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The protein complex of recombinant human insulin-like growth factor-1 and insulin‑like growth factor binding protein‑3 (rhIGF-1/rhIGFBP-3; mecasermin rinfabate), is an investigational product for the prevention of complications of prematurity. Delivery of rhIGF-1/rhIGFBP-3 is by continuous central line intravenous infusion in preterm infants until endogenous IGF-1 production begins. Protein-specific analytical methodologies were developed to evaluate the compatibility of rhIGF- 1/rhIGFBP-3 at low protein concentrations (∼2.5-10 μg/mL) expected when co-administered with other required medications in the NICU. Highly sensitive detection of the biologic potential degradants (fragments) and/or molecular modifications (oxidized species, aggregates) required the use of reversed-phase high-performance liquid chromatography and size-exclusion ultra-performance liquid chromatography coupled with mass spectrometric detection. We report on the quantification of rhIGF-1/rhIGFBP-3, its components and degradants, to a limit of quantitation of 3.1 μg/mL upon mixing with 24 commonly administered neonatal medications. Methods developed for the rhIGF-1/rhIGFBP-3 admixtures, optimized in studies with furosemide, caffeine citrate and ampicillin, demonstrated good reproducibility, linearity, and limit of detection/quantitation. Using these methods, no increase in degradation of rhIGF-1/rhIGFBP-3 components and no increase in oxidation or aggregation level was observed with caffeine citrate, while admixtures of rhIGF-1/rhIGFBP-3 with ampicillin yielded lower mass recovery of rhIGF-1/rhIGFBP-3 components, which likely resulted from adduct formation. Furosemide was found to be physically incompatible with rhIGF-1/rhIGFBP-3. Our findings support the use of these methodologies for detection of protein modifications under various clinical administration conditions, and additionally supplement physical compatibility data studies of ultra-low concentrations of rhIGF-1/rhIGFBP-3 post co-administration to preterm infants with other medications (manuscript in-preparation).

Malaria is a leading cause of death in children less than 5 years of age globally, and a common cause of fever in the returning North American traveler. New tools in the fight against malaria have been developed over the past decades: potent artemisinin derivatives; rapid diagnostic tests; long-lasting insecticidal bed nets; and a new vaccine, RTS,S/AS01. Thwarting these advances, parasite and Anopheles vector resistance are emerging. In the meantime, clinicians will continue to see malaria among febrile travelers from the tropics. Early recognition, diagnosis, and treatment can be lifesaving, but rely on the vigilance of frontline clinicians.

Conventionally, Te has primarily been used to improve the machinability of steel and its alloys. In this work, Te was used to refine the grains of an oxide-dispersion-strengthened (ODS) steel produced by additive manufacturing (AM) with fixed processing parameters. Addition of Te to the raw powder produced an ODS steel with a fine-grained microstructure, in contrast to the ODS steel manufactured without Te. Moreover, the addition of Te resulted in superior yield strength and ultimate tensile strength, which was attributed to the combined effects of grain refinement and the finer nanoparticles (NPs) composed of Te-rich composite NPs and Cr-rich NPs. For the first time, the AM technique was used to obtain grain and nanoparticle sizes of ~3.4 µm and 6 nm, respectively, from the Te-added ODS steel

Aberrant activity of the histone methyltransferase polycomb repressive complex 2 (PRC2) has been linked to several cancers, with small-molecule inhibitors of the catalytic subunit of the PRC2 enhancer of zeste homologue 2 (EZH2) being recently approved for the treatment of epithelioid sarcoma (ES) and follicular lymphoma (FL). Compounds binding to the EED subunit of PRC2 have recently emerged as allosteric inhibitors of PRC2 methyltransferase activity. In contrast to orthosteric inhibitors that target EZH2, small molecules that bind to EED retain their efficacy in EZH2 inhibitor-resistant cell lines. In this paper we disclose the discovery of potent and orally bioavailable EED ligands with good solubilities. The solubility of the EED ligands was optimized through a variety of design tactics, with the resulting compounds exhibiting in vivo efficacy in EZH2-driven tumors.

