Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various ...cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC‐derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium‐dependent phospholipid‐binding protein, was expressed in a PC cell line (CFPAC‐1)‐derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC‐derived exosomes and its involvement in PC biology.
Recent analysis of satellite data obtained during the 9 October 2012 geomagnetic storm identified the development of peaks in electron phase space density, which are compelling evidence for local ...electron acceleration in the heart of the outer radiation belt, but are inconsistent with acceleration by inward radial diffusive transport. However, the precise physical mechanism responsible for the acceleration on 9 October was not identified. Previous modelling has indicated that a magnetospheric electromagnetic emission known as chorus could be a potential candidate for local electron acceleration, but a definitive resolution of the importance of chorus for radiation-belt acceleration was not possible because of limitations in the energy range and resolution of previous electron observations and the lack of a dynamic global wave model. Here we report high-resolution electron observations obtained during the 9 October storm and demonstrate, using a two-dimensional simulation performed with a recently developed time-varying data-driven model, that chorus scattering explains the temporal evolution of both the energy and angular distribution of the observed relativistic electron flux increase. Our detailed modelling demonstrates the remarkable efficiency of wave acceleration in the Earth's outer radiation belt, and the results presented have potential application to Jupiter, Saturn and other magnetized astrophysical objects.
The variety of Borrelia burgdorferi sensu lato (B. burgdorferi) genospecies leads to distinction in clinical manifestations of Lyme borreliosis (LB). There are reports of LB clinical characteristics ...in China, where the B. burgdorferi genospecies in ticks and animal hosts are different from those in Europe and North America. During May to September in 2010 and 2011, all patients who had erythema migrans (EM, more than 5 cm in diameter) after a recent tick-bite, and sought medical care at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeastern China, were enrolled in the study. Specific PCR was used to determine the B. burgdorferi genospecies in the disseminated patients. Of 265 EM patients, B. burgdorferi DNA was detected in blood specimens from 15 of 55 disseminated patients. Sequence analyses of 5S–23S rRNA, flagellin, ospC, 16S rRNA and ospA genes revealed that 11 patients were infected with Borrelia garinii, three with Borrelia afzelii and one with Borrelia valaisiana-related genospecies. Among 15 patients, 40%, 13.3% and 13.3% manifested pruritus, pain and ulceration, respectively. Systemic symptoms, arthralgia or a swollen joint and lymphadenopathy were observed in 26.7%, 13.3% and 6.7% patients, respectively. In northeastern China, three genospecies of LB patients were detected. The B. burgdorferi genospecies identified in this study was predominantly B. garinii. A case infected with B. valaisiana-related genospecies was reported for the first time.
Local acceleration driven by whistler‐mode chorus waves is fundamentally important for accelerating seed electron populations to highly relativistic energies in the outer radiation belt. In this ...study, we quantitatively evaluate chorus‐driven electron acceleration during the 17 March 2013 storm, when the Van Allen Probes observed very rapid electron acceleration up to several MeV within ~12 hours. A clear radial peak in electron phase space density (PSD) observed near L* ~4 indicates that an internal local acceleration process was operating. We construct the global distribution of chorus wave intensity from the low‐altitude electron measurements made by multiple Polar Orbiting Environmental Satellites (POES) satellites over a broad region, which is ultimately used to simulate the radiation belt electron dynamics driven by chorus waves. Our simulation results show remarkable agreement in magnitude, timing, energy dependence, and pitch angle distribution with the observed electron PSD near its peak location. However, radial diffusion and other loss processes may be required to explain the differences between the observation and simulation at other locations away from the PSD peak. Our simulation results, together with previous studies, suggest that local acceleration by chorus waves is a robust and ubiquitous process and plays a critical role in accelerating injected seed electrons with convective energies (~100 keV) to highly relativistic energies (several MeV).
Key Points
Rapid electron acceleration with a radial PSD peak is observed during a storm
Chorus driven electron acceleration reproduces observed electron evolution
Local acceleration by chorus waves is a robust and ubiquitous process
Considerable evidences have shown that autophagy has an important role in tumor chemoresistance. However, it is still unknown whether the lncRNA HULC (highly upregulated in liver cancer) is involved ...in autophagy and chemoresistance of hepatocellular carcinoma (HCC). In this study, we for the first time demonstrated that treatment with antitumor reagents such as oxaliplatin, 5-fluorouracil and pirarubicin (THP) dramatically induced HULC expression and protective autophagy. Silencing of HULC sensitized HCC cells to the three antitumor reagents via inhibiting protective autophagy. Ectopic expression of HULC elicited the autophagy of HCC cells through stabilizing silent information regulator 1 (Sirt1) protein. The investigation for the corresponding mechanism by which HULC stabilized Sirt1 revealed that HULC upregulated ubiquitin-specific peptidase 22 (USP22), leading to the decrease of ubiquitin-mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1. Moreover, we found that miR-6825-5p, miR-6845-5p and miR-6886-3p could decrease the level of USP22 protein by binding to the 3'-untranlated region of USP22 mRNA. All the three microRNAs (miRNAs) were downregulated by HULC, which resulted in the elevation of USP22. In addition, we showed that the level of HULC was positively correlated with that of Sirt1 protein in human HCC tissues. Collectively, our data reveals that the pathway 'HULC/USP22/Sirt1/ protective autophagy' attenuates the sensitivity of HCC cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to HCC chemotherapy.
Weyl semimetals host topologically protected surface states, with arced Fermi surface contours that are predicted to propagate through the bulk when their momentum matches that of the surface ...projections of the bulk's Weyl nodes. We used spectroscopic mapping with a scanning tunneling microscope to visualize quasiparticle scattering and interference at the surface of the Weyl semimetal TaAs. Our measurements reveal 10 different scattering wave vectors, which can be understood and precisely reproduced with a theory that takes into account the shape, spin texture, and momentum-dependent propagation of the Fermi arc surface states into the bulk. Our findings provide evidence that Weyl nodes act as sinks for electron transport on the surface of these materials.
Grain refinement is a very effective method to improve the mechanical properties of materials and attracts widespread interests among researchers. However, the grain size effect on the mechanical ...properties is still unclear due to the undesirable microstructure in ultrafine grained (UFG) materials. In the present work, series of ideal materials with average grain sizes range from 0.7 μm to 30.0 μm containing high fraction of high angle grain boundaries (HAGBs), equiaxed grains and low density of dislocations were produced by friction stir processing (FSP). It was found that the Hall-Petch relationships could be classified into three stages as the grain size reduced from coarse grain to UFG regimes, which were decided by the strengthening mechanisms during tensile deformation. The strengthening effect of HAGBs (71 MPa⋅μm1/2) was almost three times of low angle grain boundaries (25 MPa⋅μm1/2), resulting in the positive deviation of Hall-Petch slope in fine grain regime by the increased specific surface area of HAGBs. The further positive deviation of the Hall-Petch slope in UFG regime was affected by the occurrence of an extra dislocation source limited strengthening mechanism, which was up to 29 MPa and reached to about 20% of the yield strength. The increased recovery rate of dislocations at HAGBs contributed to the decrease of mobile dislocation density, leading to the losing of work hardening in UFG regime during tensile deformation.
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