PFS between the two groups was similar (4.0 months vs. 4.0 months, P = 0.404). The disease control rate between the S-T and S groups were comparable (60.4% vs. 62.8%, P = 0.816). Although no chemoembolization-related deaths occurred, 13 grade 3-4 AEs occurred in the S-T group. CONCLUSIONS: The results of the real-world study demonstrated that additional chemoembolization treatment did not yield survival benefits compared to TKIs plus anti-PD-1 immunotherapy for the overall patients with advanced HCC and MPV invasion.

2.
Chem Commun (Camb) ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993023

ABSTRACT

Metal-free, photoredox-catalyzed aromatization-driven deconstructive functionalization of spiro-dihydroquinazolinones with α-CF3 alkenes is presented. The readily available spiro-dihydroquinazolinones reacted efficiently with α-CF3 alkenes during photocatalysis to give the gem-difluoroallylated and the CF3-containing quinazolin-4(3H)-ones in good yields with excellent chemoselectivity. The selectivity depends on the electron effect of substituents in α-CF3 alkenes. A wide range of four-, five-, six-, seven-, eight- and twelve-membered spiro-dihydroquinazolinones were compatible with this transformation. The protocol is also characterized by the mild and redox-neutral reaction conditions, good functional group compatibility and excellent atom economy. Mechanistic studies revealed that the reaction proceeds via a radical pathway.

3.
Opt Express ; 32(12): 20742-20761, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859448

ABSTRACT

Digital Image Correlation (DIC) is a crucial noncontact full-field optical measurement method used in various fields. However, in practical applications, DIC is affected by systematic and random noises, leading to experimental resolutions lower than theoretical ones. In this study, we proposed a laser Doppler vibrometer guided DIC to perform vibration measurements. 3D-DIC obtains a sequence of out of displacement field initially. A three-dimensional frequency domain collaborative filtering (3D-FDCF) method that utilizes Laser Doppler vibrometer (LDV) single-point data to assist in processing of the displacement field sequence pixel-wise is adopted. The 3D-FDCF method combines lowpass filtering in the spatial frequency domain with LDV-guided bandpass filtering in the temporal frequency domain. The effectiveness of the 3D-FDCF method is demonstrated through a comparison among DIC data, the filtered DIC data, and continuously scanning LDV data. The experiment results demonstrate the 3D-FDCF method's capability in measuring vibration amplitudes of several hundred nanometers with the size of a test sample of about 100 mm × 100 mm, supporting the statement of interferometric scale full-field vibration measurement by DIC with the guidance of the LDV data.

4.
Food Chem ; 457: 140079, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38901343

ABSTRACT

The unknown effect of sesame lignans on aroma formation in sesame oil via the Maillard reaction (MR) and lipid oxidation was investigated. Sesamin, sesamolin, or sesamol was added to 3 models: lysine+glucose (MR), cold-pressed sesame oil (SO), and MR + SO, and were heated at 120 °C for 60 min. All three lignans suppressed SO oxidation while increasing DPPH scavenging ability (p < 0.05). Lignans increased depletions of lysine and glucose and MR browning (p < 0.05). Lignans reduced most aroma-active pyrazines, aldehydes, ketones, alcohols, and esters (p < 0.05). Sesamol and sesamolin increased perceptions of the preferable aromas of nutty, roasted sesame, and popcorn while reducing the undesirable green and rancid aromas (p < 0.05). Sesamol demonstrated a stronger effect on lipid oxidation, MR browning, aroma formation, and sensory perception than sesamin and sesamolin. This study suggests that sesame lignans can modulate aroma formation and sensory perception of sesame oil by interacting with the MR and lipid oxidation pathways.

