Controlled Molecular Orientation through Intercalation in PVDF Thin Films: Exhibiting Ultralong Retention and Improved Leakage Current.

Ferroelectric switching and retention performance of poly(vinylidene fluoride) (PVDF) thin films improve by the incorporation of unmodified smectite montmorillonite (MMT) clay nanodielectric. In the present study, an intercalated PVDF (clay/PVDF) thin film with edge-on ß-crystallite is fabricated via a heat-controlled spin coating (HCSC) technique. This provides an efficient and simple way to fabricate the edge-on oriented crystallite lamellae with an electroactive ß-phase, facilitating nanoscale ferroelectric switching at a lower voltage compared to the face-on orientation. Here, we demonstrate the polarization retention for periods longer than 20 days (∼480 h, i.e., 1.8 × 106 s), with no degradation in switched nanoscale domains. In addition, by maintaining the relatively high dielectric constant, the incorporation of nanoclay effectively lowers the leakage current by 102 factors. The obtained memory window in the edge-on orientation is 7 V, approximately twice the memory window obtained in the face-on orientation. In short, our findings provide a simple and promising route to fabricate edge-on oriented PVDF thin films, with ultralong retention, high dielectric constant, and improved leakage current.

A Spin-Charge-Regulated Self-Powered Nanogenerator for Simultaneous Pyro-Magneto-Electric Energy Harvesting.

In view of the depletion of natural energy resources, harvesting energy from waste is a revolution to simultaneously capture, unite, and recycle various types of waste energies in flexible devices. Thus, in this work, a spin-charge-regulated pyro-magneto-electric nanogenerator is devised at a well-known ferroelectric P(VDF-TrFE) copolymer. It promptly stores thermal-magnetic energies in a "capacitor" that generates electricity at room temperature. The ferroelectric domains are regulated to slip at the interfaces (also twins) of duly promoting polarization and other properties. An excellent pyroelectric coefficient p ∼ 615 nC·m-2·K-1 is obtained, with duly enhanced stimuli of a thermal sensitivity ∼1.05 V·K-1, a magnetoelectric coefficient αme ∼8.8 mV·cm-1·Oe-1 at 180 Hz (resonance frequency), and a magnetosensitivity ∼473 V/T. It is noteworthy that a strategy of further improving p (up to 41.2 µC·m-2·K-1) and αme (up to 23.6 mV·cm-1·Oe-1) is realized in the electrically poled dipoles. In a model hybrid structure, the spins lead to switch up the electric dipoles parallel at the polymer chains in a cohesive charged layer. It is an innovative approach for efficiently scavenging waste energies from electric vehicles, homes, and industries, where abundant thermal and magnetic energies are accessible. This sustainable strategy could be useful in next-generation self-powered electronics.

Futuristic Alzheimer's therapy: acoustic-stimulated piezoelectric nanospheres for amyloid reduction.

The degeneration of neurons due to the accumulation of misfolded amyloid aggregates in the central nervous system (CNS) is a fundamental neuropathology of Alzheimer's disease (AD). It is believed that dislodging/clearing these amyloid aggregates from the neuronal tissues could lead to a potential cure for AD. In the present work, we explored biocompatible polydopamine-coated piezoelectric polyvinylidene fluoride (DPVDF) nanospheres as acoustic stimulus-triggered anti-fibrillating and anti-amyloid agents. The nanospheres were tested against two model amyloidogenic peptides, including the reductionist model-based amyloidogenic dipeptide, diphenylalanine, and the amyloid polypeptide, amyloid beta (Aß42). Our results revealed that DPVDF nanospheres could effectively disassemble the model peptide-derived amyloid fibrils under suitable acoustic stimulation. In vitro studies also showed that the stimulus activated DPVDF nanospheres could efficiently alleviate the neurotoxicity of FF fibrils as exemplified in neuroblastoma, SHSY5Y, cells. Studies carried out in animal models further validated that the nanospheres could dislodge amyloid aggregates in vivo and also help the animals regain their cognitive behavior. Thus, these acoustic stimuli-activated nanospheres could serve as a novel class of disease-modifying nanomaterials for non-invasive electro-chemotherapy of Alzheimer's disease.

