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Most non-muscle invasive bladder cancers have been treated by transurethral resection and following intravesical injection of immunotherapeutic agents. However, the delivery efficiency of therapeutic agents into bladder wall is low due to frequent urination, which leads to the failure of treatment with side effects. Here, we report a urease-powered nanomotor containing the agonist of stimulator of interferon genes (STING) for the efficient activation of immune cells in the bladder wall. After characterization, we perform in vitro motion analysis and assess in vivo swarming behaviors of nanomotors. The intravesical instillation results in the effective penetration and retention of nanomotors in the bladder. In addition, we confirm the anti-tumor effect of nanomotor containing the STING agonist (94.2% of inhibition), with recruitment of CD8 + T cells (11.2-fold compared with PBS) and enhanced anti-tumor immune responses in bladder cancer model in female mice. Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder cancer immunotherapy., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Trichomoniasis is the most prevalent curable, non-viral sexually transmitted infection (STI), with an estimated 156 million new infections in 2020. It can potentially result in adverse birth outcomes as well as infertility in men, whilst it also increases the risk of acquiring HIV and contracting other vaginal infections. It is mostly prevalent among women in low-income countries and especially in Africa and the Americas. This STI is caused by Trichomonas vaginalis (TV) and a robust, cost-effective, sensitive, specific and rapid diagnostic test is urgently required. We report the screening of 6 full-length and 4 truncated aptamers previously selected in our group for use in a microplate-based sandwich assay. The combination of dual aptamers comprising a short 14-mer truncated capture aptamer (termed A1_14mer) and a full-length non-truncated reporter aptamer (A6) was elucidated to be the optimum pair for a sensitive sandwich enzyme-linked aptamer assay (ELAA) for the detection of TV achieving a detection limit of 3.02 × 10 4  TV cells/mL. The results obtained with the A1_14mer-A6 ELAA correlate excellently with wet-mount microscopy for the detection of TV in clinical specimens, cervicovaginal lavages and vaginal swabs, highlighting the potential clinical application of this assay for cost-effective population screening and subsequent prevention of the onset of complications associated with undiagnosed and untreated TV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest None.

Background: The hypothesis of decreased neural inhibition in dementia has been sparsely studied in functional magnetic resonance imaging (fMRI) data across patients with different dementia subtypes, and the role of social and demographic heterogeneities on this hypothesis remains to be addressed., Methods: We inferred regional inhibition by fitting a biophysical whole-brain model (dynamic mean field model with realistic inter-areal connectivity) to fMRI data from 414 participants, including patients with Alzheimer's disease, behavioral variant frontotemporal dementia, and controls. We then investigated the effect of disease condition, and demographic and clinical variables on the local inhibitory feedback, a variable related to the maintenance of balanced neural excitation/inhibition., Results: Decreased local inhibitory feedback was inferred from the biophysical modeling results in dementia patients, specific to brain areas presenting neurodegeneration. This loss of local inhibition correlated positively with years with disease, and showed differences regarding the gender and geographical origin of the patients. The model correctly reproduced known disease-related changes in functional connectivity., Conclusions: Results suggest a critical link between abnormal neural and circuit-level excitability levels, the loss of grey matter observed in dementia, and the reorganization of functional connectivity, while highlighting the sensitivity of the underlying biophysical mechanism to demographic and clinical heterogeneities in the patient population., (© 2024. The Author(s).)

The detection of single nucleotide polymorphisms (SNPs) is of increasing importance in many areas including clinical diagnostics, patient stratification for pharmacogenomics, and advanced forensic analysis. In the work reported, we apply a semiautomated system for solid-phase electrochemical melting curve analysis (éMCA) for the identification of the allele present at a specific SNP site associated with an increased risk of bone fracture and predisposition to osteoporosis. Asymmetric isothermal recombinase polymerase amplification using ferrocene labeled forward primers was employed to generate single stranded redox labeled amplicons. In a first approach to demonstrate the proof of concept of combining asymmetric RPA with solid-phase éMCA, a simplified system housing a multielectrode array within a polymeric microsystem, sandwiched between two aluminum plates of a heater device, was used. Sample manipulation through the microfluidic channel was controlled by a syringe pump, and an external Ag/AgCl reference electrode was employed. Individual electrodes of the array were functionalized with four different oligonucleotide probes, each probe equivalent in design with the exception of the middle nucleotide. The isothermally generated amplicons were allowed to hybridize to the surface-tethered probes and subsequently subjected to a controlled temperature ramp, and the melting of the duplex was monitored electrochemically. A clear difference between the fully complementary and a single mismatch was observed. Having demonstrated the proof-of-concept, a device for automated éMCA with increased flexibility to house diverse electrode arrays with internal quasi-gold reference electrodes, higher resolution, and broader melting temperature range was developed and exploited for the detection of SNP hetero/homozygosity. Using the optimized conditions, the system was applied to the identification of the allele present at an osteoporosis associated SNP site, rs2741856, in 10 real fingerprick/venous blood samples, with results validated using Sanger sequencing.

