Search

Aims Methods Results Conclusion We aimed to investigate antibacterial‐induced thrombocytopenia using the China Hospital Pharmacovigilance System (CHPS) in conjunction with Visual Basic for Applications (VBA).Between September 2011 and December 2022, a 2‐phase workflow was employed to identify antibacterial‐induced thrombocytopenia, including preliminary screening in phase (I) conducted by CHPS algorithms and causality assessment by trained pharmacists in phase (II) using VBA. The incidence of thrombocytopenia in each antibacterial was calculated, and comparisons were performed between paediatric and adult patients.CHPS algorithms identified 4080 cases from 485 238 admissions (including 223 735 admissions receiving at least 1 antibacterial treatment). After ruling out cases with chemotherapy and abnormal platelet count at admission, 3832 cases were available. Using VBA, pharmacists identified 1039 cases (1246 antibacterial treatments, 28 agents) as potential thrombocytopenia instances (κ = 0.89), with an incidence of 0.46%. All antibacterial treatments correlated temporally with thrombocytopenia. Carbapenems (meropenem 1.77%), glycopeptides (vancomycin 1.55%) and lincosamides (clindamycin 0.44%) were prominent causal groups. The highest incidences of thrombocytopenia in the cephalosporins and penicillins groups were ceftazidime (2.04%) and piperacillin/tazobactam (1.24%), respectively. Among all antibacterial treatments, clindamycin showed the shortest time to onset (TTO), and erythromycin showed the longest TTO. Paediatric patients exhibited a longer TTO (61 vs. 29 h), extended time to nadir (83 vs. 37 h), lower platelet nadir count values (110 vs. 92 × 109/L), and a higher severe case proportion (12.37 vs. 3.86%) when compared with adults.Different antibacterial agents exhibit varying incidences of thrombocytopenia, with notable disparities between adults and children in the characteristics of thrombocytopenia. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p =.021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31–2.64]; p =.001), hepatic function abnormal (OR 2.75 [1.69–4.48]; p <.001), dyslipidaemia (OR 5.15 [1.87–14.13]; p =.001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management. [ABSTRACT FROM AUTHOR]

• Pyrolysis liquid (PL) of pine was innovatively used as depressant of pyrite. • PL can suppress pyrite recovery to below 10%, while galena recovery is almost unaffected. • The main functional components of PL are phenols demonstrated by TOF-SIMS and GCMS. The pyrolysis liquid of pine (PL) had a significant depression effect on pyrite, but its effect on galena was minimal. Within the pH range of 8.0–10.0, the recovery of pyrite was below 10 % upon the addition of 200 mg/L PL, whereas that of galena remained above 90 %. XPS analysis showed that the main functional groups adsorbed on the pyrite surface were C–OH and C O. TOF-SIMS analysis showed that substances containing hydroxyl groups were adsorbed on the pyrite surface. GCMS analysis indicated that the main functional components of PL were phenols. PL has great potential for use in galena and pyrite flotation separation, to achieve high-value utilization of the pyrolytic solution. [ABSTRACT FROM AUTHOR]

• Under the action of the CO 2 jet, the stress value of the rock is more likely to reach its tensile limit, resulting in the chips being peeled off from the main body more easily. • The high-pressure CO 2 jet has a positive effect on carrying rock debris. • In composite rock breaking, the optimal range of nozzle diameter is 1.5 mm, the best injection angle of CO 2 jet is 90°, the optimal stand-off distance is 20 mm. To address the low efficiency and severe thermal wear of drill bits in geothermal drilling, CO 2 (carbon dioxide) jet drilling as a new method is proposed. However, the rock-breaking and debris flow of composite rock-breaking of high-pressure CO 2 &PDC cutter in CO 2 jet drilling are crucial problems and remain unclear. Therefore, we established a discrete element model of composite rock-breaking, validated with experimental results. The rock-breaking and debris flow are investigated from the perspectives of the cutting force, rock stress and crack generation. Additionally, many impacting factors, including the stand-off distance, injection angle, nozzle diameter, and jet impact velocity, are investigated. Research results indicate that both PDC cutting and high-pressure CO 2 jet impacting would apparently contribute to the rock stress increment and crack propagation. Meanwhile, the CO 2 jet obviously contributes to rock debris carrying, consistent with the observation from high-speed photography experimental results. The affecting parameters are investigated using the discrete element method (DEM), and the findings show that the optimal values are, respectively, 90° at jet injection angle, 50 m/s at CO 2 jet velocity, 1.5 mm at nozzle diameter, and 20 mm at stand-off distance. Moreover, the jet velocity and nozzle diameter are the most influential parameters among all influencing parameters. These studies clearly illustrate the rock-breaking and debris, which are helpful for the CO 2 drilling improvement and drill bits designing for geothermal wells. [ABSTRACT FROM AUTHOR]

In this study, the pyrolysis liquid of pine (PLP) was used as a novel depressant to separate fluorite from calcite. Flotation experiments revealed that the PLP can depress the flotation of calcite, whereas its impact on fluorite was minimal. Fourier transform infrared (FTIR) spectroscopy showed that the substance adsorbed onto calcite surface hindered oleate adsorption onto calcite, but had minimal impact on fluorite. Gas chromatography-mass spectrometry analysis results presented that the main components of PLP were phenols, aldehydes, furans, and ketones. Among them, catechol and other phenolic compounds played major roles in the depression of calcite as revealed by FTIR and time-of-flight secondary ion mass spectroscopy. The increased phenol content resulted in a more pronounced depressant effect of PLP prepared at 800 °C on calcite compared with that of PLP prepared at 500 °C. This study provides a new perspective on the potential application of pyrolysis fluid in mineral flotation. [Display omitted] • Pyrolysis liquid of pine (PLP) was innovatively used as depressant in ore flotation filed. • PLP can reduce calcite recovery to below 10%, while the fluorite recovery is above 90%. • The main active components in PLP were phenols and furaldehydes. • PLP selectively adsorb on calcite surface and prevents the collector adsorption. [ABSTRACT FROM AUTHOR]

