Search

Ultrasound vascular imaging (UVI) is a valuable tool for monitoring the physiological states and evaluating the pathological diseases. Advancing from conventional two-dimensional (2D) to three-dimensional (3D) UVI would enhance the vasculature visualization, thereby improving its reliability. Row-column array (RCA) has emerged as a promising approach for cost-effective ultrafast 3D imaging with a low channel count. However, ultrafast RCA imaging is often hampered by high-level sidelobe artifacts and low signal-to-noise ratio (SNR), which makes RCA-based UVI challenging. In this study, we propose a spatial-temporal similarity weighting (St-SW) method to overcome these challenges by exploiting the incoherence of sidelobe artifacts and noise between datasets acquired using orthogonal transmissions. Simulation, in vitro blood flow phantom, and in vivo experiments were conducted to compare the proposed method with existing orthogonal plane wave imaging (OPW), row-column-specific frame-multiply-and-sum beamforming (RC-FMAS), and XDoppler techniques. Qualitative and quantitative results demonstrate the superior performance of the proposed method. In simulations, the proposed method reduced the sidelobe level by 31.3 dB, 20.8 dB, and 14.0 dB, compared to OPW, XDoppler, and RC-FMAS, respectively. In the blood flow phantom experiment, the proposed method significantly improved the contrast-to-noise ratio (CNR) of the tube by 26.8 dB, 25.5 dB, and 19.7 dB, compared to OPW, XDoppler, and RC-FMAS methods, respectively. In the human submandibular gland experiment, it not only reconstructed a more complete vasculature but also improved the CNR by more than 15 dB, compared to OPW, XDoppler, and RC-FMAS methods. In summary, the proposed method effectively suppresses the side-lobe artifacts and noise in images collected using an RCA under low SNR conditions, leading to improved visualization of 3D vasculatures.

Obtaining lignin-based graphite-like microcrystallites at a relatively low carbonization temperature is still very challenging. In this work, we report a new method based on condensed structures, for regulating graphite-like microcrystalline structures via the incorporation of 4,4'-diphenylmethane diisocyanate (MDI) into the main structure of lignin. The effects of MDI on the thermal properties of lignin and the graphite-like microcrystalline structure of lignin-based ultrafine carbon fibers were extensively studied and investigated. The incorporation of MDI decreased the thermal stability of lignin, increased the carbon yield and enhanced the formation of graphite-like microcrystallites, which are beneficial for reducing energy consumption during the preparation of lignin-based carbon fibers. The modified lignin-based ultrafine carbon fibers (M-LCFs) demonstrated satisfactory electrochemical performance, including high specific capacitance, low charge transfer resistance, and good cycle performance. The M-LCFs-3/2 electrode had a specific capacitance of 241.3 F g -1 at a current density of 0.5 A g -1 , and a residual ratio of 90.2 % after 2000 charge and discharge cycles. This study provides a new approach to control the graphite-like microcrystalline structure and electrochemical performance while also optimizing the temperature., Competing Interests: Declaration of competing interest I would like to declare on behalf of my co-authors that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Five new compounds were identified from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, involving UV, IR, NMR spectrum and HRESIMS analyses. The absolute configuration of compound 2 was proved by comparing their experimental and calculated ECD spectrum. The vitro bioactive assay of all compounds suggested that compound 1, 3, 4, 5 and 6 may have potential anti-asthmatic activities., Competing Interests: Declaration of competing interest The authors have declared that there is no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Vascular endothelial cell premature senescence plays an important part in stroke. Many microRNAs (miRNAs) are known to be involved in the pathological process of vascular endothelial cell premature senescence. The present study aimed to investigate the mechanism of hydrogen peroxide (H2O2)-induced premature senescence in human umbilical vein endothelial cells (HUVECs) and effect of miR-142-3p on hydrogen peroxide (H2O2)-induced premature senescence. HUVECs were exposed to H2O2 to establish a model premature senescence in endothelial cells. CCK-8 assay was performed to detect cell viability. Senescence-associated β-galactosidase staining assay and senescence-related proteins p16 and p21 were used to detect changes in the degree of cell senescence. RT-qPCR and Western blot were conducted to measure mRNA and protein levels, respectively. The scratch wound-healing assay, transwell assay, and EdU assay were performed to evaluate the ability of migration and proliferation, respectively. miRNA-142-3p and silencing information regulator 2 related enzyme 1 (SIRT1) binding was verified using Targetscan software and a dual-luciferase assay. We found that miRNA-142-3p is abnormally up-regulated in HUVECs treated with H2O2. Functionally, miRNA-142-3p inhibition may mitigate the degree of HUVEC senescence and improve HUVEC migration and proliferation. Mechanistically, SIRT1 was validated to be targeted by miRNA-142-3p in HUVECs. Moreover, SIRT1 inhibition reversed the effects of miRNA-142-3p inhibition on senescent HUVECs exposed to H2O2. To our knowledge, this is the first study to show that miRNA-142-3p ameliorates H2O2-induced HUVECs premature senescence by targeting SIRT1 and may shed light on the role of the miR-142-3p/SIRT1 axis in stroke treatment., (© 2024 The Author(s).)

