Targeting the chromatin structural changes of antitumor immunity

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Properties of Flare Events on M Stars from LAMOST Spectral Survey Based on Kepler and TESS Light Curves

A catalog of M stars has been published from the Large Sky Area Multi-Object Fiber Spectroscopic Telescope data release 7(LAMOST DR7).We cross-matched the LAMOST M catalog with Kepler,Kepler 2(K2)and Transiting Exoplanet Survey Satellite(TESS)surveys.We obtained the light curves from the Kepler and TESS surveys.We detected 20,047 flare events from 4053 M stars and calculated their durations,amplitudes,and energies.We analyzed the distribution of the flare durations and energies.The distributions of flare duration for Kepler,K2 and TESS peak are at 3–3.5 hr,4–6 hr and 1–1.5 hr,respectively.This may be the result of the different cadences for the three data sets.The highest regions of the flare energies of Kepler,K2 and TESS are 32–32.5,32–32.5 and31–31.5 erg in Log format,respectively.A linear relationship between flare duration and energy emerges from our analysis.The ratio of flare duration to total observational time is approximately 0.2%–0.3%for the Kepler,K2 and TESS surveys.The occurrence rate of a star with a flare event increases from the M0 to M4 subtypes.We also determined the spatial distribution of the flare rate of M stars in the Milky Way.It seems that the flare rate decreases as the vertical height increases.The power index of the flare energies is in the region of 1.53–2.32,which is similar to previous result for solar type star(2.0).Further,we examined the relationship between the flare amplitude and chromospheric intensity.The flare activity increases rapidly with the increase in the HαEW at the lower values(less approximately 2?)and it increases slowly at the higher values.

桥连氧化钨纳米线的可控合成及气敏性质

氧化钨WO_(3−x)(0≤x<1)具有丰富的氧化态、亚化学计量比晶相以及可逆的光致/电致变色特性,纳米线具有高比表面积和准一维单晶载流子传输通道,WO_(3−x)纳米线结合了上述两者的优异特性,在智能玻璃、能源转换与存储器件和气体传感器等领域有广阔的应用前景。本文从WO_(3−x)的基本性质出发,分析了液相法和气相法(气-液-固、气-固、热氧化)纳米线生长的机制及特点。其中,热氧化法无需催化剂,有望解决纳米线应用的器件化瓶颈,在<500℃下即可实现纳米线尺寸与生长位置的可控生长,实现桥连纳米线器件的高效、原位集成。随后,本文综述了桥连WO_(3−x)纳米线器件在NOx等气体分子检测中的应用进展,梳理了桥连WO_(3−x)纳米线器件在低功耗、高灵敏气体分子检测中的应用,以期为今后高灵敏、低功耗、高集成的氧化物桥连纳米线器件的开发提供参考。

NF-κB信号通路抑制剂与溶瘤麻疹病毒疫苗株协同抗肺癌的作用及机制

背景与目的肺癌已成为我国发病率和死亡率居首位的恶性肿瘤。能自我复制、选择性杀伤肿瘤的溶瘤病毒,是治疗恶性肿瘤的有效策略,而其中溶瘤麻疹病毒疫苗株因其良好的溶瘤效果,且对正常细胞无损伤或微损伤,已进入几项临床试验。本研究旨在探讨核转录因子κB(nuclear factor kappa B,NF-κB)信号通路抑制剂与溶瘤麻疹病毒疫苗株协同抗肺癌的作用及机制。方法应用Western blot方法检测MV-Edm感染人肺癌细胞A549和H1299并应用细胞自噬相关的siRNA或者应用NF-кB通路抑制剂PS1145后SQSTM1、p-IκBα、IκBα、PARP及BAX的表达水平,运用流式细胞术分析各组细胞凋亡率的变化,同时采用噻唑蓝[3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide,MTT]法检测各组细胞的存活率。结果Western blot结果显示MV-Edm感染人肺癌细胞A549和H1299后,自噬引起NF-κB通路的激活,进而抑制细胞凋亡。抑制细胞自噬可抑制NF-κB通路的激活,MV-Edm感染后p-IκBα表达水平随着感染时间有不同程度的升高,IκBα的表达水平则降低,NF-κB通路抑制剂PS1145可促进人肺癌细胞A549和H1299凋亡(P<0.01),并增强其溶瘤效果。结论NF-κB信号通路抑制剂PS1145与溶瘤麻疹病毒疫苗株联合可促进人肺癌细胞A549和H1299凋亡,并增强其溶瘤效果。