Supercritical Carbon Dioxide (SC-CO 2) fracturing can increase shale gas production and reduce carbon dioxide (CO 2) emission. In order to enhance shale fracturing, a new method of multi-times pulse SC-CO 2 jet fracturing is proposed and comprehensively studied. The results demonstrate there are more initiation positions and more complex fracture network after pulse SC-CO 2 jet fracturing due to strong impingement and pressurization. Furthermore, three types of main fracture and four types of fracture branch are observed. The main fractures mostly initiate from perforation and propagate with irregular path to the specimen edge. CO 2 absorption and fracture volume increase 77.72% and 2283%, respectively, more than that of single-pulse SC-CO 2 jet fracturing. The comparison indicates that SC-CO 2 creates more complex fracture morphology, larger fracture volume and CO 2 absorption than that of water. Moreover, the effect of influential factors, including pulse jet frequency, pulse jet pressure and pulse jet distance, are discussed thoroughly. Thus, this study provides a method of jet fracturing enhancement, and is instructive for understanding and tackling pulse jet fracturing issue related to CO 2 utilization and fracturing of shale reservoir. The method of multi-times pulse SC-CO 2 jet fracturing is proposed, and comprehensive experimental studies are conducted. The multi-times pulse SC-CO 2 jet fracturing can cause more complex fracture morphology, larger fracture volume and CO 2 absorption than that of pulse water jet fracturing, due to its low viscosity, high diffusion and compressible characteristic of SC-CO 2. Image 1 • Multi-times pulse SC-CO 2 jet fracturing was firstly proposed and studied in our manuscript. • The fracture number and fracture tortuosity increase when jet pressure and jet frequency are larger. • The multi-times pulse SC-CO 2 jet fracturing can cause more complex fracture morphology than that of water. • The frequency of pulse SC-CO 2 jet fracturing is important for the complexity of fracture. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have proven to be involved in the progression of atherosclerosis and dyslipidemia. In addition, vascular smooth muscle cells (VSMCs) phenotype switching, including VSMCs-derived foam cells formation, plays a key role in the pathogenesis of atherosclerosis. LncRNA ENST00000602558.1, one of the differentially expressed lncRNAs between coronary artery disease (CAD) patients and healthy controls identified by our previous study, was located to TG and HDL susceptibility loci, but its role and underlying mechanism in the pathogenesis of atherosclerosis remain unclear. The present study aims to explore the role and underlying mechanism of ENST00000602558.1 in the regulation of cholesterol efflux from VSMCs. ABCG1 mRNA and protein expression in VSMCs was detected using qRT-PCR and Western blot, respectively. ABCG1-mediated cholesterol efflux to HDL from VSMCs was measured by means of NBD-cholesterol fluorescence intensity. The binding of ENST00000602558.1 to p65 and p65 to ABCG1 promoter region was detected by RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively. Overexpression of ENST00000602558.1 downregulated ABCG1 mRNA and protein expression, while knockdown of ENST00000602558.1 upregulated ABCG1 mRNA and protein expression. Consistently, ENST00000602558.1 overexpression decreased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.38% (p < 0.001), and knockdown of ENST00000602558.1 increased ABCG1-mediated cholesterol efflux to HDL from VSMCs by 30.41% (p = 0.001). In addition to cholesterol efflux, overexpression of ENST00000602558.1 increased lipid accumulation and TC/TG levels, while knockdown of ENST00000602558.1 decreased lipid accumulation and TC/TG levels in VSMCs. Furthermore, we confirmed that ENST00000602558.1 regulated ABCG1 expression and ABCG1-mediated cholesterol efflux from VSMCs through binding to p65. In conclusion, ENST00000602558.1 played an important role in mediating cholesterol efflux to HDL from VSMCs by regulating ABCG1 expression through binding to p65. Image 1 • ENST00000602558.1 specifically regulated ABCG1 expression in VSMCs. • ENST00000602558.1 regulated ABCG1-mediated cholesterol efflux to HDL from VSMCs, but not ABCA1-mediated cholesterol efflux to apoA1. • ENST00000602558.1 regulated ABCG1 expression and ABCG1-mediated cholesterol efflux from VSMCs through binding to p65. [ABSTRACT FROM AUTHOR]

Abstract We developed a framework to predict and model the photodegradation of adhesion and cohesion of a silicone encapsulant for concentrator photovoltaic applications. Silicone encapsulant specimens were artificially weathered under narrow band UV filters to determine the effects of individual wavelengths within the UV spectrum on the photodegradation of the cohesion of encapsulant material and its adhesion with adjacent interfaces. The threshold wavelength, signifying the upper bound of the damaging action spectrum for the silicone, was identified from the results. In addition, specimens were artificially weathered with different relative humidities to understand the effects of moisture on the rate of photodegradation. The adhesion energy was measured using a fracture mechanics approach. The complementary delaminated surfaces were characterized to determine the failure pathway and chemistry changes resulting from photodegradation. A previously developed model was modified to account for the effects of damaging wavelengths in the terrestrial solar spectrum and reciprocity law failure due to varying UV intensity during weathering. With these modifications, the model showed good agreement with the behavior of the silicone encapsulant exposed in an outdoor solar concentrator simulating concentrator photovoltaics operating conditions. Similar studies can be adopted to develop models that can have high predictive accuracies based on accelerated aging studies. Highlights • Silicone based encapsulant degrades and embrittles from solar exposure. • Threshold wavelength for causing UV degradation of silicone encapsulant is 350 nm. • Adhesion energy drops by over 2 orders of magnitude following degradation. • Adhesion energy can be modeled as a function of temperature and solar irradiance. [ABSTRACT FROM AUTHOR]

The cleavage and secretion of pro-inflammatory cytokines IL-1β and IL-18 is regulated by NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome activation. Kupffer cells (KCs) are implicated in the pathogenesis of various liver diseases, such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and liver fibrosis. However, the role of NLRP3 played in the non-alcoholic steatohepatitis (NASH) has yet to be evaluated. In the present study, methionine-choline-deficient (MCD) diet was used to establish the mice NASH model. The expression levels of F4/80 and NLRP3 in liver tissues were evaluated, and the IL-1β and IL-18 in serum were also evaluated. KCs were isolated from wild-type (WT) mice and NLRP3 knockout (NLRP3) mice and then randomly divided into two groups: the control and palmitic acid (PA) groups. The expression levels of NLRP3, ASC, and caspase-1 in KCs were determined by RT-PCR, western blotting, and immunofluorescence. The levels of IL-1β and IL-18 in the supernatant (SN) of KCs were evaluated by enzyme-linked immunosorbent assay (ELISA). We found that KCs and NLRP3 play pro-inflammatory roles in the progression of NASH, probably through secretions of IL-1β and IL-18 by KCs induced by PA. PA could act as a kind of damage-associated molecular patterns to elevate the messenger RNA and protein expression levels of NLRP3, ASC, and caspase-1 in KCs from WT mice. In the contrast, NLRP3 deletion could inhibit the NLRP3 inflammasome upregulation and activation in KCs induced by PA. Furthermore, the levels of pro-inflammatory cytokines IL-1β and IL-18 in the SN of KCs from WT mice were all elevated with the stimulation of PA, and the increase of these cytokines in the SN was blocked by NLRP3 deletion. In conclusion, our novel findings demonstrate that NLRP3 plays a pivotal role in NASH development and pro-inflammatory cytokines IL-1β and IL-18 secretion induced by PA stimulation, and NLRP3 might be an effective potential target for the treatment of liver inflammatory diseases associated with NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) and its causal factors of hepatic insulin resistance (IR) and type 2 diabetes are rapidly growing worldwide. Developing new therapeutic methods for these conditions requires a comprehensive understanding between hepatic lipid metabolism and IR. Sterol regulatory element-binding transcription factor 1c (SREBP-1c) and carbohydrate responsive-element binding protein (ChREBP) are the major regulators of fatty acid synthase (FASN), a key enzyme of de novo fatty acid synthesis. They are induced by insulin, which directly binds to the sterol regulatory elements (SRE) or carbohydrate-responsive elements (ChORE) of the FASN promoter to induce its expression. The insulin pathway involved in NAFLD has well studied, but the role of histone modification in NAFLD is just beginning to be investigated, and there is minimal data regarding its involvement. In the current study, we investigated histone modifications in FASN under insulin stimulation. H3K4 hypertrimethylation and H3, H4 hyperacetylation in the FASN promoter was found in HepG2 cells and primary hepatocytes following insulin stimulation. We also found that insulin treatment induced the transcription factor SREBP-1c, ChREBP and could accelerate FASN expression by enhancing SREBP-1c, SRE, and ChREBP ChORE binding and inducing H3, H4 hyperacetylation at SRE, ChORE, or transcription start site (TSS) regions of the FASN promoter in hepatocellular carcinoma cell line (HepG2) and primary hepatocytes. Finally, histone acetylation could influence FASN expression by impairing SREBP-1c SRE and ChREBP ChORE binding. [ABSTRACT FROM AUTHOR]