Twelve undescribed compounds, including five flavonoids and seven phenols, were isolated from the stems of Ephedra equisetina Bunge. Their structures were elucidated by spectroscopic methods, including NMR spectroscopy and HRESIMS analysis. Their absolute configurations were elucidated by comparing their experimental and calculated ECD spectra. In the in vitro bioactive assay, all compounds were tested for their anti-asthmatic activities by releasing β-Hex in C48/80-induced RBL-2H3 cells. The β-Hex release rates of compounds 3, 8, 10, and 11 were 0.8502 ± 0.0231, 0.8802 ± 0.0805, 0.7850 ± 0.0593, and 0.8361 ± 0.0728, respectively, suggesting that compounds 3, 8, 10, and 11 have potential anti-asthmatic activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Tanshinone IIA (Tan-IIA) is the main bioactive component of Chinese herbal medicine salvia miltiorrhiza (Danshen). Sodium sulfonate of Tan-IIA is widely used in the treatment of cardiovascular and cerebrovascular diseases. Tan-IIA also has inhibitory effects on tumor cells such as gastric cancer, but its therapeutic effect and mechanism on human neuroblastoma have not been evaluated, so its pharmacological mechanism is systematically evaluated by the combined method of network pharmacology and molecular docking. PharmMapper and SwissTargetPrediction predicted 331 potential Tan-IIA-related targets, and 1,152 potential neuroblastoma-related targets were obtained from GeneCards, DisGeNET, DrugBank, OMIM and Therapeutic Target databases (TTD), 107 common targets for Tan-IIA and neuroblastoma. Through gene ontology (GO) functional annotation, Kyoto Encyclopedia of Genes and Genomesa (KEGG) pathway enrichment, protein-protein interaction (PPI) network and cytoHubba plug-in, 10 related signal pathways (Pathways in cancer, PI3K-Akt signaling pathway, Prostate cancer, etc.) and 10 hub genes were identified. The results of molecular docking showed that Tan-IIA could interact with 10 targets: GRB2, SRC, EGFR, PTPN1, ESR1, IGF1, MAPK1, PIK3R1, AKT1 and IGF1R. This study analyzed the related pathways and targets of Tan-IIA in the treatment of human neuroblastoma, as well as the potential anticancer and anti-tumor targets and related signaling pathways of Tan-IIA, which provides a reference for us to find and explore effective drugs for the treatment of human neuroblastoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Wang, Miao, Zhao, Cao, Sun, Zhang, Sui and Li.)

Six previously undescribed sesquiterpenoids, chrysanthterpenoids H-M (1-6), were isolated from the stem and leaves of Chrysanthemum morifolium Ramat. Structure elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. Furthermore, computational prediction of ECD was used to propose the absolute configurations of the compounds. All compounds were evaluated for their anti-asthma effects on RBL-2H3 cells in vitro. The results showed that Compounds 2 and 3 significantly inhibited the release of β-aminohexosidase and improved RBL-2H3 degranulation by chromogenic substrate and high-content imaging. These results suggest that Compounds 2 and 3 may exhibit anti-asthma activities., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Erectile dysfunction (ED) caused by cavernous nerve injury (CNI) is refractory to heal mainly ascribed to the adverse remodeling of the penis induced by ineffectual microvascular perfusion, fibrosis, and neurotrophins scarcity in cavernosum. Phosphodiesterase type V inhibitors (PDE5i) have been regarded as an alternative candidate drug for avoiding penile neuropathy. However, the therapeutic efficacy is severely limited due to poor accumulation under systemic medication and endogenous nitric oxide (NO) deficiency in cavernosum. Herein, an innovative liposomal microbubble (MB) loaded with both Sildenafil (one of PDE5i) and NO was designed. Ultrasound-targeted MB destruction (UTMD)-mediated efficient release and integration erectogenic agents into corpus cavernosum with high biosafety. On a bilateral CNI rat model, the multifunctional MB-cooperated UTMD improved microvascular perfusion in penis, simultaneously, alleviated hypoxia and oxidative stress, indicating successful activation of NO-cyclic guanosine monophosphate pathway. Also, evaluation of the endothelial/muscular composition, intracavernosal pressure, and neural integrity in the penis proved that coordinated intervention reversed the abnormal structural remodeling and promoted the recovery of functional erection. Our work demonstrates that MB loading Sildenafil and NO combined with UTMD hold great promise to "awaken" the efficacy of PDE5i in neurogenic ED, which provided a superior option for ensuring penile rehabilitation., Competing Interests: The authors declare no conflicts of interest. The authors declare that the figure of Schematic was designed by our team, and do not acquire from any copyrighted source, without acknowledgement., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Recently, the coding metasurface has gained significant attention due to its exceptional potential in controlling electromagnetic (EM) waves with the rapid development of wireless communication systems. Meanwhile, graphene shows tremendous promise for the implementation of reconfigurable antennas due to its high tunable conductivity and its unique property that makes it a very suitable material for realizing steerable coded states. In this paper, we first propose a simple structured beam reconfigurable millimeter wave (MMW) antenna using a novel graphene-based coding metasurface (GBCM). Different from the previous method, its coding state can be manipulated by altering the sheet impedance of graphene instead of bias voltage. Then, we design and simulate several most popular coding sequences, including dual-, quad-and single-beam-generated implement, 30° beam deflection, as well as a random coding sequence for radar cross-section (RCS) reduction. The theoretical and simulation results show that graphene has great potential for MMW manipulation applications, which lay a foundation for the subsequent development and fabrication of GBCM.

