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  • DNA dioxygenases Tet2/3 regulate gene promoter accessibility and chromatin topology in lineage-specific loci to control epithelial differentiation

    Chen, G-D.; Fatima, I.; Xu, Q,; Rozhkova, E.; Fessing, Michael Y.; Mardaryev, Andrei N.; Sharov, A.A.; Xu, G-L.; Botchkarev, Vladimir A. (2023-01)
    Execution of lineage-specific differentiation programs requires tight coordination between many regulators including Ten-eleven translocation (TET) family enzymes, catalyzing 5-methylcytosine oxidation in DNA. Here, by using Keratin 14–Cre–driven ablation of Tet genes in skin epithelial cells, we demonstrate that ablation of Tet2/Tet3 results in marked alterations of hair shape and length followed by hair loss. We show that, through DNA demethylation, Tet2/Tet3 control chromatin accessibility and Dlx3 binding and promoter activity of the Krt25 and Krt28 genes regulating hair shape, as well as regulate interactions between the Krt28 gene promoter and distal enhancer. Moreover, Tet2/Tet3 also control three-dimensional chromatin topology in Keratin type I/II gene loci via DNA methylation–independent mechanisms. These data demonstrate the essential roles for Tet2/3 in establishment of lineage-specific gene expression program and control of Dlx3/Krt25/Krt28 axis in hair follicle epithelial cells and implicate modulation of DNA methylation as a novel approach for hair growth control.
  • Investigation into the development of novel lanthanide-based luminescent colorants for application to textiles and paper materials

    Lewis, D.M.; Broadbent, P.J.; Rigout, M.L.A.; Carr, C.M.; Seaton, Colin C.; Swift, Thomas (2023)
    This article describes the synthesis and application of lanthanide-based luminophores for visualisation under short wavelength ultraviolet (UV) activation (typically 254 nm). Luminophores are chemical compounds which re-emit light of longer wavelength than typical fluorescence and phosphorescence, following photoexcitation, because of efficient energy transfer from the ligands to the lanthanide ion emission levels. The luminophores described in this article are all derived from europium and terbium metal complexes and cover the complete colour gamut. Selection of appropriate ligands allows for water solubility or water insolubility (if required pigment or disperse “dye” applications). Similar to dyeing or printing processes, the anionic complexes can be applied to polyamide fibres or to cellulosic fibres, whereas dispersions of the non-ionic complexes are suitable for polyester or cellulose acetate fibre application. The water-soluble derivatives are also suitable for ink-jet printing and the water-insoluble derivatives are suitable for lithographic or intaglio paper printing. The novel complexes are excited by radiation below 300 nm and thus cannot be activated by sunlight (the earth's atmosphere prevents light below about 300 nm reaching the surface). Accordingly, the photo-stability of the dyed materials and prints obtained is excellent. These materials could be used in security marking applications, for example bank-notes and passports, where they could replace the current fluorophores that are rendered visible under near UV light (typically 365 nm) illumination but exhibit relatively poor photo-stability. The development of an RGB (red, green and blue) colour palette for inkjet printing based on these innovative luminophores will significantly support the design of digitally printed security features.
  • Metal-organic frameworks as potential agents for extraction and delivery of pesticides and agrochemicals

    Mahmoud, L.A.M.; dos Reis, R.A.; Chen, X.; Ting, V.P.; Nayak, Sanjit (2022-12)
    Pesticide contamination is a global issue, affecting nearly 44% of the global farming population, and disproportionately affecting farmers and agricultural workers in developing countries. Despite this, global pesticide usage is on the rise, with the growing demand of global food production with increasing population. Different types of porous materials, such as carbon and zeolites, have been explored for the remediation of pesticides from the environment. However, there are some limitations with these materials, especially due to lack of functional groups and relatively modest surface areas. In this regard, metal-organic frameworks (MOFs) provide us with a better alternative to conventionally used porous materials due to their versatile and highly porous structure. Recently, a number of MOFs have been studied for the extraction of pesticides from the environment as well as for targeted and controlled release of agrochemicals. Different types of pesticides and conditions have been investigated, and MOFs have proved their potential in agricultural applications. In this review, the latest studies on delivery and extraction of pesticides using MOFs are systematically reviewed, along with some recent studies on greener ways of pest control through the slow release of chemical compounds from MOF composites. Finally, we present our insights into the key issues concerning the development and translational applications of using MOFs for targeted delivery and pesticide control.
  • Metal-organic frameworks and their biodegradable composites for controlled delivery of antimicrobial drugs

