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1.
Article in English | MEDLINE | ID: mdl-39222915

ABSTRACT

AIMS: To assess the relationship between the left ventricular remodeling parameters of cardiac magnetic resonance and NT-pro-BNP in patients with primary aldosteronism (PA). METHODS: Seventy-four PA and 39 essential hypertension patients were prospectively recruited and underwent cardiac magnetic resonance. Plasma NT-pro-BNP was measured before patients underwent cardiac magnetic resonance. Left ventricular remodeling parameters were defined as left ventricular function parameters, T1 mapping parameters, and strain parameters. Differences in continuous variables between two groups were analyzed using Student's t-test or Mann-Whitney U test. Differences in categorical variables between two groups were analyzed by chi-squared test. Spearman's correlation and linear regression were used to analyze the relationships between left ventricular remodeling parameters and plasma NT-Pro-BNP level. P<0.05 was considered as statistically significant. RESULTS: Patients with PA demonstrated higher NT-pro-BNP [86.0 (49.5, 145.5) vs. 45.0 (28.5, 73.5) pg/mL, P=0.001] and Native T1 (1227±41 vs. 1206±43 ms, P=0.015) level than essential hypertension patients. Compared to patients with normal NT-pro-BNP levels, those with abnormal levels demonstrated different left ventricular remodeling parameters. NT-pro-BNP level was independently related to native T1 (ß=0.316, P=0.006), extracellular volume (ß=0.419, P<0.001), short-axis global circumferential strain (ß=0.429, P<0.001), four-chamber global longitudinal strain (ß=0.332, P=0.002), and four-chamber global radial strain (ß=-0.334, P=0.004) in patients after adjusting for baseline characteristics. CONCLUSIONS: NT-pro-BNP level was related to left ventricular remodeling parameters derived from cardiac magnetic resonance in patients with PA. This result implies that clinicians should pay attention to NT-pro-BNP assessment in patients with PA in routine clinical assessment.

2.
Inorg Chem ; 63(37): 17149-17156, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39219455

ABSTRACT

Amine ligands have been widely applied as morphology-directing reagents in nanostructure synthesis. In this work, we explored the application of the amine ligands in the active surface growth mechanism in place of the strong thiolated ligands. Despite being weaker compared to the thiols, amine ligands such as aniline were also shown to be capable of facilitating the template-less electrodeposition of Au nanowires (NWs) on the substrate via the active surface growth mechanism. Given the close binding difference between the amine-grafted substrate and the ligands, substrate functionalization becomes critically important for effective construction of the active surface and the growth of the nanowires. Additionally, the growth with the amine ligands took place at more positive reduction potentials and is less prone to splitting and bundle formation. A systematic generality study revealed that besides the aromatic amines, long-chain aliphatic amines were also capable of facilitating nanowire growth. Given the weak binding affinity of the amine ligands, the Au NWs are readily accessible for further processing to generate sophisticated one-dimensional structures. As a demonstration, tandem electrodeposition was performed to directly obtain coaxial core-shell Au@Pt NWs with adjustable length, diameter, and shell thickness.

3.
Sci Rep ; 14(1): 21318, 2024 09 12.
Article in English | MEDLINE | ID: mdl-39266597

ABSTRACT

The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1ß, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.


Subject(s)
Apoptosis , Influenza A Virus, H1N1 Subtype , Polyethylene Glycols , Influenza A Virus, H1N1 Subtype/drug effects , Animals , Apoptosis/drug effects , Dogs , Madin Darby Canine Kidney Cells , Polyethylene Glycols/chemistry , Polyethylene Glycols/pharmacology , Inflammation/drug therapy , Antiviral Agents/pharmacology , Selenium/pharmacology , Selenium/chemistry , Reactive Oxygen Species/metabolism , Nanoparticles/chemistry , Humans , DNA Damage/drug effects
4.
Quant Imaging Med Surg ; 14(9): 6260-6272, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39281124

