Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

长链非编码RNA HOXA远端转录本在口腔鳞状细胞癌中的表达及生物学意义

目的:探讨长链非编码RNA HOXA远端转录本(HOXA transcript at the distal tip,HOTTIP)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中的表达及对OSCC细胞生物学功能的影响。方法:收集2020年1月至2021年6月在郑州大学第一附属医院接受手术治疗的52例OSCC患者,采用RT-qPCR检测HOTTIP在OSCC组织和癌旁组织以及人OSCC细胞株HSC-4、SCC-9和CAL-27和人正常口腔角质细胞株HOK中的表达水平,并分析其与OSCC患者临床病理资料及总生存期(overall survival,OS)的关系。采用CCK-8、流式细胞术、Transwell和Western blot分析下调HOTTIP或共下调HOTTIP和miR-637对CAL-27细胞增殖、凋亡、迁移、侵袭和上皮间质转化(epithelial-mesenchymal transition,EMT)能力的影响。采用双荧光素酶报告基因实验分析HOTTIP和miR-637的靶向关系。结果:与癌旁组织相比,OSCC组织中HOTTIP的表达水平明显升高(P<0.05),且与肿瘤大小、TNM分期、分化程度、淋巴结转移及OS相关(P<0.05)。与人正常口腔角质HOK细胞相比,HSC-4、SCC-9和CAL-27细胞中HOTTIP的表达明显升高(P<0.05)。下调HOTTIP后,CAL-27细胞的增殖、迁移、侵袭及EMT能力明显减弱,细胞凋亡率明显升高(P<0.05)。HOTTIP与miR-637具有靶向关系,且下调HOTTIP后,CAL-27细胞中miR-637表达明显升高(P<0.05)。同时下调HOTTIP和miR-637后,CAL-27细胞的增殖、迁移、侵袭与EMT能力明显增强,细胞凋亡率明显降低(P<0.05)。结论:HOTTIP在OSCC组织和细胞中高表达,可靶向miR-637调控OSCC细胞的增殖、凋亡、迁移、侵袭和EMT能力。

聚乙烯醇基凝胶聚合物电解质的制备及在锌离子混合电容器中的应用

锌离子混合电容器(ZIHC)兼有电池高能量密度和电容器高功率密度的特点,是下一代能源存储设备的有力竞争者,但电池型阴极-电容型阳极ZIHC的研究中使用的多为电解质溶液,容易泄漏而导致安全风险。针对这一问题,文中以纤维素、羟乙基纤维素和聚乙烯醇为原料,通过冷冻-解冻和电解液吸收的方法,快速制备了具有蜂巢状的三维网络形貌的凝胶聚合物电解质(GPE)。优化的GPE不仅具有良好力学性能(拉伸强度0.24 MPa、断裂伸长率289%),而且表现出较高的离子电导率(58.5 mS/cm)。使用GPE、二氧化锰阴极和活性炭阳极组成的ZIHC,其比电容和能量密度分别为31.5 F/g和15.0 Wh/kg,2 A/g充放电循环1.5×104次后比电容保持率约80%,展示出GPE在ZIHC领域中潜在的应用价值。原料环保和方便快捷的制备方法为能量存储和柔性可穿戴电子领域应用的GPE研究提供了新的思路。

Calculation and Analysis of TVMS Considering Profile Shifts and Surface Wear Evolution Process of Spur Gear

Profile shift is a highly effective technique for optimizing the performance of spur gear transmission systems.However,tooth surface wear is inevitable during gear meshing due to inadequate lubrication and long-term operation.Both profile shift and tooth surface wear(TSW)can impact the meshing characteristics by altering the involute tooth profile.In this study,a tooth stiffness model of spur gears that incorporates profile shift,TSW,tooth deformation,tooth contact deformation,fillet-foundation deformation,and gear body structure coupling is established.This model efficiently and accurately determines the time-varying mesh stiffness(TVMS).Additionally,an improved wear depth prediction method for spur gears is developed,which takes into consideration the mutually prime teeth numbers and more accurately reflects actual gear meshing conditions.Results show that consideration of the mutual prime of teeth numbers will have a certain impact on the TSW process.Furthermore,the finite element method(FEM)is employed to accurately verify the values of TVMS and load sharing ratio(LSR)of profile-shifted gears and worn gears.This study quantitatively analyzes the effect of profile shift on the surface wear process,which suggests that gear profile shift can partially alleviate the negative effects of TSW.The contribution of this study provides valuable insights into the design and maintenance of spur gear systems.

