Global characterization of modifications to the charge isomers of IgG antibody

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

标准物质领域发展现状及趋势

对标准物质领域国内外发展现状和趋势进行了总结。在介绍标准物质和有证标准物质基本概念及其演变的基础上,以我国国家一级、二级标准物质和国外以各国计量院为主的标准物质研发活动为重点,对标准物质研发现状、关键研发领域以及近年来推出的标准物质典型新品种等进行了分析,对国际和国内标准物质相关技术标准与规范体系的最新情况进行了介绍,并对标准物质领域重大需求与发展趋势进行了展望。

高速燃驱一拖二机组动力学特性分析

某型高速燃驱一拖二机组(高速动力涡轮-1#水力测功机-2#水力测功机)轴系支撑系统结构复杂,由结构钢架和基座组成,支撑系统刚度与轴承刚度接近,弹性不能忽略。本文基于传递矩阵法建立了复杂转子-轴承-基座系统转子动力学模型,分析了复杂耦合支撑系统三种结构的动力特性,并根据API617标准对三种支撑下的转子稳定性进行了动力学评价,为该类机组的现场动平衡提供参考和依据。

The influence of atmospheric Hg on Hg contaminations in rice and paddy soil in the Xunyang Hg mining district,China

To date, the Xunyang mercury(Hg) mining district is the only ongoing large-scale Hg mining district in China. To understand the influence of Hg contamination mode from the Hg mining and smelting activities, 27 sampling sites in the Xunyang Hg mining district were chosen in this study. Total gaseous mercury(TGM) in ambient air was measured using a Lumex-RA915 automatic Hg analyzer in2011. Rice samples and soil samples from rhizosphere were collected systematically and simultaneously. Total Hg(THg) and methylmercury(Me Hg) concentrations in rice grain and soil samples and Hg speciation with modified sequential selective extractions were measured. The local environment was seriously polluted with Hg. The TGM(302 ± 376 ng·m-3, ranging from 24 to 2220 ng·m^(-3)) in the local ambient air, THg(28 ± 30 mg·kg^(-1), ranging from 0.31 to 121 mg·kg^(-1)) and Me Hg(2.3 ± 1.9 lg·kg^(-1),ranging from 0.24 to 8.9 lg·kg^(-1)) in soil samples were at the sample level with Hg contaminated area. The THg concentration(26 ± 16 lg·kg^(-1)ranging from 4.5 to 71 lg·kg^(-1)) in most of the rice grain samples clearly exceeds the threshold level(20 lg·kg^(-1)) in the Chinese national guidelines for cereals(NY 861-2004). The inorganic mercury(IHg)(9.1 ± 5.6 lg·kg^(-1), ranging from 1.2 to 24 lg·kg^(-1)) and Me Hg(14 ± 9.8 lg·kg^(-1), ranging from 2.1 to 59 lg·kg^(-1))concentration in rice grain samples were at the same level with Hg contaminated area. The main species of Hg in paddy soils reveal strong complex Hg and residue Hg. According to the correlation analysis, a Hg pollution mode from local Hg mining and smelting was hypothesized, including Hg emission, transportation, methylation, and uptake process.

INVERSE OPALINE STRUCTURE TITANIA PHOTONIC CRYSTALS BY FUNCTIONALLY MODIFIED COLLOIDAL CRYSTALS TEMPLATING

Ordered macroporous titania photonic crystals （PCs） and photonic balls were fabricated by functional modified polymer colloidal crystals. The TiO2 PCs and balls formed through this method exhibit no cracks and lacunae in large areas on their surface and their inner structures.

Polybrominated Diphenyl Ethers in Surface Sediment from Songhua River Basin,Northeast of China

Sixty sediment samples were collected from the main Songhua River in three years. Twelve polybrominated diphenyl ether( PBDE) congeners( BDE17,28,47,66,99,100,153,154,138,183,and BDE-209) were detected to state the pollution situation. The results showed that the total concentration of total PBDEs ranges from 0. 424 to 23. 0 ng / g dry weight,with the mean of 3. 02 ng / g,and the total PBDEs concentration is at relative low level compared with those worldwide. The congener profile showed that BDE-209 is the dominant congener that accounts for more than 80. 1% of total PBDEs in sediments,followed by BDE-47 and BDE-99. These profiles are consistent with a high consumption of Deca-BDEs for the brominated flame retardant market in China. The results of spatial and seasonal observations indicated that local sources,temperature variation, and hydrologic conditions are significant factors on PBDEs concentrations. Hazard quotients suggested that PBDEs pose no potential risk to benthic organisms in detected area at present.