5.
Biochem Biophys Res Commun ; 726: 150259, 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-38909535

ABSTRACT

Hypoxic-ischemic brain damage (HIBD) in the perinatal period is an important cause of cerebral damage and long-term neurological sequelae, and can place much pressure on families and society. Our previous study demonstrated that miRNA-326 reduces neuronal apoptosis by up-regulating the δ-opioid receptor (DOR) under oxygen-glucose deprivation in vitro. In the present study, we aimed to explore the neuroprotective effects of the miRNA-326/DOR axis by inhibiting apoptosis in HIBD using neonatal miRNA-326 knockout mice. Neonatal C57BL/6 mice, neonatal miRNA-326 knockout mice, and neonatal miRNA-326 knockout mice intraperitoneally injected with the DOR inhibitor naltrindole were treated with hypoxic-ischemia (HI). Neurological deficit scores, magnetic resonance imaging, terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling, and Caspase-3, Bax, and B-cell lymphoma 2 (Bcl-2) expression were evaluated on day 2 after HI. Neurobehavioral analyses were performed on days 2 and 28 after HI. Additionally, the Morris water maze test was conducted on days 28. Compared with HI-treated neonatal C57BL/6 mice, HI-treated neonatal miRNA-326 knockout mice had higher neurological deficit scores, smaller cerebral infarction areas, and improved motor function, reaction ability, and long-term spatial learning and memory. These effects were likely the result of inhibiting apoptosis; the DOR inhibitor reversed these neuroprotective effects. Our findings indicate that miRNA-326 knockout plays a neuroprotective effect in neonatal HIBD by inhibiting apoptosis via the target gene DOR.


Subject(s)
Animals, Newborn , Apoptosis , Hypoxia-Ischemia, Brain , Mice, Inbred C57BL , Mice, Knockout , MicroRNAs , Receptors, Opioid, delta , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Hypoxia-Ischemia, Brain/genetics , Hypoxia-Ischemia, Brain/metabolism , Hypoxia-Ischemia, Brain/pathology , Receptors, Opioid, delta/genetics , Receptors, Opioid, delta/metabolism , Mice , Apoptosis/genetics , Neuroprotective Agents/pharmacology , Male
6.
Chem Sci ; 15(23): 8993-8999, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38873081

ABSTRACT

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

7.
Chem Commun (Camb) ; 60(40): 5334-5337, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38668748

ABSTRACT

A photoredox-catalyzed alkylarylation of activated alkenes via a radical C-C bond cleavage/Truce-Smiles rearrangement cascade is developed. The protocol features mild and redox-neutral conditions, broad substrate scope and excellent functional group compatibility, providing a facile and efficient approach to the long-chain distal keto-amides with all-carbon quaternary centers at the alpha position.

8.
Molecules ; 29(7)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38611880

ABSTRACT

Currently, photocatalysis of the two-dimensional (2D) conjugated phthalocyanine framework with a single Fe atom (CPF-Fe) has shown efficient photocatalytic activities for the removal of harmful effluents and antibacterial activity. Their photocatalytic mechanisms are dependent on the redox reaction-which is led by the active species generated from the photocatalytic process. Nevertheless, the molecular mechanism of CPF-Fe antimicrobial activity has not been sufficiently explored. In this study, we successfully synthesized CPF-Fe with great broad-spectrum antibacterial properties under visible light and used it as an antibacterial agent. The molecular mechanism of CPF-Fe against Escherichia coli and Salmonella enteritidis was explored through multi-omics analyses (transcriptomics and metabolomics correlation analyses). The results showed that CPF-Fe not only led to the oxidative stress of bacteria by generating large amounts of h+ and ROS but also caused failure in the synthesis of bacterial cell wall components as well as an osmotic pressure imbalance by disrupting glycolysis, oxidative phosphorylation, and TCA cycle pathways. More surprisingly, CPF-Fe could disrupt the metabolism of amino acids and nucleic acids, as well as inhibit their energy metabolism, resulting in the death of bacterial cells. The research further revealed the antibacterial mechanism of CPF-Fe from a molecular perspective, providing a theoretical basis for the application of CPF-Fe photocatalytic antibacterial nanomaterials.


Subject(s)
Antifibrinolytic Agents , Isoindoles , Multiomics , Amino Acids , Anti-Bacterial Agents/pharmacology , Escherichia coli , Indoles/pharmacology
9.
Ultramicroscopy ; 259: 113924, 2024 May.
Article in English | MEDLINE | ID: mdl-38308956

ABSTRACT

The authors of this study develop an accurate and fast method for the localization of the pattern centers (PCs) in the electron backscatter diffraction (EBSD) technique by using the model of deformation of screen moving technology. The proposed algorithm is divided into two steps: (a) Approximation: We use collinear feature points to obtain the initial value of the coordinates of the PC and the zoom factor. (b) Subdivision: We then construct a deformation function containing the three parameters to be solved, select a large region for global registration, use the inverse compositional Gauss-Newton (ICGN) to optimize the objective function, and obtain the results of iteration of the PC and the zoom factor. The proposed algorithm was applied to simulated patterns, and yielded an accuracy of measurement of the PCs that was better than 4.6×10-6 of their resolution while taking only 0.2 s for computations. Moreover, the proposed algorithm has a large radius of convergence that makes it robust to the initial estimate. We also discuss the influence of factors of mechanical instability on its results of calibration during the insertion of the detector, and show that errors in measurements caused by the tilt motion of the camera are related only to the tilt angle of its motion and the detector distance, and are unrelated to the distance moved by it.

