BL19U2:Small-angle X-ray scattering beamline for biological macromolecules in solution at SSRF

The BL19U2 at the Shanghai Synchrotron Radiation Facility is a small-angle X-ray scattering beamline dedicated to structural studies pertaining to biological macromolecules in solution.The beamline has been officially opened to users in March 2015,and since then,a series of technological innovations has been developed to optimize beamline performance,thereby significantly improving the data collection efficiency and broadening the application scope of biological small-angle X-ray scattering.BL19U2 is ideal for the high-throughput screening of weakly scattered proteins,protein assemblies,nucleic acids,inorganic nanomaterials,and organic drug molecules.This paper describes the design and overview of the BL19U2 beamline.Versatile sample environments at the experimental station and some recent scientific highlights are presented.

A Novel Method for Studying the interaction of Macromolecule with Small Molecule by Means of Affinity Capillary Electrophoresis

A novel capillary electrophoresis method coupled with on-line microdialysis using an attachable electrode has been developed to study the interaction of macromolecule with small molecule. The binding constants of bovine serum album (BSA) with D,L-tryptophan (Trp), sulfamethoxazole (SMZ) with trypsin and chymotrypsin were determined. These values are 2.3 x 10(4)L/mol for BSA-L-Trp; 1.77 x 10(3) L/mol for BSA-D-Trp in pH 7.4, 50 mmol/ L phosphate; 1.4 x 10(4) L/mol for SMZ- trypsin and 6.0 x 10(3) L/mol for SMZ-chymotrypsin in pH 6.5, 25 mmol/L Tris buffer. The proposed method has merits of speed, low sample consumption and readily available to be performed in desired physiological conditions.

Metallated Schiff-Base Macromolecules as Alternative Metalloprotein Electron Transfer Intermediates

In the construction of biosensors, enzymes function as mediators converting biological signals generated by specific biological processes, into electrochemical signals. The ideology of bio-sensor design is retention of electron transfer activity of the enzyme utilizing superior interfacial architecture. In this work a Schiff-base macromolecule has been synthesized by reflux of 2, 3-diaminonaphthalene and pyrrole-2-carboxaldehyde starting materials. The Schiff-base ligand was subsequently complexed with FeCl2?4H2O under reflux, to produce the Fe-Schiff-base complex. The Schiff-base ligand and Fe-Schiff-base complex were characterized using nuclear magnetic resonance (NMR) spectroscopy, Ultra Violet/Visible (UV/Vis) spectroscopy, Fourier transfer infrared resonance (FTIR) and electron energy loss spectroscopy (EELS) to confirm the structure of the synthesis products. NMR spectroscopy confirmed the imide linkage of Schiff-base formation as two symmetrical peaks at 8.1 and 7.7 ppm respectively. Comparison of starting materials and product spectra by UV/Vis spectroscopy confirmed the disappearance of the diaminonaphthalene peak at 250 nm as evidence of complete conversion to product. FTIR spectroscopy of the Schiff-base ligand confirmed the formation of the imine bond at 1595 cm-1. EELS spectra comparing FeCl2?4H2O and the Fe-Schiff-base complex, showed good agreement in the energy loss profiles associated with changes to the electronic arrangement of Fe d-orbitals. EDS clearly identified a spectral band for Fe (7 - 8 eV) in the Fe-Schiff-base complex. Electrochemical evaluation of the Fe-Schiff-base complex was compared to the electrochemical signature of denatured cytochrome-C using cyclic voltammetry and square wave voltammetry. The Fe2+/Fe3+ quasi-reversible behavior for iron in the metallated complex was observed at -0.430 V vs. Ag/AgCl, which is consistent with reference values for iron in macromolecular structures.

Inetetamab combined with pyrotinib and chemotherapy in the treatment of breast cancer brain metastasis: A case report

