Natural Counterparts Research Articles

Surface Ligand Engineering Ruthenium Nanozyme Superior to Horseradish Peroxidase for Enhanced Immunoassay.

Nanozymes have great potential to be used as an alternative to natural enzymes in a variety of fields. However, low catalytic activity compared with natural enzymes limits their practical use. It is still challenging to design nanozymes comparable to their natural counterparts in terms of the specific activity. In this study, a surface engineering strategy is employed to improve the specific activity of Ru nanozymes using charge-transferrable ligands such as polystyrene sulfonate (PSS). PSS-modified Ru nanozyme exhibits a peroxidase-like specific activity of up to 2820Umg-1 , which is twice that of horseradish peroxidase (1305Umg-1 ). Mechanism studies suggest that PSS readily accepts negative charge from Ru, thus reducing the affinity between Ru and ·OH. Importantly, the modified Ru-peroxidasenanozyme is successfully used to develop an immunoassay for human alpha-fetoprotein and achieves a 140-fold increase in detection sensitivity compared with traditional horseradish-peroxidase-based enzyme-linked immunosorbent assay. Therefore, this work provides a feasible route to design nanozymes with high specific activity that meets the practical use as an alternative to natural enzymes.

Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs

Phosphorus Fluoride Exchange (PFEx) represents a cutting-edge advancement in catalytic click-reaction technology. Drawing inspiration from Nature's phosphate connectors, PFEx facilitates the reliable coupling of P(V)-F loaded hubs with aryl alcohols, alkyl alcohols, and amines to produce stable, multidimensional P(V)-O and P(V)-N linked products. The rate of P-F exchange is significantly enhanced by Lewis amine base catalysis, such as 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD). PFEx substrates containing multiple P-F bonds are capable of selective, serial exchange reactions via judicious catalyst selection. In fewer than four synthetic steps, controlled projections can be deliberately incorporated along three of the four tetrahedral axes departing from the P(V) central hub, thus taking full advantage of the potential for generating three-dimensional diversity. Furthermore, late-stage functionalization of drugs and drug fragments can be achieved with the polyvalent PFEx hub, hexafluorocyclotriphosphazene (HFP), as has been demonstrated in prior research.

Tunable Structured Metal Oxides for Biocatalytic Therapeutics

AbstractThe past few decades have witnessed the flourish of creating metal oxides for biocatalytic therapeutics due to their structural diversities, feasible modifications, tunable catalytic sites, and low cost when compared to their natural enzyme counterparts. Here, in this timely review, the most recent progress and future trends in engineering tunable structured metal oxides and decoding their structure‐reactivity relationships for biocatalytic therapeutics is comprehensively summarized. At first, the fundamental activities, evaluations, and mechanisms of metal oxide‐based biocatalysts are carefully disclosed. Subsequently, the merits, design methods, and state‐of‐art achievements of different types of nanostructured and biofunctionalized metal oxides are thoroughly discussed. Thereafter, it provides detailed comments on the catalytic center modulation strategies to engineer metal oxides for efficient reactive oxygen species (ROS)‐catalysis, including atomic catalytic site engineering, heterostructures, and support effects. Furthermore, the representative applications of these ROS‐catalytic metal oxides have been systematically summarized, such as catalytic disinfections, cancer therapies, ROS scavenging and anti‐inflammations, biocatalytic sensors, as well as corresponding toxicities. Finally, current challenges and future perspectives are also highlighted. It is believed that this review can provide cutting‐edge and multidisciplinary instruction for the future design of ROS‐catalytic metal oxides and stimulate their widespread utilization in broad therapeutic applications.

