PPI Activity Research Articles

Inhibition Clathrin Mediated Endocytosis: Pitstop 1 and Pitstop 2 Chimeras.

Twenty-five chimera compounds of Pitstop 1 and 2 were synthesised and screened for their ability to block the clathrin terminal domain-amphiphysin protein-protein interaction (NTD-PPI using an ELISA) and clathrin mediated endocytosis (CME) in cells. Library 1 was based on Pitstop 2, but no notable clathrin PPI or in-cell activity was observed. With the Pitstop 1, 16 analogues were produced with 1,8-naphthalic imide core as a foundation. Analogues with methylene spaced linkers and simple amides showed a modest to good range of PPI inhibition (7.6-42.5 μM, naphthyl 39 and 4-nitrophenyl 40 respectively) activity. These data reveal the importance of the naphthalene sulfonate moiety, with no des-SO3 analogue displaying PPI inhibition. This was consistent with the observed analogue docked poses within the clathrin terminal domain Site 1 binding pocket. Further modifications targeted the naphthalene imide moiety, with the installation of 5-Br (45 a), 5-OH (45 c) and 5-propyl ether (45 d) moieties. Among them, the OH 45 c and propyl ether 45 d retained PPI inhibition, with propyl ether 45 d being the most active with a PPI inhibition IC50=7.3 μM. This is 2x more potent than Pitstop 2 and 3x more potent than Pitstop 1.

An evaluation of patient and public involvement (PPI) experience in NHS Talking Therapies for anxiety and depression services: A framework analysis and practical recommendations

AbstractObjectivePatient and public involvement (PPI) refers to the active participation of people, patients, and carers in all stages of research and service delivery development. The aim of this study was to evaluate the PPI experiences in an NHS TTad (Talking Therapies for anxiety and depression) setting and to offer practical recommendations to support PPI activity in service development.MethodA semi‐structured focus group was conducted with five participants who had previously attended a series of PPI groups in TTad services in the Northwest of England. The qualitative data collected were analysed using the INVOLVE framework, incorporating both inductive and deductive coding.ResultsTwelve subthemes emerged, reflecting positive PPI experiences: appreciating PPI contribution, respect for mental health experiences, learning opportunity for PPI members, flexibility and guidance, reimbursement for PPI time, expectations of PPI role in TTad services, availability and commitment, inclusive participation in TTad development, responding to PPI input, diversity, peer support and continued involvement in TTad service development. An additional theme, safe space, emphasised the importance of a comfortable environment and discretion.ConclusionPractical recommendations are provided to enhance recruitment, engagement, empowerment and the impact of PPI in TTad services.

A new perspective on intervertebral disc calcification-from bench to bedside.

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics: hypertrophic chondrocyte-like cell differentiation; TNAP, ENPP1, and ANK upregulation; cell death; altered Pi and PPi homeostasis; and local inflammation. Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype. It is essential to recognize that the presentation and nature of mineralization differ between AF, NP, and EP compartments. Moreover, the combination of anatomic location, genetics, and environmental stressors, such as aging or trauma, govern the predisposition to calcification. Lastly, the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis, along with disc cell death and differentiation status. While there is limited understanding of this phenotype, understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

A review of reviews exploring patient and public involvement in population health research and development of tools containing best practice guidance

IntroductionPatient and public involvement (PPI) is increasingly seen as something that is integral to research and of importance to research funders. There is general recognition that PPI is the right thing to do for both moral and practical reasons. The aim of this review of reviews is to examine how PPI can be done ‘properly’ by looking at the evidence that exists from published reviews and assessing it against the UK Standards for Public Involvement in Research, as well as examining the specific features of population health research that can make PPI more challenging.MethodsA review of reviews and development of best practice guidance was carried out following the 5-stage Framework Synthesis method.ResultsIn total 31 reviews were included. There is a lack of current research or clarity around Governance and Impact when findings are mapped against UK Standards for Public Involvement in Research. It was also clear that there is little knowledge around PPI with under-represented groups. There are gaps in knowledge about how to ensure key specific attributes of population health research are addressed for PPI team members – particularly around how to deal with complexity and the data-driven nature of the research. Four tools were produced for researchers and PPI members to further improve their PPI activity within population health research and health research more generally, including a framework of recommended actions to address PPI in population health research, and guidance on integrating PPI based on the UK Standards for Public Involvement in Research.ConclusionsFacilitating PPI in population health research is challenging due to the nature of this type of research and there is far less evidence on how to do PPI well in this context. The tools can help researchers identify key aspects of PPI that can be integrated when designing PPI within projects. Findings also highlight specific areas where more research or discussion is needed.