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P

Funder: Gerald Kerkut Charitable Trust; FundRef: http://dx.doi.org/10.13039/100012166, Funder: Rank Prize, Funder: NIHR Clinical Lectureship, Pregnancy 25-hydroxyvitamin D [25(OH)D] concentrations are associated with maternal and fetal health outcomes. Using physiological human placental perfusion and villous explants, we investigate the role of the placenta in regulating the relationships between maternal 25(OH)D and fetal physiology. We demonstrate active placental uptake of 25(OH)D3 by endocytosis, placental metabolism of 25(OH)D3 into 24,25-dihydroxyvitamin D3 and active 1,25-dihydroxyvitamin D [1,25(OH)2D3], with subsequent release of these metabolites into both the maternal and fetal circulations. Active placental transport of 25(OH)D3 and synthesis of 1,25(OH)2D3 demonstrate that fetal supply is dependent on placental function rather than simply the availability of maternal 25(OH)D3. We demonstrate that 25(OH)D3 exposure induces rapid effects on the placental transcriptome and proteome. These map to multiple pathways central to placental function and thereby fetal development, independent of vitamin D transfer. Our data suggest that the underlying epigenetic landscape helps dictate the transcriptional response to vitamin D treatment. This is the first quantitative study demonstrating vitamin D transfer and metabolism by the human placenta, with widespread effects on the placenta itself. These data demonstrate a complex interplay between vitamin D and the placenta and will inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy., CS was funded by a Gerald Kerkut Charitable Trust studentship and BA by Rank Prize and University of Southampton Vice Chancellor���s Studentships plus the MRC. KMG was supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator [NF-SI-0515-10042], NIHR Southampton 1000DaysPlus Global Nutrition Research Group [17/63/154], and NIHR Southampton Biomedical Research Centre [IS-BRC-1215-20004]), British Heart Foundation (RG/15/17/3174) and the US National Institute on Aging of the National Institutes of Health (Award No. U24AG047867). KSJ was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (ISBRC-1215-20014). The NIHR Cambridge Biomedical Research Centre is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Experimental work performed by KSJ and FH at MRC. EWL was supported by Dr Ann Prentice (UK Medical Research Council U105960371). The SWS has been supported by grants from Medical Research Council (MRC) (4050502589 [MRC LEU]), Dunhill Medical Trust, British Heart Foundation, Food Standards Agency, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, NIHR Oxford Biomedical Research Centre, University of Oxford, and the European Union���s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition, under grant agreement 289346 and the European Union���s Horizon 2020 research and innovation program (LIFECYCLE, grant agreement no. 733206). EC has been supported by the Wellcome Trust (201268/Z/16/Z) and an NIHR Clinical Lectureship. Work leading to these results was supported by the BBSRC (HDHL-Biomarkers, BB/P028179/1), as part of the ALPHABET project, supported by an award made through the ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 grant agreement number 696295. The proteomic analyses (SDG and AM) were financially supported by the National Institutes of Health (R21AI122389) and the Beckman Institute at the California Institute of Technology. This project has received funding from the European Union���s Horizon 2020 research and innovation program under the Marie Sk��odowska-Curie grant agreement InvADeRS no. 841172 to JMF. The electron microscopy image in Figure 2 was produced with help of the Biomedical imaging unit, Faculty of Medicine, University of Southampton.

Hepatic toxicosis caused by copper accumulation has been reported in most domestic species, as well as multiple small exotic mammals, including ferrets, fruit bats, and sugar gliders. The purpose of this study was to determine the signalments, clinical presentations, and histologic findings associated with hepatic copper accumulation in sugar gliders based on post-mortem histologic findings and retrospective analysis of reported antemortem clinical signs. Sugar gliders with histologic evidence of various hepatopathies were identified within the Northwest ZooPath archive. Sections of formalin-fixed, paraffin-embedded hepatic samples were stained for copper, and copper deposition was graded semiquantitatively. The prevalence of copper accumulation in the evaluated hepatopathies was 28%. Copper deposition was seen in all individuals with icterus and non-ataxia neurologic signs. Grossly, individuals with hepatic masses and nodules were 5.50 times more likely to have hepatic copper accumulation. Sugar gliders with biliary hyperplasia were 16.20 times more likely to have copper accumulation while all individuals with cholestasis had hepatic copper accumulation. The results of this study indicate that hepatic copper accumulation is frequently identified in post-mortem evaluation of sugar gliders with hepatopathy. Copper accumulation is frequently noted in individuals with icterus, neurologic abnormalities, hepatic masses, biliary hyperplasia, and cholestasis. This study details the prevalence of hepatic copper accumulation in sugar gliders and illustrates associations between copper hepatotoxicosis and other hepatic diseases.

