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Understanding electron transport with electroactive microbes is key to engineering effective and scalable bio-electrochemical technologies. Much of this electron transfer occurs through small-molecule flavin mediators that perform one-electron transfers in abiotic systems but concerted two-electron transfer in biological systems, rendering abiotic systems less efficient. To boost efficiency, the principles guiding flavin electron transfer must be elucidated, necessitating a tunable system. Ionic liquids (ILs) offer such a platform due to their chemical diversity. In particular, imidazolium-containing ILs that resemble the amino acid histidine are bio-similar electrolytes that enable the study of flavin electron transfer. Using the model IL 1-ethyl-3-methylimidazolium ([Emim][BF 4 ]), we observe concerted two-electron transfer between flavin mononucleotide and an unmodified glassy carbon electrode surface, while a one-electron transfer occurs in standard inorganic electrolytes. This work demonstrates the power of ILs to enable the mechanistic study of biological electron transfer, providing critical guidelines for improving electrochemical technologies based on these biological properties., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

As more is learned about the benefits of microbes, their potential to prevent and treat disease is expanding. Microbial therapeutics are less burdensome and costly to produce than traditional molecular drugs, often with superior efficacy. Yet, as with most medicines, controlled dosing and delivery to the area of need remain key challenges for microbes. Advances in materials to control small-molecule delivery are expected to translate to microbes, enabling similar control with equivalent benefits. In this perspective, recent advances in living biotherapeutics are discussed within the context of new methods for their controlled release. The integration of these advances provides a roadmap for the design, synthesis, and analysis of controlled microbial therapeutic delivery systems., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The serendipitous discovery of an unorthodox ionic cocrystallization system using 2-mercaptothiazolium-based ionic liquids as a crystallization milieu paves the way for the first report of crystal structures of long-chain 1-bromoalkanes. We used single crystal X-ray diffraction to determine the structures of 1-bromo-hexadecane and 1-octadecane with the aid of ionic liquids with alkyl side chains of equivalent length to the bromoalkane at room temperature. Long alkyl chains in combination with σ-hole interactions from strategically placed sulfur motifs synergistically function to crystallize the 1-bromoalkanes.

A fundamental challenge underlying the design principles of ionic liquids (ILs) entails a lack of understanding into how tailored properties arise from the molecular framework of the constituent ions. Herein, we present detailed analyses of novel functional ILs containing a triarylmethyl (trityl) motif. Combining an empirically driven molecular design, thermophysical analysis, X-ray crystallography, and computational modeling, we achieved an in-depth understanding of structure-property relationships, establishing a coherent correlation with distinct trends between the thermophysical properties and functional diversity of the compound library. We observe a coherent relationship between melting ( T m ) and glass transition ( T g ) temperatures and the location and type of chemical modification of the cation. Furthermore, there is an inverse correlation between the simulated dipole moment and the T m / T g of the salts. Specifically, chlorination of the ILs both reduces and reorients the dipole moment, a key property controlling intermolecular interactions, thus allowing for control over T m / T g values. The observed trends are particularly apparent when comparing the phase transitions and dipole moments, allowing for the development of predictive models. Ultimately, trends in structural features and characterized properties align with established studies in physicochemical relationships for ILs, underpinning the formation and stability of these new lipophilic, low-melting salts., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Architected biomaterials, as well as sound and music, are constructed from small building blocks that are assembled across time- and length-scales. Here we present a novel deep learning-enabled integrated algorithmic workflow to merge the two concepts for radical discovery of de novo protein materials, exploiting musical creativity as the foundation, and extrapolating through a recursive method to increase protein complexity by successively injecting protein chemistry into the process. Indeed, music is one of the few universal expressions that can create bridges between cultures, find associations between seemingly unrelated concepts, and can be used as a novel way to generate bio-inspired designs that derive functions from the imaginations of the creative mind. Earlier work has offered a pathway to convert proteins into sound, and sound into proteins. Here we build on this paradigm and translate a piece of classical music into matter. Based on Bach's Goldberg variations, we offer a series of case studies to convert the musical data imagined by the composer into protein design, and folded into a 3D structure using deep learning. The quest we seek to address is to identify semblances, or memories, or information content in such musical creation, that offers new insights into pattern relationships between distinct manifestations of information. Using basic local alignment search tool analysis, we find that several fragments of the new proteins display similarities to existing protein sequences found in proteobacteria among other organisms, especially in regions of low complexity and repetitive motifs. The resulting protein forms the basis for iterative musical composition, and an evolutionary paradigm that defines a variational pathway for melodic development, complementing conventional creative or mathematical methods. This paper broadens the concept of what is understood as bio-inspiration to include a broad array of systems created by humans, animals, or other natural mechanisms., (© 2021 IOP Publishing Ltd.)