BACKGROUND Breast cancer brain metastasis(BCBM)is an advanced breast disease that is difficult to treat and is associated with a high risk of death.Patient prognosis is usually poor,with reduced quality of life.In this context,we report the case of a patient with HER-2-positive BCBM treated with a macromolecular mAb(ine-tetamab)combined with a small molecule tyrosine kinase inhibitor(TKI).CASE SUMMARY The patient was a 58-year-old woman with a 12-year history of type 2 diabetes.She was compliant with regular insulin treatment and had good blood glucose control.The patient was diagnosed with invasive carcinoma of the right breast(T3N1M0 stage IIIa,HER2-positive type)through aspiration biopsy of the ipsilateral breast due to the discovery of a breast tumor in February 2019.Immunohistochemistry showed ER(-),PR(-),HER-2(3+),and Ki-67(55-60%+).Preoperative neoadjuvant chemotherapy,i.e.,the AC-TH regimen(epirubicin,cyclophosphamide,docetaxel-paclitaxel,and trastuzumab),was administered for 8 cycles.She underwent modified radical mastectomy of the right breast in November 2019 and received tocilizumab targeted therapy for 1 year.Brain metastasis was found 9 mo after surgery.She underwent brain metastasectomy in August 2020.Immunohistochemistry showed ER(-)and PR.(-),HER-2(3+),and Ki-67(10-20%+).In November 2020,the patient experienced headache symptoms.After an examination,tumor recurrence in the original surgical region of the brain was observed,and the patient was treated with inetetamab,pyrotinib,and capecitabine.Whole-brain radiotherapy was recommended.The patient and her family refused radiotherapy for personal reasons.In September 2021,a routine examination revealed that the brain tumor was considerably larger.The original systemic treatment was continued and combined with intensity-modulated radiation therapy for brain metastases,followed by regular hospitalization and routine examinations.The patient’s condition is generally stable,and she has a relatively high quality of life.This case report demonstrates that in patients with BCBM and resistance to trastuzumab,inetetamab combined with pyrotinib and chemotherapy can prolong survival.CONCLUSION Inetetamab combined with small molecule TKI drugs,chemotherapy and radiation may be an effective regimen for maintaining stable disease in patients with BCBM.

Behavior of macromolecules in adsorbed layers

A model for describing the behavior ot macromoiecuies in aosoroea layers is developed by introducing a concept of distribution density of layer thickness U based on stochastic process and probabilistic statistics. The molecular behavior of layers adsorbed on clay particle surfaces is discussed; the random distribution and its statistics of the layer thickness are given by incorporating experimental results with an ionic polyelectrolyte with the molecular weight of 1.08×106and chain charged density of 0.254.

Encoding of Primary Structures of Biological Macromolecules Within a Data Mining Perspective

An encoding method has a direct effect on the quality and the representationof the discovered knowledge in data mining systems. Biological macromolecules are encoded by stringsof characters, called primary structures. Knowing that data mining systems usually use relationaltables to encode data, we have then to re-encode these strings and transform them into relationaltables. In this paper, we do a comparative study of the existing static encoding methods, that arebased on the Biologist know-how, and our new dynamic encoding one, that is based on the constructionof Discriminant and Minimal Substrings (DMS). Different classification methods are used to do thisstudy. The experimental results show that our dynamic encoding method is more efficient than thestatic ones, to encode biological macromolecules within a data mining perspective.

A Review on Graphene Oxide Two-dimensional Macromolecules: from Single Molecules to Macro-assembly

Graphene oxide(GO), which consists of two-dimensional(2 D) sp^(2) carbon hexagonal networks and oxygen-contained functional groups, has laid the foundation of mass production and applications of graphene materials. Made by chemical oxidation of graphite, GO is highly dispersible or even solubilized in water and polar organic solvents, which resolves the hard problem of graphene processing and opens a door to wet-processing of graphene. Despite its defects, GO is easy to functionalize, dope, punch holes, cut into pieces, conduct chemical reduction, form lyotropic liquid crystal, and assemble into macroscopic materials with tunable structures and properties as a living building block. GO sheet has been viewed as a single molecule, a particle, as well as a soft polymer material. An overview on GO as a 2 D macromolecule is essential for studying its intrinsic properties and guiding the development of relevant subjects. This review mainly focuses on recent advances of GO sheets, from single macromolecular behavior to macro-assembled graphene material properties. The first part of this review offers a brief introduction to the synthesis of GO molecules. Then the chemical structure and physical properties of GO are presented, as well as its polarity in solvent and rheology behavior. Several key parameters governing the ultimate stability of GO colloidal behavior, including size, p H and the presence of cation in aqueous dispersions, are highlighted. Furthermore, the discovery of GO liquid crystal and functionalization of GO molecules have built solid new foundations of preparing highly ordered, architecture-tunable, macro-assembled graphene materials, including 1 D graphene fibers, 2 D graphene films, and 3 D graphene architectures. The GO-based composites are also viewed and the interactions between these target materials and GO are carefully discussed. Finally, an outlook is provided in this field, where GO is regarded as macromolecules, pointing out the challenges and opportunities that exist in the field. We hope that this review will be beneficial to the understanding of GO in terms of chemical structure,molecular properties, macro-assembly and potential applications, and encourage further development to extend its investigations from basic research to practical applications.

