Graphene oxide-DNA/graphene oxide-PDDA sandwiched membranes with neuromorphic function.

The behavior of polyelectrolytes in confined spaces has direct relevance to the protein mediated ion transport in living organisms. In this paper, we govern lithium chloride transport by the interface provided by polyelectrolytes, polycation, poly(diallyldimethylammonium chloride) (PDDA) and, polyanion, double stranded deoxyribonucleic acid (dsDNA), in confined graphene oxide (GO) membranes. Polyelectrolyte-GO interfaces demonstrate neuromorphic functions that were successfully applied with nanochannel ion interactions contributed, resulting in ion memory effects. Excitatory and inhibitory post-synaptic currents were tuned continuously as the number of pulses applied increased accordingly, increasing decay times. Furthermore, we demonstrated the short-term memory of a trained vs untrained device in computation. On account of its simple and safe production along with its robustness and stability, we anticipate our device to be a low dimensional building block for arrays to embed artificial neural networks in hardware for neuromorphic computing. Additionally, incorporating such devices with sensing and actuating parts for a complete feedback loop produces robotics with its own ability to learn by modifying actuation based on sensing data.

Thiadiazole-, selenadiazole- and triazole-fused anthraquinones as G-quadruplex targeting anticancer compounds.

G-quadruplex (G4) ligands attract considerable attention as potential anticancer therapeutics. In this study we proposed an original scheme for synthesis of azole-fused anthraquinones and prepared a series of G4 ligands carrying amino- or guanidinoalkylamino side chains. The heterocyclic core and structure of the terminal groups strongly affect on binding to G4-forming oligonucleotides, cellular accumulation and antitumor potency of compounds. In particular, thiadiazole- and selenadiazole- but not triazole-based ligands inhibit the proliferation of tumor cells (e.g. K562 leukemia) and stabilize primarily telomeric and c-MYC G4s. Anthraselenadiazole derivative 11a showed a good affinity to c-MYC G4 in vitro and down-regulated expression of c-MYC oncogene in cellular conditions. Further studies revealed that anthraselenadiazole 11a provoked cell cycle arrest and apoptosis in a dose- and time-dependent manner inhibiting K562 cells growth. Taken together, this work gives a valuable example that the closely related heterocycles may cause a significant difference in biological properties of G4 ligands.

Graphene oxide-polyamine preprogrammable nanoreactors with sensing capability for corrosion protection of materials.

Corrosion is one of the major issues for sustainable manufacturing globally. The annual global cost of corrosion is US$2.5 trillion (approximately 3.4% of the world's GDP). The traditional ways of corrosion protection (such as barriers or inhibiting) are either not very effective (in the case of barrier protection) or excessively expensive (inhibiting). Here, we demonstrate a concept of nanoreactors, which are able to controllably release or adsorb protons or hydroxides directly on corrosion sites, hence, selectively regulating the corrosion reactions. A single nanoreactor comprises a nanocompartment wrapped around by a pH-sensing membrane represented, respectively, by a halloysite nanotube and a graphene oxide/polyamine envelope. A nanoreactor response is determined by the change of a signaling pH on a given corrosion site. The nanoreactors are self-assembled and suitable for mass-line production. The concept creates sustainable technology for developing smart anticorrosion coatings, which are nontoxic, selective, and inexpensive.

A nanofluidic sensing platform based on robust and flexible graphene oxide/chitosan nanochannel membranes for glucose and urea detection.