Cosmetic and Pharmaceutic Products with Selected Natural and Synthetic Substances for Melasma Treatment and Methods of Their Analysis

Melasma is a fairly common condition that is the result of hyperpigmentation caused by increased melanin secretion. In the course of melasma, certain areas of the skin become darker than the rest of the epidermis. Although the pathogenesis remains incompletely clarified, several contributing factors have been identified, namely exposure to ultraviolet and visible light, family predisposition, pregnancy, and the use of exogenous hormones. Since current beauty standards associate healthy skin with its flawless and uniform color, people strive to eliminate any unaesthetic discoloration. Cosmetic and pharmaceutical products containing active substances with a whitening effect then become helpful. The most commonly used for this purpose are hydroquinone, arbutin, retinoids, organic acids (e.g., kojic, azelaic, and ellagic), and vitamins (B3, C, and E). However, the undesirable side effects they cause and the drive to replace synthetic chemicals with their natural counterparts have resulted in numerous reports on extracts of natural origin that exhibit skin-whitening effects. The purpose of this paper is to review the most recent scientific literature, which presents active substances of natural and synthetic origin with potential for the treatment of melasma. In addition, analytical techniques that can be used for qualitative and quantitative analysis of these substances present in cosmetic and pharmaceutical products will also be presented.

Urban environments provide new perspectives for forecasting vegetation phenology responses under climate warming.

Given that already-observed temperature increase within cities far exceeds the projected global temperature rise by the end of the century, urban environments often offer a unique opportunity for studying ecosystem response to future warming. However, the validity of thermal gradients in space serving as a substitute for those in time is rarely tested. Here, we investigated vegetation phenology dynamics in China's 343 cities and empirically test whether phenological responses to spatial temperature rise in urban settings can substitute for those to temporal temperature rise in their natural counterparts based on satellite-derived vegetation phenology and land surface temperature from 2003 to 2018. We found prevalent advancing spring phenology with "high confidence" and delaying autumn phenology with "medium confidence" under the context of widespread urban warming. Furthermore, we showed that space cannot substitute for time in predicting phenological shifts under climate warming at the national scale and for most cities. The thresholds of ~11°C mean annual temperature and ~600 mm annual precipitation differentiated the magnitude of phenological sensitivity to temperature across space and through time. Below those thresholds, there existed stronger advanced spring phenology and delayed autumn phenology across the spatial urbanization gradients than through time, and vice versa. Despite the complex and diverse relationships between phenological sensitivities across space and through time, we found that the directions of the temperature changes across spatial gradients were converged (i.e., mostly increased), but divergent through temporal gradients (i.e., increased or decreased without a predominant direction). Similarly, vegetation phenology changes more uniformly over space than through time. These results suggested that the urban environments provide a real-world condition to understand vegetation phenology response under future warming.

Modified foredune eco-morphology in southeast Australia

Human activities are playing increasingly significant roles in the dynamics and evolution of coastal dunes, one of the most intensively used environments on Earth. Not only do beaches and adjacent foredunes provide tourism and recreational uses but they also form an important buffer between coastal settlements and the ocean. Modified or “urbanised” foredunes often differ from their natural counterparts in terms of characteristics such as location, dimension, orientation, topographic variability, sediment features, mobility, and the degree to which they can initiate and/or develop further through natural processes (e.g. progradation). Much of this research has been focused on dunes found in Europe and the USA, with limited work done elsewhere. The availability of LiDAR-derived topographic data for the entire coast enables a state-wide assessment of foredune morphology in New South Wales (NSW), and a basis for determining the effects of human modification. This study examines the current morphological characteristics of foredunes in NSW, by comparing modified with natural settings, to understand how human activities and uses have impacted foredune morphology. Results show highly modified incipient and established foredunes were significantly narrower and reached lower elevations, consequently with smaller volumes of sand than their more natural counterparts. On average, both highly modified established and incipient dunes were half the size of the unmodified systems, and on average modified dunes had volumes of ∼350 m3 m−1, whereas unmodified dunes contained sand volumes of ∼740 m3 m−1. By lowering dune elevation and sand volumes, human modifications have created environments that are more exposed and potentially vulnerable to erosion, placing coastal properties, infrastructure and communities (especially those found behind modified dune systems) at greater risk of erosion, coastal flooding and inundation, particularly during storm events.

Synthesis of Carlina Oxide Analogues and Evaluation of Their Insecticidal Efficacy and Cytotoxicity.

