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Yueyao Jiang, Chenqi Liu, Wanchen Zhai, Ning Zhuang, Tengfei Han, Zhiying Ding School of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaCorrespondence: Zhiying DingSchool of Pharmaceutical Sciences, Jilin University, Changchun 130021, People’s Republic of ChinaTel +8613843180286Email dzy@jlu.edu.cnBackground: Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer’s disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems.Purpose: The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration.Methods: The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency.Results: Optimized HupA-NE had a particle size of 15.24±0.67 nm, polydispersity index (PDI) of 0.128±0.025, and zeta potential of −4.48±0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2±0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE.Conclusion: Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.Keywords: nanoemulsion, lactoferrin, brain targeting, intranasal delivery

Abstract Background Cystathionine accumulates selectively in 1p/19q-codeleted gliomas, and can serve as a possible noninvasive biomarker. This study aims to optimize the echo time (TE) of point-resolved spectroscopy (PRESS) for cystathionine detection in gliomas, and evaluate the diagnostic accuracy of PRESS for 1p/19q-codeletion identification. Methods The TE of PRESS was optimized with numerical and phantom analysis to better resolve cystathionine from the overlapping aspartate multiplets. The optimized and 97 ms TE PRESS were then applied to 84 prospectively enrolled patients suspected of glioma or glioma recurrence to examine the influence of aspartate on cystathionine quantification by fitting the spectra with and without aspartate. The diagnostic performance of PRESS for 1p/19q-codeleted gliomas were assessed. Results The TE of PRESS was optimized as (TE1, TE2) = (17 ms, 28 ms). The spectral pattern of cystathionine and aspartate were consistent between calculation and phantom. The mean concentrations of cystathionine in vivo fitting without aspartate were significantly higher than those fitting with full basis-set for 97 ms TE PRESS (1.97 ± 2.01 mM vs. 1.55 ± 1.95 mM, p

A detailed experimental study of supersonic, Mach 2, flow over a three-dimensional cavity was conducted using shadowgraph visualization, unsteady surface pressure measurements, and particle image velocimetry. Large-scale structures in the cavity shear layer and visible disturbances inside the cavity were clearly observed. A large recirculation zone and high-speed reverse flow was revealed in the cavity. In addition, supersonic micro jets were used at the leading edge to suppress flow unsteadiness within the cavity. With a minimal mass flux (blowing coefficient [B.sub.c] = 0.0015), the activation of micro jets led to reductions of up to 20 dB in the amplitudes of cavity tones and of more than 9 dB in the overall sound pressure levels. The microjet injection also modified the cavity mixing layer and resulted in a significant reduction in the flow unsteadiness inside the cavity as revealed by the shadowgraphs and the velocity-field measurements.

Abstract Background This study aimed to evaluate the artificial intelligence (AI)-based coronary artery calcium (CAC) quantification and regional distribution of CAC on non-gated chest CT, using standard electrocardiograph (ECG)-gated CAC scoring as the reference. Methods In this retrospective study, a total of 405 patients underwent non-gated chest CT and standard ECG-gated cardiac CT. An AI-based algorithm was used for automated CAC scoring on chest CT, and Agatston score on cardiac CT was manually quantified. Bland-Altman plots were used to evaluate the agreement of absolute Agatston score between the two scans at the patient and vessel levels. Linearly weighted kappa (κ) was calculated to assess the reliability of AI-based CAC risk categorization and the number of involved vessels on chest CT. Results The AI-based algorithm showed moderate reliability for the number of involved vessels in comparison to measures on cardiac CT (κ = 0.75, 95% CI 0.70–0.79, P

The research aims to examine the distribution of porosity and the combined heat and moisture movement while grains are being dried. This research concerns the porosity and flow of soybeans with different particle size ratios and the drying of soybeans with varying particle temperatures. Due to the similarity in shape between soybeans and balls, this article adopts a ball shape to study the heat and moisture transfer of soybean particles, which can also be used for the study of grains with similar shapes, such as mung beans and red beans. Random models of soybeans with varying proportions were created using modeling software Edem and UG. UDF programming was added to the preprocessing software Fluent to analyze the porosity, airstream allocation, and the interaction of temperature and moisture transfer in packed beds with various cylinder-to-particle size ratios and particle temperatures. A packed bed of soybeans was created, and the study examined the impact of cylinder-to-particle size ratios of 4.44, 5.6, and 6.25 on porosity. The results show that the radial porosity in the packed bed displays a fluctuating profile, with partial porosity increasing as the cylinder-to-particle size ratio increases. Increasing the ratio of cylinder size to particle size exacerbated the tortuosity of the flow paths within the packed bed. Simultaneously, the particle temperature increases, leading to a rise in the instantaneous heat transfer during the drying process, strengthening the ratio of moisture transfer within the packed bed. The method effectively models during convective heat and mass transfer in the liquid facies, as well as thermal and mass spread in the solid facies. The results of this study have been validated on physical models. The air temperature of 273 K is considered during the simulation process

