Synthesis of nucleoside-peptide conjugate with disulfide bond as linker at C-5 of uridine

In order to prepare pyrimidine nucleoside-peptide conjugate concisely, we developed a one-pot synthetic strategy. Started from uridine, 5-S-acetyl-thiomethyl-2＇,3 ＇-di-O-isopropylidene-uridine （4） was synthesized as the key intermediate in four steps. Under acidic condition, compound 4 was deprotected and reacted with PySS-R （8, 12, 15, Py = 2-pyridyl, R = amino acid or peptide） in one pot to form uridine conjugates （9, 13, 2） with disulfide bond as linker.

Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles(PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxelfatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cistrans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

Prediction Method of Protein Disulfide Bond Based on Pattern Selection

The effect of the different training samples is different for the classifier when pattern recognition system is established. The training samples were selected randomly in the past protein disulfide bond prediction methods, therefore the prediction accuracy of protein contact was reduced. In order to improve the influence of training samples, a prediction method of protein disulfide bond on the basis of pattern selection and Radical Basis Function neural network has been brought forward in this paper. The attributes related with protein disulfide bond are extracted and coded in the method and pattern selection is used to select training samples from coded samples in order to improve the precision of protein disulfide bond prediction. 200 proteins with disulfide bond structure from the PDB database are encoded according to the encoding approach and are taken as models of training samples. Then samples are taken on the pattern selection based on the nearest neighbor algorithm and corresponding prediction models are set by using RBF neural network. The simulation experiment result indicates that this method of pattern selection can improve the prediction accuracy of protein disulfide bond.

Solubility of disulfide-bonded proteins in the cytoplasm of Escherichia co/i and its “oxidizing” mutant

AIM: To study the influence of redox environment of Escherichia coli (E(?) coli) cytoplasm on disulfide bond formation of recombinant proteins. METHODS: Bovine fibrobllast growth factor (BbFGF) was selected as a model of simple proteins with a single disulfide bond and free cysteines. Anti-HBsAg single-chain Fv (HBscFv), an artificial multidomain protein, was selected as the model molecule of complex protein with 2 disulfide bonds. A BbFGF-producing plasmid, pJN-BbFGF, and a HBscFv producing-plasmid, pQE-HBscFv, were constructed and transformed into E(?)coli strains BL21(DE3) and M15[pREP4] respectively. At the same time, both plasmids were transformed into a reductase-deficient host strain,E(?)coli Origami(DE3). The 4 recombinant E(?)coli strains were cultured and the target proteins were purified. Solubility and bioactivity of recombinant BbFGF and HBscFv produced in different host strains were analyzed and compared respectively. RESULTS: All recombinant E(?)coli strains could efficiently produce target proteins. The level of BbFGF in BL21(DE3) was 15-23% of the total protein, and was 5-10% in Origami (DE3). In addition, 65% of the BbFGF produced in BL21(DE3) formed into inclusion body in the cytoplasm, and all the target proteins became soluble in Origami (DE3). The bioactivity of BbFGF purified from Origami(DE3) was higher than its counterpart from BL21(DE3). The ED50 of BbFGF from Origami(DE3) and BL21(DE3) was 1.6 μg/L and 2.2 μg/L, respectively. Both HBscFv formed into inclusion body in the cytoplasm of M15[pQE-HBscFv] or Origami[pQE-HBscFv]. But the supernatant of Origami [pQE-HBscFv] lysate displayed weak bioactivity and its counterpart from M15[pQE-HBscFv] did not display any bioactivity. The soluble HBscFv in Origami[pQE-HBscFv] was purified to be 1-2 mg/L and its affinity constant was determined to be 2.62×107 mol/L. The yield of native HBscFv refolded from inclusion body in M15[pQE-HBscFv] was 30-35 mg/L and the affinity constant was 1.98×107 mol/L. There was no significant difference between the bioactivity of HBscFvs refolded from the inclusion bodies produced in different host strains. CONCLUSION: Modification of the redox environment of E(?)coli cytoplasm can significantly improve the folding of recombinant disulfide-bonded proteins produced in it.

Ultrathin organic polymer with p-πconjugated structure for simultaneous photocatalytic disulfide bond generation and CO_(2)reduction

Combining photocatalytic organic reactions with CO_(2)reduction is an efficient solar energy utilization mode,but it is still limited by the organic species that can be matched and the low conversion.Herein,ultrathin organic polymer with p-πconjugated structure(TPP)was rationally designed and prepared,and showed a high yield of CO(15.2 mmol g^(-1))and conversion of SAS coupled products(100%),far exceeding the organic polymer with P=O structure.The enhanced photoredox activity of TPP is ascribed to the orbital interaction between the p-orbital on phosphorus and theπ-orbitals of aromatic,which can accelerate the photoinduced charge carrier separation and improve the CO_(2)adsorption capacity.TPP can also be used for the dehydrocoupling of various benzyl mercaptans to the corresponding SAS bond products.This work provides a new concept for the efficient synthesis of disulfide bonds combined with CO_(2)reduction in a photoreaction system.

