Carbodiimide-Driven Toughening of Interpenetrated Polymer Networks.

Recent work has demonstrated that temporary crosslinks in polymer networks generated by chemical "fuels" afford materials with large, transient changes in their mechanical properties. This can be accomplished in carboxylic-acid-functionalized polymer hydrogels using carbodiimides, which generate anhydride crosslinks with lifetimes on the order of minutes to hours. Here, the impact of the polymer network architecture on the mechanical properties of transiently crosslinked materials was explored. Single networks (SNs) were compared to interpenetrated networks (IPNs). Notably, semi-IPN precursors that give IPNs on treatment with carbodiimide give much higher fracture energies (i.e., resistance to fracture) and superior resistance to compressive strain compared to other network architectures. A precursor semi-IPN material featuring acrylic acid in only the free polymer chains yields, on treatment with carbodiimide, an IPN with a fracture energy of 2400 J/m2, a fourfold increase compared to an analogous semi-IPN precursor that yields a SN. This resistance to fracture enables the formation of macroscopic complex cut patterns, even at high strain, underscoring the pivotal role of polymer architecture in mechanical performance.

Silky Liquid Metal Electrodes for On-Skin Health Monitoring.

Next generation on-skin electrodes will require soft, flexible, and gentle materials to provide both high-fidelity sensing and wearer comfort. However, many commercially available on-skin electrodes lack these key properties due to their use of rigid hardware, harsh adhesives, uncomfortable support structures, and poor breathability. To address these challenges, this work presents a new device paradigm by joining biocompatible electrospun spider silk with printable liquid metal to yield an incredibly soft and scalable on-skin electrode that is strain-tolerant, conformable, and gentle on-skin. These electrodes, termed silky liquid metal (SLiM) electrodes, are found to be over five times more breathable than commercial wet electrodes, while the silk's intrinsic adhesion mechanism allows SLiM electrodes to avoid the use of harsh artificial adhesives, potentially decreasing skin irritation and inflammation over long-term use. Finally, the SLiM electrodes provide comparable impedances to traditional wet and other liquid metal electrodes, offering a high-fidelity sensing alternative with increased wearer comfort. Human subject testing confirmed the SLiM electrodes ability to sense electrophysiological signals with high fidelity and minimal irritation to the skin. The unique properties of the reported SLiM electrodes offer a comfortable electrophysiological sensing solution especially for patients with pre-existing skin conditions or surface wounds.

Forced labour risk is pervasive in the US land-based food supply.

Social risk assessments and case studies of labour conditions in food production primarily focus on specific subpopulations, regions and commodities. To date, research has not systematically assessed labour conditions against international standards across diverse, complex food products. Here we combine data on production, trade, labour intensity and qualitative risk coding to quantitatively assess the risk of forced labour embedded in the US land-based food supply, building on our previous assessment of fruits and vegetables. We demonstrate that animal-based proteins, processed fruits and vegetables, and discretionary foods are major contributors to forced labour risk and that 62% of total forced labour risk stems from domestic production or processing. Our findings reveal the widespread risk of forced labour present in the US food supply and the necessity of collaborative action across all countries-high, middle and low income-to eliminate reliance on labour exploitation.

Measurement of diets that are healthy, environmentally sustainable, affordable, and equitable: A scoping review of metrics, findings, and research gaps.