Compounds isolated from botanical sources represent innovative and promising alternatives to conventional insecticides. Carlina oxide is a compound isolated from Carlina acaulis L. (Asteraceae) essential oil (EO) with great potential as bioinsecticide, being effective on various arthropod vectors and agricultural pests, with moderate toxicity on non-target species. Since the production from the wild source is limited, there is the need of exploring new synthetic routes for obtaining this compound and analogues with improved bioactivity and lower toxicity. Herein, the chemical synthesis of carlina oxide analogues was developed. Their insecticidal activity was assessed on the vectors Musca domestica L. and Culex quinquefasciatus Say, and their cytotoxicity was evaluated on a human keratinocyte cell line (HaCaT). The compounds' activity was compared with that of the natural counterparts EO and carlina oxide. In housefly tests, the analogues were comparably effective to purified carlina oxide. In Cx. quinquefasciatus assays, the meta-chloro analogue provided a significantly higher efficacy (LC50 of 0.71 μg mL-1) than the EO and carlina oxide (LC50 1.21 and 1.31 μg mL-1, respectively) and a better safety profile than carlina oxide on keratinocytes. Overall, this study can open the way to an agrochemical production of carlina oxide analogues employable as nature-inspired insecticides.

The selection of a hydrophobic 7-phenylbutyl-7-deazaadenine-modified DNA aptamer with high binding affinity for the Heat Shock Protein 70

Nucleic acids aptamers often fail to efficiently target some proteins because of the hydrophilic character of the natural nucleotides. Here we present hydrophobic 7-phenylbutyl-7-deaadenine-modified DNA aptamers against the Heat Shock Protein 70 that were selected via PEX and magnetic bead-based SELEX. After 9 rounds of selection, the pool was sequenced and a number of candidates were identified. Following initial screening, two modified aptamers were chemically synthesised in-house and their binding affinity analysed by two methods, bio-layer interferometry and fluorescent-plate-based binding assay. The binding affinities of the modified aptamers were compared with that of their natural counterparts. The resulting modified aptamers bound with higher affinity (low nanomolar range) to the Hsp70 than their natural sequence (>5 µM) and hence have potential for applications and further development towards Hsp70 diagnostics or even therapeutics.

Proteomic Shotgun and Targeted Mass Spectrometric Datasets of Cerebrospinal Fluid (Liquor) Derived from Patients with Vestibular Schwannoma

Vestibular schwannomas are relatively rare intracranial tumors compared to other brain tumors. Data on the molecular features, especially on schwannoma proteome, are scarce. The 41 cerebrospinal fluid (liquor) samples were obtained during the surgical removal of vestibular schwannoma. Obtained peptide samples were analyzed by shotgun LC-MS/MS high-resolution mass spectrometry. The same peptide samples were spiked with 148 stable isotopically labeled peptide standards (SIS) followed by alkaline fractionation and scheduled multiple reaction monitoring (MRM) for quantitative analysis. The natural counterparts of SIS peptides were mapped onto 111 proteins that were Food and Drug Administration (FDA)-approved for diagnostic use. As a result, 525 proteins were identified by shotgun LC-MS/MS with high confidence (at least two peptides per protein, FDR < 1%) in liquor samples. Absolute quantitative concentrations were obtained for 54 FDA-approved proteins detected in at least five experimental samples. Since there is lack of data on the molecular landscape of vestibular schwannoma, the obtained datasets are unique and one of the first in its field.

Mechanical characterisation of new Sand-Hemihydrate rock-analogue material: Implications for modelling of brittle crust processes

