We report the rational design of metal-organic layers (MOLs) that are built from [Hf6 O4 (OH)4 (HCO2 )6 ] secondary building units (SBUs) and Ir[bpy(ppy)2 ]+ - or [Ru(bpy)3 ]2+ -derived tricarboxylate ligands (Hf-BPY-Ir or Hf-BPY-Ru; bpy=2,2'-bipyridine, ppy=2-phenylpyridine) and their applications in X-ray-induced photodynamic therapy (X-PDT) of colon cancer. Heavy Hf atoms in the SBUs efficiently absorb X-rays and transfer energy to Ir[bpy(ppy)2 ]+ or [Ru(bpy)3 ]2+ moieties to induce PDT by generating reactive oxygen species (ROS). The ability of X-rays to penetrate deeply into tissue and efficient ROS diffusion through ultrathin 2D MOLs (ca. 1.2 nm) enable highly effective X-PDT to afford superb anticancer efficacy.

Polypyrrole/carbon nanotube (PPy/CNT) composite nanowires were prepared by a template-directed electrochemical synthetic route, involving plating of PPy into the pores of a host membrane in the presence of shortened and carboxylated CNT dopants (without added electrolyte). Cyclic voltammetric growth profiles indicate that the CNT is incorporated within the growing nanowire and serves as the sole charge-balancing "counterion". Transmission electron microscopy images indicate high-quality straight PPy/CNT nanowires with a smooth and featureless surface and a uniform diameter. The presence of the CNT dopant imparts high conductivity (Ohmic I-V behavior) onto these PPy/CNT nanowires. By combining the attractive properties of CNTs, conducting polymers, and nanowires, the new nanocomposite opens up new opportunities, ranging from chemical sensors to molecular electronic devices.

Electrically conductive biodegradable polymer membranes were prepared by mixing conductive polypyrrole particles with poly(L-lactic acid) solution followed by solution casting and solvent evaporation. Multi-well electrical cell culture plates were fabricated to host electrically stimulated cell culture and monitor parameters. Human cutaneous fibroblasts were cultured on conductive membranes with or without electrical stimulation (ES). Cell count, MTT, Hoechst staining, and SEM were performed to characterize the cells. The membranes supported the adhesion and proliferation of the fibroblasts in both the presence and absence of ES. In the presence of direct electrical field strength of 100 mV/mm, cell viability on the PPy/PLLA membranes at 2 and 24 h was 2.2- and 4.0-fold (p < 0.05) respectively of that on the same membranes without ES. Direct electrical current ranging from 2.5 to 250 microA/mm had no effect on the viability of cells cultured on the gold-coated Petri dish. Electrical field applied to conductive biodegradable polymer surfaces is therefore an effective approach to upregulate the mitochondrial activity of human skin fibroblasts.

BACKGROUND

Efficient cardiac function requires synchronous ventricular contraction. After myocardial infarction, the nonconductive nature of scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive biomaterial polymer that restores impulse propagation could synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue, allowing them to contribute to global heart function.

RESULTS

We created a conductive polymer by grafting pyrrole to the clinically tested biomaterial chitosan to create a polypyrrole (PPy)-chitosan hydrogel. Cyclic voltammetry showed that PPy-chitosan had semiconductive properties lacking in chitosan alone. PPy-chitosan did not reduce cell attachment, metabolism, or proliferation in vitro. Neonatal rat cardiomyocytes plated on PPy-chitosan showed enhanced Ca(2+) signal conduction in comparison with chitosan alone. PPy-chitosan plating also improved electric coupling between skeletal muscles placed 25 mm apart in comparison with chitosan alone, demonstrating that PPy-chitosan can electrically connect contracting cells at a distance. In rats, injection of PPy-chitosan 1 week after myocardial infarction decreased the QRS interval and increased the transverse activation velocity in comparison with saline or chitosan, suggesting improved electric conduction. Optical mapping showed increased activation in the border zone of PPy-chitosan-treated rats. Echocardiography and pressure-volume analysis showed improvement in load-dependent (ejection fraction, fractional shortening) and load-independent (preload recruitable stroke work) indices of heart function 8 weeks after injection.

