Computational Simulation of Aptamer-target Binding Mechanisms

Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.

DNA binding mechanism of WhiB4 from Mycobacterium tuberculosis

Mycobacterium tuberculosis(Mtb),the pathogen of tuberculosis,has latently infected about one-third of the world's population and may lead to severe clinical symptoms and death.The WhiB4 protein,a transcription factor,plays a crucial role in the survival and pathology of Mtb.WhiB4 leads to the condensation of mycobacterial nucleoids and regulates the expression of genes involved in central metabolism,respiration,and maintaining redox homeostasis.Here,we report the solution structure of reduced apo-WhiB4 monomer,which consists of an unstructured N-terminal domain with four cysteine residues and a helix-turnhelix C-terminal domain that plays a major role in DNA binding.The C-terminal domain of WhiB4 binds DNA at the minor groove,with five positively charged lysine/arginine residues contacting DNA sugar-phosphate backbones through electrostatic interactions.AT-rich DNA sequences with narrower minor grooves are more preferred by WhiB4.The binding affinity of a single C-terminal domain of WhiB4 is weak.When oxidized,WhiB4 can form dimers and oligomers in different forms through disulfide bonds,which should significantly enhance its DNA binding ability through multivalent effect and change the local structure of target genes and influence their transcription.These structural features form the basis for WhiB4 to function as a redox-sensitive transcription factor in Mtb.

Risk assessment and binding mechanisms of potentially toxic metals in sediments from different water levels in a coastal wetland

The excessive accumulation of potentially toxic metals(Pb and Cd)in coastal wetlands is among the main factors threateningwetland ecosystems.However,the effects ofwater table depth(WTD)on the risk and binding mechanisms of potentially toxic metals in sediments remain unclear.Here,sediments from different WTD obtained from a typical coastal wetland were evaluated using a newly developed strategy based on chemical extraction methods coupled with high-resolution spectroscopy.Our findings indicated that the WTD of the coastal wetland fluctuates frequently and the average enrichment factor for Pb was categorized as minor,whereas Cd enrichment was categorized as moderate.High-resolution spectroscopy techniques also demonstrated that organic functional groups and partly inorganic compounds(e.g.,Fe-O/Si-O)played a vital role in the binding of Pb and Cd to surface sediments.Additionally,mineral components rather than organic groups were mainly bound to thesemetals in the bottom sediments.Collectively,our findings provide key insights into the potential health effects and binding characteristics of potentially toxic metals in sediments,as well as their dynamic behavior under varying sediment depths at a microscale.

A novel and promising engineering application of carbon dots:Enhancing the chloride binding performance of cement

Corrosion of reinforcement induced by chloride invasion is extensively considered as the dominating deterioration mechanism of reinforced concrete(RC)structures,leading to serious safety hazards and tremendous economic losses.However,it still lacks well dispersive and cost-efficient nanomaterials to improve the anti-chloride-corrosion ability of RC structures.Herein,specific carbon dots(CDs)with high dispersity and low cost are deliberately designed,successfully prepared by hydrothermal processing,and then firstly applied to immensely enhance chloride binding performance of cement,thereby contributing to suppressing the corrosion of reinforcement.Specifically,the tailored CDs are composed of the carbon core with highly crystalline sp^(2)C structures and oxygen-containing groups connecting on the carbon core;The typical equilibrium test confirms that with respect to that of the blank cement paste,the chloride binding capacity of cement paste involving 0.2 wt%(by weight of cement)CDs is increased by 109% after 14-day exposure to 3 mol/L Na Cl solution;according to comprehensive analyses of phase compositions,the chloride binding mechanism of CDs-modified cement is rationally attributed to the fact that the incorporation of CDs advances the formation of calcium silicate hydrate(C-S-H)gels and Friedel's salt(Fs),thus enormously enhancing the physically adsorbed and chemically bound chloride ions of cement pastes.This work not only firstly provides a novel high-dispersity and low-cost nanomaterial toward the durability enhancement of RC structures,but also broadens the application of CDs in the field of engineering,conducing to stimulating their industrialization development.