自产氧抗菌光动力纳米体系对炎症调节和成骨分化的影响

目的:探讨自产氧的抗菌光动力纳米体系--F@Ce6⁃M对炎症调节和成骨分化的影响。方法:构建F@Ce6⁃M并对其进行表征、生物安全性的评价。使用630 nm光照射牙龈卟啉单胞菌(P.gingivalis)菌液处理小鼠成纤维细胞L929,建立炎症模型,分别加入F@Ce6和F@Ce6⁃M并设立相应对照组。实时荧光定量PCR检测促炎因子和抗炎因子的基因表达水平,评价F@Ce6⁃M介导的抗菌光动力治疗(aPDT)对炎症调节的影响;通过免疫荧光检测NF⁃κB/p65亚基易位情况,分析F@Ce6⁃M的免疫调节机制;通过实时荧光定量PCR检测成骨相关基因表达,并采用碱性磷酸酶(ALP)进行染色,评价F@Ce6⁃M在炎症微环境中对前成骨细胞成骨分化的调控作用。结果:实时荧光定量PCR结果显示,与阴性对照组相比,F@Ce6⁃M介导aPDT能明显降低白细胞介素(IL)⁃6、IL⁃1β、肿瘤坏死因子(TNF)⁃α基因表达,并且效果明显优于F@Ce6⁃M未光照组(P<0.05);而各组间转化生长因子(TGF)⁃β1、精氨酸(Arg)⁃1和IL⁃10的基因表达差异无统计学意义(P>0.05)。在巨噬细胞中NF⁃κB/p65易位的免疫荧光实验中,F@Ce6⁃M光照组可抑制NF⁃κB/p65亚基转位(P<0.05)。对于成骨标志物基因表达水平,与阴性对照组相比,光照组ALP、Runt相关转录因子2(RUNX2)、Ⅰ型胶原蛋白(COL⁃1)、骨钙蛋白(OCN)基因表达量显著上升,F@Ce6⁃M光照组的基因表达量升高最为显著(P<0.05)。在ALP染色实验中,光照组的ALP活性水平显著上升,F@Ce6⁃M光照组ALP活性水平升高最为显著(P<0.05)。结论:自产氧的抗菌光动力纳米体系能够减少促炎因子的释放,并对成骨细胞的成骨潜能有显著的恢复作用,从而增强aPDT治疗牙周炎的效果。

Effects of curcumin on sodium currents of dorsal root ganglion neurons in type 2 diabetic neuropathic pain rats

Along with the development of economy and society, type 2 diabetic mellitus(T2DM) has become one of the most common diseases at the global level. As one of the complications of T2 DM, diabetic neuropathic pain(DNP) stubbornly and chronically affects the health and life of human beings. In the pain field, dorsal root ganglion(DRG) is generally considered as the first stage of the sensory pathway where the hyperexcitability of injured neurons is associated with different kinds of peripheral neuropathic pains. The abnormal electrophysiology is mainly due to the changed properties of voltage-gated sodium channels(VGSCs) and the increased sodium currents(INa). Curcumin is an active ingredient extracted from turmeric and has been demonstrated to ameliorate T2 DM and its various complications including DNP effectively. The present study demonstrates that the INa of small-sized DRG neurons are significantly increased with the abnormal electrophysiological characteristics of VGSCs in type 2 diabetic neuropathic pain rats. And these abnormalities can be ameliorated efficaciously by a period of treatment with curcumin.

Catalyst-modified perovskite hollow fiber membrane for oxidative coupling of methane