10.
Cell Stem Cell ; 31(2): 212-226.e7, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38232727

ABSTRACT

The effects of exercise on fibro-adipogenic progenitors (FAPs) are unclear, and the direct molecular link is still unknown. In this study, we reveal that exercise reduces the frequency of FAPs and attenuates collagen deposition and adipose formation in injured or disused muscles through Musclin. Mechanistically, Musclin inhibits FAP proliferation and promotes apoptosis in FAPs by upregulating FILIP1L. Chromatin immunoprecipitation (ChIP)-qPCR confirms that FoxO3a is the transcription factor of FILIP1L. In addition, the Musclin/FILIP1L pathway facilitates the phagocytosis of apoptotic FAPs by macrophages through downregulating the expression of CD47. Genetic ablation of FILIP1L in FAPs abolishes the effects of exercise or Musclin on FAPs and the benefits on the reduction of fibrosis and fatty infiltration. Overall, exercise forms a microenvironment of myokines in muscle and prevents the abnormal accumulation of FAPs in a Musclin/FILIP1L-dependent manner. The administration of exogenous Musclin exerts a therapeutic effect, demonstrating a potential therapeutic approach for muscle atrophy or acute muscle injury.


Subject(s)
Gene Expression Regulation , Muscle Proteins , Muscles , Transcription Factors , Humans , Adipogenesis , Cell Differentiation , Fibrosis , Homeostasis , Muscle, Skeletal/metabolism , Muscles/metabolism , Transcription Factors/metabolism , Animals , Mice , Muscle Proteins/metabolism
11.
Insects ; 14(11)2023 Oct 28.
Article in English | MEDLINE | ID: mdl-37999038

ABSTRACT

Due to changes in light intensity, varying degrees of aphid aggregation, and small scales in the climate chamber environment, accurately identifying and counting aphids remains a challenge. In this paper, an improved YOLOv5 aphid detection model based on CNN is proposed to address aphid recognition and counting. First, to reduce the overfitting problem of insufficient data, the proposed YOLOv5 model uses an image enhancement method combining Mosaic and GridMask to expand the aphid dataset. Second, a convolutional block attention mechanism (CBAM) is proposed in the backbone layer to improve the recognition accuracy of aphid small targets. Subsequently, the feature fusion method of bi-directional feature pyramid network (BiFPN) is employed to enhance the YOLOv5 neck, further improving the recognition accuracy and speed of aphids; in addition, a Transformer structure is introduced in front of the detection head to investigate the impact of aphid aggregation and light intensity on recognition accuracy. Experiments have shown that, through the fusion of the proposed methods, the model recognition accuracy and recall rate can reach 99.1%, the value mAP@0.5 can reach 99.3%, and the inference time can reach 9.4 ms, which is significantly better than other YOLO series networks. Moreover, it has strong robustness in actual recognition tasks and can provide a reference for pest prevention and control in climate chambers.

12.
Front Plant Sci ; 14: 1250844, 2023.
Article in English | MEDLINE | ID: mdl-37860254

ABSTRACT

Introduction: Accurate and timely detection of plant stress is essential for yield protection, allowing better-targeted intervention strategies. Recent advances in remote sensing and deep learning have shown great potential for rapid non-invasive detection of plant stress in a fully automated and reproducible manner. However, the existing models always face several challenges: 1) computational inefficiency and the misclassifications between the different stresses with similar symptoms; and 2) the poor interpretability of the host-stress interaction. Methods: In this work, we propose a novel fast Fourier Convolutional Neural Network (FFDNN) for accurate and explainable detection of two plant stresses with similar symptoms (i.e. Wheat Yellow Rust And Nitrogen Deficiency). Specifically, unlike the existing CNN models, the main components of the proposed model include: 1) a fast Fourier convolutional block, a newly fast Fourier transformation kernel as the basic perception unit, to substitute the traditional convolutional kernel to capture both local and global responses to plant stress in various time-scale and improve computing efficiency with reduced learning parameters in Fourier domain; 2) Capsule Feature Encoder to encapsulate the extracted features into a series of vector features to represent part-to-whole relationship with the hierarchical structure of the host-stress interactions of the specific stress. In addition, in order to alleviate over-fitting, a photochemical vegetation indices-based filter is placed as pre-processing operator to remove the non-photochemical noises from the input Sentinel-2 time series. Results and discussion: The proposed model has been evaluated with ground truth data under both controlled and natural conditions. The results demonstrate that the high-level vector features interpret the influence of the host-stress interaction/response and the proposed model achieves competitive advantages in the detection and discrimination of yellow rust and nitrogen deficiency on Sentinel-2 time series in terms of classification accuracy, robustness, and generalization.

