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Fe-based catalysts are efficient systems for CO2 conversion via reverse water-gas shift (rWGS) reaction. Nevertheless, the nature of the active phase, namely metallic iron, iron oxide or iron carbide remains a subject of debate which our paper is meant to close. Fe0 is a much better catalyst for the rWGS than Fe3C. The activity of Fe0 can be promoted by the addition of Cs and Cu whose presence hinders iron carburisation while favouring both higher conversion and enhanced selectivity. When the samples are aged in the rWGS reaction mixture during stability test a new phase appear: Fe5C2, resulting in a more active but less selective catalysts than Fe0 for the rWGS reaction. Hence our results indicate that we could potentially achieve an optimal activity/selective balance upon finely tuning the proportion Fe/Fe5C2. Beyond the fundamental information concerning active phase we have observed the presence of advanced Fischer-Tropsch-like products at ambient pressure opening new opportunities for the design of hybrid rWGS/Fischer-Tropsch systems.

A novel quasi-reflectionless bandpass filter (BPF) using double-sided parallel-strip line (DSPSL) is proposed in this letter. It is composed of a BPF and two symmetric absorptive bandstop filters (ABSFs) terminated by a pair of resistors that can dissipate the input untransmitted signal energy. Through detailed analysis, the high characteristic impedance is required for the open-circuited stubs of the ABSFs to enhance the selectivity. This cannot be realized in traditional microstrip designs, but it can be obtained easily by offsetting the DSPSL. Meanwhile, the BPF with T-shaped structure consists of a half-wavelength (λ/2) DSPSL with a centrally-loaded λ/2 stub, which answers for generating two transmission zeros (TZs) to achieve better out-of-band suppression. For demonstration, a prototype is designed, fabricated and measured, and the simulated and measured results with good agreement are presented.

For memory to be efficient, people need to remember important information. This involves selective encoding and retrieval operations to maximise the recall of valuable information at the expense of less important information. While past research has examined this in terms of strategic encoding operations, we investigated differences in the dynamics of retrieval in value-directed remembering tasks with younger adults under full and divided attention during encoding as well as in older adults. Participants typically initiated recall with the first presented, last presented, or highest valued words and also strategically organised retrieval according to information value such that high-value words tended to be recalled before low-value words. However, the average value of older adults’ first recalled word was greater than that of younger adults, likely contributing to their enhanced selectivity. In addition, there were no differences in lag-conditional-response probabilities in younger adults under full or divided attention, but older adults showed impairments in the retrieval of items sharing contextual features with nearby items, while younger adults relied more on temporal-contextual cues to recall words. Together, this study suggests that both strategic encoding and strategic retrieval operations contribute to selectivity for valuable information and older adults may be able to maximise retrieval operations despite displaying impairments in temporal binding during encoding and an overall recall deficit.

The promoted activity and enhanced selectivity of electrocatalysts is commonly ascribed to specific structural features such as surface facets, morphology, and atomic defects. However, unraveling the factors that really govern the direct electrochemical reduction of CO2 (CO2 RR) is still very challenging since the surface state of electrocatalysts is dynamic and difficult to predict under working conditions. Moreover, theoretical predictions from the viewpoint of thermodynamics alone often fail to specify the actual configuration of a catalyst for the dynamic CO2 RR process. Herein, we re-survey recent studies with the emphasis on revealing the dynamic chemical state of Cu sites under CO2 RR conditions extracted by in situ/operando characterizations, and further validate a critical link between the chemical state of Cu and the product profile of CO2 RR. This point of view provides a generalizable concept of dynamic chemical-state-driven CO2 RR selectivity that offers an inspiration in both fundamental understanding and efficient electrocatalysts design.

Copper-based materials could produce a series of products through the CO2 electroreduction reaction, and are regarded as the most promising catalysts to produce fuels and value-added chemicals using renewable energy sources. However, the competitive hydrogen evolution reaction (HER) is a daunting challenge for the selectivity of carbonaceous products. Here, a hydrophobic electrode surface was constructed by modifying the CuO nanowire electrode with a thick Nafion overlayer, which exhibited enhanced selectivity toward the CO2 RR (especially for CO) and suppressed HER activity. This work highlights the importance of hydrophobicity in the selectivity of CO2 reduction and hints at the additional role of Nafion in powder-based catalyst electrodes.