VOCs分子的半导体型传感器识别检测研究进展

具有体积小、功耗低、灵敏度高、硅工艺兼容性好等优点的金属氧化物半导体(MOS)气体传感器现已广泛地应用于军事、科研和国民经济的各个领域。然而MOS传感器的低选择性阻碍了其在物联网(IoT)时代的应用前景。为此,本文综述了解决MOS传感器选择性的研究进展,主要介绍了敏感材料性能提升、电子鼻和热调制三种改善MOS传感器选择性的技术方法,阐述了三种方法目前所存在的问题及其未来的发展趋势。同时,本文还对比介绍了机器嗅觉领域主流的主成分分析(PCA)、线性判别分析(LDA)和神经网络(NN)模式识别/机器学习算法。最后,本综述展望了具有数据降维、特征提取和鲁棒性识别分类性能的卷积神经网络(CNN)深度学习算法在气体识别领域的应用前景。基于敏感材料性能的提升、多种调制手段与阵列技术的结合以及人工智能(AI)领域深度学习算法的最新进展,将会极大地增强非选择性MOS传感器的挥发性有机化合物(VOCs)分子识别能力。

Bacterial Cellulose Templated p-Co3O4/n-ZnO Nanocomposite with Excellent VOCs Response Performance

In this work,p-type Co3O4 decorated n-type ZnO(Co3O4/ZnO)nanocomposite was designed with the assistance of bacterial cellulose template.Phase composition,morphology and element distribution were investigated by XRD,SEM,HRTEM,EDS mapping and XPS.Volatile organic compounds(VOCs)sensing measurements indicated a noticeable improvement of response and decrease of working temperature for Co3O4/ZnO sensor,in comparison with pure ZnO,i.e.,the response towards 100 ppm acetone was 63.7(at a low working temperature of 180℃),which was 26 times higher than pure ZnO(response of 2.3 at 240℃).Excellent VOCs response characteristics could be ascribed to increased surface oxygen vacancy concentration(revealed by defect characterizations),catalytic activity of Co3O4 and the special p-n heterojunction structure,and bacterial cellulose provides a facile template for designing diverse functional heterojunctions for VOCs detection and other applications.

Numerical simulation and analysis of lithium plasma during low-pressure DC arc discharge

Alkali metal DC arc discharge has the characteristics of easy ionization,low power consumption,high plasma temperature and ionization degree,etc,which can be applied in aerospace vehicles in various ways.In this paper,we calculate the physical property parameters of lithium vapor,one of the major alkali metals,and analyze the discharge characteristics of lithium plasma with the magnetohydrodynamic(MHD)model.The discharge effects between constant current and voltage sources are also compared.It is shown that the lithium plasma of DC arc discharge has relatively high temperature and current density.The peak temperature can reach tens of thousands of K,and the current density reaches 6 x 107 A m 2.Under the same rated power,the plasma parameters of the constant voltage source discharge are much higher than those of the constant current source discharge,which can be used as the preferred discharge mode for aerospace applications.

幼儿园国学启蒙教育的实践与探索分析

近年来,我国传统文化的传承后继乏力问题逐渐成为社会热点问题,引发了社会各界的讨论与深思。我国作为世界四大文明古国之一,且是其中唯一传统文化未出现断绝的古老国家,历史底蕴丰富、具有独特、完备的社会发展与传承精神价值,以及书法艺术等文化精髓。因此为提高我国传统文化的传承力度,笔者从根源处着手,对幼儿园国学启蒙教育的实践探索以及国学启蒙教学的必要性开展深入研究。

An Improved Dynamic Friction Rejection Attitude Stability Control Strategy

The attitude stability control of under actuated spacecraft that used two reaction wheels in the presence of dynamic friction disturbance is handled. A novel improved control approach with a combination of a singular control law based on quaternion and extended state observer (ESO) is employed to establish a stabilization control so as to restrain the effect of friction. The corresponding simulation results demonstrate the highly stable accuracy and performance compensated dynamic friction. Furthermore if there is a non zero initial condition in under actuated axis the attitude stability can be enhanced with a magnetic torquer. Simulations for a nano spacecraft denote a potential application value in pointing accuracy using two reaction wheels and a magnetic torquer.

