3D numerical study of tumor blood perfusion and oxygen transport during vascular normalization

The changes of blood perfusion and oxygen transport in tumors during tumor vascular normalization are studied with 3-dimensional mathematical modeling and numerical simulation. The models of tumor angiogenesis and vascular-disrupting are used to simulate ＂un-normalized＂ and ＂normalized＂ vasculatures. A new model combining tumor hemodynamics and oxygen transport is developed. In this model, the intravasculartransvascular-interstitial flow with red blood cell（RBC） delivery is tightly coupled, and the oxygen resource is produced by heterogeneous distribution of hematocrit from the flow simulation. The results show that both tumor blood perfusion and hematocrit in the vessels increase, and the hypoxia microenvironment in the tumor center is greatly improved during vascular normalization. The total oxygen content inside the tumor tissue increases by about 67%, 51%, and 95% for the three approaches of vascular normalization,respectively. The elevation of oxygen concentration in tumors can improve its metabolic environment, and consequently reduce malignancy of tumor cells. It can also enhance radiation and chemotherapeutics to tumors.

High efficiency ETM-free perovskite cell composed of CuSCN and increasing gradient CH_(3)NH_(3)PbI_(3)

To enhance device performance and reduce fabrication cost,a series of electron transporting material(ETM)-free perovskite solar cells(PSCs)is developed by TCAD Atlas.The accuracy of the physical mode of PSCs is verified,due to the simulations of PEDOT:PSS-CH_(3)NH_(3)PbI_(3)-PCBM and CuSCN-CH_(3)NH_(3)PbI_(3)-PCBM p-i-n PSCs showing a good agreement with experimental results.Different hole transporting materials(HTMs)are selected and directly combined with n-CH_(3)NH_(3)PbI_(3),and the CuSCN-CH_(3)NH_(3)PbI_(3) is the best in these ETM-free PSCs.To further study the CuSCN-CH_(3)NH_(3)PbI_(3) PSC,the influences of back electrode material,gradient band gap,thickness,doping concentration,and bulk defect density on the performance are investigated.Energy band and distribution of electric field are utilized to optimize the design.As a result,the efficiency of CuSCN-CH_(3)NH_(3)PbI_(3) PSC is achieved to be 26.64%.This study provides the guideline for designing and improving the performances of ETM-free PSCs.

A flexible ultra-broadband metamaterial absorber working on whole K-bands with polarization-insensitive and wide-angle stability

For potential military applications, a flexible metamaterial absorber(MMA) working on whole K-bands with totalthickness of 3.367 mm, ultra-broadband, polarization-insensitive, and wide-angle stability is presented based on frequencyselective surface(FSS). The absorber is composed of polyvinyl chloride(PVC) layer, polyimide(PI) layer, and poly tetra fluoro ethylene(PTFE) layer, with a sandwich structure of PVC–PI–PTFE–metal plate. Periodic conductive patterns play a crucial role in the absorber, and in traditional, it is designed on the upper surface of PI layer to form LC resonance. Different from commonly absorber, all the patterns are located on the lower surface of the PI layer in this work, and hence the impedance matching and absorptivity are improved in this purposed absorber. The flexible absorber with patterns on lower surface of the PI layer is compared with that on upper surface of the PI layer, the difference and the reasons are explained by absorption mechanism based on equivalent circuit model, and surface current density and electric field distribution are used to analyze resonance peaks. Absorptivity is greater than 90% in a frequency range of 10.47 GHz–45.44 GHz with relative bandwidth of 125.1%, covering the whole Ku, K, Ka, and some of X, U bands, especially containing the whole K bands from 12 GHz to 40 GHz. Radar cross section(RCS) is reduced at least 10 dB in 11.48 GHz–43.87 GHz frequency ranges,and absorption remained about 90% when the incident angle changed from 0°to 55°. The purposed absorber is fabricated,measured, and experiment results show good agreement with theoretical analysis and numerical simulation. After bonded on outer surface of different cylinders with diameters of 200 mm and 100 mm, the absorption of MMA is approximately reduced 10% and 20% respectively, which shows good conformal character with surface of various curvatures. Due to the attractive performance on strong absorption in the whole K-bands, flexible and easy conformal, our design exhibits broad potential application in radar stealth and sensors.

