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BACKGROUND: Carotid atherosclerosis plaque rupture is an important cause of myocardial infarction and stroke. The effective segmentation of ultrasound images of carotid atherosclerotic plaques aids clinicians to accurately assess plaque stability. At present, this procedure relies mainly on the experience of the medical practitioner to manually segment the ultrasound image of the carotid atherosclerotic plaque. This method is also time-consuming. OBJECTIVE: This study intends to establish an automatic intelligent segmentation method of ultrasound images of carotid plaque. METHODS: The present study combined the U-Net and DenseNet networks, to automatically segment the ultrasound images of carotid atherosclerotic plaques. The same test set was selected and segmented using the traditional U-Net network and the ResUNet network. The prediction results of the three network models were compared using Dice (Dice similarity coefficient), and VOE (volumetric overlap error) coefficients. RESULTS: Compared with the existing U-Net network and ResUNet network, the Dense-UNet network exhibited an optimal effect on the automated segmentation of the ultrasound images. CONCLUSION: The Dense-UNet network could realize the automatic segmentation of atherosclerotic plaque ultrasound images, and it could assist medical practitioners in plaque evaluation.

Background Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy. Methods Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel "BEL-7402+HUVEC" co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test. Results The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery. Conclusion CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.

Desertification and water body eutrophication are two severe environmental problems worldwide. To alleviate these two problems simultaneously, a new idea, introducing aquatic cyanobacteria (AC) fro...

Background Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. Methods HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15–20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE −−); otherwise, the image was labeled equivocal (LGE + −). Results In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman’s rho = 0.61, p Conclusions Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.

Cancer-associated fibroblasts (CAFs) play a crucial role in facilitating tumor invasion and metastasis, which act as the "soil" in the tumor microenvironment (TME). Accordingly, it would be a promising strategy to enhance the antitumor effect by killing both tumor cells and CAFs simultaneously. Herein, novel TME acid-responsive liposomes for co-delivery of IRI and 398 (IRI&398-s-LPs) were developed, in which the rapid release of both drugs could be triggered under acidic conditions. Notably, a CT-26/3T3 cell co-culture system was used to mimic the real TME both in vitro and in vivo. Cellular immunofluorescence revealed that IRI&398-s-LPs could efficiently decrease the activation of CAFs. In vitro cytotoxicity evaluation demonstrated that IRI&398-s-LPs exhibited higher cytotoxicity than the other liposomal formulations in the CT-26 and CT-26/3T3 cell co-culture system. In vivo NIRF imaging showed that the IRI&398-s-LPs could increase drug accumulation in the tumor sites. Furthermore, IRI&398-s-LPs not only presented superior in vivo anti-tumor activity in CT-26 bearing BALB/c mice, but also enhanced the effect in CT-26/3T3 cell bearing mice with decreased collagen and CAF biomarker expression. Furthermore, IRI&398-s-LPs also presented superior anti-metastatic efficiency in a lung metastasis model. These results indicated that this combinational strategy for eliminating both tumor cells and CAFs provides a new approach for cancer therapy, and the prepared TME-responsive liposomes for co-delivery of drugs hold promising clinical application prospects.

Tumour microenvironment provides the 'soil' for tumour growth. Besides tumour cells, there are also numbers of stromal cells, extracellular matrix and other components in the tumour microenvironment. In the past years, kinds of ligands and markers specifically high-expressed on the surface of the tumour stromal cells have been explored, which can be used as the therapeutic targets for cancer treatment. Recently, the antitumor drugs by targeting stromal cells, including small-molecular inhibitor and large-molecular monoclonal antibody, have been widely discovered and applied in clinic attributed to their specific targeting ability. Moreover, the targeted drug delivery system also paid more and more attentions due to their desired profiles in increased accumulation at tumour sites, enhanced antitumor ability and less toxicity and side effects. Therefore, it is of great significance to find and construct drug delivery systems targeting tumour stromal cells. In this review, we discussed the widely recognised therapeutic targets on tumour stromal cells, besides, the current status on the targeting drugs as well as the drug delivery systems were also highlighted.

The occurrence and distribution of 20 subtypes of antibiotic resistance genes (ARGs), conferring sulfonamide, tetracycline, macrolide, β-lactam, aminoglycoside, or quinolone antibiotic resistance, were investigated in urban dust samples collected from the surfaces of three megacities (Beijing, Tianjin, and Shijiazhuang) of northern China. Real-time polymerase chain reaction indicated that the abundance of ARGs and 16S rRNA genes was significantly higher in the summer than in the winter. A total of 80 antibiotic-resistant bacteria were isolated and identified, and 12 of those species were identified as opportunistic pathogens. An isolated pathogen Acinetobacter sp. was proven to be able to transfer antibiotic resistance, which highlights the potential risk that an urban dust-associated ARG poses to public health. Deep 16S rRNA sequencing indicated high heterogeneity of bacterial communities among cities in the summer, but great homogeneity in the winter. In the summer, Enterococcus, Massilia, and Anthrobac...