Macromolecules Mimicking Backbones of Nucleic and Teichoic Acids.Synthesis,Some Properties and Applications

1 Results Several methods have been elaborated in this laboratory allowing preparation of macromolecules with phosphodiester bonds,and having sequence of atoms similar as in the chains of biomacromolecules - nucleic or teichoic acids (TA),namely:-(C)n-O-PO-,where n=2 (for teichoic acids) or 3.These methods,to be discussed in the lecture,are based on the ring-opening polymerization,transesterification,and recently elaborated direct addition of phosphoric acid to diepoxides.For the first time an attempt h...

Diversity of culturable heterotrophic bacteria from the Mariana Trench and their ability to degrade macromolecules

The Mariana Trench is the deepest location on earth and harbors unique microbial communities as evidenced by 16S rRNA gene amplicon and metagenomic sequencing.Obtaining culturable microorganisms from the Mariana Trench will contribute to a further understanding of hadal biogeochemical processes and act as a unique microbial reservoir with potential applications.Here,825 bacterial strains,identified by 16S rRNA gene sequencing,were isolated from 12 water depths(0-10,400 m)of the Mariana Trench with 2216E and R2A media at 4℃ or 28℃ on four cruises during 2015-2017.These bacteria belong to four phyla,nine classes,27 orders,45 families and 108 genera.Alphaproteobacteria,Gammaproteobacteria,Actinobacteria_c,Bacilli and Flavobacteriia were the most abundant classes,accounting for 37.9%,33.0%,11.8%,8.6%and 8.0%of the total bacterial isolates,respectively.2216E and R2A media were found to have a better selectivity to Bacilli and Flavobacteriia,respectively.Fifty strains were potential novel bacterial species with a 16S rRNA gene similarity<98.65%,and a higher percentage of novel strains were obtained from R2A than 2216E medium.Additionally,301(150 species)out of 354 strains(178 species)selected from each depth could degrade at least one of the ten kinds of macromolecules tested.These results indicate that there is a high diversity of culturable bacteria in the Mariana Trench and they can produce a variety of extracellular enzymes.Our study provides a valuable resource of microorganisms for investigating their biogeochemical roles in the Mariana Trench and for industrial applications.

Microorganism-derived biological macromolecules for tissue engineering

According to literature,certain microorganism productions mediate biological effects.However,their beneficial characteristics remain unclear.Nowadays,scientists concentrate on obtaining natural materials from live creatures as new sources to produce innovative smart biomaterials for increasing tissue reconstruction in tissue engineering and regenerative medicine.The present review aims to introduce microorganism-derived biological macromolecules,such as pullulan,alginate,dextran,curdlan,and hyaluronic acid,and their available sources for tissue engineering.Growing evidence indicates that these materials can be used as biological material in scaffolds to enhance regeneration in damaged tissues and contribute to cosmetic and dermatological applications.These natural-based materials are attractive in pharmaceutical,regenerative medicine,and biomedical applications.This study provides a detailed overview of natural-based biomaterials,their chemical and physical properties,and new directions for future research and therapeutic applications.

Adsorption/desorption of toluene on a hypercrosslinked polymeric resin in a highly humid gas stream

In many sources of volatile organic compounds (VOCs), large amounts of water vapor come from the air and the reactors. The relative humidity (RH) of exhaust gas is normally >60% and is supersaturated. Maintaining the property of adsorbent on VOCs in a highly humid gas stream is a serious industrial problem. In this study, the adsorption/desorption behavior of toluene in a micro-mesoporous polymeric resin was investigated in a highly humid environment to explore the influence of abound water vapor on resin adsorption and regeneration. This resin could selectively adsorb toluene at an RH of 80%, and its adsorption property was unaffected by the presence of water vapor. In the case of humidity saturation, the resin displayed a high adsorption capacity at a moisture content of <30%. Therefore, the polymer resin is an excellent water-resistant adsorbent of VOCs. In the regenerative experiment, the resin maintained its original adsorption capability after four adsorption/ desorption cycles of toluene purging with nitrogen gas at 120℃. The resin exhibited excellent regeneration performance at high humidity.

