双荧光标记的人高骨转移肺腺癌细胞株的建立及其转录组学特征分析

背景与目的骨是肺腺癌常见的转移部位,但肺腺癌骨转移的机制尚不明确。目前肺腺癌骨转移机制研究缺乏易于示踪且稳定高骨转移的肺腺癌细胞模型,因此,本研究旨在建立绿色荧光蛋白(green f luorescent protein,GFP)和萤火虫荧光素酶(firefly luciferase,LUC)双标记的人高骨转移肺腺癌细胞株,为肺腺癌骨转移的研究提供新的实验工具。方法人肺腺癌细胞系A549-GFP-LUC经左心室注射至裸鼠体内构建骨转移模型,经连续3次体内驯化,获取人高骨转移肺腺癌细胞株A549-GFP-LUC-BM3;CCK-8(cell counting kit-8)、克隆形成实验比较A549-GFP-LUC-BM3细胞株和亲本细胞的体外增殖能力,划痕实验、Transwell实验以及Western blot比较迁移和侵袭能力;并进一步将A549-GFP-LUC-BM3细胞和亲本细胞行测序转录组学分析。结果成功建立人高骨转移肺腺癌细胞A549-GFP-LUC-BM3,相较于亲本细胞,该细胞骨转移发生率显著提高,且体外增殖、迁移和侵袭能力显著增强。转录组学测序结果显示,相较于亲本细胞,A549-GFP-LUC-BM3细胞中共筛选到差异基因2954个,其中1021个基因上调,1933个基因下调;基因本体(Gene Ontology,GO)功能富集显示差异基因主要定位于细胞外周、质膜以及细胞外基质等细胞组分,分子功能主要富集在信号受体结合、钙离子结合和细胞外基质结构成分等,生物过程富集在细胞黏附和生物黏附等;京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析显示差异基因在细胞色素P450(cytochrome P450,CYP)对外源性物质的代谢、视黄醇代谢、细胞黏附分子、CYP对药物代谢、类固醇激素的生物合成以及核因子κB(nuclear factor kappa B,NF-κB)信号通路上显著富集。结论成功建立GFP和LUC双标记的人高骨转移肺腺癌细胞株,该细胞株在生物学行为水平和转录组测序水平均提示具有高骨转移潜能。

Numerical study on the blocking effect of skin on Flash-Ball Impact and damage assessment

To explore the response law of non-lethal large-size kinetic energy projectiles to blunt attack on skin tissue,and to evaluate the skin injury characteristics of the attacked personnel and the use safety of kinetic energy projectiles.Based on the LS-DYNA simulation software,a three-layer skin simulation model and a Flash-Ball rubber bullet model are established,and the force-time and deformation-time biomechanical corridors of the Flash-Ball rubber bullet impacting human skin tissue are obtained.The corridor curve and the energy transfer and diffusion are analyzed and compared.The safety evaluation of the damage caused by the rubber bullet shooting a human body at different distances is carried out using the empirical formula of the penetration limit.Finally,the safe shooting distance is obtained.The results show that the model used in the simulation has a good correlation with the experimental data,its biomechanical corridor characteristics are different from those of conventional vehicle impact and smallsize projectile response characteristics.The energy transfer and action time of medium and low-speed impact may cause greater damage.The fat layer is the largest energy absorption unit.The minimum safe shooting distance to ensure skin tissue from penetrating damage is 15.8 m,and the limit specific kinetic energy of skin damage is 7.88 J/cm^(2).This study can be extended to the study of biomechanical response law and safety evaluation under the impact of the same type of large kinetic energy projectile,which provides an important theoretical reference for the police to use large kinetic energy projectiles to conduct safe shooting in peacekeeping operations.