Introduction: Research on the impacts of dietary patterns on human and planetary health is a rapidly growing field. A wide range of metrics, datasets, and analytical techniques has been used to explore the role of dietary choices/constraints in driving greenhouse gas (GHG) emissions, environmental degradation, health and disease outcomes, and the affordability of food baskets. Many argue that each domain is important, but few have tackled all simultaneously in analyzing diet-outcome relationships. Methods: This paper reviews studies published between January 2015 and December 2021 (inclusive) that examined dietary patterns in relation to at least two of the following four thematic pillars: (i) planetary health, including, climate change, environmental quality, and natural resource impacts, (ii) human health and disease, (iii) economic outcomes, including diet cost/affordability, and (iv) social outcomes, e.g., wages, working conditions, and culturally relevant diets. We systematically screened 2,425 publications by title and abstract and included data from 42 eligible publications in this review. Results: Most dietary patterns used were statistically estimated or simulated rather than observed. A rising number of studies consider the cost/affordability of dietary scenarios in relation to optimized environmental and health outcomes. However, only six publications incorporate social sustainability outcomes, which represents an under-explored dimension of food system concerns. Discussion: This review suggests a need for (i) transparency and clarity in datasets used and analytical methods; (ii) explicit integration of indicators and metrics linking social and economic issues to the commonly assessed diet-climate-planetary ecology relationships; (iii) inclusion of data and researchers from low- and middle-income countries; (iv) inclusion of processed food products to reflect the reality of consumer choices globally; and (v) attention to the implications of findings for policymakers. Better understanding is urgently needed on dietary impacts on all relevant human and planetary domains simultaneously.

Chemically Fueled Reinforcement of Polymer Hydrogels.

Carbodiimide-fueled anhydride bond formation has been used to enhance the mechanical properties of permanently crosslinked polymer networks, giving materials that exhibit transitions from soft gels to covalently reinforced gels, eventually returning to the original soft gels. Temporary changes in mechanical properties result from a transient network of anhydride crosslinks, which eventually dissipate by hydrolysis. Over an order of magnitude increase in the storage modulus is possible through carbodiimide fueling. The time-dependent mechanical properties can be modulated by the concentration of carbodiimide, temperature, and primary chain architecture. Because the materials remain rheological solids, new material functions such as temporally controlled adhesion and rewritable spatial patterns of mechanical properties have been realized.

KRAS G12D mutation in Brunner gland adenoma.

Brunner gland lesions (BGLs) encompass benign proliferations of the homonymous glands and have been designated as hyperplasia, adenoma (BGA), hamartoma or nodule. In general terms, lesions larger than 0.5 cm are considered true neoplasia with unknown malignant potential and unclear pathogenesis. Genetic alterations have seldom been reported in BGL, and include SMAD4/DPC4 and LRIG1, but not KRAS (Kirsten rat sarcoma viral oncogene homologue) to the best of our knowledge.We present the case of a man in his 60s, evaluated for iron deficiency anaemia harbouring a 1.5 cm BGA found by duodenoscopy. Immunohistochemistry failed to reveal microsatellite instability, and next-generation sequencing revealed a KRAS G12D point mutation.

Neurothekeoma With PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M Genetic Alterations.

ABSTRACT: Neurothekeoma, a lesion of possible fibrohistiocytic origin, is a rare, benign, superficial soft tissue tumor, histologically subclassified in 3 types: myxoid, cellular, or mixed. It clinically presents as a solitary, pink to brown nodule, ranging from 0.3 to 2.0 cm. Four point mutations (PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M) were identified by next-generation sequencing of a neurothekeoma presenting in the left inner thigh of a 53-year-old man. We highlight novel genetic alterations (SMO G461S and ERBB3 L77M) and previously known mutations (PI3KCA w552* and ALK P1469S) that play a role in other pathogenic pathways, but to the best of our knowledge, these have not yet been reported in neurothekeoma.

Extrusion 3D printing of keratin protein hydrogels free of exogenous chemical agents.

