Analysis of a Typical Case of Meteorological Service in Tangpu Reservoir

The continuous rainy precipitation process from February to March in 2019 was selected to analyze the effect of meteorological service in Tangpu Reservoir basin,so as to sum up service experience and then lay a better foundation for subsequent services.In response to the rainy weather from December 2018 to early 2019,three rounds of flood discharge were carried out in Tangpu Reservoir.During February-March in 2019,the hit rate of short-term area rainfall forecast for Tangpu Reservoir was 80.0%.Compared with the median of forecast interval,the average absolute error was 7.6 mm,and the relative error was 32.7%.The large deviation in the forecast from March 27 to 28 was deeply analyzed,and it is found that the main reasons were excessive reliance on and trust in a single model,insufficient correction of the actual situation,and insufficient judgment of the nature of precipitation.For the future reservoir meteorological service,three aspects of thinking were put forward,such as further strengthening the sharing of hydrological and meteorological information,improving the forecasting ability,and deepening the research of runoff forecast models.

Design and analysis of the Macao Science Satellite-1's laser retro-reflector array

The origin and spatial-temporal variation of the Earth’s magnetic field(EMF)is one of the important scientific problems that has long been unsolved.The Macao Science Satellite-1(MSS-1)under construction is China’s first high-precision EMF measurement satellite.To satisfy the highly precise requirements of the MSS-1 orbit measurement,a light,high-precision,four-prism laser retroreflector array was designed.It weighs approximately 285 g,its effective reflection area is greater than 1.77 cm^(2),and its size is 100×100×41 mm.The laser retro-reflector array has excellent performance,and it can achieve a ranging precision at the subcentimeter level for satellite laser ranging.It will be developed and installed on the MSS-1 as a power-free load for high-precision orbit measurement and accurate orbit calibration.The MSS-1 is planned to be brought into the International Laser Ranging Service observations.More than 31satellite laser ranging stations in the International Laser Ranging Service around the world will be able to measure the MSS-1 with long arcs,which will support the scientific mission of high-precision EMF exploration.

Influences of various space current systems on the geomagnetic field in near-Earth space

Ground and space-based observations of the geomagnetic field are usually a superposition of different sources from the Earth’s core,lithosphere,ocean,ionosphere,and magnetosphere,and also from field-aligned currents coupling the ionosphere and magnetosphere—the meridional currents that connect the two hemispheres and the induced currents due to the variations of fields over time.The fluctuation of magnetic fields generated by these highly dynamic space currents greatly limits the accuracy of the geomagnetic models.In order to better accomplish the scientific objectives of Macao Science Satellite-1(MSS-1),and to improve existing geomagnetic field models,we present here for the first time a self-consistent coupling of solar wind,magnetosphere,and ionosphere,which represents the most developed numerical simulation method for space physics research so far,making it possible to quantify the contribution of different current systems to the total observed magnetic field(B).The results show that numerical simulation can capture main magnetic disturbance characteristics with significant precision.Partial ring current is a major contributor to the latitudinal magnetic perturbation near the equator.Magnetopause and magnetotail currents affect the radial magnetic perturbation around the mid-latitudes.Field-aligned and Pedersen currents produce significant longitudinal and latitudinal magnetic perturbations at high latitudes.

A WSN Node Fault Diagnosis Model Based on BRB with Self-Adaptive Quality Factor

Wireless sensor networks (WSNs) operate in complex and harshenvironments;thus, node faults are inevitable. Therefore, fault diagnosis ofthe WSNs node is essential. Affected by the harsh working environment ofWSNs and wireless data transmission, the data collected by WSNs containnoisy data, leading to unreliable data among the data features extracted duringfault diagnosis. To reduce the influence of unreliable data features on faultdiagnosis accuracy, this paper proposes a belief rule base (BRB) with a selfadaptivequality factor (BRB-SAQF) fault diagnosis model. First, the datafeatures required for WSN node fault diagnosis are extracted. Second, thequality factors of input attributes are introduced and calculated. Third, themodel inference process with an attribute quality factor is designed. Fourth,the projection covariance matrix adaptation evolution strategy (P-CMA-ES)algorithm is used to optimize the model’s initial parameters. Finally, the effectivenessof the proposed model is verified by comparing the commonly usedfault diagnosis methods for WSN nodes with the BRB method consideringstatic attribute reliability (BRB-Sr). The experimental results show that BRBSAQFcan reduce the influence of unreliable data features. The self-adaptivequality factor calculation method is more reasonable and accurate than thestatic attribute reliability method.