The potential impact of increased whole grain consumption among Chinese adults on reducing healthcare costs and carbon footprint

Excessive consumption of refined grains harms human health and ecosystem viability.Whole grains,as a healthy and sustainable alternative to refined grains,can benefit individual health by providing dietary fiber,B vitamins,and bioactive substances.Additionally,they aid in improving the environment due to their higher extraction rate and lower carbon emission during the processing stage.However,few studies have attempted to evaluate the economic and social benefits of increasing the amount of whole grain in grain intake.This paper estimates the potential savings in healthcare costs and reduced food carbon footprints(CFs)that could result from a shift toward whole grain consumption following the Chinese Dietary Guidelines(CDG).We investigate hypothetical scenarios where a certain proportion(5–100%)of Chinese adults could increase their whole grain intakes as proposed by CDG to meet the average shortfall of 30.2 g.In that case,the healthcare costs for associated diseases(e.g.,type2 diabetes mellitus(T2DM),cardiovascular disease(CVD),and colorectal cancer(CRC))are expected to reduce by a substantial amount,from USD 2.82 to 56.37 billion;the carbon emission levels are also projected to decrease by0.24–5.72 million tons.This study provides compelling evidence that advocating for the transition towards greater consumption of whole grain products could benefit individual health,the environment,and society,by reducing both healthcare costs and carbon emissions.

Description of martensitic transformation kinetics in Fe-C-X(X = Ni,Cr,Mn,Si) system by a modified model

Controlling the content of athermal martensite and retained austenite is important to improving the mechanical properties of high-strength steels,but a mechanism for the accurate description of martensitic transformation during the cooling process must be addressed.At present,frequently used semi-empirical kinetics models suffer from huge errors at the beginning of transformation,and most of them fail to exhibit the sigmoidal shape characteristic of transformation curves.To describe the martensitic transformation process accurately,based on the Magee model,we introduced the changes in the nucleation activation energy of martensite with temperature,which led to the varying nucleation rates of this model during martensitic transformation.According to the calculation results,the relative error of the modified model for the martensitic transformation kinetics curves of Fe-C-X(X = Ni,Cr,Mn,Si) alloys reached 9.5% compared with those measured via the thermal expansion method.The relative error was approximately reduced by two-thirds compared with that of the Magee model.The incorporation of nucleation activation energy into the kinetics model contributes to the improvement of its precision.

Taxing sugar-sweetened beverages in China:By volume or sugar content? A consumer welfare approach

Using scanner data on the consumption of packaged liquid beverages by Chinese urban households,we estimated the price elasticity of various beverages and compared the effects of volume-based versus sugar-content-based taxation strategies on consumer welfare.Compared to the volume-based tax,the sugar-content-based beverage tax was predicted to cost less in compensating variation under the same amount of sugar reduced,indicating that taxation based on sugar content may be more efficient in preserving consumer welfare.Further comparison across different socioeconomic groups reveals that,given current beverage consumption status in China,the efficiency advantage of the sugar-content-based taxation strategy is more pronounced than that of the volume-based taxation.Our conclusions can provide insights for the food industry and the government to reduce the sugar content in beverages.

Theoretical insights into the structures and fundamental properties of pnictogen nitrides

Recent experimental advancements reported a chemical reaction between antimony and nitrogen under high temperature and high pressure,yielding crystalline antimony nitride(Sb_(3)N_(5))with an orthorhombic structure.Motivated by this statement,we calculate the stability,elastic properties,electronic properties and energy density of the Cmc2_(1) structure for pnictogen nitrides X_(3)N_(5)(X=P,As,Sb,and Bi)using first-principles calculations combined with particle swarm optimization algorithms.Calculations of formation enthalpies,elastic constants and phonon spectra show that P_(3)N_(5),As_(3)N_(5) and Sb_(3)N_(5) are thermodynamically,mechanically and kinetically stable at 35 GPa,whereas Bi_(3)N_(5) is mechanically and kinetically stable but thermodynamically unstable.The computed electronic density of states shows strong covalent bonding between the N atoms and the phosphorus group atoms in the four compounds,confirmed by the calculated electronic localization function.We also calculate the energy densities for Sb_(3)N_(5) and find it to be a potentially high-energy-density material.