In this work, we investigated the effects of a single covalent link between hydrogen bond donor species on the behavior of deep eutectic solvents (DESs) and shed light on the resulting interactions at molecular scale that influence the overall physical nature of the DES system. We have compared sugar-based DES mixtures, 1:2 choline chloride/glucose [DES (g) ] and 1:1 choline chloride/trehalose [DES (t) ]. Trehalose is a disaccharide composed of two glucose units that are connected by an α-1,4-glycosidic bond, thus making it an ideal candidate for comparison with glucose containing DES (g) . The differential scanning calorimetric analysis of these chemically close DES systems revealed significant difference in their phase transition behavior. The DES (g) exhibited a glass transition temperature of -58 °C and behaved like a fluid at higher temperatures, whereas DES (t) exhibited marginal phase change behavior at -11 °C and no change in the phase behavior at higher temperatures. The simulations revealed that the presence of the glycosidic bond between sugar units in DES (t) hindered free movement of sugar units in trehalose, thus reducing the number of interactions with choline chloride compared to free glucose molecules in DES (g) . This was further confirmed using quantum theory of atoms in molecule analysis that involved determination of bond critical points (BCPs) using Laplacian of electron density. The analysis revealed a significantly higher number of BCPs between choline chloride and sugar in DES (g) compared to DES (t) . The DES (g) exhibited a higher amount of charge transfer between the choline cation and sugar, and better interaction energy and enthalpy of formation compared to DES (t) . This is a result of the ability of free glucose molecules to completely surround choline chloride in DES (g) and form a higher number of interactions. The entropy of formation for DES (t) was slightly higher than that for DES (g) , which is a result of fewer interactions between trehalose and choline chloride. In summary, the presence of the glycosidic bond between the sugar units in trehalose limited their movement, thus resulting in fewer interactions with choline chloride. This limited movement in turn diminishes the ability of the hydrogen bond donor to disrupt the molecular packing within the lattice structure of the hydrogen bond acceptor (and vice versa), a crucial factor that lowers the melting point of DES mixtures. This inability to move due to the presence of the glycosidic bond in trehalose significantly influences the physical state of the DES (t) system, making it behave like a semi-solid material, whereas DES (g) behaves like a liquid material at room temperature.

We developed lipid-like ionic liquids, containing 2-mercaptoimidazolium and 2-mercaptothiazolinium headgroups tethered to two long saturated alkyl chains, as carriers for in vitro delivery of plasmid HEK DNA into 293T cells. We employed a combination of modular design, synthesis, X-ray analysis, and computational modeling to rationalize the self-assembly and desired physicochemical and biological properties. The results suggest that thioamide-derived ionic liquids may serve as a modular platform for lipid-mediated gene delivery. This work represents a step toward understanding the structure-function relationships of these amphiphiles with long-range ordering and offering insight into design principles for synthetic vectors based on self-assembly behavior.

Numerous non-covalent inter-actions link together discrete mol-ecules in the crystal structure of the title compound, 2C 20 H 26 N 2 O 2 2+ ·4Cl - ·H 2 O {systematic name: 4-[(5-ethenyl-1-azonia-bicyclo-[2.2.2]octan-2-yl)(hy-droxy)meth-yl]-6-meth-oxy-quinolin-1-ium dichloride hemihydrate}. A combination of hydrogen bonding between acidic H atoms and the anions in the asymmetric unit forms a portion of the observed hydrogen-bonded network. π-π inter-actions between the aromatic portions of the cation appear to play a role in the formation of the long-range ordering. One ethyl-ene double bond was found to be disordered. The disorder extends to the neighboring carbon and hydrogen atoms., (© Anderson et al. 2021.)