Osteoporosis is a multifactorial disease influenced by genetic and environmental factors, which contributes to an increased risk of bone fracture, but early diagnosis of this disease cannot be achieved using current techniques. We describe a generic platform for the targeted electrochemical genotyping of SNPs identified by genome-wide association studies to be associated with a genetic predisposition to osteoporosis. The platform exploits isothermal solid-phase primer elongation with ferrocene-labeled nucleoside triphosphates. Thiolated reverse primers designed for each SNP were immobilized on individual gold electrodes of an array. These primers are designed to hybridize to the SNP site at their 3'OH terminal, and primer elongation occurs only where there is 100% complementarity, facilitating the identification and heterozygosity of each SNP under interrogation. The platform was applied to real blood samples, which were thermally lysed and directly used without the need for DNA extraction or purification. The results were validated using Taqman SNP genotyping assays and Sanger sequencing. The assay is complete in just 15 min with a total cost of 0.3€ per electrode. The platform is completely generic and has immense potential for deployment at the point of need in an automated device for targeted SNP genotyping with the only required end-user intervention being sample addition., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The overall objective of this work is the evaluation of different competitive aptamer assays based on inductively coupled plasma mass spectrometry (ICP-MS) detection for the determination of β-conglutin (food protein allergen from lupin) in flour samples. To this end, two competitive aptamer assay schemes were developed using either thiolated aptamers chemisorbed onto gold nanoparticles (AuNPs) or biotinylated aptamers linked to streptavidin-AuNPs. The influence of ICP-MS detection mode (i.e., conventional vs single particle) on assay performance was explored. In the case of the thiolated aptamer, the limit of detection (LoD) obtained using the single particle mode was improved 2-fold as compared to the LoD provided by the conventional mode. With regards to the biotinylated aptamer, the use of the conventional mode provided a 5-fold improvement of LoD as compared to that obtained for the single particle one. Using the optimized conditions, the best LoD of 2 pM was obtained with the biotinylated aptamer operating with conventional ICP-MS detection. When compared to previous reports using the same aptamer in a competitive assay, the developed method significantly improved the LoD by at least an order of magnitude. Different flour samples containing lupin were successfully analyzed according to European Conformity guidelines for the analysis of food contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Retaining glycoside hydrolases use acid/base catalysis with an enzymatic acid/base protonating the glycosidic bond oxygen to facilitate leaving-group departure alongside attack by a catalytic nucleophile to form a covalent intermediate. Generally, this acid/base protonates the oxygen laterally with respect to the sugar ring, which places the catalytic acid/base and nucleophile carboxylates within about 4.5-6.5 Å of each other. However, in glycoside hydrolase (GH) family 116, including disease-related human acid β-glucosidase 2 (GBA2), the distance between the catalytic acid/base and the nucleophile is around 8 Å (PDB: 5BVU) and the catalytic acid/base appears to be above the plane of the pyranose ring, rather than being lateral to that plane, which could have catalytic consequences. However, no structure of an enzyme-substrate complex is available for this GH family. Here, we report the structures of Thermoanaerobacterium xylanolyticum β-glucosidase ( Tx GH116) D593N acid/base mutant in complexes with cellobiose and laminaribiose and its catalytic mechanism. We confirm that the amide hydrogen bonding to the glycosidic oxygen is in a perpendicular rather than lateral orientation. Quantum mechanics/molecular mechanics (QM/MM) simulations of the glycosylation half-reaction in wild-type Tx GH116 indicate that the substrate binds with the nonreducing glucose residue in an unusual relaxed 4 C 1 chair at the -1 subsite. Nevertheless, the reaction can still proceed through a 4 H 3 half-chair transition state, as in classical retaining β-glucosidases, as the catalytic acid D593 protonates the perpendicular electron pair. The glucose C6OH is locked in a gauche , trans orientation with respect to the C5-O5 and C4-C5 bonds to facilitate perpendicular protonation. These data imply a unique protonation trajectory in Clan-O glycoside hydrolases, which has strong implications for the design of inhibitors specific to either lateral protonators, such as human GBA1, or perpendicular protonators, such as human GBA2., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A spherical dielectric particle can sustain the so-called whispering-gallery modes (WGMs), which can be regarded as circulating electromagnetic waves, resulting in the spatial confinement of light inside the particle. Despite the wide adoption of optical WGMs as a major light confinement mechanism in salient practical applications, direct imaging of the mode fields is still lacking and only partially addressed by simple photography and simulation work. The present study comprehensively covers this research gap by demonstrating the nanoscale optical-field visualization of self-interference of light extracted from excited modes through experimentally obtained photon maps that directly portray the field distributions of the excited eigenmodes. To selectively choose the specific modes at a given light emission detection angle and resonance wavelength, we use cathodoluminescence-based scanning transmission electron microscopy supplemented with angle-, polarization-, and wavelength-resolved capabilities. Equipped with semi-analytical simulation tools, the internal field distributions of the whispering-gallery modes reveal that radiation emitted by a spherical resonator at a given resonance frequency is composed of the interference between multiple modes, with one or more of them being comparatively dominant, leading to a resulting distribution featuring complex patterns that explicitly depend on the detection angle and polarization. Direct visualization of the internal fields inside resonators enables a comprehensive understanding of WGMs that can shed light on the design of nanophotonic applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Commercially available titanium alloys such as Ti-6Al-4V are established in clinical use as load-bearing bone implant materials. However, concerns about the toxic effects of vanadium and aluminum have prompted the development of Al- and V-free β-Ti alloys. Herein, a new alloy composed of non-toxic elements, namely Ti-18Mo-6Nb-5Ta (wt%), has been fabricated by arc melting. The resulting single β-phase alloy shows improved mechanical properties (Young's modulus and hardness) and similar corrosion behavior in simulated body fluid when compared with commercial Ti-6Al-4V. To increase the cell proliferation capability of the new biomaterial, the surface of Ti-18Mo-6Nb-5Ta was modified by electrodepositing calcium phosphate (CaP) ceramic layers. Coatings with a Ca/P ratio of 1.47 were obtained at pulse current densities, -j c , of 1.8-8.2 mA/cm 2 , followed by 48 h of NaOH post-treatment. The thickness of the coatings has been measured by scanning electron microscopy from an ion beam cut, resulting in an average thickness of about 5 μm. Finally, cytocompatibility and cell adhesion have been evaluated using the osteosarcoma cell line Saos-2, demonstrating good biocompatibility and enhanced cell proliferation on the CaP-modified Ti-18Mo-6Nb-5Ta material compared with the bare alloy, even outperforming their CaP-modified Ti-6-Al-4V counterparts.