The analogue materials play a critical role in dynamically scaled experiments, defining the processes that can be simulated and the structures observable in the model. The dynamic scaling enables the direct comparison between the model and its natural counterpart. To obtain such a model the physical and mechanical properties of the analogue material must be scaled with respect to the rock prototype. A large variety of materials have been applied in analogue modelling studies to address the physical and mechanical requirements for the simulation of (i) upper crust, (ii) middle crust and (iii) lower crust and mantle processes. Nevertheless, the development of new model materials represents a continuous improvement of the analogue modelling techniques.We investigated the mechanical and physical properties of a new Granular Rock-Analogue Material (GRAM) (introduced in Massaro et al. (2022)) and its component materials. GRAM is an ultra-weak artificial sandstone composed of quartz sand cemented with gypsum, capable to deform by tensile and shear failure under variable stress conditions. GRAM aggregates in different mixing ratios (from 1% to 4% in weight of hemihydrate powder) were systematically tested with ring-shear tests and uniaxial compression tests. The relationships between the hemihydrate content and the mechanical properties of GRAM were examined. Additionally, the sample preparation procedure of GRAM was investigated, evaluating the impact of the residual water content on the mechanical properties of GRAM aggregates and defining a standard preparation procedure. Finally, GRAM was compared to natural rocks and to other granular materials applied in analogue modelling studies, in terms of physical and mechanical properties, application to physical modelling and dynamic scaling. It was underlined how the application of GRAM aggregates in dynamically scaled experiments can enhance the comprehension of the fault and fracture processes occurring at the scale of the damage zone.

Transmembrane signaling by a synthetic receptor in artificial cells

Signal transduction across biological membranes is among the most important evolutionary achievements. Herein, for the design of artificial cells, we engineer fully synthetic receptors with the capacity of transmembrane signaling, using tools of chemistry. Our receptors exhibit similarity with their natural counterparts in having an exofacial ligand for signal capture, being membrane anchored, and featuring a releasable messenger molecule that performs enzyme activation as a downstream signaling event. The main difference from natural receptors is the mechanism of signal transduction, which is achieved using a self-immolative linker. The receptor scaffold is modular and can readily be re-designed to respond to diverse activation signals including biological or chemical stimuli. We demonstrate an artificial signaling cascade that achieves transmembrane enzyme activation, a hallmark of natural signaling receptors. Results of this work are relevant for engineering responsive artificial cells and interfacing them and/or biological counterparts in co-cultures.

An Artificial Miniaturized Peroxidase for Signal Amplification in Lateral Flow Immunoassays.

Signal amplification strategies are widely used for improving the sensitivity of lateral flow immunoassays (LFiAs). Herein, the artificial miniaturized peroxidase Fe(III)-MimochromeVI*a (FeMC6*a), immobilized on gold nanoparticles (AuNPs), is used as a strategy to obtain catalytic signal amplification in sandwich immunoassays on lateral flow strips. The assay scheme uses AuNPs decorated with the mini-peroxidase FeMC6*a and anti-human-IgG as a detection antibody (dAb), for the detection of human-IgG, as a model analyte. Recognition of the analyte by the capture and detection antibodies is first evidenced by the appearance of a red color in the test line (TL), due to the accumulation of AuNPs. Subsequent addition of 3,3',5,5'-tetramethylbenzidine (TMB) induces an increase of the test line color, due to the TMB being converted into an insoluble colored product, catalyzed by FeMC6*a. This work shows that FeMC6*a acts as an efficient catalyst in paper, increasing the sensitivity of an LFiA up to four times with respect to a conventional LFiA. Furthermore, FeMC6*a achieves lower limits of detection that are found in control experiments where it is replaced with horseradish peroxidase (HRP), its natural counterpart. This study represents a significant proof-of-concept for the development of more sensitive LFiAs, for different analytes, based on properly designed artificial metalloenzymes.

Biomimetic Janus film fabricated via cryogenic electrospinning for gastrointestinal mucosa repair

Substantial mucosa defects in gastrointestinal tracts are difficult to repair, causing high mortality. Existing artificial mucosa studies overlooked the natural surface texture and the paracrine action between epithelial cells and fibroblasts, leading to an incomplete repair of the mucosa. Here, a Janus film with an exterior surface having a ridge-like texture and an interior flat surface to mimic the anatomical pattern of natural mucosa in digestive tracts is obtained through cryogenic electrospinning (e-spinning). Inspired by the natural mucosa surface textures, biopolymer nanofiber assemblies are employed to replicate the micro-ridges of the exterior layer of mucosa, while the flat surface mimics the morphology of the inferior layer. Hence, the exterior surface of Janus film bolsters epithelial cells' proliferation through the macro pores between fiber assemblies and the nanopores on fibers. In addition, the Janus film realizes a bilayer epithelium/lamina propria reconstruction by culturing epithelial cells and fibroblasts on different sides of the Janus film. Moreover, the Janus film assists the paracrine action between epithelial cells and fibroblasts while insulating their direct contact, an essential mimicry of the natural counterpart. In summary, it is proved that the Janus film will be a promising repair solution for mucosa defects in digestive tracts.