Abstract Reactive oxygen species (ROS) are closely associated with the progression of diabetic cardiomyopathy (DCM) and can be regarded as one of its early biomarkers. Magnetic resonance imaging (MRI) is emerging as a powerful tool for the detection of cardiac abnormalities, but the sensitive and direct ROS‐response MRI probe remains to be developed. This restricts the early diagnosis of DCM and prevents timely clinical interventions, resulting in serious and irreversible pathophysiological abnormalities. Herein, a novel ROS‐response contrast‐enhanced MRI nanoprobe (RCMN) is developed by multi‐functionalizing fluorinated carbon nanosheets (FCNs) with multi‐hydroxyl and 2,2,6,6‐tetramethylpiperidin‐1‐oxyl groups. RCMNs capture ROS and then gather in the heart provisionally, which triggers MRI signal changes to realize the in vivo detection of ROS. In contrast to the clinical MRI agents, the cardiac abnormalities of disease mice is detected 8 weeks in advance with the assistance of RCMNs, which greatly advances the diagnostic window of DCM. To the best of the knowledge, this is the first ROS‐response metal‐free T2‐weighted MRI probe for the early diagnosis of DCM mice model. Furthermore, RCMNs can timely scavenge excessively produced ROS to alleviate oxidative stress.

Erianin is an active constituent of Dendrobium candidum. In this work, 18F-fluoroethoxylerianin ([18F]FEE), a 18F-Labeled erianin analogue, was designed and synthesized to evaluate the properties of erianin and related analogues by in vivo PET imaging. The initial product was separated and purified by liquid-phase separation module Explora LC and simple homemade solid-phase extraction, and high purity [18F]FEE was finally obtained. The radiochemical purity of [18F]FEE was determined by Radio-TLC and Radio-HPLC. [18F]FEE showed good stability in normal saline and serum, and could be quickly eliminated from mice. Cell experiments, biological distribution, and small-animal PET/CT further showed that [18F]FEE had a high uptake rate in HepG2 tumor cells, and showed good imaging ability in a HepG2 tumor model. The results of this study indicate that the synthesized 18F-labeled erianin analogue is an effective new probe for positron emission tomography (PET) imaging of HepG2 hepatocellular carcinoma, which provides an intuitive and reliable theoretical basis for the development of erianin as an anticancer drug.

Under the background of rural revitalization strategy, art intervention in rural areas, as a new way of rural construction in China, is attracting more and more attention since various art practices have appeared in Chinese villages during the last decade. Art intervention in rural areas has multi-dimensional benefits such as improving rural landscape, promoting villagers' income, enhancing community connections, and promoting cultural inheritance. On the basis of clarifying the connotation and typical modes of art intervention in rural areas in China, this paper constructs and analyzes the benefit hierarchy of art intervention in rural areas based on Maslow's hierarchy of needs theory, and selects Xiaozhou and Fenghe villages in Guangzhou as typical cases to identify the benefit characteristics and problems of two modes of artist-led and capital-led art intervention through field investigation. Although previous studies have focused more on specific cases of art intervention in rural areas, which have revealed the work procedure and achievements in detail, the comparison of their differences and a systematic construction of the influence are still worth discussing. The research results show that: (1) Art intervention in rural areas is a typical mode of rural revitalization in which the government, capital, artists and cultural groups realize multi-level benefits such as rural landscape beautification, tourism economic benefits, community creation and governance, and local cultural inheritance through art practice in the context of rural revitalization. According to different driving subjects, the art intervention in rural areas can be divided into two types: artist-led and capital-led. (2) Art intervention in rural areas has four levels of benefits: material, economic, social and cultural, showing the characteristics of progression by level. (3) The artist-led type plays a significant role in realizing high-level benefits, while the low-level benefits are lacking; the capital-led type plays a significant role in realizing low-level benefits, while the high-level benefits are lacking. (4) Building a multi-party cooperation model with the collaboration of capital and artists, government support, and villagers' participation can combine the advantages of the benefits of the two modes and make the rural practice of art intervention more replicable. In summary, this study divides the practices of art intervention in rural China into two types: artist-led and capital-led, constructs the four-level benefits hierarchy based on Maslow's hierarchy of needs theory, compares the four-level benefits between Xiaozhou village and Fenghe village, and summarizes the benefit differences between the artist-led mode and the capital-led mode. For its contributions, it innovatively applies Maslow's hierarchy of needs theory into the study of art intervention from a theoretical perspective and enriches the case study of art intervention in rural China and explores the characteristics from a practical perspective.