Background: Evidence on the association of low physical activity (PA) with depression or anxiety is well established. Yet, evidence on the association between PA and comorbid anxiety/depression remains scarce, especially in low- and middle-income countries (LMICs). Thus, this study explored this relationship among adults aged ≥18 years from 46 LMICs., Methods: Cross-sectional, community-based data were analyzed from the World Health Survey (WHS). Multivariable multinomial logistic regression analysis was conducted to examine the association between low PA and comorbid anxiety/depression with no anxiety or depression as the base category., Results: 237,023 participants [mean (SD) age = 38.4 (16.0) years; 50.8 % female] were included in the analysis. Low PA was significantly associated with depression alone (OR = 1.33; 95%CI = 1.12-1.57) and anxiety alone (OR = 1.37; 95%CI = 1.23-1.53), while the OR was highest among those with comorbid anxiety/depression (OR = 1.75; 95%CI = 1.52-2.01)., Conclusion: Low PA is associated with particularly increased odds for comorbid anxiety/depression. Increasing PA may have a beneficial effect on the prevention of comorbid anxiety/depression. However, future longitudinal research establishing the direction of this relationship is warranted., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Free-electron-based spectroscopies can reveal the nanoscale optical properties of semiconductor materials and nanophotonic devices with a spatial resolution far beyond the diffraction limit of light. However, the retrieved spatial information is constrained to the excitation space defined by the electron beam position, while information on the delocalization associated with the spatial extension of the probed optical modes in the specimen has so far been missing, despite its relevance in ruling the optical properties of nanostructures. In this study, we demonstrate a cathodoluminescence method that can access both excitation and emission spaces at the nanoscale, illustrating the power of such a simultaneous excitation and emission mapping technique by revealing a subwavelength emission position modulation as well as by visualizing electromagnetic energy transport in nanoplasmonic systems. Besides the fundamental interest of these results, our technique grants us access into previously inaccessible nanoscale optical properties.

Mucinases of human gut bacteria cleave peptide bonds in mucins strictly depending on the presence of neighboring O-glycans. The Akkermansia muciniphila AM0627 mucinase cleaves specifically in between contiguous (bis) O-glycans of defined truncated structures, suggesting that this enzyme may recognize clustered O-glycan patches. Here, we report the structure and molecular mechanism of AM0627 in complex with a glycopeptide containing a bis-T (Galβ1-3GalNAcα1-O-Ser/Thr) O-glycan, revealing that AM0627 recognizes both the sugar moieties and the peptide sequence. AM0627 exhibits preference for bis-T over bis-Tn (GalNAcα1-O-Ser/Thr) O-glycopeptide substrates, with the first GalNAc residue being essential for cleavage. AM0627 follows a mechanism relying on a nucleophilic water molecule and a catalytic base Glu residue. Structural comparison among mucinases identifies a conserved Tyr engaged in sugar-π interactions in both AM0627 and the Bacteroides thetaiotaomicron BT4244 mucinase as responsible for the common activity of these two mucinases with bis-T/Tn substrates. Our work illustrates how mucinases through tremendous flexibility adapt to the diversity in distribution and patterns of O-glycans on mucins., (© 2022. The Author(s).)

Although urban greening is universally recognized as an essential part of sustainable and climate-responsive cities, a growing literature on green gentrification argues that new green infrastructure, and greenspace in particular, can contribute to gentrification, thus creating social and racial inequalities in access to the benefits of greenspace and further environmental and climate injustice. In response to limited quantitative evidence documenting the temporal relationship between new greenspaces and gentrification across entire cities, let alone across various international contexts, we employ a spatially weighted Bayesian model to test the green gentrification hypothesis across 28 cities in 9 countries in North America and Europe. Here we show a strong positive and relevant relationship for at least one decade between greening in the 1990s-2000s and gentrification that occurred between 2000-2016 in 17 of the 28 cities. Our results also determine whether greening plays a "lead", "integrated", or "subsidiary" role in explaining gentrification., (© 2022. The Author(s).)

Non-volatile magnetic random-access memories (MRAMs), such as spin-transfer torque MRAM and next-generation spin-orbit torque MRAM, are emerging as key to enabling low-power technologies, which are expected to spread over large markets from embedded memories to the Internet of Things. Concurrently, the development and performances of devices based on two-dimensional van der Waals heterostructures bring ultracompact multilayer compounds with unprecedented material-engineering capabilities. Here we provide an overview of the current developments and challenges in regard to MRAM, and then outline the opportunities that can arise by incorporating two-dimensional material technologies. We highlight the fundamental properties of atomically smooth interfaces, the reduced material intermixing, the crystal symmetries and the proximity effects as the key drivers for possible disruptive improvements for MRAM at advanced technology nodes., (© 2022. Springer Nature Limited.)