The role of cholesterol metabolism in lung cancer

Elevated serum cholesterol metabolism is associated with a reduced risk of lung cancer.Disrupted cholesterol metabolism is evident in both lung cancer patients and tumor cells.Inhibiting tumor cell cholesterol uptake or biosynthesis pathways,through the modulation of receptors and enzymes such as liver X receptor and sterolregulatory element binding protein 2,effectively restrains lung tumor growth.Similarly,promoting cholesterol excretion yields comparable effects.Cholesterol metabolites,including oxysterols and isoprenoids,play a crucial role in regulating cholesterol metabolism within tumor cells,consequently impacting cancer progression.In lung cancer patients,both the cholesterol levels in the tumor microenvironment and within tumor cells significantly influence cell growth,proliferation,and metastasis.The effects of cholesterol metabolism are further mediated by the reprogramming of immune cells such as T cells,B cells,macrophages,myeloid-derived suppressor cells,among others.Ongoing research is investigating drugs targeting cholesterol metabolism for clinical treatments.Statins,targeting the cholesterol biosynthesis pathway,are widely employed in lung cancer treatment,either as standalone agents or in combination with other drugs.Additionally,drugs focusing on cholesterol transportation have shown promise as effective therapies for lung cancer.In this review,we summarized current research regarding the rule of cholesterol metabolism and therapeutic advances in lung cancer.

表观遗传学在恶性肿瘤发生发展和治疗中的新进展

表观遗传学修饰与肿瘤的发生发展密切相关,其主要通过DNA甲基化、组蛋白修饰、非编码RNA调控和染色质结构重构等方式对基因功能和表达水平进行调控,从而影响肿瘤的进展。目前针对表观遗传学的药物已经逐渐应用于恶性肿瘤的治疗,常见的药物类型包括DNA甲基转移酶抑制剂和组蛋白去乙酰化酶抑制剂,但此类药物仍存在诸多不足之处广泛的临床应用仍需要进一步的研究,令人鼓舞的是表观遗传药物与多种抗肿瘤药物联合应用已表现出巨大的应用潜力。本文就表观遗传学在恶性肿瘤的发生发展机制和相关药物的新进展进行了综述。

血浆中CDO1甲基化在肺癌早期诊断中的作用研究

背景与目的肺癌的发生率和死亡率常居所有恶性肿瘤的首位,DNA甲基化作为表观遗传学之一参与肿瘤的发生发展过程,CDO1作为抑癌基因常在肿瘤发生早期便会发生甲基化改变,因此本研究旨在探讨CDO1甲基化在肺癌早期诊断中的价值。方法收集肿瘤患者和健康人群的外周血液样本,游离DNA通过亚硫酸盐修饰并结合实时荧光定量PCR检测CDO1在外周血中的甲基化水平。结果肺癌患者的外周血的基因甲基化水平明显高于肺部良性疾病患者及健康人群。肺癌患者CDO1的甲基化水平在性别、淋巴结转移和肿瘤原发灶-淋巴结-转移(tumornode-metastasis, TNM)分期的分层比较中存在显著性差异(P<0.05)。CDO1对肺癌诊断的灵敏度和特异性分别为52.2%和78.6%。其诊断的整体准确度明显高于应用于临床的肿瘤标志物而且对I期、II期患者的诊断灵敏度表现最好(40.8%, 47.1%)。此外,CDO1可有效增加多项联检中诊断的灵敏性。结论检测CDO1的甲基化水平对肺癌的早期诊断具有潜在的巨大优势。

Recycle of Wastewater from Lead-Zinc Sulfide Ore Flo-tation Process by Ozone/BAC Technology