Indium can efficiently mediate the Reformatsky reaction of iododifluoroacetylketones with aldehydes to afford the corresponding α,α-difluoro-β-hydroxyketones in high yield in pure water This reaction has excellent substrate suitability and functional group selectivity and provides an efficient approach for the synthesis of bioactive molecules containing the α,α-difluoro-β-hydroxyketone pharmacophore.

The self-cleaning ability of superhydrophobic metal surfaces has attracted extensive attention. The preparation of superhydrophobic material using the coating method is a common processing method. In this experiment, aluminum fins were processed by laser etching and perfluorinated two-step coating. The aluminum surface was modified using a femtosecond laser and 1H,1H,2H,2H- perfluorooctane triethoxysilane (PFOTES). A superhydrophobic aluminum surface with excellent mechanical stability and self-cleaning properties was obtained with the superhydrophobic contact angle (WCA) of 152.8° and the rolling angle (SA) of 0.6°. The results show that the superhydrophobic surface has an excellent cleaning effect compared with an ordinary surface in unit time. Then, a wear resistance test of the superhydrophobic surface was carried out by using the physical wear method. The results show that physical wear had a low influence on the hydrophobic property of the specimen surface. Finally, the Vickers hardness analysis found that the superhydrophobic surface hardness was significantly better than the ordinary surface hardness compared with the superhydrophobic surface hardness. Based on the excellent self-cleaning properties, wear resistance, and robustness of superhydrophobic materials, the laser-etched and perfluorinated superhydrophobic aluminum fins designed and manufactured in this study have broad application prospects in improving the heat transfer efficiency of finned heat exchangers.

Abstract In this paper, the boundedness of the classic Hardy operator and its adjoint on Hardy spaces is obtained. We also discuss the boundedness for the commutators generated by the classic Hardy operator and its adjoint with B M O $BMO$ and C M O ( R + ) $CMO(\mathbb{R}^{+})$ functions on Hardy spaces.

Background: Arterial aging is characterized by decreased vascular function, caused by arterial stiffness (AS), and vascular morphological changes, caused by arterial dilatation. We analyzed the relationship of pre-AS and AS, as assessed by cardio ankle vascular index (CAVI), with arterial diameters (AD) at nine levels, from the aortic sinus to the abdominal aorta, as measured by artificial intelligence (AI) on non-enhanced chest computed tomography (CT) images.Methods: Overall, 801 patients who underwent both chest CT scan and arterial elasticity test were enrolled. Nine horizontal diameters of the thoracic aorta (from the aortic sinuses of Valsalva to the abdominal aorta at the celiac axis origin) were measured by AI using CT. Patients were divided into non-AS (mean value of the left and right CAVIs [M.CAVI] < 8), pre-AS (8 ≤ M.CAVI < 9), and AS (M.CAVI ≥ 9) groups. We compared AD differences among groups, analyzed the correlation of age, ADs, and M.CAVI or the mean pressure-independent CAVI (M.CAVI0), Furthermore, we evaluated the risk predictors and the diagnostic value of the nine ADs for pre-AS and AS.Results: The AD at mid descending aorta (MD) correlated strongest with CAVI (r = 0.46, p < 0.001) or M.CAVI0 (r = 0.42, p < 0.001). M.CAVI was most affected by the MD AD and by age. An increase in the MD AD independently predicted the occurrence of pre-AS or AS. For MD AD, every 4.37 mm increase caused a 14% increase in the pre-AS and AS risk and a 13% increase in the AS risk. With a cut-off value of 26.95 mm for the MD AD, the area under the curve (AUC) for identifying the risk of AS was 0.743. With a cut-off value of 25.15 mm, the AUC for identifying the risk of the stage after the prophase of AS is 0.739.Conclusions: Aging is associated with an increase in AD and a decrease in arterial elasticity. An increase in AD, particularly at the MD level is an independent predictor of AS development.