The work herein describes the electrochemical detection of heavy metal ions, specifically cadmium and lead. The introduction and modification of functional groups such as Schiff bases leads to an enhanced sensitivity of the electrode to analytes. In this study, a platinum electrode has, for the first time, been modified with poly(3,4-ethylenedioxythiophene) (PEDOT/Schiff base) in CH2Cl2 containing Bu4NPF6 to detect cadmium(II) and lead(II) ions. The structures and morphologies of the polymer coatings were characterised via Fourier transform infrared spectroscopy and scanning electron microscopy, respectively. The electrochemical synthesis and redox state response in monomer-free synthesised films have been studied via cyclic voltammetry. Moreover, the effect of scan rate on the electrochemical behaviour of the modified electrodes was also studied. The voltammetric findings have been used to calculate the surface coverage required for the polymer films and the stability of polymer electrodes in the monomer-free solutions. Square wave voltammetry was applied for the determination of cadmium(II) and lead(II) ion concentrations and to assess the effects of pH on aqueous samples. The limits of detection for the modified electrode for cadmium(II) and lead(II) were found to be 0.95 μg L−1 and 1.84 μg L−1, respectively. These findings revealed that modified films can be considered good candidates for application in electrochemical detection devices.

Mutations in the cardiac ryanodine receptor type 2 (RyR2) have been linked to a variety of cardiac arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). RyR2 is regulated by calmodulin (CaM), and mutations that disrupt their interaction can cause aberrant calcium release, leading to an arrhythmia. It was recently shown that increasing the RyR2-CaM binding affinity could rescue a defective CPVT-related RyR2 channel to near wild-type behavior. However, the interactions that determine the binding affinity at the RyR2-CaM binding interface are not well understood. In this study, we identify the key domains and interactions, including several new interactions, involved in the binding of CaM to RyR2. Also, our comparison between the wild-type and V3599K mutant suggests how the RyR2-CaM binding affinity can be increased via a change in the central and N-terminal lobe binding contacts for CaM. This computational approach provides new insights into the effect of a mutation at the RyR2-CaM binding interface, and it may find utility in drug design for the future treatment of cardiac arrhythmias.

Roof-shaped host compounds trans-α,α,α′,α′-tetraphenyl-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethanol H3 and trans-α,α,α′,α′-tetra(p-chlorophenyl)-9,10-dihydro-9,10-ethanoanthracene-11,12-dimethanol H6 were assessed for their host potential and selectivity behaviour when presented with single or mixed guest solvents comprising o-xylene, m-xylene, p-xylene and ethylbenzene (o-Xy, m-Xy, p-Xy and EB). H3 included each solvent with 3:1 host:guest ratios, while the ratios preferred by H6 were more varied (4:3, 1:1 and 3:2). More importantly, the selectivity behaviour of these two host compounds was observed to be entirely different: H3 possessed only a very modest preference for o-Xy (37.9–68.2%) when recrystallized from various equimolar binary, ternary and quaternary guest mixtures, while H6 was considerably more selective, preferring m-Xy (the least favoured guest of H3) with selectivities ranging from 57.7 to 91.4% in analogous conditions. The latter result was obtained in o-Xy/m-Xy mixtures and demonstrates that H6 may be employed as a purification tool for mixtures of these two xylenes via host–guest chemistry protocols. A single crystal diffraction experiment on 3(H3)·o-Xy (containing the preferred guest of H3) revealed that the guest was retained in the host crystal by means of a singular (host)m-Ar–H···π(guest) interaction that measured 2.73 A (148°) as well as numerous other host···guest interactions involving only the aromatic protons of the free host phenyl groups and the guest methyl protons or aromatic carbons and protons (2.20–2.54 A, 121–125°). Thermal analyses explained the preference of H3 for o-Xy, while these were less informative for the complexes of H6.

