The disseminated neoplastic foci of malignant gliomas are essentially responsible for the limited efficacy of current available therapeutic modalities. Bone marrow-derived stem cells (BMSCs) have the ...ability to migrate into these tumors and even track infiltrating tumor cells, making them to be promising cellular vehicles for delivering therapeutic agents to glioma cells. The herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy with a potent bystander effect has been considered as one of the most promising therapeutic strategies for malignant gliomas. In this study, we evaluate the anti-glioma effect of suicide gene therapy using BMSCs expressing HSV-TK combined with overexpression of connexin 43 (Cx43), which can restore the gap junction of intercellular communication and may enhance the bystander effect of suicide gene therapy. To assess the potential of BMSCs to track glioma cells, a spheroid co-culture system in matrigel was used to show that some BMSCs migrated to C6 glioma cell microspheres. Transwell assay showed the tumor tropic property of BMSCs. In addition, BrdU-labeled BMSCs injected directly into the cerebral hemisphere opposite to the established C6 rat gliomas were capable of migrating into the xenograft gliomas. C6 cell growth was more intensively inhibited by HSV-TK/GCV treatment mediated by BMSCs, and could be further enhanced by combination with Cx43 transfection into glioma cells. The same result was observed in vivo by the growth of C6 gliomas and the survival analysis of rats bearing C6 glioma. In conclusion, Cx43 combined with HSV-TK/GCV gene therapy using BMSCs as vehicles was highly effective in a rat glioma model and therefore hold great potential as a novel approach for the gene therapy of human malignant gliomas.
Planetary magnetospheres receive plasma and energy from the Sun or moons of planets and consequently stretch magnetic field lines. The process may last for varied timescales at different planets. ...From time to time, energy is rapidly released in the magnetosphere and subsequently precipitated into the ionosphere and upper atmosphere. Usually, this energy dissipation is associated with magnetic dipolarization in the magnetosphere.This process is accompanied by plasma acceleration and field‐aligned current formation, and subsequently auroral emissions are often significantly enhanced. Using measurements from multiple instruments on board the Cassini spacecraft, we reveal that magnetic dipolarization events at Saturn could reoccur after one planetary rotation and name them as recurrent dipolarizations. Three events are presented, including one from the dayside magnetosphere, which has no known precedent with terrestrial magnetospheric observations. During these events, recurrent energizations of plasma (electrons or ions) were also detected, which clearly demonstrate that these processes shall not be simply attributed to modulation of planetary periodic oscillation, although we do not exclude the possibility that the planetary periodic oscillation may modulate other processes (e.g., magnetic reconnection) which energizes particles. We discuss the potential physical mechanisms for generating the recurrent dipolarization process in a comprehensive view, including aurora and energetic neutral atom emissions.
Plain Language Summary
Using measurements from the Cassini spacecraft, we reveal a new feature of magnetic dipolarization at Saturn, that is, the magnetic signature repeat after one planetary rotation, which is named recurrent dipolarization. Up to hundreds of kiloelectron volt electrons and ions are identified for the recurrent dipolarization events, suggesting that these particles have experienced efficient acceleration and cannot be purely due to planetary modulation. It remains a mystery why the magnetic dipolarization process associated with energetic ions and electrons could reoccur after one planetary rotation. Moreover, dipolarization process in Saturn's dayside magnetosphere is reported for the first time at Saturn, which has no known precedent with terrestrial or other planetary magnetospheric observations. The results demonstrate that magnetosphere‐ionosphere coupling dynamics at Saturn and Earth have fundamental similarities and differences.