Peripheral nerves have emerged as the important components in tumor microenvironment (TME), which could activate hepatic stellate cells (HSCs) by secreting substance P (SP), leading to hepatocellular carcinoma (HCC) invasion and metastasis. Herein, we proposed a novel anti-HCC concept of blocking “SP-HSCs-HCC” axis for omnidirectional inhibition of HCC development. To pursue this aim, the novel CAP/GA-sHA-DOX NPs were developed for targeted co-delivery of capsaicin (CAP) and doxorubicin (DOX) using glycyrrhetinic acid (GA) modified sulfated-HA (sHA) as nanocarriers. Among that, CAP could inhibit the activation of HSCs as an inhibitor of SP. Notably, to real mimic “SP-HSCs-HCC” axis for in vitro and in vivo evaluation, both “SP + LX-2+BEL-7402” co-cultured cell model and “SP + m-HSC + H22” co-implantation mice model were attempted for the first time. Furthermore, in vivo anti-HCC effects were performed in three different tumor-bearing models: subcutaneous implantation of H22 or “SP + m-HSC + H22”, intravenous injection of H22 for lung metastasis, and orthotopic implantation of H22 for primary HCC. Our results showed that CAP/GA-sHA-DOX NPs could be efficiently taken up by tumor cells and activated HSCs (aHSCs) simultaneously, and effectively inhibit tumor drug-resistance and migration by blocking SP-induced HSCs activation. In addition, CAP/GA-sHA-DOX NPs exhibited low ECM deposition, less tumor angiogenesis , and superior in vivo anti-HCC effects. The anti-HCC mechanisms revealed that CAP/GA-sHA-DOX NPs could down-regulate the expression level of Vimentin and P-gp, reverse epithelial-mesenchymal transition (EMT) of tumor cells. In brief, the nano-sized combination therapy based on GA-sHA-DOX polymers could effectively inhibit drug-resistance and metastasis of HCC by blocking “SP-HSCs-HCC” axis, which provides a promising approach for cancer therapy.

Use of echocardiography to evaluate the characteristics of right heart and pulmonary artery of Tibetans with hepatic hydatidosis living in a high plateau area. We recruited 222 Tibetan adults diagnosed with hydatidosis from June 2016 to June 2017 in Shiqu and Seda areas of Tibet; 40 healthy control from the same area, denoted as the high plateau group. We also include 755 Healthy adults of Han nationality living in the plain from the EMINCA study as the low altitude group. Compared to high plateau group, hydatidosis individuals showed decreased RVADed, RVTDed, increased E(T)/A(T) and reduced RVFAC and TAPSE (p < 0.05). The 2 groups did not differ in the incidence rate of tricuspid regurgitation (TR) and pulmonary regurgitation (PR) (63.9% vs. 55.0%, p = 0.281 and 15.3% vs. 5.0%, p = 0.135, respectively) or incidence of pulmonary hypertension (PH) (13.9% vs. 20.5%, p = 0.167). PH risk did not differ between hydatidosis individuals and high plateau controls (OR 0.559, 95% CI 0.243-1.287). The RVADed and TAPSE were higher and E(T)/A(T) was lower for high plateau group than low altitude group (p < 0.05). The decreased right ventricular size and reduced diastolic and systolic function were found in Tibetans with hydatidosis. Hepatic hydatidosis had no significant effect on the incidence of pulmonary hypertension in Tibetans. Healthy Tibetans showed increased right ventricular size, decreased diastolic function, and increased systolic function compared to the Han counterparts.

Desertification and eutrophication are two global environmental problems human beings face. Inoculating cyanobacteria to form biocrusts is considered an effective technology to inhibit desertification. The main limitation of biocrust formation is the lack of propagules and nutrients in deserts. A possible low cost source of propagules and nutrients is eutrophic water containing aquatic cyanobacteria (AC), nitrogen and phosphorus. In this study, we fabricated a network-structured nanocomposite (designated as MC) using a metal-organic framework (MOF) and carboxymethyl cellulose (CMC). MC, with a large specific surface area and numerous surface groups, had a high retention capacity for water and nutrients and good biosafety. The combination of AC-containing water (ACW) and MC could provide a suitable microenvironment in the soil, promote the growth of desert cyanobacteria (DC), formation of biocrusts and inhibition of desertification. This study provides a novel approach to simultaneously relieve desertification and eutrophication.