Background: The aim of this study was to explore the predictive values of quantitative CT indices of the total lung and lung lobe tissue at discharge for the pulmonary diffusion function of coronavirus disease 2019 (COVID-19) patients at 5 months after symptom onset. Methods: A total of 90 patients with moderate and severe COVID-19 underwent CT scans at discharge, and pulmonary function tests (PFTs) were performed 5 months after symptom onset. The differences in quantitative CT and PFT results between Group 1 (patients with abnormal diffusion function) and Group 2 (patients with normal diffusion function) were compared by the chi-square test, Fisher’s exact test or Mann–Whitney U test. Univariate analysis, stepwise linear regression and logistic regression were used to determine the predictors of diffusion function in convalescent patients. Results: A total of 37.80% (34/90) of patients presented diffusion dysfunction at 5 months after symptom onset. The mean lung density (MLD) of the total lung tissue in Group 1 was higher than that in Group 2, and the percentage of the well-aerated lung (WAL) tissue volume (WAL%) of Group 1 was lower than that of Group 2 (all p < 0.05). Multiple stepwise linear regression identified only WAL and WAL% of the left upper lobe (LUL) as parameters that positively correlated with the percent of the predicted value of diffusion capacity of the lungs for carbon monoxide (WAL: p = 0.002; WAL%: p = 0.004), and multiple stepwise logistic regression identified MLD and MLDLUL as independent predictors of diffusion dysfunction (MLD: OR (95%CI): 1.011 (1.001, 1.02), p = 0.035; MLDLUL: OR (95%CI): 1.016 (1.004, 1.027), p = 0.008). Conclusion: At five months after symptom onset, more than one-third of moderate and severe COVID-19 patients presented with diffusion dysfunction. The well-aerated lung and mean lung density quantified by CT at discharge could be predictors of diffusion function in convalesce.

High response, stable operation, small volume active vibration damping system and other intelligent hydraulic equipment have become the inevitable trend of future development. A compact low-pulsation gerotor pump is designed to meet these requirements, the theoretical flow pulsation of 8/9 tooth gerotor pump is analysed, and its pressure pulsation characteristics are also studied in this paper. The combined pulsation buffer is placed at the bottom valve plate high-pressure port of pumps. High-pressure oil passes through the honeycomb damping hole and enters the diaphragm volume chamber of the accumulator to form a combined pulsation buffer. Considering the effect of the pulsation buffer structure to reduce flow pulsation at different speeds, a test bench for high-speed gerotor pump pulsation characteristics is built, and the pressure pulsation of the gerotor pump with and without pulsation buffer is analysed at different speeds. Results show that the pressure pulsation frequency increases with pump speed. When the speed reaches 5500 r/min, 8/9 tooth gerotor pump without pulsation buffer outlet pressure pulsation reached 13.797% and that with pulsation buffer outlet pressure pulsation decreased to 9.871%, showing a 28.46% decline rate. At pump rotation speeds are 1500 r/min and 2500 r/min, the pulsation reduction ratios are 37.78% and 35.36%. The pressure pulsation of the gerotor pump can be evidently reduced by designing a combined pulsation buffer in this paper. Therefore, this high-speed and low-pulsation gerotor pump is suitable for active vibration damping system and other intelligent hydraulic equipment.

Background: In this study, our focus was on pulmonary sequelae of coronavirus disease 2019 (COVID-19). We aimed to develop and validate CT-based radiomic models for predicting the presence of residual lung lesions in COVID-19 survivors at three months after discharge. Methods: We retrospectively enrolled 162 COVID-19 confirmed patients in our hospital (84 patients with residual lung lesions and 78 patients without residual lung lesions, at three months after discharge). The patients were all randomly allocated to a training set (n = 114) or a test set (n = 48). Radiomic features were extracted from chest CT images in different regions (entire lung or lesion) and at different time points (at hospital admission or at discharge) to build different models, sequentially, or in combination, as follows: (1) Lesion_A model (based on the lesion region at admission CT); (2) Lesion_D model (based on the lesion region at discharge CT); (3) Δlesion model (based on the lesion region at admission CT and discharge CT); (4) Lung_A model (based on the lung region at admission CT); (5) Lung_D model (based on the lung region at discharge CT); (6) Δlung model (based on the lung region at admission CT and discharge CT). The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the predictive performances of the radiomic models. Results: Among the six models, the Lesion_D and the Δlesion models achieved better predictive efficacy, with AUCs of 0.907 and 0.927, sensitivity of 0.898 and 0.763, and specificity of 0.855 and 0.964 in the training set, and AUCs of 0.875 and 0.837, sensitivity of 0.920 and 0.680, and specificity of 0.826 and 0.913 in the test set, respectively. Conclusions: The CT-based radiomic models showed good predictive effects on the presence of residual lung lesions in COVID-19 survivors at three months after discharge, which may help doctors to plan follow-up work and to reduce the psychological burden of COVID-19 survivors.