    Livesey, T.C.; Mahmoud, L.A.M.; Katsikogianni, Maria G.; Nayak, Sanjit (2023-01)
    Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition to ongoing efforts on preventive strategies and infection control, there is ongoing research towards the development of novel vaccines, antimicrobial agents, and optimised diagnostic practices to address AMR. However, developing new therapeutic agents and medicines can be a lengthy process. Therefore, there is a parallel ongoing worldwide effort to develop materials for optimised drug delivery to improve efficacy and minimise AMR. Examples of such materials include functionalisation of surfaces so that they can become self-disinfecting or non-fouling, and the development of nanoparticles with promising antimicrobial properties attributed to their ability to damage numerous essential components of pathogens. A relatively new class of materials, metal-organic frameworks (MOFs), is also being investigated for their ability to act as carriers of antimicrobial agents, because of their ultrahigh porosity and modular structures, which can be engineered to control the delivery mechanism of loaded drugs. Biodegradable polymers have also been found to show promising applications as antimicrobial carriers; and, recently, several studies have been reported on delivery of antimicrobial drugs using composites of MOF and biodegradable polymers. This review article reflects on MOFs and polymer-MOF composites, as carriers and delivery agents of antimicrobial drugs, that have been studied recently, and provides an overview of the state of the art in this highly topical area of research.
  • RNA-sequencing muscle plasticity to resistance exercise training and disuse in youth and older age

    Fernandez-Gonzalo, R.; Willis, Craig R.G.; Etheridge, T.; Deane, C.S. (2022-12)
    Maintenance of skeletal muscle mass and function is critical to health and wellbeing throughout the lifespan. However, disuse through reduced physical activity (e.g., sedentarism), immobilisation, bed rest or microgravity has significant adverse effects on skeletal muscle health. Conversely, resistance exercise training (RET) induces positive muscle mass and strength adaptations. Several studies have employed microarray technology to understand the transcriptional basis of muscle atrophy and hypertrophy after disuse and RET, respectively, to devise fully effective therapeutic interventions. More recently, rapidly falling costs have seen RNA-sequencing (RNA-seq) increasingly applied in exploring muscle adaptations to RET and disuse. The aim of this review is to summarise the transcriptional responses to RET or disuse measured via RNA-seq in young and older adults. We also highlight analytical considerations to maximise the utility of RNA-seq in the context of skeletal muscle research. The limited number of muscle transcriptional signatures obtained thus far with RNA-seq are generally consistent with those obtained with microarrays. However, RNA-seq may provide additional molecular insight, particularly when combined with data-driven approaches such as correlation network analyses. In this context, it is essential to consider the most appropriate study design parameters as well as bioinformatic and statistical approaches. This will facilitate the use of RNA-seq to better understand the transcriptional regulators of skeletal muscle plasticity in response to increased or decreased use.
  • Carbon and nitrogen isotope analysis for dietary reconstruction and carbon and nitrogen incremental dentine analysis

    Delaney, s.; Murphy, E.; Beaumont, Julia; Cassidy, L.; Drain, D.; Gillig, N.; Gormley, S.; Halstead, L.; Jackson, I.; Jones, M.; et al. (Transport Infrastructure Ireland, 2022-12)
    In 2015, a previously unknown enclosed settlement and burial ground was found near the summit of a low hill in Ranelagh townland, just north of Roscommon town. The site—officially designated Ranelagh 1, and hereafter referred to variously as ‘the Ranelagh site’, ‘the site at Ranelagh’ or simply ‘Ranelagh’—was excavated over a 54-week period by Excavation Director Shane Delaney for Irish Archaeological Consultancy (IAC) Ltd between October 2015 and October 20161 . Excavations revealed that the site was established during the fourth century AD; for over 1,000 years, until the final phase of burial activity proper concluded there shortly after AD 1400, the site would have been a prominent feature in both the geographical and psychological landscape of the time. Cillín (children’s) burials continued at the site until about AD 1650, further asserting this prominence.
  • Editorial: Women in integrative physiology: 2021