We report three well-defined types of Au nanoparticles (NPs) protected by rigid macrocyclic cucurbit[n]uril (CB[n]) (CB[n]-Au), which are prepared via the supramolecular self-assembly of the precursors. CB[n]-Au shows excellent catalytic activity and selectivity, with a performance that can be maintained for up to 72 h in the electroreduction of CO2 to CO. The effects of the structural features of different CB[n]s on the electrocatalytic performance of the Au NPs have been revealed for the first time.

Significant technical advancements in phosphopeptide enrichment have enabled the identification of thousands of p-peptides (mono and multiply phosphorylated) in a single experiment. However, it is still not possible to enrich all p-peptide species in a single step. A range of new techniques and materials has been developed, with the potential to provide a step-change in phosphopeptide enrichment. The first half of this review contains a tutorial for new potential phosphoproteomic researchers; discussing the key steps of a typical phosphoproteomic experiment used to investigate canonical phosphorylation sites (serine, threonine and tyrosine). The latter half then show-cases the latest developments in p-peptide enrichment including: i) Strategies to mitigate non-specific binding in immobilized metal ion affinity chromatography and metal oxide affinity chromatography protocols; ii) Techniques to separate multiply phosphorylated peptides from monophosphorylated peptides (including canonical from non-canonical phosphorylated peptides), or to simultaneously co-enrich other post-translational modifications; iii) New hybrid materials and methods directed towards enhanced selectivity and efficiency of metal-based enrichment; iv) Novel materials that hold promise for enhanced phosphotyrosine enrichment. A combination of well-understood techniques and materials is much more effective than any technique in isolation; but the field of phosphoproteomics currently requires benchmarking of novel materials against current methodologies to fully evaluate their utility in peptide based proteoform analysis.

Significance The selectivity of binding of colloidal particles is an important research topic for the field of targeted drug delivery. Extensive theoretical work has shown that high selectivity can be obtained by using multivalent weak interactions. Here we provide comprehensive experimental proof using DNA-coated particles. The ligand–receptor affinity is varied by changing the number of complementary bases, showing that fewer complementary bases yield a higher binding selectivity. The experimental data and corresponding numerical model simulations demonstrate the scaling behavior between molecular density, molecular affinity, and resulting density selectivity of interparticle binding. These results are important for the design of novel systems for targeted nanoparticle drug delivery., Targeted drug delivery critically depends on the binding selectivity of cargo-transporting colloidal particles. Extensive theoretical work has shown that two factors are necessary to achieve high selectivity for a threshold receptor density: multivalency and weak interactions. Here, we study a model system of DNA-coated particles with multivalent and weak interactions that mimics ligand–receptor interactions between particles and cells. Using an optomagnetic cluster experiment, particle aggregation rates are measured as a function of ligand and receptor densities. The measured aggregation rates show that the binding becomes more selective for shorter DNA ligand–receptor pairs, proving that multivalent weak interactions lead to enhanced selectivity in interparticle binding. Simulations confirm the experimental findings and show the role of ligand–receptor dissociation in the selectivity of the weak multivalent binding.

Hydrogenation of dimethyl oxalate (DMO) is one of the key steps in the route of ethylene glycol (EG) production from syngas. Cu/SiO2 catalysts prepared by the ammonia evaporation method are reporte...

In-depth understanding of the catalytic active sites is of paramount importance for the design of efficient electrocatalysts for CO2 conversion. Here we highlight the structural evolution of SnO2 nanosheets for electrocatalytic CO2 reduction. The transformation of SnO2 into metallic Sn would occur on the surface of catalyst during the catalytic process, followed by enhanced selectivity and activity for the conversion of CO2 to HCOOH. Electrocatalytic characterization and structural analysis demonstrate that the metallic Sn derived from structural evolution plays a dominant role in the CO2 reduction to HCOOH. This work deepens the understanding of the catalytic mechanism and provides a new pathway for the rational design of advanced electrocatalysts for CO2 reduction. Ministry of Education (MOE) National Research Foundation (NRF) We acknowledge the support from the National Research Foundation(NRF),Prime Minister’s Office, Singapore, under its Campus for Research Excellence and Technological Enterprise(CREATE) program. We also acknowledge financial support from start-up grant, College of Engineering, Nanyang Technological University, and the academic research fund AcRF tier1 (M4012076RG118/18),Ministry of Education, Singapore

The design of molecularly selective interfaces can lead to efficient electrochemically-mediated separation processes. The fast growing development of electroactive materials has resulted in new electroresponsive adsorbents and membranes, with enhanced selectivity, higher uptake capacities, and improved energy performance. Here, we review progress on the interfacial design for electrochemical separations, with a focus on chemical and biological applications. We discuss the development of new electrode materials and the underlying mechanisms for selective molecular binding, highlighting areas of growing interest such as metal recovery, waste recycling, gas purification, and protein separations. Finally, we emphasize the need for integration between molecular level interface design and electrochemical engineering for the development of more efficient separation processes. We envision that electrochemical separations can play a key role towards the electrification of the chemical industry and contribute towards new approaches for process intensification.