Reactive oxygen species for therapeutic application: Role of piezoelectric materials.

This perspective article emphasizes the significant role of reactive oxygen species (ROS) in in vivo remedial therapy of various diseases and complications, capitalizing on their potential reactivity. Among the various influencers, herein, piezoelectric materials driven ROS generation activity is primarily considered. Intrinsic non-centrosymmetry of piezoelectric materials makes them suitable for distinct dipole formation in the presence of external mechanical stimuli. Such characteristics prompt the positioning of opposite charged carriers to execute associated redox transformations that effectively participate to generate ROS in the aqueous media of the cell cytoplasm, organelles and nucleus. The immense reactivity of piezoelectric material driven ROS is fostered to terminate cellular toxicity or curtail tumor cell growth, due to their higher specificity. This perspective considers the conjugated performance of piezoelectric materials and ultrasound which can remotely generate electrical charges that promote ROS production for therapeutic application. In particular, a substantial synopsis is provided for the remedial activity of numerous piezocatalytic materials in tumor cell apoptosis, antibacterial treatment, dental care and neurological disorders. Subsequently, the report precisely demonstrates the methods involving various spectrophotometric approaches for the analysis of the ROS. Finally, the key challenges of piezoelectric material-based therapy are discussed and systematic future progress is outlined.

Hydrogen Bonding-Assisted Complete Ferroelectric ß-Phase Conversion in Poly(vinylidene fluoride) Thin Films: Exhibiting an Excellent Memory Window and Long Retention.

Organic nonvolatile memory with low power consumption is a critical research demand for next-generation memory applications. Ferroelectric switching characteristics of poly(vinylidene fluoride) (PVDF) thin films modified with a trace amount of hydrated Cu salt (CuCl2·2H2O) are explored in the present study. Herein, a Cu salt-mediated PVDF (Cu/PVDF) thin film with preferential edge-on ß-crystallites is fabricated through the orientation-controlled spin coating (OCSC) technique. This work proposes a convenient and effective approach to produce edge-on-oriented electroactive PVDF thin films with a high degree of polar ß-phase, so as to realize the favorable switching under low operating voltages. Herein, chemically modified PVDF is anticipated to form a complex intermediate, which attains its stability by undergoing favorable hydrogen bonding that reorients the C-C structure of PVDF to obtain the ß-conformation. Such information is verified by X-ray photoelectron spectroscopy (XPS). Grazing incidence Fourier transform infrared (GI-FTIR) spectroscopy revealed that the Cu salt incorporated into the PVDF matrix favored the formation of the electroactive ß-phase with edge-on crystallite lamellae. Consequently, the Cu/PVDF thin film demonstrates a good contrast between electric field-assisted written and erased data bits in the piezoresponse force microscopy (PFM) phase image. Furthermore, to obtain the ferroelectric memory window, a metal-ferroelectric-insulator-semiconductor (MFIS) diode with Cu/PVDF as a ferroelectric layer has been fabricated. The capacitance-voltage (C-V) characteristic of the MFIS diode exhibits a memory window of 12 V with a long-term retention behavior (∼longer than 7 days). In a nutshell, we tried to represent a clear understanding of the interfacial interactions of the Cu salt with PVDF, which favor the edge-on formation that results in the promising low-voltage ferroelectric switching and excellent retention response, where any additional electrical poling and/or external stretching is completely possible to be ruled out, thus offering a new prospect for the evolution of devices with long-lasting nonvolatile memories.

Bio-piezoelectric phenylalanine-αß-dehydrophenylalanine nanotubes as potential modalities for combinatorial electrochemotherapy in glioma cells.