Parent-of-origin-dependent (epi)genetic factors are important determinants of prenatal development that program adult phenotype. However, data on magnitude and specificity of maternal and paternal genome effects on fetal bone are lacking. We used an outbred bovine model to dissect and quantify effects of parental genomes, fetal sex, and nongenetic maternal effects on the fetal skeleton and analyzed phenotypic and molecular relationships between fetal muscle and bone. Analysis of 51 bone morphometric and weight parameters from 72 fetuses recovered at day 153 gestation (54% term) identified six principal components (PC1-6) that explained 80% of the variation in skeletal parameters. Parental genomes accounted for most of the variation in bone wet weight (PC1, 72.1%), limb ossification (PC2, 99.8%), flat bone size (PC4, 99.7%), and axial skeletal growth (PC5, 96.9%). Limb length showed lesser effects of parental genomes (PC3, 40.8%) and a significant nongenetic maternal effect (gestational weight gain, 29%). Fetal sex affected bone wet weight (PC1, p < 0.0001) and limb length (PC3, p < 0.05). Partitioning of variation explained by parental genomes revealed strong maternal genome effects on bone wet weight (74.1%, p < 0.0001) and axial skeletal growth (93.5%, p < 0.001), whereas paternal genome controlled limb ossification (95.1%, p < 0.0001). Histomorphometric data revealed strong maternal genome effects on growth plate height (98.6%, p < 0.0001) and trabecular thickness (85.5%, p < 0.0001) in distal femur. Parental genome effects on fetal bone were mirrored by maternal genome effects on fetal serum 25-hydroxyvitamin D (96.9%, p < 0.001) and paternal genome effects on alkaline phosphatase (90.0%, p < 0.001) and their correlations with maternally controlled bone wet weight and paternally controlled limb ossification, respectively. Bone wet weight and flat bone size correlated positively with muscle weight (r = 0.84 and 0.77, p < 0.0001) and negatively with muscle H19 expression (r = -0.34 and -0.31, p < 0.01). Because imprinted maternally expressed H19 regulates growth factors by miRNA interference, this suggests muscle-bone interaction via epigenetic factors., (© 2014 American Society for Bone and Mineral Research.)

Objective: To determine changes in Canine Brief Pain Inventory scores for dogs with osteoarthritis after administration of a monoclonal antibody (mAb) against nerve growth factor (NGF) that was modified by use of a proprietary process for administration to dogs., Animals: 11 adult dogs., Procedures: Dogs received the anti-NGF mAb (0.2 mg/kg, IV) at various evaluation times during the study period; at other evaluation times, dogs received an equivalent volume of PBS solution IV. Owners determined Canine Brief Pain Inventory pain severity (PS) and pain interference (PI) scores immediately before (baseline) and 2, 4, and 6 weeks after administration of the anti-NGF mAb; owners were unaware of the evaluation time at which the mAb had been administered., Results: Compared with baseline PS scores (median, 4.75; range, 0.75 to 8.5), dogs had significantly lower PS scores 2 weeks (median, 3; range, 1 to 5.5) and 4 weeks (median, 2.25; range, 0.25 to 7.25) after administration of anti-NGF mAb. Compared with baseline PI scores (median, 5.33; range, 1.17 to 9.33), dogs had significantly lower PI scores 2 weeks (median, 3; range, 0.67 to 6.83) and 4 weeks (median, 3.33; range, 0.67 to 6.67) after administration of anti-NGF mAb. The PS and PI scores 6 weeks after mAb administration were lower than baseline scores, although values were not significantly different., Conclusions and Clinical Relevance: Results of this study suggested the evaluated anti-NGF mAb decreased PS and PI scores for 4 weeks after administration. This treatment may be effective for alleviation of signs of pain in dogs with osteoarthritis for up to 4 weeks.

In veterinary medical education, the use of animals or cadaveric tissue as a component of teaching practice is common. Teachers are required, during the process of ethical review, to apply the 3 Rs principle (replacement, refinement, reduction) whenever they consider using animals during a teaching exercise. This often involves use of replacement strategies, such as utilization of video footage or simulation-based training. However, aside from legislative or ethical requirements imposed by a country's regulatory framework on the institution, students are often the key advocates for using alternative teaching practices that do not make use of animals. This has prompted many institutions with veterinary and other life sciences teaching programs to develop student-conscientious objection policies to the use of animals in teaching. In this article, we discuss the procedures implemented to make provision for student-conscientious objectors at a new Australian Veterinary School, at the University of Adelaide. We also describe the processes to provide information to students and faculty on this issue and to facilitate information gathering on alternatives.

Postnatal myofibre characteristics and muscle mass are largely determined during fetal development and may be significantly affected by epigenetic parent-of-origin effects. However, data on such effects in prenatal muscle development that could help understand unexplained variation in postnatal muscle traits are lacking. In a bovine model we studied effects of distinct maternal and paternal genomes, fetal sex, and non-genetic maternal effects on fetal myofibre characteristics and muscle mass. Data from 73 fetuses (Day153, 54% term) of four genetic groups with purebred and reciprocal cross Angus and Brahman genetics were analyzed using general linear models. Parental genomes explained the greatest proportion of variation in myofibre size of Musculus semitendinosus (80-96%) and in absolute and relative weights of M. supraspinatus, M. longissimus dorsi, M. quadriceps femoris and M. semimembranosus (82-89% and 56-93%, respectively). Paternal genome in interaction with maternal genome (P<0.05) explained most genetic variation in cross sectional area (CSA) of fast myotubes (68%), while maternal genome alone explained most genetic variation in CSA of fast myofibres (93%, P<0.01). Furthermore, maternal genome independently (M. semimembranosus, 88%, P<0.0001) or in combination (M. supraspinatus, 82%; M. longissimus dorsi, 93%; M. quadriceps femoris, 86%) with nested maternal weight effect (5-6%, P<0.05), was the predominant source of variation for absolute muscle weights. Effects of paternal genome on muscle mass decreased from thoracic to pelvic limb and accounted for all (M. supraspinatus, 97%, P<0.0001) or most (M. longissimus dorsi, 69%, P<0.0001; M. quadriceps femoris, 54%, P<0.001) genetic variation in relative weights. An interaction between maternal and paternal genomes (P<0.01) and effects of maternal weight (P<0.05) on expression of H19, a master regulator of an imprinted gene network, and negative correlations between H19 expression and fetal muscle mass (P<0.001), suggested imprinted genes and miRNA interference as mechanisms for differential effects of maternal and paternal genomes on fetal muscle.