The integration of biocatalysis with chemocatalysis combines the excellent selectivity of the former with the robust reactivity of the latter and offers many advantages, such as lower cost, higher yield, enhanced selectivity, as well as less waste generation. In spite of the challenge of incompatibilities between different classes of catalysts, recent advances in synthetic chemistry and biology provide ample opportunities for multistep cascade transformations that combine biocatalysis and chemocatalysis. Herein, we review recent progress in merging biocatalysis with chemocatalysis, highlighting selected examples of photo-/electricity-driven biotransformations and recently developed strategies for addressing the catalyst incompatibility issue.

Background: Tankyrases are known for their multifunctionalities within the poly(ADPribose) polymerases family and playing vital roles in various cellular processes which include the regulation of tumour suppressors. Tankyrases, which exist in two isoforms; Tankyrase 1 and 2, are highly homologous and an integral part of the Wnt β -catenin pathway that becomes overly dysregulated when hijacked by pro-carcinogenic machineries. Methods: In this review, we cover the distinct roles of the Tankyrase isoforms and their involvement in the disease pathogenesis. Also, we provide updates on experimentally and computationally derived antagonists of Tankyrase whilst highlighting the precedence of integrative computer-aided drug design methods towards the discovery of selective inhibitors. Results: Despite the high prospects embedded in the therapeutic targeting and blockade of Tankyrase isoforms, the inability of small molecule inhibitors to achieve selective targeting has remained a major setback, even until date. This explains numerous incessant drug design efforts geared towards the development of highly selective inhibitors of the respective Tankyrase isoforms since they mediate distinct aberrancies in disease progression. Therefore, considering the setbacks of conventional drug design methods, can computer-aided approaches actually save the day? Conclusion: The implementation of computer-aided drug design techniques in Tankyrase research could help complement experimental methods and facilitate ligand/structure-based design and discovery of small molecule inhibitors with enhanced selectivity.

Exploration of the synergistic effect in catalysis upon simultaneous utilization of two sources of power, ultrasound and light, is barely explored and remains a challenging issue. A crucial reason behind this is the difficulty in designing and constructing a well-defined sonophotoreactor capable of taking advantage of the benefits of combining sonochemistry and photochemistry. Herein, we present our successful reactor and a detailed study regarding how the utilization of ultrasonication can act as a process intensification tool for selective and partial photooxidation of a biomass derived model compound, benzyl alcohol. The main outcome was the enhanced selectivity in the case of sonophotocatalysis compared to photocatalysis. This selectivity was ascribed to the effects derived from the cavitation phenomena, leading to phenomena such as hot spot formation and jetting. Our study can act as guidance towards understanding the unique effects of ultrasound irradiation as a hybrid process intensification method (HPIM) towards application in more complex chemical reactions and manipulation of the nanocatalysts’ photoreactivity in catalytic valorization applications.

Metal–organic frameworks (MOFs) have been extensively studied for enhancing the performances of fluorescent probes based on the host–guest chemistry, while the selectivity enhancement of fluorescent probes through integration into MOFs is still relatively rare. In this work, Cd:ZnS QDs were integrated into ZIF-8 that could specifically interact with Cu2+ for fluorescence sensing. The fluorescence of Cd:ZnS QDs was quenched by Cu2+ based on cation exchange, while this phenomenon was also observed in the presence of Mn2+, Co2+ and Ni2+. By contrast, only Cu2+ induced the fluorescence quenching of Cd:ZnS QDs@ZIF-8 as a result of its specific interaction with ZIF-8. In addition, Cd:ZnS QDs@ZIF-8 displayed a fast response of 1 min and a low detection limit of 16 nM toward Cu2+, and moreover, it was successfully applied to detecting Cu2+ in water samples with spiked recoveries ranging from 90.1 to 109.8%. These results indicate that integration into ZIF-8 is an efficient strategy to enhance the selectivity of fluorescent probes toward Cu2+.