ABSTRACT

Background: Colorectal cancer (CRC) is commonly assessed by computed tomography (CT), but the associated radiation exposure is a major concern. This study aimed to quantitatively and qualitatively compare the image quality of virtual non-contrast (VNC) images reconstructed from arterial and portal venous phases with that of true non-contrast (TNC) images in patients with CRC to assess the potential of TNC images to replace VNC images, thereby reducing the radiation dose. Methods: A total of 69 patients with postoperative pathologically confirmed CRC at the West China Hospital of Sichuan University between May 2022 and April 2023 were enrolled in this cross-sectional study. The CT protocol included the acquisition of TNC images, arterial and portal venous phase images; the VNC images were reconstructed from the two postcontrast phase images. Several parameters, including the CT attenuation value, absolute attenuation error, imaging noise [standard deviation (SD)], signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), were measured in multiple abdominal structures for both the TNC and VNC images. Two blinded readers assessed the subjective image quality using a five-point scale. Interobserver agreement was evaluated using interclass correlation coefficients (ICCs). The paired t-test and Wilcoxon signed-rank test were used to compare the objective and subjective results between the TNC and VNC images. Individual measurements of radiation doses for the TNC scan and contrast scan protocols were recorded. Results: A total of 2,070 regions of interest (ROIs) of the 69 patients were analyzed. Overall, the VNC images exhibited significantly lower attenuation values and SD values than the TNC images in all tissues, except for the abdominal aorta, portal vein, and spleen. The mean absolute attenuation errors between the VNC and TNC images were all less than 10 Hounsfield units (HU). The percentages of absolute attenuation errors less than 5 and 10 HU in the VNC images from the arterial phase (VNCa) were 78.99% and 97.97%, respectively, while those from the portal venous phase (VNCp) were 81.59% and 96.96%, respectively. The absolute attenuation errors between the TNC and VNCa images were smaller than those between the TNC and VNCp images for tumors [VNCaerror: 2.77, interquartile range (IQR) 1.77-4.22; VNCperror: 3.27, IQR 2.68-4.30; P=0.002]. The SNR values and CNR values in the VNC images were significantly higher than those in the TNC images for all tissues, except for the portal vein and spleen. The image quality was rated as excellent (represented by a score of 5) in the majority of the TNC and VNC images; however, the VNC images scored lower than the TNC images. Eliminating the TNC phase resulted in a reduction of approximately 37.99% in the effective dose (ED). Conclusions: The VNC images provided accurate CT attenuation, good image quality, and lower radiation doses than the TNC images in CRC, and the VNCa images showed minimal differences in the CT attenuation of the tumors.

5.
Insights Imaging ; 15(1): 224, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39298070

ABSTRACT

OBJECTIVES: To investigate the feasibility of a deep learning-constrained compressed sensing (DL-CS) method in non-contrast-enhanced modified DIXON (mDIXON) coronary magnetic resonance angiography (MRA) and compare its diagnostic accuracy using coronary CT angiography (CCTA) as a reference standard. METHODS: Ninety-nine participants were prospectively recruited for this study. Thirty healthy subjects (age range: 20-65 years; 50% female) underwent three non-contrast mDIXON-based coronary MRA sequences including DL-CS, CS, and conventional sequences. The three groups were compared based on the scan time, subjective image quality score, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The remaining 69 patients suspected of coronary artery disease (CAD) (age range: 39-83 years; 51% female) underwent the DL-CS coronary MRA and its diagnostic performance was compared with that of CCTA. RESULTS: The scan time for the DL-CS and CS sequences was notably shorter than that of the conventional sequence (9.6 ± 3.1 min vs 10.0 ± 3.4 min vs 13.0 ± 4.9 min; p < 0.001). The DL-CS sequence obtained the highest image quality score, mean SNR, and CNR compared to CS and conventional methods (all p < 0.001). Compared to CCTA, the accuracy, sensitivity, and specificity of DL-CS mDIXON coronary MRA per patient were 84.1%, 92.0%, and 79.5%; those per vessel were 90.3%, 82.6%, and 92.5%; and those per segment were 98.0%, 85.1%, and 98.0%, respectively. CONCLUSION: The DL-CS mDIXON coronary MRA provided superior image quality and short scan time for visualizing coronary arteries in healthy individuals and demonstrated high diagnostic value compared to CCTA in CAD patients. CRITICAL RELEVANCE STATEMENT: DL-CS resulted in improved image quality with an acceptable scan time, and demonstrated excellent diagnostic performance compared to CCTA, which could be an alternative to enhance the workflow of coronary MRA. KEY POINTS: Current coronary MRA techniques are limited by scan time and the need for noise reduction. DL-CS reduced the scan time in coronary MR angiography. Deep learning achieved the highest image quality among the three methods. Deep learning-based coronary MR angiography demonstrated high performance compared to CT angiography.

