生物分子液-液相分离的物理化学机制

近年来,有关生物分子通过液-液相分离机制进行组织定位、功能调控的研究发展迅速。相分离产生的聚集体在众多细胞活动事件中发挥了关键作用。这些聚集体的生物功能是以相分离的物理化学性质为基础的。本文将从相分离聚集体的基本性质、相图、微观结构,相分离的统计热力学、实验和分子模拟研究等方面阐释相分离物理化学机制研究相关进展。对于生物分子相分离的重要功能体系进行了列举和归纳,收集了相分离研究的模式体系,探讨了生物分子相分离的生物功能同物理化学机制之间的关系,总结了生物分子相分离的调控机制和调控分子的设计方法,并对生物分子相分离物理化学机制研究的未来发展方向进行了展望。

Development Trend Analysis of Computer Management Information System

Based on the retrospect and analysis of the main points of the development of computer management information system,on the basis of the study of relevant data such as enterprise units,mass media,personal information and information security,and according to the actual situation of our country,this paper intentionally and systematically collects relevant research materials on the role of management information system in the survival and development of enterprises,and aims at one or more merits.To study its impact,this paper focuses on three aspects:application analysis,development direction and implementation strategy,which can provide strong reference and guidance for the application of enterprise computer management system.

Characterization of the P450 Monooxygenase LobP1 as C-32 Hydroxylase in Lobophorin Biosynthesis

Lobophorins(LOBs)belong to a large family of spirotetronate antibiotics with antibacterial and antitumor activities.In this study,we demonstrated the function of LobP1,a P450 monooxygenase encoded in the LOB biosynthetic gene cluster,by in vivo deletion and in vitro biochemical assays.The disruption of lobP1 led to the isolation of three new LOBs derivatives(3-5)and three known ones(6-8)without the hydroxyl group at C-32.LobP1 was shown to have relatively broad substrate scope.Determining the kinetic parameters of LobP1 towards different substrates revealed that LobP1 preferred substrate with a nitrosugar.The new LOBs 3-5 displayed significant antibacterial activities against Bacillus subtilis and Micrococcus luteus with MIC values of 0.125 to 1μg·mL^(-1),and the major product LOB E(6)from the∆lobP1 mutant showed moderate cytotoxic activities against several cancer cell lines.

Talachalasins A-C,Undescribed Cytochalasans with a 16β-Methyl or 2-Oxabicyclo[3.3.1]nonan-3-one unit from the Deep-Sea-Derived Fungus Talaromyces muroii sp.SCSIO 40439

Comprehensive Summary Talachalasins A-C(1-3),three new cytochalasans(CYTs),were isolated from deep-sea-derived fungus Talaromyces muroii sp.SCSIO 40439.The structures of 1-3,including absolute configurations,were determined based on HRESIMS,NMR spectroscopic data,ECD comparison,and single crystal X-ray diffraction analysis.Talachalasins A-C(1-3)represented the first examples of cytochalasans possessing a unique 16β-methyl group,distinct from>500 reported CYTs.Talachalasin C(3)was an unprecedented 20,21-seco-cytochalasans characterized by a 2-oxabicyclo[3.3.1]nonan-3-one unit.Talachalasin A(1)displayed moderate cytotoxic activity against four tumor cell lines(IC_(50)3.40-10.02μM).Talachalasin B(2)showed comparable anti-RSV and HSV-1 activities(IC5012.5μM or IC5020.0μM).

Specific pupylation as IDEntity reporter(SPIDER)for the identification of protein-biomolecule interactions

Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.