Concentrator photovoltaic (CPV) modules operate in extreme conditions, including enhanced solar flux, elevated operating temperature, and frequent thermal cycling. Coupled with active environmental species such as oxygen and moisture, the operating conditions pose a unique materials challenge for guaranteeing operational lifetimes of greater than 25 years. Specifically, the encapsulants used in the optical elements are susceptible to environmental degradation during operation. For example, the interfaces must remain in contact to prevent optical attenuation and thermal runaway. We developed fracture mechanics based metrologies to characterize the adhesion of the silicone encapsulant and its adjacent surfaces, as well as the cohesion of the encapsulant. Further, we studied the effects of weathering on adhesion using an outdoor concentrator operating in excess of 1100 times the AM1.5 direct irradiance and in indoor environmental chambers with broadband ultraviolet (UV) irradiation combined with controlled temperature and humidity. We observed a sharp initial increase in adhesion energy followed by a gradual decrease in adhesion as a result of both outdoor concentrator exposure and indoor UV weathering. We characterized changes in mechanical properties and chemical structures using XPS, FTIR, and DMA to understand the fundamental connection between mechanical strength and the degradation of the silicone encapsulant. We developed physics based models to explain the change in adhesion and to predict operational lifetimes of the materials and their interfaces. [ABSTRACT FROM AUTHOR]

Abstract: Non-alcoholic fatty liver disease (NAFLD) has emerged as a common public health problem that can progress to end-stage liver disease. Although the function of aquaglyceroporin-9 (AQP9) as a glycerol channel has been proven, the mechanism of AQP9 in the development of NAFLD is poorly understood. To investigate the effect of hepatic glycerol uptake inhibition, we utilized a lentivirus-associated RNA interference technique to knock down the expression of hepatic AQP9 in high fat diet (HFD)-induced NAFLD in rodents. Male Sprague–Dawley rats were fed with a standard chow diet or HFD for 8weeks. Rats fed a HFD were separated into 3 groups: HFD, control and transfection group, which were injected with equivalent amounts of PBS, lentivirus-scramble and lentivirus-shRNA-AQP9 through the hepatic portal vein. The results showed a remarkable decrease in the expression of AQP9 mRNA and protein in liver for the transfection group. Furthermore, less hepatic steatosis occurred when compared to the HFD and control groups after 8weeks. Our results indicate a potential role for AQP9 in the pathogenesis of hepatic steatosis. [Copyright &y& Elsevier]

Abstract: The simulation of exit wavefunctions of a TEM sample is carried out by both the conventional multislice (C-MS) method and the real space multislice (RS–MS) method, with a series of different slice thicknesses. Surprisingly, the results calculated by the RS–MS method remain constant to seven significant figures when the slice thicknesses are changed within a wide range, while those calculated by the C-MS method change significantly. From the mathematical point of view, the C-MS method is only a first order approximation of the RS–MS method. Thus, the calculation precision of the RS–MS method is much higher than that of the C-MS method. Or to achieve the same precision, the slice thickness for the RS–MS method can be taken as two orders of magnitude larger than for the C-MS method in the simulation. As a result, the calculation speed for the RS–MS method may be even faster than that for the C-MS method in some cases. For the two advantages stated above, the RS–MS method may be more suitable for precise calculations. [Copyright &y& Elsevier]

Abstract: The simulation of the high order Laue zone (HOLZ) diffractions of monoclinic and triclinic crystals is a very complicated problem. The conventional multislice (MS) method suffers from the problem of infinity of the phase grating size. To avoid the difficulty of the infinity, Chen et al. arranged the phase grating plane along the ab plane of the crystal lattice. In this paper we introduce a new method which allows the incident and exit wavefunction planes perpendicular to the zone axis without the difficulty of infinity. We name the method half analytical method. The results calculated by half analytical method are in good agreement with those calculated by the conventional MS method. [Copyright &y& Elsevier]

A completely different formulation for simulation of the high order Laue zone (HOLZ) diffractions is derived. It refers to the new method, i.e. the Taylor series (TS) method. To check the validity and accuracy of the TS method, we take polyvinglidene fluoride (PVDF) crystal as an example to calculate the exit wavefunction by the conventional multi-slice (CMS) method and the TS method. The calculated results show that the TS method is much more accurate than the CMS method and is independent of the slice thicknesses. Moreover, the pure first order Laue zone wavefunction by the TS method can reflect the major potential distribution of the first reciprocal plane. [ABSTRACT FROM AUTHOR]

The bedding plane of shale is related to anisotropic mechanical property, which apparently affects the shale fracturing. To investigate the influence of shale bedding on the fracture morphology and perforation damage under Supercritical Carbon Dioxide (SC–CO 2) jet fracturing, the experiments were comprehensively studied via the macro fracture analysis, strain monitoring, Scanning Electron Microscope (SEM) test and Energy Dispersive Spectroscopy (EDS) test. The results demonstrated that the average Young's Modulus (YM) and Uniaxial Compressive Strength (UCS) of shale specimen with the bedding plane angle of 0° is 9.37 times and 2.89 times of the shale specimen with bedding plane angle of 90°, respectively. During jet fracturing, both the jet pressure and existing bedding are beneficial for fracture initiating and propagating naturally along the weak bedding planes, and shear fracture can enhance the fracture complexity. When the perforation distributes in the direction perpendicular to the bedding plane, the less strain can be obtained, and the mass loss and CO 2 absorption of shale specimen significantly increase by 350% and 300%, respectively, as the jet pressure increases from 25 MPa to 50 MPa, which is larger than the shale specimen with bedding plane angle of 0°. The perforation damage is explored after jet fracturing via SEM and EDS, and it is found the direction of perforation perpendicular to the bedding plane is beneficial for micro-cracks generation, and leads to 10% decline of carbon (C) and oxygen (O) elements in the samples. These studies clearly show the influence of the bedding plane angle on the fracture morphology and perforation damage, which are crucial for SC-CO 2 fracturing and CO 2 storage in shale reservoir. Fig. 1 The Effect of bedding plane on the fractures and perforation damage during SC-CO 2 jet fracturing. The effect of shale bedding on the fracture morphology and perforation damage under SC-CO 2 jet fracturing is comprehensively studied via experiments. Both the jet pressure and existing bedding are beneficial for fracture initiating and propagating naturally along the weak bedding planes under jet fracturing, and shear fracture between the bedding plane can enhance the fracture complexity, inducing the deterioration of microscopic morphology and shale composition. Image 1 • The influence of shale bedding on the fracture morphology and perforation damage was firstly conducted. • Both jet pressure and shale bedding are crucial for fracture initiating and propagating along the weak bedding planes. • The shale with bedding plane angle of 0° is beneficial to fractures generation and the carbon (C) & oxygen (O) reduction. • SC-CO 2 jet not only increase micro-crack and tiny core, but also cause 10% decline of carbon (C) and oxygen (O). [ABSTRACT FROM AUTHOR]