Enhanced Photovoltage for Inverted Perovskite Solar Cells Using Delafossite CuCrO_(2) Hole Transport Material

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS)has been widely adopted as hole transport material(HTM)in inverted perovskite solar cells(PSCs),due to high optical transparency,good mechanical flexibility,and high thermal stability;however,its acidity and hygroscopicity inevitably hamper the long-term stability of the PSCs and its energy level does not match well with perovskite materials with a relatively low open-circuit voltage.In this work,p-type delafossite CuCrO_(2)nanoparticles synthesized through hydrothermal method was employed as an alternative HTM for triple cation perovskite[(FAPbI_(3))_(0.87)(MAPbBr_(3))_(0.13)]_(0.92)(CsPbI_(3))_(0.08)(possessing better photovoltaic performance and stability than conventional CH3NH3PbI3)based inverted PSCs.The average open-circuit voltage of PSCs increases from 908 mV of the devices with PEDOT:PSS HTM to 1020 m V of the devices with CuCrO_(2)HTM.Ultraviolet photoemission spectroscopy demonstrates the energy band alignment between CuCrO_(2)and perovskite is better than that between PEDOT:PSS and perovskite,the electrochemical impedance spectroscopy indicates CuCrO_(2)-based PSCs exhibit larger recombination resistance and longer charge carrier lifetime than PEDOT:PSS-based PSCs,which contributes to the high VOCof CuCrO_(2)HTM-based PSCs.

Absolute parameters and observed flares in the M-type detached eclipsing binary 2MASS J04100497+2931023

The eclipsing binary 2 MASS J04100497+2931023(J04100497+2931023) is classified its spectral type of M0±2 V on basis of a low-resolution spectral survey by the Large Sky Area Multi-Object Fiber Spectroscopic Telescope(LAMOST). The low-resolution spectra exhibit strong single-peak emission in the Hα line. We obtained the radial velocities of this binary by means of the Cross-Correlation Function method from the LAMOST medium-resolution spectra. Both components of J04100497+2931023 indicate strong emissions in the Hα line. We performed follow-up photometric observations of J04100497+2931023 using the Xinglong 85 cm telescope of National Astronomical Observatories, Chinese Academy of Sciences. We obtained its full light curve in V RI filters. We first determined their absolute parameters from simultaneously radial velocity and light curves by the Wilson-Devinney program. From our new light curves, we detected three flares for the first time, including one convective flare. The amplitudes,durations, energies, and spectral indices of three flares were also determined. J04100497+2931023 was monitored for approximately 29 h, which indicates that the flare rate is 0.1 flare per hour. We conclude that J04100497+2931023 is a low-mass detached eclipsing binary with strong magnetic activity.

Experimental Study on Flexural Behavior of Post-Tensioning Bonded Partially Prestressed Ultra-High Strength Concrete Beams

This paper presents the results of four partially prestressed ultra-high strength concrete beams in flexure. The test results are used to evaluate the effects of prestressing tendon depth and area on flexure behavior of specimen beams. The test results indicate that: the cracking load,yielding load,peak load and stiffness postcracking of specimen beams are enhanced by reducing prestressing tendon depth or increasing prestressing tendon area, and the flexural ductility is improved by increasing prestressing tendon depth or reducing prestressing tendon area. The effect of complex reinforcement index considering the strength of the equivalence principle and the reinforcement position on loading levels under serviceability limit state,flexural strength and displacement ductility factor are studied. The influence coefficient of prestressing tendon kpis introduced in the complex reinforcement index. As the complex reinforcement index increases, the loading levels under serviceability limit state and flexural strength increases linearly,and the displacement ductility factor decreases linearly. The test results also verify the conventional beam flexural theory based on the plane cross-section assumption for predicting ultimate flexural strength of partially prestressed ultra-high strength concrete beams is valid. After the introduction of the coefficient kp,the calculation method of cracks in code for design of concrete structure in china are appropriated for the specimen beams.