Characterization of organic matter in total suspended particles by thermodesorption and pyrolysis-gas chromatography-mass spectrometry

The organic matter in tropospheric aerosol plays an important role in atmospheric physical and chemical processes. The bulk of organic matter, representing a significant proportion of the total suspended particulate （TSP） mass, is bound to polymeric material whose structure and properties are largely unknown. Here we used thermodesorption gas chromatography/mass spectrometry （Td-GC/MS） to study organic compounds of low molecular mass and pyrolysis gas chromatography/mass spectrometry （Py-GC/MS） to characterize the chemical structure of macromolecules in TSP samples collected in different seasons from different sites in Guangzhou. n-Alkanes, fatty acids and nitriles were the predominant compounds in the thermodesorption products, whereas aromatics, fatty acids, nitriles and n-alkanes/alkenes were the major compounds in the pyrolysates. The results indicated that aromatics were main units in macromolecules. The fatty acids and nltriles formed from carboxylic ammonium salts were detected in both thermodesorption products and pyrolysates at a certain concentration, indicating the importance of these compounds in TSP formation. The TSP source mainly determined the occurrence of compounds in samples from urban, suburban and forest sites, whereas the TSP source and formation process maybe controlled the seasonal variation in compounds detected. High levels of nitriles in summer samples from suburban and forest sites coincide with the release of ammonium from the land and of fatty acids from vegetation at these sites.

Enrichment and immobilization of macromolecular analytes on a porous membrane utilizing permeation drag

Enrichment and immobilization of analytes by chemical bonding or physical adsorption is typically the first step in many commonly used analytical techniques. In this paper, we discuss a permeation drag based technique as an alternative approach for carrying out location-specific immobilization of macro- molecular analytes. Fluorescein isothiocyanate （FITC） labeled macromolecules and their complexes were enriched near the surface of ultrafiltration membranes and detected by direct visual observation and fluorescence imaging. The level of macromolecule enrichment at the immobilization sites could be controlled by manipulating the filtration rate and thereby the magnitude of permeation drag. Higher enrichment as indicated by higher fluorescence intensity was observed at higher filtration rates. Also, larger macromolecules were more easily enriched. The feasibility of using this technique for detecting immunocomplexes was demonstrated by carrying out experiments with FITC labeled bovine serum al- bumin （FITC-BSA） and its corresponding antibody. This permeation drag based enrichment technique could potentially be developed further to suit a range of analytical applications involving more sophis- ticated detection methods.

PREPARATION OF PERFLUOROOCTANOYL-MODIFIED POLY(VINYL-ALCOHOL)S AND THEIR ADSORPTION AT AN AIR-WATER INTERFACE

Perfluorooctanoyl modified poly(vinyl alcohol)s (FPVA) were prepared by means of substituting a small amount of hydroxyl groups on the backbone of poly(vinyl alcohol), for which the initial degree of polymerization is equal to 1750. The substitution extent, defined by the number of substituting units in a chain, for the four FPVA samples was in the range of 0.5-5 perfluorooctanoyl groups per chain. The FPVA samples with the highest substitution extent still had good solubility in water. It was shown by experimental measurement at 30.0 +/- 0.1 degreesC that the surface tension of the aqueous solution of the highest substituted FPVA decreased to 16.6 mN/m at a higher concentration, e.g. about 0.1 g/mL. Obviously, macromolecules of FPVA exhibit a very strong tendency to adsorb at the air-water interface, because the hydrophobic perfluorooctanoyl groups in FPVA have a very high surface activity as they are in small molecular fluorinated surfactants. The chain conformation of such a model polymer adsorbed on the air-water interface was also discussed.

An Efficient Multi-Scale Modelling Approach for ssDNA Motion in Fluid Flow

The paper presents a multi-scale modelling approach for simulating macromolecules in fluid flows. Macromolecule transport at low number densities is frequently encountered in biomedical devices, such as separators, detection and analysis systems. Accurate modelling of this process is challenging due to the wide range of physical scales involved. The continuum approach is not valid for low solute concentrations, but the large timescales of the fluid flow make purely molecular simulations prohibitively expensive. A promising multi-scale modelling strategy is provided by the meta-modelling approach considered in this paper. Meta-models are based on the coupled solution of fluid flow equations and equations of motion for a simplified mechanical model of macromolecules. The approach enables simulation of individual macromolecules at macroscopic time scales. Meta-models often rely on particle-corrector algorithms, which impose length constraints on the mechanical model. Lack of robustness of the particle-corrector algorithm employed can lead to slow convergence and numerical instability. A new FAst Linear COrrector （FALCO） algorithm is introduced in this paper, which significantly improves computational efficiency in comparison with the widely used SHAKE algorithm. Validation of the new particle corrector against a simple analytic solution is performed and improved convergence is demonstrated for ssDNA motion in a lid-driven micro-cavity.