Even though some numerical simulations and experiments of high-pressure CO 2 jetting have conducted, the concerns of the flowing field and induced strain response during SC-CO 2 jet fracturing are still unclear. Thus, this study is aimed to investigate the SC-CO 2 jetting flow field and strain response in the rock via directly High-Speed Photography (HSP) and strain analysis. The development of SC-CO2 jet in high ambient pressure and limited perforation was analyzed. And the effect of jet pressure, ambient pressure and jet distance on the flow field and strain variation on organic glass was comprehensively studied. According to the results of the flow field of, it is found that the length of the jet core grows with the jet velocity gradually increasing in the time of (0.5–8)x104 μs level when SC-CO 2 jet starts to penetrate into the perforation and the wall-attached jet appears in the ambient vessel. when the jet pressure varied from 15 MPa to 55 Ma, the penetration depth sharply grows and the maximum strain increases approximately 9.4 times. When the ambient pressure is 8.5 MPa, the optimal jet distance is 6 mm because of the largest penetration depth and maximum strain value. Reducing the ambient pressure to 5.5 MPa, the optimal jet distance rise up to 10 mm. It is concluded that there is optimal jet distance under low ambient pressure, and reducing jet distance is better for the jet fracturing under high ambient pressure. Finally, the relationship between the flow field and strain variation is investigated and discussed by combining the HSP images and strain curves. The above research would be helpful for understanding the flow characteristic and its influence on strain variation around perforation under the ambient environment, which is meaningful for improve the operation procedure of CO 2 fracturing. The schematic program of instantaneous flow field during SC-CO 2 jet fracturing. To investigated the SC-CO 2 jetting flow field and strain response in the rock, the SC-CO 2 jet fracturing was directly explored by High-Speed Photography and strain analysis. The results indicated that there a strong relationship between the jet flow and strain response, and both the pressurization and impingement, which is related to the jet pressure and ambient pressure, works together to dominated the strain variation. Image 1 • The flow field of SC-CO 2 three phases, which are the initial phase, developing phase and stable phase, respectively. • Jet core can not easily penetrate into the perforation under low jet pressure and high ambient pressure. • The optimal jet distance is depended on both jet pressure and ambient pressure due to the jet expansion. • There is a strong relationship between the jet flow and strain response. [ABSTRACT FROM AUTHOR]

NAK-associated protein 1 (NAP1) is involved in NF-κB activation and interferon (IFN) induction in human and mammal; however, the role of teleost NAP1 in innate immunity remains unknown. In this paper, NAP1 homologue of black carp (Mylopharyngodon piceus) has been cloned and characterized. Black carp NAP1 (bcNAP1) migrated around 47 kDa in immunoblot assay and was identified as a cytosolic protein by immunofluorescent staining. bcNAP1 showed little IFN promoter-inducing ability in the reporter assay and bcNAP1 presented no antiviral activity against either grass carp reovirus (GCRV) or spring viremia of carp virus (SVCV) in the plaque assay. However, when co-expressed with black carp MDA5 (bcMDA5), bcNAP1 enhanced bcMDA5-mediated IFN promoter induction in the reporter assay. Accordingly, the plaque assay data demonstrated that the antiviral activity of bcMDA5 against both GCRV and SVCV was upregulated by bcNAP1. Additionally, the association between bcNAP1 and bcMDA5 has been identified through immunofluorescent staining and co-immunoprecipitation (co-IP) assay. Thus, the data generated in this study support the conclusion that bcNAP1 interacts with bcMDA5 and up-regulates bcMDA5-mediated antiviral signaling during host innate immune activation. • bcNAP1 interacts with bcMDA5. • bcNAP1 enhances bcMDA5-mediated IFN promoter induction. • The antiviral activity of bcMDA5 against both GCRV and SVCV is up-regulated by bcNAP1. [ABSTRACT FROM AUTHOR]

Supercritical carbon dioxide (SC-CO2) jet fracturing is a promising alternative for shale gas fracturing instead of water. However, most studies pay more attention to the fracture generation and ignore the flow characteristic of SC-CO2 jet fracturing in limited perforation scenarios. To accurately explore the flow field in a limited perforation tunnel, a numerical model of a SC-CO2 jet in a limited perforation tunnel before fracture initiation is established based on the corresponding engineering background. The comparison between the numerical simulation and experiments has proved that the model is viable for this type of analysis. By using the numerical method, the flow field of the SC-CO2 jet fracturing is analyzed, and influencing factors are discussed later. The verification and validation show that the numerical model is both reliable and accurate. With the dramatic fluctuating of turbulent mixing in a fully developed region, there is an apparent increase in the CO2 density and total pressure during limited perforation. When the z increases from 10 times r0 to 145 times r0, the velocity on the perforation wall surface would decrease below 0 m/s, resulting in backflow in the perforation tunnel. The structure of the nozzle, including the outlet length and outlet diameters, significantly affects the axial velocity and boosting pressure in the perforation tunnel. The highest total pressure exists when the nozzle length-to-radius ratio is 2. The maximum velocity of the jet core drops from 138.7 to 78 m/s, and the "hydraulic isolating ring" starts disappearing when the radius changes from 1 to 1.5 mm. It is necessary to increase the aperture ratio as much as possible to ensure pressurization but not over 1. Based on a similar theory high-speed photography results clearly show that the SC-CO2 develops to fully jetting in only 0.07 s and a strong mixing exists in the annular region between the jet core and the surroundings, according with the numerical simulation. This study should be helpful for scholars to comprehensively understand the interaction between the SC-CO2 jet and perforation, which is beneficial for studying SC-CO2 fracturing. [ABSTRACT FROM AUTHOR]