We present the development of a health-monitoring nanofluidic membrane utilizing biocompatible and biodegradable graphene oxide, chitosan, and graphene quantum dots. The nanoconfinement provided by graphene oxide nanolayers encapsulates chitosan molecules, allowing for their conformational changes and switchable hydrophobic-hydrophilic behavior in response to pH variations. This low-dimensional membrane operates as an array of nanofluidic channels that can release quantum dots upon pH change. The photoluminescence emission from quantum dots enables rapid and reliable optical visualization of pH changes, facilitating efficient human health monitoring. To ensure fouling prevention and enable multiple usages, we adopt a design approach that avoids direct contact between biomarkers and the nanochannels. This design strategy, coupled with good mechanical properties (Young's modulus of 5.5 ± 0.7 GPa), preserves the integrity and functionality of the sensors for repeated sensing cycles. Furthermore, leveraging the memory effect, our sensors can be reloaded with graphene quantum dots multiple times without significant loss of selectivity, achieving reusability. The wide-ranging capabilities of 2D materials and stimuli-responsive polymers empower our sustainable approach to designing low-dimensional, robust, and flexible sensing materials. This approach allows for the integration of various biorecognition elements and signal transduction modes, expanding the versatility and applications of the designed materials.

Angstrom-Confined Electrochemical Synthesis of Sub-Unit-Cell Non-Van Der Waals 2D Metal Oxides.

Bottom-up electrochemical synthesis of atomically thin materials is desirable yet challenging, especially for non-van der Waals (non-vdW) materials. Thicknesses below a few nanometers have not been reported yet, posing the question how thin can non-vdW materials be electrochemically synthesized. This is important as materials with (sub-)unit-cell thickness often show remarkably different properties compared to their bulk form or thin films of several nanometers thickness. Here, a straightforward electrochemical method utilizing the angstrom-confinement of laminar reduced graphene oxide (rGO) nanochannels is introduced to obtain a centimeter-scale network of atomically thin (<4.3 Å) 2D-transition metal oxides (2D-TMO). The angstrom-confinement provides a thickness limitation, forcing sub-unit-cell growth of 2D-TMO with oxygen and metal vacancies. It is showcased that Cr2 O3 , a material without significant catalytic activity for the oxygen evolution reaction (OER) in bulk form, can be activated as a high-performing catalyst if synthesized in the 2D sub-unit-cell form. This method displays the high activity of sub-unit-cell form while retaining the stability of bulk form, promising to yield unexplored fundamental science and applications. It is shown that while retaining the advantages of bottom-up electrochemical synthesis, like simplicity, high yield, and mild conditions, the thickness of TMO can be limited to sub-unit-cell dimensions.

Design, Synthesis and In Vitro Investigation of Cabozantinib-Based PROTACs to Target c-Met Kinase.

(1) Background: This investigation aimed at developing a series of c-Met-targeting cabozantinib-based PROTACs. (2) Methods: Purification of intermediate and target compounds was performed using column chromatography, in vitro antiproliferation activity was measured using a standard MTT assay and a c-Met degradation assay was performed via the immunoblotting technique. (3) Results: Several compounds exhibited antiproliferative activity towards different cell lines of breast cancer (T47D, MDA-MB-231, SKBR3, HCC1954 and MCF7) at the same level as parent cabozantinib and 7-demethyl cabozantinib. Two target conjugates, bearing a VHL-ligand as an E3-ligase binding moiety and glycol-based linkers, exhibited the effective inhibition of c-Met phosphorylation and an ability to decrease the level of c-Met in HCC1954 cells at micromolar concentrations. (4) Conclusions: Two compounds exhibit c-Met inhibition activity in the nanomolar range and can be considered as PROTAC molecules due to their ability to decrease the total level of c-Met in HCC1954 cells. The structures of the offered compounds can be used as starting points for further evaluation of cabozantinib-based PROTACs.

Heterocyclic ring expansion yields anthraquinone derivatives potent against multidrug resistant tumor cells.