CONCLUSIONS

We synthesized a biocompatible conductive biomaterial (PPy-chitosan) that enhances biological conduction in vitro and in vivo. Injection of PPy-chitosan better maintained heart function after myocardial infarction than a nonconductive polymer.

The specific capture and remotely controlled release of the EpCAM-positive cancer cells from biotin-doped polypyrrole (Ppy) films in response to an electrical potential is presented. As Ppy allows the direct incorporation of biotin molecules during the electrochemical process, densely packed biotin molecules can serve as the binding sites for streptavidin-tagged biomolecular complexes. This study demonstrates not only the enhanced capture and enrichment of EpCAM-positive cancer cells but also "on-demand" release of the viable cells from conductive Ppy in an electrical-potential-dependent way. This novel approach is of great importance in a diverse range of applications, and in particular in cancer diagnostics and screening.

Pancreatic polypeptide and neuropeptide Y share 50% amino acid homology (18 out of 36 residues), suggesting that they may have common ancestral origins. cDNA clones complementary to human mRNAs encoding pancreatic polypeptide and neuropeptide Y were used to detect specific human genomic DNA sequences in human-mouse somatic cell hybrid lines. The pancreatic polypeptide gene (PPY) segregated with human chromosome 17, while the neuropeptide Y gene (NPY) segregated with human chromosome 7. Examination of cell hybrids with chromosomal rearrangements assigned PPY to the p11.1-qter region and NPY to the pter-q22 region of their respective chromosomes.

This study evaluated the in vivo biocompatibility and biodegradation behavior of a novel polypyrrole (PPy)/poly(D,L-lactide) (PDLLA) composite and PPy-coated poly(D,L-lactide-co-glycolide) membranes. Test membranes were implanted subcutaneously in rats for 3-120 days. The biocompatibility was assessed by quantifying the alkaline and acid phosphatase secretion, the immunohistochemical staining of the ED-2-positive macrophages, and the histology at the tissue/material interface. The degradation was investigated using scanning electron microscopy. Pure PDLLA and poly(D,L-lactide-co-glycolide) membranes were used as references, whereas expanded polytetrafluoroethylene and a commercial styrene-butadiene rubber were used as controls. The enzyme activity of the PPy-containing specimens was shown to be similar to that of the references. The histological findings were consistent with the enzymatic results, showing a mild-to-moderate acute inflammation followed by a resolution of the inflammatory response with a decrease in inflammatory cells for each biodegradable membrane. The tissue reactions to the PPy, which was either in the form of nanoparticles or surface coating, were comparable to the response to the neighboring biodegradable materials. Elevated ED-2-positive macrophage populations appeared as early as day 3 in the loose connective tissue surrounding the implants. The density of these populations was related to the degree of inflammation. Scanning electron microscopy showed that the degradation of the PPy/PDLLA composite was not affected by the presence of PPy.

The nude trait in the rat is transmitted in an autosomal recessive manner and is associated with thymic aplasia, T-cell deficiency, and hairlessness. Congenic rats homozygous for the RNU (Rowett nude) locus are important models in the study of inflammatory disease, tumor growth, and transplant rejection. The RNU locus has not been previously mapped, and the nature of the gene product is unknown. To determine the map location of this gene, a single F344.rnu/rnu (athymic nude congenic Fischer rat) male congenic rat was bred with 3 LEW/N (NIH stock Lewis rat) female rats to produce F1 progeny. Twelve F1 brother-sister breeding pairs were established. Forty-nine phenotypically nude F2 offspring (198 total) were obtained. Linkage analysis done on F2 DNA revealed highly significant cosegregation between the nude phenotype and eight polymorphic markers located on Chromosome (Chr) 10. The tightest linkages were with: MYH3 (embryonic, skeletal myosin heavy chain) and SHBG (sex hormone-binding globulin), giving 2 point lod scores of 20.2, and 20.0, respectively. The map order and map distances, determined by multipoint linkage calculations, were: RR24-(16.1 cM)-MYH3-(3.5 cM)-SHBG-(4.7 cM)-RNU-(11.9 cM)-F16F2-(24.1 cM)-CLATP (citrate lyase ATPase)-(2.4 cM)-ACE (angiotensin converting enzyme)/PPY (pancreatic polypeptide)-(14.1 cM)-RR1023. The position of the RNU locus in the rat corresponds closely with that of the recently reported nu locus in the mouse. This finding suggests that the nude phenotype in the rat and the mouse arise from defects in homologous genes.