Key Points
We report a recurrent type of magnetic dipolarization at Saturn
The associated processes could efficiently accelerate electrons and ions to tens to hundreds of kiloelectron volts
Corotation of magnetosphere and planetary periodic oscillation are suggested as possible mechanisms
Understanding structural responses of metal-organic frameworks (MOFs) to external stimuli such as the inclusion of guest molecules and temperature/pressure has gained increasing attention in many ...applications, for example, manipulation and manifesto smart materials for gas storage, energy storage, controlled drug delivery, tunable mechanical properties, and molecular sensing, to name but a few. Herein, neutron and synchrotron diffractions along with Rietveld refinement and density functional theory calculations have been used to elucidate the responsive adsorption behaviors of defect-rich Zr-based MOFs upon the progressive incorporation of ammonia (NH
) and variable temperature. UiO-67 and UiO-bpydc containing biphenyl dicarboxylate and bipyridine dicarboxylate linkers, respectively, were selected, and the results establish the paramount influence of the functional linkers on their NH
affinity, which leads to stimulus-tailoring properties such as gate-controlled porosity by dynamic linker flipping, disorder, and structural rigidity. Despite their structural similarities, we show for the first time the dramatic alteration of NH
adsorption profiles when the phenyl groups are replaced by the bipyridine in the organic linker. These molecular controls stem from controlling the degree of H-bonding networks/distortions between the bipyridine scaffold and the adsorbed NH
without significant change in pore volume and unit cell parameters. Temperature-dependent neutron diffraction also reveals the NH
-induced rotational motions of the organic linkers. We also demonstrate that the degree of structural flexibility of the functional linkers can critically be affected by the type and quantity of the small guest molecules. This strikes a delicate control in material properties at the molecular level.
Magnetic holes (MHs), characteristic structures where the magnetic field magnitude decreases significantly, have been frequently observed in space plasmas. Particularly, small size magnetic holes ...(SSMHs) which the scale is less than or close to the proton gyroradius are recently detected in the magnetospheric plasma sheet. In this study of Cluster observations, by the timing method, the minimum directional difference (MDD) method, and the spatiotemporal difference (STD) method, we obtain the propagation velocity of SSMHs in the plasma flow frame. Furthermore, based on electron magnetohydrodynamics (EMHD) theory we calculate the velocity, width, and depth of the electron solitary wave and compare it to SSMH observations. The result shows a good accord between the theory and the observation.
Key Points
The velocity of small size magnetic holes in the plasma flow is calculated
The results show that they are propagating in the plasma flow
The structure velocity agrees with the electron soliton velocity
Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most ...important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3'-coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense- and siRNA-treated groups than the control groups. Our results demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.
Experiments consisting of dense‐phase pneumatic conveying of pulverized coal using nitrogen were carried out in an experimental test facility, with a conveying pressure of up to 4 MPa. The influences ...of the conveying differential pressure, the coal moisture content, the gas volume flow rate and the superficial velocity, on the solid‐gas ratios, were investigated. The Shannon entropy analysis of the pressure fluctuation time series was developed to reveal the flow characteristics. By investigation of the distribution of the Shannon entropy at different conditions, the flow stability and the evolutional tendency of Shannon entropy, in different regimes and regime transition processes, were revealed, and the relationship between Shannon entropy and the flow regime was also established. The results indicate that the solid‐gas ratio and the Shannon entropy rise with increases in conveying differential pressure. The solid‐gas ratio and the Shannon entropy reveal preferable correlation with the superficial gas velocity. Shannon entropy is different for different flow regimes, and can be used to identify the flow regimes. Both the mass flow rate and the Shannon entropy, decrease with increases in moisture content. Shannon entropy analysis is a feasible approach to researching the characteristics of the flow regime, the flow stability and the flow regime transitions in dense‐phase pneumatic conveying systems, at high pressure.
Shannon entropy analysis is a feasible approach to researching the characteristics of the flow regime, the flow stability and the flow regime transitions, in dense‐phase pneumatic conveying systems, at high pressure. Such analysis is reported for the dense‐phase pneumatic conveying of pulverized coal.
Background and Aim
Commonly used classifications for colorectal lesions (CLs) include the Narrow Band Imaging (NBI) International Colorectal Endoscopic (NICE) and Japan NBI Expert Team (JNET) ...classifications. However, both lack a sessile serrated adenoma/polyp (SSA/P) category. This has been addressed by the modified Sano's (MS) and Workgroup serrAted polypS and Polyposis (WASP) classifications. This study aims to compare the accuracy of wNICE and wJNET (WASP added to both) with the stand‐alone MS classification.
Methods
Patients undergoing colonoscopy at an Australian tertiary hospital who had at least one CL detected were prospectively enrolled. In the exploratory phase, CLs were characterized in real time with NBI and magnification using all classifications. In the validation phase, CLs were assessed with both NBI and Blue Laser Imaging (BLI) by four external endoscopists in Japan. The primary outcome was the comparison of wJNET and MS. Secondary outcomes included comparisons among all classifications and the calculation of interrater reliability.