Due to the modulation of tiny frequency offset on the array elements, a frequency diverse array (FDA) jammer can generate multiple range-dimension point false targets, and many deception jamming methods against SAR using an FDA jammer have been studied. However, the potential of the FDA jammer to generate barrage jamming has rarely been reported. In this paper, a barrage jamming method against SAR using an FDA jammer is proposed. To achieve two-dimensional (2-D) barrage effect, the stepped frequency offset of FDA is introduced to generate range-dimensional barrage patches, and the micro-motion modulation is employed to increase the extent of barrage patches along the azimuth direction. Mathematical derivations and simulation results demonstrate the validity of the proposed method in generating flexible and controllable barrage jamming.

Synthetic transmit aperture (STA) imaging benefits from the two-way dynamic focusing to achieve optimal lateral resolution and contrast resolution in the full field of view, at the cost of low frame rate (FR) and low signal-to-noise ratio (SNR). In our previous studies, compressed sensing based synthetic transmit aperture (CS-STA) and minimal l 2 -norm least squares (LS-STA) methods were proposed to recover the complete STA dataset from fewer Hadamard-encoded plane wave (PW) transmissions. Results demonstrated that, compared with STA imaging, CS/LS-STA can maintain the high resolution of STA in the full field of view and improve the contrast in the deep region with increased FR. However, these methods would introduce errors to the recovered STA datasets and subsequently produce severe artifacts to the beamformed images, especially in the shallow region. Recently, we discovered that the theoretical explanation for the error introduced in the LS-STA-based recovery is that the LS-STA method neglects the null space component of the real STA dataset. To deal with this problem, we propose to train a convolutional neural network under the null space learning framework (CNN-Null) to estimate the missing null space component) for high-accuracy recovery of the STA dataset from fewer Hadamard-encoded PW transmissions. The mapping between the low-quality STA dataset (i.e., the range space component of the real STA dataset recovered using the LS-STA method) and the missing null space component of the real STA dataset was learned by the network with the high-quality STA dataset (obtained using full Hadamard-encoded STA imaging, HE-STA) as training labels. The performance of the proposed CNN-Null method was compared with the baseline LS-STA, conventional STA, and HE-STA methods, in terms of visual quality, normalized root-mean-square error (NRMSE), generalized contrast-to-noise ratio (gCNR), and lateral full width at half maximum (FWHM). The results demonstrate that the proposed method can greatly improve the recovery accuracy of the STA datasets (lower NRMSE) and therefore effectively suppress the artifacts presented in the images (especially in the shallow region) obtained using the LS-STA method (with a gCNR improvement of 0.4 in the cross-sectional carotid artery images). In addition, the proposed method can maintain the high lateral resolution of STA with fewer (as low as 16) PW transmissions, as LS-STA does.

Epimesatines A-I, nine undescribed prenylated flavonoids, along with ten known analogues, were isolated from the aerial parts of Epimedium sagittatum Maxim. The structures and absolute configurations of epimesatines A-I were determined using a combination of spectroscopic data, Rh 2 (OCOCF 3 ) 4 -induced electronic circular dichroism (ECD) experiments, ECD comparisons, and X-ray crystallography analysis. Epimesatines A and I displayed notable activities on the viabilities of human non-small cell lung cancer (NSCLC) A549 cells with IC 50 values of 1.77 and 9.97 μM, respectively. Furthermore, epimesatines A and I significantly inhibited the expression of sphingosine kinase 1 (SPHK1) in A549 cells. In addition, none of these compounds showed obvious toxicity on normal human lung bronchial epithelial BEAS-2B cells., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Five new triterpenoids, oenotheralanosterols C-G ( 1 - 5 ), with seven known triterpenoidcompounds, namely 2 α ,3 α ,19 α -trihydroxy-24-norurs4,12-dien-28-oic acid ( 6 ), 3 β ,23-dihydroxy-1-oxo-olean-12-en-28-oic acid ( 7 ), remangilone C ( 8 ), knoxivalic acid A ( 9 ), termichebulolide ( 10 ), rosasecotriterpene A ( 11 ), androsanortriterpene C ( 12 ), were extracted and separated from the dichloromethane part of Oenothera biennis L. The anti-pulmonary fibrosis activities of all the compounds against TGF- β 1-induced damage tonormal human lung epithelial (BEAS-2B) cells were investigated in vitro. The results showed that compounds 1- 2 , 6 , 8 , and 11 exhibited significant anti-pulmonary fibrosis activities, with EC 50 values ranging from 4.7 μM to 9.9 μM.

The outer steel tube in a concrete-filled steel tubular (CFST) column confines the core concrete and improves the compressive strength of the core concrete. When there is a notch damage in the tube, the confinement effect may be affected. The confinement effects of the notched steel tube in rectangular CFST columns were systematically investigated by using numerical approaches. Refined three-dimensional finite element models with advanced concrete constitutive relations were established. With the verified finite element modeling method, full-sized square CFST columns with horizontal, vertical, or diagonal notches at different locations of the steel tube were simulated. Stress distributions and deformation modes of the steel tube and core concrete were analyzed. Columns with a horizontal notch at the plate center location displayed a higher axial strength reduction than those with vertical notches. A parametric study was performed to investigate the influences of concrete strengths, steel strengths, steel ratios, notch length to column width ratios, and notch angles on the compressive strengths of the rectangular CFST columns. A practical design formula was proposed based on the obtained results. The proposed formula could effectively predict the influences of different notches on the confinement effect in the notched CFST columns.