Highlights • KCs and NLRP3 exerted pro-inflammatory effects on the development of NASH. • PA induced mtDNA release from the mitochondria to the cytoplasm. • The mtDNA-NLRP3 inflammasome complex was formed upon PA stimulation. Abstract Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in many developed and developing countries worldwide. It has been well established that the chronic sterile inflammation caused by the NLRP3 inflammasome is closely related to NAFLD development. Kupffer cells (KCs) are involved in the pathogenesis of various liver diseases. We used methionine choline-deficient diets to establish a mouse nonalcoholic steatohepatitis (NASH) model. The expression and formation of the NLRP3 inflammasome in the KCs from the mouse and cell models were determined by Western blotting and co-immunoprecipitation. Evidence of mitochondrial DNA (mtDNA) release was determined by live cell labeling and imaging. KCs and the NLRP3 inflammasome exerted proinflammatory effects on the development and progression of NASH through secretion of the proinflammatory cytokine IL-1β. NLRP3, ASC and Caspase-1 protein expression levels in KCs from NASH mouse livers were significantly higher than those in KCs from NLRP3−/− mice, and the number of NLRP3 inflammasome protein complexes was significantly higher in KCs from NASH mouse livers, whereas these protein complexes could not be formed in NLRP3−/− mice. In in vitro experiments, palmitic acid (PA) decreased the mitochondrial membrane potential and subsequently induced mtDNA release from the mitochondria to the cytoplasm. NLRP3 inflammasome expression was substantially increased, and mtDNA-NLRP3 inflammasome complexes formed upon PA stimulation. Our data suggest that mtDNA released from mitochondria during PA stimulation causes NLRP3 inflammasome activation, providing a missing link between NLRP3 inflammasome activation and NASH development, via binding of cytosolic mtDNA to the NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (MET ex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study. Enrolled treatment-naïve (1L) or pre-treated (2L+) patients with aNSCLC with a MET ex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles. PROs were collected at baseline and every six weeks thereafter using EORTC QLQ-C30 global health status/quality of life (GHS/QoL), QLQ-LC13 symptoms, and EQ-5D-5L visual analogue scale (VAS) questionnaires. As of 6 January 2020, 27/28 1L and 65/69 2L+ patients had completed PROs at baseline; compliance rates remained >70%. Cough improved early, with meaningful improvements (≥10-point change from baseline) observed throughout cycles (mean change from baseline [SD] by week 7: 1L −13.0 [39.9], 2L+ −8.2 [28.4]; week 43: 1L −28.2 [26.7], 2L+ −10.5 [27.3]). QoL, assessed by GHS/QoL and VAS, improved by week 7 in 1L and 2L+ patients, with improvements generally sustained over time. Median time to definitive deterioration (TTDD) in GHS/QoL was 16.6 months (95% CI: 9.7, not estimable [NE]) in 1L and 12.4 months (95% CI: 4.2, 19.4) in 2L+ patients. Median TTDD for dyspnoea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE) for 1L and 2L+ patients, respectively, and NE for cough and chest pain. Capmatinib was associated with clinically meaningful improvements in cough and preserved QoL, further supporting its use in patients with MET ex14-mutated aNSCLC. ClinicalTrials.gov registry number: NCT02414139. • Capmatinib is indicated for advanced NSCLC with MET exon 14 skipping alterations. • We present the analysis of the patient-reported outcomes from the GEOMETRY mono-1 trial. • Patient-reported outcomes included the EORTC QLQ-C30, EORTC QLQ-LC13, and EQ-5D-5L. • Capmatinib led to clinically meaningful improvements in cough and preserved QoL. • Benefit was observed for both treatment-naïve and previously treated patients. [ABSTRACT FROM AUTHOR]

Background The relationship between diet, lifestyle and cognition of old adults has been indicated in several population-based studies. However, the conclusions derived from these studies are inconsistent. Methods A cross-sectional study was carried out in 894 old Chinese adults aged 50 and above. Cognitive function of the participants was measured by using Montreal Cognitive Assessment (MoCA) test. Demographic characteristics and lifestyle was collected with a questionnaire. A semi-quantified FFQ method was used for dietary intake survey. Results Comparing with normal subjects, mild cognition impairment (MCI) patients were characterized as old age and lower education ( P < 0.01). The nuts and cooking oil intake of MCI patients was less than the normal subjects ( P < 0.05). Fruit and vegetable intake will benefit orientation, name and attention ability in the elderly ( P < 0.05). Fruit and vegetable juice drinking will benefit abstraction ability ( P < 0.01).Subjects with regular reading and housekeeping habit had better cognition ( P < 0.01). Conclusions Nuts, vegetables and fruit-rich diet might decrease the risk of cognition impairment. Reading and housekeeping help to maintain healthy cognition in the elderly. [ABSTRACT FROM AUTHOR]

Stearoyl-CoA desaturase 1 (SCD1) is a key regulator in the mechanisms of cell proliferation, survival and transformation to cancer, and autophagy also plays a critical role in hepatocellular carcinoma (HCC). However, whether SCD1 mediates autophagy in HCC remains unknown. In this study, we observed significantly elevated SCD1 expression levels and evident suppression of autophagy in HCC, and the positive SCD1 expression and autophagy defect were independently correlated with poor prognosis of HCC patients. We also found that the inhibition of SCD1 by a pharmacological inhibitor reduced cell viability and induced apoptosis and autophagy of human HCC cells in a dose- and time-dependent manner. Moreover, the pharmacological inhibition of AMPK supported the hypothesis that the induction of autophagy caused by SCD1 inhibition relied on AMPK stimulation. Furthermore, the human HCC cells death triggered by inhibition of SCD1 was partly involved in autophagy-induced apoptosis via AMPK signaling. Our findings reveal a novel role for SCD1 in the regulation of autophagy via AMPK signaling and provide mechanistic input for the clinical exploration that the combination of SCD1 inhibition with autophagy induction may be attractive for the management of HCC. [ABSTRACT FROM AUTHOR]

The parallel track scraping principle of conventional PDC bits largely limits the cutting efficiency and working life in deep formations. Cross-cutting polycrystalline diamond compact (PDC) bit may be an efficient drilling tool that increases the rock-breaking efficiency through both cross-cutting and alternate-cutting modes of the PDC cutter. The motion track equation of the cross-cutting PDC bit was derived by using the compound coordinate system, and the motion track was analyzed. Meanwhile, through the unit experiment and discrete element simulation, the cutting force, volume-specific load, and crack propagation were analyzed under different cutting modes. Through establishing a nonlinear dynamic model of the bit-rock system, the speed-up mechanism of the novel bit was analyzed based on rock damage, rock stress state, and motion characteristic of the bit during the rock-breaking process. Compared with unidirectional cutting, cross-cutting produces less cutting force, more brittle fracture, and a greater decrease of formation strength. The novel PDC bit can put more rock elements into a tensile stress condition than a conventional PDC bit, and the plastic energy dissipation ratio of the cross-cutting PDC bit is lower while the damage energy consumption ratio is higher than they are for conventional bits, which is beneficial to increasing the ratio of fracture failure and improving rock-breaking efficiency. Laboratory drilling tests show that the cross-cutting PDC bit can create mesh-like bottom-hole features. Drilling contrast experiments show that a mesh-like bottom-hole pattern can be obtained by using the cross-cutting PDC bit, of which the ROP is obviously higher than that of the conventional bit when drilling in sandstone or limestone formation. Meanwhile, the influence of deviation angle, weight on bit, and rock properties on cutting efficiency of the cross-cutting PDC bit are studied. [ABSTRACT FROM AUTHOR]