Chemical modifications of anthraquiones are aimed at novel derivatives with improved antitumor properties. Emergence of multidrug resistance (MDR) due to overexpression of transmembrane ATP binding cassette transporters, in particular, MDR1/P-glycoprotein (Pgp), can limit the use of anthraquinone based drugs. Previously we have demonstrated that annelation of modified five-membered heterocyclic rings with the anthraquinone core yielded a series of compounds with optimized antitumor properties. In the present study we synthesized a series of anthraquinone derivatives with six-membered heterocycles. Selected new compounds showed the ability to kill parental and MDR tumor cell lines at low micromolar concentrations. Molecular docking into the human Pgp model revealed a stronger interaction of 2-methylnaphtho[2,3-g]quinoline-3-carboxamide 17 compared to naphtho[2,3-f]indole-3-carboxamide 3. The time course of intracellular accumulation of compound 17 in parental K562 leukemia cells and in Pgp-positive K562/4 subline was similar. In contrast, compound 3 was readily effluxed from K562/4 cells and was significantly less potent for this subline than for K562 cells. Together with reported strategies of drug optimization of the anthracycline core, these results add ring expansion to the list of perspective modifications of heteroarene-fused anthraquinones.

Soft Hydrogel Actuator for Fast Machine-Learning-Assisted Bacteria Detection.

We demonstrate that our bio-electrochemical platform facilitates the reduction of detection time from the 3-day period of the existing tests to 15 min. Machine learning and robotized bioanalytical platforms require the principles such as hydrogel-based actuators for fast and easy analysis of bioactive analytes. Bacteria are fragile and environmentally sensitive microorganisms that require a special environment to support their lifecycles during analytical tests. Here, we develop a bio-electrochemical platform based on the soft hydrogel/eutectic gallium-indium alloy interface for the detection of Streptococcus thermophilus and Bacillus coagulans bacteria in various mediums. The soft hydrogel-based device is capable to support bacteria' viability during detection time. Current-voltage data are used for multilayer perceptron algorithm training. The multilayer perceptron model is capable of detecting bacterial concentrations in the 104 to 108 cfu/mL range of the culture medium or in the dairy products with high accuracy (94%). Such a fast and easy biodetection is extremely important for food and agriculture industries and biomedical and environmental science.

Periodic Self-Assembly of Poly(ethyleneimine)-poly(4-styrenesulfonate) Complex Coacervate Membranes.

Coacervation is a self-assembly strategy based on the complexation of polyelectrolytes, which is utilized in biomedicine and agriculture, as well as automotive and textile industries. In this paper, we developed a new approach to the on-demand periodic formation of polyelectrolyte complexes through a Liesegang-type hierarchical organization. Adjustment of reaction conditions allows us to assemble materials with a tunable spatiotemporal geometry and establish materials' production cycles with a regulated periodicity. The proposed methodology allows the membrane to self-assemble when striving to reach balance and self-heal after exposure to external stimuli, such as potential difference and high pH. Using chronopotentiometry, K+ ion permeability behavior of the PEI-PSS coacervate membranes was demonstrated. The periodically self-assembled polyelectrolyte nanomembranes could further be integrated into novel energy storage devices and intelligent biocompatible membranes for bionics, soft nanorobotics, biosensing, and biocomputing.

Graphene-Based Technologies for Tackling COVID-19 and Future Pandemics.

The COVID-19 pandemic highlighted the need for rapid tools and technologies to combat highly infectious viruses. The excellent electrical, mechanical and other functional properties of graphene and graphene-like 2D materials (2DM) can be utilized to develop novel and innovative devices to tackle COVID-19 and future pandemics. Here, the authors outline how graphene and other 2DM-based technologies can be used for the detection, protection, and continuous monitoring of infectious diseases including COVID-19. The authors highlight the potential of 2DM-based biosensors in rapid testing and tracing of viruses to enable isolation of infected patients, and stop the spread of viruses. The possibilities of graphene-based wearable devices are discussed for continuous monitoring of COVID-19 symptoms. The authors also provide an overview of the personal protective equipment, and potential filtration mechanisms to separate, destroy or degrade highly infectious viruses, and the potential of graphene and other 2DM to increase their efficiency, and enhance functional and mechanical properties. Graphene and other 2DM could not only play a vital role for tackling the ongoing COVID-19 pandemic but also provide technology platforms and tools for the protection, detection and monitoring of future viral diseases.

Electrically Controlled Thermal Radiation from Reduced Graphene Oxide Membranes.