Eight years of community structure monitoring through recreational citizen science at the "SS Thistlegorm" wreck (Red Sea).

Large artificial coral reef communities, such as those thriving on sunken shipwrecks, tend to mirror those of nearby natural coral reefs and their long-term dynamics may help future reef resilience to environmental change. We examined the community structure of the world-renown "SS Thistlegorm" wreck in the northern Red Sea from 2007 through 2014, analyzing data collected during the recreational citizen science Red Sea monitoring project "Scuba Tourism for the Environment". Volunteer divers collected data on 6 different diving parameters which included the date of the dive, maximum depth, average depth, temperature, dive time, hour of dive, and gave an abundance estimation of sighted taxa from a list of 72 target taxa. Although yearly variations in community structure were significant, there was no clear temporal trend, and 71 of all 72 target taxa were sighted throughout the 8 years. The 5 main taxa driving variations among year clusters in taxa presence/absence (Soft Tree Coral-Dendronephthya spp., Giant Moray-Gymnothorax javanicus, Squirrel Fish-Sargocentron spp., Humpback Batfish-Platax spp., and Caranxes-Carangidae) and taxa abundance (Soft Tree Coral, Giant Moray, Red Sea Clownfish-Amphiprion bicinctus, Napoleon Wrasse-Cheilinus undulatus, and Caranxes) data were determined. The "SS Thistlegorm" provides a compelling example of how artificial coral reefs can sustain a well-established community structure similar to those of their natural counterparts.

Trophic Assessment of an Artificial Kelp Eisenia bicyclis Bed Off the Eastern Coast of Korea Based on Stable Isotope Analyses

Effective trophic assessment of restoration success after the creation of an artificial habitat is essential for ecological management. In this study, to evaluate the ecological trophic function of restored kelp beds of artificial macroalgal reefs (AMRs) attached with the kelp species Eisenia bicyclis, we compared carbon and nitrogen stable isotope ratios of organic matter sources and macrobenthic consumers and isotopic indices of functional feeding groups between artificial and reference (natural bed and barren ground, respectively) habitats. There were no significant differences in isotopic values of consumer feeding groups (except for carnivores) and their potential food sources between the artificial and natural sites, suggesting that resource diversity and resource use by consumers was similar across all sites. The isotopic data also exhibited similar or relatively higher trophic niches of feeding groups at the artificial site compared to those at the natural site, indicating that the artificial kelp bed can play important roles in similar ecological functions and services as a natural counterpart. In addition, the present study revealed that the isotopic ranges and niche indices of feeding groups were significantly wider at the artificial and natural kelp beds compared to those at the barren ground, suggesting the trophic importance of macroalgal-derived organic matter to consumer nutrition in coastal ecosystems. Overall, our results support the conclusion that the creation of an Eisenia bicyclis kelp bed by the AMRs may lead to the restoration success of the macroalgae habitat through the recovery of the ecological function of a natural food web structure.

Preprint Highlight: A synthetic signaling network imitating the action of immune cells in response to bacterial metabolism

Synthetic cells, built using approaches from bottom-up synthetic biology, aim to mimic biological functions of their natural counterparts. However, engineering multilevel coordination of signaling networks remains challenging. This study demonstrates a minimalist synthetic signaling network mimicking netosis, an innate immune system response that traps and elicits an antimicrobial response against pathogens. Modular DNA particles were activated by the pH shift induced by E. coli metabolism, generating a sticky DNA-cholesterol network that evolved over time to trap the bacteria. Then, giant unilamellar vesicles containing an antibiotic were permeabilized by the DNA particles, reducing the growth of E. coli. The development of this synthetic signaling cascade has implications for artificial cells in therapeutics, biofilm research, biomaterials, and bioremediation. This preprint has been assigned the following badges: New Materials, New Methods. Read the preprint on bioRxiv ( Walczak et al., 2023 ): https://doi.org/10.1101/2023.02.02.526524 .