Magnetic activity and orbital parameters of CC Com based on photometric data,LAMOST low-and medium-resolution spectra

In this paper,we present four sets of photometric VRI light curves,and several LAMOST low and medium resolution spectra of contact binary CC Com.We revised the orbital parameters by simultaneously combining with previously published radial velocity measurements using the WilsonDevinney program.We used light curves at different observational times to obtain the starspot parameters.The values of the starspot radius are variable in short-and long-term scales,and their longitudes are stable.We updated the orbital period change of CC Com,and analyzed the periodic variation.The period of CC Com decreases at a rate of 4.66(±0.20)×10^(-11)d yr^(-1),which may be due to mass transfer from the secondary component to the primary component.The oscillation of its orbital period with a period of17.18(0.08)years and amplitude of 0.0018(1)d may be caused by the light time effect(LITE)via a third body of 0.06 M☉dwarf or magnetic activity cycle.Furthermore,we obtained one optical spectrum from the LAMOST survey,which gives the spectral type of CC Com as K7±2 V.Strong emissions exist in the Ha,and Ca 11 H&K lines in the observed spectrum,indicating strong chromospheric activity on CC Com.In the 12 LAMOST medium-resolution spectra,the EWs of Ha line are variable along the phase and time,which may be a plage or flare event.

Transmission characteristics of EM wave in a finite thickness plasma

One of the key factors for solving the problems of re-entry communication interruption is electromagnetic（EM） wave transmission characteristics in a plasma.Theoretical and experimental studies were carried out on specific transmission characteristics for different plasma sheath characteristic under thin sheath condition in re-entry state.The paper presents systematic studies on the variations of wave attenuation characteristics versus plasma sheath thickness L,collision frequency ν,electron density n e and wave working frequency f in a φ 800 mm high temperature shock tube.In experiments,L is set to 4 cm and 38 cm.ν is 2 GHz and 15 GHz.n e is from 1×10 10 cm（-3） to 1×10 13 cm（-3）,and f is set to 2,5,10,14.6 GHz,respectively.Meanwhile,Wentzel-Kramers-Brillouin（WKB） and finite-difference time-domain（FDTD） methods are adopted to carry out theoretical simulation for comparison with experimental results.It is found that when L is much larger than EM wavelength λ（thick sheath） and ν is large,the theoretical result is in good agreement with experimental one,when sheath thickness L is much larger than λ,while ν is relatively small,two theoretical results are obviously different from the experimental ones.It means that the existing theoretical model can not fully describe the contribution of ν.Furthermore,when L and λ are of the same order of magnitude（thin sheath）,the experimental result is much smaller than the theoretical values,which indicates that the current model can not properly describe the thin sheath effect on EM attenuation characteristics.

Immunopeptidome mining reveals a novel ERS-induced target in T1D

Autoreactive CD8^(+)T cells play a key role in type 1 diabetes(T1D),but the antigen spectrum that activates autoreactive CD8^(+)T cells remains unclear.Endoplasmic reticulum stress(ERS)has been implicated inβ-cell autoantigen generation.Here,we analyzed the major histocompatibility complex class I(MHC-I)-associated immunopeptidome(MIP)of isletβ-cells under steady and ERS conditions and found that ERS reshaped the MIP ofβ-cells and promoted the MHC-I presentation of a panel of conventional self-peptides.Among them,OTUB2_(58-66 ) showed immunodominance,and the corresponding autoreactive CD8^(+)T cells were diabetogenic in nonobese diabetic(NOD)mice.High glucose intake upregulated pancreatic OTUB2 expression and amplified the OTUB2_(58-66 )-specific CD8^(+)T-cell response in NOD mice.Repeated OTUB2_(58-66 )administration significantly reduced the incidence of T1D in NOD mice.Interestingly,peripheral blood mononuclear cells(PBMCs)from patients with T1D,but not from healthy controls,showed a positive IFN-γresponse to human OTUB2 peptides.This study provides not only a new explanation for the role of ERS in promotingβ-cell-targeted autoimmunity but also a potential target for the prevention and treatment of T1D.The data are available via ProteomeXchange with the identifier PXD041227.

