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Respiratory failure is one of the major causes of mortality and morbidity all over the world. Therapeutic options to treat respiratory failure remain limited. The objective of this study was to evaluate the gas transfer performance of a newly developed miniature portable integrated pediatric pump-lung device (PediPL) with small membrane surface for respiratory support in an acute ovine respiratory failure model. The respiratory failure was created in six adult sheep using intravenous anesthesia and reduced mechanical ventilation at 2 breaths/min. The PediPL device was surgically implanted and evaluated for respiratory support in a venovenous configuration between the right atrium and pulmonary artery. The hemodynamics and respiratory status of the animals during support with the device gas transfer performance of the PediPL were studied for 4 h. The animals exhibited respiratory failure 30 min after mechanical ventilation was reduced to 2 breaths/min, indicated by low oxygen partial pressure, low oxygen saturation, and elevated carbon dioxide in arterial blood. The failure was reversed by establishing respiratory support with the PediPL after 30 min. The rates of O2 transfer and CO2 removal of the PediPL were 86.8 and 139.1 mL/min, respectively. The results demonstrated that the PediPL (miniature integrated pump-oxygenator) has the potential to provide respiratory support as a novel treatment for both hypoxia and hypercarbia. The compact size of the PediPL could allow portability and potentially be used in many emergency settings to rescue patients suffering acute lung injury. [ABSTRACT FROM AUTHOR]

Background: Corheart 6 (Corheart) is a newly developed magnetically levitated continuous‐flow left ventricular assist device currently undergoing multicenter clinical trials in China. Featuring a small size, minimal weight, and low power consumption, the Corheart aims to improve pump hemocompatibility, reduce adverse events, and enhance the quality of life of heart failure patients. Methods: Computational simulations assessed flow field, shear stress, and washout, while in vitro and in vivo experiments were performed to further demonstrate hemocompatibility. Results: Numerical results show that the flow path in the Corheart blood pump is well designed. There is no significantly high shear stress in the majority of the flow domain. Short secondary flow paths and small pump size (small priming volume) provide good washing (0.049 and 0.165 s to remove 55% and 95% old blood, respectively), allowing low hemolysis levels both in computational and in vitro hemolysis tests (in vitro hemolysis index ranges from 0.00092 ± 0.00006 g/100 L to 0.00134 ± 0.00019 g/100 L). Good hemocompatibility was further evidenced by ten 60‐day sheep implants tested with relatively low flow rates of 2.0 ± 0.2 L/min; the results showed no hemolysis or thrombosis. Conclusions: Numerical and experimental results shed light on the fluid dynamics characteristics and hemocompatibility of the Corheart. It is believed that the Corheart will provide more promising possibilities for minimally invasive implantation techniques and for those patients with a small body surface area. [ABSTRACT FROM AUTHOR]

Abstract: Background: Large animal models serve as a critical link in the translation of basic science to clinical practice. However, large animal models of myocardial infarction (MI), especially large size MI, have been associated with high mortality because of arrhythmia. The prophylactic effect of amiodarone and lidocaine were retrospectively reviewed in our ovine MI model. Materials and methods: A total of 114 Dorset hybrid sheep with 25%–30% MI were included in the present study. The sheep were prophylactically treated with amiodarone plus lidocaine before ligation of the four to six coronary artery branches supplying the apex of the heart (arrhythmia prevention [AP] group, n = 45) and with epinephrine (shock prevention [SP] group, n = 49), respectively. The sheep without prophylactic treatment (no prevention [NP] group, n = 20) were used as the control group. The incidence of arrhythmia requiring treatment, mortality due to arrhythmia, hemodynamics, and arterial blood gas values during surgery were analyzed in these three groups. Results: No significant difference was found in infarct size among the three groups. The incidence of arrhythmia requiring treatment was significantly decreased in the AP group compared with that in the NP or SP groups (4.4% for AP versus 35% for NP and 45% for SP groups; P < 0.05). The mortality due to lethal arrhythmia was 2.2% in the AP group, significantly lower than that in the NP group (15%) or SP group (18.4%). Other than the heart rate, no significant differences were found in the hemodynamic data between the AP and NP groups. Metabolic acidosis was not observed in any group, as indicated by the pH and lactate values. Conclusions: Prophylactic amiodarone plus lidocaine decreased the mortality due to lethal arrhythmia after acute MI in our sheep model without significant negative effects on the hemodynamics. However, epinephrine improved the hemodynamics but also increased the mortality due to lethal arrhythmia. Thus, prophylactic amiodarone plus lidocaine is recommended to improve the stability in a large MI animal model. [Copyright &y& Elsevier]