Photocatalytic degradation of anionic and cationic dyes over PPy/CuFe2O4 nanocomposite under visible-light and bactericidal action

BackgroundPopulation growth upsurges the need for clean water. Therefore, finding a reliable solution to extract water from the huge industrial and domestic wastewater is very important. Aim of this study investigated the performance of adding of Cufe2O4 over PPy-structure in visible-light assisted dyes photocatalysis and antibacterial activity. MethodHere, PPy@Cufe2O4 nanocomposite was prepared via co-precipitation technique and characterized by XRD, DLS, FTIR, TEM, SEM, PL, DRS, and VSM analyses. At first, PPy@Cufe2O4 was applied to photocatalytic degradation of Direct Blue and Basic Yellow, and the parameters which impact the overall dye removal like pH, contact-time, contaminants initial concentration, and photocatalyst dosage were studied. In the second part, the antibacterial features of PPy@Cufe2O4 toward Staphylococcus aureus and Escherichia coli were studied using disk diffusion and Streaking methods. Significant findingsAccording to the DRS analysis, the bandgap of Cufe2O4, polypyrrole, and the PPy@Cufe2O4 were 2.4, 1.35, and 1.91, respectively. The best photocatalytic performance of PPy@Cufe2O4 was achieved at pH=3.5 for direct blue and pH=11 for Basic Yellow. The kinetic studies were validated by the pseudo-first order model, which was suitable for describing the experimental data. Our results proposed that the linkage of Cufe2O4 over PPy-structure could be an alternative approach to better improving the photocatalytic activity of PPy. The antibacterial test results revealed that the PPy@Cufe2O4 has high antibacterial performance toward Escherichia coli compared to Staphylococcus aureus.

Supramolecular Host-Guest Interaction-Driven Electrochemical Recognition for Pyrophosphate and Alkaline Phosphatase Analysis.

We report an electrochemical biosensor based on the supramolecular host-guest recognition between cucurbit[7]uril (CB[7]) and L-phenylalanine-Cu(II) complex for pyrophosphate (PPi) and alkaline phosphatase (ALP) analysis. First, L-Phe-Cu(II) complex is simply synthesized by the complexation of Cu(II) (metal node) with L-Phe (bioorganic ligand), which can be immobilized onto CB[7] modified electrode via host-guest interaction of CB[7] and L-Phe. In this process, the signal of the complex-triggered electro-catalytic reduction of H2 O2 can be captured. Next, due to the strong chelation between PPi and Cu(II), a biosensing system of the model "PPi and Cu(II) premixing, then adding L-Phe" was designed and the platform was applied to PPi analysis by hampering the formation of L-Phe-Cu(II) complex. Along with ALP introduction, PPi can be hydrolyzed to orthophosphate (Pi), where abundant Cu(II) ions are released to form L-Phe-Cu(II) complex, which gives rise to the catalytic reaction of complex to H2 O2 reduction. The quantitative analysis of H2 O2 , PPi and ALP activity was achieved successfully and the detection of limits are 0.067 μM, 0.42 μM and 0.09 mU/mL (S/N=3), respectively. With its high sensitivity and selectivity, cost-effectiveness, and simplicity, our analytical system has great potential to for use in diagnosis and treatment of ALP-related diseases.

