Recent advances in wearable sensor technologies offer new opportunities for improving dietary adherence. However, despite their tremendous promise, the potential of wearable chemical sensors for guiding personalized nutrition solutions has not been reported. Herein, we present an epidermal biosensor aimed at following the dynamics of sweat vitamin C after the intake of vitamin C pills and fruit juices. Such skin-worn noninvasive electrochemical detection of sweat vitamin C has been realized by immobilizing the enzyme ascorbate oxidase (AAOx) on flexible printable tattoo electrodes and monitoring changes in the vitamin C level through changes in the reduction current of the oxygen cosubstrate. The flexible vitamin C tattoo patch was fabricated on a polyurethane substrate and combined with a localized iontophoretic sweat stimulation system along with amperometric cathodic detection of the oxygen depletion during the enzymatic reaction. The enzyme biosensor offers a highly selective response compared to the common direct (nonenzymatic) voltammetric measurements, with no effect on electroactive interfering species such as uric acid or acetaminophen. Temporal vitamin C profiles in sweat are demonstrated using different subjects taking varying amounts of commercial vitamin C pills or vitamin C-rich beverages. The dynamic rise and fall of such vitamin C sweat levels is thus demonstrated with no interference from other sweat constituents. Differences in such dynamics among the individual subjects indicate the potential of the epidermal biosensor for personalized nutrition solutions. The flexible tattoo patch displayed mechanical resiliency to multiple stretching and bending deformations. In addition, the AAOx biosensor is shown to be useful as a disposable strip for the rapid in vitro detection of vitamin C in untreated raw saliva and tears following pill or juice intake. These results demonstrate the potential of wearable chemical sensors for noninvasive nutrition status assessments and tracking of nutrient uptake toward detecting and correcting nutritional deficiencies, assessing adherence to vitamin intake, and supporting dietary behavior change.

Multiple myeloma is the most common haematological malignancy yet currently it remains incurable. For decades the mainstay in therapy has been non-targeted approaches including genotoxic agents and immunosuppressants. With myeloma predominantly affecting an elderly population, who are vulnerable to aggressive therapy, these non-specific approaches have resulted in poor survival. However, in recent years an explosion of collaborative research into myeloma has identified molecular interactions between myeloma cells and the bone marrow microenvironment as promoting myeloma development and associated complications such as bone lesions due to osteolysis. At the same time, a better understanding of the adhesion molecules, cytokines and signalling pathways involved in myeloma has led to the development of new targeted therapies, which are improving the quality of life for patients and significantly extending median patient survival. This review explores the current understanding of molecular pathways that promote myeloma progression and lead to bone destruction, with particular reference to the influence of interactions with the bone marrow microenvironment. It describes molecular targets for therapy with reference to the new therapeutics and their improved efficacy. While the outlook for myeloma patients has improved in recent years as a result of these new approaches, drug resistance remains a problem and future therapies will also need to address the molecular mechanisms of resistance in order to improve further the outcome for patients with this disease.

Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.

Thrombomodulin (Thbd) exerts pleiotropic effects on blood coagulation, fibrinolysis, and complement system activity by facilitating the thrombin-mediated activation of protein C and thrombin-activatable fibrinolysis inhibitor and may have additional thrombin- and protein C (pC)-independent functions. In mice, complete Thbd deficiency causes embryonic death due to defective placental development. In this study, we used tissue-selective and temporally controlled Thbd gene ablation to examine the function of Thbd in adult mice. Selective preservation of Thbd function in the extraembryonic ectoderm and primitive endoderm via the Meox2Cre-transgene enabled normal intrauterine development of Thbd-deficient (Thbd−/−) mice to term. Half of the Thbd−/− offspring expired perinatally due to thrombohemorrhagic lesions. Surviving Thbd−/− animals only rarely developed overt thrombotic lesions, exhibited low-grade compensated consumptive coagulopathy, and yet exhibited marked, sudden-onset mortality. A corresponding pathology was seen in mice in which the Thbd gene was ablated after reaching adulthood. Supplementation of activated PC by transgenic expression of a partially Thbd-independent murine pC zymogen prevented the pathologies of Thbd−/− mice. However, Thbd−/− females expressing the PC transgene exhibited pregnancy-induced morbidity and mortality with near-complete penetrance. These findings suggest that Thbd function in nonendothelial embryonic tissues of the placenta and yolk sac affects through as-yet-unknown mechanisms the penetrance and severity of thrombosis after birth and provide novel opportunities to study the role of the natural Thbd-pC pathway in adult mice and during pregnancy.

Combating the ongoing COVID-19 pandemic has put the spotlight on nutritional support of the immune system through consumption of vitamins C and D. Accordingly, there are urgent demands for an effective on-the-spot multi-vitamin self-testing platform that monitors the levels of these immune-supporting micronutrients for guiding precision nutrition recommendations. Herein, we present a compact bioelectronic dual sensor chip aimed at frequent on-the-spot simultaneous monitoring of the salivary vitamin C and D dynamics. The new bioelectronic chip combines a new electrocatalytic vitamin C amperometric assay along with competitive vitamin D immunoassay on neighboring electrodes, to perform selective and cross-talk free detection of both vitamins in a 10-μL saliva sample within 25 min. The distinct vitamin C or D temporal profiles obtained for different individuals after vitamin supplementation indicate the potential of the new bioelectronic chip strategy for enhancing personalized nutrition towards guiding dietary interventions to meet individual nutrition needs and promote immune system health.