BACKGROUND: The infant Jarvik 2000 heart is a very small, hermetically sealed, intracorporeal, axial-flow ventricular assist device (VAD) designed for circulatory support in neonates and infants. The anatomic fit, short-term biocompatibility and hemodynamic performance of the device were evaluated in a neonate piglet model. METHODS: The infant Jarvik 2000 heart with two different blade profiles (low- or high-flow blade design) was tested in 6 piglets (8.8±0.9 kg). Using a median sternotomy, the pump was placed in the left ventricle through the apex without cardiopulmonary bypass. An outflow graft was anastomosed to the ascending aorta. Hemodynamics and biocompatibility were studied for 6 hours. RESULTS: All 6 pumps were implanted without complication. Optimal anatomic positioning was found with the pump body inserted 2.4 cm into the left ventricle. Hemodynamics demonstrated stability throughout the 6-hour duration. The pump flow increased from 0.27 to 0.95 liter/min at increasing speeds from 18 to 31 krpm for the low-flow blade design, whereas the pump flow increased from 0.54 liter/min to 1.12 liters/min at increasing speeds from 16 krpm to 31 krpm for the high-flow blade design. At higher speeds, >80% of flow could be supplied by the device. Blood chemistry and final pathology demonstrated no acute organ injury or thrombosis for either blade design. CONCLUSIONS: The infant Jarvik 2000 heart is anatomically and biologically compatible with an short-term neonate piglet model. This in vivo study demonstrates the future feasibility of this device for clinical use. [ABSTRACT FROM AUTHOR]

Background: To provide long-term ambulatory cardiopulmonary and respiratory support for adult patients, a novel wearable artificial pump-lung device has been developed. The design features and in vitro and acute in vivo performance of this device are reported. Methods: This device features a uniquely designed hollow-fiber membrane bundle integrated with a magnetically levitated impeller that together form one ultracompact pump-lung device, which can be placed like current paracorporeal ventricular assist devices to allow ambulatory support. The device is 117 mm in length and 89 mm in diameter and has a priming volume of 115 ml. In vitro hydrodynamic, gas transfer and biocompatibility experiments were carried out in mock flow-loops using ovine blood. Acute in vivo characterization was conducted in an ovine model by surgically implanting the device between right atrium and pulmonary artery. Results: The in vitro results show that the device with a membrane surface area of 0.8 m2 was capable of pumping blood from 1 to 4 liters/min against a wide range of pressures and transferring oxygen at a rate of up to 180 ml/min at a blood flow of 3.5 liters/min. Standard hemolysis tests demonstrated low hemolysis at the targeted operating condition. The acute in vivo results also confirmed that the device can provide sufficient oxygen transfer with excellent biocompatibility. Conclusions: Based on in vitro and acute in vivo study findings, this highly integrated wearable pump-lung device can provide efficient respiratory support with good biocompatibility and it is ready for long-term evaluation. [Copyright &y& Elsevier]

Abstract: In recent years, utilizing nanoparticles as delivery system for drug targeting delivery has raised increasing interest. In this study, glycidyl methacrylate derivatized dextran (Dex-GMA) nanoparticles encapsulating basic fibroblast growth factor (bFGF) have been prepared inside the aqueous cores of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/n-hexane reverse micelles. These nanoparticles were identified to be uniformly spherical in shape with an average size of 109.57±2.09nm. And 90.2% of the nanoparticles were in a narrow size range of 80–110nm. The release of bFGF from the nanoparticles is completely and sustained as long as 35 days. The impact of the nanoparticles on mouse bone marrow mesenchymal stem cells (BMSCs) was assessed with cell cytotoxicity/viability and adhesion assay. Those studies show that the Dex-GMA nanoparticles prepared by water-in-oil micro-emulsion systems with aprotic solvent adding are novel, effective and biocompatible delivery system for bioactive protein. [Copyright &y& Elsevier]