Three luminescent cyclometalated iridium(III) bis-biotin complexes [Ir(N(wedge)C)(2)(N(wedge)N)](PF(6)) (HN(wedge)C = 2-(4-(N-(6-(biotinamido)hexyl)aminomethyl)phenyl)pyridine, HppyC6B, N(wedge)N = 2,2'-bipyridine, bpy (1); HN(wedge)C = 2-phenylpyridine, Hppy, N(wedge)N = 4,4'-bis((2-(biotinamido)ethyl)aminocarbonyl)-2,2'-bipyridine, bpyC2B2 (2); HN(wedge)C = Hppy, N(wedge)N = 4,4'-bis((2-((6-(biotinamido)hexanoyl)amino)ethyl)aminocarbonyl)-2,2'-bipyridine, bpyC2C6B2 (3)) and one tris-biotin complex [Ir(ppyC6B)(2)(bpyC6B)](PF(6)) (bpyC6B = 4-((6-(biotinamido)hexyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine) (4) have been synthesized and characterized. The biotin-free complex [Ir(ppy)(2)(bpyC4)](PF(6)) (bpyC4 = 4,4'-bis(n-butylaminocarbonyl)-2,2'-bipyridine) (5) has also been prepared for comparison studies. Upon photoexcitation, all the complexes displayed intense and long-lived greenish-yellow to red triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi (Ir) ->> pi*(N(wedge)N)) emission in fluid solutions at room temperature and in low-temperature glass. Cyclic voltammetric studies revealed iridium(IV/III) oxidation at about +1.21 to + 1.29 V and diimine-based reductions at about -1.07 to -1.39 V versus SCE. The interactions of the bis-biotin and tris-biotin complexes with avidin have been studied by 4'-hydroxyazobenzene-2-carboxylic acid (HABA) assays, emission titrations, and dissociation assays. The possibility of these complexes as cross-linkers for avidin has been examined by microscopy studies using avidin-conjugated green fluororescent microspheres and size-exclusion HPLC analysis. Utilization of these luminescent iridium(III) biotin complexes in signal amplification has been demonstrated using avidin-coated nonfluorescent microspheres and complex 3 as an example. Additionally, the lipophilicity of all the complexes has been determined by reversed-phase HPLC. The cytotoxicity of these iridium(III) complexes toward the human cervix epithelioid carcinoma (HeLa) cell line has been evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assays. Furthermore, the cellular uptake of the complexes has been examined by ICP-MS, laser-scanning confocal microscopy, and flow cytometry.

A complex low-repetitive human DNA probe (BAC RP11-35B4) together with two microdissection-derived region-specific probes of the multicolor banding (MCB) probe-set for chromosome 1 were used to re-analyze the evolution of human chromosome 1 in comparison to four ape species. BAC RP11-35B4 derives from 1q21 and contains 143 kb of non-repetitive DNA; however, it produces three specific FISH signals in 1q21, 1p12 and 1p36.1 of Homo sapiens (HSA). Human chromosome 1 was studied in comparison to its homologues in Hylobates lar (HLA), Pongo pygmaeus (PPY), Gorilla gorilla (GGO) and Pan troglodytes (PTR). A duplication of sequences homologous to human 1p36.1 could be detected in PPY plus an additional signal on PPY 16q. The region homologous to HSA 1p36.1 is also duplicated in HLA, and split onto chromosomes 7q and 9p; the region homologous to HSA 1q21/1p12 is present as one region on 5q. Additionally, the breakpoint of a small pericentric inversion in the evolution of human chromosome 1 compared to other great ape species could be refined. In summary, the results obtained here are in concordance with previous reports; however, there is evidence for a deletion of regions homologous to human 1p34.2->>p34.1 during evolution in the Pongidae branch after separation of PPY.