EDU-GAN:Edge Enhancement Generative Adversarial Networks with Dual-Domain Discriminators for Inscription Images Denoising

Recovering high-quality inscription images from unknown and complex inscription noisy images is a challenging research issue.Different fromnatural images,character images pay more attention to stroke information.However,existingmodelsmainly consider pixel-level informationwhile ignoring structural information of the character,such as its edge and glyph,resulting in reconstructed images with mottled local structure and character damage.To solve these problems,we propose a novel generative adversarial network(GAN)framework based on an edge-guided generator and a discriminator constructed by a dual-domain U-Net framework,i.e.,EDU-GAN.Unlike existing frameworks,the generator introduces the edge extractionmodule,guiding it into the denoising process through the attention mechanism,which maintains the edge detail of the restored inscription image.Moreover,a dual-domain U-Net-based discriminator is proposed to learn the global and local discrepancy between the denoised and the label images in both image and morphological domains,which is helpful to blind denoising tasks.The proposed dual-domain discriminator and generator for adversarial training can reduce local artifacts and keep the denoised character structure intact.Due to the lack of a real-inscription image,we built the real-inscription dataset to provide an effective benchmark for studying inscription image denoising.The experimental results show the superiority of our method both in the synthetic and real-inscription datasets.

Transforming agri-food systems for multiple wins in nutrition,inclusion and environment

The call for agri-food system transformation is urgent in many global development agendas(UN 2023).Food systems have contributed to economic prosperity and feeding the world,but they are also associated with numerous challenges,including climate change,continued hunger,poor diets and malnutrition,and increasing disparities(Webb et al.2020;Fanzo et al.2021).

金属单原子催化剂增强硫正极动力学的研究进展

单质硫具有理论能量密度高(2600 Wh·kg^(−1))、放电比容量高(1672 mAh·g^(−1))、成本低等优势,是锂硫电池的理想正极材料。然而,在充放电过程中硫正极迟缓的反应动力学显著地限制了锂硫电池的性能。金属单原子催化剂(SMACs)具有独特的电子结构、金属含量低、理论上100%的原子利用率、催化活性高等优势,其不仅有效地促进了不同中间相的转化反应,而且可为含硫物质提供丰富的锚定位点,从而显著优化硫正极氧化还原反应动力学、多硫化物的穿梭行为和锂硫电池电化学性能。本文以剖析金属单原子催化剂与硫正极间的相互作用为出发点,结合其催化效应表征技术,重点解析了不同类型单原子催化剂的构筑策略、活性调控及其优化硫正极氧化还原行为的机制,展望了金属单原子催化剂在锂硫电池领域面临的挑战和未来发展方向。

骨科植入物无机抗菌涂层的研究现状

植入物感染是骨科最常见和最严重的并发症之一,也是导致植入手术失败的重要原因。当细菌在植入物表面形成生物膜后会极难消除,并吸附更多的细菌和真菌。大量研究表明,通过采用表面改性技术可有效减少致病菌的黏附和聚积,进而预防植入物周围感染。本文首先分析了细菌生物膜在骨科植入物表面的形成过程以及金属抗菌剂的抗菌机制。然后综述了目前国内外使用最广泛的一些金属基无机抗菌涂层及其相关的制备工艺,讨论了这些涂层在应用中存在的问题和改善方法,并展望了未来无机抗菌涂层的发展方向,包括协同抗菌型涂层和促成骨型抗菌涂层等。

Recent Advances on Challenges and Strategies of Manganese Dioxide Cathodes for Aqueous Zinc-Ion Batteries