Water body extraction can help eco-environmental policymakers to intuitively grasp surface water resources. Remote sensing technology can accurately and quickly extract surface water information, which is of great significance for monitoring surface water changes. Fengyun satellite images have the advantages of high time resolution and multispectral bands. This provides important image data suitable for high-frequency surface water monitoring. Based on Fengyun 3 medium resolution spectral imager (FY-3/MERSI) data, 7 methods were applied in this study, which include single-band threshold method, water body index method, knowledge decision tree classification method, supervised classification method, unsupervised classification method, spectral matching based on discrete particle swarm optimization (SMDPSO), and improved spectral matching based on discrete particle swarm optimization with linear feature enhancement (SMDPSO+LFE). These methods were used to extract the land surface water of Poyang Lake, check the samples from the Landsat image with similar times to the FY-3 images, and calculate the classification accuracy via the confusion matrix. The results showed that the overall classification accuracy (OA) of the SMDPSO+LFE is 97.64%, and the Kappa coefficient is 0.95. To analyze the stability of the surface water extracted by SMDPSO+LFE in different regions, this paper selected eight test sites with different surface water types, landscapes, and terrains to extract surface water. Based on an analysis of the land surface water results at the eight test sites, every OA in the eight sites was higher than 94.5%, the Kappa coefficient was greater than 0.88. In conclusion, the SMDPSO+LFE is found to be the most suitable method among the 7 methods and effectively distinguish between different surface water bodies and backgrounds with good stability. [ABSTRACT FROM AUTHOR]

Image registration plays a vital role in the mosaic process of multiple UAV (Unmanned Aerial Vehicle) images acquired from different spatial positions of the same scene. Aimed at the problem that many fast registration methods cannot provide both high speed and accuracy simultaneously for UAV visible light images, this work proposes a novel registration framework based on a popular baseline registration algorithm, ORB—the Oriented FAST (Features from Accelerated Segment Test) and Rotated BRIEF (Binary Robust Independent Elemental Features) algorithm. First, the ORB algorithm is utilized to extract image feature points fast. On this basis, two bidirectional matching strategies are presented to match obtained feature points. Then, the PROSRC (Progressive Sample Consensus) algorithm is applied to remove false matches. Finally, the experiments are carried out on UAV image pairs about different scenes including urban, road, building, farmland, and forest. Compared with the original version and other state-of-the-art registration methods, the bi-matching ORB algorithm exhibits higher accuracy and faster speed without any training or prior knowledge. Meanwhile, its complexity is quite low for on-board realization. [ABSTRACT FROM AUTHOR]

The scarcity of donor organs has led to the development of devices that provide optimal long-term respiratory or cardiopulmonary support to bridge recipients as they wait for lung and/or heart transplantation. This study was designed to evaluate the 30-day in vivo performance of the newly developed pediatric pump-lung ( PediPL) for cardiopulmonary support using a juvenile sheep model. The PediPL device was placed surgically between the right atrium and descending aorta in eight sheep (25.4-31.2 kg) and evaluated for 30 days. Anticoagulation was maintained with continuous heparin infusion (activated clotting time 150-200 s). The flow rate was measured continually, and gas transfer was measured daily. Plasma free hemoglobin, platelet activation, hematologic data, and blood biochemistry were assessed twice a week. Sheep were euthanized after 30 days. The explanted devices were examined for gross thrombosis. Six sheep survived for 30-32 days. During the study, the oxygen transfer rate of the devices was 54.9 ± 13.2 mL/min at a mean flow rate of 1.14 ± 0.46 L/min with blood oxygen saturation of 95.4% ± 1.7%. Plasma free hemoglobin was 8.2 ± 3.7 mg/dL. Platelet activation was 5.35 ± 2.65%. The animals had normal organ chemistries except for surgery-related transient alterations in kidney and liver function. Although we found some scattered thrombi on the membrane surfaces of some explanted devices during the necropsy, the device function and performance did not degrade. The PediPL device was capable of providing cardiopulmonary support with long-term reliability and good biocompatibility over the 30-day duration and offers the potential option for bridging pediatric patients with end-stage heart or lung disease to heart and/or lung transplantation. [ABSTRACT FROM AUTHOR]