Numerical analysis and experimental research on detection of welding defects in pipelines based on magnetic flux leakage

Regular inspection of long-distance oil and gas pipelines plays an important role in ensuring the safe transportation of oil and gas,and inspection on welding defects is an important part of the inspection process.Magnetic flux leakage(MFL)is an electromagnetic non-destructive testing technique which has been commonly utilized to detect welding defects in pipelines.In the present study,Maxwell electro-magnetic simulation software was used to carry out numerical study on the welding defects in pipelines,including incomplete penetration and undercut.TheФ406 pipeline with a wall thickness of 7 mm was selected as the study case to establish the numerical model.Setting the life-off value at 1 mm,the distribution of magnetic leakage field was investigated for pipeline without defect,pipeline with incomplete penetration defect and pipeline with undercut defect respectively,the characteristic values describing the depth and width of defects were found.Furthermore,quantified equations which can be used to describe the defect depth were proposed.Finally,experimental research was carried out to validate the effectiveness of the numerical model,and the experimental results showed good consistence with the numerical calculation results.The research results indicate that,it is technically feasible and reliable to diagnose the incomplete penetration and undercut welding defects in pipelines using MFL.

FLC调控植物成花的分子机制研究新进展

FLC是植物成花关键抑制因子,主要通过结合到其下游2个关键的成花促进基因(FT和SOC1)启动子上而抑制二者的表达。此外,还可以与其它调控因子结合调控开花。然而,关于FLC在成花调控中的具体分子机制仍需深入研究。该文主要结合8条成花调控遗传途径,梳理近年来与FLC相关的新进展,并展望了未来的研究方向。

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites

The outbreak of coronavirus disease(COVID-19)caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths.Currently,there is no specific viral protein-targeted therapeutics.Viral nucleocapsid protein is a potential antiviral drug target,serving multiple critical functions during the viral life cycle.However,the structural information of SARS-CoV-2 nucleocapsid protein remains unclear.Herein,we have determined the 2.7 A crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein.Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain,the surface electrostatic potential characteristics between them are distinct.Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside theβ-sheet core.Complemented by in vitro binding studies,our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain,guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

珠江口沉积物来源链霉菌SCSIO 40020中bafilomycins的鉴定及其生物合成基因簇的异源表达

【目的】从珠江口沉积物来源的菌株SCSIO 40020中分离bafilomycins,并对其生物合成基因簇进行克隆和异源表达研究。【方法】通过分析菌株SCSIO 40020的16S rRNA基因序列并构建系统发育树以鉴定菌种,以柱层析法和制备色谱法对次级代谢产物进行分离纯化,借助波谱学手段完成单体化合物的结构鉴定,采用生物信息学分析定位bafilomycins的生物合成基因簇,通过筛选菌株SCSIO 40020基因组的细菌人工染色体文库和接合转移将bafilomycins生物合成基因簇导入3种链霉菌进行异源表达,利用高效液相色谱检测异源表达菌株的发酵产物。【结果】菌株SCSIO 40020被鉴定为链霉菌属菌株,从其发酵产物中分离鉴定了2个单体化合物bafilomycins A1和D。克隆了链霉菌SCSIO 40020中bafilomycins的生物合成基因簇并推导了其生物合成途径,在3种链霉菌中表达产生了bafilomycins。【结论】从珠江口环境中获得了一株产生bafilomycins的链霉菌SCSIO 40020,成功建立了该菌株次级代谢产物生物合成基因簇的异源表达体系,并首次在链霉菌Streptomyces lividans SBT18、Streptomyces coelicolor M1154和Streptomyces albus J1074中进行了表达,获得了bafilomycins,为后续bafilomycins结构类似物的生产和链霉菌SCSIO 40020中新结构活性化合物的挖掘奠定了基础。

Enhanced Magnetostriction of a Narrow Hysteresis Tb_(0.26)Dy_(0.54)Ho_(0.20)Fe_2 Alloy

In this work,a magnetic annealing method used to enhance the magnetostrictive property of a narrow hysteresis alloy Tb_(0.26)Dy_(0.54)Ho_(0.20)Fe_2 is reported.Cylindrical-rod shaped specimen with <110> crystal orientation was fabricated using zone-melting unidirectional solidification technique,followed by annealing in a transverse magnetic field of 366 kA/m.The crystal orientation and bi-phase solidified morphology can be retained after magnetic annealing.A high magnetostriction of 1.508×10-3 was obtained in the magnetically annealed specimen,which is 25.2% larger than the untreated one.Simultaneously,the magnetostriction hysteresis width is slightly enlarged from 4.45 to 6.36 kA/m,which is still much lower than that of the Ho-free Tb0.3Dy0.7Fe2 alloy.The additional anisotropy which is induced by magnetic annealing,as reflected by the magnetic hysteresis loops,is responsible for the enhancement of magnetostrictive performance.