A solid-state flexible supercapacitor (SC) based on organic-inorganic composite structure was fabricated through an "in situ growth for conductive wrapping" and an electrode material of polypyrrole (PPy)-MnO2 nanoflakes-carbon fiber (CF) hybrid structure was obtained. The conductive organic material of PPy greatly improved the electrochemical performance of the device. With a high specific capacitance of 69.3 F cm(-3) at a discharge current density of 0.1 A cm(-3) and an energy density of 6.16 × 10(-3) Wh cm(-3) at a power density of 0.04 W cm(-3), the device can drive a commercial liquid crystal display (LCD) after being charged. The organic-inorganic composite active materials have enormous potential in energy management and the "in situ growth for conductive wrapping" method might be generalized to open up new strategies for designing next-generation energy storage devices.

Titanium and its alloys are widely used in load-bearing implants as a result of their excellent mechanical properties and corrosion resistance. In order to improve their performances with respect to osseointegration, the use of bioactive coatings has been suggested. Polypyrrole (PPy) has been chosen as coating polymer because of its ability to be electrochemically grown directly onto metallic substrates, of any shape and dimension, leading to remarkably adherent overlayers. This polymer, in addition to protecting the metal implant against corrosion, could be surface modified with biologically active molecules able to stimulate positive interactions with bone tissue. In this work, PPy electrosynthesis on both titanium and Ti-Al-V substrates has been investigated. The chemical composition and the morphology of the polymeric films, deposited under different conditions, were evaluated by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively.

The purpose of this work was to investigate the potential biomedical application of novel aligned electrospun polypyrrole (PPy)/poly(styrene-beta-isobutylene-beta-styrene) (SIBS) fibers. After successfully aligning the electroactive PPy/SIBS fibers based on our modified electrospinning method, we demonstrated that neurite outgrowth from PC12 cells could be highly orientated parallel to the aligned PPy/SIBS fibers. Physical interactions between the nerve cells and PPy/SIBS fibers through filopodia "sensing" were observed using atomic force microscopy. These observations indicate a role of contact guidance as a mechanism for the observed alignment. This work highlights the capacity for electroactive PPy/SIBS fibers to support and guide nerve cell differentiation through topographic cues, which is a highly desirable characteristic in medical implants for neurological applications.

Drosophila protein phosphatase Y (PPY) displays 64% amino acid identity to protein serine/threonine phosphatase 1 (PP1) and 39% to protein phosphatase 2A (PP2A). Here we show by expression of cDNA in bacteria, that PPY is a protein serine phosphatase and that its biochemical properties are distinct from PP1 in both substrate specificity and regulation by the thermostable inhibitory proteins inhibitor 1 and inhibitor 2. We also demonstrate that PPY is a novel testis specific protein phosphatase by analysis of both mRNA and protein distribution. More precise immunolocalisation within the testis, using affinity purified anti-PPY protein and anti-PPY peptide antibodies, shows that PPY is present in somatic cyst cells, which encase the germ cells. The predominant location of PPY is in the nuclei of both head and tail cyst cells throughout the length of the testis except for the apical tip. The distribution of PPY, coupled with its unique biochemical properties, suggests that PPY may be required to prevent cyst cell division, increase transcription for provision of nutrients to the germ cells and/or provide a signal for spermatocyte differentiation.