The biocrust formation by cyanobacteria inoculation is considered to be a substantial and promising biotechnology method for combating desertification. However, due to the harsh ecological environment in desert, it is difficult to form stable biocrust quickly on sand surface. Herein, we fabricated a network-structured nanocomposite as nano-sand-stabilizer (named as AC) using attapulgite (ATP) and carboxymethyl cellulose (CMC). The AC with abundant ‒COOH and ‒OH had a high retention water capacity and could bind sand particles together through netting effect, providing a stable and suitable microenvironment for growth of mixed cyanobacteria (MC). A one-year field experiment confirmed that synergistic effect of AC and MC could improve the soil nutrition content and microbial structure, which was beneficial for biocrust formation and sand fixation. Therefore, this study provides a new method for fast sand fixation and promoting the biocrust formation, which could achieve the goal of sustainable desert restoration.

The aim of this study was to assess left ventricular (LV) energy loss (EL) using vector flow mapping in patients with prediabetes (pre-DM) and type 2 diabetes mellitus (DM). Thirty pre-DM patients, 51 DM patients, and 38 controls were studied by transthoracic echocardiography. EL-total, EL-base, EL-mid and EL-apex climaxed at different phases. Compared with controls, pre-DM and DM patients showed increased EL-total during slow ejection, isovolumic relaxation, rapid filling and slow filling (p < 0.05). Similarly, EL-base, EL-mid and EL-apex increased during certain phases. Stepwise multiple regression analysis revealed that the early transmitral valve blood flow velocity E, the late transmitral valve blood flow velocity A, the ratio of E/A, LV peak torsion, diastolic untwisting velocity, vortex circulation and area were independently associated with EL during different phases (all p

Objectives The present study aimed to investigate the effect of potent rosuvastatin therapy on plaque mechanical stabilization as seen on IVUSE. Methods 14 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 13, 7 rabbits received rosuvastatin (1.5 mg/kg/day), and the other 7 received an equal volume of saline. IVUS images of abdominal aortas were acquired, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Results Control rabbits showed a significant increase in shear strain (SS) and area strain (AS) in total plaques. The rosuvastatin group showed no change in SS and AS, but serum TG and LDL-C levels were reduced, with less lipid deposition, macrophage infiltration, production of proinflammatory cytokines and apoptosis in plaques. The changes in SS and AS from baseline between groups significantly differed (SS: 1.15 (1.96) % vs. −0.99 ± 2.83%, p = 0.013; AS: 1.25 (2.29) % vs. −1.67 ± 5.05%, p = 0.022). At follow-up, for controls, strain values were increased in the shoulder of eccentric plaques (SS: 2.66 ± 1.31% vs. 4.86 ± 1.93%, p = 0.016; AS: 4.45 ± 2.33% vs. 7.91 ± 2.74%, p = 0.009) but not the plaque body. Changes in SS and AS in the plaque shoulder differed between the control and rosuvastatin groups (SS: 2.20 ± 2.17% vs. −0.87 ± 3.31%, p = 0.028; AS: 2.10 (4.61) % vs. −2.75 ± 5.97%, p = 0.009). Conclusion Rosuvastatin therapy in rabbits with atherosclerotic plaques led to less vulnerable plaque features. IVUSE is a very sensitive technique for detecting pharmacologically-induced mechanical changes in rabbit atherosclerotic plaques.

Nano-based drug delivery systems have been widely applied in cancer therapy, among that, particle sizes may affect the delivery efficiency of nanocarriers. The purpose of this study was to evaluate the potential impacts of particle size on tumor therapy, in consideration of this, lipid/glycocholic acid mixed micelles (LGs) were designed as the model nanocarriers. Doxorubicin (DOX) loaded LGs with two different particle sizes at around 10 nm and 100 nm, respectively, were successfully prepared by controlling the ratio of EPC to GAH. In vitro release study showed that the release behaviors of DOX in mixed micelles with two different particle sizes was basically consistent and showed sustained release. DOX-LGs at 10 nm exhibited higher cellular uptake capacity, compared with DOX-LGs at 100 nm. Besides, in vivo NIFR imaging also demonstrated that DOX-LGs at 10 nm had more accumulation in tumor site. Furthermore, DOX-LGs at 10 nm presented both higher in vitro cytotoxicity and superior in vivo antitumor activity than that of 100 nm. In vivo safety evaluations showed that the mixed micelles had lower toxicities than free DOX solution formulations. These results indicated that the nanoparticles with smaller particle size could improve the profiles in cellular uptake, tumor accumulation as well as anti-tumor efficacy, which would provide a theoretical principle for the design of nanoparticles.