Objective. Synthetic transmit aperture (STA) ultrasound imaging is well known for ideal focusing in the full field of view. However, it suffers from low signal-to-noise ratio (SNR) and low frame rate, because each transducer element must be activated individually. In our previous study, we encoded all the transducer elements with partial Hadamard matrix and reconstructed the complete STA dataset with compressed sensing (CS) algorithm (CS-STA). As all the elements are activated in each transmission and the number of transmissions is smaller than that of STA, this method can achieve higher SNR and higher frame rate. Its main drawback is the time-consuming CS reconstruction (∼hours). In this study, we propose to accelerate the complete STA dataset reconstruction with minimal l 2 -norm least squares method. Approach. Partial Hadamard apodized plane wave (PW) transmissions were performed to acquire the PW dataset. Thereafter, the complete STA dataset can be reconstructed from the PW dataset with minimal l 2 -norm least squares method. Due to the orthogonality of partial Hadamard matrix, the minimal l 2 -norm least squares solution can be easily calculated. Main results. The proposed method is tested with simulation data and experimental phantom and in-vivo data. The results demonstrate that the proposed method achieves ∼5 × 10 3 times faster reconstruction speed than CS algorithm. The simulation results demonstrate that the proposed method is capable of achieving the same accuracy as the conventional CS-STA method for the STA dataset reconstruction. The simulations, phantom and in-vivo experiments show that the proposed method is capable of improving the generalized contrast-to-noise ratio (gCNR) and SNR with maintained spatial resolution and fewer transmissions, compared with STA. Significance. In conclusion, the improved image quality and reduced computational time of LS-STA pave the way for its real-time applications in the clinics., (© 2022 Institute of Physics and Engineering in Medicine.)

The change of microvasculature is associated with the occurrence and development of many diseases. Ultrafast power Doppler imaging (uPDI) is an emerging technology for the visualization of microvessels due to the development of ultrafast plane wave (PW) imaging and advanced clutter filters. However, the low signal-to-noise ratio (SNR) caused by unfocused transmit of PW imaging deteriorates the subsequent imaging of microvasculature. Nonlocal means (NLM) filtering has been demonstrated to be effective in the denoising of both natural and medical images, including ultrasound power Doppler images. However, the feasibility and performance of applying an NLM filter on the ultrasound radio frequency (RF) data have not been investigated so far. In this study, we propose to apply an NLM filter on the spatiotemporal domain of clutter filtered blood flow RF data (St-NLM) to improve the quality of uPDI. Experiments were conducted to compare the proposed method with three different methods (under various similarity window sizes), including conventional uPDI without NLM filtering (Non-NLM), NLM filtering on the obtained power Doppler images (PD-NLM), and NLM filtering on the spatial domain of clutter filtered blood flow RF data (S-NLM). Phantom experiments, in vivo contrast-enhanced human spinal cord tumor experiments, and in vivo contrast-free human liver experiments were performed to demonstrate the superiority of the proposed St-NLM method over the other three methods. Qualitative and quantitative results show that the proposed St-NLM method can effectively suppress the background noise, improve the contrast between vessels and background, and preserve the details of small vessels at the same time. In the human liver study, the proposed St-NLM method achieves 31.05-, 24.49-, and 11.15-dB higher contrast-to-noise ratios (CNRs) and 36.86-, 36.86-, and 15.22-dB lower noise powers than Non-NLM, PD-NLM, and S-NLM, respectively. In the human spinal cord tumor, the full-width at half-maximums (FWHMs) of vessel cross Section are 76, 201, and [Formula: see text] for St-NLM, Non-NLM, and S-NLM, respectively. The proposed St-NLM method can enhance the microvascular visualization in uPDI and has the potential for the diagnosis of many microvessel-change-related diseases.

Purpose: As a typical chronic kidney disease (CKD), hypertensive nephrosclerosis (HN) is a common syndrome of hypertension, characterized by chronic kidney microvascular damage. Early diagnosis of microvascular damage using conventional ultrasound imaging encounters challenges in sensitivity and specificity owing to the inherent diffraction limit. Ultrasound localization microscopy (ULM) has been developed to obtain microvasculature and microvascular hemodynamics within the kidney, and would be a promising tool for the early diagnosis of CKD., Methods: In this study, the advantage of quantitative indexes obtained by using ULM (mean arterial blood flow speeds of different segments of interlobular arteries) over indexes obtained using conventional clinical serum (β2-microglobulin, serum urea nitrogen, and creatinine) and urine (24-h urine volume and urine protein) tests and ultrasound Doppler imaging (peak systolic velocity [PSV], end-diastolic velocity [EDV], and resistance index [RI]) and contrast-enhanced ultrasound imaging (CEUS; rise time [RT], peak intensity [IMAX], mean transit time [mTT], and area under the time-intensity curve [AUC]) for early diagnosis of HN were investigated. Examinations were carried out on six spontaneously hypertensive rats (SHR) and five normal Wistar-Kyoto (WKY) rats at the age of 10 weeks., Results: The experimental results show that the indicators derived from conventional clinical inspections (serum and urine tests) and ultrasound imaging (PSV, EDV, RI, RT, IMAX, mTT, and AUC) do not show significant difference between hypertensive and healthy rats (p > 0.05), while the TTP of the SHR group (28.52 ± 5.52 s) derived from CEUS is significantly higher than that of the WKY group (18.68 ± 7.32 s; p < 0.05). The mean blood flow speed in interlobular artery of SHR (12.47 ± 1.06 mm/s) derived from ULM is significantly higher than that of WKY rats (10.13 ± 1.17 mm/s; p < 0.01)., Conclusion: The advantages of ULM over conventional clinical inspections and ultrasound imaging methods for early diagnosis of HN were validated. The quantitative results show that ULM can effectively diagnose HN at the early stage by detecting the blood flow speed changes of interlobular arteries. ULM may promise a reliable technique for early diagnosis of HN in the future., (© 2022 American Association of Physicists in Medicine.)