Numerical simulation of the sensor output on Macao Science Satellite-1

Macao Science Satellite-1(MSS-1)will be launched at the early of 2023 into a near-circular orbit.The mission is designed to measure the Earth’s geomagnetic field with unpreceded accuracy through a new perspective.The most important component installed on the satellite,to ensure high accuracy,is the deployable boom(Optical Bench).A Vector Field Magnetometer(VFM),an Advanced Stellar Compass(ASC),and a Couple Dark State Magnetometers(CDSM)are deployed on the deployable boom.In order to maximize the mission’s scientific output,a numerical simulator on MSS-1’s deployable boom was required to evaluate the adaptability of all devices on the deployable boom and assist the satellite’s data pre-processing.This paper first briefly describes the synthesis of the Earth’s total magnetic field and then describes the method simulating the output of scalar and vector magnetometers.Finally,the calibration method is applied to the synthetic magnetometer data to analyze the possible noise/error of the relevant instruments.Our results show that the simulator can imitate the disturbance of different noise sources or errors in the measuring system,and is especially useful for the satellite’s data processing group.

Image-based visualization of stents in mechanical thrombectomy for acute ischemic stroke:Preliminary findings from a series of cases

BACKGROUND Mechanical thrombectomy is the most effective treatment for great cerebral artery embolization within a set time window.Typically,an arteriogram does not show the localization of the stent after release and whether a thrombus is captured or not.Thus,improving the visualization of a stent in interventional therapy will be helpful for clinicians.AIM To analyze stent imaging findings to enhance clinicians’understanding of a special circumstance,wherein a Solitaire AB retrievable stent was visible during the imaging of a thrombus capture that improved the success rate of stent-based mechanical thrombectomy.METHODS This was a retrospective study with four acute ischemic stroke(AIS)patients who underwent stent-based mechanical thrombectomy.RESULTS Patient 1 was a 64-year-old man admitted after 5 h of confusion;angiography revealed basilar artery occlusion.We inserted a stent into the left posterior cerebral artery-P2 segment and visualized the expanded stent that successfully captured a thrombus.Patient 2 was a 74-year-old man admitted with confusion,which lasted approximately 3 h.Angiography revealed a left middle cerebral artery(MCA)-M1 segment occlusion.A stent was deployed in the distal M2 segment,and we could visualize the stent by capturing the thrombus.Patient 3 was a 74-year-old woman admitted after experiencing left hemiplegia for 3 h.We deployed a stent at the distal right MCAM2 segment,and the developing stent captured a large thrombus.Patient 4 was an 82-year-old man who presented with confusion for 3 h.A developing stent was placed in the distal left MCA-M1 segment,which captured a large thrombus and several fragmented thrombi.CONCLUSION To the best of our knowledge,this is the first report of stent imaging in patients with AIS.We demonstrated the usefulness and substantial potential of stent imaging in stent-based mechanical thrombectomy for AIS.

xMgO-(1-x)CaO-SiO2玻璃结构的拉曼光谱研究

制备了系列Mg置换Ca的硅酸盐[xMgO-(1-x)CaO-SiO2(x=0~1,Δx=0.05)]玻璃,采用波长532 nm脉冲激光测得其拉曼光谱。同时,运用量子化学从头计算法搭建钙硅酸盐和镁硅酸盐结构团簇模型,并采用精细结构,对该镁钙硅酸盐系列玻璃拉曼光谱进行解析,并对其微结构信息进行定量分析。随着Mg相对浓度的增加,Si-Ob-Si键角分布变宽、Mg离子渗入能力和无序性较Ca离子大,使不同类型Qi结构之间更为融合,相互勾联。这将导致Mg置换Ca的硅酸盐熔体高温粘度呈现增大的趋势。

Neuroprotective effects of the immunodepressant FTY720 on caspase-3 expression and neural apoptosis in a rat model of acute spinal cord injury