A bio-impedance chip has been developed for real-time monitoring of the kinetics of epithelial cell monolayers in vitro. The human bronchial epithelial cell line (16-HBE 14o-) was cultured in Transwells creating a sustainable and interactive model of the airway epithelium. Conducting polymer polypyrrole (PPy) doped with polystyrene sulfonate (PSS) was electrochemically deposited onto the surface of gold-plated electrodes to reduce the influence of the electrical double layer on the impedance measurements. Finite element and equivalent circuit models were used to model and determine the electrical properties of the epithelial cell monolayer from the impedance spectra. Electrically tight, confluent monolayers of 16 HBE 14o- cells were treated with increasing concentrations of either Triton X-100 to solubilize cell membranes or ethylene glycol-bis(2-aminoethyl-ether)-N,N,N'N'-tetraacetic acid (EGTA) to disrupt cell-cell adhesion. Experimental impedance data showed that disruption of epithelial barrier function in response to Triton X-100 and EGTA can be successfully measured by the bio-impedance chip. The results were consistent with the conventional hand-held trans-epithelial electrical resistance measurements. Immunofluorescent staining of the ZO-1 tight junction protein in the untreated and treated 16HBEs was performed to verify the disruption of the tight junctions by EGTA.

We demonstrate that surface modified nanocellulose fibers (NCFs) can be used as substrates to synthesize supercapacitor electrodes with the highest full electrode-normalized gravimetric (127 F g(-1)) and volumetric (122 F cm(-3)) capacitances at high current densities (300 mA cm(-2) ≈ 33 A g(-1)) until date reported for conducting polymer-based electrodes with active mass loadings as high as 9 mg cm(-2). By introducing quaternary amine groups on the surface of NCFs prior to polypyrrole (PPy) polymerization, the macropore volume of the formed PPy-NCF composites can be minimized while maintaining the volume of the micro- and mesopores at the same level as when unmodified or carboxylate groups functionalized NCFs are employed as polymerization substrates. Symmetric, aqueous electrolyte-based, devices comprising these porosity-optimized electrodes exhibit device-specific volumetric energy and power densities of 3.1 mWh cm(-3) and 3 W cm(-3) respectively; which are among the highest values reported for conducting polymer electrodes in aqueous electrolytes. The functionality of the devices is verified by powering a red light-emitting diode with the device in different mechanically challenging states.

A unified strategy involving visible-light-induced iminyl-radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac-[Ir(ppy)3 ] as a photoredox catalyst, the acyl oximes were converted by 1 e(-) reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N-containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible-light-induced iminyl-radical formation was successfully applied to a five-step concise synthesis of benzo[c]phenanthridine alkaloids.

A nanohybrid of gold nanoparticles, polypyrrole, and reduced graphene oxide sheets (named as Au-PPy-rGO) was achieved by electrochemical deposition of reduced graphene oxide with pyrrole and the introduction of gold nanoparticles. Acetylcholinesterase (AChE) was further encapsulated in a silica matrix and immobilized on the Au-PPy-rGO nanocomposite by co-deposition with (NH4)2SiF6. The presence of PPy helped to avoid the aggregation of rGO caused by van der Waals interactions between individual sheets and significantly increased the surface area of the modified electrode. The obtained Au-PPy-rGO nanocomposite not only showed excellent conductivity but also exhibited a high electrocatalytic activity and specific affinity for thiocholine, the hydrolysis product of the enzyme, and thus an improved detection sensitivity. Since AChE molecules were protected by the circumambient silica matrix, which provided a biocompatible environment and facilitated mass transport, the fabricated AChE biosensor displayed high stability and excellent activity together with a fast response to organophosphorus pesticides. Under optimum conditions, the biosensor led to the rapid and sensitive detection of paraoxon-ethyl from 1.0 nM to 5 μM with a detection limit of 0.5 nM.