Adriamycin (ADR) is an effective antineoplastic drug; the clinical application of ADR is limited due to fatal heart dysfunction. Exenatide has antioxidant, anti-apoptotic and anti-inflammatory properties. It can alleviate heart damage induced by ischaemia-reperfusion injury. Thus, we assumed that exenatide would produce protective effects on ADR-induced heart dysfunction. Mice were treated with exenatide 1 h prior to every ADR treatment for 20 days. Left ventricular function and performance were assessed by echocardiography. Additionally, H9c2 cells were pretreated with exenatide followed by ADR, and intracellular reactive oxygen species (ROS) and cell viability, as well as the lactate dehydrogenase (LDH) and the creatine kinase MB (CK-MB), were subsequently measured. Flow cytometry and TUNEL staining were applied to assess the effect of exenatide on cardiac damage caused by ADR. Western blot and RT-PCR were performed to detect the effect of exenatide on apoptosis-related genes (Bcl-2 and Bax) and inflammation-related genes and/or proteins (tumour necrosis factor-α, interleukin-6, nuclear factor-κB, and p53). Echocardiography showed that cardiac dysfunction caused by ADR was significantly improved by treatment with exenatide. ADR mice had harmful changes in the levels of ROS and CK-MB/LDH production, as well as the targeted apoptotic and inflammatory molecules, and these effects were also reversed by exenatide. In vitro, exenatide mitigated ADR-induced oxidative stress and CK-MB/LDH production, as well as Annexin V+/PI+ and TUNEL+ apoptosis in H9c2 cells. In conclusion, our research demonstrated the potential protective effects of exenatide on ADR-induced heart dysfunction through suppressing oxidative stress, apoptosis and inflammation. • Cardiac dysfunction caused by adriamycin can be significantly improved by administration with exenatide. • Exenatide alleviates adriamycin-induced heart dysfunction through suppressing oxidative stress, apoptosis and inflammation. • These results highlight the therapeutic potential of exenatide for preventing adriamycin induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background and aims Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be extensively explored. Thus, the present study aims to study expression patterns, biological functions, and diagnostic value of lncRNAs in CAD. Methods Using microarray, we performed the transcriptome-wide lncRNA and mRNAs expression profile of peripheral blood mononuclear cells (PBMCs) of 93 CAD patients and 48 healthy controls. Gene Ontology (GO) and pathway analysis for differentially expressed mRNAs were used to investigate underlying biological associations of differentially expressed lncRNAs, and path-net was created to depict interactions of significant pathways. qRT-PCR was used to validate selected lncRNAs in 412 CAD patients and 295 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether lncRNAs could be used in the diagnosis of CAD patients. Finally, the functional significance of validated lncRNAs was determined in THP-1-derived macrophages. Results We identified 1210 lncRNAs and 890 mRNAs differentially expressed from the expression profile and validated 7 lncRNAs. Two novel lncRNA biomarkers, ENST00000444488.1 and uc010yfd.1, together with CAD risk factors, had the better performance for discrimination of CAD patients from healthy controls, and ENST00000444488.1 could diagnose acute myocardial infarction (AMI) patients. The knockdown of 20 ENST00000444488.1, uc010yfd.1, ASO3973 and ENST00000602558.1 affected the expression of inflammation-related genes and their nearby genes in THP-1-derived macrophages, respectively. Conclusions We offered a transcriptome-wide overview of aberrantly expressed lncRNAs in CAD patients, and identified two novel lncRNA biomarkers for diagnosing CAD. Loss of validated lncRNAs regulated the expression of inflammation-related genes and their nearby genes. [ABSTRACT FROM AUTHOR]

Supercritical carbon dioxide (SC-CO 2 ) jet is now widely considered to have good potential for use in the field of oil–gas exploration and development due to the unique natural properties of SC-CO 2 fluid, and because it offers many advantages over a water jet in various applications. In order to take better advantage of the SC-CO 2 jet, a jet-driven Helmholtz oscillation nozzle was applied to produce a self-excited oscillation pulsed SC-CO 2 jet (SOPSJ). The impingement characteristics of the SOPSJ were investigated experimentally with respect to the impinging pressure oscillation peak and amplitude, as well as the oscillating frequency. A preliminary theoretical exploration of the relationship between the oscillation characteristics and the unique properties of the SC-CO 2 fluid was performed. Numerous impinging pressure tests were conducted with the use of different chamber lengths of Helmholtz nozzle under inlet pressures of 25, 30, 35 and 40 MPa, ambient pressures of 10 MPa, and fluid temperature of 330 K. The results show that compared with the continuous jet the SOPSJ has a greater impinging pressure peak. However, this only happens within a relatively small range of standoff distance depending on the chamber length and the inlet pressure. The maximum peaks are approximately 1.33, 1.29, 1.25 and 1.19 times those of the continuous jets corresponding to inlet pressures of 25, 30, 35, and 40 MPa, respectively. Moreover, the optimal chamber length for obtaining the maximum impinging pressure oscillation peak always leads to the largest amplitude under each inlet pressure. However, this is not true for the other chamber lengths that deviate from the optimal one. In addition, the increase in inlet pressure can cause relatively high dominant frequencies, and the frequency distribution range of the SOPSJ is close to that of the pulsed air–water jet but far from that of the self-excited oscillation pulsed water jet (SOPWJ). [ABSTRACT FROM AUTHOR]

To observe the associations between single nucleotide polymorphisms (SNPs) of nicotinamide N-methyltransferase (NNMT) gene and sport performance and to analyse genotype associations of the associated SNPs with sport performance and relative maximal oxygen uptake (...O2max). Participants were selected from 685 Chinese Han male college students. The completion times of a 1000-m run and a 50-m run were used to reflect sport performance, respectively. Nineteen tagSNPs were genotyped with Polymerase chain reaction-ligase detection reaction. Relative ...O2max was directly determined with a cardiopulmonary function analyser. A significant association was found between rs2256292 and 1000-m run performance, but no significant association was found between any tagSNPs and 50-m run performance. The genotype associations of rs2256292 with 1000-m run performance and with relative ...O2max were both significant under the recessive model (CC vs. CG + GG). No tagSNP in NNMT is significantly associated with 50-m run performance but rs2256292 is significantly associated with 1000-m run performance. The genotype associations of rs2256292 with sport performance are significant under recessive model, and a higher relative ...O2max may be the physiological reason for minor homozygote CC carriers being of the better 1000-m runners. [ABSTRACT FROM AUTHOR]