Morphologies and evolution of intermetallic compounds formed between Sn_(1.0)Ag_(0.7)Cu composite solder and Cu substrate

This study investigated the morphologies of the intermetallic compounds(IMC)formed during soldering reaction between Sn_(1.0)Ag_(0.7)Cu-1.0SnO_(2) composite solder and Cu substrate at various temperatures.The prismtype Cu_(6)Sn_(5) forms when the soldering temperature is 260or 2800C,while those grains transform from prism type to scallop type at the temperatures of 300 and 320℃.It can be found that the morphologies of Cu6Sn5 grains affect adsorption of Ag_(3)Sn nanoparticles during soldering reaction.The scallop-type grains with a higher growth rate need to adsorb large amounts of Ag_(3)Sn particles.In terms of mechanical behavior,the shear strength of solder joint is improved from 40 to 46 MPa at soldering temperature of 300℃.In addition,the thickness of IMC increases with the extension of aging time.During aging,the morphology of Cu6Sn5 grains remains scallop type,but the number of Ag_(3)Sn nanoparticles is reduced largely.The scallop-type Cu^(6)Sn_(5) can increase in size and flatten in morphology with the aging time increasing.

血管生成素抑制雄激素性秃发区毛乳头细胞中I型胶原和纤维连接蛋白表达的研究

目的探讨血管生成素抑制雄激素性秃发区毛乳头细胞中I型胶原和纤维连接蛋白表达的作用及可能机制。方法分离培养雄激素性秃发区毛乳头细胞，实时定量荧光PCR检测雄激素受体mRNA在不同传代次数毛乳头细胞中的相对表达量，CCK8法检测0、10、20、40、80、160μg／L血管生成素对含或不含0．1nmol／L二氢睾酮培养基培养的毛乳头细胞增殖的影响。取生长融合的第l代毛乳头细胞传代后分为3组：对照组（不用二氢睾酮或血管生成素处理）、0．1nmol／L二氢睾酮组、0．1nmol／L二氢睾酮＋80μg／L血管生成素组。作用48h后，用实时荧光定量PCR检测I型胶原基因、纤维连接蛋白和转化生长因子β1（TGF-β1）mRNA的表达，Western印迹检测I型胶原、纤维连接蛋白、TGF一β1、p-Smad2和p-Smad3蛋白的表达。实验数据采用单因素方差分析、LSD检验和独立样本t检验进行分析。结果体外培养的雄激素性秃发区毛乳头细胞随着传代次数增加，雄激素受体mRNA相对表达量明显降低（P〈0．05）。细胞增殖实验发现，20-160μg／L血管生成素明显拮抗0．1nmol／L二氢皋酮对毛乳头细胞增殖的抑制作用（均P〈0．05）。与对照组相比，二氢睾酮组I型胶原基因、纤维连接蛋白和TGF一β1mRNA显著升高，但二氢睾酮＋血管生成素组较二氢睾酮组I型胶原基因mRNA（1．563±0．143比4．329±0．165）、纤维连接蛋白mRNA（1．290±0．063比2．156-4-0．115）和TGF-β1mRNA（1．136-4-0．098比1．707±0．100）显著降低（均P〈0．05）。而且，血管生成素还能明显抑制由二氢睾酮诱导的毛乳头细胞中I型胶原、纤维连接蛋白、TGF-β1、p-Smad2和p-Smad3蛋白的表达（均P〈0．05）。结论血管生成素在体外能够抑制雄激紊陆秃发区毛乳头细胞中细胞外基质成分I型胶原和纤维连接蛋白的表达，其机制可能与其下调TGF-β1表达及抑制TGF-β1／Smad信号通路的活化有关。

Role of interstitial flow in tumor migration through 3D ECM

Cancer invasion in tissue is simultaneously regulated by chemical and mechanical cues.Evidences suggest that interstitial flow plays a critical role in tumor metastasis.On one hand,the distribution of chemokines around cell is influenced by flow.On the other hand,interstitial flow may reconfigure the alignment of fiber matrix,which greatly changes the contact force between cell and extracellular matrix.In this study,we have upgraded a model by which we can quantitatively investigate the influence of flow on tumor cell migration.A hydrodynamic analysis of shear stress on a slender body is introduced to simulate the fiber realignment.Factors such as subtle flow and cell-matrix interaction which dominate tumor migration are integrated in this novel model.Simulation results show interstitial flow facilitates tumor cell migration in the flow direction.Moreover,the flow-related chemical and mechanical cues have a synergistic effect on the migration.This model provides better understanding on cancer metastasis and helps design vitro experiment precisely.

Targeting papain-like protease for broad-spectrum coronavirus inhibition

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics.Drugging the multi-functional papain-like protease(PLpro)domain of the viral nsp3 holds promise.However,none of the known coronavirus PLpro inhibitors has been shown to be in vivo active.Herein,we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity,including against the Sarbecoviruses(SARSCoV-1 and SARS-CoV-2),Merbecovirus(MERS-CoV),as well as the Alphacoronavirus(hCoV-229E and hCoVOC43).Importantly,F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice.F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage,as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity.Despite the significant difference of substrate recognition,mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue,whereas an allosteric inhibitor of MERSPLpro interacting with its 271E position.Our proof-ofconcept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anticoronavirus agents.The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.