Mass-transport-limited catalysis and membrane transport can be characterized by concentration profiles surrounding active surfaces. Scanning electrochemical microscopy (SECM) is a tool that has been used to measure concentration profiles; however, the presence and geometry of the tip can distort these profiles due to hindered diffusion, which in turn alters chemical behavior at the catalytic surface. To fully characterize the behavior of surface features such as catalytic sites, it is essential to account for and analytically remove the effect of tip presence. In this work, atomic force microscopy-based SECM (AFM-SECM) measurements over poly(tetrafluoroethylene) (PTFE) and gold electrode surfaces are used to measure negative and positive-feedback approach curves, respectively. By inversely fitting these approach curves with a finite element method (FEM) model, we derive kinetic and geometric tip parameters that characterize the effect of tip presence. Tip effects may be removed in the model to estimate concentration profiles and reaction properties for the case where no tip is present. A maximum 120% increase in the concentration at one tip radii above the surface is observed due to the presence of the tip, where the concentration field is compressed vertically, in proportion to surface feature size and tip separation. Conical AFM-SECM tips, with a higher ratio of tip height to the base size, introduce less concentration distortion than disk-shaped AFM-SECM tips.

Biodiesel is a renewable fuel with several advantages over petro-based fuels and is conventionally produced by the transesterification of triglycerides with alcohols. Chemical interesterification of triglycerides is a good alternative as compared to transesterification, as it yields a value-added compound, triacetin, as a co-product instead of the already abundant commodity, glycerol. In this work, interesterification of soybean oil was carried out with methyl acetate to co-produce biodiesel and triacetin, using calcined hydrotalcite as a heterogeneous base catalyst. Several base catalysts were tested for this reaction. Calcined Mg-Al hydrotalcite (Mg:Al mole ratio – 3:1) was found as the best catalyst for achieving 95.9 % conversion of soybean oil triglycerides in 4 h and yielding 5.3 % selectivity of triacetin along with the value-added intermediates - monoacetindiglycerides and diacetinmonoglycerides, produced with a selectivity of 46 % and 48.7 %, respectively. The optimum reaction conditions were found at an oil to methyl acetate mole ratio of 1:50, catalyst loading of 0.04 g/cm3 and a temperature of 200 oC. The catalysts were fully characterized before and after the reaction, and were found to possess high surface area with both basic and acidic sites. The effect of various reaction conditions on the rate of reaction, conversion of triglycerides and selectivity of triacetin were studied. The concentration profiles of the reactants, intermediates and products obtained at different temperatures were used to obtain the kinetic rate constants and the activation energy of each parallel step was evaluated. Reusability studies showed that the catalyst was stable and reusable up to three cycles.

Parkinson’s disease (PD) is a chronic neurological disorder associated with the misfolding of alpha-synuclein (α-syn) into aggregates within nerve cells that contribute to their neurodegeneration. Recent evidence suggests α-syn aggregation may begin in the gut and travel to the brain along the vagus nerve, with microbes potentially a trigger initiating α-syn misfolding. However, the effects α-syn alterations on the gut virome have not been investigated. In this study, we show longitudinal faecal virome changes in rats administered either monomeric or preformed fibrils (PFF) of α-syn directly into their enteric nervous system. Differential changes in rat viromes were observed when comparing monomeric and PFF α-syn, with alterations compounded by the addition of LPS. Changes in rat faecal viromes were observed after one month and did not resolve within the study’s five-month observational period. These results suggest that virome alterations may be reactive to host α-syn changes that are associated with PD development., Stockdale et al. assess longitudinal faecal virome changes in a rat model of Parkinson’s Disease (PD) in which either monomeric or preformed fibrils (PFF) of α-synuclein were administered directly into their enteric nervous system. They demonstrate that virome alterations are potentially reactive to host α-synuclein changes that are associated with PD development.