Insights on conducting digital patient and public involvement in dementia research during the COVID-19 pandemic: supporting the development of an “E-nabling digital co-production” framework

BackgroundThe rapid transition to digital working, accelerated due to the response to the COVID-19 pandemic, has impacted the involvement of patients and public in research. This paper presents experiences of engaging in digital Patient and Public Involvement (e-PPI) in dementia research since the lockdowns, offering recommendations regarding future digital and hybrid working. Furthermore, it introduces a co-produced framework for researchers, PPI coordinators and public contributors to identify and discuss challenges and opportunities provided by e-PPI.MethodsTwo online workshops and one individual interview were performed with a group of researchers and PPI coordinators with experience in PPI in dementia research, and with an existing dementia PPI group having some experience of working online during the pandemic. The project was constructed as a PPI activity, with the MindTech Involvement Team (PPI group) involved in the entire process, and a collaborative data analysis process was adopted.ResultsAfter refinement of the coding structure, the MindTech Involvement Team and Project Leaders identified four main themes, resulting in the ‘E-nabling Digital Co-production' Framework. During this framework development, different positions were expressed, associated with the transition to digital working. Two main themes were shared by the participating groups regarding e-PPI: wider potential reach without geographical constraints, and the perception of more business-like sessions with reduced opportunities for social interactions and communication. Specifically for dementia research, whilst e-PPI may allow public contributors to attend more meetings, potentially mutually supportive environments provided by face-to-face meetings could be diminished, with carers experiencing a possible reduction in informal respite opportunities.ConclusionsThrough involving public contributors, researchers, and PPI coordinators with a focus on digital PPI in dementia research, we were able to further refine and co-produce the ‘E-nabling Digital Co-production' Framework. Demonstrating potential for analysis of benefits and limitations within e-PPI, it was possible to identify both general insights and those specific to dementia research. However, the most significant contribution of the framework is the potential to support local journeys of co-production in ongoing digital and hybrid public involvement activities.

Investigation of electrical conductivity and radical scavenging activity of boron phosphate filled polypyrrole nanocomposites

ABSTRACT In this study, the effects of the nanoscaled boron phosphate (BP) addition to polypyrrole (PPy) were investigated. Firstly, the composites containing different weight ratios of BP were prepared and characterized using Fourier-Transform Infrared-attenuated total reflection (FTIR-ATR), UV-vis, X-ray diffraction (XRD), and scanning electron microscopy analyzes. FTIR-ATR analyzes indicated the electrostatic interactions between PPy and BP molecules whereas UV-vis analyzes showed that charge carrier concentration increased with the addition of BP. The electrical conductivity measurements indicated that the electrical conductivity of the pristine PPy increased from 11.1 Scm−1 to 160.6 Scm−1 with the addition of 20% BP by weight. Furthermore, with the addition of 20% BP, the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH •) scavenging activity of PPy was significantly increased from 30.59 ± 0.5% to 49.18 ± 1.17% while 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS•+) scavenging activity improved from 21.97 ± 1.07% to 29.70 ± 0.04%. The observed data have shown that electrically conductive PPy/BP nanocomposites can be a promising component for antioxidant materials.

Value, transparency, and inclusion: A values-based study of patient involvement in musculoskeletal research.

Patient and public involvement work (PPI) is essential to good research practice. Existing research indicates that PPI offers benefits to research design, conduct, communication, and implementation of findings. Understanding how PPI works and its value helps to provide information about best practice and highlight areas for further development. This study used a values-based approach to reporting PPI at a Research Unit focused on musculoskeletal conditions within a UK medical school. The study was conducted between October 2019 and January 2020 using Gradinger's value system framework as a theoretical basis. The framework comprises three value systems each containing five clusters. All PPI members and researchers who had attended PPI groups were invited to participate. Participants completed a structured questionnaire based on the value system framework; PPI members also provided further information through telephone interviews. Data were deductively analysed using a framework approach with data mapped onto value systems. Twelve PPI members and 17 researchers took part. Views about PPI activity mapped onto all three value systems. PPI members felt empowered to provide their views, and that their opinions were valued by researchers. It was important to PPI members that they were able to 'give back' and to do something positive with their experiences. Researchers would have liked the groups to be more representative of the wider population, patients highlighted that groups could include more younger members. Researchers recognised the value of PPI, and the study highlighted areas where researchers members might benefit from further awareness. Three areas for development were identified: (i) facilitating researcher engagement in training about the value and importance of PPI in research; (ii) support for researchers to reflect on the role that PPI plays in transparency of healthcare research; (iii) work to further explore and address aspects of diversity and inclusion in PPI.

Impacts of COVID-19 on clinical research in the UK: A multi-method qualitative case study.