Lead-zinc sulphide ore contains lead sulphide (galena), and zinc sulphide (sphalerite). In the first flotation stage, galena is rendered hydrophobic with an organic collector such as xanthate, while sphalerite is kept from floating by depressants, and in the second flotation stage, activator was used to activated zinc flotation. Since the organic regent used are different in the two flotation stage, wastewater from the second zinc flotation stage can’t be directly recycled to the first lead flotation stage. Wastewater from flotation process for concentrating lead-zinc sulphide ore often containing organic compounds such as diethyldithiocarbamate(DDTC), xanthate, terpenic oil(2# oil) and thionocarbamate esters (Z-200), are environmentally hazardous. Their removal from contaminated water and the reuse of the water is one of the main challenges facing lead-zinc sulphide ore processing plants. In this study, synthetic wastewater containing DDTC, xanthate, 2# oil and Z-200 at concentrations ranging from 21 to 42 mg/L was fed into an Ozone/Biological activated carbon (BAC) reactor. Analyses of the effluent indicated a chemical oxygen demand (COD) removal over 86.21% and Total organic carbon (TOC) removal over 90.00% were achieved under Hydraulic retention time (HRT) of 4h and O3 feeding concentration of 33.3mg/L. The effluent was further recycled to the lab scale lead concentrating process and no significant difference was found in compare with fresh water. Furthermore, lead-zinc sulphide mineral concentrating process was carried out at lab scale. The produced wastewater was treated by Ozone/BAC reactor at O3 feeding concentration of 16.7mg/L and HRT of 4h. The effluent analysis showed that TOC removal was 74.58%. This effluent was recycled to the lab scale lead-zinc sulphide mineral concentrating process and the recovery of lead was not affected. The results showed that by using Ozone/BAC technology, the lead-zinc sulphide mineral processing wastewater could be recycled.

Particle-in-cell simulation for effect of anode temperature on discharge characteristics of a Hall effect thruster

Propellant gas flow has an important impact on the ionization and acceleration process of Hall effect thrusters （HETs）. In this paper, a particle-in-cell numerical method is used to study the effect of the anode temperature, i.e., the flow speed of the propellant gas, on the discharge characteristics of a HET. The simulation results show that, no matter the magnitude of the discharge voltage, the calculated variation trends of performance parameters with the anode temperature are in good agreement with the experimental ones presented in the literature. Further mechanism analysis indicates that the magnitude of the electron temperature is responsible for the two opposing variation laws found under different discharge voltages. When the discharge voltage is low, the electron temperature is low, and so is the intensity of the propellant ionization; the variation of the thruster performance with the anode temperature is thereby determined by the variation of the neutral density that affects the propellant utilization efficiency. When the discharge voltage is high, the electron temperature is large enough to guarantee a high degree of the propellant utilization no matter the magnitude of the anode temperature. The change of the thruster performance with the anode temperature is thus dominated by the change of the electron temperature and consequently the electron-neutral collisions as well as the electron cross-field mobility that affect the current utilization efficiency.

Eff ects of climate change on the potential habitat distribution of swimming crab Portunus trituberculatus under the species distribution model

Over the last decades,the species distribution model(SDM)has become an essential tool for studying the potential eff ects of climate change on species distribution.In this study,an ensemble SDM was developed to predict the changes in species distribution of swimming crab Portunus trituberculatus across diff erent seasons in the future(2050s and 2100s)under the climate scenarios of Representative Concentration Pathway(RCP)4.5 and RCP8.5.Results of the ensemble SDM indicate that the distribution of this species will move northward and exhibit evident seasonal variations.Among the four seasons,the suitable habitat for this species will be signifi cantly reduced in summer,with loss rates ranging from 45.23%(RCP4.5)to 88.26%(RCP.8.5)by the 2100s.The loss of habitat will mostly occur in the East China Sea and the southern part of the Yellow Sea,while a slight increase in habitat will occur in the northern part of the Bohai Sea.These fi ndings provide an information forecast for this species in the future.Such forecast will be helpful in improving fi shery management under climate change.

Unlocking Biomolecular Activity through Pd-Catalyzed Azides Reduction

Comprehensive Summary Pd-mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules,precise regulation of protein function,and cellular engineering.However,the availability of cleavable"caging"groups is quite limited,and their application in nucleic acid modification has seldom been reported.Herein,we introduce a method based on Pd-catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules.We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function,followed by the release of biological activity through Pd-catalyzed NaBH4 reduction amination reaction.This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes,prodrugs,and to regulate the biological function of RNA,including reverse transcription extension,binding to ligands,and cleavage activity of the CRISPR-Cas system.All results confirm that this strategy provides an efficient and controllable"OFF to ON"biological switch,capable of achieving significant regulatory effects substoichiometrically,and is expected to be extended to other biological applications.