Development of novel nanomaterial-based co-reactant is highly desired for enhancing ECL intensity and widespread analytical applications. Herein, we report the distinct role of amine-functionalized carbon quantum dots (f-CQDs) as a co-reactant, for the first time, augmenting the ECL property of Ru(bpy)32+ and demonstrating for biopharmaceutical (butein) detection. Unlike conventional co-reactants like tripropylamine (TPrA), 2-(dibutylamino)ethanol (DBAE), and pristine CQDs, the f-CQDs as a co-reactant yield superior ECL of Ru(bpy)32+. More importantly, the ECL intensity is independent of types of noble metals, metal oxide surfaces, and dissolved oxygen. Notably, the ECL intensity of Ru(bpy)32+–f-CQDs is linearly quenched with an increased concentration of butein, whereas no changes were observed with conventional co-reactants. ECL functionality of Ru(bpy)32+–f-CQDs has no interference with other similar phytochemicals and antioxidants. Enhanced selectivity is observed due to the formation of polyaminoquinone-like structures, which is confirmed by in situ spectroelectrochemical (UV–vis) and FT-IR studies. The present result envisaged that f-CQDs could be an alternative co-reactant for TPrA/DBAE, raising the ECL of Ru(bpy)32+ suitable for analytical studies.

Cu is a catalyst that can electrochemically reduce CO2 to a variety of industrially important carbon products, but often with poor selectivity and low current density. Alloying Cu with other metals...

International audience; The long-standing history of platinum coordination complexes in nucleic acid recognition attests to the unique suitability of such species for therapeutic applications. Here, we report the synthetic exploration and development of a family of di-imine ligands, and their platinum(II) complexes, elaborated on a 3-(2-pyridyl)-[1,2,4]triazolo[4,3-a]pyridine platform which, in its unsubstituted form, has recently been shown to display exceptional capabilities for guanine quadruplex (G4) targeting. The identification of facile, high-yielding synthetic methods for the derivatization of this platform for the incorporation of additional sites of interactions with guanine quadruplex loops and grooves, along with the optimization of platinum(II) complexation methods, are discussed. Gratifyingly, preliminary biophysical screening of this novel family of binders validates all but one family members as robust G4 binders and highlights enhanced selectivity for quadruplex versus duplex DNA compared to the parent compound. These results bear promise for practical developments based on this platform.

Small ubiquitin-like modifiers (SUMO) and ubiquitin are frequent post-translational modifications of proteins that play pivotal roles in all cellular processes. We previously reported mass spectrometry-based proteomics methods that enable profiling of lysines modified by endogenous SUMO or ubiquitin in an unbiased manner, without the need for genetic engineering. Here we investigated the applicability of precursor mass filtering enabled by MaxQuant.Live to our SUMO and ubiquitin proteomics workflows, which efficiently avoided sequencing of precursors too small to be modified but otherwise indistinguishable by mass-to-charge ratio. Using precursor mass filtering, we achieved a much higher selectivity of modified peptides, ultimately resulting in up to 30% more SUMO and ubiquitin sites identified from replicate samples. Real-time exclusion of unmodified peptides by MQL resulted in 90% SUMO-modified precursor selectivity from a 25% pure sample, demonstrating great applicability for digging deeper into ubiquitin-like modificomes. We adapted the precursor mass filtering strategy to the new Exploris 480 mass spectrometer, achieving comparable gains in SUMO precursor selectivity and identification rates. Collectively, precursor mass filtering via MQL significantly increased identification rates of SUMO- A nd ubiquitin-modified peptides from the exact same samples, without the requirement for prior knowledge or spectral libraries.