Bio-piezoelectric materials are endowed with characteristic features such as non-invasiveness, small energy attenuation and deep tissue penetrability. Thus, they have the ability to serve as both diagnostic and therapeutic modalities for targeting and treating various dreaded disorders scourging mankind. Herein, piezoelectric nanotubes derived from a modified amino acid-containing dipeptide, phenylalanine-αß-dehydrophenylalanine (Phe-ΔPhe; FΔF), possessing acoustic stimulation-triggered reactive oxygen species (ROS) generating ability, were employed and projected for achieving a piezo-active response enabled anti-cancer effect in glioma cells. A model anti-cancer drug doxorubicin (Dox) was also loaded into the nanotubes and the combined system depicted enhanced ROS production and cell killing under an acoustically developed piezo-catalytic environment. Cellular level assessment studies demonstrated that the dipeptide based piezoelectric nanotubes could lead to an increase in the cellular Ca2+ ion concentration, further inducing ROS-triggered cytotoxicity accompanied by high therapeutic efficacy in C6 glioma cells. Overall, our structures have the uniqueness of serving as acoustic stimulus-driven, wireless, and non-invasive electro-chemotherapeutic agents for enabling heightened cancer cell killing and may complement other chemotherapeutic modalities for treating the disease.

Lead-Free Perovskite Cs3Bi2I9-Derived Electroactive PVDF Composite-Based Piezoelectric Nanogenerators for Physiological Signal Monitoring and Piezo-Phototronic-Aided Strain Modulated Photodetectors.

In recent years, lead-free perovskite materials are exponentially emerging in photovoltaic and optoelectronic applications due to their low toxicity and superior optical properties. On the other hand, the demand for flexible, wearable, and lightweight optoelectronic devices is significantly growing in sensor and actuator technologies. In this scenario, lead-free perovskite-based flexible piezoelectric polymer composites have sparked considerable attention in this field due to their excellent piezo-, pyro-, ferroelectric, and photovoltaic properties. Thus, in this work, a long-term stable lead-free Cs3Bi2I9-PVDF composite is introduced. The in situ growth of the Cs3Bi2I9 perovskite induces 92% yield of the electroactive phase in the PVDF matrix. The possible mechanism behind the electroactive ß-phase transformation is presented via interfacial interactions of PVDF moieties with the Cs3Bi2I9 (CBI) perovskite, which also give rise to long-term environmental stability. Next, a piezoelectric nanogenerator (PNG) has been fabricated with the Cs3Bi2I9-PVDF composite for mechanical energy harvesting, biophysiological motion monitoring, and voice recognitions that have potential utility in the health-care sector. Furthermore, a photodetector is developed to realize the piezo-phototronic effect. It exhibits a fast photoswitching behavior with rise and decay times of 141 and 278 ms, respectively. Thus, it is confirmed that the flexible Cs3Bi2I9-PVDF composite has shown tremendous potential to be used as an optical signal-modulated piezo-responsive wearable sensor.

A comparative study on chemical characterization and properties of surface active compounds from Gram-positive Bacillus and Gram-negative Ochrobactrum strains utilizing pure hydrocarbons and waste mineral lubricating oils.

Mineral lubricating oils are widely used in various industrial sectors for their applications in maintenance and functioning of machineries. However, indiscriminate dumping of these used oils have resulted in polluting the natural reservoirs which subsequently destroys ecological balance. Bacteria can emulsify or lower surface tension between phases of immiscible substrates and can acquire them as their carbon and energy sources. Such a phenomenon is mediated by production of extracellular polymers which can function as eminent surface active compounds based on their surfactant or emulsifying nature. The comparison between bacterial strains (Gram-positive Bacillus stratosphericus A15 and Gram-negative Ochrobactrum pseudintermedium C1) on utilization of pure straight chain hydrocarbons, waste mineral lubricating oils as sole carbon source and chemical characterization of the synthesized surface active compounds were studied. Characterization analysis by Ultraviolet Visible spectrophotometry, Fourier transform infrared spectroscopy, Nuclear Magnetic Resonance spectroscopy, Carbon-Hydrogen-Nitrogen analysis has given detailed structural elucidation of surface active compounds. The contrasting nature of bacterial strains in utilization of different hydrocarbons of waste mineral lubricating oils was observed in Gas Chromatography-Mass Spectroscopy analysis. The variation between both strains in utilization of hydrocarbons can be manifested in chemical structural differences and properties of the produced surface active compounds. Scanning Electron Microscopy has given detailed insight into the microstructural difference of the compounds. The utilization of lubricating oils can address waste disposal problem and offer an economical feasible approach for bacterial production of surface active compounds. Our results suggest that these surface active compounds can maneuver applications in environmental bioremediation and agriculture, pharmaceuticals and food as functional biomaterials.