Coccoliths are plates of biogenic calcium carbonate secreted by calcifying marine phytoplankton; annually these phytoplankton are responsible for exporting >1 billion tonnes (1015 g) of calcite to the deep ocean. Rapid and reliable methods for assessing the degree of calcification are technically challenging because the coccoliths are micron sized and contain picograms (pg) of calcite. Here we pioneer an opto‐eletrochemical acid titration of individual coccoliths which allows 3D reconstruction of each individual coccolith via in situ optical imaging enabling direct inference of the coccolith mass. Coccolith mass ranging from 2 to 400 pg are reported herein, evidencing both inter‐ and intra‐species variation over four different species. We foresee this scientific breakthrough, which is independent of knowledge regarding the species and calibration‐free, will allow continuous monitoring and reporting of the degree of coccolith calcification in the changing marine environment., Acid dissolution enables 3D image reconstruction of coccoliths, providing mass estimation in the range of 2 to 400 picograms.

Lebanon is a Middle Eastern country located on the eastern Mediterranean coast. Compared to other countries in the MENA (Middle East North Africa) region, Lebanon is considered the richest in water resources. However, due to inadequate water management, Lebanese water resources are under stress. Water pollution is one of the main problems causing major concerns. The contamination of Lebanese surface water originates predominantly from the discharge of untreated municipal and industrial wastewater. With only a few studies investigating the level of water contamination in Lebanon, this research is the first to report the level of platinum in numerous rivers, three wastewater treatment plants, and two untreated sewage outfalls in coastal areas across Lebanon. To determine the platinum levels, an Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) method was developed and validated in compliance with the ICH guidelines. The method demonstrated acceptable sensitivity with LOQ and LOD equal to 2.35 and 0.56 ng L−1, respectively. The level of total platinum in the Lebanese water samples ranged between 22.44–53.32 ng L−1. These concentrations were all above the baseline concentration of platinum in tap water indicated by WHO and aligned with previous studies in other countries. Although the baseline concentration of platinum in Lebanese water resources is unknown and the source of the total platinum detected in this study could not be identified, these preliminary findings could serve as a foundation for future research.

Over the past 25 years, collective evidence has demonstrated that the DNA base-pair stack serves as a medium for charge transport chemistry in solution and on DNA-modified gold surfaces. Since this charge transport depends sensitively upon the integrity of the DNA base pair stack, perturbations in base stacking, as may occur with DNA base mismatches, lesions, and protein binding, interrupt DNA charge transport (DNA CT). This sensitivity has led to the development of powerful DNA electrochemical sensors. Given the utility of DNA electrochemistry for sensing and in response to recent literature, we describe critical protocols and characterizations necessary for performing DNA-mediated electrochemistry. We demonstrate DNA electrochemistry with a fully AT DNA sequence using a thiolated preformed DNA duplex and distinguish this DNA-mediated chemistry from that of electrochemistry of largely single-stranded DNA adsorbed to the surface. We also demonstrate the dependence of DNA CT on a fully stacked duplex. An increase in the percentage of mismatches within the DNA monolayer leads to a linear decrease in current flow for a DNA-bound intercalator, where the reaction is DNA-mediated; in contrast, for ruthenium hexammine, which binds electrostatically to DNA and the redox chemistry is not DNA-mediated, there is no effect on current flow with mismatches. We find that, with DNA as a well hybridized duplex, upon assembly, a DNA-mediated pathway facilitates the electron transfer between a well coupled redox probe and the gold surface. Overall, this report highlights critical points to be emphasized when utilizing DNA electrochemistry and offers explanations and controls for analyzing confounding results.