In Silico Disulfide Bond Engineering to Improve Human LEPTIN Stability

Enhancing the stability of biomolecules is one of the hot topics in industry.In this study,we enhanced the stability of an important protein called LEPTIN.LEPTIN is a hormone secreted by fat cells playing an essential role in body weight and composition,and its deficiency can result in several disorders.The treatment of related LEPTIN dysfunctions is often available in the form of injection.To decrease the cost and the frequency of its applications can be achieved by increasing its lifetime through engineering LEPTIN.In this study,to engineer LEPTIN,we have introduced disulfide bonds.Disulfide By Design server was used to predict the suitable nominate pairs,which suggested three pairs of amino acids to be mutated to cysteine for disulfide bond formation.Additionally,to further evaluate the effect of combined mutations,we combined these three nominated pairs to produce three more mutants.In order to assess the effect of introduced mutations,molecular dynamic(MD)simulation was performed.The result suggests that Mutant-1 is more stable in comparison to wild-type and the other mutants.Moreover,docking results showed that the introduced mutation does not affect the receptor binding performance;therefore,it can be considered a suitable choice for future protein engineering.

A Self-Healing and Nonflammable Cross-Linked Network Polymer Electrolyte with the Combination of Hydrogen Bonds and Dynamic Disulfide Bonds for Lithium Metal Batteries

The self-healing solid polymer electrolytes(SHSPEs)can spontaneously eliminate mechanical damages or micro-cracks generated during the assembly or operation of lithium-ion batteries(LIBs),significantly improving cycling performance and extending service life of LIBs.Here,we report a novel cross-linked network SHSPE(PDDP)containing hydrogen bonds and dynamic disulfide bonds with excellent self-healing properties and nonflammability.The combination of hydrogen bonding between urea groups and the metathesis reaction of dynamic disulfide bonds endows PDDP with rapid self-healing capacity at 28°C without external stimulation.Furthermore,the addition of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide(EMIMTFSI)improves the ionic conductivity(1.13×10^(−4)S cm^(−1)at 28°C)and non-flammability of PDDP.The assembled Li/PDDP/LiFePO_(4)cell exhibits excellent cycling performance with a discharge capacity of 137 mA h g^(−1)after 300 cycles at 0.2 C.More importantly,the self-healed PDDP can recover almost the same ionic conductivity and cycling performance as the original PDDP.

Improving the Heat Resistance ofβ-1,4 Glucanase by Introducing Disulfide Bonds

Each possible pair of residues inβ-1,4 glucanase for disulfide formation was assessed using online websites,and four pairs L28C-S256C,Q41C-P278C,S122C-N163C and A184C-A215C were selected.Accordingly,four recombinant plasmids pET28a(+)EccslH28,pET28a(+)EccslH41,pET28a(+)EccslH122 and pET28a(+)EccslH184 were prepared and transformed into E.coli to express the recombinant enzymes.Then analysis on enzymatic properties showed that T50 of the recombinant enzymes was increased from 10 min for EccslHt2 to 90 min for EccslH28 and 40 min for EccslH41 at 70℃,while their optimum pH value and pH stability were not affected,which proved that the introduction of disulfide bond improved the thermal stability ofβ-1,4 glucanase.

Simultaneous Reduction of Nitro Group and S-S Bond in Nitrodisulfides by Samarium Diiodide: A New Approach to Benzothiazolines

Nitrodisulfides were reduced by SmI2/HMPA in anhydrous THF at room temperature to produce active intermediates (samarium thiolates and amides), which were 'living' double-anions and reacted smoothly with aldehydes or ketones to afford benzothiazolines in good yields under mild and neutral conditions.

A Prediction Method of Protein Disulfide Bond Based on Hybrid Strategy

A prediction method of protein disulfide bond based on support vector machine and sample selection is proposed in this paper. First, the protein sequences selected are en-coded according to a certain encoding, input data for the prediction model of protein disulfide bond is generated;Then sample selection technique is used to select a portion of input data as training samples of support vector machine;finally the prediction model training samples trained is used to predict protein disulfide bond. The result of simulation experiment shows that the prediction model based on support vector ma-chine and sample selection can increase the prediction accuracy of protein disulfide bond.