Mycotoxins are toxic compounds produced by fungi, which represent a risk to the food and feed supply chain, having an impact on health and economies. A high percentage of feed samples have been reported to be contaminated with more than one type of mycotoxin. Systematic, cost-effective and simple tools for testing are critical to achieve a rapid and accurate screening of food and feed quality. In this review, we describe the various aptamers that have been selected against mycotoxins and their incorporation into optical and electrochemical aptasensors, outlining the strategies exploited, highlighting the advantages and disadvantages of each approach. The review also discusses the different materials used and the immobilization methods employed, with the aim of achieving the highest sensitivity and selectivity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heavy-metal-free colloidal nanocrystals are gaining due attention as low-cost, semiconducting materials for solution-processed optoelectronic applications. One common limitation of such materials is their limited carrier transport and trap-assisted recombination, which impede the performance of thick photoactive layers. Here we mix small-size and large-size AgBiS 2 nanocrystals to judiciously favour the band alignment in photovoltaic and photodetector devices. The absorbing layer of these devices is fabricated in a gradient fashion in order to maximise charge transfer and transport. We implement this strategy to fabricate mixed AgBiS 2 thin film solar cells with a power conversion of 7.3%, which significantly surpasses the performance of previously reported devices based on single-batch AgBiS 2 nanocrystals. Additionally, this approach allows us to fabricate devices using thicker photoactive layers that show lower dark currents and external quantum efficiencies exceeding 40% over a broad bandwidth - covering the visible and near infrared range beyond 1 μm, thus unleashing the potential of colloidal AgBiS 2 nanocrystals in photodetector applications.

Objectives: To investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders., Design: Cohort study., Setting: The South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register., Participants: A large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30-F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register., Primary and Secondary Outcome Measures: Falls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures., Results: Of 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures., Conclusions: Over a mean 5 years' follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Selective spectral detection of ultraviolet (UV) radiation is highly important across numerous fields from health and safety to industrial and environmental monitoring applications. Herein, a nontoxic, visible-blind, quantum dot (QD)-based sensing scheme that expands the spectral coverage of silicon complementary metal-oxide-semiconductor (CMOS) sensors into the UV, enabling efficient UV detection without affecting the sensor performance in the visible and UV-band discrimination, is reported. This scheme uses zinc magnesium oxide (ZnMgO) QDs with compositionally tunable absorption across UV and high photoluminescence quantum yield in the visible. The efficient luminescence and large Stokes shift of these QDs are exploited herein to act as an efficient downconverting material that enhances the UV sensitivity of Si-photodetectors (Si-PDs). A Si-PD integrated with the QDs results in a ninefold improvement in photoresponsivity from 0.83 to 7.5 mA W -1 at 260 nm. Leveraging the tunability of these QDs, a simple UV-band identification scheme is further reported, which uses two distinct-bandgap ZnMgO QDs stacked in a tandem architecture whose spectral emission color depends on the UV-band excitation light. The downconverting stack enables facile discrimination of UV light using a standard CMOS image sensor (camera) or by the naked eye and avoids the use of complex optics., (© 2022 Wiley-VCH GmbH.)

The formation of supramolecular complexes between C 60 and a molecular nanographene endowed with both positive and negative curvatures is described. The presence of a corannulene moiety and the saddle shape of the molecular nanographene allows the formation of complexes with 1:1, 1:2, and 2:1 stoichiometries. The association constants for the three possible supramolecular complexes were determined by 1 H NMR titration. Furthermore, the stability of the three complexes was calculated by theoretical methods that also predict the photoinduced electron transfer from the curved nanographene to the electron acceptor C 60 . Time-resolved transient absorption measurements on the ns-time scale showed that the addition of C 60 to NG-1 solutions and photo-exciting them at 460 nm leads to the solvent-dependent formation of new species, in particular the formation of the one-electron reduced form of C 60 in benzonitrile was observed., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged at the end of 2019, resulting in the ongoing COVID-19 pandemic. The high transmissibility of the virus and the substantial number of asymptomatic individuals have led to an exponential rise in infections worldwide, urgently requiring global containment strategies. Reverse transcription-polymerase chain reaction is the gold standard for the detection of SARS-CoV-2 infections. Antigen tests, targeting the spike (S) or nucleocapsid (N) viral proteins, are considered as complementary tools. Despite their shortcomings in terms of sensitivity and specificity, antigen tests could be deployed for the detection of potentially contagious individuals with high viral loads. In this work, we sought to develop a sandwich aptamer-based assay for the detection of the S protein of SARS-CoV-2. A detailed study on the binding properties of aptamers to the receptor-binding domain of the S protein in search of aptamer pairs forming a sandwich is presented. Screening of aptamer pairs and optimization of assay conditions led to the development of a laboratory-based sandwich assay able to detect 21 ng/mL (270 pM) of the protein with negligible cross-reactivity with the other known human coronaviruses. The detection of 375 pg of the protein in viral transport medium demonstrates the compatibility of the assay with clinical specimens. Finally, successful detection of the S antigen in nasopharyngeal swab samples collected from suspected patients further establishes the suitability of the assay for screening purposes as a complementary tool to assist in the control of the pandemic., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The development of antimicrobial surfaces has become a high priority in recent times. There are two ongoing worldwide health crises: the COVID-19 pandemic provoked by the SARS-CoV-2 virus and the antibiotic-resistant diseases provoked by bacteria resistant to antibiotic-based treatments. The need for antimicrobial surfaces against bacteria and virus is a common factor to both crises. Most extended strategies to prevent bacterial associated infections rely on chemical based-approaches based on surface coatings or biocide encapsulated agents that release chemical agents. A critical limitation of these chemistry-based strategies is their limited effectiveness in time while grows the concerns about the long-term toxicity on human beings and environment pollution. An alternative strategy to prevent bacterial attachment consists in the introduction of physical modification to the surface. Pursuing this chemistry-independent strategy, we present a fabrication process of surface topographies [one-level (micro, nano) and hierarchical (micro+nano) structures] in polypropylene (PP) substrates and discuss how wettability, topography and patterns size influence on its antibacterial properties. Using nanoimprint lithography as patterning technique, we report as best results 82 and 86% reduction in the bacterial attachment of E. coli and S. aureus for hierarchically patterned samples compared to unpatterned reference surfaces. Furthermore, we benchmark the mechanical properties of the patterned PP surfaces against commercially available antimicrobial films and provide evidence for the patterned PP films to be suitable candidates for use as antibacterial functional surfaces in a hospital environment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Elsevier B.V. All rights reserved.)