Aqueous zinc-ion batteries(AZIBs)are regarded as promising electrochemical energy storage devices owing to its low cost,intrinsic safety,abundant zinc reserves,and ideal specific capacity.Compared with other cathode materials,manganese dioxide with high voltage,environmental protection,and high theoretical specific capacity receives considerable attention.However,the problems of structural instability,manganese dissolution,and poor electrical conductivity make the exploration of high-performance manganese dioxide still a great challenge and impede its practical applications.Besides,zinc storage mechanisms involved are complex and somewhat controversial.To address these issues,tremendous efforts,such as surface engineering,heteroatoms doping,defect engineering,electrolyte modification,and some advanced characterization technologies,have been devoted to improving its electrochemical performance and illustrating zinc storage mechanism.In this review,we particularly focus on the classification of manganese dioxide based on crystal structures,zinc ions storage mechanisms,the existing challenges,and corresponding optimization strategies as well as structure-performance relationship.In the final section,the application perspectives of manganese oxide cathode materials in AZIBs are prospected.

物理化学理论课与实验课的融合教学模式探索

开展物理化学理论课与实验课相融合的教学。理论课教学过程中找准切入点融入实验原理,加深学生对知识的理解,调动学生的学习兴趣和求知欲,课堂气氛活跃,学生融入课堂并互动。实验课上引导学生学习实验设计思路与方法,提出严格的数据记录与处理要求,学生实验报告的逻辑性增强,可独立对实验结果进行讨论,能够正确分析实验误差可能的原因,对实验方案、方法和仪器可提出改进的意见和建议。通过理论课与实验课融合的教学模式可培养学生的逻辑思维能力和实践能力。该教学模式的实施需要学校和系部强有力的政策保障。

Regulating solid electrolyte interphases on phosphorus/carbon anodes via localized high-concentration electrolytes for potassium-ion batteries

The resourceful and inexpensive red phosphorus has emerged as a promising anode material of potassium-ion batteries(PIBs) for its large theoretical capacities and low redox potentials in the multielectron alloying/dealloying reactions,yet chronically suffering from the huge volume expansion/shrinkage with a sluggish reaction kinetics and an unsatisfactory interfacial stability against volatile electrolytes.Herein,we systematically developed a series of localized high-concentration electrolytes(LHCE) through diluting high-concentration ether electrolytes with a non-solvating fluorinated ether to regulate the formation/evolution of solid electrolyte interphases(SEI) on phosphorus/carbon(P/C) anodes for PIBs.Benefitting from the improved mechanical strength and structural stability of a robust/uniform SEI thin layer derived from a composition-optimized LHCE featured with a unique solvation structure and a superior K+migration capability,the P/C anode with noticeable pseudocapacitive behaviors could achieve a large reversible capacity of 760 mA h g^(-1)at 100 mA g^(-1),a remarkable capacity retention rate of 92.6% over 200 cycles at 800 mA g^(-1),and an exceptional rate capability of 334 mA h g^(-1)at8000 mA g^(-1).Critically,a suppressed reduction of ether solvents with a preferential decomposition of potassium salts in anion-derived interfacial reactions on P/C anode for LHCE could enable a rational construction of an outer organic-rich and inner inorganic-dominant SEI thin film with remarkable mechanical strength/flexibility to buffer huge volume variations and abundant K+diffusion channels to accelerate reaction kinetics.Additionally,the highly reversible/durable full PIBs coupling P/C anodes with annealed organic cathodes further verified an excellent practical applicability of LHCE.This encouraging work on electrolytes regulating SEI formation/evolution would advance the development of P/C anodes for high-performance PIBs.

Learning-Based Dynamic Connectivity Maintenance for UAV-Assisted D2D Multicast Communication

Unmanned aerial vehicles(UAVs) enable flexible networking functions in emergency scenarios.However,due to the movement characteristic of ground users(GUs),it is challenging to capture the interactions among GUs.Thus,we propose a learningbased dynamic connectivity maintenance architecture to reduce the delay for the UAV-assisted device-todevice(D2D) multicast communication.In this paper,each UAV transmits information to a selected GU,and then other GUs receive the information in a multi-hop manner.To minimize the total delay while ensuring that all GUs receive the information,we decouple it into three subproblems according to the time division on the topology:For the cluster-head selection,we adopt the Whale Optimization Algorithm(WOA) to imitate the hunting behavior of whales by abstracting the UAVs and cluster-heads into whales and preys,respectively;For the D2D multi-hop link establishment,we make the best of social relationships between GUs,and propose a node mapping algorithm based on the balanced spanning tree(BST) with reconfiguration to minimize the number of hops;For the dynamic connectivity maintenance,Restricted Q-learning(RQL) is utilized to learn the optimal multicast timeslot.Finally,the simulation results show that our proposed algorithms perfor better than other benchmark algorithms in the dynamic scenario.