钙钛矿太阳电池电子传输层与光吸收层的界面工程

钙钛矿太阳电池(PSCs)自2009年出现至今经历了光伏领域前所未有的快速发展,目前经认证的最高光电转换效率已超过23%,极具应用前景。界面工程是提升PSCs性能的有效途径之一,本文回顾了PSCs中电子传输层和钙钛矿光吸收层间界面工程的主要研究工作,根据作用效果将相关研究按照改善钙钛矿光吸收层质量、提高电子传输层与钙钛矿层间的能级匹配度和提升电池稳定性等三类进行了梳理和总结,并对电子传输层和钙钛矿光吸收层间界面工程的前景进行了展望。

Carrier Cells for Delivery of Oncolytic Measles Virus into Tumors：Determinants of Efficient Loading

Oncolytic measles virus(OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies(NAbs) against the hemagglutinin(H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV.Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment. To this end, we systematically evaluated the antitumor efficacy of OMV using different loading strategies; this involved varying the in vitro loading duration and loading dose of OMV. We found that improved oncolysis of carrier cells was achieved by a prolonged loading duration in the absence of NAbs. However, the enhanced oncolytic effect was abrogated in the presence of NAbs. Further, we found that the expression of H protein on the surface of carrier cells was predominantly determined by the loading duration rather than the loading dose. Finally, we showed that NAbs blocked viral transfer by targeting H protein prior to the occurrence of cell-to-cell interactions. Our results provide comprehensive information on the determinants of an effective loading strategy for carrier cell-based virotherapy; these results may be useful for guiding the application of OMV as an antitumor agent in clinical practice.

An altered CD8^(+) T cell epitope of insulin prevents type 1 diabetes in humanized NOD mice

Autoreactive CD8^(+)T cells,which play an indispensable role inβcell destruction,represent an emerging target for the prevention of type 1 diabetes(T1D).Altered peptide ligands(APLs)can efficiently induce antigen-specific T cells anergy,apoptosis or shifts in the immune response.Here,we found that HLA-A*0201-restricted CD8^(+)T cell responses against a primaryβ-cell autoantigen insulin epitope InsB15–14 were present in both NOD.β2m null.HHD NOD mice and T1D patients.We generated several APL candidates for InsB15–14 by residue substitution at the p6 position.Only H6F exhibited an inhibitory effect on mInsB1_(5–14)-specific CD8^(+)T cell responses in vitro.H6F treatment significantly reduced the T1D incidence,which was accompanied by diminished autoreactive CD8^(+)T cell responses to mInsB15-14,inhibited infiltration of CD8^(+)and CD4^(+)T cells in the pancreas and reduced pro-inflammatory cytokine production in pancreatic and splenic T cells in NOD.β2m^(null).HHD mice.Mechanistically,H6F treatment significantly augmented a tiny portion of CD8^(+)CD25^(+)Foxp3^(+)T cells in the spleen and especially in the pancreas.This subset exhibited typical Treg phenotypes and required peptide-specific restimulation to exert immunosuppressive activity.Therefore,this APL H6F may be a promising candidate with potential clinical application value for antigen-specific prevention of T1D.

Achieving the Goals of Healthy China 2030 Depends on Increasing Smoking Cessation in China:Comparative Findings from the ITC Project in China,Japan,and the Republic of Korea

Summary Tobacco smoking is the number one preventable cause of disease and death in China as it is globally.Indeed,the toll of smoking in China is much greater than its status as the world’s most populous country.There is a persistent and continuing need for China to implement the measures specified in the global tobacco control treaty,the World Health Organization(WHO)Framework Convention on Tobacco Control(FCTC),which China ratified in 2005.

四阶测度微分方程第一特征值的极小值问题

给定有限的弹性力,引起梁弯曲的最小压缩负荷是多少?从数学上讲,这对应于四阶测度微分方程在Dirichlet边界条件下的第一特征值的极小化问题.本文将建立四阶测度微分方程第一特征值的变分刻画,然后给出第一特征值极小化问题的完整解答.从而在数学上回答了上述物理问题.