Investigation of photoinduced electron transfer (PET) in a series of experimentally reported complexes of fullerene with phosphangulene oxides shows that the replacement of O atoms in the bridge of phosphangulene with S atoms promotes efficient and ultrafast ET from phosphangulene oxide to fullerene in PGOOSS⊃C60 and PGOSSS⊃C60 complexes. The results obtained can be useful for the development of photovoltaic devices based on phosphangulenes.

The marine toxin tetrodotoxin (TTX) poses a great risk to public health safety due to its severe paralytic effects after ingestion. Seafood poisoning caused by the consumption of contaminated marine species like pufferfish due to its expansion to nonendemic areas has increased the need for fast and reliable detection of the toxin to effectively implement prevention strategies. Liquid chromatography-mass spectrometry is considered the most accurate method, although competitive immunoassays have also been reported. In this work, we sought to develop an aptamer-based assay for the rapid, sensitive, and cost-effective detection of TTX in pufferfish. Using capture-SELEX combined with next-generation sequencing, aptamers were identified, and their binding properties were evaluated. Finally, a highly sensitive and user-friendly hybrid antibody-aptamer sandwich assay was developed with superior performance compared to several assays reported in the literature and commercial immunoassay kits. The assay was successfully applied to the quantification of TTX in pufferfish extracts, and the results obtained correlated very well with a competitive magnetic bead-based immunoassay performed in parallel for comparison. This is one of the very few works reported in the literature of such hybrid assays for small-molecule analytes whose compatibility with field samples is also demonstrated.

The human brain consists of specialized areas that flexibly interact to form a multitude of functional networks. Complementary to this notion of modular organization, brain function has been shown to vary along a smooth continuum across the whole cortex. We demonstrate a mathematical framework that accounts for both of these perspectives: harmonic modes. We calculate the harmonic modes of the brain's functional connectivity graph, called "functional harmonics," revealing a multi-dimensional, frequency-ordered set of basis functions. Functional harmonics link characteristics of cortical organization across several spatial scales, capturing aspects of intra-areal organizational features (retinotopy, somatotopy), delineating brain areas, and explaining macroscopic functional networks as well as global cortical gradients. Furthermore, we show how the activity patterns elicited by seven different tasks are reconstructed from a very small subset of functional harmonics. Our results suggest that the principle of harmonicity, ubiquitous in nature, also underlies functional cortical organization in the human brain., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Multimorbidity is common among older adults from low- and middle-income countries (LMICs). Social participation has a role in protecting against negative health consequences, yet its association with multimorbidity is unclear, particularly in LMICs. Thus, this study investigated the relationship between physical multimorbidity and social participation among older adults across 6 LMICs., Method: Cross-sectional, community-based data including adults aged 65 years and older from 6 LMICs were analyzed from the WHO Study on Global AGEing and adult health survey. The association between 11 individual chronic conditions or the number of chronic conditions (independent variable) and social participation (range 0-10 with higher scores indicating greater social participation; dependent variable) was assessed by multivariable linear regression analysis., Results: 14,585 individuals (mean age 72.6 [SD 11.5] years; 54.9% females) were included. Among individual conditions, hearing problems, visual impairment, and stroke were significantly associated with lower levels of social participation. Overall, an increasing number of chronic conditions was dose-dependently associated with lower levels of social participation (e.g., ≥4 vs 0 conditions: β = -0.26 [95% CI = -0.39, -0.13]). The association was more pronounced among males than females., Discussion: Older people with multimorbidity had lower levels of social participation in LMICs. Future longitudinal studies are warranted to further investigate temporal associations, and whether addressing social participation can lead to better health outcomes among older people with multimorbidity in LMICs., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Well-defined fullerene-PEG conjugates, C 60 -PEG ( 1 ) and two C 70 -PEG ( 2 and 3 with the addition sites on ab- [6,6] and cc- [6,6]-junctions), were prepared from their corresponding Prato monoadduct precursors. The resulting highly water-soluble fullerene-PEG conjugates 1 - 3 were evaluated for their DNA-cleaving activities and reactive oxygen species (ROS) generation under visible light irradiation. Unexpectedly, photoinduced cleavage of DNA by C 60 -PEG 1 was much higher than that by C 70 -PEG 2 and 3 with higher absorption intensity, especially in the presence of an electron donor (NADH). The preference of photoinduced ROS generation from fullerene-PEG conjugates 1 - 3 via the type II (energy transfer) or the type I (electron transfer) photoreaction was found to be dependent on the fullerene core (between C 60 and C 70 ) and functionalization pattern of C 70 (between 2 and 3 ). This was clearly supported by the electron transfer rate obtained from cyclic voltammetry data and computationally estimated relative rate of each step of the type II and the type I reactions, with the finding that type II energy transfer reactions occurred in the inverted Marcus regime while type I electron transfer reactions proceeded in the normal Marcus regime. This finding on the disparity in the pathways of photoinduced reactions ( type I versus type II ) provides insights into the behavior of photosensitizers in water and the design of photodynamic therapy drugs., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Current state-of-the-art functional magnetic resonance imaging (fMRI) offers remarkable imaging quality and resolution, yet, the intrinsic dimensionality of brain dynamics in different states (wakefulness, light and deep sleep) remains unknown. Here we present a method to reveal the low dimensional intrinsic manifold underlying human brain dynamics, which is invariant of the high dimensional spatio-temporal representation of the neuroimaging technology. By applying this intrinsic manifold framework to fMRI data acquired in wakefulness and sleep, we reveal the nonlinear differences between wakefulness and three different sleep stages, and successfully decode these different brain states with a mean accuracy across participants of 96%. Remarkably, a further group analysis shows that the intrinsic manifolds of all participants share a common topology. Overall, our results reveal the intrinsic manifold underlying the spatiotemporal dynamics of brain activity and demonstrate how this manifold enables the decoding of different brain states such as wakefulness and various sleep stages., (© 2021. The Author(s).)