Microcantilever sensors for biochemical detection

Microcantilever is one of the most popular miniaturized structures in micro-electromechanical systems(MEMS).Sensors based on microcantilever are ideal for biochemical detection,since they have high sensitivity,high throughput,good specification,fast response,thus have attracted extensive attentions.A number of devices that are based on static deflections or shifts of resonant frequency of the cantilevers responding to analyte attachment have been demonstrated.This review comprehensively presents state of art of microcantilever sensors working in gaseous and aqueous environments and highlights the challenges and opportunities of microcantilever biochemical sensors.

绿色建筑评价标准在北京老城平房院落更新改造中的适应性分析与建议

在国家“双碳”战略目标下,针对北京老城平房院落更新改造难以达到绿色建筑高等级评价、难以有力支撑首都功能核心区落实双碳目标的工作任务等问题,从老城街巷肌理尺度、平房院落空间格局、社区运维绿色转型等方面出发,逐条分析现有绿色建筑评价标准的安全耐久、健康舒适、生活便利、资源节约和环境宜居5个类别、100个评价条目在北京老城的适应性并提出删改建议。对探索构建匹配北京老城平房院落的绿色评价新体系具有参照意义,对全国各地老城区的绿色低碳更新具有普适借鉴意义。经分析,有17项条目建议剔除,11项条目建议调整,另建议新增“砖木结构延寿利用、院落空间格局传承、功能适宜性提升、立面风貌协调”4个评分项条目。

Optimization of decoupling combustion characteristics of coal briquettes and biomass pellets in household stoves

Burning coal briquettes or biomass pellets in household decoupling stoves is of significance to the reduction of residential pollutant emissions such as NO and CO. In order to make full use of the superiority of decoupling combustion technology, the household stoves should be specially designed and optimized to adapt to fuel types and combustion characteristics. Using numerical simulation and experimental validation, this study quantitatively clarified that the reducibility of devolatilization char plays an important role in the suppression of NO emission in the decoupling combustion of coal, while the reducibility of pyrolysis gases has a dominant effect on the reduction of NO in the decoupling combustion of biomass. An optimal parameter combination of throat height and grate angle was obtained for the simultaneous suppression of NO and CO emissions in the household decoupling stove burning coal briquettes. Two types of decoupling stoves were developed to enable the clean combustion of biomass pellets. The A-type biomass stove with a multi-pass smoke tunnel shows a better comprehensive NO and CO reduction effectiveness than the B-type biomass stove consisting of a two-stage grate structure and an S-shaped pyrolysis chamber. The optimal structural parameters provided references for the design and manufacture of commercial decoupling coal and biomass stoves.

A two-step method to detect broadcast ephemeris unavailable periods caused by BeiDou satellite orbital maneuvers

The space constellation of the BeiDou navigation satellite system(BDS) is a hybrid constellation containing medium earth orbit(MEO) satellites, geostationary earth orbit(GEO) satellites, and inclined geosynchronous orbit(IGSO) satellites. Due to the geosynchronous characteristics of GEO and IGSO, GEO satellites and IGSO satellites often need to perform orbital maneuvers, which can affect the signal-inspace(SIS) availability performance of BeiDou satellites. A two-step detection method for BeiDou satellite orbital maneuvers has been proposed in this paper. The first step is to identify orbital maneuvers based on time series analysis of broadcast ephemeris, and the second step is to verify orbital maneuvers based on bidirectional orbit prediction. The two-step detection method was used to detect the orbital maneuvers of BeiDou satellites in 2019. Through the double guarantees of identification and verification,the detection accuracy of BeiDou satellite orbital maneuvers has been effectively improved. And the orbital maneuver detection results are continued to be used to assess the SIS availability of BeiDou satellites. The results show that the availability loss of GEO satellite orbital maneuvers is about 0.45%-1.07%, and the availability loss of IGSO satellite orbital maneuvers is about 0.12%-0.19%.