6.
Animals (Basel) ; 14(16)2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39199818

ABSTRACT

Duck adenovirus Type 3 (DAdV-3) severely affects the health of ducks; however, its pathogenicity in chickens remains unknown. The objectives of this study were to evaluate the pathogenicity and major pathological changes caused by DAdV-3 in chickens. Viral DNA was extracted from the liver of the Muscovy duck, and the fiber-2 and hexon fragments of DAdV-3 were amplified through polymerase chain reaction (PCR). The evolutionary tree revealed that the isolated virus belonged to DAdV-3, and it was named HE-AN-2022. The mortality rate of chicks that received inoculation with DAdV-3 subcutaneously via the neck was 100%, while the mortality rate for eye-nose drop inoculation was correlated with the numbers of infection, with 26.7% of chicks dying as a result of exposure to multiple infections. The main symptoms exhibited prior to death were hepatitis-hydropericardium syndrome (HHS), ulceration of the glandular stomach, and a swollen bursa with petechial hemorrhages. A histopathological examination revealed swelling, necrosis, lymphocyte infiltration, and basophilic inclusion bodies in multiple organs. Meanwhile, the results of quantitative real-time PCR (qPCR) demonstrated that DAdV-3 could affect most of the organs in chickens, with the gizzard, glandular stomach, bursa, spleen, and liver being the most susceptible to infection. The surviving chicks had extremely high antibody levels. After the chickens were infected with DAdV-3 derived from Muscovy ducks, no amino acid mutation was observed in the major mutation regions of the virus, which were ORF19B, ORF66, and ORF67. On the basis of our findings, we concluded that DAdV-3 infection is possible in chickens, and that it causes classic HHS with ulceration of the glandular stomach and a swollen bursa with petechial hemorrhages, leading to high mortality in chickens. The major variation domains did not change in Muscovy ducks or in chickens after infection. This is the first study to report DAdV-3 in chickens, providing a new basis for preventing and controlling this virus.

7.
Biosens Bioelectron ; 264: 116614, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39126904

ABSTRACT

The precision of previous cancer research based on tumor spheroids, especially the microgel-encapsulating tumor spheroids, was limited by the high heterogeneity in the tumor spheroid size and shape. Here, we reported a user-friendly solenoid valve-based sorter to reduce this heterogeneity. The artificial intelligence algorithm was employed to detect and segmentate the tumor spheroids in real-time for the size and shape calculation. A simple off-chip solenoid valve-based sorting actuation module was proposed to sort out target tumor spheroids with the desired size and shape. Utilizing the developed sorter, we successfully uncovered the drug response variations on cisplatin of lung tumor spheroids in the same population but with different sizes and shapes. Moreover, with this sorter, the precision of drug testing on the spheroid population level was improved to a level comparable to the precise but complex single spheroid analysis. The developed sorter also exhibits significant potential for organoid morphology and sorting for precision medicine research.


Subject(s)
Biosensing Techniques , Microgels , Spheroids, Cellular , Humans , Spheroids, Cellular/pathology , Spheroids, Cellular/drug effects , Microgels/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Lung Neoplasms/pathology , Lung Neoplasms/drug therapy , Cisplatin/pharmacology , Cisplatin/therapeutic use , Drug Screening Assays, Antitumor , Equipment Design , Cell Line, Tumor , Artificial Intelligence
8.
Chemosphere ; 364: 143002, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39097111

ABSTRACT

Lanthanum-modified bentonite (LMB) combined with submerged macrophytes (SM) has been a conventional means of eutrophication management in lakes in recent years, and is one of the most important methods for P removal. However, trends in nutrients and sediment enzymes at the water-sediment interface during this process have not been systematically assessed, and there are still some gaps in how abiotic properties drive changes in enzyme activity. Here, we show changes in aquatic environmental conditions under the action of different ratios of modified bentonite (0, 10%, 20%, and 30%) in combination with SM (Vallisneria natans, Potamogeton lucens, and Hydrilla verticillate) and quantify their effects on sediment enzyme activities. The results showed that the nutrient cycling at the water-sediment interface was facilitated by the combined effect of SM and LMB, which effectively reduced the overlying water nutrient concentration, increased the sediment enzyme activity and enhanced the N cycling process. Partial least squares structural equation model (PLS-SEM) showed that sediment parameters strongly influenced changes in enzyme activity, with NO3-N as the main controlling factors. Our study fills in the process of changing environmental conditions in lake water under geoengineered materials combined with macrophyte measures, especially the changes in biological properties enzyme activities, which contributes to a clearer understanding of nutrient fluxes during the management of eutrophication in lakes.