    Helfer, Gisela; Kadmiel, M.; Jethwa, P.H. (2022-09)
  • Co-designing an intervention to improve the process of deprescribing for older people living with frailty in the United Kingdom

    Silcock, Jonathan; Marques, Iuri; Olaniyan, Janice; Raynor, D.K.; Baxter, H.; Gray, N.; Zaidi, S.T.R.; Peat, George W.; Fylan, Beth; Breen, Liz; et al. (Elsevier, 2023-02)
    Background: In older people living with frailty, polypharmacy can lead to preventable harm like adverse drug reactions and hospitalisation. Deprescribing is a strategy to reduce problematic polypharmacy. All stakeholders should be actively involved in developing a person-centred deprescribing process that involves shared decision-making. Objective: To co-design an intervention, supported by a logic model, to increase the engagement of older people living with frailty in the process of deprescribing. Design: Experience-based co-design is an approach to service improvement, which uses service users and providers to identify problems and design solutions. This was used to create a person-centred intervention with the potential to improve the quality and outcomes of the deprescribing process. A ‘trigger film’ showing older people talking about their healthcare experiences was created and facilitated discussions about current problems in the deprescribing process. Problems were then prioritised and appropriate solutions were developed. Review located the solutions in the context of current processes and procedures. An ideal care pathway and a complex intervention to deliver better care were developed. Setting and participants: Older people living with frailty, their informal carers and professionals living and/or working in West Yorkshire, England, UK. Deprescribing was considered in the context of primary care. Results: The current deprescribing process differed from an ideal pathway. A complex intervention containing seven elements was required to move towards the ideal pathway. Three of these elements were prototyped and four still need development. The complex intervention responded to priorities about (a) clarity for older people about what was happening at all stages in the deprescribing process and (b) the quality of one-to-one consultations. Conclusions: Priorities for improving the current deprescribing process were successfully identified. Solutions were developed and structured as a complex intervention. Further work is underway to (a) complete the prototyping of the intervention and (b) conduct feasibility testing.
  • Psychology for the Common Good: The Interdependence of Citizenship, Justice, and Well-being across the Globe

    Prilleltensky, I.; Di Martino, Salvatore; Ness, O. (Frontiers in Psychology, 2022-11)
  • Design of a graphene oxide-BODIPY conjugate for glutathione depletion and photodynamic therapy

    Reina, G.; Ruiz Estrada, Amalia; Richichi, B.; Biagiotti, G.; Giacomazzo, G.E.; Jacquemin, L.; Nishina, Y.; Ménard-Moyon, C.; Al-Jamal, W.T.; Bianco, A. (2022-01)
    Boron dipyrromethene derivates (BODIPYs) are promising photosensitisers (PSs) for cancer treatment using photodynamic therapy (PDT). This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivate for glutathione (GSH) depletion and PDT. The functionalisation of GO with a 3,5-dichloro-8-(4-boronophenyl) BODIPY via a diol derivatisation with the phenyl boronic acid moiety at the meso position of the BODIPY core, allowed to preserve the intrinsic properties of GO. We demonstrated that both chlorine atoms were substituted by GSH in the presence of glutathione transferase (GST), inducing a relevant bathochromic shift in the absorption/emission features and thus generating the active PS. Ex vitro assessment using cell lysates containing cytoplasmatic GST revealed the intracellular catalytic mechanism for the nucleophilic substitution of the GO-BODIPY adduct with GSH. Confocal microscopy studies showed important differences in the cellular uptake of free BODIPY and GO-BODIPY and revealed the coexistence of GO-BODIPY, GO-BODIPY-GS, and GO-BODIPY-GS2 species inside vesicles and in the cytoplasm of the cells after 24 h of incubation. In vitro biocompatibility and safety of GO and GO-BODIPY were evaluated in 2D and 3D models of prostate adenocarcinoma cells (PC-3), where no toxicity was observed up to 100 µg ml−1 of GO/GO-BODIPY in all treated groups 24 h post-treatment (cell viability > 90%). Only a slight decrease to 80% at 100 µg ml−1 was observed after 48 h of incubation. We demonstrated the efficacy of a GO adduct containing an α-chlorine-substituted BODIPY for the simultaneous depletion of intracellular GSH and the photogeneration of reactive oxygen species using a halogen white light source (5.4 mW cm−2) with a maximum in the range of 500–800 nm, which significantly reduced cell viability (<50%) after irradiation. Our study provides a new vision on how to apply BODIPY derivates and potentiate the toxicity of PDT in prostate and other types of cancer.
  • When stuff gets old: material surface characteristics and the visual perception of material change over time