A novel, mixed-linker metal−organic framework (MOF) was synthesized, and the resulting macromolecular assembly had enhanced activity and stability in comparison to the isostructural CuBTC (aka HKUST-1). Mixtures of 5-aminoisophthalic acid (AIA) and 1,3,5-benzenetricarboxylic acid (BTC) were combined at different ratios to incorporate aryl amine groups into the MOF that were readily amenable to postsynthetic modification. As one example, the amine groups were reacted with decanoyl chloride (DC) through the formation of amide linkages, which overcame a major shortcoming of CuBTC by stabilizing the MOF toward ammonia vapor during breakthrough experiments and to liquid water for over 24 h. Furthermore, the MOF modified with DC exhibited ∼70% increases in CO₂/N₂ and CO₂/H₂O selectivity at flue gas relevant conditions relative to CuBTC. The modified MOFs had increased compatibility with polyacrylonitrile, poly(styrene-block-isoprene-block-styrene), and poly(styrene-block-ethylene-ranbutylene-block-styrene) polymers, which made them ideal for incorporation in polymer fibers and composite films and reduced defects generally associated with polymer−nanoparticle systems. Finally, the AIA and DC-modified MOFs had significantly enhanced moisture stability relative to unmodified CuBTC. Overall, this facile modification route provides the framework for higher-performance materials in applications such as filtration, gas storage, and flue gas scrubbing, among many others.

Various routes of phenylacetylene and styrene hydrogenation on the Pd(100) surface were studied by the DFT-PBE density functional method. The three-layer model of the Pd53 cluster was used for the description of the Pd(100) surface. The Gibbs activation energy of hydrogenation of a phenylacetylene molecule adsorbed according to the di-σ type was shown to be 21.7 kcal mol−1, whereas that of a styrene molecule was 23.4 kcal mol−1. The Gibbs activation energy for the strongly adsorbed di-μ-structure of phenylacetylene is significantly higher (35.2 kcal mol−1). The difference in Δ≠G298 values of the reaction of phenylacetylene and styrene hydrogenation explains the enhanced selectivity to styrene, but this difference is lower than the earlier calculated value for the Pd(111) surface. According to the calculations, a low coverage of the Pd(100) surface should favor the formation of stable fourfold site di-μ-structures of adsorbed phenylacetylene, which can result in a sharp decrease in the phenylacetylene hydrogenation rate and a decrease in the selectivity of hydrogenation to styrene.

While many synthetic nanotubes with a hydrophobic lumen and fast molecular transport have been developed, decorating the interior of these channels with polar and/or responsive functional groups remains challenging. In transmembrane proteins like the aquaporin and M2 channels, the presence of histidine residues in a mostly hydrophobic channel has led to enhanced selectivity and pH-based activation. Herein, we report the synthesis of Bzim-CP, a cyclic octapeptide that contains a benzimidazole functionality as a chemical and structural mimic of histidine. Bzim-CP undergoes different protonation states, forms subnanometer nanotubes, and projects two different ionizable functionalities into the lumen. Present studies open up synthetic possibilities to functionalize subnanometer porous channels as a basis toward understanding new transport phenomena.

The selective electrochemical reduction of CO2 to value-added products is a useful strategy for the local storage of intermittent energy sources as chemical fuels and the recycling of industrial CO...

Adsorbents that undergo structural changes in the presence of adsorbate molecules are an interesting new class of materials, which could offer enhanced selectivity, purity and recovery in separation technology. To date however, their application in such technology is hampered by the lack of a simple, consistent thermodynamic framework, which can effectively describe and predict theiradsorption behaviour under a range of conditions. This becomes especially true for their behaviour in multicomponent adsorbate mixtures, for which experimental data is limited and cumbersome to obtain. Here we present how the relatively simple Rigid Adsorbent Lattice Fluid model successfully and accurately predicts stepped isotherms in the breathing MOF, MIL-53 (Al) in the presence of CO2 and CH4. Breathing transitions are predicted solely on the basis of the different densities of the material’s two structural configurations and their associated Gibbs energies. Hysteresis effects can easily be included by considering the structures’ osmotic stress, which can be calculated readily from the lattice fluid expressions. The model can be parameterised with a minimum of experimental or simulated data, subsequently becoming predictive, and since the model has its origins in statistical mechanics, no prior assumptions, such as Langmuir type behaviour are required, presenting a major advantage over existing (semi)-empirical models. The approach shown in this study shouldfurthermore be generic and should equally well apply to other flexible adsorbents.

Gas molecules are known to interact with two-dimensional (2D) materials through surface adsorption where the adsorption-induced charge transfer governs the chemiresistive sensing of various gases. Recently, titanium carbide (Ti

To date, chemoresistive gas sensors based on metal oxide semiconductors (MOS) have been the most attractive sensor types for the practical application. However, with the emerging concept of Internet of Everything, high operating temperatures over 300 °C of the gas sensors based on MOS must be reduced to achieve low power consumption and overcome a limited battery capacity of mobile devices. The 2-dimensional materials like MoS2 have been, therefore, one of the most recently studied materials for gas sensors with capability of operation at significantly lower temperatures. However, lacking selectivity toward various target gas species limited their application to gas sensors. Herein, we investigated the effects of noble metals (Pd and Au) decoration on the gas sensing properties of MoS2 thin films. Due to the electronic sensitization of the noble metal catalysts and the formation of Pd hydride, overall gas responses and selectivity were significantly improved toward tests gas species. These results provide clear understandings on the effects of the surface noble metal catalysts on gas sensing properties of MoS2.