BACKGROUND：Studies on the immunodepressant FTY720 have primarily focused on organ transplantation and autoimmune disease therapy.However,the effects on caspase-3 expression and neural apoptosis following acute spinal cord injury remain uncertain.OBJECTIVE：To elucidate the underlying mechanism of the immunodepressant FTY720 to alleviate spinal cord injury by inhibiting expression of caspase-3 and neural apoptosis.DESIGN,TIME AND SETTING：A randomized,controlled,animal experiment was performed at Central Laboratory of the Second Affiliated Hospital of Dalian Medical University from April to July 2009.MATERIALS：FTY720 was provided by Wuhan Yuancheng Technology Developing,China.METHODS：A total of 120 Sprague Dawley rats were randomly assigned to sham-surgery,model,and FTY720 groups.Spinal cord injury at the T9-10 segment was induced in model groups using the free-fall method.Following establishment of spinal cord injury at the T9-10 segment in the FTY720 group,rats were treated with an intragastric injection of 0.3 mL saline-diluted FTY720 （3 mg/kg）.MAIN OUTCOME MEASURES：At 6,12,24,48,and 72 hours following spinal cord injury,caspase-3 expression was detected using streptavidin-peroxidase immunohistochemistry,and neural apoptosis was detected using the TUNEL method.RESULTS：Positive caspase-3 expression and neural apoptosis was not observed in the sham-surgery group at the various time points.The number of apoptotic cells increased with time after acute spinal cord injury,peaked at 24 hours following injury,and then gradually reduced.However,neural apoptosis remained at a high level.Caspase-3 expression positively correlated with neural apoptosis （r= 0.864,P〈 0.05）.Caspase-3 expression and neural apoptosis significantly decreased following FTY720 therapy （P〈 0.05）.CONCLUSION：FTY720 significantly reduced caspase-3 expression and neural apoptosis in a rat model of acute spinal cord injury.

Efficacy and economic analysis of Ex- PRESS implantation versus trabeculectomy in uncontrolled glaucoma： a systematic review and Meta-analysis

AIM：To systematically review the current evidence based on the efficacy and cost of Ex-PRESS implantation and trabeculectomy（Trab）for uncontrolled glaucoma.·METHODS：Clinical trials were identified by electronic databases（Pub Med,EMBASE,ISI Web of science and Cochrane library）,and data,such as intraocular pressure（IOP）,the complete and qualified success rate,the postoperative complications and the cost,were exacted from these relevant studies.Weighted mean difference（WMD）,odds ratio（OR）and 95%confidence intervals（CIs）were calculated and were pooled using a randomeffects model.·RESULTS：Eleven relevant publications and two abstracts met the inclusion criteria.The efficacy of ExPRESS was similar to that of Trab in the percentage of IOP reduction（IOPR%）at 1,2y（WMD：-2.01;95%CI：-7.92-3.90;=0.50 and WMD：2.89;95%CI：-8.05-13.83;=0.60,respectively）.Ex-PRESS possessed a significant higher complete and qualified success rate（OR：1.59;95%CI：1.07-2.35;=0.02 and OR：1.74;95%CI：1.06-2.86;=0.03,respectively）.Moreover,Ex-PRESS exerted a significantly lower frequency of hypotony and hyphema than Trab（OR：0.39;95%CI：0.21-0.72;=0.003 and OR：0.27;95%CI：0.10-0.69;=0.003,respectively）.However,there was no consistent result on the cost between the two groups according to the previous three studies.·C ONCLUSION：Both Trab and Ex-PRESS have equivalent efficacy in lowering IOP,yet Ex-PRESS had a lower risk of hypotony and hyphema than Trab.Nevertheless,whether the cost of Ex-PRESS was less than that of Trab should be further investigated to ensure evidence-based conclusion in the long run.

Combination of ranibizumab with photodynamic therapy vs ranibizumab monotherapy in the treatment of age-related macular degeneration: a systematic review and meta-analysis of randomized controlled trials

AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy(PDT)vs ranibizumab monotherapy in the treatment of age-related macular degeneration(AMD).METHODS:The Cochrane Central Register of Controlled Trials(CENTRAL)in the Cochrane Library,Pubmed,and Embase were searched.There were no language or data restrictions in the search for trials.Only randomized controlled trials(RCTs)were included.Methodological quality of the literatures was evaluated according to the Jadad Score.RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review,among which four of them were included in quantitative analysis.The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity(BCVA)change vs baseline at month 12 compared with that of the combination treatment group,and the statistical difference was significant(WMD,-2.61;95%CI,-5.08 to-0.13;P=0.04).However,after the removal of one study,the difference between the two groups showed no significant difference(WMD,-2.29;95%CI,-4.81 to 0.23;P=0.07).Meanwhile,no significant central retinal thickness(CRT)reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up.Nevertheless,the combination group tended to have a greater reduction in CRT(WMD,-4.13μm;95%CI,-25.88to 17.63,P=0.71).The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference(RR,0.72;95%CI,0.54 to 0.95;P=0.02).Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month12 between the two groups(RR,0.93;95%CI,0.76 to1.15;P=0.52).The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group.As major adverse events,the differences in the number of eye pain,endophthalmitis,hypertension and arterial thromboembolic events were not significant between the two groups,and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision,the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference.Compared with the combination of ranibizumab and PDT,patients treated with ranibizumab monothearpy may gain more visual acuity(VA)improvement.The combination treatment group had a tendency to reduce the number of ranibizumab retreatment.Both the two treatment strategies were well tolerated.

MRI Manif estions Correlate with Survival of Glioblastoma Multiforme Patients

Objective To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma multiforme(GBM). Methods The magnetic resonance imaging(MRI) images of 30 glioblastoma patients were collected.Imaging features including degrees of contrasted area,edema surrounding the tumor,and intensity in T2-weighted imaging were selected to determine their correlation with patient survival.The relationship between imaging and survival time was studied using SPSS 19.0 software.KaplanMeier survival analysis and log-rank test were used to compare the survival curves. Results Patients with <5%contrasted enhancement area of tumor had longer overall survival(OS) than those with >5%contrasted enhancement area of tumor.Patients without edema surrounding the tumor had longer OS than those with edema.Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. Conclusions Some MR imaging features including degrees of contrasted area,edema surrounding the tumor,and intensity in T2- weighted imaging are correlated with the survival of patients with GBM.These features can serve as prognostic indicators for GBM patients.

Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis

AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P&#x02264;0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P&#x0003c;0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P&#x0003c;0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.

Study on the discharge mechanism and EM radiation characteristics of Trichel pulse discharge in air

The Trichel pulse stage is an unstable stage of negative corona discharge that can also involve electromagnetic(EM)radiation signals.In this paper,the discharge mechanism and radiation characteristics of the Trichel pulse are studied in the needle-plate electrode configuration.The Trichel pulse currenl and its EM radiation signals are measured at different applied voltages.The results show that Trichel pulse discharge changes from the nindom pulse stage to the continuous pulse stage as the applied voltage increases.During these different stages,the normalized shape of the Trichel pulses remains unchanged,while the frequency of the EM radiation generated by the discharge remains unchanged.The discharge mechanism and EM radiation characteristics of the Trichel pulse are theoretically analyzed in the different stages.Both the positive ion sheath and the negative ion cloud play key roles in the formation of the Trichel pulse.The EM radiati on signal is generated by the rapidly changing Trichel pulse current,and the Trichel pulse current waveform determines the characteristics of the EM radiation signal.

Spatial pattern and drivers of urbanization in China's mid-level developing urban agglomeration:A case study of Chang-Zhu-Tan

Urban agglomeration has become the main form of regional spatial organization in China.While most of the existing studies of urban agglomeration in China have focused on the eastern coastal areas,urban agglomeration with mid-level development in the rest of the country has been overlooke1.To better understand the urbanization process of the mid-level developing urban agglomeration,this study investigated the clustering pattern and the drivers of both urban population and firm dynamics during 2005-2015 in the Changsha-Zhuzhou-Xiangtan(Chang-Zhu-Tan)urban agglomeration of China using the methods ofkernel density estimation and geographic detection.Our results show that centralization was obvious,although decentralization also occurred in Chang-Zhu-Tan,and that the spatial agglomeration was promoted by several factors,such as administrative resources,location advantage,labor cost,and consumption capacity.Some problems hindering the development of this region were also discovered:administrative resources played a critical role in urbanization because small towns and villages did not receive enough attention,and the effect of local policy was not as beneficial as expected.These findings partly explain the relatively slow development of mid-level developing urban agglomerations and have important implications for promoting healthier urbanization.