Prolonged generation of multi-lineage blood cells in wild-type animals from pluripotent stem cells.

Regenerating prolonged multi-lineage hematopoiesis from pluripotent stem cells (PSCs), an unlimited cell source, is a crucial aim of regenerative hematology. In this study, we used a gene-edited PSC line and revealed that simultaneous expression of three transcription factors, Runx1, Hoxa9, and Hoxa10, drove the robust emergence of induced hematopoietic progenitor cells (iHPCs). The iHPCs engrafted successfully in wild-type animals and repopulated abundant and complete myeloid-, B-, and T-lineage mature cells. The generative multi-lineage hematopoiesis distributed normally in multiple organs, persisted over 6months, and eventually declined over time with no leukemogenesis. Transcriptome characterization of generative myeloid, B, and Tcells at the single-cell resolution further projected their identities to natural cell counterparts. Thus, we provide evidence that co-expression of exogenous Runx1, Hoxa9, and Hoxa10 simultaneously leads to long-term reconstitution of myeloid, B, and T lineages using PSC-derived iHPCs as the cell source.

Localized Spontaneous Chiroptical Response in Disordered Plasmonic Nanoaggregates

Metamaterials exhibiting orders-of-magnitude enhanced artificial chiroptical response than natural counterparts have been intensely investigated. The underlying principle of these chiral responses heavily hinges on an elaborate nanostructure fabrication to generate either intrinsic geometry chirality or handedness-dependent mode interference. Here, we unveil that localized spontaneous chiroptical response can be leveraged by plasmonic nanoaggregates with a disordered coupling effect. The near-field coupling among disordered individual gold nanoparticles leads to localized hot spots that are sensitive to the handedness of light. As a consequence, the nearby nanoparticles showcase near-unity circular dichroism in linear absorption to left- and right-circularly polarized light. It directly leads to a subsequent selective photothermal deformation of plasmonic nanoparticles, which produces prominent nonlinear circular dichroism in two-photon fluorescence by circular polarization beams. Such localized spontaneous chirality is then experimentally evidenced by nanoscale multiplexing watermarks in polychromatic beams with left- and right-circular polarizations. Our results might open a new strategy to tailor the chiroptical response in disordered photonic systems and facilitate the study of chiral light–matter interactions at the deep-subwavelength regime.

Microphase separation of living cells

Self-organization of cells is central to a variety of biological systems and physical concepts of condensed matter have proven instrumental in deciphering some of their properties. Here we show that microphase separation, long studied in polymeric materials and other inert systems, has a natural counterpart in living cells. When placed below a millimetric film of liquid nutritive medium, a quasi two-dimensional, high-density population of Dictyostelium discoideum cells spontaneously assembles into compact domains. Their typical size of 100 μm is governed by a balance between competing interactions: an adhesion acting as a short-range attraction and promoting aggregation, and an effective long-range repulsion stemming from aerotaxis in near anoxic condition. Experimental data, a simple model and cell-based simulations all support this scenario. Our findings establish a generic mechanism for self-organization of living cells and highlight oxygen regulation as an emergent organizing principle for biological matter.

Neural Logic Circuits: An evolutionary neural architecture that can learn and generalize

We introduce Neural Logic Circuits (NLC), an evolutionary, weightless, and learnable neural architecture loosely inspired by the neuroplasticity of the brain. This new paradigm achieves learning by evolution of its architecture through reorganization of augmenting synaptic connections and generation of artificial neurons functioning as logic gates. These neural units mimic biological nerve cells stimulated by binary input signals and emit excitatory or inhibitory pulses, thus executing the “all-or-none” character of their natural counterparts. Unlike Artificial Neural Networks (ANN), our model achieves generalization ability without intensive weight training and dedicates computational resources solely to building network architecture with optimal connectivity. We evaluated our model on well-known binary classification datasets using advanced performance metrics and compared results with modern and competitive machine learning algorithms. Extensive experimental data reveal remarkable superiority of our initial model, called NLCv1, on all test instances, achieving outstanding results for implementation of this new paradigm.