Four new benzoylamide derivatives, lepidiumamide B-E ( 1 - 4 ), were isolated from the seeds of Lepidium apetalum Willd. The structures were determined by a combination of MS and NMR analyses. All compounds were evaluated for their protective effects against NRK-52e cell injury induced by lipopolysaccharide (LPS) in vitro. These compounds showed significantly protective activity and ameliorated LPS-induced NRK52e cells via the Nrf2/Keap1 pathway. The discovery of these active compounds is important for the prevention and treatment of renalinjury.

Compressed sensing-based synthetic transmit aperture (CS-STA) was previously proposed to recover the full radio-frequency (RF) channel dataset of synthetic transmit aperture (STA) from that of a smaller number of randomly apodized plane wave (PW) transmissions. In this way, the imaging frame rate (FR) and contrast are improved with maintained spatial resolution, compared with those of STA. Because CS-STA reconstruction is repeated for all receive elements and RF samples (with a high sampling frequency), the recovery of STA dataset in RF domain is time-consuming. In the meantime, a large amount of RF data needs to be transferred and stored, resulting in an increase of system complexity and required memory space. In this study, CS-STA is extended to in-phase/quadrature (IQ) domain (with lower sampling frequency) for the recovery of baseband STA IQ dataset to accelerate the CS-STA reconstruction by reducing the amount of data to be processed. More importantly, CS-STA reconstruction using IQ data is of practical importance, as clinical ultrasound systems typically record baseband IQ signal instead of RF signal. Simulations, phantom and in vivo experiments verify the feasibility of CS-STA in IQ domain for the recovery of STA dataset. More specifically, CS-STA using IQ data achieves similar image quality and appreciably improves reconstruction speed (by ∼3 times) compared with that using RF data. These findings demonstrate that IQ-domain CS-STA is capable of relieving the computational and storage burdens, which may facilitate the implementation of CS-STA in practical ultrasound systems., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A new polyacetylene glucoside, Dendranacetylene A (1), and a known compound 8E-decaene-4,6-diyn-1-O- β -d-glucopyranosyl-(1"→2")- β -d-glucopyranoside (2) were isolated from the flowers of Dendranthema morifolium (Ramat.) kitam. The chemical structures of these compounds were elucidated by NMR and HR-ESI-MS analysis, and comparing these results with data reported in literatures. Additionally, the anti-inflammatory effects of compounds 1 and 2 were evaluated on RAW264.7 murine macrophage cells induced by lipopolysaccharide (LPS). The two compounds significantly inhibited the NO production in LPS-induced RAW 264.7 murine macrophage cells and exhibited anti-inflammatory effects.

Rehmanniae Radix Praeparata is the processed products of the root of Rehmannia glutinosa. It has been used as a Traditional Chinese Medicine for thousands of years, and it has been found to possess widely pharmacological activities. In this study, three new 2,2'-difurylketone derivatives (rehmanniaeketone A-C) and two new chromones [3,8-dihydroxy-2-(2-hydroxyethyl)chromone and 3,8-dihydroxy-2-[(2-O-α-D-galactopyranosyloxy)ethyl]chromone] were isolated from the Rehmanniae Radix Praeparata. Furthermore all of the compounds were subjected to cytotoxic testing against the human lung carcinoma A549 cells. The cytotoxic results showed that rehmanniaeketone B and rehmanniaeketone C exhibited more stronger inhibition effects on the cell activity of A549 cells with the IC 50 5.23 μM and 2.05 μM than other compounds. And 3,8-dihydroxy-2-(2-hydroxyethyl)chromone exhibited moderately inhibitory activity with the IC 50 61 μM. Rehmanniaeketone A and 3,8-dihydroxy-2-[(2-O-α-D-galactopyranosyloxy]chromone showed no inhibitory effects., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Purpose: This research aims to investigate the intervention and mechanism of 50% acetone extract of C. officinalis leaves (SZYY) on melanoma xenografts., Patients and Methods: Tumor size and cardiac function were measured via ultrasound. The accumulation of 2-deoxy-D-glucose (2-DG) in tumor tissue was examined with near-infrared in vivo imaging. Flow cytometry was performed to assess apoptosis and reactive oxygen species (ROS) levels in tumor and immune cells in spleen. The levels of inflammatory cytokines in serum were detected by cytometric bead array. The expression of proliferation-, apoptosis-, and angiogenesis-related proteins in tumor cells was measured to evaluate the underlying mechanisms. Subsequently, the effects of four compounds separated from SZYY on the proliferation and migration of A375 cells and STAT3 signaling were examined. The peak identification and contents of the four components were performed via high-performance liquid chromatography (HPLC). Finally, we evaluated the inhibitory effects of STAT3 overexpression on the cytotoxic activity of four constituents in A375 cells., Results: SZYY inhibited the growth and glycolysis of melanoma xenograft in mice, improved cardiac function, increased the percentages of macrophages, neutrophils, and lymphocytes in spleen, reduced the levels of IL-6, IL-17A, TNF-α, and IFN-γ in serum, promoted apoptosis and oxidative stress in tumor tissues, and inhibited STAT3 phosphorylation and expression of angiogenic factors. Chemical analysis showed that SZYY is rich in loganin, rutin, triohimas C, and triohimas D, which all could restrain the proliferation and migration of A375 cells and inhibit the phosphorylation and nuclear translocation of STAT3. Moreover, STAT3 overexpression could diminish the cytotoxic activity of four compounds on A375 cells., Conclusion: SZYY could exert anti-melanoma effects via inhibiting STAT3 signaling to induce apoptosis and inhibit tumor angiogenesis. Its active ingredients might be loganin, rutin, triohimas C, and triohimas D., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Xu et al.)