13.
Biomed Pharmacother ; 168: 115598, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37820565

ABSTRACT

Cerebral infarction (CI) has become one of the leading causes of death and acquired disability worldwide. Astragaloside IV (AST IV), one of the basic components of Astragalus membranaceus, has a protective effect on CI. However, the underlying mechanism has not been conclusively elucidated. Therefore, this study aims to explore the underlying mechanism of AST IV improving brain injury after CI. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to simulate cerebral infarction injury in SD rats and HUVECs cells. Neurologic score, Evans blue, TTC and HE staining were used to observe brain injury in rats. Cell viability and migration were measured in vitro. Angiogenesis was detected by immunofluorescence and tube formation assay, and cell cycle was detected by flow cytometry. Western blot was used to find the expression of related proteins. Molecular docking, virtual mutation, site-directed mutagenesis, MST, and lentivirus silencing were used for target validation. The results showed that AST IV alleviated neurological impairment and promoted angiogenesis after CI. Moreover, AST IV greatly increased the transcription levels of SIRT6 and SIRT7, but had no effect on SIRT1-SIRT5, and promoted cell viability, migration, angiogenesis and S phase ratio in OGD/R-induced HUVECs. Furthermore, AST IV up-regulated the protein expressions of CDK4, cyclin D1, VEGFA and VEGF2R. Interestingly, AST IV not only bound to SIRT7, but also increased the expression of SIRT7. Silencing SIRT7 by lentivirus neutralizes the positive effects of AST IV. Taken together, the present study revealed that AST IV may improve brain tissue damage after CI by targeting SIRT7/VEGFA signaling pathway to promote angiogenesis.


Subject(s)
Brain Injuries , Brain Ischemia , Reperfusion Injury , Sirtuins , Rats , Animals , Rats, Sprague-Dawley , Molecular Docking Simulation , Signal Transduction , Oxygen/metabolism , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/drug therapy , Reperfusion Injury/metabolism , Brain Ischemia/metabolism , Sirtuins/genetics , Sirtuins/metabolism
14.
HardwareX ; 15: e00460, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37693635

ABSTRACT

The pipe conveying fluid is a classic fluid structure interaction experiment. First studied for industrial applications such as liners and pipelines, it became a "paradigm" of non-linear dynamics in the same way as the vertical rotating shaft. Hundreds of papers studying different pipe instabilities and different phenomena with various numerical and analytical methods have been published in the last decades. However, many studies lack the comparison with experimental data to validate the analytical models and numerical simulations. Indeed, designing and building a pipe conveying fluid experimental setup can prove to be a long and a burdensome process. This paper presents an easy to build pipe conveying fluid experimental setup built in the LM2 laboratory at Polytechnique Montréal. Fig. 1 presents the global architecture of this experimental rig. This large scale setup uses relatively high speed cameras to track the pipe in three dimensions. It does not require heavy construction or major plumbing and electrical work. Moreover, it is removable and can be modified easily to observe different phenomena with various large scale pipes or boundary conditions. Lastly, it is relatively inexpensive as it costs less than 20 000 US dollars including all the sensors and acquisition systems.