We demonstrate a fabrication procedure of hybrid devices that consist of reduced graphene oxide films supported by porous polymer membranes that host ionic solutions. We find that we can control the thermal radiation from the surface of reduced graphene oxide through a process of electrically driven reversible ionic intercalation. Through a comparative analysis of the structural, chemical, and optical properties of our reduced graphene oxide films, we identify that the dominant mechanism leading to the intercalation-induced reduction of light emission is Pauli blocking of the interband recombination of charge carriers. We inspect the capabilities of our devices to act as a platform for the electrical control of mid-infrared photonics by observing a bias-induced reduction of apparent temperature of hot surfaces visualized through an infrared thermal camera.

Thiophene-2-carboxamide derivatives of anthraquinone: A new potent antitumor chemotype.

The anthraquinone scaffold has long been known as a source of efficacious antitumor drugs. In particular, the various chemical modifications of the side chains in this scaffold have yielded the compounds potent for the wild type tumor cells, their counterparts with molecular determinants of altered drug response, as well as in vivo settings. Further exploring the chemotype of anticancer heteroarene-fused anthraquinones, we herein demonstrate that derivative of anthra[2,3-b]thiophene-2-carboxamide, (compound 8) is highly potent against a panel of human tumor cell lines and their drug resistant variants. Treatment with submicromolar or low micromolar concentrations of 8 for only 30 min was sufficient to trigger lethal damage of K562 chronic myelogenous leukemia cells. Compound 8 (2.5 µM, 3-6 h) induced an apoptotic cell death as determined by concomitant activation of caspases 3 and 9, cleavage of poly(ADP-ribose) polymerase, increase of Annexin V/propidium iodide double stained cells, DNA fragmentation (subG1 fraction) and a decrease of mitochondrial membrane potential. Neither a significant interaction with double stranded DNA nor strong inhibition of the DNA dependent enzyme topoisomerase 1 by 8 were detectable in cell free systems. Laser scanning confocal microscopy revealed that some amount of 8 was detectable in mitochondria as early as 5 min after the addition to the cells; exposure for 1 h caused significant morphological changes and clustering of mitochondria. The bioisosteric analog 2 in which the thiophene ring was replaced with furan was less active although the patterns of cytotoxicity of both derivatives were similar. These results point at the specific role of the sulfur atom in the antitumor properties of carboxamide derivatives of heteroarene-fused anthraquinone.

All-Dielectric Nanostructures with a Thermoresponsible Dynamic Polymer Shell.

We suggest a new strategy for creating stimuli-responsive bio-integrated optical nanostructures based on Mie-resonant silicon nanoparticles covered by an ensemble of similarity negatively charged polyelectrolytes (heparin and sodium polystyrene sulfonate). The dynamic tuning of the nanostructures' optical response is due to light-induced heating of the nanoparticles and swelling of the polyelectrolyte shell. The resulting hydrophilic/hydrophobic transitions significantly change the shell thickness and reversible shift of the scattering spectra for individual nanoparticles up to 60 nm. Our findings bring novel opportunities for the application of smart nanomaterials in nanomedicine and bio-integrated nanophotonics.

Silver melamine thin film as a flexible platform for SERS analysis.

New SERS detection platforms are required for the quick and easy preparation of sensing devices for food, agriculture, and environmental science. For quantitative sensing, it is important that a sensing material, in addition to efficient sensing, provides extraction and concentration of the target molecules such as toxic pesticides or healthy vitamins. We design such films adopting the Liesegang rings formation process that includes the reaction-diffusion of silver nitrate and melamine followed by the precipitation of different intermediates and their reduction by light in a pectin medium. Surprisingly, we find that the presence of melamine provides an excellent substrate for the extraction of pollutants at the solid-liquid interface giving rise to a powerful but easy and fast method for the quantification of fruits' quality. The complex silver and melamine containing films show high sensitivity even at relatively low silver concentrations.

Programmable Soft-Matter Electronics.