Subject(s)
Bentonite , Eutrophication , Geologic Sediments , Lakes , Lanthanum , Geologic Sediments/chemistry , Bentonite/chemistry , Lanthanum/chemistry , Lakes/chemistry , Phosphorus/chemistry , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Potamogetonaceae , Nitrogen , Enzymes/metabolism , Hydrocharitaceae
9.
Tomography ; 10(7): 970-982, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39058045

ABSTRACT

OBJECTIVE: Functional magnetic resonance imaging (fMRI) has been applied to assess the microstructure of the kidney. However, it is not clear whether fMRI could be used in the field of kidney injury in patients with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: This study included 20 patients with AAV. Diffusion kurtosis imaging (DKI) and blood oxygen level-dependent (BOLD) scanning of the kidneys were performed in AAV patients and healthy controls. The mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) parameters of DKI, the R2* parameter of BOLD, and clinical data were further analyzed. RESULTS: In AAV patients, the cortex exhibited lower MD but higher R2* values compared to the healthy controls. Medullary MK values were elevated in AAV patients. Renal medullary MK values showed a positive correlation with serum creatinine levels and negative correlations with hemoglobin levels and estimated glomerular filtration rate. To assess renal injury in AAV patients, AUC values for MK, MD, FA, and R2* in the cortex were 0.66, 0.67, 0.57, and 0.55, respectively, and those in the medulla were 0.81, 0.77, 0.61, and 0.53, respectively. CONCLUSIONS: Significant differences in DKI and BOLD MRI parameters were observed between AAV patients with kidney injuries and the healthy controls. The medullary MK value in DKI may be a noninvasive marker for assessing the severity of kidney injury in AAV patients.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Oxygen , Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnostic imaging , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Male , Female , Middle Aged , Aged , Oxygen/blood , Kidney/diagnostic imaging , Kidney/pathology , Magnetic Resonance Imaging/methods , Adult , Diffusion Magnetic Resonance Imaging/methods , Case-Control Studies , Glomerular Filtration Rate , Diffusion Tensor Imaging/methods
10.
Oncogene ; 43(30): 2295-2306, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38858591

ABSTRACT

Circulating tumor cells (CTCs) play a critical role as initiators in tumor metastasis, which unlocks an irreversible process of cancer progression. Regarding the fluid environment of intravascular CTCs, a comprehensive understanding of the impact of hemodynamic shear stress on CTCs is of profound significance but remains vague. Here, we report a microfluidic circulatory system that can emulate the CTC microenvironment to research the responses of typical liver cancer cells to varying levels of fluid shear stress (FSS). We observe that HepG2 cells surviving FSS exhibit a marked overexpression of TLR4 and TPPP3, which are shown to be associated with the colony formation, migration, and anti-apoptosis abilities of HepG2. Furthermore, overexpression of these two genes in another liver cancer cell line with normally low TLR4 and TPPP3 expression, SK-Hep-1 cells, by lentivirus-mediated transfection also confirms the critical role of TLR4 and TPPP3 in improving colony formation, migration, and survival capability under a fluid environment. Interestingly, in vivo experiments show SK-Hep-1 cells, overexpressed with these genes, have enhanced metastatic potential to the liver and lungs in mouse models via tail vein injection. Mechanistically, TLR4 and TPPP3 upregulated by FSS may increase FSS-mediated cell survival and metastasis through the p53-Bax signaling pathway. Moreover, elevated levels of these genes correlate with poorer overall survival in liver cancer patients, suggesting that our findings could offer new therapeutic strategies for early cancer diagnosis and targeted treatment development.


Subject(s)
Neoplastic Cells, Circulating , Humans , Cell Line, Tumor , Microfluidics , Stress, Physiological , Female , Animals , Mice , Cell Movement , Single-Cell Analysis , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Cell Survival , Anoikis , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Prognosis
11.
Adv Sci (Weinh) ; 11(30): e2401069, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38874129

ABSTRACT

In recent decades, research on Extracellular Vesicles (EVs) has gained prominence in the life sciences due to their critical roles in both health and disease states, offering promising applications in disease diagnosis, drug delivery, and therapy. However, their inherent heterogeneity and complex origins pose significant challenges to their preparation, analysis, and subsequent clinical application. This review is structured to provide an overview of the biogenesis, composition, and various sources of EVs, thereby laying the groundwork for a detailed discussion of contemporary techniques for their preparation and analysis. Particular focus is given to state-of-the-art technologies that employ both microfluidic and non-microfluidic platforms for EV processing. Furthermore, this discourse extends into innovative approaches that incorporate artificial intelligence and cutting-edge electrochemical sensors, with a particular emphasis on single EV analysis. This review proposes current challenges and outlines prospective avenues for future research. The objective is to motivate researchers to innovate and expand methods for the preparation and analysis of EVs, fully unlocking their biomedical potential.