15.
Front Plant Sci ; 14: 1230886, 2023.
Article in English | MEDLINE | ID: mdl-37621882

ABSTRACT

Pepper leaf disease identification based on convolutional neural networks (CNNs) is one of the interesting research areas. However, most existing CNN-based pepper leaf disease detection models are suboptimal in terms of accuracy and computing performance. In particular, it is challenging to apply CNNs on embedded portable devices due to a large amount of computation and memory consumption for leaf disease recognition in large fields. Therefore, this paper introduces an enhanced lightweight model based on GoogLeNet architecture. The initial step involves compressing the Inception structure to reduce model parameters, leading to a remarkable enhancement in recognition speed. Furthermore, the network incorporates the spatial pyramid pooling structure to seamlessly integrate local and global features. Subsequently, the proposed improved model has been trained on the real dataset of 9183 images, containing 6 types of pepper diseases. The cross-validation results show that the model accuracy is 97.87%, which is 6% higher than that of GoogLeNet based on Inception-V1 and Inception-V3. The memory requirement of the model is only 10.3 MB, which is reduced by 52.31%-86.69%, comparing to GoogLeNet. We have also compared the model with the existing CNN-based models including AlexNet, ResNet-50 and MobileNet-V2. The result shows that the average inference time of the proposed model decreases by 61.49%, 41.78% and 23.81%, respectively. The results show that the proposed enhanced model can significantly improve performance in terms of accuracy and computing efficiency, which has potential to improve productivity in the pepper farming industry.

16.
BMC Pregnancy Childbirth ; 23(1): 513, 2023 Jul 13.
Article in English | MEDLINE | ID: mdl-37442957

ABSTRACT

BACKGROUND: Weight management has been an important component of the service in obstetric care offered to pregnant women. Current gestational weight gain recommendations were primarily for the general obstetric population, raising concern about the applicability to women with gestational diabetes mellitus (GDM). We aimed to assess the difference in weight progression and adherence to the recommended gestational weight gain targets between women with gestational diabetes mellitus (GDM) and women with normal glucose tolerance (NGT). METHODS: This was a hospital-based retrospective study of 56,616 pregnant women (9,430 GDM women and 47,186 NGT women) from Guangzhou between 2017 and 2021. The average change in weight progression was estimated based on serial weight measurements throughout pregnancy, using a mixed effects model with a random intercept to account for repeated measures of the same individual. RESULTS: Women with GDM gained less weight (12.07 [SD 5.20] kg) than women with NGT (14.04 [SD 5.04] kg) throughout pregnancy. Before OGTT, a small difference was observed in the average change in weight progression between the two groups (GDM, 0.44 kg/week vs. NGT, 0.45 kg/week, p < 0.001), however, this gap widened significantly after the test (0.34 vs. 0.50 kg/week, p < 0.001). GDM individuals were identified with an approximately 4-fold increased proportion of insufficient weight gain (41.1% vs. 10.4%) and a 2-fold decreased proportion of excessive weight gain (22.6% vs. 54.2%) compared to NGT individuals. These results were consistently observed across different BMI categories, including underweight (insufficient: 52.7% vs. 19.9%; excessive: 15.6% vs. 35.3%), normal weight (insufficient 38.2% vs. 7.4%; excessive: 22.2% vs. 57.3%), and overweight/obese (insufficient: 43.1% vs. 9.8%; excessive: 30.1% vs. 68.8%). CONCLUSION: Weight progression varied significantly between GDM and NGT individuals, resulting in a substantial difference in identifying insufficient and excessive weight gain between the two groups under current gestational weight gain guidelines.


Subject(s)
Diabetes, Gestational , Gestational Weight Gain , Pregnancy , Female , Humans , Diabetes, Gestational/epidemiology , Retrospective Studies , Weight Gain , Obesity/epidemiology , Glucose , Body Mass Index
17.
Org Lett ; 25(30): 5563-5568, 2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37477589

ABSTRACT

A redox-neutral copper-catalyzed cascade reaction involving alkoxyl radical-mediated ring expansion/1,4-difunctionalization of 1,3-enynes was developed, offering a straightforward approach to the tetra-substituted allenes with macrolactone, CN, and CF3 functional groups. Remarkably, incorporation of the NH2 group onto the 1,3-enyne moiety enabled further cyclization to give a unique scaffold containing a lactone and an indole moiety.