Photoinduced electron transfer is studied in a series of inclusion complexes of structurally modified phenine nanotubes (pNT) with C 70 using the TD-DFT method. Analysis of electronic properties of the complexes shows that the electron transfer is infeasible in pNT_4d⊃C 70 built on the tetrameric array of [6]cyclo-meta-phenylene ([6]CMP) units. However, replacing one or more [6]CMP units with a coronene moiety enables electron transfer from pNT to C 70 . The generation of the charge separated states from the lowest locally excited states occurs on a sub-nanosecond time scale. Depending on the number of the [6]CMP units, the charge recombination rate varies from 1.8 ⋅ 10 7 to 3.1 ⋅ 10 2  s -1 , i. e., five orders of magnitude., (© 2021 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

A number of non-covalently bound donor-acceptor dyads, consisting of C 60 as the electron acceptor and cycloparaphenylene (CPP) as the electron donor, have been reported. A hypsochromic shift of the charge transfer (CT) band in polar medium has been found in [10]CPP⊃Li + @C 60 . To explore this anomalous effect, we study inclusion complexes [10]CPP⊃Li + @C 60 -MP, [10]CPP⊃C 60 -MPH + , and [10]CPP⊃C 60 -PPyMe + formed by fulleropyrrolidine derivatives and [10]CPP using the DFT/TDDFT approach. We show that the introduction of a positively charged fragment into fullerene stabilizes CT states that become the lowest-lying excited states. These charge-separated states can be generated by the decay of locally excited states on a nanosecond to picosecond time scale. The distance of the charged fragment to the center of the fullerenic cage and its accessibility to the solvent determine the strength of the hypsochromic shift., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Dopamine (DA) is one of the main neurotransmitters found in the central nervous system and has a vital role in the function of dopaminergic (DArgic) neurons. A progressive loss of this specific subset of cells is one of the hallmarks of age-related neurodegenerative disorders such as Parkinson's disease (PD). Symptomatic therapy for PD has been centered in the precursor l-DOPA administration, an amino acid precursor of DA that crosses the blood-brain barrier (BBB) while DA does not, although this approach presents medium- to long-term side effects. To overcome this limitation, DA-nanoencapsulation therapies are actively being searched as an alternative for DA replacement. However, overcoming the low yield of encapsulation and/or poor biodistribution/bioavailability of DA is still a current challenge. Herein, we report the synthesis of a family of neuromelanin bioinspired polymeric nanoparticles. Our system is based on the encapsulation of DA within nanoparticles through its reversible coordination complexation to iron metal nodes polymerized with a bis-imidazol ligand. Our methodology, in addition to being simple and inexpensive, results in DA loading efficiencies of up to 60%. In vitro , DA nanoscale coordination polymers (DA-NCPs) exhibited lower toxicity, degradation kinetics, and enhanced uptake by BE(2)-M17 DArgic cells compared to free DA. Direct infusion of the particles in the ventricle of rats in vivo showed a rapid distribution within the brain of healthy rats, leading to an increase in striatal DA levels. More importantly, after 4 days of nasal administrations with DA-NCPs equivalent to 200 μg of the free drug per day, the number and duration of apomorphine-induced rotations was significantly lower from that in either vehicle or DA-treated rats performed for comparison purposes. Overall, this study demonstrates the advantages of using nanostructured DA for DA-replacement therapy.

Theories of epidemiologic transition analyze the shift in causes of mortality due to changes in risk factors over time, and through processes of urbanization and development by comparing risk factors between countries or over time. These theories do not account for health inequities such as those resulting from environmental injustice, in which minority and lower income residents are more likely to be exposed to environmental hazards or have less access to environmental goods. Neighborhoods with histories of environmental injustice are also at risk for gentrification as they undergo environmental improvements and new greening projects. We aimed to understand how environmental injustice, urban renewal and green gentrification could inform the understanding of epidemiologic risk transitions. We examined 7 case neighborhoods in cities in the United States and Western Europe which were representative in terms of city region and type, which 1) had experienced a history of environmental injustice and 2) exhibited evidence of recent processes of urban renewal and/or gentrification. In each city, we conducted semi-structured qualitative interviews (n = 172) with city representatives, activists, non-profits, developers and residents. Respondents reported health implications of traditional (heavy pollutants, poor social conditions), transitional (decontamination, new amenities), new (gentrification, access to amenities), and emerging (displacement, climate-related risks, re-emergence of traditional exposures) exposures. Respondents reported renewed, complexified and overlapping exposures leading to poor mental and physical health and to new patterns of health inequity. Our findings point to the need for theories of environmental and epidemiologic risk transitions to incorporate analysis of trends 1) on a city-scale, acknowledging that segregation and patterns of environmental injustice have created unequal conditions within cities and 2) over a shorter and more recent time period, taking into account worsening patterns of social inequity in cities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chemically active Janus particles sustain non-equilibrium spatial variations in the chemical composition of the suspending solution; these induce hydrodynamic flow and (self-)motility of the particles. Direct mapping of these fields has so far proven to be too challenging. Therefore, indirect methods are needed, e.g., deconvolving the response of "tracer" particles to the activity-induced fields. Here, we study experimentally the response of silica particles, sedimented at a wall, to active Pt/silica Janus particles. The latter are either immobilized at the wall, with the symmetry axis perpendicular or parallel to the wall, or motile. The experiments reveal complex effective interactions that are dependent on the configuration and on the state of motion of the active particle. Within the framework of a coarse-grained model, the behavior of tracers near an immobilized Janus particle can be captured qualitatively once activity-induced osmotic flows on the wall are considered., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