Selective synthesis of higher oxygenates (linear α-alcohols and α-aldehydes, C 2 + OH) from syngas is highly attractive but remains challenging owing to the low C 2 + OH selectivity and low catalytic stability. Herein we introduce a multifunctional catalyst composed of CoMn and CuZnAlZr oxides that dramatically increased the oxygenates selectivity to 58.1 wt %, where more than 92.0 wt % of the produced oxygenates are C 2 + OH. Notably, the total selectivity to value-added chemicals including oxygenates and olefins reached 80.6 wt % at CO conversion of 29.0 % with high stability. The appropriate component proximity can effectively suppress the formation of the undesired C1 products, and the selectively propulsion of reaction network by synergetic effect of different components contributes to the enhanced selectivity to higher oxygenates. This work provides an alternative strategy for the rational design of new catalysts for direct conversion of syngas into higher oxygenates with co-production of olefins.

The selective precipitation of zinc from zinc–nickel sulfate solution with the Zn/Ni molar ratio of 20:1 was studied. Dropwise addition of 0.5 mol/L NaOH solution into the zinc–nickel sulfate solution containing 0, 0.01, 0.02, 0.03 and 0.04 mol/L ethylene diamine tetraacetate (EDTA) as a chelating agent was done. The equilibrium analysis of precipitation pathway was performed using Visual MINTEQ program. The equilibrium analysis showed that the presence of small amounts of EDTA can prevent nickel precipitation in alkaline conditions without any negative effect on zinc precipitation. On this basis, more than 90% of zinc could be precipitated as a product with about 50% Zn and only 0.11% Ni at pH=9.0 merely as a result of the presence of 0.03 mol/L EDTA in the solution. The stirring time of 120 min after precipitation was found to be essential for more complete separation. The X-ray diffraction studies on the precipitate revealed that the precipitated phase was Zn4(OH)6SO4.4H2O.

Selective hydrogen peroxide (H2O2) electrogeneration by oxygen reduction reaction (ORR) is an efficient and promising synthetic method for H2O2 production. Herein, we build a particular inorganic–organic interface to enhance the electrocatalytic selectivity of reduced graphene oxide (rGO) aerogels for H2O2 electrogeneration by modifying rGO aerogels with polyethyleneimine (PEI). The three-dimensional porous structure of aerogels and the steric hindrance effect of PEI on rGO endow PEI-functionalized rGO (rGO/PEI) aerogels with enhanced selectivity (90.7%), production rate (106.4 mmol gcat–1 h–1), and durability for H2O2 electrogeneration by the two-electron pathway of ORR.

Chemical separations account for about 50% of costs and energy use associated with chemical and petrochemical manufacturing, corresponding to about 10% of all energy use in the U.S. Membrane separations are highly energy efficient, simple to operate, scalable, and portable. Broader use of membranes is limited by the selectivity of available membranes, mostly confined to the separation of species about an order of magnitude or more different in size in the liquid phase. This perspective focuses on new approaches for creating liquid filtration membranes that can perform more challenging separations. We first discuss the selectivity mechanisms of currently available membranes and compare them with the operation of biological systems that exhibit enhanced selectivity. Then, we review some approaches for creating isoporous membranes with narrow pore size distributions for enhanced size-based selectivity. We discuss biological systems that exhibit selectivity based on factors beyond size and how they can inspir...

Antibody-drug conjugates (ADCs) are a new generation of anticancer therapeutics with enhanced selectivity against the target cancer cells over the conventional chemotherapeutic agents. Such conjugates help in delivery of drugs with enhanced therapeutic performance, thus creating a highly target-specific and cytotoxic-anticancer therapy with the advantage of a wide therapeutic window. Several drug molecules have been investigated in this regard for improving their anticancer activity with the help of antibodies of specific targeting ability to the human cancers. ADCs also help in reducing the toxicity of chemotherapeutic agents by transforming them into the inactive agents.