Image reconstruction from radio-frequency (RF) data is crucial for ultrafast plane wave ultrasound (PWUS) imaging. Compared with the traditional delay-and-sum (DAS) method based on relatively imprecise assumptions, sparse regularization (SR) method directly solves the inverse problem of image reconstruction and has presented significant improvement in the image quality when the frame rate remains high. However, the computational complexity of SR is too high for practical implementation, which is inherently associated with its iterative process. In this work, a deep neural network (DNN), which is trained with an incorporated loss function including sparse regularization terms, is proposed to reconstruct PWUS images from RF data with significantly reduced computational time. It is remarkable that, a self-supervised learning scheme, in which the RF data are utilized as both the inputs and the labels during the training process, is employed to overcome the lack of the "ideal" ultrasound images as the labels for DNN. In addition, it has been also verified that the trained network can be used on the RF data obtained with steered plane waves (PWs), and thus the image quality can be further improved with coherent compounding. Using simulation data, the proposed method has significantly shorter reconstruction time (∼10 ms) than the conventional SR method (∼1-5 mins), with comparable spatial resolution and 1.5-dB higher contrast-to-noise ratio (CNR). Besides, the proposed method with single PW can achieve higher CNR than DAS with 75 PWs in reconstruction of in-vivo images of human carotid arteries., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

A new bisepoxylignan dendranlignan A (A1) and the known compound lantibeside D (D2) was isolated from Chrysanthemum Flower, the dried capitulum of Dendranthema morifolium (Ramat.) kitam. Their structures were determined on the basis of extensive spectroscopic methods, including 1D-NMR, 2D-NMR and MS data. Additionally, A1 and D2 were evaluated for their effects on the production of inflammatory mediators in H9c2 cardiomyocytes stimulated with lipopolysaccharide (LPS). Results demonstrated that A1 and D2 decreased LPS-induced production of inflammatory cytokines TNF-α, IL-2 and IFN-γ in H9c2 cells. Both compounds also decreased the nuclear localization of c-JUN, p-P65 and p-IRF3, but did not affect the level of TLR4. Molecular docking indicated that A1 and D2 occupied the ligand binding sites of TLR4-MD2. In the present study, we for the first time discovered a new bisepoxylignan compound A1, and found that this compound has a potential to inhibit inflammation by inhibiting TLR4 signaling., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Based on our previous research, a series of targeting hepatocellular carcinoma complexes, [R-Glycyrrhetinic acid-CH 2 C 2 H-[Co 2 (CO) 6 ] (R = H, 1; R = NSAIDs-COOH, 2-4; R = Aromatic acid, 5-7; R = Amino acid, 8-10), were synthesized. The test showed they are slow CO releasers. Using HeLa, A549, HT-29, SMMC7721 and HepG2 cells as models, their activities against tumor cell proliferation were firstly evaluated. The resulting data show all the complexes displayed a good anti-proliferation activity against the HepG2 and SMMC-7721 liver cancer cells, and their IC 50 values were in the range of 10.07-66.06 µM; compared with cis-platin (DDP), their activities were comparable or even better under the same condition. Among them, complexes 3, 4, 6 and 9 exhibited higher anti-proliferation activities against HepG2 and SMMC-7721 cell lines than the other cell lines. To confirm further these complexes have selectivity to the liver cells, the uptakes of complexes 3, 4, 6 and 9 by HepG2, HT-29, A549 and SMMC7721 cell lines were studied. The results show the cell uptake rates of the complexes by HepG2 cells and SMMC7721 cells were much greater than by other cells under the same condition. In following tests, the tested complexes displayed higher activities in inhibiting NF-kB, COX-2 and iNOS; and they induced HepG2 cells apoptosis by mitochondrial pathway, which assessed by staining with different fluorescent reagent DAPI, PI, Mito-Tracker Green and DCFH-DA. Meanwhile, the tested complexes up-regulated the expression levels of caspase-3 and Bax, down-regulated the Bcl-2 expression. In addition, they had no effect on zebrafish embryo survival, embryo hatching, embryonic movement, zebrafish malformation and zebrafish movement at below 0.5 µM. This suggests the complexes are potential candidates to be used in clinic for liver cancers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