Subject(s)
Extracellular Vesicles , Extracellular Vesicles/metabolism , Humans
12.
J Multidiscip Healthc ; 17: 2499-2509, 2024.
Article in English | MEDLINE | ID: mdl-38799011

ABSTRACT

Purpose: This study aimed to evaluate the feasibility of ultrafast (2 min) cervical spine MRI protocol using a deep learning-assisted 3D iterative image enhancement (DL-3DIIE) system, compared to a conventional MRI protocol (6 min 14s). Patients and Methods: Fifty-one patients were recruited and underwent cervical spine MRI using conventional and ultrafast protocols. A DL-3DIIE system was applied to the ultrafast protocol to compensate for the spatial resolution and signal-to-noise ratio (SNR) of images. Two radiologists independently assessed and graded the quality of images from the dimensions of artifacts, boundary sharpness, visibility of lesions and overall image quality. We recorded the presence or absence of different pathologies. Moreover, we examined the interchangeability of the two protocols by computing the 95% confidence interval of the individual equivalence index, and also evaluated the inter-protocol intra-observer agreement using Cohen's weighted kappa. Results: Ultrafast-DL-3DIIE images were significantly better than conventional ones for artifacts and equivalent for other qualitative features. The number of cases with different kinds of pathologies was indistinguishable based on the MR images from ultrafast-DL-3DIIE and conventional protocols. With the exception of disc degeneration, the 95% confidence interval for the individual equivalence index across all variables did not surpass 5%, suggesting that the two protocols are interchangeable. The kappa values of these evaluations by the two radiologists ranged from 0.65 to 0.88, indicating good-to-excellent agreement. Conclusion: The DL-3DIIE system enables 67% spine MRI scan time reduction while obtaining at least equivalent image quality and diagnostic results compared to the conventional protocol, suggesting its potential for clinical utility.

13.
Addict Biol ; 29(4): e13394, 2024 04.
Article in English | MEDLINE | ID: mdl-38627958

ABSTRACT

Individuals with methamphetamine use disorder (MUD) often experience anxiety and depressive symptoms during abstinence, which can worsen the likelihood of relapse. Thus, it is essential to understand the neuro-mechanism behind methamphetamine use and its associated emotional withdrawal symptoms in order to develop effective clinical strategies. This study aimed to evaluate associations between emotional withdrawal symptoms and structural covariance networks (SCNs) based on cortical thickness (CTh) across the brain. The CTh measures were obtained from Tl-weighted MRI data from a sample of 48 males with MUD during abstinence and 48 male healthy controls. The severity of anxiety and depressive symptoms was assessed by the Hamilton Anxiety Scale (HAMA) and depression (HAMD) scales. Two important nodes belonging to the brain reward system, the right rostral anterior cingulate cortex (rACC) and medial prefrontal cortex (medPFC), were selected as seeds to conduct SCNs and modulation analysis by emotional symptoms. MUDs showed higher structural covariance between the right rACC and regions in the dorsal attention, right frontoparietal, auditory, visual and limbic networks. They also displayed higher structural covariance between the right medPFC and regions in the limbic network. Moreover, the modulation analysis showed that higher scores on HAMA were associated with increased covariance between the right rACC and the left parahippocampal and isthmus cingulate cortex in the default mode network. These outcomes shed light on the complex neurobiological mechanisms underlying methamphetamine use and its associated emotional withdrawal symptoms and may provide new insights into the development of effective treatments for MUD.


Subject(s)
Emotions , Substance Withdrawal Syndrome , Humans , Male , Brain/diagnostic imaging , Anxiety/diagnostic imaging , Magnetic Resonance Imaging , Brain Mapping , Substance Withdrawal Syndrome/diagnostic imaging
14.
Chem Biodivers ; 21(6): e202400463, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38606752

ABSTRACT

One novel compound, (R)-3, 6-diethoxy-4-hydroxycyclohex-3-en-1-one (1) and thirteen known compounds were isolated from the waste tobacco leaves. The structures of two compounds (1-2) were confirmed and attributed firstly by the extensive spectroscopic data, including 1D/2D NMR, IR, HR-ESI-MS, CD, and ECD spectra. Notably, seven compounds (2, 3, 9, 10, 11, 12, and 13) exhibited better tyrosinase inhibitory activity than the positive control kojic acid. The binding modes of these compounds revealed that their structure formed strong hydrogen bonds and van der Waals forces with the active sites of tyrosinase. These results indicated that waste tobacco leaves are good resources for developing tyrosinase inhibitors.