Regulating CRISPR/Cas9 Using Streptavidin-Biotin Interactions

Comprehensive Summary Currently,CRISPR/Cas9 technology has found widespread applications across various domains.However,the utility of CRISPR/Cas9 is encumbered by issues pertaining to its reliability and safety,primarily stemming from the uncontrolled activity of the system.Therefore,the design and development of CRISPR/Cas9 systems with controllable activity is of paramount importance.Biotin,characterized by its small molecular weight,and streptavidin,distinguished by its substantial spatial steric hindrance,can be harnessed as an ideal OFF switch(termed a"bioactivity brake")due to their interaction characteristics.In this work,we present a strategy that employs the streptavidin-biotin interaction as a"brake system"for CRISPR/Cas9,effectively allowing for the shutdown of the enzymatic activity of CRISPR/Cas9.

Effect of yttrium and manganese addition on catalytic soot combustion activity and anti-high-temperature stability of CeO_(2) catalyst

In order to analyze the influence of the addition of yttrium and manganese on the soot combustion performance and high temperature stability of CeO_(2) catalyst,a series of Y/Mn-modified CeO_(2) catalysts were prepared.The effects of structural properties,textural properties,oxygen vacancies,Ce^(3+),surface adsorbed oxygen species,reduction properties and desorption properties of oxygen species on the activity were analyzed by various characterization methods.The results of the activity test show that the addition of manganese is beneficial to enhancement of the activity,while the addition of yttrium increases the amount of reactive oxygen species,but decreases the activity.After aging at 700℃,the activity of the CeMn catalyst decreases most sharply,while the catalytic activity of the CeY catalyst can be maintained to a certain extent.Interestingly,the addition of yttrium and manganese at the same time can stabilize the activity.The fundamental reason is that yttrium and manganese move to the surface of the solid solution after aging,which increases the reduction performance of the catalyst,thus contributing to the increase of activity.Although the activity of CeYMn catalyst decreases after aging at 800℃,it is still higher than that of other catalysts aged at 700℃.

Lean methane combustion over zeolite-supported Pd catalysts:Structure-performance relationship and deactivation mechanism

Zeolites are a promising support for Pd catalysts in leanmethane(CH_(4))combustion.Herein,three types of zeolites(H-MOR,H-ZSM-5 and H-Y)were selected to estimate their structural effects and deactivation mechanisms in CH_(4)combustion.We show that variations in zeolite structure and surface acidity led to distinct changes in Pd states.Pd/H-MOR with external high-dispersing Pd nanoparticles exhibited the best apparent activity,with activation energy(Ea)at 73 kJ/mol,while Pd/H-ZSM-5 displayed the highest turnover frequency(TOF)at 19.6×10^(−3)sec^(−1),presumably owing to its large particles with more step sites providing active sites in one particle for CH_(4)activation.Pd/H-Y with dispersed PdO within pore channels and/or Pd2+ions on ion-exchange sites yielded the lowest apparent activity and TOF.Furthermore,Pd/H-MOR and Pd/H-ZSM-5 were both stable under a dry condition,but introducing 3 vol.%H_(2)O caused the CH_(4)conversion rate on Pd/H-MOR drop from 100%to 63%and that on Pd/H-ZSM-5 decreased remarkably from 82%to 36%.The former was shown to originate fromzeolite structural dealumination,and the latter principally owed to Pd aggregation and the loss of active PdO.

Geographically driven shifts in land use influence phytoplankton community patterns in the Inner Mongolian Plateau lakes