Purpose: The impact of proton pump inhibitors (PPIs) on the pharmacokinetics (PK) and efficacy of ceritinib was evaluated.Methods: A healthy subject drug-drug interaction (DDI) study was conducted to assess the effect of esomeprazole on the PK of a single 750 mg dose of ceritinib. To further investigate the impact of PPIs on the PK and efficacy of ceritinib in ALK-positive cancer patients, two subgroup analyses were performed. Analysis 1 evaluated ceritinib steady-state trough concentration (Ctrough,ss) and overall response rate (ORR) by concomitant use of PPIs in patients from the ASCEND-1, -2, and -3 studies; analysis 2 evaluated ceritinib single-dose and steady-state AUC0-24h and C max by concomitant PPI use in patients from ASCEND-1 using a definition of PPI usage similar to that used in the healthy subject study.Results: In the healthy subject study, co-administration of a single 750 mg dose of ceritinib with esomeprazole 40 mg for 6 days decreased ceritinib AUC0-∞ by 76% and C max by 79%. However, based on subgroup analysis 1, patients had similar C trough,ss and ORR regardless of concomitant PPI usage. Based on analysis 2, co-administration of a single 750 mg ceritinib dose with PPIs for 6 days in patients suggested less effect on ceritinib exposure than that observed in healthy subjects as AUC0-24h decreased by 30% and C max decreased by 25%. No clinically meaningful effect on steady-state exposure was observed after daily dosing.Conclusions: Long-term administration of ceritinib with PPIs does not adversely affect the PK and efficacy of ceritinib in ALK-positive cancer patients. [ABSTRACT FROM AUTHOR]

Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide. Our previous works indicate that NNMT is involved in the body mass index and energy metabolism, and recently the association between a SNP (rs694539) of NNMT and a variety of cardiovascular diseases was reported. At present, more than 200 NNMT single nucleotide polymorphisms (SNPs) have been identified in the databases of the human genome projects; however, the association between rs694539 variation and hyperlipidemia has not been reported yet, and whether there are any SNPs in NNMT significantly associated with hyperlipidemia is still unclear. In this paper, we selected 19 SNPs in NNMT as the tagSNPs using Haploview software (Haploview 4.2) first and then performed a case-control study to observe the association between these tagSNPs and hyperlipidemia and finally applied physiological approaches to explore the possible mechanisms through which the NNMT polymorphism induces hyperlipidemia. The results show that a SNP (rs1941404) in NNMT is significantly associated with hyperlipidemia, and the influence of rs1941404 variation on the resting energy expenditure may be the possible mechanism for rs1941404 variation to induce hyperlipidemia. [ABSTRACT FROM AUTHOR]

Thermal barrier coatings (TBCs) usually exhibit an uncertain lifetime owing to their scattering mechanical properties and severe service conditions. To consider these uncertainties, a reliability assessment method is proposed based on failure probability analysis. First, a limit state equation is established to demarcate the boundary between failure and safe regions, and then the failure probability is calculated by the integration of a probability density function in the failure area according to the first- or second-order moment. It is shown that the parameters related to interfacial failure follow a Weibull distribution in two types of TBC. The interfacial failure of TBCs is significantly affected by the thermal mismatch of material properties and the temperature drop in service. [ABSTRACT FROM AUTHOR]

In this paper, acoustic emission (AE) and digital image correlation methods were applied to monitor interface cracking in thermal barrier coatings under compression. The interface failure process can be identified via its AE features, including buckling, delamination incubation and spallation. According to the Fourier transformation of AE signals, there are four different failure modes: surface vertical cracks, opening and sliding interface cracks, and substrate deformation. The characteristic frequency of AE signals from surface vertical cracks is 0.21 MHz, whilst that of the two types of interface cracks are 0.43 and 0.29 MHz, respectively. The energy released of the two types of interface cracks are 0.43 and 0.29 MHz, respectively. Based on the energy released from cracking and the AE signals, a relationship is established between the interface crack length and AE parameters, which is in good agreement with experimental results. [ABSTRACT FROM AUTHOR]

Objectives Approximately 15% of patients with multiple myeloma (MM) exhibit a t(4;14) translocation, which often results in constitutive activation of the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 3 (FGFR3). This study evaluated the efficacy and safety of dovitinib, an RTK inhibitor with in vitro inhibitory activity against FGFR, in patients with relapsed or refractory MM with or without t(4;14) translocation. Methods Adult patients with relapsed or refractory MM who had received ≥2 prior regimens were enrolled in this multicenter, 2-stage, phase 2 trial. Patients were grouped based on their t(4;14) status. Dovitinib (500 mg/day orally) was administered on a 5-days-on/2-days-off schedule. The primary endpoint was overall response rate by local investigator review (per International Myeloma Working Group criteria). In non-responding patients, treatment could continue with the addition of low-dose dexamethasone. Results In total, 43 patients (median age, 63 years) were enrolled (13 t(4;14) positive, 26 t(4;14) negative, and 4 t(4;14) status non-interpretable). Patients had received a median of 5 prior regimens. Median duration of treatment was 8.7 weeks in the t(4;14)-positive group and 3.7 weeks in the t(4;14)-negative group. None of the patients on dovitinib had objective responses. The stable disease rate was 61.5% in the t(4;14)-positive group and 34.6% in the t(4;14)-negative group. Overall, 39 patients (90.7%) had adverse events suspected to be related to study drug, most commonly diarrhea (60.5%), nausea (58.1%), vomiting (46.5%), and fatigue (32.6%). Conclusion Dovitinib showed no single-agent activity in relapsed or refractory MM but may stabilize disease in some t(4;14)-positive patients. [ABSTRACT FROM AUTHOR]

Graphene nanosheets (GNSs) reinforced copper matrix composites have been considered as the potential copper materials with high strength and high conductivity. Here, the high-strength GNSs/Cu composites were fabricated by accumulative roll bonding (ARB). The ARBed GNSs/Cu composites manifested a good interfacial bonding and a significant grain refinement. The average spacing of high-angle boundaries along the normal direction was less than 150 nm after 6 ARB cycles, which was finer than that of the ARBed Cu. In addition, there existed a nano-layer with grain sizes of 50–70 nm and the high-density deformation-twins at the interface. The tensile strength of the ARBed materials enhanced with the number of cycles. After six cycles, the tensile strength of GNSs/Cu composites reached 496 MPa. This strength was 275 and 33 MPa higher than those of the annealed copper and the ARBed copper, respectively due to the strain hardening and grain refinement. Furthermore, the addition of GNSs into Cu matrix accelerated the grain refinement and the strength improvement. [ABSTRACT FROM AUTHOR]