Keratins are a class of intermediate filament proteins that can be obtained from numerous sources including human hair. Materials fabricated from keratins offer desirable characteristics as scaffolds for tissue engineering, including intrinsic cell adhesion sequences and tunable degradation kinetics. The capacity to create 3D printed constructs from keratin-based bio-inks generates unique opportunities for spatial control of scaffold physicochemical properties to direct scaffold functions in ways not readily achieved through other means. The aim of this study was to leverage the controllable rheological properties of keratin hydrogels to create a strategy for extrusion 3D printing of keratin bio-inks without the use of exogenous rheological modifiers, crosslinking agents, or photocurable resins. The rheological properties of keratin hydrogels were tuned by varying two parameters: (a) the ratio of keratose (obtained by oxidative extraction of keratin) to kerateine (obtained by reductive extraction of keratin); and (b) the weight percentage of total keratin protein in the gel. A computational model of the dispensing nozzle for a commercially available extrusion 3D printer was developed to calculate the needed pneumatic printing pressures based on the known rheological properties of the gels. Keratin hydrogel constructs, of varying keratose/kerateine ratios and total keratin weight percentages, were 3D printed in cylindrical geometries via extrusion 3D printing. Rheology and degradation studies showed that gels with greater relative kerateine content exhibited greater flow resistance and slower degradation kinetics when submerged in phosphate buffered saline solution at 37 °C, owing to the presence of cysteine residues in kerateine and the capability of forming disulfide bonds. Total keratin weight percentage was found to influence gel yield stress, with possible implications for tuning filament fidelity. Findings from this work support the use of keratose/kerateine ratio and total keratin weight percentage as handles for modulating rheological characteristics of keratin hydrogels to enhance printability and control scaffold properties.

Revealing global risks of labor abuse and illegal, unreported, and unregulated fishing.

Labor abuse on fishing vessels and illegal, unreported and unregulated (IUU) fishing violate human rights, jeopardize food security, and deprive governments of revenues. We applied a multi-method approach, combining new empirical data with satellite information on fishing activities and vessel characteristics to map risks of labor abuse and IUU fishing, understand their relationships, and identify major drivers. Port risks were globally pervasive and often coupled, with 57% of assessed ports associated with labor abuse or IUU fishing. For trips ending in assessed ports, 82% were linked to labor abuse or IUU fishing risks. At-sea risk areas were primarily driven by fishing vessel flags linked to poor control of corruption by the flag state, high ownership by countries other than the flag state, and Chinese-flagged vessels. Transshipment risk areas were related to the gear type of fishing vessels engaged in potential transshipment and carrier vessel flags. Measures at port offer promise for mitigating risks, through the Port State Measures Agreement for IUU fishing, and ensuring sufficient vessel time at port to detect and respond to labor abuse. Our results highlight the need for coordinated action across actors to avoid risk displacement and make progress towards eliminating these socially, environmentally and economically unsustainable practices.

Aromatic foldamers as molecular springs in network polymers.

Polymer networks crosslinked with spring-like ortho-phenylene (oP) foldamers were developed. NMR analysis indicated the oP crosslinkers were well-folded. Polymer networks with oP-based crosslinkers showed enhanced energy dissipation and elasticity compared to divinylbenzene crosslinked networks. The energy dissipation was attributed to the strain-induced reversible unfolding of the oP units. Energy dissipation increased with the number of helical turns in the foldamer.

3D-Printed Self-Healing Elastomers for Modular Soft Robotics.

Advances in materials, designs, and controls are propelling the field of soft robotics at an incredible rate; however, current methods for prototyping soft robots remain cumbersome and struggle to incorporate desirable geometric complexity. Herein, a vat photopolymerizable self-healing elastomer system capable of extreme elongations up to 1000% is presented. The material is formed from a combination of thiol/acrylate mixed chain/step-growth polymerizations and uses a combination of physical processes and dynamic-bond exchange via thioethers to achieve full self-healing capacity over multiple damage/healing cycles. These elastomers can be three dimensional (3D) printed with modular designs capable of healing together to form highly complex and large functional soft robots. Additionally, these materials show reprogrammable resting shapes and compatibility with self-healing liquid metal electronics. Using these capabilities, subcomponents with multiple internal channel systems were printed, healed together, and combined with functional liquid metals to form a high-wattage pneumatic switch and a humanoid-scale soft robotic gripper. The combination of 3D printing and self-healing elastomeric materials allows for facile production of support-free parts with extreme complexity, resulting in a paradigm shift for the construction of modular soft robotics.

Heat- and Light-Responsive Materials Through Pairing Dynamic Thiol-Michael and Coumarin Chemistry.