The catalytic oxidative cou pling of methane(OCM)to C_(2) hydrocarbons(C_(2)H_(6) and C_(2)H_(4))represents one of the most effective ways to convert natural gas to more useful products,which can be performed effectively using La_(0.6)Sr0.4Co_(0.2)Fe_(0.8)O_(3-δ)(LSCF)perovskite hollow fiber membrane microreactor.In this work,the effects of adding a thin BaCe_(0.8)Gd_(0.2)O_(3-δ)(BCG)catalyst film onto the inner LSCF fiber surface as the OCM catalyst and a porous Ba0.5Sr_(0.5)Co_(0.8)Fe_(0.2)O_(3-δ)(BSCF)perovskite layer onto the outer LSCF surface to improve the oxygen permeation were evaluated.Between 700℃and 1000℃,methane conversion increased in the order of uncoated,BCG and BSCF-coated,and BCG-coated LSCF hollow fiber while Coselectivity and C_(2)-yield increased in the order of BCG and BSCF-coated,uncoated,and BCG-coated LSCF hollow fiber.Oxygen permeation flux at the same temperature range,on the other hand,was enhanced in the order of uncoated,BCG-coated,and BCG and BSCF-coated LSCF hollow fiber.This finding demonstrates the complex interplay between oxygen permeation and OCM performance.The BCG and BSCFcoated hollow fiber was also subjected to thermal cycles between 850℃and 900℃for up to 175 hours during which the fiber showed minor degradation in oxygen permeation fluxes and relatively stable OCM performance.

SARS-CoV-2 and innate immunity:the good,the bad,and the"goldilocks"

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of immunity.Knowledge about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged therapeutically.The humoral response to SARS-CoV-2 infection has been the focus of intense research,and the role of the innate immune system has received significantly less attention.Here,we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense systems.We also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

Continuous-wave operation of 1550 nm low-threshold triple-lattice photonic-crystal surface-emitting lasers

Benefitting from narrow beam divergence,photonic crystal surface-emitting lasers are expected to play an essential role in the ever-growing fields of optical communication and light detection and ranging.Lasers operating with 1.55μm wavelengths have attracted particular attention due to their minimum fiber loss and high eye-safe threshold.However,high interband absorption significantly decreases their performance at this 1.55μm wavelength.Therefore,stronger optical feedback is needed to reduce their threshold and thus improve the output power.Toward this goal,photonic-crystal resonators with deep holes and high dielectric contrast are often used.Nevertheless,the relevant techniques for high-contrast photonic crystals inevitably complicate fabrication and reduce the final yield.In this paper,we demonstrate the first continuous-wave operation of 1.55μm photonic-crystal surface-emitting lasers by using a‘triple-lattice photonic-crystal resonator’,which superimposes three lattice point groups to increase the strength of in-plane optical feedback.Using this geometry,the in-plane 180°coupling can be enhanced threefold compared to the normal single-lattice structure.Detailed theoretical and experimental investigations demonstrate the much lower threshold current density of this structure compared to‘single-lattice’and‘double-lattice’photonic-crystal resonators,verifying our design principles.Our findings provide a new strategy for photonic crystal laser miniaturization,which is crucial for realizing their use in future high-speed applications.

食品甜味剂的检测及其标准物质研究现状

目前,低糖饮食已成为当代消费者的一种主流生活,而食品级甜味剂仍存在不合格生产和不规范使用等安全问题。已有研究表明,过量使用甜味剂会引起一定的代谢风险、生物毒性,甚至对水体环境造成污染。因此,食品及环境中甜味剂的监测工作和相关标准物质的研究对保障食品安全和生态环境健康有着重要意义。我国《食品添加剂使用标准》中允许使用的甜味剂包括天然甜味剂、磺胺类甜味剂、二肽类甜味剂、三氯蔗糖等;不同甜味剂的溶解性、稳定性以及毒性大小均有一定差异性。液相色谱是一种甜味剂通用检测方法,检测结果的好坏关键在于检测器的选择,不同结构的甜味剂适用的检测器不同。通过对不同甜味剂的理化性质及分析方法进行整理,可为相关标准物质的研制提供一定参考信息。通过调研可知,美国、加拿大、英国、欧洲等国外甜味剂标准物质/标准品已有多于13种(6种天然甜味剂、4种磺胺类甜味剂、3种二肽类甜味剂等),我国已申请的甜味剂有证标准物质共6种(D-甘露糖醇、甜蜜素、糖精钠、安赛蜜、三氯蔗糖和阿力甜),很多天然甜味剂以及二肽类甜味剂未查询到相关有证标准物质信息,无法满足我国食品检测等行业的需求。随着新型甜味剂种类的增多,有必要持续关注相关研究,完善相关甜味剂的检测技术以及标准物质品种,更为有效地监督食品质量,保障食品安全。

On the rumpling mechanism in nanocrystalline coatings:Improved by reactive magnetron sputtering with oxygen