Phytoplankton play an irreplaceable role as producers in maintaining lake ecosystems.Nevertheless,scant attention has been given to investigating the dispersion of phytoplankton communities and the factors influencing them across expansive areas.In this study,we present the results of a survey on the distribution of phytoplankton community and the effects of different driving factors in 11 lakes along Inner Mongolia in July–August 2020.Non-metric multidimensional scaling analysis and variance decomposition(VPA)were used to elucidate the distribution of phytoplankton communities and the response of drivers.A total of 169 species of phytoplankton from 8 phyla were detected.Both the abundance and diversity of phytoplankton in the Inner Mongolia lakes showed a trend of high in the east and low in the west(with Daihai Lake as the boundary).The Margalef index of phytoplankton significantly negatively correlated with salinity(r=−0.707,P<0.05)and total dissolved solids(r=−0.720,P<0.05),and both density and biomass highly significantly positively correlated with the suspended solids,Chlorophyll a and trophic level index.The VPA explained 38.9%of the changes in the phytoplankton community with the highest rate of explanation of land use.Therefore,preventing anthropogenic impacts,as well as reducing nutrient loads,can effectively ensure the ecological diversity of lake phytoplankton in lake populations with large geographical spans and varying levels of nutrients.

Long-Lasting Filtration of Oily Water by Anti-Fouling Underwater Oleophobic Sand Particles

The produced water from the oilfield was purified with filter material and then injected back into the ground.The serpentine filter material was easy to harden with the increase in filtration amount,which affected the water quality.A superhydrophilic/underwater oleophobic serpentine filter material was successfully prepared by a simple method of coating modification,which exhibited long-lasting filtration of oily water,good filtration and anti-fouling properties,and resistance to harden.The film-forming material of the superhydrophilic/underwater oleophobic coating was composed of SiO_(2) particles with small size,which could completely and evenly cover the filter particle.The weight loss was only 7.6%after mechanical stirring for 90 min.Compared with the original filter material,the superhydrophilic/underwater oleophobic serpentine filter material showed a better anti-fouling ability and resistance to harden.The filtration of crude oil emulsion and oil slick sewage showed a better backwashing performance.After 35 cycles of continuous filtration of suspended solids in wastewater,the backwashing rate reached 78.4%.The results provided an effective method for the filtration of oily wastewater in the oilfield.

Sm^(2+)ions boost ammonia electrooxidation reaction on samarium oxide anode for hydrogen generation in non-aqueous electrolyte

Ammonia has garnered recognition as a zero-carbon fuel due to its high-density hydrogen storage capacity and its convenience for storage and transportation.To address the challenges associated with the direct usage of ammonia,the development of NH_(3)-to-H_(2)conversion technologies has emerged as a promising and effective approach.Herein,we present for the first time that crystallized Sm_(2)O_(3−x)electrodes demonstrate high and stable electrocatalytic activities,including N_(2)evolution rate and Faradaic efficiency,for ammonia electrolysis in a non-aqueous electrolyte.It was observed that Sm^(2+)ions in samarium oxide play an indispensable role in the ammonia electrooxidation reaction on the anodes.Furthermore,the mechanism of ammonia electrooxidation has also been elucidated,laying the foundation for a better understanding of the relationship between local structure and electrochemical properties in order to facilitate research on Pt-free electrocatalysts for the electrolysis of ammonia into H_(2).

Streptavidin-Biotin Complexes as Tools for Modulating an Important DNA Episgenetic Modification

DNA 5-formylcytosine(5fC)is a prominent epigenetic modification within biological systems.Recent investigations have shed light on its pivotal role in governing cell fate,gene expression,and disease pathways.However,our comprehension of the precise control of the 5f site structure to influence its functionality remains limited.In this study,we have successfully achieved precise control over 5fc activity by harnessing the interaction between streptavidin and biotin.This research underscores the potential application of interactions between biomacromolecules and small molecules in advancing the field of DNA epigenetic functional regulation.

AVA:An automated and AI-driven intelligent visual analytics framework

With the incredible growth of the scale and complexity of datasets,creating proper visualizations for users becomes more and more challenging in large datasets.Though several visualization recommendation systems have been proposed,so far,the lack of practical engineering inputs is still a major concern regarding the usage of visualization recommendations in the industry.In this paper,we proposed AVA,an open-sourced web-based framework for Automated Visual Analytics.AVA contains both empiric-driven and insight-driven visualization recommendation methods to meet the demands of creating aesthetic visualizations and understanding expressible insights respectively.The code is available at https://github.com/antvis/AVA.