Objective: Cardiogenic shock (CS) often occurs in patients suffering from rapidly progressing end‐stage heart failure or acute myocardial infarction. Mechanical circulatory support may be used for patients who do not respond to medication or revascularization to stabilize hemodynamics. Extracorporeal ventricular assist device (Extra‐VAD) has been reported to be successful for patients with cardiogenic shock. This study aimed to evaluate the 30‐day in‐vivo performance and safety of a newly developed Extra‐VAD with maglev centrifugal pump technology, MoyoAssist®. Method: The study was conducted with 6 healthy ovine models, weighing 43.2 ~ 59.6 kg. Cannulation was performed with a 34 Fr venous cannula surgically connected to the left arterial appendage and a 24 Fr arterial cannula inserted into descending aorta. The pump flow rate was maintained at 2 ~ 3 L/min to provide sufficient cardiac support without suction. Activated clotting time was maintained within the range of 150 ~ 250 s. Results: No device‐related adverse events occurred throughout the study. Plasma‐free hemoglobin results were within the acceptable range of ventricular assist device therapy (<40 mg/dl). MGS01 had an anticoagulation management related bleeding event and was terminated on day 29. All other sheep's biochemical test results were stable. The autopsy showed no embolism or thrombus formation and no end‐organ damage. Conclusion: This study demonstrated that the MoyoAssist® Extra‐VAD is able to provide cardiac support effectively and safely and may provide a new alternative choice for patients with CS in China. [ABSTRACT FROM AUTHOR]

Aims Shear stress-induced apoptosis is one of the leading problems in seeding cells of tissue-engineered blood vessels (TEBVs). We aim to determine the human bone mesenchymal stem cell (hBMSC) apoptosis under shear stress and its possible mechanism. Main methods hBMSCs were subjected to 3-, 10-, and 30-dyn/cm 2 shear stress in vitro. Cell multiplication and apoptosis were analyzed by flow cytometry. Apoptosis-related genes were screened by a microarray and evidenced by real-time polymerase chain reaction (RT-PCR). hBMSCs were treated with the human recombinant cell inhibitor of apoptosis protein 1 (cIAP1) and its inhibitor, direct IAP-binding protein with low pl (DIABLO), and then cell apoptosis was analyzed. Key findings Exposure to shear stress (3 dyn/cm 2 for > 6 h) activated apoptosis progress of hBMSCs. However, the same degree of shear stress (3 dyn/cm 2 for 6 h) did not induce apoptosis. Microarray screening and RT-PCR revealed that Bcl-2-related ovarian killer (BOK) and apoptotic protease-activating factor 1 (APAF1), key molecules of the mitochondrial apoptosis pathway, were markedly upregulated under 3-dyn/cm 2 shear stress. Then, we observed that cIAP1, a Caspase 9 inhibitor, was elevated under 3 dyn/cm 2 at short-time exposure (2 or 6 h), and it was reduced at long-time exposure (24 h). When treated with human recombinant cIAP1, Caspase 3 activity and LDH release of hBMSCs were decreased, and vice versa when treated with DIABLO. Significance cIAP1 attenuates hBMSC apoptosis when cells were exposed to shear stress through the regulation of the BOK–APAF1–Caspase 9–Caspase 3 pathway. It may present a pharmacological target to enhance hBMSC biological function in the application of TEBVs. [ABSTRACT FROM AUTHOR]