Clinical research has been central to the global response to COVID-19, and the United Kingdom (UK), with its research system embedded within the National Health Service (NHS), has been singled out globally for the scale and speed of its COVID-19 research response. This paper explores the impacts of COVID-19 on clinical research in an NHS Trust and how the embedded research system was adapted and repurposed to support the COVID-19 response. Using a multi-method qualitative case study of a research-intensive NHS Trust in London UK, we collected data through a questionnaire (n = 170) and semi-structured interviews (n = 24) with research staff working in four areas: research governance; research leadership; research delivery; and patient and public involvement. We also observed key NHS Trust research prioritisation meetings (40 hours) and PPI activity (4.5 hours) and analysed documents produced by the Trust and national organisation relating to COVID-19 research. Data were analysed for a descriptive account of the Trust's COVID-19 research response and research staff's experiences. Data were then analysed thematically. Our analysis identifies three core themes: centralisation; pace of work; and new (temporary) work practices. By centralising research prioritisation at both national and Trust levels, halting non-COVID-19 research and redeploying research staff, an increased pace in the setup and delivery of COVID-19-related research was possible. National and Trust-level responses also led to widescale changes in working practices by adapting protocols and developing local processes to maintain and deliver research. These were effective practical solutions borne out of necessity and point to how the research system was able to adapt to the requirements of the pandemic. The Trust and national COVID-19 response entailed a rapid large-scale reorganisation of research staff, research infrastructures and research priorities. The Trust's local processes that enabled them to enact national policy prioritising COVID-19 research worked well, especially in managing finite resources, and also demonstrate the importance and adaptability of the research workforce. Such findings are useful as we consider how to adapt our healthcare delivery and research practices both at the national and global level for the future. However, as the pandemic continues, research leaders and policymakers must also take into account the short and long term impact of COVID-19 prioritisation on non-COVID-19 health research and the toll of the emergency response on research staff.

Gold nanoclusters reversible switches based on aluminum ions-triggered for detection of pyrophosphate and acid phosphatase activity

Gold nanoclusters (AuNCs) were synthesized using glutathione (GSH) as a reducing agent and stabilizer. The aluminum ions could trigger the aggregation of AuNCs, causing a significant fluorescence, owing to the more vital coordination between Al3+ and pyrophosphate (PPi), AuNCs-Al3+ was disaggregated with the addition of PPi, resulting in a considerable fluorescence quench of the system. When acid phosphatase (ACP) was present, PPi was consumed by ACP, which inhibited the disaggregation of AuNCs. Based on the principle of Al3+ and PPi inducing aggregation-disaggregation of AuNCs accompanied by fluorescence enhancement-quenching, a novel method was established for fluorescence "turn-on-off-on" detection of PPi and ACP activity. The PPi detection limit was determined to be 0.1 µM in the linear range of 0.3-100 µM (R2 = 0.9995). The ACP detection limit was determined to be 4.16 U L−1 in the linear range of 15.0-80.0 U L−1 (R2 = 0.9970). The proposed GSH-AuNCs biosensor exhibits excellent sensing efficiency and has been introduced to determine PPi and ACP in real samples with satisfactory results.

In vitro algicidal effect of polypyrrole on Prototheca species isolates from bovine mastitisAlgicidal activity of polypyrrole on Prototheca spp.

Algae of the genus Prototheca are microorganisms involved in the occurrence of diseases in humans and animals. In bovine species, Prototheca spp. cause environmental mastitis, productive losses in dairy herds, mainly leading to the discard of infected cows. Currently, there are no effective anti-Prototheca spp. drugs to combat this infection. Thus, the search for an efficacious therapy for Prototheca spp. infections have become essential. Highly soluble polypyrrole (Ppy) is a molecule with known antimicrobial activity. This study aimed to characterize Prototheca spp. isolates from bovine mastitis as well as to evaluate the susceptibility profile and to verify the morphological alterations on Prototheca spp. isolates treated with Ppy. In this research, 36 Brazilian isolates of Prototheca spp. were characterized by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) assay for the mitochondrial cytB gene. Additionally, Ppy algicidal activity against these isolates of Prototheca spp. was assessed by minimal microbicidal concentration method in microplates. Further, scanning electron microscopy (SEM) was performed in order to verify the morphological alterations on Prototheca spp. isolates in response to Ppy. The isolates were characterized as belonging to Prototheca zopfii genotype 2 (35/36) and Prototheca blaschkeae (1/36). Ppy had an algicidal effect on all isolates tested at concentrations ranging from 15.625μg ml-1 to 62.5μg ml-1. SEM showed changes on planktonic and sessile P. zopfii, including a decrease of the number of cells with the presence of an amorphous substance involving the cells. The algicidal activity of Ppy suggests the therapeutic potential of this molecule in the prevention and treatment of Prototheca spp. in bovine mastitis.