    De Korte, Ellen E.M.; Logan, A.J.; Bloj, Marina (2022-11)
    Materials’ surfaces change over time due to chemical and physical processes. These processes can significantly alter a material’s visual appearance, yet we can recognise the material as the same. The present study examined the extent of changes the human visual system can detect in specific materials over time. Participants (N = 5) were shown images of different materials (Banana, Copper, Leaf) from an existing calibrated set of photographs. Participants indicated which image pair (of the 2 pairs shown) displayed the largest difference. Estimated perceptual scales showed that observers were able to rank the images of aged materials systematically. Next, we examined the role that global and local changes in material surface colour play in the perception of material change. We altered the information about colour and geometrical distribution in the images used in the first experiment, and participants repeated the task with the altered images. Our results showed significant differences between individual observers. Most importantly, participants’ ability to rank the images varied with material type. The leaf images were particularly affected by our alteration of the geometrical distribution. Together, our findings show the factors contributing to the perception of material change over time.
  • Using routine healthcare data to evaluate the impact of the Medicines at Transitions Intervention (MaTI) on clinical outcomes of patients hospitalised with heart failure: protocol for the Improving the Safety and Continuity Of Medicines management at Transitions of care (ISCOMAT) cluster randomised controlled trial with embedded process evaluation, health economics evaluation and internal pilot

    Moreau, L.A.; Holloway, I.; Fylan, Beth; Hartley, S.; Cundill, B.; Fergusson, A.; Alderson, S.; Alldred, David P.; Bojke, C.; Breen, Liz; et al. (2022-04)
    Introduction Heart failure affects 26 million people globally, approximately 900 thousand people in the UK, and is increasing in incidence. Appropriate management of medicines for heart failure at the time of hospital discharge reduces readmissions, improves quality of life and increases survival. The Improving the Safety and Continuity Of Medicines management at Transitions (ISCOMAT) trial tests the effectiveness of the Medicines at Transition Intervention (MaTI), which aims to enhance self-care and increase community pharmacy involvement in the medicines management of heart failure patients. Methods and analysis ISCOMAT is a parallel-group cluster randomised controlled trial, randomising 42 National Health Service trusts with cardiology wards in England on a 1:1 basis to implement the MaTI or treatment as usual. Around 2100 patients over the age of 18 admitted to hospital with heart failure with at least moderate left ventricular systolic dysfunction within the last 5 years, and planned discharge to the geographical area of the cluster will be recruited. The MaTI consists of training for staff, a toolkit for participants, transfer of discharge information to community pharmacies and a medicines reconciliation/review. Treatment as usual is determined by local policy and practices. The primary outcome is a composite of all-cause mortality and heart failure-related hospitalisation at 12 months postregistration obtained from national electronic health records. The key secondary outcome is continued prescription of guideline-indicated therapies at 12 months measured via patient-reported data and Hospital Episode Statistics. The trial contains a parallel mixed-methods process evaluation and an embedded health economics study.
  • The Bioarchaeology of Disability: A population-scale approach to investigating disability, physical impairment, and care in archaeological communities