Subject(s)
Enzyme Inhibitors , Monophenol Monooxygenase , Nicotiana , Plant Leaves , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Plant Leaves/chemistry , Nicotiana/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/isolation & purification , Molecular Structure , Structure-Activity Relationship , Molecular Docking Simulation
15.
J Am Chem Soc ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38489242

ABSTRACT

We present the first example of an 99TcO4- anion entrapped within the cavity of a silver cluster, revealing an unprecedented photoinduced charge transfer phenomenon. [Ag24(C≡CtBu)20(99TcO4)]·(BF4)3 (denoted as 99TcO4-@Ag24) was successfully synthesized and structurally characterized. Single-crystal X-ray diffraction and Raman spectroscopy reveal that the tetrahedral structure of the 99TcO4- anion sustains significant symmetry breaking with weakened Tc-O bond strength under confinement within the Ag24(C≡CtBu)204+ cluster. Notably, 99TcO4-@Ag24 exhibits a broadband electronic absorption spectrum in the visible region, which was absent for the other 99TcO4--containing compounds. Density functional theory calculations elucidate that host-guest electrostatic interactions result in an electron polarization effect between the 99TcO4- anion core and the Ag24 cationic shell. The emergence of an absorption band in 99TcO4-@Ag24 is rationalized by intermolecular charge transfer from the Ag24 electronic states to the lowest unoccupied molecular orbitals of 99TcO4- instead of the intramolecular electron transition observed in other 99TcO4--containing compounds.

16.
IEEE Trans Nanobioscience ; 23(2): 378-388, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38442045

ABSTRACT

The efficient application of the newly developed gene-editing method CRISPR/Cas9 requires more accurate intracellular gene delivery. Traditional delivery approaches, such as lipotransfection and non-viral delivery methods, must contend with major problems to overcome the drawbacks of low efficiency, high toxicity, and cell-type dependency. The high-throughput microdroplet-based single-cell transfection method presented herein provides an alternative method for delivering genome-editing reagents into single living cells. By accurately controlling the number of exogenous plasmids in microdroplets, this method can achieve high-efficiency delivery of nucleic acids to different types of single cells. This paper presents a high-throughput quantitative DNA transfection method for single cells and explores the optimal DNA transfection conditions for specific cell lines. The transfection efficiency of cells at different concentrations of DNA in microdroplets is measured. Under the optimized transfection conditions, the method is used to construct gene-knockout cancer cell lines to determine specific gene functions through the CRISPR/Cas9 knockout system. In a case study, the migration ability of TRIM72 knockout cancer cells is inhibited, and the tumorigenicity of cells in a zebrafish tumor model is reduced. A single-cell microfluidic chip is designed to achieve CRISPR/Cas9 DNA transfection, dramatically improving the transfection efficiency of difficult-to-transfect cells. This research demonstrates that the microdroplet method developed herein has a unique advantage in CRISPR/Cas9 gene-editing applications.


Subject(s)
CRISPR-Cas Systems , Zebrafish , Animals , CRISPR-Cas Systems/genetics , Gene Knockout Techniques , Zebrafish/genetics , Transfection , DNA
17.
PLoS One ; 19(2): e0298207, 2024.
Article in English | MEDLINE | ID: mdl-38330049

ABSTRACT

PURPOSE: To compare the ability of diffusion parameters obtained by stretched-exponential and kurtosis models of diffusion-weighted imaging (DWI) to distinguish between patients with primary aldosteronism (PA) and healthy controls (HCs) in renal assessment. MATERIALS AND METHODS: A total of 44 participants (22 patients and 22 HCs) underwent renal MRI with an 11 b-value DWI sequence and a 3 b-value diffusion kurtosis imaging (DKI) sequence from June 2021 to April 2022. Binary logistic regression was used to construct regression models combining different diffusion parameters. Receiver-operating characteristic (ROC) curve analysis and comparisons were used to evaluate the ability of single diffusion parameters and combined diffusion models to distinguish between the two groups. RESULTS: A total of six diffusion parameters (including the cortical anomalous exponent term [α_Cortex], medullary fractional anisotropy [FA_Medulla], cortical FA [FA_Cortex], cortical axial diffusivity [Da_Cortex], medullary mean diffusivity [MD_Medulla] and medullary radial diffusivity [Dr_Medulla]) were included, and 10 regression models were studied. The area under the curve (AUC) of Dr_Medulla was 0.855, comparable to that of FA_Cortex and FA_Medulla and significantly higher than that of α_Cortex, Da_Cortex and MD_Medulla. The AUC of the Model_all parameters was 0.967, comparable to that of Model_FA (0.946) and Model_DKI (0.966) and significantly higher than that of the other models. The sensitivity and specificity of Model_all parameters were 87.2% and 95%, respectively. CONCLUSION: The Model_all parameters, Model_FA and Model_DKI were valid for differentiating between PA patients and HCs with similar differentiation efficacy and were superior to single diffusion parameters and other models.