Surface rumpling is detrimental to high temperature protective coatings as it shortens their lifetime and leads to adhesion losses and unexpected corrosion degradation.The driving force and mass transport mechanism behind of rumpling remains to be clarified.In the present investigation,we subjected two types of nanocrystalline coating systems to avoid the influence of interdiffusion on rumpling study.One group was an ordinary nanocrystalline coating,and the other group was designed and prepared with trace oxygen by reactive magnetron sputtering.Systematic cyclic oxidation test at 1100°C was also car-ried out.Results show the ordinary nanocrystalline coating oxidized rapidly,which leads to the fast consumption of Al and the acceleration of phase transition in the coating.Meanwhile,severe surface rumpling is observed due to the stress release of nanocrystals through plastic deformation.Besides,the reactive doping of oxygen can significantly reduce the consumption process of Al in nanocrystalline coat-ing.The rumpling is controlled due to the improvement of coefficient of thermal expansion and Young’s modulus of the coating.Thereafter,the cyclic oxidation resistance is improved.

Wavelength-tunable multi-point pump semiconductor disk laser based on an intra-cavity transmission grating

We report a wavelength-tunable multi-point pump scheme of the semiconductor disk lasers(SDLs).By designing an external cavity of SDL with an intra-cavity transmission grating,multiple pump gain regions share the same resonator.The effect of the intra-cavity grating on the output laser power,wavelength,and beam quality was investigated.The emission wavelength could be tuned over a bandwidth of~18 nm.With multi-point pumping,we achieve the laser output power with almost no loss,and further improvement is limited by the thermal effect.The changes in the beam are due to the mode selectivity by the intra-cavity grating.

液相色谱-质谱法检测甲磺酸沙非胺中基因毒性杂质

甲磺酸沙非胺主要用于治疗帕金森病,建立了甲磺酸沙非胺中基因毒性杂质((S)-4-(((1-氨基-1-氧丙烷-2-甲基)氨基)甲基)苯甲磺酸酯)的液相色谱-质谱联用检测方法。样品溶于甲醇,经YMC-Triart C18(4.6 mm×100 mm,3μm)分离,0.1%甲酸水和0.1%甲酸甲醇梯度洗脱,采用多反应监控(MRM)模式正离子扫描进行定量检测。该方法具有较好的专属性,目标化合物在1.53~30.54 ng/mL的浓度范围内线性关系良好(R2>0.99);检出限为0.76 mg/kg,定量限为1.53 mg/kg;加标回收率为98.5%~99.90%,RSD为0.83%~2.10%。该方法灵敏度高,准确可靠,可应用于甲磺酸沙非胺的质量监控。

中国体外诊断试剂溯源研究进展

比较了欧盟与美国在体外诊断试剂溯源研究的进展情况,综述了中国体外诊断试剂行业参考物质研制情况、参考方法以及参考实验室发展情况,对体外诊断试剂行业溯源性研究的现状进行了总结,并对面临的挑战与发展方向进行了展望。

LncDACH1 promotes mitochondrial oxidative stress of cardiomyocytes by interacting with sirtuin3 and aggravates diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM)is a common complication in diabetic patients.The molecular mechanisms of DCM remain to be fully elucidated.The intronic long noncoding RNA of DACH1(lnc DACH1)has been demonstrated to be closely associated with heart failure and cardiac regeneration.In this study,we investigated the role of lnc DACH1 in DCM and the underlying molecular mechanisms.The expression of lnc DACH1 was increased in DCM hearts and in high glucose-treated cardiomyocytes.Knockout of lnc DACH1 reduced mitochondrial oxidative stress,cell apoptosis,cardiac fibrosis and hypertrophy,and improved cardiac function in DCM mice.Overexpression of lnc DACH1 exacerbated mitochondria-derived reactive oxygen species(ROS)level and apoptosis,decreased activity of manganese superoxide dismutase(Mn-SOD);while silencing of lnc DACH1 attenuated ROS production,mitochondrial dysfunction,cell apoptosis,and increased the activity of Mn-SOD in cardiomyocytes treated with high glucose.Lnc DACH1 directly bound to sirtuin3(SIRT3)and facilitated its degradation by ubiquitination,therefore promoting mitochondrial oxidative injury and cell apoptosis in mouse hearts.In addition,SIRT3 silencing abrogated the protective effects of lnc DACH1 deficiency in cardiomyocytes.In summary,lnc DACH1 aggravates DCM by promoting mitochondrial oxidative stress and cell apoptosis via increasing ubiquitination-mediated SIRT3 degradation in mouse hearts.Inhibition of lnc DACH1 represents a novel therapeutic strategy for the intervention of diabetic cardiomyopathy.