Prospective bioremediation of toxic heavy metals in water by surfactant exopolysaccharide of Ochrobactrum pseudintermedium using cost-effective substrate.

Globally, the underlying peril of cumulative toxicity of heavy metals in water bodies contaminated by industrial effluents is a matter of great concern to the environmentalists. Heavy metals like lead, cadmium, and nickel are particularly liable for this. Such toxic water is not only hazardous to human health but also harmful to aquatic animals. Remedial measures are being taken by physico-chemical techniques, but most of them are neither eco-friendly nor cost-effective. Biological means like bioaccumulation of heavy metals by viable bacteria are often tedious. In the present study, biosorption of heavy metals is successfully expedited by surfactant exopolysaccharide (SEPS) of Ochrobactrum pseudintermedium C1 as a simple, safe, and economically sustainable option utilizing an easily available and cost-effective substrate like molasses extract. Its efficacy in bioremediation of toxic heavy metals like cadmium, nickel, and lead have been studied by UV-Vis spectrophotometry and verified by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). FTIR and zeta potential studies have also been carried out to explore this novel biosorption potential. Results are conclusive and promising. Moreover, this particular SEPS alone can remediate all these three toxic heavy metals in water. For futuristic applications, it might be a prospective and cost-effective resource for bioremediation of toxic heavy metals in aqueous environment.

Mesoporous carbon nanospheres derived from agro-waste as novel antimicrobial agents against gram-negative bacteria.

Porous carbon nanospheres were synthesized from agro-waste garlic peels by a one-pot facile and easy to scale-up pyrolysis method. Surface morphology and structural features of the nanospheres have been studied by field emission scanning electron microscopy, energy-dispersive spectroscopy, X-ray diffraction, and Raman spectroscopy. Fourier transform infrared spectroscopy (FTIR) and N2 adsorption desorption experiments were explored to detect surface functionality, surface area, and porosity. Average particle diameter of the synthesized nanospheres was 31 ± 6.3 nm and zeta potential of - 25.2 mV ± 1.75 mV. Nanoscale carbon was mesoporous in nature with type IV isotherms, mean pore diameter of 15.2 nm, and total pore volume of 0.032 cm3/g. Minimum inhibitory concentration and minimum bactericidal concentration values of carbon nanospheres against Escherichia coli are 480 ± 0.5 µg/ml and 495 ± 0.5 µg/ml, respectively. Synthesized nanospheres exhibited gram-selective antimicrobial action against Escherichia coli probably linked to membrane deformity due to interaction of nanocarbon with the bacterial membrane. Carbon nanospheres resulting from waste to wealth transformation emerged as promising candidates for antibacterial application. Graphical abstract.

Surfactant exopolysaccharide of Ochrobactrum pseudintermedium C1 has antibacterial potential: Its bio-medical applications in vitro.