Neural mechanisms of feature binding

An object is usually composed of different features(e.g.,color,orientation,and motion),which are processed by segregated visual pathways and represented by functionally specialized brain areas.However,we perceive an object as a coherent whole,rather than its isolated features.How we integrate those isolated features and achieve a precise perception of objects is a fundamental challenge for the visual system,which is referred to as the binding problem.

Simultaneous removal of Cd(Ⅱ)and As(Ⅴ)by ferrihydrite-biochar composite:Enhanced effects of As(Ⅴ)on Cd(Ⅱ)adsorption

The coexistence of cadmium(Cd(Ⅱ))and arsenate(As(Ⅴ))pollution has long been an environmental problem.Biochar,a porous carbonaceous material with tunable functionality,has been used for the remediation of contaminated soils.However,it is still challenging for the dynamic quantification and mechanistic understanding of the simultaneous sequestration of multi-metals in biochar-engineered environment,especially in the presence of anions.In this study,ferrihydrite was coprecipitated with biochar to investigate how ferrihydritebiochar composite affects the fate of heavy metals,especially in the coexistence of Cd(Ⅱ)and As(Ⅴ).In the solution system containing both Cd(Ⅱ)and As(Ⅴ),the maximum adsorption capacities of ferrihydrite-biochar composite for Cd(Ⅱ)and As(Ⅴ)reached 82.03μmol/g and 531.53μmol/g,respectively,much higher than those of the pure biochar(26.90μmol/g for Cd(Ⅱ),and 40.24μmol/g for As(Ⅴ))and ferrihydrite(42.26μmol/g for Cd(Ⅱ),and 248.25μmol/g for As(Ⅴ)).Cd(Ⅱ)adsorption increased in the presence of As(Ⅴ),possibly due to the changes in composite surface charge in the presence of As(Ⅴ),and the increased dispersion of ferrihydrite by biochar.Further microscopic and mechanistic results showed that Cd(Ⅱ)complexed with both biochar and ferrihydrite,while As(Ⅴ)was mainly complexed by ferrihydrite in the Cd(Ⅱ)and As(Ⅴ)coexistence system.Ferrihydrite posed vital importance for the co-adsorption of Cd(Ⅱ)and As(Ⅴ).The different distribution patterns revealed by this study help to a deeper understanding of the behaviors of cations and anions in the natural environment.

Supporting Consistency in Linked Specialized Engineering Models Through Bindings and Updating

Currently, some commercial software applications support users to work in an integrated environment. However, this is limited to the suite of models provided by the software vendor and consequently it forces all the parties to use the same software. In contrast, the research described in this paper investigates ways of using standard software applications, which may be specialized for different professional domains. These are linked for effective transfer of information and a binding mechanism is provided to support consistency. The proposed solution was implemented using a CAD application and an independent finite element application in order to verify the theoretical aspects of this work.

Characterization of Interfacial Bonding Mechanism for Graphene-Modified Powder Metallurgy Nickle-Based Superalloy

A modified FGH96 superalloy using 0.1 wt% graphene was successfully prepared using the wet mixing method. The interracial bonding mechanism between the graphene and the superalloy matrix was characterized using optical micro- scope, scanning electronic microscope, transmission electronic microscope and X-ray tomography. The results revealed that the graphene could be dispersed uniformly inside the matrix of the superalloy, and the bonding interface between graphene and the superalloy showed a rather diffusion instead of abrupt distinction, suggesting that the interface was formed via chemical fusion rather than a mechanical combination. The uniform dispersity of the graphene inside the superalloy matrix could improve the tensile properties significantly, including tensile strength, plasticity and yield strength. The existence of the graphene at the fracture surface further verified that the graphene could increase the effective bearing force of the material during the tensile test.