Experimental investigation and thermodynamic modeling of the U-Nb system

The phase equilibria and thermodynamic properties of the U-Nb system were investigated through experiments and thermodynamic modeling.In the experiments,a series of samples with different content of Nb were prepared by arc melting.The Nb content covers the entire composition range of the U-Nb binary system.After solidification,the samples were annealed and then analyzed by X-ray diffraction,scanning electron microscopy,energy dispersive X-ray spectroscopy,differential scanning calorimeter and neutron diffraction.The equilibrium phases,including γ1(U-rich bcc),αU,and γ2(U-depleted bcc),were determined in detail from the experimental characterization.The occurrence of the invariant reaction γ1→αU+γ2 was confirmed,and the reaction temperature and composition were accurately identified.Moreover,the experimental findings clarify the dispute between the Dwight and Terekhov theories regarding the phase region(i.e.,whether the phase region is αU+γ1 or βU+γ2).Furthermore,the U-Nb phase diagram was reassessed by incorporating the present experimental data and previously published reliable experimental data from the literature.A set of self-consistent thermodynamic parameters were developed using CALPHAD(Calculation of phase diagrams),and the calculations reasonably agree with the experimental observations.

Fatigue Damage Mechanism of AL6XN Austenitic Stainless Steel at High Temperatures

By the combination of transmission electron microscope, neutron diffraction and small-angle neutron scattering methods, mechanical fatigue behavior of AL6XN austenitic stainless steel was investigated in the temperature range of 400–600 °C. At 400 °C, in addition to the occurrence of dynamic strain aging, the formation of short-range order was evidenced from the forbidden electron diffraction spot of 1/3 {422} in face-centered cubic(fcc) structure viewed down [111] zone axis, which facilitate the planar slip mode of dislocation and result in the work hardening during the fatigue deformation. The fatigue damage is mainly dominated by the accumulation of planar slip band and the interaction among various slip systems. With increasing temperature, precipitates of chi phase, Laves phase and sigma phase were formed during the fatigue tests at 500 and 600 °C. An increase in precipitation content at 600 °C has also been confirmed by both scanning electron microscope and small-angle neutron scattering analysis. The dislocation pileup originating from the uncoordinated deformation between precipitate and austenitic matrix is an important fatigue damage leading to crack. The continuous cycle softening behavior was also observed on the fatigue curve at 600 °C, which is considered to be caused by dynamic recovery.

Engineering a zinc binding site into the de novo designed protein DS119 with a βαβ structure

Functional proteins designed de novo have potential application in chemical engineering,agriculture and healthcare.Metal binding sites are commonly used to incorporate functions.Based on a de novo designed protein DS119 with aβαβstructure,we have computationally engineered zinc binding sites into it using a home-made searching program.Seven out of the eight designed sequences tested were shown to bind Zn2+with micromolar affinity,and one of them bound Zn2+with 1:1 stoichiometry.This is the first time that metalloproteins with anα,βmixed structure have been designed from scratch.

A simple and facile iodination method of didechlorotiacumicin B and aromatic compounds

Tiacumicin B(also known as fidaxomicin or difimicin)is a marketed 18-membered macrolide antibiotic for the treatment of Clostridium difficile infections.Tiacumicin B is structurally characterized with two chlorine atoms substituted on the aromatic ring,which is installed by the halogenase Tia M.During the study on halide compatibility of Tia M,a facile and nonenzymatic iodination method of didechlorotiacumicin B was discovered,requiring Na I,acid and air for iodination at room temperature.This method was also amenable to other 9 aromatic substrates with electron-rich sites for iodination.