From VIB‑to VB‑Group Transition Metal Disulfides:Structure Engineering Modulation for Superior Electromagnetic Wave Absorption

The laminated transition metal disulfides(TMDs),which are well known as typical two-dimensional(2D)semiconductive materials,possess a unique layered structure,leading to their wide-spread applications in various fields,such as catalysis,energy storage,sensing,etc.In recent years,a lot of research work on TMDs based functional materials in the fields of electromagnetic wave absorption(EMA)has been carried out.Therefore,it is of great significance to elaborate the influence of TMDs on EMA in time to speed up the application.In this review,recent advances in the development of electromagnetic wave(EMW)absorbers based on TMDs,ranging from the VIB group to the VB group are summarized.Their compositions,microstructures,electronic properties,and synthesis methods are presented in detail.Particularly,the modulation of structure engineering from the aspects of heterostructures,defects,morphologies and phases are systematically summarized,focusing on optimizing impedance matching and increasing dielectric and magnetic losses in the EMA materials with tunable EMW absorption performance.Milestones as well as the challenges are also identified to guide the design of new TMDs based dielectric EMA materials with high performance.

基于JK落重和Bond球磨功指数试验的铁矿石碎磨特性及流程模拟计算

弓长岭选厂目前采用传统的“三段一闭路破碎”、“阶段磨矿”的碎磨工艺流程,存在生产工艺流程长且磨矿能耗偏高等问题。因此拟在粗碎后增加(半)自磨作业,降低进入球磨物料的粒度,以期降低磨矿作业能耗,优化碎磨作业工艺流程,提高选厂的作业生产能力,降低磨矿作业生产成本。试验原料铁矿石品位为28.27%,其中铁主要以磁铁矿的形式存在,脉石主要为SiO2,含量为48.61%。以鞍钢弓长岭选厂作业流程中粗碎产品进行JK落重试验,细碎产品进行Bond球磨功指数试验,对矿石的碎磨特性参数进行深入研究。研究结果表明,矿石的冲击破碎模型t10=70.099×(1-exp-0.647×Ecs),其中A为冲击粉碎参数,其值为70.099,b为0.647,A×b为45.354,矿石的抗冲击破碎能力属于中等级别,且随着颗粒粒度的减小而增大;矿石磨蚀系数ta为0.361,抗磨蚀能力为中等级别;矿石的相对密度为3.26。Bond球磨功指数试验获得的功指数Wib=11.7665kWh/t,属于中硬矿石,可以采用(半)自磨工艺。半自磨机设计给矿粒度为F80=160mm,最终产品粒度P80=86μm,JKsimMet软件模拟结果表明,需要2台Φ8.8m×5.1m半自磨机(装机功率7000kW)可满足生产要求。该试验结果对后续选厂工艺流程的优化具有重要意义。

Accelerating Oxygen Electrocatalysis Kinetics on Metal-Organic Frameworks via Bond Length Optimization

Metal-organic frameworks(MOFs)have been developed as an ideal platform for exploration of the relationship between intrinsic structure and catalytic activity,but the limited catalytic activity and stability has hampered their practical use in water splitting.Herein,we develop a bond length adjustment strategy for optimizing naphthalene-based MOFs that synthesized by acid etching Co-naphthalenedicarboxylic acid-based MOFs(donated as AE-CoNDA)to serve as efficient catalyst for water splitting.AE-CoNDA exhibits a low overpotential of 260 mV to reach 10 mA cm^(−2)and a small Tafel slope of 62 mV dec^(−1)with excellent stability over 100 h.After integrated AE-CoNDA onto BiVO_(4),photocurrent density of 4.3 mA cm^(−2)is achieved at 1.23 V.Experimental investigations demonstrate that the stretched Co-O bond length was found to optimize the orbitals hybridization of Co 3d and O 2p,which accounts for the fast kinetics and high activity.Theoretical calculations reveal that the stretched Co-O bond length strengthens the adsorption of oxygen-contained intermediates at the Co active sites for highly efficient water splitting.

Theoretical study on non-sequential double ionization of carbon disulfide with different bond lengths in linearly polarizedlaser fields

By using a two-dimensional Monte-Carlo classical ensemble method, we investigate the double ionization（DI） process of the CS_2 molecule with different bond lengths in an 800-nm intense laser field. The double ionization probability presents a ＂knee＂ structure with equilibrium internuclear distance R = 2.9245 a.u.（a.u. is short for atomic unit）. As the bond length of CS increases, the DI probability is enhanced and the ＂knee＂ structure becomes less obvious. In addition,the momentum distribution of double ionized electrons is also investigated, which shows the momentum mostly distributed in the first and third quadrants with equilibrium internuclear distance R = 2.9245 a.u. As the bond length of CS increases,the electron momentum becomes evenly distributed in the four quadrants. Furthermore, the energy distributions and the corresponding trajectories of the double-ionized electrons versus time are also demonstrated, which show that the bond length of CS in the CS_2 molecule plays a key role in the DI process.