Recent advances in diverse nanosystems for nitric oxide delivery in cancer therapy

Gas therapy has been proven to be a promising and advantageous treatment option for cancers.Studies have shown that nitric oxide(NO)is one of the smallest structurally significant gas molecules with great potential to suppress cancer.However,there is controversy and concern about its use as it exhibits the opposite physiological effects based on its levels in the tumor.Therefore,the anti-cancer mechanism of NO is the key to cancer treatment,and rationally designed NO delivery systems are crucial to the success of NO biomedical applications.This review summarizes the endogenous production of NO,its physiological mechanisms of action,the application of NO in cancer treatment,and nano-delivery systems for delivering NO donors.Moreover,it briefly reviews challenges in delivering NO from different nanoparticles and the issues associated with its combination treatment strategies.The advantages and challenges of various NO delivery platforms are recapitulated for possible transformation into clinical applications.

Identifying potential compounds from Bacopa monnieri(brahmi)against coxsackievirus A16 RdRp targeting HFM disease(tomato flu)

Hand,foot,and mouth disease(HFMD),primarily instigated by Coxsackievirus A16(CVA16),poses a serious health concern,necessitating effective therapeutic interventions.The RNA-dependent RNA polymerase(RdRp)of CVA16 emerges as a promising drug target for HFMD treatment.This study presents an in-silico pipeline for the identification of potential RdRp inhibitors against CVA16.A library of 91 natural compounds derived from Bacopa monnieri(brahmi)was virtually screened against the CVA16 RdRp.Here,Bacobitacin D emerged as a promising hit molecule,forming 8 hydrogen bonds including key catalytic site residues(Asp^(238)and Asp^(329))within the RdRp active site.Further,molecular dynamics(MD)simulations and MM/GBSA binding free energy calculations was applied on the top three hits that were selected based on exhaustive docking scores(≤-9.55 kcal/mol).Bacobitacin D exhibited sustainable stability,as evidenced by minimal deviation(RMSD=0.75±0.02 nm)during a 100 ns MD simulation.Importantly,Bacopaside IV exhibited the lowestΔGTOTAL binding free energy(-23.70 kcal/mol),while Bacobitacin D displayed a comparableΔGTOTAL of19.14 kcal/mol.Structural interpretation of the most populated cluster derived from MD simulations showed direct interactions of Bacobitacin D with pivotal catalytic residues,including Asp^(238)and Ser^(289).This comprehensive study confirmed Bacobitacin D as a potent inhibitor of CVA16 RdRp,offering a potential avenue for therapeutic intervention against HFMD.Experimental validation is required to confirm the inhibitory action of Bacobitacin D against HFMD.

Strategies of binder design for high-performance lithium-ion batteries:a mini review

Developing high-performance lithium-ion batteries (LIBs) with high energy density, rate capability and long cycle life are essential for the ever-growing practical application. Among all battery components, the binder plays a key role in determining the preparation of electrodes and the improvement of battery performance, in spite of a low usage amount. The main function of binder is to bond the active material, conductive additive and current collector together and provide electron and ion channels to improve the kinetics of electrochemical reaction. With the ever-increasing requirement of high energy density by LIBs, technical challenges such as volume expansion and active material dissolution are attracting worldwide attentions, where binder is thought to provide a new solution.There are two main categories (organic solvent soluble binder and water-soluble binder) and abundant polar functional groups providing adhesion ability. It is of great significance to timely summarize the latest progress in battery binders and present the principles for designing novel binders with both robust binding interaction and outstanding electrode stabilization function. This review begins with an introduction of the binding mechanism and the related binding forces, including mechanical interlocking forces and interfacial forces. Then, we discussed four different strategies (the enhancement of binding force,the formation of three-dimensional (3D) network, the enhancement of conductivity and binders with special functions) for constructing ideal binder system in order to satisfy the specific demands of different batteries, such as LIBs and lithium–sulfur (Li–S) batteries. Finally, some prospective and promising directions of binder design are proposed based on the existing and emerging binders and guide the development of the next-generation LIBs.