A polypyrrole based conducting scaffold was developed by incorporating polypyrrole-alginate (PPy-Alg) blend with chitosan using lyophilization technique and employed this composite as a substrate for bone tissue engineering. PPy-Alg blend was developed by oxidative chemical synthesis of polypyrrole using FeCl3 as oxidizing agent and characterized. The physiochemical characterization of the scaffold was done using SEM, FT-IR along with porosity measurement, swelling and in vitro degradation studies. Surface conductivity of the scaffolds was analyzed using Scanning Electrochemical microscopy (SECM). Results from cell viability and cell proliferation with MG-63 cells using Alamar blue assay confirmed the cytocompatible nature of the developed scaffold. In vitro biomineralization ability of the scaffold was assessed and thus the effectiveness of PPy-Alg/chitosan scaffold in the field of tissue engineering was evaluated.

Trifluoromethyl (CF3) and difluoromethyl (CF2H) groups are versatile structural motifs, especially in the fields of pharmaceuticals and agrochemicals. Thus, the development of new protocols for tri- and difluoromethylation of various skeletons has become a vital subject to be studied in the field of synthetic organic chemistry. For the past decades, a variety of fluoromethylating reagents have been developed. In particular, bench-stable and easy-to-use electrophilic fluoromethylating reagents such as the Umemoto, Yagupolskii-Umemoto, Togni, and Hu reagents serve as excellent fluoromethyl sources for ionic and carbenoid reactions. Importantly, the action of catalysis has become a promising strategy for developing new fluoromethylations. For the past several years, photoredox catalysis has emerged as a useful tool for radical reactions through visible-light-induced single-electron-transfer (SET) processes. Commonly used photocatalysts such as [Ru(bpy)3](2+) and fac-[Ir(ppy)3] (bpy = 2,2'-bipyridine; ppy = 2-pyridylphenyl) have potential as one-electron reductants strong enough to reduce those fluoromethylating reagents, resulting in facile generation of the corresponding fluoromethyl radicals. Therefore, if we can design proper reaction systems, efficient and selective radical fluoromethylation would proceed without any sacrificial redox agents, i.e., via a redox-neutral process under mild reaction conditions: irradiation with visible light, including sunlight, below room temperature. It should be noted that examples of catalytic fluoromethylation of compounds with carbon-carbon multiple bonds have been limited until recent years. In this Account, we will focus on our recent research on photoredox-catalyzed fluoromethylation of carbon-carbon multiple bonds. First, choices of the photocatalyst and the fluoromethylating reagent and the basic concept involving a redox-neutral oxidative quenching cycle are explained. Then photocatalytic trifluoromethylation of olefins is discussed mainly. Trifluoromethylative difunctionalization reactions, i.e., simultaneous introduction of the CF3 group and a different functional group across carbon-carbon double bonds, are in the middle of the discussion. Oxy-, amino-, and ketotrifluoromethylation allow us to synthesize various organofluorine compounds bearing C(sp(3))-CF3 bonds. In addition, the synthesis of valuable trifluoromethylated alkenes is also viable when the olefins have an appropriate leaving group or undergo deprotonation. The present reaction system features high functional group compatibility and high regioselectivity. Furthermore, future prospects, especially trifluoromethylative difunctionalization of alkynes and difluoromethylation of alkenes, are also discussed.

Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy), a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs). NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS), tosylate (TsO), perchlorate (ClO(4)) and chloride (Cl), showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS) but low on PPy containing TsO, ClO(4) and Cl. On PPy(DBS), NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS) created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS) films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs.

Nerve guidance conduits (NGCs) are FDA-approved devices used to bridge gaps across severed nerve cables and help direct axons sprouting from the proximal end toward the distal stump. In this article, we present the development of a novel electrically conductive, biodegradable NGC made from a polypyrrole-block-polycaprolactone (PPy-PCL) copolymer material laminated with poly(lactic-co-glycolic acid) (PLGA). The PPy-PCL has a bulk conductivity ranging 10-20 S/cm and loses 40 wt % after 7 months under physiologic conditions. Dorsal root ganglia (DRG) grown on flat PPy-PCL/PLGA material exposed to direct current electric fields (EF) of 100 mV/cm for 2 h increased axon growth by 13% (± 2%) toward either electrode of a 2-electrode setup, compared with control grown on identical substrates without EF exposure. Alternating current increased axon growth by 21% (±3%) without an observable directional preference, compared with the same control group. The results from this study demonstrate PLGA-coated PPy-PCL is a unique biodegradable material that can deliver substrate EF stimulation to improve axon growth for peripheral nerve repair.