Herein, we report a dual dye competitive screening method for the identification of five boronic acid functionalized synthetic lectins (SLs) that are selective for prostate-associated targets with the goal of detecting and staging prostate cancer. This method uses differently labeled normal (RWEP-1) and diseased (PC3) cell membrane extracts in a competitive binding assay to identify SLs that bind either the cancerous or normal extracts but not both. Subsequent studies examined the efficacy of these new SL hits in an array format to discriminate six prostate cell lines. The SL array was able to (a) classify the prostate cell lines with 83% accuracy, (b) discriminate the same cell lines based on their metastatic potential (noncancerous/healthy, cancerous/lowly metastatic, and cancerous/metastatic) with 96% classification accuracy, and (c) exhibit enhanced selectivity for prostate-derived versus colon-derived cell lines. Further analysis delineated the contribution from each SL in these studies, providing a focused SL array having potential utility as a cancer diagnostic.

A critical property of many therapies is their selective binding to specific target populations. Exceptional specificity can arise from high-affinity binding to unique cell surface targets. In many cases, however, therapeutic targets are only expressed at subtly different levels relative to off-target cells. More complex binding strategies have been developed to overcome this limitation, including multi-specific and multi-valent molecules, but these create a combinatorial explosion of design possibilities. Therefore, guiding strategies for developing cell-specific binding are critical to employ these tools. Here, we extend a multi-valent binding model to multi-ligand and multi-receptor interactions. Using this model, we explore a series of mechanisms to engineer cell selectivity, including mixtures of molecules, affinity adjustments, and valency changes. Each of these strategies maximizes selectivity in distinct cases, leading to synergistic improvements when used in combination. Finally, we identify situations in which selectivity cannot be derived through passive binding alone to highlight areas in need of new developments. In total, this work uses a quantitative model to unify a comprehensive set of design guidelines for engineering cell-specific therapies.Summary pointsAffinity, valency, and other alterations to target cell binding provide enhanced selectivity in specific situations.Evidence for the effectiveness and limitations of each strategy are abundant within the drug development literature.Combining strategies can offer enhanced selectivity.A simple, multivalent ligand-receptor binding model can help to direct therapeutic engineering.

Metal-Organic frameworks (MOFs), especially MOF-based composites, performed an irreplaceable role in the material fields. By virtue of the tailorability of MOFs, core-shell MOFs@MOFs composites with diverse designability and enhanced selectivity have inspired infinite scientific interest. This review will highlight an up-to-date overview of the designability and enhanced selectivity of core-shell MOFs@MOFs composites, covering the synthetic strategies of an epitaxial growth method, postsynthetic modification, and one-pot synthesis as well as the synergistic selective performance of the synthesized MOFs@MOFs in catalysis, adsorption and separation, and molecular recognition. Finally, the potential development trend and challenges toward core-shell MOFs@MOFs are addressed.

To make optimal decisions in uncertain circumstances flexible adaption of behaviour is required; exploring alternatives when the best choice is unknown, exploiting what is known when that is best. Using a detailed computational model of the basal ganglia, we propose that switches between exploratory and exploitative decisions can be mediated by the interaction between tonic dopamine and cortical input to the basal ganglia. We show that a biologically detailed action selection circuit model of the basal ganglia, endowed with dopamine dependant striatal plasticity, can optimally solve the explore-exploit problem, estimating the true underlying state of a noisy Gaussian diffusion process. Critical to the model’s performance was a fluctuating level of tonic dopamine which increased under conditions of uncertainty. With an optimal range of tonic dopamine, explore-exploit decision making was mediated by the effects of tonic dopamine on the precision of the model action selection mechanism. Under conditions of uncertain reward pay-out, the model’s reduced selectivity allowed disinhibition of multiple alternative actions to be explored at random. Conversely, when uncertainly about reward pay-out was low, enhanced selectivity of the action selection circuit was enhanced, facilitating exploitation of the high value choice. When integrated with phasic dopamine dependant influences on cortico-striatal plasticity, the model’s performance was at the level of the Kalman filter which provides an optimal solution for the task. Our model provides an integrative account of the relationship between phasic and tonic dopamine and the action selection function of the basal ganglia and supports the idea that this subcortical neural circuit may have evolved to facilitate decision making in non-stationary reward environments, allowing a number of experimental predictions with relevance to abnormal decision making in neuropsychiatric and neurological disease.