Investigation of the Elasticity of Polymer Nanoparticle by Vibrating Scanning Polarization Force Microscopy

The elasticity of an individual polymer nanoparticle may be greatly different from that of the bulk one. Understanding the properties of individual particles such as elasticity and deformation under external forces is of great importance in controlling the final structures and functions of bulk materials. We study the compression properties of single polyethylenimine （PEI） particles using vibrating scanning polarization force microscopy. By controllably imaging PEI particles at different vibration amplitude set-point values, it is demonstrated that we can compress the single PEI nanoparticle with an atomic force microscopy tip in different loads. Based on the force-height and force-strain curves obtained, Young＇s moduli of PEI （5-160 MPa） in three force regions are estimated according to the Hertz model The results indicate that PEI has excellent elasticity, which may contribute to its high efficiency as vectors in gene transfection.

COMPUTER SIMULATION OF NON-NEWTONIAN FLOW AND MASS TRANSPORT THROUGH CORONARY ARTERIAL STENOSIS

A numerical analysis of Newtonian and non-Newtonian flow in an axi-symmetric tube with a local constriction simulating a stenosed artery under steady and pulsatile flow conditions war carried out. Bared on these results, the concentration fields of LDL ( (low-density lipoprotein) and Albumin were discussed. According to the results, in great details the macromolecule transport influences of wall shear stress, non-Newtonian fluid character and the scale of the molecule etc are given. The results of Newtonian fluid flow and non-Newtonian fluid flow, steady flow and pulsatile flow are compared. These investigations can provide much valuable information about the correlation between the flow properties, the macromolecule transport and the development of atherosclerosis.

PDBlocal:A web-based tool for local inspectionof biological macromolecular 3D structures

Functional research on biological macromolecules must fcus on specific loca regions.PDBlocal is aweb-based tool developed to overcome the limitations of traditional molecular visualization tools forthre-dimensional(3D)inspection of local regions.PDBlocal provides an intuitive and easy-to-manipulate web page interface and some new useful functions.It can kep loca regions flashing,display sequence text that is dynamically consistent with the 3D structure in local appearance undermultiple local manipulations,use two scenes to help users inspect the same local region withdifferent statuses,list all historical manipulation statuses with a tree structure,llow users toannotate regions ofinterest,and save ll historical statuses and other data to a web server for futureresearch.PDBlocal has met expectations and shown satisfactory performance for both expert andnovice users.This tool is available at http:/labsystem.scuec.edu.cn/pdblocal/.

Studies on the Self-condensing Vinyl Living Radical Polymerization of a Novel Acrylate Inimer

A novel acrylate inimer, 2-（2-chloroacetyloxy） ethyl acrylate, was prepared by the reaction of 2-hydroxyethyl acrylate with chloroacetyl chloride in the presence of triethylamine. The self-condensing vinyl living radical polymerization of the inimer was studied and the hyperbranched macromolecules containing ester linkages on their backbone were prepared. All the polymerization products were characterized by 1H NMR. The polymerization degree and the branching parameter were calculated based on the 1H NMR spectra. It has been shown that this inimer exhibits a very distinctive polymerization behavior. Similar to step-growth polymerization, the polymerization degree of the products formed increased exponentially during the early stage of the polymerization, and then the increasing rate slowed down. However, the inimer remained present throughout the polymerization consistent with conventional free radical polymerization. Also, if much longer polymerization time was used, the polymerization system would become gel due to the crosslinking reaction derived from radical-radical recombination. As a result of the unequal reactivity of -CH2Cl and >CHCl, an almost linear product was obtained at a molar ratio of bipy to inimer=0.05, while a relatively high ratio of bipy to inimer 1 favored the formation of the branched structure. The macromolecules formed at a high ratio of bipy to inimer 1 exhibited an excellent solubility in organic solvents such as acetone.

Molecular Environment of Reserving Information (M.E.R.I. Technology)

The idea of application from DNA information organization for providing the next generation super-computers has been proposed by lessons learned from nature. Thus, molecular environment of reserving information was considered as succeeding generation of a mother-board project containing some subcategories with various applications. MERI, constructed based on the binary coding system using DNA synthesizer machine, enables retrievable reading of molecular structures using DNA sequencer machine. It has high capacity for reservation of information about 1.212 × 1011 Kb/cm2 with long-term stability. It can be used in various fields of science and technology regarding its high capacity, small size and safety measures.