Electrochemiluminescence (ECL) is a highly successful technique used in commercial immunoassays for clinical diagnosis. Developing an ECL-based multiplex immunoassay, with the potential to enable high-throughput detection of multiple biomarkers simultaneously, remains a current research interest yet is limited by a narrow choice of ECL luminophores. Herein we report the synthesis, photophysics, electrochemistry, and ECL of several new ruthenium(II) and iridium(III) complexes, three of which are eventually used as signal reporters for multiplex immunoassay. The ECL behaviors of individual luminophores and their mixtures were investigated in multiple modes, including light intensity, spectrum, and image measurements. The spectral peak separation between Ru(bpy)2(dvbpy)2+ (bpy = 2,2'-bipyridine, dvbpy = 4,4'-bis(4-vinylphenyl)-2,2'-bipyridine), and Ir(dFCF3ppy)2(dtbbpy)+ (dFCF3ppy = 3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl, dtbbpy = 4,4'-bis( tert-butyl)-2,2'-bipyridine) was up to 145 nm, thus providing the spectrum-resolved possibility of identifying light signals. The potential-resolved ECL signals were achieved for the mixtures of Ir(ppy)3 (ppy = 2-phenylpyridine) with either Ru(bpy)2(dvbpy)2+ or Ir(dFCF3ppy)2(dtbbpy)+, due to the self-annihilation ECL of Ir(ppy)3 at higher potentials, as confirmed by electrochemistry-coupled mass spectrometry. A multiplex immunoassay free of spatial spotting antibodies on plates or substrates was ultimately devised by combining luminophore-loaded polymer beads with the homogeneous sandwich immunoreaction. Using potential and spectrum dual-resolved ECL as the readout signal, simultaneous recognition of three antigens, namely, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (β-HCG), was demonstrated in a single run for a sample volume of 300 μL. These results contribute to the understanding of ECL generation by multiple luminophores and devising spot-free multiplex immunoassays with less sample consumption.

Natural polysaccharides cellulose, hemicelluloses, inulin etc., galactooligosaccharides (GOS), and fructooligosaccharides (FOS) play a significant role in the improvement of gut microbiota balance and human health. These polysaccharides prevent pathogen adhesion that stimulates the immune system and gut barrier function by servicing as fermentable substrates for the gut microbiota. The gut microbiota plays a key role in the fermentation of non-digestible carbohydrates (NDCs) fibres. Moreover, the gut microbiota is responsible for the production of short-chain fatty acids (SCFAs) like acetate, propionate and butyrate. Acetate is the most abundant and it is used by many gut commensals to produce propionate and butyrate in a growth-promoting cross-feeding process. The dietary fibres affect the gut microbiome and play vital roles in signaling pathways. The SCFAs, acetate, butyrate, and propionate have been reported to affect on metabolic activities at the molecular level. Acetate affects the metabolic pathway through the G protein-coupled receptor (GPCR) and free fatty acid receptor 2 (FFAR2/GPR43) while butyrate and propionate transactivate the peroxisome proliferator-activated receptors_γ (PPAR_γ/NR1C3) and regulate the PPAR_γ target gene Angptl4 in colonic cells of the gut. The FFAR2 signaling pathway regulates the insulin-stimulated lipid accumulation in adipocytes and inflammation, however peptide tyrosine-tyrosine (PPY) and glucagon-like peptide 1 regulates appetite. The NDCs via gut microbiota dependent pathway regulate glucose homeostasis, gut integrity and hormone by GPCR, NF-kB, and AMPK-dependent processes.

Keywords: Dietary fibre; Gut integrity; Gut microbiota; Metabolites; Non-digestible carbohydrates; Short-chain fatty acids; Signaling.