Abstract: Background: The underlying molecular mechanisms of the remodeling after myocardial infarction (MI) remain unclear. The purpose of this study was to investigate the role of a survival pathway (PI3K/Akt) and an apoptosis pathway (calcineurin/BAD) in the remodeling after MI in a large animal model. Methods: Ten Dorset hybrid sheep underwent 25% MI in the left ventricle (LV, n=10). Five sheep were used as sham control. The regional strain was calculated from sonomicrometry. Apoptosis and the activation of the PI3K/Akt and calcineurin/BAD pathways were evaluated in the non-ischemic adjacent zone and the remote zone relative to infarct by immunoblotting, immunoprecipitation, and immunofluorescence staining. Results: Dilation and dysfunction of LV were present at 12weeks after MI. The regional strain in the adjacent zone was significantly higher than in the remote zone at 12weeks (36.6±4.0% vs 9.5±3.6%, p< 0.05). Apoptosis was more severe in the adjacent zone than in the remote zone. The PI3K/Akt and calcineurin/BAD pathways were activated in the adjacent zone. Dephosphorylation and translocation of BAD were evident in the adjacent zone. Regional correlation between the strain and the expression of calcineurin/BAD indicated that the activation was strain-related (R 2 =0.46, 0.48, 0.39 for calcineurin, BAD, mitochondrial BAD, respectively, p <0.05). Conclusions: The PI3K/Akt survival and calcineurin/BAD apoptotic pathways were concomitantly activated in the non-ischemic adjacent zone after MI. The calcineurin/BAD pathway is strain related and its imbalanced activation may be one of the causes of progressive remodeling after MI. [Copyright &y& Elsevier]

Abstract: Aims: Evidence has indicated U50,488H, a selective κ-opioid receptor (κ-OR) agonist, administered before ischemia attenuates apoptosis and infarction during ischemia and reperfusion (I/R). However, it remains unclear whether U50,488H postconditioning reduces apoptosis during I/R. This study was designed, therefore, to test the hypothesis that U50,488H administered at the onset of reperfusion inhibits cardiomyocyte apoptosis and to investigate the underlying mechanisms. Main methods: Male Sprague–Dawley rats were subjected to myocardial ischemia and reperfusion(MI/R) and were randomized to receive either vehicle, U50,488H, U50,488H plus Nor-BNI, a selective κ-OR antagonist, U50,488H plus wortmannin, a specific inhibitor of phosphoinositide 3′-kinase (PI3K), or U50,488H plus L-NAME, a nitric oxide synthase inhibitor (NOS inhibitor), immediately prior to reperfusion. In vitro study was performed on cultured neonatal cardiomyocytes subjected to simulated ischemia/reperfusion. Key findings: Treatment with U50,488H resulted in increases in Akt and endothelial nitric oxide synthase (eNOS) phosphorylation with secondary NO production both in vivo and in vitro and these effect were completely blocked by wortmannin and specific Akt inhibitor(AI). L-NAME treatment had no effect on Akt and eNOS phosphorylation; but, significantly reduced NO production. Moreover, treatment with U50,488H markedly reduced myocardial apoptotic death. Treatment with wortmannin and specific Akt inhibitor abolished the anti-apoptotic effect of U50,488H. L-NAME also significantly attenuated the anti-apoptotic effect of U50,488H. Significance: These results demonstrate that U50,488H administered immediately prior to reperfusion increases Akt phosphorylation through a PI3-kinase-dependent mechanism and reduces postischemic myocardial apoptosis. Phosphorylation of eNOS with secondary NO production contribute significantly to the anti-apoptotic effect of U50,488H postconditioning. [Copyright &y& Elsevier]

As a pre-clinical assessment, the present study aimed to investigate the safety and effectiveness of a novel valved pulmonary arterial conduit constructed entirely from biomaterials by transplanting it in the outflow tract of the right ventricle in sheep. Under extracorporeal circulation, the valved pulmonary arterial conduit was used to replace the pulmonary artery of sheep with a beating heart. The performance was assessed at 30, 90 and 180 days post-surgery. Hemodynamic and structural changes were evaluated, and safety was assessed after 180 postoperative days. The hemodynamic effect and biosafety of the implant were further evaluated by observing the changes in various pressure indicators of the heart, echocardiographic results, anatomical and pathological examination results, liver and kidney functions, routine blood tests, a blood coagulation test, and other test results following implantation of the purely biotic valved conduit. The conduit was successfully implanted in 12 sheep and no mortality occurred postoperatively. During the 180-day follow-up, there was no obvious stenosis or regurgitation of the right ventricular outflow tract and pulmonary valve after valved conduit implantation. The findings of autopsy, pathology and laboratory examinations were unremarkable. The implantation of this biosynthetic vascular graft into animals meets the safety and effectiveness requirements for clinical application. This pulmonary arterial conduit has potential clinical application for children with complex congenital heart disease who require pulmonary artery reconstruction to achieve a radical cure. [ABSTRACT FROM AUTHOR]