(CaO-SiO_(2))-xAl_(2)O_(3)三元系玻璃微结构的拉曼光谱定量研究

本文采用气动悬浮装置成功制备了(CaO-SiO_(2))-xAl_(2)O_(3)(x=0,6,12,18,24,30)的一系列玻璃,并通过拉曼光谱技术结合量子化学从头计算方法、^(27)Al魔角旋转核磁共振技术(^(27)Al MAS-NMR)对其结构进行了定性及定量研究。研究结果表明,当碱度R(CaO/SiO_(2))=1时,随着Al_(2)O_(3)的加入,硅酸盐结构转变为铝硅酸盐结构。当x≤18时,Al主要以[^(Ⅳ)AlO_(4)]形式参与网络形成,并在x=18时达到最大,同时也观察到了[^(Ⅴ)AlO_(5)]、[^(Ⅵ)AlO_(6)]的存在;当x>18时,[^(Ⅳ)AlO_(4)]相对含量减少,[^(Ⅴ)AlO_(5)]、[^(Ⅵ)AlO_(6)]增加。拉曼光谱精细解谱的结果表明,Al的加入大大增加了体系的复杂性和无序性,具体表现为精细结构Qijklm含量的无规律变化,但对初级结构Q_(i)含量的影响不大,并主要以Q_(2)形式存在。

Precise Positions of Triton in 2010–2014 based on Gaia-DR2

With unique orbital and physical characteristics,Triton is a very important target because it may contain information of the origin and evolution of the solar system.Besides space explorations,ground-based observations over long time also play a key role on research of Triton.High-precision positions of Triton obtained from ground telescopes are of great significance for studying its orbital evolution and the physical properties of Neptune.As a long-term observational target,Triton has been observed by the 1.56 m telescope of Shanghai Astronomical Observatory since 1996.In this paper,based on our AAPPDI software and with Gaia DR2 as the reference catalog,604 positions of Triton during 2010–2014 are calculated,with standard errors of 19–88 mas.A comparison between our results and the ephemeris(DE431+nep096)is also given.

Hemodynamic Shear Stress Regulates the Survival of Circulating Tumour Cells Through Piezo1-Actomyosin-Mediated YAP/TAZ Nuclear Translocation

It is critical to combat tumor metastasis by eradicating disseminated tumor cells in any step during the metastasis process.After entering the blood circulation system,tumor cells are in suspension and experience considerable levels of fluid shear stress.However,the influence of hemodynamic shear stress on the survival of CTCs and the underlying mechanotransduction mechanisms remain unclear.This study shows that fluid shear stress can eliminate the majority of CTCs and the viability of suspended tumor cells depends on the stress magnitude,indicating that tumor cells can sense and respond to fluid shear stress.Mechanistically,the expression of Piezo1 but not Piezo2 is greatly upregulated in suspended tumor cells after shear stress treatment.Inhibiting/activating Piezo1 increases/decreases the viability of suspended tumor cells in shear flow,which depends on Piezo1-mediated calcium entry.These findings suggest that Piezo1 may be the major mechanosensor by which suspended tumor cells sense fluid shear stress.As the downstream effector of Piezo1,actomyosin in tumor cells is significantly activated under increasing shear stress.Its activity influences the survival of CTCs in shear flow and rescues the effects of Piezo1 on tumor cell survival,suggesting that hemodynamic shear stress regulates the survival of CTCs through Piezo1 mediated actomyosin activity.Importantly,fluid shear stress considerably up-regulates YAP/TAZ activity of suspended tumor cells and promotes their nuclear translocation in a magnitude-dependent manner.Inhibiting YAP/TAZ enhances the viability of suspended tumor cells in shear stress,while activating their activity decreases tumor cell survival,suggesting that YAP/TAZ activation promotes the apoptosis of suspended tumor cells,which is different from the findings that YAP/TAZ facilitates the survival of adherent cells to shear flow.Further,blocking the nuclear import of YAP/TAZ inactivates the sensation of suspended tumor cells to fluid shear flow and attenuates the dependence of tumor cell survival on different magnitudes of hemodynamic shear stress.The influence of Piezo1-actomyosin pathway on suspended tumor cells can be rescued by YAP/TAZ activity,suggesting that Piezo1-mediated signaling induces tumor cell apoptosis via nuclear translocation of YAP/TAZ.In addition,fluid shear stress can also activate the expressions of LATS1/2 and MST1/2 in Hippo pathway through Piezo1,which is known to inhibit YAP/TAZ activity.Silencing/activating LATS1/2 or MST1/2 inhibits/enhances the viability of CTCs under shear stress,the effects of which can be further rescued by YAP/TAZ.These findings suggest that the responses of suspended tumor cells to hemodynamic shear stress are partially mediated by Hippo signaling.After nuclear translocation,YAP/TAZ directly bind p73/PUMA,which further promotes the transcription of pro-apoptotic genes and induces the apoptosis of suspended tumor cells.In summary,these findings show that hemodynamic shear stress considerably influences the survival of CTCs in blood circulation.We have identified the calcium channel Piezo1 as a novel mechanosensor for the response of CTCs to fluid shear stress.Hemodynamic shear stress induces the apoptosis of suspended tumor cells through Piezo1-actomyosin-YAP/TAZ-p73/PUMA signaling,which is different from the mechanotranduction mechanisms for tumor cells in adherent.Therefore,this study has unveiled the novel mechanosensor of suspended CTCs in response to fluid shear stress and the subsequent mechanisms and identified Piezo1 and YAP/TAZ as the potential therapeutic targets,through which CTCs may be effectively eradicated in the vasculature to prohibit tumor metastasis.