Covalency competition induced selective bond breakage and surface reconstruction in manganese cobaltite towards enhanced electrochemical charge storage

Manganese cobaltite(MnCo_(2)_(4))is a promising electrode material because of its attractive redox chemistry and excellent charge storage capability.Our previous work demonstrated that the octahedrally-coordinated Mn are prone to react with the hydroxyl ions in alkaline electrolyte upon electrochemical cycling and separates on the surface of spinel to reconstruct into d-MnO_(2) nanosheets irreversibly,thus results in a change of the reaction mechanism with Kþion intercalation.However,the low capacity has greatly limited its practical application.Herein,we found that the tetrahedrally-coordinated Co_(2) þions were leached when MnCo_(2)_(4) was equilibrated in 1 mol L^(-1) HCl solution,leading to the formation of layered CoOOH on MnCo_(2)_(4) surface which is originated from the covalency competition induced selective breakage of the CoT–O bond in CoT–O–CoO and subsequent rearrangement of free Co_(6) octahedra.The as-formed CoOOH is stable upon cycling in alkaline electrolyte,exhibits conversion reaction mechanism with facile proton diffusion and is free of massive structural evolution,thus enables utilization of the bulk electrode material and realizes enhanced specific capacity as well as facilitated charge transfer and ion diffusion.In general,our work not only offers a feasible approach to deliberate modification of MnCo_(2)_(4)'s surface structure,but also provides an in-depth understanding of its charge storage mechanism,which enables rational design of the spinel oxides with promising charge storage properties.

Transient liquid phase bonding of DD5 superalloy using a designed interlayer: microstructure and mechanical properties

Nickel based single crystal superalloy is currently widely used as the material for turbine blades in aerospace engines.However,metallurgical defects during the manufacturing process and damage during harsh environmental service are inevitable challenges for turbine blades.Therefore,bonding techniques play a very important role in the manufacturing and repair of turbine blades.The transient liquid phase(TLP)bonding of DD5 Ni-based single crystal superalloy was performed using the designed H1 interlayer.A new third-generation Ni-based superalloy T1 powder was mixed with H1 powder as another interlayer to improve the mechanical properties of the bonded joints.The res-ults show that,such a designed H1 interlayer is beneficial to the improvement of shear strength of DD5 alloy bonded joints by adjusting the bonding temperature and the prolongation of holding time.The maximum shear strength at room temperature of the joint with H1 interlayer reached 681 MPa when bonded at 1260℃for 3 h.The addition of T1 powder can effectively reduce holding time or relatively lower bond-ing temperature,while maintaining relatively high shear strength.When 1 wt.%T1 powder was mixed into H1 interlayer,the maximum room temperature shear strength of the joint bonded at 1260℃reached 641 MPa,which could be obtained for only 1 h.Considering the bonding temperature and the efficiency,the acceptable process parameter of H1+5 wt.%T1 interlayer was 1240℃/2 h,and the room tem-perature shear strength reached 613 MPa.

Hybrid bonding of GaAs and Si wafers at low temperature by Ar plasma activation

High-quality bonding of 4-inch GaAs and Si is achieved using plasma-activated bonding technology.The influence of Ar plasma activation on surface morphology is discussed.When the annealing temperature is 300℃,the bonding strength reaches a maximum of 6.2 MPa.In addition,a thermal stress model for GaAs/Si wafers is established based on finite element analysis to obtain the distribution of equivalent stress and deformation variables at different temperatures.The shape varia-tion of the wafer is directly proportional to the annealing temperature.At an annealing temperature of 400℃,the maximum protrusion of 4 inches GaAs/Si wafers is 3.6 mm.The interface of GaAs/Si wafers is observed to be dense and defect-free using a transmission electron microscope.The characterization of interface elements by X-ray energy dispersion spectroscopy indi-cates that the elements at the interface undergo mutual diffusion,which is beneficial for improving the bonding strength of the interface.There is an amorphous transition layer with a thickness of about 5 nm at the bonding interface.The preparation of Si-based GaAs heterojunctions can enrich the types of materials required for the development of integrated circuits,improve the performance of materials and devices,and promote the development of microelectronics technology.