    Bohling, Solange N.; Croucher, Karina T.; Buckberry, Jo (2022-09)
    Objective: This research introduces ‘The Bioarchaeology of Disability’ (BoD), a population-scale approach which allows for a comprehensive understanding of disability in past communities through a combination of palaeopathological, funerary, and documentary analyses. Methods: The BoD consists of three phases: 1) Contextualisation includes period-specific literature review; 2) Data collection consists of palaeopathological re-analysis of individuals with physical impairment and collation of mortuary treatment data; and 3) Analysis incorporates qualitative and quantitative comparison of the funerary treatment of individuals with and without physical impairment to explore contemporary perceptions of disability. Materials: The BoD is demonstrated through a case study investigation of disability in later Anglo-Saxon England (c.8th-11th centuries AD) which included four burial populations (Ntotal=1,543; Nimpaired=28). Results: Individuals with disability could be buried with normative or non-normative treatment (e.g., stone/clay inclusions, non-normative body positioning), and in marginal, non-marginal, and central locations. Conclusions: The overall funerary variation for individuals with disability was relatively slight, which may suggest that political and religious factors were influencing normative funerary treatment of disabled individuals. The funerary variability that was observed in disabled individuals was probably influenced by individual and community-specific beliefs. Significance: This research describes a population-scale approach to archaeological disability studies that can be replicated in other archaeological contexts. Limitations: Individuals with non-skeletal physical impairment (e.g., soft tissue, mental) cannot be analysed osteologically and are not considered by the BoD. Suggestions for further research: The BoD should be applied to different archaeological communities around the world to better understand disability in the past.
  • The osteological evidence for execution in Anglo-Saxon England

    Mattison, A.; Williams-Ward, Michelle L.; Buckberry, Jo; Hadley, D.M.; Holgate, R. (BAR Publishing, 2022)
    This paper reviews the osteological evidence for execution in Anglo-Saxon England, which, in the cases of modern analysis, can reveal considerable detail about the methods of decapitation, in particular, and it also provides a critical appraisal of the considerably less reliable antiquarian reports. We suggest that secure evidence for execution, principally decapitation, can be identified through modern osteological analysis but it is limited, and we also argue that assertions made in antiquarian excavation reports about apparent examples of execution need to be treated with caution.
  • The dark satanic mills: Evaluating patterns of health in England during the Industrial Revolution

    Buckberry, Jo; Crane-Kramer, G. (2022-12)
    Objective: this research seeks to investigate the impact the Industrial Revolution had on the population of England. Materials: Pre-existing skeletal data from 1154 pre-Industrial (1066–1700AD) and 4157 industrial (1700–1905) skeletons from 21 cemeteries (N = 5411). Methods: Context number, sex, age-at-death, stature and presence/absence of selected pathological conditions were collated. The data were compared using chi square, Kolmogorov-Smirnov, t-tests and logistic regression (α = 0.01). Results: There was a statistically significant increase in cribra orbitalia, periosteal reactions, rib lesions, fractures, rickets, osteoporosis, osteoarthritis, enamel hypoplasia, dental caries and periapical lesions in the industrial period. Osteomyelitis decreased from the pre-industrial to industrial period. Conclusion: Our results confirm the Industrial Revolution had a significant negative impact on human health, however the prevalence of TB, treponemal disease, maxillary sinusitis, osteomalacia, scurvy, gout and DISH did not change, suggesting these diseases were not impacted by the change in environmental conditions. Significance: This is the largest study of health in the Industrial Revolution that includes non-adults and adults and considers age-at-death alongside disease status to date. This data supports the hypothesis that the Rise of Industry was associated with a significant decline in general health, but not an increase in all pathologies. Limitations: This meta-analysis relies upon previously gathered data and diagnosis from a large number of researchers. Incomplete skeletons were often excluded from analyses. Few rural cemeteries were available for inclusion. Suggestions for further research: Data from unpublished and ongoing excavations should be investigated. Comparison with historical data is encouraged.
  • Routine omics collection is a golden opportunity for European human research in space and analog environments