The low efficacy of current conventional treatments for bacterial infections increases mortality rates worldwide. To alleviate this global health problem, we propose drug-free enzyme-based nanomotors for the treatment of bacterial urinary-tract infections. We develop nanomotors consisting of mesoporous silica nanoparticles (MSNPs) that were functionalized with either urease (U-MSNPs), lysozyme (L-MSNPs), or urease and lysozyme (M-MSNPs), and use them against nonpathogenic planktonic Escherichia coli . U-MSNPs exhibited the highest bactericidal activity due to biocatalysis of urea into NaHCO 3 and NH 3 , which also propels U-MSNPs. In addition, U-MSNPs in concentrations above 200 μg/mL were capable of successfully reducing 60% of the biofilm biomass of a uropathogenic E. coli strain. This study thus provides a proof-of-concept, demonstrating that enzyme-based nanomotors are capable of fighting infectious diseases. This approach could potentially be extended to other kinds of diseases by selecting appropriate biomolecules.

Low cost, multinary colloidal quantum dots (QDs) based on environmentally friendly elements, with bright, narrow-width, tunable near-infrared (NIR) luminescence are promising alternatives to Cd and Pb chalcogenide QDs for in vivo bio-imaging, LED and sensing applications. Herein, we demonstrate Pb/Cd free solution-processed colloidal luminescent Ag 2 ZnSnS 4 -ZnS (AZTS-ZnS) core-shell QDs with precise control over the ZnS shell thickness and thereby its optical properties. Unlike indium based multinary (I-III-VI group) core-shell QDs these nanocrystals show a narrow photoluminescence (PL) full width at half maximum (fwhm) of 105-110 meV in the first NIR window. By monitoring the starting AZTS core size, we achieve tunable emission over a small NIR window in these QDs with the best PL quantum yield (PLQY) of 17.4%., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The discovery of the GFP-type dye DFHBI that becomes fluorescent upon binding to an RNA aptamer, termed Spinach, led to the development of a variety of fluorogenic RNA systems that enable genetic encoding of living cells. In view of increasing interest in small RNA aptamers and the scarcity of their photophysical characterisation, this paper is a model study on Baby Spinach, a truncated Spinach aptamer with half its sequence. Fluorescence and fluorescence excitation spectra of DFHBI complexes of Spinach and Baby Spinach are known to be similar. Surprisingly, a significant divergence between absorption and fluorescence excitation spectra of the DFHBI/RNA complex was observed on conditions of saturation at large excess of RNA over DFHBI. Since absorption spectra were not reported for any Spinach-type aptamer, this effect is new. Quantitative modelling of the absorption spectrum based on competing dark and fluorescent binding sites could explain it. However, following reasoning of fluorescence lifetimes of bound DFHBI, femtosecond-fluorescence lifetime profiles would be more supportive of the notion that the abnormal absorption spectrum is largely caused by trans-isomers formed  within the cis-bound DFHBI/RNA complex. Independent of the origin, the unexpected discrepancy between absorption and fluorescence excitation spectra allows for easily accessed screening and insight into the efficiency of a fluorogenic dye/RNA system.

One strategy to decrease the incidence of hospital-acquired infections is to avoid the survival of pathogens in the environment by the development of surfaces with antimicrobial activity. To study the antibacterial behaviour of active surfaces, different approaches have been developed of which ISO 22916 is the standard. To assess the performance of different testing methodologies to analyse the antibacterial activity of hydrophobic surface patterned plastics as part of a Horizon 2020 European research project. Four different testing methods were used to study the antibacterial activity of a patterned film, including the ISO 22916 standard, the immersion method, the touch-transfer inoculation method, and the swab inoculation method, this latter developed specifically for this project. The non-realistic test conditions of the ISO 22916 standard showed this method to be non-appropriate in the study of hydrophobic patterned surfaces. The immersion method also showed no differences between patterned films and smooth controls due to the lack of attachment of testing bacteria on both surfaces. The antibacterial activity of films could be demonstrated by the touch-transfer and the swab inoculation methods, that more precisely mimicked the way of high-touch surfaces contamination, and showed to be the best methodologies to test the antibacterial activity of patterned hydrophobic surfaces. A new ISO standard would be desirable as the reference method to study the antibacterial behaviour of patterned surfaces.