\u201cPROUD to have been involved\u201d: an evaluation of participant and community involvement in the PROUD HIV prevention trial

BackgroundThe PROUD trial, a HIV prevention trial in men who have sex with men and trans women, set out to involve community representatives and trial participants in several ways. PROUD also aimed to evaluate participant involvement, to learn lessons and make recommendations for future clinical trials.MethodsTwo structured surveys, one of participant and community representatives involved in the PROUD study, and the other of researchers from the PROUD team, were carried out in 2017. The results from the surveys were reviewed quantitatively and qualitatively, and themes emerging from the data identified and synthesised.ResultsSurvey invitations were sent to 88 involved participants, 11 community representatives and 10 researchers. The overall response rate was 55% (60/109). Overall, participants were younger than community representatives, and the majority were from Greater London. As expected, participants were predominantly involved in participant involvement meetings and community representatives in management committees.Participants and community representatives cited different motivations for getting involved in PROUD. Overall, participants were positive about their involvement; only two participants rated their experience unfavourably. Community representatives were also broadly positive. Most participants and all community representatives felt their involvement made a difference to the trial, themselves and / or the organisations they represented. However, some participant answers reflected the impact of participation in the trial rather than involvement in PPI activities.Researchers felt that PPI had positive impact across the entire trial cycle. Half felt they would have liked there to have been more PPI activity in PROUD. Researchers noted some challenges and recommendations for the future, including need for adequate funding, more engagement in PPI by all researchers, the need for PPI expertise to facilitate involvement activities and training and mentoring in PPI.ConclusionsInvolving clinical trial participants and wider community representatives as active partners in PPI is feasible and valuable in trials. Researchers are encouraged to consider and appropriately resource participant involvement and prospectively evaluate all PPI within their trials.

Synthesis, characterization, and solution studies of polyoxometalate-doped conducting polymers

The present research focus is to design a new catalyst by doping polyoxometalate (POM) in conducting polymers. Polypyrrole (PPy)-doped Keggin type POM [PMO12O40]3− with various molar concentrations were synthesized using the coprecipitation method. The doped samples were synthesized and characterized using spectral techniques such as Fourier transform infrared spectra, which show the presence of extended functional groups, and scanning electron microscopic morphology exhibits a square-shaped structure. X-Ray diffraction results reveal crystallite size of around 40 nm. The conductivity of PPy is 3.3 × 10−6 S cm−1, whereas polyacid-doped polypyrrole has resulted in increased conductivity of 7.12 × 10−5 S cm−1. The antimicrobial activity of PPy revealed a better antibacterial activity due to the presence of the NH group and aromatic ring in the structure.

Preparation of Li (tri-(4-carboxyphenyl) amine) doped polypyrrole as cathode material of lithium ion batteries and its electrochemical performances