H 2 S donors are substitutes of H 2 S with various biological activities like inhibiting the inflammatory response and protecting myocardial cells from injury. In order to confirm whether the H 2 S donors have drug-like properties, two series thiophosphamide H 2 S donors were evaluated including toxicity, bioactivity and pharmacokinetic properties in vivo and in vitro. The following results were obtained. Firstly, all the compounds released H 2 S under measuring condition; with the increase of pH value, the H 2 S release rate of all the compounds decreased and the amount reduced, but pH value had little effect on the maximum release of H 2 S. Secondly, in the organs and tissues of rats, the compounds released H 2 S in the same way as in PBS. In plasma, compound 1 reached the C max after administration 55 min, and no compound 1 was detected after 12 h; for compound 18, the C max reached only after administration 100 min, and after 6 h, compound 18 was not detected; in organs and tissues, the H 2 S-release rates were different from those in PBS, but the mechanism of H 2 S release was the same. Thirdly, in the test of toxicity, all the compounds displayed low toxicities to 5 cancer cells and W138 cell lines; compounds 1 and 18 had slight effect on the physiological tissue and function of rat liver at low concentration; the compounds had almost no effect on the hatching rate, survival rate of zebrafish embryos, and the spontaneous movement of zebrafish embryos at below 0.5 μM, but when they were over 1 μM, the compounds displayed inhibitory effect in the manner of concentration dependence. Fourthly, in the course of anti-inflammatory test, all the tested compounds significantly reduced the level of TNF-α and increased the level of IL-10; when they were 100 μM, the levels of IL-10 were three times as high as those in the control group. Among them, compounds 10 and 18 displayed stronger activities than the others. In addition, the compounds protected H9c2 cells from injure and improved myocardial injury through anti-oxidation pathway. In summary, the compounds have druglike properties due to low toxicity, better activity and good pharmacokinetic property. Therefore, they have potential to be as candidates to investigate further., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Based on the structures of nicotinic acid and chlorfibrate, a series of new H 2 S donors were synthesized and their anti-atherosclerosis activities using Ox-LDL RAW 264.6 cells as model were evaluated. The release test showed that all the compounds could release H 2 S effectively and showed low cytotoxicity. In the bioactivity experiments, compounds 1, 3, 9 and 14 increased the survival rate of HUVEC cells treated by ox-LDL; among four compounds, compounds 1 and 3 displayed higher activity than the others. In the foam cell model, compounds 1 and 3 were found to inhibit the formation of foam cells and significantly reduced the content of TC and FC in foam cells. They had more obvious effects on lipid reduction than those of nicotinic acid and chlorfibrate. In anti-oxidation, compounds 1 and 3 significantly reduced ROS and MDA and increased the expression level of SOD, whereas the precursor compounds, niacin and chlorfibrate had little antioxidant effect. In addition, both compounds also inhibited the inflammatory response in foam cells, with reducing pro-inflammatory factor TNF-α and increasing anti-inflammatory cytokine IL-10. WB assay showed that the tested compounds inhibited the expression levels PI3K, Akt and NF-κb proteins. In conclusion, the compounds as H 2 S donors could protect HUVEC cells from damage and inhibit the formation of foam cells by inhibiting PI3K/Akt/NF-κb signal pathway. All these suggest the compounds have potential to be candidate for anti-atherosclerosis medicines., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

On the basis of our previous study, the H 2 S donors based on nonsteroidal anti-inflammatory drugs (NSAIDs) were further evaluated with regard to the following aspects: animal blood and urine analyses, liver and kidney toxicities, gastrointestinal protection, anti-hypertension, and myocardial protection. The test results showed that after the successive administration of the compound for 14 days, the number of white blood cells in the blood of rats reduced, and protein and leukocytes appeared in urine; further, α-lipoic-acid-acetaminophen ester ( 1 ) and ibuprofen-ADTOH ester ( 2 ) had a certain effect on the physiological tissue and function of rat liver, and their side-effects on the kidneys were obvious. However, when compared with NSAIDs as the precursors, the tested compounds displayed much fewer side-effects; particularly, for the gastrointestinal mucosa of rats, there were hardly any side-effects. Moreover, all the three compounds decreased blood pressures in spontaneously hypertensive rats in a concentration-dependent manner, even though this antihypertensive effect was weaker than those induced by nifedipine and captopril. In addition, three compounds protected H9c2 cells from injury via an antioxidation pathway; and they improved myocardial injury in spontaneously hypertensive rats. Compound 2 is the derivative of ibuprofen and has lower toxicity to rat cardiomyocytes than ibuprofen. Therefore, it may become a better substitute of ibuprofen in patients due to its lower cardiotoxicity.