Cone calorimeter and controlled atmosphere cone calorimeter experiments were conducted on various samples. The intent of the tests was to examine the behavior of uniform and composite samples in a range of thicknesses, irradiances, and oxygen concentrations. Single, uniform layers of acrylonitrile butadiene styrene (ABS) were compared to a composite mix, comprising of ABS with a surface layer of cardboard and a secondary layer of polyethylene bubble wrap (intended to represent a potential storage arrangement). The horizontal samples have been tested at irradiances of 25 and 50 kW/m2 and oxygen concentrations of 20.95%, 17%, and 15% to examine a range of significant variables. Results for the uniform arrangement indicated various correlations, previously observed in the works of others, such as the relationships typically described between applied heat flux, ignitability, heat release rate and the effect of the introduction of hypoxic conditions. However, results were shown to change significantly when samples were arranged to feature composite layers. A hypothesized cause of the behavioral change, namely the soot and char residual introduced from the incomplete combustion of the cardboard layer, highlights further important variables that require consideration in material testing under hypoxic conditions. Such variables, namely specific material behaviors and sample orientation, must be sufficiently captured in the design methodologies of systems reliant upon the introduction of hypoxic conditions. It is concluded that sufficiently capturing a wider range of variables in burning materials under hypoxic conditions will introduce further design resilience and help optimize fire protection/prevention methods. (Less)

Antibiotic-resistant Gram-negative bacteria are emergent pathogens, causing millions of infections worldwide. While there are several classes of antibiotics that are effective against Gram-positive bacteria, the outer membrane (OM) of Gram-negative bacteria excludes high-molecular-weight hydrophobic antibiotics, making these species intrinsically resistant to several classes of antibiotics, including polyketides, aminocoumarins, and macrolides. The overuse of antibiotics such as β-lactams has also promoted the spread of resistance genes throughout Gram-negative bacteria, including the production of extended spectrum β-lactamases (ESBLs). The combination of innate and acquired resistance makes it extremely challenging to identify antibiotics that are effective against Gram-negative bacteria. In this study, we have demonstrated the synergistic effect of outer membrane-permeable cationic polyurethanes with rifampicin, a polyketide that would otherwise be excluded by the OM, on different strains of E. coli, including a clinically isolated uropathogenic multidrug-resistant (MDR) E. coli. Rifampicin combined with a low-dose treatment of a cationic polyurethane reduced the MIC in E. coli of rifampicin by up to 64-fold. The compositions of cationic polyurethanes were designed to have low hemolysis and low cell cytotoxicity while maintaining high antibacterial activity. Our results demonstrate the potential to rescue the large number of available OM-excluded antibiotics to target normally resistant Gram-negative bacteria via synergistic action with these cationic polyurethanes, acting as a novel antibiotic adjuvant class.

Wearable and implantable bioelectronics have experienced remarkable progress over the last decades. Bioelectronic devices provide seamless integration between electronics and biological tissue, offering unique functions for healthcare applications such as real-time and online monitoring and stimulation. Organic semiconductors and silicon-based flexible electronics have been dominantly used as materials for wearable and implantable devices. However, inherent drawbacks such as low electronic mobility, particularly in organic materials, instability, and narrow band gaps mainly limit their full potential for optogenetics and implantable applications. In this context, wide-band-gap (WBG) materials with excellent electrical and mechanical properties have emerged as promising candidates for flexible electronics. With a significant piezoelectric effect, direct band gap and optical transparency, and chemical inertness, these materials are expected to have practical applications in many sectors such as energy harvesting, optoelectronics, or electronic devices, where lasting and stable operation is highly desired. Recent advances in micro/nanomachining processes and synthesis methods for WBG materials led to their possible use in soft electronics. Considering the importance of WBG materials in this fast-growing field, the present paper provides a comprehensive Review on the most common WBG materials, including zinc oxide (ZnO) for II–VI compounds, gallium nitride (GaN) for III–V compounds, and silicon carbide (SiC) for IV–IV compounds. We first discuss the fundamental physical and chemical characteristics of these materials and their advantages for biosensing applications. We then summarize the fabrication techniques of wide-band-gap semiconductors, including how these materials can be transferred from rigid to stretchable and flexible substrates. Next, we provide a snapshot of the recent development of flexible WBG materials-based wearable and implantable devices. Finally, we conclude with perspectives on future research direction.