Archaea are major contributors to biogeochemical cycles and energy metabolism among soil microorganisms under extremely acidic and high-temperature conditions, however, the biodiversity and ecological function of archaea in biological soil crusts (BSCs) of desert ecosystems are not fully understood. Here, we used Illumina MiSeq sequencing and microbial functional gene array (GeoChip 5.0) to test the following hypotheses: (1) the composition and function related to biogeochemical cycles of the archaeal community would change significantly in the development process of BSCs; and (2) the key factors driving these changes may be soil biogeochemical properties. The results showed that the diversity, abundance, and functional potential of the archaeal community showed their highest levels in 5-year-old BSCs. The dominant phyla were Thaumarchaeota, Euryarchaeota, and an unclassified phylum in the archaeal community during BSC succession. The functional genes of the archaeal community were mainly involved in carbon (C) and nitrogen (N) cycles, and the functions of the three dominant phyla were complementary in these cycles. Moreover, redundancy analysis showed that soil biogeochemical properties were negatively related to the composition and function of the archaeal community during BSC succession, and the soil C:N ratio might be the major limiting factor. These results provided evidences for our hypotheses and revealed that the archaeal community played an important ecological role in the early development stage of BSCs, and might be pioneer species of soil microbial communities during BSC succession.

To assess the elastic mechanical properties of atherosclerotic plaque with different morphological properties by intravascular ultrasound elastography (IVUSE). 30 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 12, 2 plaques with moderate echo from each rabbit were chosen for in situ imaging, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Shear strain (SS) and area strain (AS) were greater for eccentric than centripetal plaque (SS: 2.65(2.45)% vs. 1.79 ± 0.97%, p

The present study was to investigate in vitro the rat cardiomyocyte injury with targeting of home-made perfluorocarbon lipid particles with avidin-biotin interaction. Neonatal rat cardiomyocytes were cultured in vitro and divided into two groups: TNF-alpha activated group and non-activated group. Those in the TNF-alpha activated group were exposed to 200 ng/ml TNF-alpha solution for 6 hours and then cardiomyocytes in both groups were pretargeted with biotinylated ICAM-1 monoclonal antibodies, and were exposed to streptavidin, and then to homemade green fluorescently-labeled biotinylated perfluorocarbon lipid particles. Cardiomyocytes nucleus stained with Hoechst. The results were detected with fluorescence microscope. As a result, in TNF-alpha activated group, around blue fluorescent cardiomyocytes nucleus, a great amount of green fluorescent particles were found, while there were few green fluorescent particles in non-TNF activated group. It has been shown that ICAM-1 is expressed in the surface of cardiomyocytes when they are stimulated by TNF-alpha. Perfluorocarbon lipid particles associated with ICAM-1 monoclonal antibodies can be targeted to injured cardiomyocytes by avidin-biotin interaction.

To analyze longitudinal motion of infarcted myocardium and ischemic myocardium with a new echocardiographic technology of velocity vector imaging (VVI), and to assess its accuracy.From December 2007 to January 2008, 6 patients suffered acute anterior myocardial infarction (MI group), 9 patients had myocardial ischemia (over 70% stenosis of anterior descending branch, MS group) and 16 healthy subjects (control group) were included. The long axis view and 2-chambers view of left ventricle at the apex of heart were acquired with Siemens Sequoia 512 ultrasound system. The longitudinal velocity, displacement, strain and strain rate were analyzed with off-line Syngo US workplace software.In normal myocardial group, longitudinal peak systolic velocity (Vs) and peak displacement (D) decreased progressively from base level to apex level in anterior wall and anterior septum (P0.05), while peak strain (S) and peak systolic strain rate (SRs) kept the same in three levels (P0.05). S and SRs significantly decreased in all segments of infarcted myocardium (P0.05), compared with normal and ischemic myocardium. In ischemic myocardium, only base and middle segmental S of anterior wall decreased (P0.05). A myocardial S lower than -6.94% in at least one ventricular segment showed best sensitivity (100%) and specificity (100%) for detecting an infarcted left ventricle. A myocardial SRs lower than -0.81% at least in one ventricular segment showed 100% sensitivity and 80% specificity, and lower than -0.46% showed 83% sensitivity and 100% specificity.VVI is a useful tool for assessing myocardial regional function. Especially, S and SRs are useful predictors of the presence of regional dysfunction in infarcted myocardium.

The present study aimed to investigate the association between potent rosuvastatin therapy and plaque mechanical stabilization imaged by IVUSE. 14 purebred New Zealand rabbits underwent a high-cholesterol diet, then balloon-induced abdominal aorta endothelium injury after 2 weeks. Seven rabbits