Cell Mechanics Regulates Cellular Uptake of Graphene Quantum Dot for Specifically Targeting Cancer Stem Cells

Cancer stem cells(CSCs)are the driving force for sustainable tumor growth and metastasis and responsible for drug resistance and cancer relapse.Nanoparticle-based drug delivery has been demonstrated to be effective in combating tumor growth.However,it has been challenging to selectively eliminate CSCs due to the lack of a general signature for a spectrum of cancers.It is known that CSCs from various types of cancer show lower stiffness compared to non-CSCs.It remains unclear whether low stiffness in CSCs influences cellular uptake in nanoparticle-based drug delivery and thus the chemotherapy efficacy.Graphene quantum dot(GQD)is emerging as a promising carrier material in delivering anti-cancer drugs.We found that breast CSCs were softer than conventional cancer cells,which were further softer compared to healthy breast tissue cells.Importantly,soft CSCs uptook more GQD than conventional cancer cells,while stiff breast cancer cells with relatively low stiffness uptook more GQD than healthy breast cells.Softening cells by pharmacologically inhibiting actomyosin activity using either siRNA or actomyosin inhibitors significantly enhanced the cellular uptake of GQD in breast cancer cells but not CSCs,while stiffening cells by activating actomyosin using CA-MLCK/ROCK or actomyosin activators considerably suppressed the nanoparticle uptake in both cancer cells and CSCs.GQD could specifically target CSC because of low cell stiffness of CSC in breast cancer cell line MCF-7 and MDA-MB-231.Further regulating cell stiffness reflected that decreasing breast cancer cell stiffness by inhibiting actomyosin activity using blebbistatin could promote GQD uptake.Vice versa,stiffening cancer cell by activating actomyosin decreased GQD uptake.The attachment of anti-cancer drug doxorubicin did not alter the trend of GQD uptake in neither soften nor stiffen cancer cells.Actomyosin activity regulates cellular uptake ofGQD might through clathrin and caveolin-mediated endocytosis.Cancer cells are softer than normal cells from the same organ,CSC are softer than non-CSC.Thus we further confirmed that the GQD uptake of normal breast cell line MCF-10 is less than breast cancer cell line MCF-7 and MDA-MB-231.Suggesting the clinical significance that using GQD as drug carrier targeting softer cells could reduce side effects to normal tissue cells.Since CSC are softer than non-CSC,GQD could decreased the percentage of CSC in whole cancer cell population by targeting softer cells.These results suggesting that it would be possible to target cancer cells and CSC by targeting from a perspective of cell mechanical difference.High uptake of nanoparticles in soft cancer cells could not be explained by their differential membrane potentials.Mechanistically,low cell mechanics or inhibiting actomyosin activity activated both clathrin and caveolin-mediated endocytosis signaling pathways,while high cell mechanics or activating actomyosin suppressed these signalings.Pharmacologically inhibiting clathrin or caveolin-mediated endocytosis signaling significantly decreased GQD uptake in CSCs and in conventional breast cancer cells when actomyosin was suppressed.Further,GQD conjugated with doxorubicin could be specifically delivered into CSCs with low stiffness and eliminated more CSCs in the presence of both CSCs and non-CSCs.Taken together,these data reveal the regulatory role of cell mechanics in cellular uptake of nanoparticles and demonstrate that GQD can be utilized to specifically eliminate CSCs,which have important implications in nanoparticle-based drug delivery for cancer therapy.