The integration of metal–organic frameworks (MOFs) with polymer fibres enables the formation of fibrous composite materials with advantages over traditional single-component polymer films and mixed-matrix membranes. In comparison with mixed-matrix membranes, MOF–polymer fibrous composites offer improved molecular transport through the material and easier access to the active sites of MOFs. These attributes make fibrous composites appealing for clothing, personal protective equipment, air purification and filtration, biomedical equipment and delivery of therapeutics, along with detection and sensing applications. In this Review, we outline approaches for the incorporation of MOFs into, or onto, polymer fibres and present some applications for MOF–polymer fabrics. The integration of MOFs and polymers can either occur prior to fibre formation (namely, MOF-first), via particle deposition (resulting in either covalent or non-covalent attachment) of MOFs to the fibre or by in situ MOF growth after fibre formation (namely, fibre-first). We focus on the structure–processing–activity relationships — for example, MOF loading, MOF crystal size, polymer concentration and processing parameters — that impact the behaviour of fibrous composites. We conclude with a discussion of research avenues that can advance this burgeoning field. Composites made from metal–organic frameworks and polymer fibres are gaining popularity in many applications because of their tailorable morphologies and properties. This Review summarizes various methods for fabricating these composites, explores structure–processing–activity relationships and discusses future research opportunities.

Introduction There are almost a million people with heart failure (HF) in the UK; the incidence increases sharply with age. Older adults receive less evidence-based therapy with few trials specifically examining therapeutic efficacy in older age groups representative of a contemporary UK HF population. Concern that efficacy is less in older adults may underlie under-prescription. With important recent advances in HF therapy, we reviewed the contemporary evidence base for any signal of different efficacy in older adults. Methods We reviewed recent RCTs of medical therapy for heart failure alongside meta-analyses updated with recent therapies including Angiotensin-Neprilysin inhibitors and SGLT2 inhibitors. For those trials in which effect size was presented for age subgroups we compared the effect size. Results Of 68 randomised controlled trials, 10 presented effect sizes for different age groups. The median average cut-off between younger and older age groups was 66 years (IQR 65 to 72.5 years) and the highest cut-off used was 75 years. The median hazard ratio was 0.77 (IQR 0.67 to 0.80) for the younger age group and 0.76 (IQR 0.73 to 0.88) for the older age group. In 8 of the 10 trials, the effect size in the oldest age group was statistically significant on its own including Sacubitril-Valsartan and Dapagliflozin. Conclusion When considering the medical therapeutic armamentarium for heart failure as a totality, there is no evidence it is any less effective in older adults than younger adults. The recent Zannad et al cross-trial analysis supported this showing significant additional life years in the patients over 80 years on HF therapy. Whilst there may be practical and frailty-related reasons for not prescribing life-prolonging therapy, the proportional survival benefits of these medications is similar in older adults. This should be utilised where practically possible and discussed with patients when making an informed choice.

Background Soil acidity causes an increase in the solubility of toxic aluminium (Al), inhibiting root growth and limiting plant access to soil water and nutrients. Toxicity of Al decreases growth and development more in Al-sensitive than Al-resistant wheat (Triticum aestivum L.) genotypes. Applying magnesium (Mg) may alleviate Al toxicity in acidic soil. It is unclear if growing Al-resistant wheat, coupled with Mg application, will enhance wheat growth and physiological responses in acidic soil. Wheat was grown in the reconstituted acidic soil profile in a three-factor glasshouse experiment comprising foliar Mg at [Mg] = 0 and 200 mg L-1 (using magnesium sulfate), wheat genotypes ES8 (Al sensitive) and ET8 (Al resistant), and four soil treatments [non-amended soil (pH0.1 M CaCl2 4.0); 100% of the recommended lime dose in subsoil to raise pH to 6.0; or 20 mg Mg kg-1 soil to the whole soil profile (as magnesium sulfate or magnesium chloride)]. Results Applying foliar Mg to Al-resistant wheat significantly increased shoot dry weight (24%), subsoil root dry weight (12%), subsoil coarse (>0.2 mm in diameter) root length (12%), net photosynthetic rate (28%), and total leaf area (10%) compared with plants not treated with foliar Mg. Combining foliar Mg application with subsoil liming increased the subsoil total root length by 1.3-fold compared with zero foliar Mg. Without foliar Mg, subsoil liming and soil Mg amendment significantly (by 10%) enhanced shoot growth and total leaf area compared with non-amended soil. Conclusion Growing an Al-resistant genotype coupled with applying Mg foliarly and to soil improved wheat growth in an acidic soil. © 2021 Society of Chemical Industry.