The host response to titanium alloy (Ti-6Al-4V) is not always favorable as a fibrous layer may form at the skeletal tissue-device interface, causing aseptic loosening. Recently, sphene (CaTiSiO(5)) ceramics were developed by incorporating Ti in the Ca-Si system, and found to exhibit improved chemical stability. The aim of this study is to evaluate the in vitro response of human osteoblast-like cells, human osteoclasts and human microvascular endothelial cells to sphene ceramics and determine whether coating Ti-6Al-4V implants with sphene enhances anchorage to surrounding bone. The study showed that sphene ceramics support human osteoblast-like cell attachment with organized cytoskeleton structure and express increased mRNA levels of osteoblast-related genes. Sphene ceramics were able to induce the differentiation of monocytes to form functional osteoclasts with the characteristic features of f-actin and alpha(v)beta(3) integrin, and express osteoclast-related genes. Human endothelial cells were also able to attach and express the endothelial cell markers ZO-1 and VE-Cadherin when cultured on sphene ceramics. Histological staining, enzyme histochemistry and immunolabelling were used for identification of mineralized bone and bone remodelling around the coated implants. Ti-6Al-4V implants coated with sphene showed new bone formation and filled the gap between the implants and existing bone in a manner comparable to that of the hydroxyapatite coatings used as control. The new bone was in direct contact with the implants, whereas fibrous tissue formed between the bone and implant with uncoated Ti-6Al-4V. The in vivo assessment of sphene-coated implants supports our in vitro observation and suggests that they have the ability to recruit osteogenic cells, and thus support bone formation around the implants and enhance osseointegration.

Calcium phosphate ceramics are widely used as coating materials to orthopedic implants and are found to enhance initial bony ingrowth by stimulating osseous apposition to the implant surface. In this study, two novel calcium orthophosphate materials were selected for coating onto the commonly used orthopedic implant material Ti-6Al- 4V. One was calcium alkali orthophosphate with the crystalline phase Ca10[K/Na](PO4)7 with a small addition of SiO2 (AW-Si) and the other was calcium orthophosphate composed of 70 mol % fluorapatite, Ca10(PO4)6F2 and 30 mol % CaZr4(PO4)6 (FA7Z). The coated implants were placed in cortical and cortico-cancellous bone of sheep femur for six weeks. Retrieved samples were tested for osseointegration and mechanical strength. It was found that both coatings produced enhanced bone/implant contact rate compared to the control when implanted in cortico-cancellous bone. This study demonstrates that the two coatings have the capability of encouraging bone growth, and hence the potential for being used as coating materials on Ti implants.

A retrospective multi-centre study was carried out in order to compare outcomes between cemented and uncemented total hip arthoplasties (THA). A quantitative orthopaedic outcome assessment scoring system was devised in order to relate functional outcome to a numerical score, to allow comparison between treatments and amongst centres. The system combined a radiographic score and a clinical score. Lower scores reflect better outcomes than higher scores. Consecutive cases of THA were included from two specialist practices between July 2002 and December 2005. The study included 46 THA patients (22 uncemented THA followed for 8.3 +/- 4.7M and 24 cemented THA for 26.0 +/- 15.7M) with a mean age of 4.4 +/- 3.3 years at surgery. Multi-variable linear and logistical regression analyses were performed with adjustments for age at surgery, surgeon, follow-up time, uni- versus bilateral disease, gender and body weight. The differences between treatment groups in terms of functional scores or total scores were not significant (p > 0.05). Radiographic scores were different between treatment groups. However, these scores were usually assessed within two months of surgery and proved unreliable predictors of functional outcome (p > 0.05). The findings reflect relatively short-term follow-up, especially for the uncemented group, and do not include clinician-derived measures, such as goniometry and thigh circumference. Longer-term follow-up for the radiographic assessments is essential. A prospective study including the clinician-derived outcomes needs to be performed in order to validate the outcome instrument in its modified form.