Results
A total of 483 CLs were evaluated in real time in the exploratory phase, and four sets of 30 CL images (80 on NBI and 40 on BLI) were scored in the validation phase. For high‐confidence diagnoses, MS accuracy was superior to wJNET in both the exploratory (86% vs 79%, P < 0.05) and validation (85% vs 69%, P < 0.05) phases. The interrater reliability was substantial for all classifications (κ = 0.74, 0.69, and 0.63 for wNICE, wJNET, and MS, respectively).
Conclusions
MS classification achieved the highest accuracy in both the exploratory and validation phases. MS can differentiate serrated and adenomatous polyps as a stand‐alone classification.
Many classifications have been propose to characterize colorectal lesions but few include SSA/Ps.Comparison between classifications that have this potential lack in the literature.This study compares the WASP+NICE, WASP+JNET and MS classifications with NBI and BLI imaging.
Large-scale artificial plantations in mountainous areas of Southwest China have changed land use status and aggravated land degradation risk (LDR). This study taking Menglian County as an example, ...optimizes land use in 2025 to reduce the regional LDR, by integrating Grey Linear Programming (GLP) and CLUE-S model. Results showed that: The high-risk and medium-risk levels are main LDR types in Menglian County, accounting for 56.36% of total area. The regions with high LDR consistent with the distribution of concentrated garden land and cultivated land. The regions with low LDR consistent with the forestland. While the distribution of medium-risk regions relates to small plots garden land and cultivated land. In the optimization results, the LDR reduced 461.80, 168.95 and 34.23 in three schemes respectively, comparing to 2015. Thereinto, the strict-demand scheme has good applicability and guidance for study area relatively, in which the LDR is reduced while ensuring sustainable development. After spatial allocation, garden land, cultivated land, forestland and construction land tend to be centralized. It is effective for solving the optimal problem of mountainous land resource by integrating GLP and CLUE-S. The methods and results can provide a scientific reference for controlling LDR in mountainous area in Southwest China.
For slowing down the too fast metabolic velocity and increasing the bioavailability of cordycepin, four
N-acyl-(propionyl-, octanoyl-, lauroyl- and stearoyl-) cordycepin derivatives were synthesized ...chemically and their pharmacokinetic profiles were investigated in this study. The results show that time of maximum concentration (
T
max) and half-life (
t
1/2) would be elongated with the increase of the alkyl chain length, but maximum concentration (
C
max) and area under concentration–time curve (AUC) increased initially, then decreased when the number of alkyl carbon exceeded eight. The
T
max,
C
max and AUC of
N-octanoyl-cordycepin were nearly 4, 30 and 68 times, respectively, higher than that of cordycepin. All derivatives could be transformed into cordycepin
in vivo and the concentration of transformed cordycepin was proportional to that of derivatives. It indicated that
N-octanoyl modification could decrease the metabolic velocity and increase the bioavailability of cordycepin to the maximum, thus it might be a promising prodrug of cordycepin.
Display omitted Four novel compounds of cordycepin
N-acyl derivatives with a normal alkyl chain were synthesized firstly and their pharmacokinetic and structure–activity relationship were investigated.
Coronavirus disease 2019 (COVID-19) has become a worldwide public health emergency; unfortunately, there is currently no treatment for improving outcomes or reducing viral-clearance times in infected ...patients. The aim of the present study was to evaluate the efficacy of interferon (IFN) with or without lopinavir and ritonavir as antiviral therapeutic option for treating COVID-19 infection.
The present study enrolled 148 patients that received either standard care, treatment with IFN alfa-2b, or IFN alfa-2b combined with lopinavir plus ritonavir. Viral testing was performed using Reverse-Transcription Polymerase Chain Reaction (RT-PCR).
There was no significant difference in the viral-clearance time at 28 days after treatment between patients receiving standard care and those receiving anti-viral treatments. However, the average viral-clearance time of patients receiving standard care (14 days) was shorter than that for patients receiving IFN alfa-2b or IFN alfa-2b combined with lopinavir plus ritonavir (15.5 or 17.5 days) (p<0.05). Patients treated with IFN alfa-2b within five days or IFN alfa-2b combined with lopinavir plus ritonavir after three days of symptoms exhibited shorter viral-clearance times than the other groups (p<0.05). Moreover, viral-clearance times were significantly longer in patients receiving standard care or anti-viral treatment 5 days after symptoms appeared than those of patients who received these treatments within five days of symptom onset (p<0.05).
Early symptomatic treatment is most critical for maximizing amelioration of COVID-19 infection. Anti-viral treatment might have complicated effect on viral-clearance.
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