Since the advent of biologics in human welfare various bio-molecules have been explored. Different bacterial exopolysaccharides have proved their worth in many industrial and commercial applications. In this perspective, while exploring a surfactant exopolysaccharide of Ochrobactrum pseudintermedium C1, it is strikingly observed that it possesses a potent antibacterial property which encourages its bio-medical applications. Following isolation and purification of the said exopolysaccharide, its structural configuration and functional attributes are studied by several analytical procedures involving FTIR, 13C- NMR, CHN-analysis, estimation of zeta potential, XRD-study and digital tensiometry. When treated with pathological samples in vitro, it distinctly elicits its antibacterial property by exhibiting a characteristic zone of inhibition. Combined with a standard antibiotic (like ciprofloxacin), it enhances the action of antibiotic also. Mechanism of its antibacterial action is evaluated by crystal violet entrapment assay with UV-vis spectrophotometry, bacterial cell viability assay by trypan blue staining and SEM study. Results show that its basic surfactant property, anionic character, crystalline nature and scaffolding architecture are supposed to facilitate its antibacterial property which is manifested by its capability of disrupting bacterial cell envelope causing eventual cell death. In the current global scenario, an increasing threat of antibiotic resistance is prevailing due to their indiscriminate use. If used as an adjuvant with a judicious dose of antibiotic, this bio-molecule might play a significant role in bio-medicine to combat such threat.

Ni foam electrode solution impregnated with Ni-Fe X (OH) Y catalysts for efficient oxygen evolution reaction in alkaline electrolyzers.

Oxygen evolution reaction (OER) is a demanding step within the water splitting process for its requirement of a high overpotential. Thus, to overcome this unfavourable kinetics, an efficient catalyst is required to expedite the process. In this context, we report on Ni foam functionalised with low cost iron (Fe) and iron hydroxide (Fe(OH) X ), wet chemically synthesized as OER catalysts. The prepared catalyst based on iron hydroxide precipitate shows a promising performance, exhibiting an overpotential of 270 mV (at a current density of 10 mA cm-2 in 1 M KOH solution), an efficient Tafel slope of ∼50 mV dec-1 and stable chronopotentiometry. The promising performance of the anode was further reproduced in the overall water splitting reaction with a two electrode cell. The overall reaction requires a lower potential of 1.508 V to afford 10 mA cm-2, corresponding to 81.5% electrical to fuel efficiency.

Exploring two contrasting surface-active exopolysaccharides from a single strain of Ochrobactrum utilizing different hydrocarbon substrates.

During production and characterization of exopolysaccharides (EPS) of Ochrobactrum pseudintermedium C1, it was observed that an experimental change in the basic hydrocarbon type of substrate for bacterial utilization led to elicitation of different surface-active properties in the EPS produced. In the sugar substrate, it elicited surfactant property, while in oil substrates it elicited emulsifying property, which indicated that the EPS might be different. Consequently, attention was focused on a detailed analysis of this substrate-specific EPS. Utilizing waste sugar, edible, and mineral oil substrates, EPS produced in each situation was characterized. Besides estimating surface activity and thermostability, each substrate-specific EPS was analyzed by Fourier-transform infrared spectroscopy, gas chromatography-mass spectroscopy, 1 H-nuclear magnetic resonance, and matrix-assisted laser desorption/ionization-time of flight mass spectroscopy to find any structural difference. The results were significantly contrasting although the similarity in molecular mass suggested a basic similarity in polysaccharide structure. Morphological differences were also evident both macroscopically and microscopically with scanning electron microscopy. As the surface-active property of EPS was dependent on the substrate utilized, their structural differences might account for it. These diverse surface activities of EPS produced by a single bacterial strain simply by changing the nature of substrate would also augment their bioapplications. Moreover, utilization of waste and easily available substrates should make such applications convenient, ecofriendly, and cost-worthy.

Towards a better production of bacterial exopolysaccharides by controlling genetic as well as physico-chemical parameters.

Bacterial extracellular polymeric substances, which are basically bacterial metabolites, have currently become a subject of great concern of modern day microbiologists and biotechnologists. Among these metabolites, bacterial exopolysaccharides or EPS, in particular, have gained a significant importance. EPS are formed by the bacteria in their late exponential or stationary phase of growth under special situations for specific purposes. They take part in the formation of bacterial biofilms. There is a great diversity in the types of EPS. Strikingly enough, a same species of bacterium can produce different types of EPS under different situations. The importance of EPS is largely because of their different applications in various industries. Now that the bacterial EPS has got the potentiality to become an upcoming tool in various futuristic applications of human benefit, the focus currently develops towards how better they can be produced in the laboratory by promoting the favorable factors for their production. While studying with different EPS forming bacteria, both the intrinsic factors like genetic configuration of the bacteria and the extrinsic factors like culture conditions under the influence of different physico-chemical parameters in order to maximize the EPS production have been taken into consideration. Both the factors have proved their worth. Hence, towards a better outcome for EPS production, it is indicated that a genetic manipulation of the bacteria should be synchronized with a proper selection of its culture condition by controlling different physico-chemical parameters.