Subject(s)
Diffusion Magnetic Resonance Imaging , Hyperaldosteronism , Humans , Diffusion Magnetic Resonance Imaging/methods , Kidney/diagnostic imaging , Diffusion Tensor Imaging/methods , Magnetic Resonance Imaging/methods , Hyperaldosteronism/diagnostic imaging
18.
Cardiovasc Diabetol ; 23(1): 48, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38302987

ABSTRACT

BACKGROUND: The impact of the coexistence of type 2 diabetes mellitus (T2DM) in patients with non-ischemic dilated cardiomyopathy (DCM) on clinical profiles, myocardial fibrosis, and outcomes remain incompletely understood. METHOD: A total of 1152 patients diagnosed with non-ischemic DCM were prospectively enrolled from June 2012 to October 2021 and categorized into T2DM and non-T2DM groups. Clinical characteristics, cardiac function, and myocardial fibrosis evaluated by CMR were compared between the two groups. The primary endpoint included both all-cause mortality and heart transplantation. Cause of mortality was classified into heart failure death, sudden cardiac death, and non-cardiac death. Cox regression analysis and Kaplan-Meier analysis were performed to identify the association between T2DM and clinical outcomes. Propensity score matching (PSM) cohort including 438 patients was analyzed to reduce the bias from confounding covariates. RESULTS: Among the 1152 included DCM patients, 155 (13%) patients had T2DM. Patients with T2DM were older (55 ± 12 vs. 47 ± 14 years, P < 0.001), had higher New York Heart Association (NYHA) functional class (P = 0.003), higher prevalence of hypertension (37% vs. 21%, P < 0.001), atrial fibrillation (31% vs. 16%, P < 0.001), lower left ventricular (LV) ejection fraction (EF) (23 ± 9% vs. 27 ± 12%, P < 0.001), higher late gadolinium enhancement (LGE) presence (55% vs. 45%, P = 0.02), and significantly elevated native T1 (1323 ± 81ms vs. 1305 ± 73ms, P = 0.01) and extracellular volume fraction (ECV) (32.7 ± 6.3% vs. 31.3 ± 5.9%, P = 0.01) values. After a median follow-up of 38 months (interquartile range: 20-57 months), 239 patients reached primary endpoint. Kaplan-Meier analysis showed that patients with T2DM had worse clinical outcomes compared with those without T2DM in the overall cohort (annual events rate: 10.2% vs. 5.7%, P < 0.001). T2DM was independently associated with an increased risk of primary endpoint in the overall (Hazard ratio [HR]: 1.61, 95% CI: 1.13-2.33, P = 0.01) and PSM (HR: 1.54, 95% CI: 1.05-2.24, P = 0.02) cohorts. Furthermore, T2DM was associated with a higher risk of heart failure death (P = 0.006) and non-cardiac death (P = 0.02), but not sudden cardiac death (P = 0.16). CONCLUSIONS: Patients with T2DM represented a more severe clinical profile and experienced more adverse outcomes compared to those without T2DM in a large DCM cohort. TRIAL REGISTRATION: Trial registration number: ChiCTR1800017058; URL: https://www. CLINICALTRIALS: gov .


Subject(s)
Cardiomyopathy, Dilated , Diabetes Mellitus, Type 2 , Heart Failure , Humans , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Contrast Media , Prospective Studies , Magnetic Resonance Imaging, Cine/adverse effects , Gadolinium , Prognosis , Stroke Volume , Fibrosis , Heart Failure/diagnosis , Predictive Value of Tests
19.
J Cardiovasc Magn Reson ; 26(1): 101002, 2024.
Article in English | MEDLINE | ID: mdl-38237899