    Cope, H.; Willis, Craig R.G.; MacKay, M.J.; Rutter, L.A.; Toh, L.S.; Williams, P.M.; Herranz, R.; Borg, J.; Bezdan, D.; Giacomello, S.; et al. (2022-10)
    Widespread generation and analysis of omics data have revolutionized molecular medicine on Earth, yet its power to yield new mechanistic insights and improve occupational health during spaceflight is still to be fully realized in humans. Nevertheless, rapid technological advancements and ever-regular spaceflight programs mean that longitudinal, standardized, and cost-effective collection of human space omics data are firmly within reach. Here, we consider the practicality and scientific return of different sampling methods and omic types in the context of human spaceflight. We also appraise ethical and legal considerations pertinent to omics data derived from European astronauts and spaceflight participants (SFPs). Ultimately, we propose that a routine omics collection program in spaceflight and analog environments presents a golden opportunity. Unlocking this bright future of artificial intelligence (AI)-driven analyses and personalized medicine approaches will require further investigation into best practices, including policy design and standardization of omics data, metadata, and sampling methods.
  • Multi-isotopic study of the earliest medieval inhabitants of Santiago de Compostela (Galicia, Spain)

    Perez-Ramallo, P.; Grandal-d´Anglade, A.; Organista, E.; Santos, E.; Chivall, D.; Rodriguez-Varela, R.; Gotherstrom, A.; Etxeberria, F.; Ilgner, J.; Fernandes, R.; et al. (Springer, 2022-10)
    Santiago de Compostela is, together with Rome and Jerusalem, one of the three main pilgrimage and religious centres for Catholicism. The belief that the remains of St James the Great, one of the twelve apostles of Jesus Christ, is buried there has stimulated, since their reported discovery in the 9th century AD, a significant flow of people from across the European continent and beyond. Little is known about the practical experiences of people living within the city during its rise to prominence, however. Here, for the first time, we combine multi-isotope analysis (δ13C, δ15N, δ18Oap, δ13Cap, and 87Sr/86Sr) and radiocarbon dating (14C) of human remains discovered at the crypt of the Cathedral of Santiago to directly study changes in diet and mobility during the first three centuries of Santiago’s emergence as an urban centre (9th-12th centuries AD). Together with assessment of the existing archaeological data, our radiocarbon chronology broadly confirms historical tradition regarding the first occupation of the site. Isotopic analyses reveal that the foundation of the religious site attracted migrants from the wider region of the northwest corner of the Iberian Peninsula, and possibly from further afield. Stable isotope analysis of collagen, together with information on tomb typology and location, indicates that the inhabitants of the city experienced increasing socioeconomic diversity as it became wealthier as the hub of a wide network of pilgrimage. Our research represents the potential of multidisciplinary analyses to reveal insights into the origins and impacts of the emergence of early pilgrimage centres on the diets and status of communities within Christian medieval Europe and beyond.
  • Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age

    Deane, C.S.; Phillips, B.E.; Willis, Craig R.G.; Wilkinson, D.J.; Smith, K.; Higashitani, N.; Williams, J.P.; Szewczyk, N.J.; Atherton, P.J.; Higashitani, A.; et al. (2022-09)
    Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14-3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation.
  • Interfacial cocrystallization using oily phase via liquid−liquid phase separation

    Sajid, Asim; Alsirawan, M.H.D. Bashir; Seaton, Colin C.; Swift, Thomas; Pagire, Sudhir K.; Vangala, Venu R.; Kelly, Adrian L.; Paradkar, Anant R. (2022-10)
    Cocrystals consist of two molecules bonded together in a single crystal lattice giving rise to wide applications including improving solubility of poorly soluble pharmaceuticals. Cocrystallization reaction occurs in the oily phase of liquid–liquid phase separation (LLPS) after it is mixed with coformers. Indomethacin–saccharin cocrystal formation was monitored in situ, and the kinetics of crystallization were determined. The crystallization rates show that the process can be proposed to prevent unwanted oily phase formation during LLPS.

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