Chlorination is the most popular method for disinfecting swimming pool water; however, although pathogens are being killed, many toxic compounds, called disinfection by-products (DBPs), are formed. Numerous epidemiological publications have associated the chlorination of pools with dysfunctions of the respiratory system and with some other diseases. However, the findings concerning these associations are not always consistent and have not been confirmed by toxicological studies. Therefore, the health effects from swimming in chlorinated pools and the corresponding stress reactions in organisms are unclear. In this study, we show that although the growth and behaviors of experimental rats were not affected, their health, training effects and metabolic profiles were significantly affected by a 12-week swimming training program in chlorinated water identical to that of public pools. Interestingly, the eyes and skin are the organs that are more directly affected than the lungs by the irritants in chlorinated water; instead of chlorination, training intensity, training frequency and choking on water may be the primary factors for lung damage induced by swimming. Among the five major organs (the heart, liver, spleen, lungs and kidneys), the liver is the most likely target of DBPs. Through metabolomics analysis, the corresponding metabolic stress pathways and a defensive system focusing on taurine were presented, based on which the corresponding countermeasures can be developed for swimming athletes and for others who spend a lot of time in chlorinated swimming pools. [ABSTRACT FROM AUTHOR]

Summary: Background: An unmet medical need exists for patients with metastatic renal cell carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. Fibroblast growth factor (FGF) pathway activation has been proposed as a mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors. We therefore compared dovitinib with sorafenib as third-line targeted therapies in patients with metastatic renal cell carcinoma. Methods: In this multicentre phase 3 study, patients with clear cell metastatic renal cell carcinoma who received one previous VEGF-targeted therapy and one previous mTOR inhibitor were randomly assigned through an interactive voice and web response system to receive open-label dovitinib (500 mg orally according to a 5-days-on and 2-days-off schedule) or sorafenib (400 mg orally twice daily) in a 1:1 ratio. Randomisation was stratified by risk group and region. The primary endpoint was progression-free survival (PFS) assessed by masked central review. Efficacy was assessed in all patients who were randomly assigned and safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01223027. Findings: 284 patients were randomly assigned to the dovitinib group and 286 to the sorafenib group. Median follow-up was 11·3 months (IQR 7·9–14·6). Median PFS was 3·7 months (95% CI 3·5–3·9) in the dovitinib group and 3·6 months (3·5–3·7) in the sorafenib group (hazard ratio 0·86, 95% CI 0·72–1·04; one-sided p=0·063). 280 patients in the dovitinib group and 284 in the sorafenib group received at least one dose of study drug. Common grade 3 or 4 adverse events included hypertriglyceridaemia (38 [14%]), fatigue (28 [10%]), hypertension (22 [8%]), and diarrhoea (20 [7%]) in the dovitinib group, and hypertension (47 [17%]), fatigue (24 [8%]), dyspnoea (21 [7%]), and palmar-plantar erythrodysaesthesia (18 [6%]) in the sorafenib group. The most common serious adverse event was dyspnoea (16 [6%] and 15 [5%] in the dovitinib and sorafenib groups, respectively). Interpretation: Dovitinib showed activity, but this was no better than that of sorafenib in patients with renal cell carcinoma who had progressed on previous VEGF-targeted therapies and mTOR inhibitors. This trial provides reference outcome data for future studies of targeted inhibitors in the third-line setting. Funding: Novartis Pharmaceuticals Corporation. [ABSTRACT FROM AUTHOR]

TGA (Thermal Gravimetric Analysis) was used to research on Ni-based, Fe-based, Cu-based and Co-based prepared oxygen carriers, and the TG test curves reflect the carbon deposition characteristics of different prepared oxygen carriers and indicate that the Cu-based oxygen carrier can restrain carbon deposition to some extent. When combustion reaction of CO was conducted in the tube furnace, adopting the method of feeding water vapour into the furnace can avoid carbon deposition effectively. Finally, the XRD (X-Ray Diffraction) was used to scan the reaction product to evaluate the anti-carbon effect of the experiment. Compared with the no steam condition, it can be found that the characteristic peaks of carbon are disappeared on feeding steam condition, and carbon deposition controlled by the addition of steam is confirmed further. [ABSTRACT FROM AUTHOR]

Supercritical carbon dioxide (SC-CO 2) jets are of increasing interest in drilling and completion engineering due to their superiority over water jets. To understand the nature of SC-CO 2 jets and improve performance, the flow characteristics of SC-CO 2 jets were experimentally investigated, followed by rock breaking tests. Flow images of the jet under various operating conditions were captured by a high speed CCD camera. A comparative analysis of an SC-CO 2 jet flow with classical theories and other types of jet flows was performed. The results show that the submerged environment can greatly affect the characteristics of SC-CO 2 jets. When injecting into a gaseous CO 2 environment, the saturation curve is crossed and intense phase transition occurs in the jet flow. The jet appears as a classical single-phase gas/gas turbulent shear layer. Whereas, under an SC-CO 2 submerged environment, shock waves can be found in the jet flow. The initial instability and spreading rate reduce with the increase in inlet pressure. The jet behaves as a typical compressible jet. These features are different from water jets and are most likely the reason for the better rock breaking performance of SC-CO 2 jets. Further, SC-CO 2 jets under a gaseous CO 2 submerged environment are prone to result in large and shallow breaking pits, while the jets under an SC-CO 2 environment tends to cause small and deep breaking pits. • Flow characteristics of an SC-CO 2 jet were experimentally studied. • Submerged environment can greatly affect the SC-CO 2 jet flow and rock breaking. • Intense phase transition occurs in the jet discharging into gaseous CO 2. • The jet sprayed into SC-CO 2 behaves as a typical compressible jet. • Shock waves can be found in the jet ejected into SC-CO 2. [ABSTRACT FROM AUTHOR]

Supercritical carbon dioxide (SC-CO 2) fracturing has attracted considerable attention on exploiting shale gas and tight gas. This study investigated the influence of the perforation orientation on fracture initiation and propagation induced by SC-CO 2 fracturing through a series of laboratory fracturing experiments under tri-axial stress states and water was also used as a fracturing fluid to compare with SC-CO 2. It was found that breakdown pressure increases with the increase of perforation angle according to the pressure curves in SC-CO 2 fracturing and hydraulic fracturing. AE energy characteristic has shown that AE energy release rate of SC-CO 2 fracturing is larger than that of hydraulic fracturing, indicating that fractures induced by SC-CO 2 fracturing are more complex. Fracture geometry and energy surges verified that there were more fractures induced by SC-CO 2 fracturing with increase of the perforation orientation angle. It was observed that hydraulic fracturing mainly induced a bi-wing fracture while SC-CO 2 fracturing induced bi-wing and tri-wing fracture. At low perforation angle (α ≤ 45°), perforation orientation has little influence on fracture propagation direction and fracture extends along the direction of the maximum principle direction in SC-CO 2 fracturing. At high perforation angle (α ≥ 60°), fracture propagation shows an independence of loading stress, fractures may extend in three directions. The findings are beneficial for further understanding the mechanism of SC-CO 2 fracturing and optimizing perforation parameters in SC-CO 2 field fracturing. • Fracture induced by SC-CO 2 fracturing is more complex that hydraulic fracturing. • The larger the perforation angle, the more complex the fracture formed by SC-CO 2 fracturing. • Fracture propagation shows an independency of stress condition at high perforation angle. [ABSTRACT FROM AUTHOR]