Shear Stress Regulates Tumor Cell Mechanics and Actomyosin-Dependent Survival and Chemoresistance

Metastasis is the main cause of cancer death,and tumor cells mainly disseminate to the distal organs through the blood circulation,in which they experience considerable levels of fluid shear stress.CTCs are heterogeneous with diverse subpopulations of distinct genotypes and phenotypes and the frequency of CTCs is correlated with poor prognosis and overall survival in cancer patients.Less than 0.01%of them may eventually generate metastatic tumors in secondary sites,indicating the inefficiency of metastasis.Nevertheless,metastasis accounts for over 90%of cancer-related deaths,suggesting that a subpopulation of CTCs are able to survive the metastatic process and form metastases.To target metastasis,it is thus essential to understand the roles of various factors during dissemination in the survival and functions of CTCs.However,the effects of hemodynamic shear stress on biophysical properties and functions of CTCs in suspension are not fully understood.This study was to investigate the effect of hemodynamic shear stress on the survival and anti-chemotherapy ability of suspended circulating tumor cells during metastasis,and the effect of actomyosin activity on this regulation.In this study,we developed a circulatory system to generate physiologic levels of hemodynamic shear stress,which mimicked certain important aspects of the CTC microenvironment in blood circulation.The survival of tumor cells in suspension,as a model for real CTCs,under different shear stress and circulation duration was examined.We found that the majority of breast tumor cells s in suspension can be eliminated by hemodynamic shear stress.The surviving cells exhibit unique biophysical properties,including significantly retarded cell adhesion,mesenchymal-like cell morphology,and reduced F-actin expression and cellular stiffness.Cancer stem cells which has been reported in other papers have lower stiffness compared with conventional tumor cells showed significantly higher survival in blood flow.Importantly,low actomyosin activity promotes the survival of CTCs in blood shear flow while high actomyosin activity inhibits tumor cells surviving shear stress treatment.These findings might be explained by the up-and down-regulation of the anti-apoptosis genes.Soft surviving tumor cells held survival advantages in shear flow and higher resistance to chemotherapy.Metastasis is closely linked with chemoresistance.However,the underlying mechanisms have not been fully understood,in particular,the roles of hemodynamic shear stress and actomyosin-dependent cell mechanics in drug resistance of CTCs remain unclear.Inhibiting actomyosin activity in suspended tumor cells enhanced chemoresistance,while activating actomyosin suppressed this ability.These findings might be associated with the corresponding changes in multidrug resistance related genes.Our study unveils the regulatory roles of actomyosin in the survival and drug resistance of circulating tumor cells in hemodynamic shear flow,which imply the importance of fluid shear stress and actomyosin activity in tumor metastasis.Our findings reveal a new mechanism by which circulating tumor cells are able to survive hemodynamic shear stress and chemotherapy and may offer a new potential strategy to target circulating tumor cells in shear flow and combat chemoresistance through actomyosin.

The research objectives and observational possibilities for fast moving near-Earth asteroids

The paper describes observations of fast-moving near-Earth asteroids(NEAs) made with the small ground-based telescopes of National Time Service Center of Chinese Academy of Science(NTSC of CAS) and Research Institute "Mykolaiv Astronomical Observatory"(RI MAO) by the rotating-drift-scan CCD(RDS CCD) technique. This technique is used to obtain the point images of both the studied objects and reference stars. The results of ongoing follow-up observations of NEAs are discussed. The residual differences(O-C) between the observed and calculated positions from JPL ephemeris were generally small for these asteroids. The standard deviations of these differences were typically ±(0.2′′-0.3′′) in both coordinates for objects with apparent velocity which substantially exceed FWHM for the given exposure time. The results of comparative statistics for such observations from the MPC database show that this is a good level of precision for NEAs. Moreover, the telescopes with the RDS CCD technique implemented can observe the NEAs that closely approach the Earth and with enough observations can improve the precision of determining their orbital elements and impact predictions.