The Li (tri-(4-carboxyphenyl) amine) (Li-TCPA2) doped polypyrrole (PPy-Li-TCPA2) composites were successfully prepared by in-situ chemical oxidation using pyrrole and Li-TCPA2 as raw materials. The structure, morphology, electrochemical properties of prepared materials were characterized by fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), specific surface area test (BET), scanning electron microscopy (SEM), cyclic voltammogram (CV) and electrochemical impedance spectra (EIS), respectively. Also, the charge-discharge properties of the prepared composites were studied by galvanostatic charge-discharge testing. The results demonstrated that as-prepared composite material exhibited a reversible redox process at 2.0–4.0 V. And the discharge specific capacity for PPy-Li-TCPA2 (2:1) and PPy-Li-TCPA2 (6:1) are 50.4 mAh·g−1 and 63.7 mAh·g−1 as measured at 30 mA·g−1 between 2.0 and 4.0 V, while PPy-Li-TCPA2 (4:1) exhibited the discharge specific capacity of 91.1 mAh·g−1, which were remarkably higher than that of the pure PPy (29.5 mAh·g−1) under the same experimental conditions. At the same time, PPy-Li-TCPA2 (4:1) has improved rate performance and stable cycleability. The excellent electrochemical properties are attributed to the introduction of Li-TCPA2 as dopant, which improved the electrical conductivity and the redox activity of PPy. Furthermore, the resulted well-dispersed particle structure of the composite as well as its improved specific surface area for doped PPy facilitated to the contact of the electrolyte with the active material, leading to the increased utilization ratio of active material and the enhanced electrochemical performances.

Identification of Salmonella Typhimurium Peptidyl-prolyl cis-trans Isomerase B (PPIase B) and Assessment of their Role in the Protein Folding.

Peptidyl-prolyl cis-trans isomerase (PPIases) enzyme plays a vital role in protein folding. It catalyses the cis-trans isomerisation of peptide bonds, an essential step for newly synthesized protein to acquire its correct functional conformation in both prokaryotes and eukaryotes. The present study showed the biochemical and molecular characterisation of cyclophilins (PpiB), a type of peptidyl-prolyl isomerases proteins from the pathogenic bacteria Salmonella Typhimurium. Salmonella Typhimurium is one of the leading serovars responsible for human and animal salmonellosis globally, with the majority of human cases originating through the food chain. Here successful expression and purification of PpiB protein have been demonstrated and LC-MS based analyses showed high protein score and similarity with other PPi protein. Further the enzymatic activity of the purified recombinant PpiB was determined using Succinyl-Ala-Phe-Pro- Phe-p nitroanilide as substrate and enzyme-catalysed reaction. Km and Vmax were calculated and found to be Vm = 1.023 ± .06400 min/μg, Km = 0.6219 ± 0.1701 μM, respectively. We have reported for the first time the presence of Salmonella PPIase-B (PpiB) protein isoforms in salmonella genome having PPi activity. Taken together, our data clearly showed that Salmonella Cyclophilin B (PpiB) protein is active and involved in diverse biological processes and highly similar to the different domain of Cyclophilin proteins.

Multifunctional Polypyrrole-silver Coated Layered Double Hydroxides Embedded into a Biodegradable Polymer Matrix for Enhanced Antibacterial and Gas Barrier Properties

In this study, polypyrrole-silver coated layered double hydroxides (LDHs@PPy-Ag) was prepared by chemical polymerization of pyrrole (Py) with silver ions. Silver nanoparticles (AgNPs) could be uniformly reduced onto PPy coatings in situ by redox reaction during simultaneous polymerization process. And LDHs@PPy-Ag/poly(ε-caprolactone) (PCL) nanocomposites were fabricated by solution casting method. It is revealed that spherical AgNPs are loaded on PPy coatings uniformly. Particularly, compared with pure PCL, LDHs@PPy-Ag/PCL nanocomposites with incorporation of only 1 wt% LDHs@PPy-Ag show a 17% increase in tensile strength (36.5 MPa) and a 29% increase in elongation at break (822%). Upon PPy-Ag coatings onto original LDHs, oxygen relative permeability of LDHs@PPy-Ag/PCL nanocomposites decreases to 52% with the same addition. Meanwhile, due to the double antibacterial activity of PPy and AgNPs, the antibacterial rate of LDHs@PPy-Ag reaches 100%. And the corresponding LDHs@PPy-Ag/PCL nanocomposites also show outstanding antibacterial activity. Considering the superiority of their comprehensive performance, antibacterial LDHs@PPy-Ag/PCL nanocomposites can be used further for the application as biodegradable polymeric active packaging materials.