18.
Int J Cardiol ; 387: 131109, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37271284

ABSTRACT

BACKGROUND: Atherosclerosis is a chronic inflammatory disease with its molecular basis incompletely understood. Here, we determined whether the Golgi phosphoprotein 73 (GP73), a novel protein highly related to inflammation and disrupted lipid metabolism, was involved in the development of atherosclerosis. METHODS: Public microarray databases of human vascular samples were analyzed for expression patterns. Apolipoprotein-E-gene-deficient (ApoE-/-) mice (8-week-old) were randomly assigned to either a chow diet group or a high-fat diet group. The levels of serum GP73, lipid profiles and key inflammatory cytokines were determined by ELISA. The aortic root plaque was isolated and used for by Oil Red O staining. PMA-differentiated THP-1 macrophages were transfected with GP73 small interfering RNA (siRNA) or infected with adenovirus expressing GP73, and then stimulated with oxidized low density lipoprotein (ox-LDL). The expressions of pro-inflammatory cytokines and signal pathway key targets were determined by ELISA kit and Western blot respectively. In addition, ichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to measure the intracellular ROS levels. RESULTS: The expressions of GP73 and NLRP3 were substantially upregulated in human atherosclerotic lesions. There were significant linear correlations between GP73 and inflammatory cytokines expressions. High-fat diet-induced atherosclerosis and increased levels of plasma inflammatory mediators (IL-1ß, IL-18, and TNF-α) were observed in ApoE-/- mice. Besides, the expressions of GP73 in the aorta and serum were significantly upregulated and positively correlated with the NLRP3 expression. In the THP-1 derived macrophages, ox-LDL treatment upregulated the expressions of GP73 and NLRP3 proteins and activated the inflammatory responses in a concentration-dependent and time-dependent manner. Silencing of GP73 attenuated the inflammatory response and rescued the decreased migration induced by ox-LDL, inhibiting the NLRP3 inflammasome signaling and the ROS and p-NF-κB activation. CONCLUSIONS: We demonstrated that GP73 promoted the ox-LDL-induced inflammation in macrophages by affecting the NF-κB/NLRP3 inflammasome signaling, and may play a role in atherosclerosis.


Subject(s)
Atherosclerosis , Inflammasomes , Humans , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NF-kappa B/metabolism , Phosphoproteins/metabolism , Reactive Oxygen Species/metabolism , Mice, Knockout, ApoE , Lipoproteins, LDL/metabolism , Signal Transduction , Macrophages/metabolism , Inflammation/metabolism , Tumor Necrosis Factor-alpha , Atherosclerosis/genetics , Apolipoproteins E
19.
Chem Sci ; 14(19): 5220-5225, 2023 May 17.
Article in English | MEDLINE | ID: mdl-37206389

ABSTRACT

An efficient alkoxyl radical-triggered ring expansion/cross-coupling cascade was developed under cheap metal catalysis. Through the metal-catalyzed radical relay strategy, a wide range of medium-sized lactones (9-11 membered) and macrolactones (12, 13, 15, 18, and 19-membered) were constructed in moderate to good yields, along with diverse functional groups including CN, N3, SCN, and X groups installed concurrently. Density functional theory (DFT) calculations revealed that reductive elimination of the cycloalkyl-Cu(iii) species is a more favorable reaction pathway for the cross-coupling step. Based on the results of experiments and DFT, a Cu(i)/Cu(ii)/Cu(iii) catalytic cycle is proposed for this tandem reaction.

20.
Ultramicroscopy ; 247: 113697, 2023 May.
Article in English | MEDLINE | ID: mdl-36804629

ABSTRACT

High-resolution electron backscattering diffraction (HR-EBSD) was used to measure rotations and elastic strains by matching diffraction patterns based on cross-correlation. However, the subset-based phase correlation algorithm was unable to determine pattern shifts accurately when large rotations occurred. In this paper, a new matching algorithm was proposed to measure pattern shifts and recover the elastic strain and lattice rotation with finite deformation theory. The algorithm was implemented in two steps: (a) Integral pixel matching: The pixel-related information of the Kikuchi patterns was mapped to the original three-dimensional sphere to obtain the image projected in parallel by using the feature points as the pattern center through the transformation of its spatial coordinates. The correlation between the images projected in parallel before and after deformation was then obtained. The locations of the integral pixels were determined by the peaks of the surface of correlation obtained by traversing all pixels in the search area. (b) subpixel refinement: the locations of subpixels were obtained by FAGN with an appropriate shape function involving rotation and translation. The algorithm was applied to dynamic simulated test sets, and its results were compared with those of the first-pass cross-correlation and the second-pass cross-correlation method with remapping. The proposed method was more robust in the case of rotation and solved the problem that displacement vectors could not be accurately measured when a larger lattice rotation occurred. The mean errors of the measured displacement, rotation, and strain components were 0.02 pixel, 0.5×10-4rad, and 1×10-4, respectively. Compared with the second-pass cross-correlation method, the angle of rotation was more precisely extracted.

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