ABSTRACT

BACKGROUND: The prognostic value of follow-up cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) patients is unclear. We aimed to investigate the prognostic value of cardiac function, structure, and tissue characteristics at mid-term CMR follow-up. METHODS: The study population was a prospectively enrolled cohort of DCM patients who underwent guideline-directed medical therapy with baseline and follow-up CMR, which included measurement of biventricular volume and ejection fraction, late gadolinium enhancement, native T1, native T2, and extracellular volume. During follow-up, major adverse cardiac events (MACE) were defined as a composite endpoint of cardiovascular death, heart transplantation, and heart-failure readmission. RESULTS: Among 235 DCM patients (median CMR interval: 15.3 months; interquartile range: 12.5-19.2 months), 54 (23.0%) experienced MACE during follow-up (median: 31.2 months; interquartile range: 20.8-50.0 months). In multivariable Cox regression, follow-up CMR models showed significantly superior predictive value than baseline CMR models. Stepwise multivariate Cox regression showed that follow-up left ventricular ejection fraction (LVEF; hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.91-0.96; p < 0.001) and native T1 (HR, 1.01; 95% CI, 1.00-1.01; p = 0.030) were independent predictors of MACE. Follow-up LVEF ≥ 40% or stable LVEF < 40% with T1 ≤ 1273 ms indicated low risk (annual event rate < 4%), while stable LVEF < 40% and T1 > 1273 ms or LVEF < 40% with deterioration indicated high risk (annual event rate > 15%). CONCLUSIONS: Follow-up CMR provided better risk stratification than baseline CMR. Improvements in the LVEF and T1 mapping are associated with a lower risk of MACE.


Subject(s)
Cardiomyopathy, Dilated , Heart Transplantation , Magnetic Resonance Imaging, Cine , Predictive Value of Tests , Stroke Volume , Ventricular Function, Left , Humans , Cardiomyopathy, Dilated/diagnostic imaging , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/mortality , Male , Female , Prospective Studies , Middle Aged , Time Factors , Risk Factors , Risk Assessment , Adult , Aged , Prognosis , Patient Readmission , Ventricular Remodeling , Disease Progression
20.
J Magn Reson Imaging ; 60(2): 675-685, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38174826

ABSTRACT

BACKGROUND: Hepatic alterations are common aftereffects of heart failure (HF) and ventricular dysfunction. The prognostic value of liver injury markers derived from cardiac MRI studies in nonischemic dilated cardiomyopathy (DCM) patients is unclear. PURPOSE: Evaluate the prognostic performance of liver injury markers derived from cardiac MRI studies in DCM patients. STUDY TYPE: Prospective. POPULATION: Three hundred fifty-six consecutive DCM patients diagnosed according to ESC guidelines (age 48.7 ± 14.2 years, males 72.6%). FIELD STRENGTH/SEQUENCE: Steady-state free precession, modified Look-Locker inversion recovery T1 mapping and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences at 3 T. ASSESSMENT: Clinical characteristics, conventional MRI parameters (ventricular volumes, function, mass), native myocardial and liver T1, liver extracellular volume (ECV), and myocardial LGE presence were assessed. Patients were followed up for a median duration of 48.3 months (interquartile range 42.0-69.9 months). Primary endpoints included HF death, sudden cardiac death, heart transplantation, and HF readmission; secondary endpoints included HF death, sudden cardiac death, and heart transplantation. Models were developed to predict endpoints and the incremental value of including liver parameters assessed. STATISTICAL TESTS: Optimal cut-off value was determined using receiver operating characteristic curve and Youden method. Survival analysis was performed using Kaplan-Meier and Cox proportional hazard. Discriminative power of models was compared using net reclassification improvement and integrated discriminatory index. P value <0.05 was considered statistically significant. RESULTS: 47.2% patients reached primary endpoints; 25.8% patients reached secondary endpoints. Patients with elevated liver ECV (cut-off 34.4%) had significantly higher risk reaching primary and secondary endpoints. Cox regression showed liver ECV was an independent prognostic predictor, and showed independent prognostic value for primary endpoints and long-term HF readmission compared to conventional clinical and cardiac MRI parameters. DATA CONCLUSIONS: Liver ECV is an independent prognostic predictor and may serve as an innovative approach for risk stratification for DCM. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.


Subject(s)
Cardiomyopathy, Dilated , Liver , Magnetic Resonance Imaging , Humans , Male , Middle Aged , Female , Cardiomyopathy, Dilated/diagnostic imaging , Prognosis , Prospective Studies , Adult , Liver/diagnostic imaging , Liver/pathology , Magnetic Resonance Imaging/methods , Contrast Media , Gadolinium , Myocardium/pathology , Heart/diagnostic imaging , Biomarkers
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