[Display omitted] • The assumed multiple shallow mines are actually-two supergiant gold deposits with >1000 t Au reserves in Jiaodong gold province. • The geometric distribution of orebodies of deposits is related with kinematics of ore-controlling faults. • The Weideshan intrusive suite formed in 121.3–116.7 Ma provides thermodynamic conditions for gold mineralization. • The metallogenetic scenario for Jiaodong type gold deposits is referred as "thermal doming-extension metallogenesis". Based on the new deep exploration results, the gold reserves of Jiaojia gold deposit and Sanshandao gold deposit of the Jiaodong gold province, eastern North China Craton (NCC), exceed 1300 and 1200 tons, respectively. Both deposits are distributed along adjacent faults of Jiaojia and Sanshandao, respectively, forming a globally significant supergiant deposit. The main orebodies are preserved along two low-angle steps on the faults, with Jiaojia orebodies deposited in left-stepping bends, and Sanshandao orebodies deposited in right-stepping bends. The above geometric distribution of orebodies of these two deposits is clearly related to the kinematics of the ore-controlling faults. Weideshan suite is the largest Cretaceous magmatic rocks in the Jiaodong peninsula, which is considered as a profound impact on the gold mineralization in Jiaodong. LA-ICP-MS U-Pb dating of magmatic zircons from the associated Weideshan suite granitoid yields ages of 121.3 ± 2.1 Ma and 116.7 ± 1.7 Ma, which are consistent with mineralization age of the gold deposits (ca. 120 Ma). On the basis of regional geological data, our study indicates that the large-scale magmatic activities in the Early Cretaceous of Weideshan suite provide thermodynamic conditions for gold mineralization. A metallogentic model suggests that the formation of Jiaodong type gold deposits may have involved a thermal doming-extension process during the Mesozoic decratonization of NCC. In the Early Cretaceous, mantle upwelling and crust-mantle interaction triggered magmatism and fluid activities. These activities were simultaneous with granitoid doming, crustal extension and detachment faulting, upgrading Au of gold deposits. Mantle-derived gold-bearing fluid mixed with crust-derived gold-bearing fluid precipitated from remelting lower crust, forming gold-rich fluid reservoir and producing gold-poor Weideshan suite granitoid. Subsequently, granitoid doming, crustal extension and detachment faulting occurred. This process provides both favorable channels for ore-forming fluid migration and potential locations for enriching and trapping fluids, forming supergiant ore deposits. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the biocompatibility of a newly developed long-term wearable artificial pump-lung ( APL) in a clinically relevant ovine animal model. The wearable APL device was implanted in five sheep through left thoracotomy. The device was connected between the right atrium and pulmonary artery and evaluated for 30 days. Three sheep were used as the sham control. Platelet activation was assessed by measuring platelet surface P-selectin ( CD62 P) expression with flow cytometry and plasma soluble P-selectin with an enzyme-linked immunosorbent assay. Thrombotic deposition on the device components and hollow fiber membranes were analyzed with digital imaging and scanning electron microscopy. Surface P-selectin of the APL and sham groups changed significantly over the study period, but without significant differences between the two groups. Soluble P-selectin for the two groups peaked in the first 24 h after the surgery. Soluble P-selectin of the APL group remained slightly elevated over the study period compared to the presurgical baseline value and was slightly higher compared to that of the sham group. Plasma free hemoglobin remained in the normal ranges in all the animals. In spite of the surgery-related alteration in laboratory tests and elevation of platelet activation status, the APL devices in all the animals functioned normally (oxygen transfer and blood pumping) during the 30-day study period. The device flow path and membrane surface were free of gross thrombus. Electron microscopy images showed only scattered thrombi on the fibers (membrane surface and weft). In summary, the APL exhibited excellent biocompatibility. Two forms of platelet activation, surgery-related and device-induced, in the animals implanted with the wearable APL were observed. The limited device-induced platelet activation did not cause gross thrombosis and impair the long-term device performance. [ABSTRACT FROM AUTHOR]