Enzyme-powered nanomotors are an exciting technology for biomedical applications due to their ability to navigate within biological environments using endogenous fuels. However, limited studies into their collective behavior and demonstrations of tracking enzyme nanomotors in vivo have hindered progress toward their clinical translation. Here, we report the swarming behavior of urease-powered nanomotors and its tracking using positron emission tomography (PET), both in vitro and in vivo. For that, mesoporous silica nanoparticles containing urease enzymes and gold nanoparticles were used as nanomotors. To image them, nanomotors were radiolabeled with either 124 I on gold nanoparticles or 18 F-labeled prosthetic group to urease. In vitro experiments showed enhanced fluid mixing and collective migration of nanomotors, demonstrating higher capability to swim across complex paths inside microfabricated phantoms, compared with inactive nanomotors. In vivo intravenous administration in mice confirmed their biocompatibility at the administered dose and the suitability of PET to quantitatively track nanomotors in vivo. Furthermore, nanomotors were administered directly into the bladder of mice by intravesical injection. When injected with the fuel, urea, a homogeneous distribution was observed even after the entrance of fresh urine. By contrast, control experiments using nonmotile nanomotors (i.e., without fuel or without urease) resulted in sustained phase separation, indicating that the nanomotors' self-propulsion promotes convection and mixing in living reservoirs. Active collective dynamics, together with the medical imaging tracking, constitute a key milestone and a step forward in the field of biomedical nanorobotics, paving the way toward their use in theranostic applications., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Circularly polarized light (CPL) is currently receiving much attention as a key ingredient for next-generation information technologies, such as quantum communication and encryption. CPL photon generation used in those applications is commonly realized by coupling achiral optical quantum emitters to chiral nanoantennas. Here, we explore a different strategy consisting in exciting a nanosphere-the ultimate symmetric structure-to produce CPL emission along an arbitrary direction. Specifically, we demonstrate chiral emission from a silicon nanosphere induced by an electron beam based on two different strategies: either shifting the relative phase of degenerate orthogonal dipole modes or interfering electric and magnetic modes. We prove these concepts both theoretically and experimentally by visualizing the phase and polarization using a fully polarimetric four-dimensional cathodoluminescence method. Besides their fundamental interest, our results support the use of free-electron-induced light emission from spherically symmetric systems as a versatile platform for the generation of chiral light with on-demand control over the phase and degree of polarization.

Self-testing is a procedure for characterizing quantum resources with the minimal level of trust. Up to now it has been used as a device-independent certification tool for particular quantum measurements, channels, and pure entangled states. In this work we introduce the concept of self-testing more general entanglement structures. More precisely, we present the first self-tests of an entangled subspace-the five-qubit code and the toric code. We show that all quantum states maximally violating a suitably chosen Bell inequality must belong to the corresponding code subspace, which remarkably includes also mixed states.

The evolution of new protein functions is dependent upon inherent biophysical features of proteins. Whereas, it has been shown that changes in protein dynamics can occur in the course of directed molecular evolution trajectories and contribute to new function, it is not known whether varying protein dynamics modify the course of evolution. We investigate this question using three related ß-lactamases displaying dynamics that differ broadly at the slow timescale that corresponds to catalytic turnover yet have similar fast dynamics, thermal stability, catalytic, and substrate recognition profiles. Introduction of substitutions E104K and G238S, that are known to have a synergistic effect on function in the parent ß-lactamase, showed similar increases in catalytic efficiency toward cefotaxime in the related ß-lactamases. Molecular simulations using Protein Energy Landscape Exploration reveal that this results from stabilizing the catalytically-productive conformations, demonstrating the dominance of the synergistic effect of the E014K and G238S substitutions in vitro in contexts that vary in terms of sequence and dynamics. Furthermore, three rounds of directed molecular evolution demonstrated that known cefotaximase-enhancing mutations were accessible regardless of the differences in dynamics. Interestingly, specific sequence differences between the related ß-lactamases were shown to have a higher effect in evolutionary outcomes than did differences in dynamics. Overall, these ß-lactamase models show tolerance to protein dynamics at the timescale of catalytic turnover in the evolution of a new function., (Copyright © 2020 Alejaldre, Lemay-St-Denis, Perez Lopez, Sancho Jodar, Guallar and Pelletier.)

During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2 ) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.

Recently synthesized porphyrin-cycloparaphenylene (ZnP-[10]CPP) junction is a powerful platform to develop useful organic photovoltaic devices. In this work, we computationally study photoinduced electron transfer processes in the supramolecular complex ZnP-[10]CPP⊃C 60 and its Li + -doped derivative. The most striking finding is charge-separated (CS) bands in ZnP-[10]CPP⊃Li + @C 60 with opposite response to solvent polarity. Besides CS bands that demonstrate a bathochromic shift, there exist CS transitions showing a rarely observed hypsochromic shift. The rates of energy transfer, charge separation, and charge recombination in the supramolecular complexes are computed by using the semiclassical approach. These estimates suggest that the both types of CS states can be efficiently populated in polar media by decay of locally excited states.

A triquinoline cationic moiety (TQ⋅H + ) has recently been designed as a novel molecular unit for supramolecular chemistry. In addition to some useful features, TQ⋅H + has strong electron-acceptor properties, which renders the molecular cation a unique element in nanochemistry. TQ⋅H + is found to form complexes with coronene (COR) and cycloparaphenylene (CPP). In this work, we report a computational study of photoinduced electron transfer in supramolecular complexes TQ⋅H + -COR, TQ⋅H + ⊂[12]CPP and (TQ⋅H + -COR)⊂[12]CPP. The electron-transfer rates are estimated by using the semi-classical approach. The results are compared with the data previously obtained for a structurally similar inclusion complex Li + @C 60 ⊂[10]CPP. In particular, we found a red solvatochromic shift for charge-shift bands in the TQ⋅H + -complexes unlike a blueshift showed by Li + @C 60 ⊂[10]CPP. This distinction is explored in terms of electronic and structural features of the systems., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)