A series of H 2 SCO dual-donors [Mn(CO) 4 CS 2 NR 1 R 2 ] was synthesized, and evaluated from toxicity and bioactivity. The COH 2 S measuring test showed all the complexes not only released CO, but released H 2 S. The resulting data of cytotoxicity showed all the complexes had activities against the cell proliferation; among them, complexes 1, 2 and 7 displayed higher activities than the others, and their potencies were close to cis-platinum (DDP); whereas the precursors A 1 -A 22 had almost no activities against all five tumor cell lines and W138 cell line proliferation. It is worth noting that complex 1 displayed the highest activity to MCF-7, complex 2 displayed the highest activity to HePG2, and complex 7 showed selectivity inhibition to both A549 and HeLa. The developmental toxicities of the complex were assessed using zebrafish embryos. The results showed complexes 1 and 2 had effect on the mortality and hatching rate of zebrafish embryos in dose-dependent manner. They caused zebrafish malformations when they were over 10 μM. Meanwhile, they displayed dose-dependent toxicities to larval zebrafish. In the test of bio-activities, complexes 1 and 2 had strong anti-inflammatory activities; they not only down-regulated the expression levels of iNOS and TNF-α, up-regulated the expression of HO-1 and IL-10, but also up-regulated COX-2 levels. In contrast, the precursor compound (A 1 or A 2 ) displayed lower anti-inflammatory activity than the corresponding complex, which suggests both the CO and H 2 S from the complex took synergistic effects in the process of anti-inflammation. In addition, the complex showed antihypertensive effect and myocardial protection. This effect also possibly resulted from this synergistic effect. All these suggest the complexes have potential to be candidate medicines., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Ten uridine derivatives (lepidiumuridine B-K) were isolated from the seeds of Lepidium apetalum Willd. Lepidiumuridine B-J were previously undescribed compounds, and were structurally characterized using analysis of their NMR and MS data. Lepidiumuridine C, D, I, and J increased cell proliferation and expression of ERα in the MCF-7 cell line. In addition, blockage of ERα completely abolished cell proliferation and expression of ERα in MCF-7 cells, suggesting that the proliferation effects of lepidiumuridine C, D, I, and J were ERα-mediated. The uridine derivatives might belong to undescribed phytoestrogens., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

There has been great interest in phytoestrogens, which are polyhydric compounds that are derived from plants and have a structure similar to that of the mammalian steroid hormone 17 β -estradiol. The present study examined the estrogenic effects of a new natural uridine derivative, lepidiumuridine A (LA), that was isolated from the seeds of Lepidium apetalum . The structure was clarified and determined via analysis of extensive spectroscopic data interpretation. The activity of LA was investigated by measuring the levels of estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), and the uterus growth in mice. The proliferation experiment of MCF-7 breast cancer cells was also conducted. Western blot, in-cell western, and antagonist assays with methyl piperidino-pyrazole (MPP) were used for exploring the mechanism of the effects of LA. The results showed that LA elevated the uterine coefficient, the levels of E2, and FSH significantly. In addition, LA significantly elevated ER α expression in the uterus and MCF-7 cells. MPP inhibited the proliferation of LA-stimulated MCF-7 cell and ER α expression in MCF-7 cells. Taken together, LA had an estrogen-like effect, which was mainly mediated by the estrogen receptor ER α .

Hypoxic stressors contribute to neuronal death in many brain diseases. Astrocyte processes surround most neurons and are therefore anatomically well-positioned to shield them from hypoxic injury. Excitatory amino acid transporters (EAATs), represent the sole mechanism of active reuptake of glutamate into the astrocytes and neurons and are essential to dampen neuronal excitation following glutamate release at synapses. Glutamate clearance impairment from any factors is bound to result in an increase in hypoxic neuronal injury. The brain energy metabolism under hypoxic conditions depends on monocarboxylate transporters (MCTs) that are expressed by neurons and glia. Previous co-immunoprecipitation experiments revealed that MCT4 directly modulate EAAT1 in astrocytes. The reduction in both surface proteins may act synergistically to induce neuronal hyperexcitability and excitotoxicity. Therefore we hypothesized that astrocytes would respond to hypoxic conditions by enhancing their expression of MCT4 and EAAT1, which, in turn, would enable them to better support neurons to survive lethal hypoxia injury. An oxygen deprivation (OD) protocol was used in primary cultures of neurons, astrocytes, and astrocytes-neurons derived from rat hippocampus, with or without MCT4-targeted short hairpin RNA (shRNA) transfection. Cell survival, expression of MCT4, EAAT1, glial fibrillary acidic protein and neuronal nuclear antigen were evaluated. OD resulted in significant cell death in neuronal cultures and up-regulation of MCT4, EAAT1 expression respectively in primary cell cultures, but no injury in neuron-astrocyte co-cultures and astrocyte cultures. However, neuronal cell death in co-cultures was increased exposure to shRNA-MCT4 prior to OD. These findings demonstrate that the MCT4-mediated expression of EAAT1 is involved in the resistance to hypoxia injury in astrocyte-neuron co-cultures.

Objective: To compared 3 approaches to establishing Balb/c mouse models of hind-limb ischemia suitable for studies of regenerative medicine., Methods: Thirty eight-week-old male Balb/c mice were randomly divided into 3 groups for establishing models of hind-limb ischemia by both ligating and transecting the femoral artery proximal to the origin of the deep femoral artery branch, ligating the femoral artery proximal to the origin of the deep femoral artery branch, or ligating the femoral artery distal to the femoral artery trunk. The mice were continuously observed for 5 days after the operation, and hind-limb blood perfusion was monitored by laser Doppler imaging on the second postoperative day., Results: All the 3 surgical approaches caused blood flow block in the hind-limbs of the mice. In mice with ligation and transaction of the femoral artery proximal to the origin of the deep femoral artery branch, dry gangrene occurred in the whole hind-limb. Dry gangrene also occurred in the legs and paws of mice with ligation of the femoral artery proximal to the origin of the deep femoral artery branch. In mice with femoral artery ligation distal to the origin of the deep femoral artery branch, the sole of the foot was dry with scaling skin and necrosis of several digits; microscopically examination revealed a large quantity of necrotic muscles accompanied by muscle regeneration., Conclusion: Ligating the femoral artery distal to the origin of the deep femoral artery branch can be optimal for establishing Balb/c mouse models of hind-limb ischemia.