Assessment of synergistic antibacterial activity of combined biosurfactants revealed by bacterial cell envelop damage.

Besides potential surface activity and some beneficial physical properties, biosurfactants express antibacterial activity. Bacterial cell membrane disrupting ability of rhamnolipid produced by Pseudomonas aeruginosa C2 and a lipopeptide type biosurfactant, BS15 produced by Bacillus stratosphericus A15 was examined against Staphylococcus aureus ATCC 25923 and Escherichia coli K8813. Broth dilution technique was followed to examine minimum inhibitory concentration (MIC) of both the biosurfactants. The combined effect of rhamnolipid and BS15 against S. aureus and E. coli showed synergistic activity by expressing fractional inhibitory concentration (FIC) index of 0.43 and 0.5. Survival curve of both the bacteria showed bactericidal activity after treating with biosurfactants at their MIC obtained from FIC index study as it killed >90% of initial population. The lesser value of MIC than minimum bactericidal concentration (MBC) of the biosurfactants also supported their bactericidal activity against both the bacteria. Membrane permeability against both the bacteria was supported by amplifying protein release, increasing of cell surface hydrophobicity, withholding capacity of crystal violet dye and leakage of intracellular materials. Finally cell membrane disruption was confirmed by scanning electron microscopy (SEM). All these experiments expressed synergism and effective bactericidal activity of the combination of rhamnolipid and BS15 by enhancing the bacterial cell membrane permeability. Such effect of the combination of rhamnolipid and BS15 could make them promising alternatives to traditional antibiotic in near future.

Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.

APD334 was discovered as part of our internal effort to identify potent, centrally available, functional antagonists of the S1P1 receptor for use as next generation therapeutics for treating multiple sclerosis (MS) and other autoimmune diseases. APD334 is a potent functional antagonist of S1P1 and has a favorable PK/PD profile, producing robust lymphocyte lowering at relatively low plasma concentrations in several preclinical species. This new agent was efficacious in a mouse experimental autoimmune encephalomyelitis (EAE) model of MS and a rat collagen induced arthritis (CIA) model and was found to have appreciable central exposure.

(7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists.

S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.

Complementary asymmetric routes to (R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate.

Two distinct and scalable enantioselective approaches to the tricyclic indole (R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate, an important synthon for a preclinical S1P(1) receptor agonist, are reported. Route 1 employs a modified version of Smith's modular 2-substituted indole synthesis as the key transformation. Route 2 involves a highly enantioselective CuH-catalyzed 1,4-hydrosilylation as the stereodefining step. Both routes can be performed without chromatography to provide multigram quantities of the tricycle in ≥98% ee.

Fused tricyclic indoles as S1P1 agonists with robust efficacy in animal models of autoimmune disease.

Two series of fused tricyclic indoles were identified as potent and selective S1P(1) agonists. In vivo these agonists produced a significant reduction in circulating lymphocytes which translated into robust efficacy in several rodent models of autoimmune disease. Importantly, these agonists were devoid of any activity at the S1P(3) receptor in vitro, and correspondingly did not produce S1P(3) mediated bradycardia in telemeterized rat.

Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation.

A series of pyrimidine analogues derived from ATC0175 were potent antagonists of human MCH-R1 in vitro. Significantly improved receptor selectivity was achieved with several analogues from this series, but no improvement in brain partitioning was noted. One example from this series was shown to inhibit food intake and decrease body weight in a chronic study. However no clear correlation between the pharmacodynamic effect and the pharmacokinetic data with respect to brain concentration was discernible leading us to conclude that the observed effect was most likely not due to interaction with the MCH-R1.