Zinc ion-triggered aggregation induced emission enhancement of dual ligand co-functionalized gold nanoclusters based novel fluorescent nanoswitch for multi-component detection

Herein, a zinc ion (Zn2+)-triggered aggregation induced emission enhancement (AIEE) fluorescence “on-off-on” nanoswitch was fabricated for inorganic pyrophosphate (PPi) and inorganic pyrophosphatase (PPase) activity detection. Dual ligand functionalized Au NCs were utilized as the substrate of the AIEE nanoswitch. The introduction of Zn2+ can cause Au NCs aggregated along with the enhanced fluorescence. After the addition of PPi, aggregated Au NCs disaggregated along with decreased fluorescence due to the competitive combination between PPi and Zn2+ (on-off). When PPase was introduced, PPi was hydrolyzed and release Zn2+, resulting in aggregated Au NCs along with enhanced fluorescence again (off-on). On the basis of this, highly selective and sensitive detection PPi (liner range from 0.1 to 300 μM) and PPase activity (liner range from 0.1 to 10 mU) can be achieved. The detection limits are 0.04 μM for PPi and 0.03 mU for PPase, respectively. Furthermore, the as-prepared Zn2+-triggered AIEE nanoswitch was successfully used for quantitative analysis of PPase activity in human serum with satisfactory spiked recoveries, and applied for the inhibitors screening.

Involving patients and the public in medical and health care research studies: An exploratory survey on participant recruiting and representativeness from the perspective of study authors.

Research on patient and public involvement so far concentrates on defining involvement, describing its methods, and analyzing involvement practices in various individual research disciplines. There is little empirical data on the process of and aims for selecting (lay) PPI participants, and to what extend they can and should be representative of the population at large. To explore practices and perceptions on these issues and on future PPI conduct more generally, we sent an electronic survey to authors who published involvement activities as part of their studies in medical and social science journals. We identified such authors with a systematic search of five databases and applied descriptive statistics for analysis. Of those who returned the survey (n = 127 of 315; 40%), most had previously conducted involvement activities (73%). 45% reported more than one type of involvement, e.g. consultation and deliberation and participation (14%) and to have recruited more than one type of participant for their PPI activity (56%), e.g. ‘lay publics’ and ‘expert publics’ (33% of 71). Representativeness was often seen as a crucial objective when selecting PPI participants, while less than half found it very easy (9%) or rather easy (34%) to select participants. Many respondents considered achieving good representativeness difficult (52%) or very difficult (17%). They identified significant respective challenges and desired more guidance on various aspects of planning and conducting PPI (56%). 55% thought that the concept of “involvement” should be changed or improved. We conclude that recruiting lay people for PPI activities and deciding about and handling representativeness are controversial in current PPI practice, given the manifold challenges mentioned by the survey respondents. Our findings may inform further research particularly regarding–the potentially many cases of–unpublished PPI.

Membrane and nucleus targeting for highly sensitive cancer cell detection using pyrophosphate and alkaline phosphatase activity-mediated fluorescence switching of functionalized carbon dots.

A specific membrane and nucleus targeted fluorescence OFF-ON-OFF system, using the dodecane/sulfobetaine group of functionalized carbon dots (CD) with a copper ion (Cu2+-CD) based on the presence of pyrophosphate (PPi) molecules and alkaline phosphatase (ALP) activity, for cancer cell detection was designed. The biosensor could be effectively transported from the cytosol to the nucleus in MDAMB cells, but not in MDCK cells due to the response to a change in pH by CD functionalized with zwitterionic groups. The biosensor also showed a membrane-selective regulated route for fusion of long alkyl chain grafted-CD on cell membranes. As a potential sensor, the fluorescence of the prepared Cu2+-CD was significantly quenched due to aggregation. In human cancer MDAMB cells, a nearly complete restoration of the fluorescence intensity of the Cu2+-CD was observed because of the high levels of intracellular PPi, which preferentially bound to Cu2+. After 10 min, in the MDAMB cells, re-quenching of the CD fluorescence occurred because of the high level of intracellular ALP, which can hydrolyze PPi and release the Cu2+ to re-aggregate the CD. In contrast to MDAMB cells, MDCK cells did not show an obvious response to the specific intracellular biomolecules, thus, enabling the biosensor to be used to distinguish between cancer and normal cells. In conclusion, this biosensor has the potential to be a simple and sensitive cancer diagnostic tool that can differentiate normal cells from cancer cells on coated surfaces and in aqueous states.