Electrolyte-mediated dense integration of graphene-MXene films for high volumetric capacitance flexible supercapacitors

High conductivity two-dimensional(2D)materials have been proved to be potential electrode materials for flexible supercapacitors because of its outstanding chemical and physical properties.However,electrodes based on 2D materials always suffer from limited electrolyte-accessible surface due to the restacking of the 2D sheets,hindering the full utilization of their surface area.In this regard,an electrolyte-mediated method is used to integrate dense structure reduced graphene oxide/MXene(RGM)-electrolyte composite films.In such composite films,reduced graphene oxide(RGO)and MXene sheets are controllable assembly in compact layered structure with electrolyte filled between the layers.The electrolyte layer between RGO and MXene sheets forms continuous ion transport channels in the composite films.Therefore,the RGM-electrolyte composite films can be used directly as self-supporting electrodes for supercapacitors without additional conductive agents and binders.As a result,the composite films demonstrate enhanced volumetric specific capacity,improved volumetric energy density and higher power density compared with both pure RGO electrode and porous composite electrode prepared by traditional methods.Specifically,when the mass ratio of MXene is 30%,the electrode delivers a volumetric specific capacity of 454.9 F·cm^(−3) with a high energy density of 39.4 Wh·L^(−1).More importantly,supercapacitors based on the composite films exhibit good flexibility electrochemical performance.The investigation provides a new approach to synthesize dense structure films based on 2D materials for application in high volumetric capacitance flexible supercapacitors.

NICKEL(Ⅱ)ion-intercalated MXene membranes for enhanced H_(2)/CO_(2) separation

Hydrogen fuel has been embraced as a potential long-term solution to the growing demand for clean energy.A membrane-assisted separation is promising in producing high-purity H_(2).Molecular sieving membranes(MSMs)are endowed with high gas selectivity and permeability because their well-defined micropores can facilitate molecular exclusion,diffusion,and adsorption.In this work,MXene nanosheets intercalated with Ni^(2+) were assembled to form an MSM supported on Al_(2)O_(3) hollow fiber via a vacuum-assisted filtration and drying process.The prepared membranes showed excellent H_(2)/CO_(2) mixture separation performance at room temperature.Separation factor reached 615 with a hydrogen permeance of 8.35×10^(-8) mol·m^(-2)·s^(-1) ·Pa^(-1).Compared with the original Ti_(3)C_(2)T_(x)/Al_(2)O_(3) hollow fiber membranes,the permeation of hydrogen through the Ni^(2+)-Ti_(3)C_(2)T_(x)/Al_(2)O_(3) membrane was considerably increased,stemming from the strong interaction between the negatively charged MXene nanosheets and Ni^(2+).The interlayer spacing of MSMs was tuned by Ni^(2+).During 200-hour testing,the resultant membrane maintained an excellent gas separation without any substantial performance decline.Our results indicate that the Ni2+tailored Ti_(3)C_(2)T_(x)/Al_(2)O_(3) hollow fiber membranes can inspire promising industrial applications.

Attributes,challenges and future directions of community resilience

With the continuous development of human society, the damage to the natural environment is becoming increasingly large, causing crisis events to occur frequently. In recent years, the study of community resilience is becoming popular among scholars because of its perspective on disaster prevention and mitigation. In this study, we apply database retrieval to untangle community resilience-related papers from multiple directions. We analyze the connotation, attribute, and composition of community, resilience, and community resilience comprehensively by summarizing important issues and research progress in community resilience. Challenges and shortcomings faced by community resilience development are also determined. Moreover, we put forward the research directions that future research can focus on. Through literature review, current research on community resilience focuses on the following aspects: "infrastructure construction," "crowd in the community," "economic resilience,""social capital," and "measurement of community resilience." Such research is not yet systematic and relatively decentralized. The attention to collective resilience in the community is relatively weak, which makes achieving the goal of "people-oriented and systematic control" difficult.Therefore, this study states that the development of future community resilience should stand from the perspective of"system of system" and build on knowledge and tools of various relevant domains. Therefore, public needs and participation are highlighted as breakthrough points. The research should integrate infrastructure and economic resilience, social resource allocation, network connection,and other aspects to build a holistic and functional resilient community.