The hydrogels of the polyelectrolytes polyethylenimine and poly(acrylic acid) are used to form a thin-layer interface on the gallium-indium eutectic alloy's surface. The proposed method of gradually increasing the applied voltage reveals the possibility of formation of electronic components: diode, capacitor, resistor, and memristor. The components can be changed to each other many times. A multilayer perceptron model with one hidden layer and 12 nodes allows identifying hydrogels' composition and automatically setting the desired architecture of electronic components. The design of electronic components makes it possible to easy-to-produce new electronic parts and programmable soft-matter electronics.

Two-dimensional adaptive membranes with programmable water and ionic channels.

Membranes are ubiquitous in nature with primary functions that include adaptive filtering and selective transport of chemical/molecular species. Being critical to cellular functions, they are also fundamental in many areas of science and technology. Of particular importance are the adaptive and programmable membranes that can change their permeability or selectivity depending on the environment. Here, we explore implementation of such biological functions in artificial membranes and demonstrate two-dimensional self-assembled heterostructures of graphene oxide and polyamine macromolecules, forming a network of ionic channels that exhibit regulated permeability of water and monovalent ions. This permeability can be tuned by a change of pH or the presence of certain ions. Unlike traditional membranes, the regulation mechanism reported here relies on specific interactions between the membranes' internal components and ions. This allows fabrication of membranes with programmable, predetermined permeability and selectivity, governed by the choice of components, their conformation and their charging state.

Sustainable Personal Protective Clothing for Healthcare Applications: A Review.

Personal protective equipment (PPE) is critical to protect healthcare workers (HCWs) from highly infectious diseases such as COVID-19. However, hospitals have been at risk of running out of the safe and effective PPE including personal protective clothing needed to treat patients with COVID-19, due to unprecedented global demand. In addition, there are only limited manufacturing facilities of such clothing available worldwide, due to a lack of available knowledge about relevant technologies, ineffective supply chains, and stringent regulatory requirements. Therefore, there remains a clear unmet need for coordinating the actions and efforts from scientists, engineers, manufacturers, suppliers, and regulatory bodies to develop and produce safe and effective protective clothing using the technologies that are locally available around the world. In this review, we discuss currently used PPE, their quality, and the associated regulatory standards. We survey the current state-of-the-art antimicrobial functional finishes on fabrics to protect the wearer against viruses and bacteria and provide an overview of protective medical fabric manufacturing techniques, their supply chains, and the environmental impacts of current single-use synthetic fiber-based protective clothing. Finally, we discuss future research directions, which include increasing efficiency, safety, and availability of personal protective clothing worldwide without conferring environmental problems.

Amides of pyrrole- and thiophene-fused anthraquinone derivatives: A role of the heterocyclic core in antitumor properties.

Heteroarene-fused anthraquinone derivatives represent a class of perspective anticancer drug candidates capable of targeting multiple vital processes including drug resistance. Taking advantage of previously demonstrated potential of amide derivatives of heteroarene-fused anthraquinones, we herein dissected the role of the heterocyclic core in antitumor properties. A new series of naphtho[2,3-f]indole-3- and anthra[2,3-b]thiophene-3-carboxamides was synthesized via coupling the respective acids with cyclic diamines. New compounds demonstrated a submicromolar antiproliferative potency close to doxorubicin (Dox) against five tumor cell lines of various tissue origin. In contrast to Dox, the new compounds were similarly cytotoxic for HCT116 colon carcinoma cells (wild type p53) and their isogenic p53 knockout counterparts. Modification of the heterocyclic core changed the targeting properties: the best-in-series naphtho[2,3-f]indole-3-carboxamide 8 formed more affine complexes with DNA duplex than furan and thiophene analogs, a property that can be translated into a stronger inhibition of topoisomerase 1 mediated DNA unwinding. At tolerable doses the water soluble derivative 8 significantly inhibited tumor growth (up to 79%) and increased the lifespan (153%) of mice bearing P388 lymphoma transplants. Together with better solubility for parenteral administration and well tolerance by animals of the indole derivative 8 indicates prospects for further search of new antitumor drug candidates among the heteroarene-fused anthraquinones.