Unraveling high efficiency multi-step sodium storage and bidirectional redox kinetics synergy mechanism of cobalt-doping vanadium disulfide anode

Sodium-based storage devices based on conversion-type metal sulfide anodes have attracted great atten-tion due to their multivalent ion redox reaction ability.However,they also suffer from sodium polysul-fides(NaPSs)shuttling problems during the sluggish Na^(+) redox process,leading to"voltage failure"and rapid capacity decay.Herein,a metal cobalt-doping vanadium disulfide(Co-VS_(2))is proposed to simulta-neously accelerate the electrochemical reaction of VS_(2) and enhance the bidirectional redox of soluble NaPSs.It is found that the strong adsorption of NaPSs by V-Co alloy nanoparticles formed in situ during the conversion reaction of Co-VS_(2) can effectively inhibit the dissolution and shuttle of NaPSs,and ther-modynamically reduce the formation energy barrier of the reaction path to effectively drive the complete conversion reaction,while the metal transition of Co elements enhances reconversion kinetics to achieve high reversibility.Moreover,Co-VS_(2) also produce abundant sulfur vacancies and unsaturated sulfur edge defects,significantly improve ionic/electron diffusion kinetics.Therefore,the Co-VS_(2) anode exhibits ultrahigh rate capability(562 mA h g^(-1) at 5 A g^(-1)),high initial coulombic efficiency(~90%)and 12,000 ultralong cycle life with capacity retention of 90%in sodium-ion batteries(SIBs),as well as impressive energy/power density(118 Wh kg^(-1)/31,250 W kg^(-1))and over 10.000 stable cycles in sodium-ion hybrid capacitors(SIHCs).Moreover,the pouch cell-type SIHC displays a high-energy density of 102 Wh kg^(-1) and exceed 600 stable cycles.This work deepens the understanding of the electrochemical reaction mechanism of conversion-type metal sulfide anodes and provides a valuable solution to the shuttlingofNaPSs inSIBsandSIHCs.

Protein Disulfide Isomerase and Its Potential Function on Endoplasmic Reticulum Quality Control in Diatom Phaeodactylum tricornutum

PDI is a molecular chaperone and plays an important role in Endoplasmic Reticulum quality control (ERQC).PDI participates in the refolding of the misfolded/unfolded proteins to maintain cellular homeostasis under differentstresses. However, bioinformatic characteristics and potential functions of PDIs in diatom Phaeodactylumtricornutum (Pt) are still unknown so far. Hence, the genome-wide characteristics of PtPDI proteins in P. tricornutumwere first studied via bioinformatic and transcriptomic methods. 42 PtPDI genes were identified from thegenome of P. tricornutum. The motif, protein structure, classification, number of introns, phylogenetic relationship,and the expression level of 42 PtPDI genes under the tunicamycin stress were analyzed. A pair of tandemduplicated genes (PtPDI15 and PtPDI18) was observed in P. tricornutum. The 42 PtPDIs with different genecharacteristics were divided into three independent clades, indicating different evolutional relationships and functionsof these PtPDIs. The 14 up-regulated PtPDI genes under the tunicamycin treatment might have a positiveeffect on the ER quality control of the unfolded/misfolded proteins, while the 7 down-regulated PtPDIs mightnegatively affect the ERQC. The characteristics of all 42 PtPDIs and their proposed working model here providea comprehensive understanding of the PtPDIs gene family. The differential expression of 21 PtPDIs will be usefulfor further functional study in the ERQC.

Biomass valorization via electrocatalytic carbon–carbon bond cleavage

Renewable electrocatalytic upgrading of biomass feedstocks into valuable chemicals is one of the promising strategies to relieve the pressure of traditional energy-based systems.Through electrocatalytic carbon–carbon bond cleavage of high selectivity,various functionalized molecules,such as organic acids,amides,esters,and nitriles,have great potential to be accessed from biomass.However,it has merely received finite concerns and interests in the biorefinery.This review first showcases the research progress on the electrocatalytic conversion of lipid/sugar-and lignin-derived molecules(e.g.,glycerol,mesoerythritol,xylose,glucose,1-phenylethanol,and cyclohexanol)into organic acids via specific carbon–carbon bond scission processes,with focus on disclosing reaction mechanisms,recognizing actual active species,and collecting feasible modification strategies.For the guidance of further extensive studies on biomass valorization,organic transformations via a variety of reactions,including decarboxylation,ring-opening,rearrangement,reductive hydrogenation,and carboxylation,are also disclosed for the construction of similar carbon skeletons/scaffolds.The remaining challenges,prospective applications,and future objectives in terms of biomass conversion are also proposed.This review is expected to provide references to develop renewed electrocatalytic carbon–carbon bond cleavage transformation paths/strategies for biomass upgrading.