Prompting Large Language Models with Knowledge-Injection for Knowledge-Based Visual Question Answering

Previous works employ the Large Language Model(LLM)like GPT-3 for knowledge-based Visual Question Answering(VQA).We argue that the inferential capacity of LLM can be enhanced through knowledge injection.Although methods that utilize knowledge graphs to enhance LLM have been explored in various tasks,they may have some limitations,such as the possibility of not being able to retrieve the required knowledge.In this paper,we introduce a novel framework for knowledge-based VQA titled“Prompting Large Language Models with Knowledge-Injection”(PLLMKI).We use vanilla VQA model to inspire the LLM and further enhance the LLM with knowledge injection.Unlike earlier approaches,we adopt the LLM for knowledge enhancement instead of relying on knowledge graphs.Furthermore,we leverage open LLMs,incurring no additional costs.In comparison to existing baselines,our approach exhibits the accuracy improvement of over 1.3 and 1.7 on two knowledge-based VQA datasets,namely OK-VQA and A-OKVQA,respectively.

新型稠环电子受体的界面修饰对钙钛矿太阳能电池性能的影响

钙钛矿太阳能电池(perovskite solar cells, PSCs)因具有能量转换效率(power conversion efficiency, PCE)高、成本低、易于大面积制造等优点而被科学家们广泛关注.氧化物电子传输层的合理界面设计及修饰对提高器件的PCE和工作长期稳定性有着十分重要的意义.因此,本文采用一种含有烷基噻吩基侧链的稠环电子受体材料3,9-二(2-亚甲基-(3-(1,1-二氰甲烯基)-茚酮))-5,5,11,11-四(5-己基噻吩)-二噻吩并[2,3-d:2′,3′-d′]-s-引达省[1,2-b:5,6-b′]二噻吩(3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(5-hexylthienyl)-dithieno[2,3-d:2′,3′-d′]-s-indaceno[1,2-b:5,6-b′]dithiophene, ITIC-Th)修饰TiO2电子传输层,制备高效稳定的平面结PSCs.研究结果显示,ITIC-Th的界面修饰改善了TiO2薄膜的形貌、接触角等性质,促进了钙钛矿晶粒的高质量生长,大幅度减少了器件表界面的电荷复合,明显提升了光生载流子的抽取率和输运效率,使经ITIC-Th界面修饰的PSC的PCE从未经界面修饰的15.43%显著提高到18.91%.与此同时,器件稳定性的研究结果显示,在室温和湿度为30%的条件下,经ITICTh界面修饰的PSC的PCE在放置约1000 h后依然保持原来的90%,明显高于未经界面修饰的PSC.研究结果对PSC光伏性能的提升具有重要的实际应用价值和学术意义.

Epidemic transition of environmental health risk during China's urbanization

China has experienced rapid urbanization in recent decades along with dramatic economic growth. Previous studies have shown that urbanization has both positive and negative effects on health. However, there is a lack of research on the overall effects of urbanization on the epidemic transition of environmental health risks considering various pathways in China. In the present study, we studied the contributions of different aspects of urbanization in China to epidemic transitions using provincial and multi-year （1995, 2000, 2005, and 2010） panel data. Statistical models with fixed and random effects were developed to explore the impacts of different urbanization indicators on the overall epidemic tran- sition of environmental health （general model） and the changes in cause-specific mortality rates of typ- ical diseases （cause-specific models）. The results show that the impacts of non-communicable diseases continue to grow during the urbanization process in China. The ratio of communicable disease-related mortality to non-communicable disease-related mortality continues to decrease over time. The general model shows that the improved medical conditions （coefficient =-0.0011, P= 0.037）, the improved urban infrastructure （e.g., tap water supply） （coefficient = -0.00065, P 〈 0,001）, and the rise in income （coefficient = -0.00027, P = 0.047） during the urbanization process are important factors that promote this overall epidemic transition. The cause-specific models show that the mechanisms behind the general model are complicated. More attention should be paid to non-communicable diseases in urban health management. Specific health policies for different diseases should incorporate the considerations of dif- ferent impact pathwavs of urbanization,