Covalent adaptable networks (CANs) based on the thiol-Michael (TM) linkages can be thermal and pH responsive. Here, a new vinyl-sulfone-based thiol-Michael crosslinker is synthesized and incorporated into acrylate-based CANs to achieve stable materials with dynamic properties. Because of the reversible TM linkages, excellent temperature-responsive re-healing and malleability properties are achieved. In addition, for the first time, a photoresponsive coumarin moiety is incorporated with TM-based CANs to introduce light-mediated reconfigureability and postpolymerization crosslinking. Overall, these materials can be on demand dynamic in response to heat and light but can retain mechanical stability at ambient condition.

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach.

Colorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could "reawaken" after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.

Risk of forced labour embedded in the US fruit and vegetable supply.

Sustainable food consumption studies have largely focused on promoting human health within ecological limits. Less attention has been paid to social sustainability, in part because of limited data and models. Globally, agriculture has one of the highest incidences of forced labour, with exploitative conditions enabled by low margins, domestic labour scarcity, inadequate legal protections for workers and high labour requirements. Here we assess the forced labour risk embedded in the US retail supply of fruits and vegetables using distinct datasets and a new forced labour risk scoring method. We demonstrate that there is risk of forced labour in a broad set of fruit and vegetable commodities, with a small number of commodities accounting for a substantial fraction of total risk at the retail supply level. These findings signal potential trade-offs and synergies across dimensions of food system sustainability and the need for novel research approaches to develop evidence-based forced labour risk mitigation strategies.

Self-Replicating RNAs Drive Protective Anti-tumor T Cell Responses to Neoantigen Vaccine Targets in a Combinatorial Approach.

Historically poor clinical results of tumor vaccines have been attributed to weakly immunogenic antigen targets, limited specificity, and vaccine platforms that fail to induce high-quality polyfunctional T cells, central to mediating cellular immunity. We show here that the combination of antigen selection, construct design, and a robust vaccine platform based on the Synthetically Modified Alpha Replicon RNA Technology (SMARRT), a self-replicating RNA, leads to control of tumor growth in mice. Therapeutic immunization with SMARRT replicon-based vaccines expressing tumor-specific neoantigens or tumor-associated antigen were able to generate polyfunctional CD4+ and CD8+ T cell responses in mice. Additionally, checkpoint inhibitors, or co-administration of cytokine also expressed from the SMARRT platform, synergized to enhance responses further. Lastly, SMARRT-based immunization of non-human primates was able to elicit high-quality T cell responses, demonstrating translatability and clinical feasibility of synthetic replicon technology for therapeutic oncology vaccines.

CD8+ T cells mediate protection against Zika virus induced by an NS3-based vaccine.

Zika virus (ZIKV) is associated with congenital malformations in infants born to infected mothers, and with Guillain-Barré syndrome in infected adults. Development of ZIKV vaccines has focused predominantly on the induction of neutralizing antibodies, although a suboptimal antibody response may theoretically enhance disease severity through antibody-dependent enhancement (ADE). Here, we report induction of a protective anti-ZIKV CD8+ T cell response in the HLA-B*0702 Ifnar1-/- transgenic mice using an alphavirus-based replicon RNA vaccine expressing ZIKV nonstructural protein NS3, a potent T cell antigen. The NS3 vaccine did not induce a neutralizing antibody response but elicited polyfunctional CD8+ T cells that were necessary and sufficient for preventing death in lethally infected adult mice and fetal growth restriction in infected pregnant mice. These data identify CD8+ T cells as the major mediators of ZIKV NS3 vaccine-induced protection and suggest a new strategy to develop safe and effective anti-flavivirus vaccines.

Chemically fueled covalent crosslinking of polymer materials.

Transiently crosslinked dynamic polymer networks are developed, using carbodiimide hydration to link carboxylic acids as anhydrides. From aqueous polymer solutions, non-equilibrium hydrogels are transiently formed, which dissolve upon anhydride hydrolysis. The materials can be refueled using a subsequent injection of carbodiimide. The gels exhibit higher storage moduli compared to transient supramolecular gels as a result of their covalent crosslinks.