Carbon materials and their metal composites for biomedical applications: A short review.

Carbon materials and their hybrid metal composites have garnered significant attention in biomedical applications due to their exceptional biocompatibility. This biocompatibility arises from their inherent chemical stability and low toxicity within biological systems. This review offers a comprehensive overview of carbon nanomaterials and their metal composites, emphasizing their biocompatibility-focused applications, including drug delivery, bioimaging, biosensing, and tissue engineering. The paper outlines advancements in surface modifications, coatings, and functionalization techniques designed to enhance the biocompatibility of carbon materials, ensuring minimal adverse effects in biological systems. A comprehensive investigation into hybrid composites integrating carbon nanomaterials is conducted, categorizing them as fullerenes, carbon quantum dots, carbon nanotubes, carbon nanofibers, graphene, and diamond-like carbon. The concluding section addresses regulatory considerations and challenges associated with integrating carbon materials into medical devices. This review culminates by providing insights into current achievements, challenges, and future directions, underscoring the pivotal role of carbon nanomaterials and their metal composites in advancing biocompatible applications.

Oligomerization and a distinct tRNA-binding loop are important regulators of human arginyl-transferase function.

The arginyl-transferase ATE1 is a tRNA-dependent enzyme that covalently attaches an arginine molecule to a protein substrate. Conserved from yeast to humans, ATE1 deficiency in mice correlates with defects in cardiovascular development and angiogenesis and results in embryonic lethality, while conditional knockouts exhibit reproductive, developmental, and neurological deficiencies. Despite the recent revelation of the tRNA binding mechanism and the catalytic cycle of yeast ATE1, the structure-function relationship of ATE1 in higher organisms is not well understood. In this study, we present the three-dimensional structure of human ATE1 in an apo-state and in complex with its tRNA cofactor and a peptide substrate. In contrast to its yeast counterpart, human ATE1 forms a symmetric homodimer, which dissociates upon binding of a substrate. Furthermore, human ATE1 includes a unique and extended loop that wraps around tRNAArg, creating extensive contacts with the T-arm of the tRNA cofactor. Substituting key residues identified in the substrate binding site of ATE1 abolishes enzymatic activity and results in the accumulation of ATE1 substrates in cells.

Career decisions and aspirations of early-career nurses: Insights from a qualitative interpretative description study.

AIM: To explore the career decisions and aspirations of early-career registered nurses in New Brunswick, Canada. DESIGN: A qualitative study using an interpretive description approach was conducted. METHODS: Semi-structured one-on-one interviews were conducted with a purposive sample of nurses (n = 22) currently working in New Brunswick, Canada, with up to 5 years of experience from February to April 2022. RESULTS: Participants described diverse career paths and aspirations. Personal factors affecting these included the desire for meaningful work, career satisfaction, work-life balance, spending time with family, working in a preferred location, and finances. Professionally, working conditions were the dominant factor influencing early-career nurses' career decisions and aspirations. Participants described how short staffing, safety, support, and scheduling influenced their day-to-day work, mental and physical health, job and career satisfaction, and intent to leave. CONCLUSION: The findings highlighted the abundant and diverse career opportunities available to nurses early in their careers. Early-career nurses are interested in finding nursing positions with a high degree of person-job fit and value opportunities for ongoing professional education and growth. IMPACT: This study in New Brunswick, Canada, explores early-career nurses' career decisions and aspirations during nursing shortages and the pandemic, emphasizing the importance of person-job fit. Recommendations include improving working conditions and career pathways to enhance the sustainability of the nursing profession. REPORTING METHOD: Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Intergranular Shielding for Ultrafine-Grained Mo-Doped Ni-Rich Li[Ni0.96 Co0.04 ]O2 Cathode for Li-Ion Batteries with High Energy Density and Long Life.

Deploying Ni-enriched (Ni≥95 %) layered cathodes for high energy-density lithium-ion batteries (LIBs) requires resolving a series of technical challenges. Among them, the structural weaknesses of the cathode, vigorous reactivity of the labile Ni4+ ion species, gas evolution and associated cell swelling, and thermal instability issues are critical obstacles that must be solved. Herein, we propose an intuitive strategy that can effectively ameliorate the degradation of an extremely high-Ni-layered cathode, the construction of ultrafine-scale microstructure and subsequent intergranular shielding of grains. The formation of ultrafine grains in the Ni-enriched Li[Ni0.96 Co0.04 ]O2 (NC96) cathode, achieved by impeding particle coarsening during cathode calcination, noticeably improved the mechanical durability and electrochemical performance of the cathode. However, the buildup of the strain-resistant microstructure in Mo-doped NC96 concurrently increased the cathode-electrolyte contact area at the secondary particle surface, which adversely accelerated parasitic reactions with the electrolyte. The intergranular protection of the refined microstructure resolved the remaining chemical instability of the Mo-doped NC96 cathode by forming an F-induced coating layer, effectively alleviating structural degradation and gas generation, thereby extending the battery's lifespan. The proposed strategies synergistically improved the structural and chemical durability of the NC96 cathode, satisfying the energy density, life cycle performance, and safety requirements for next-generation LIBs.

Characterization and chemical modulation of p62/SQSTM1/Sequestosome-1 as an autophagic N-recognin.

In the Arg/N-degron pathway, single N-terminal (Nt) residues function as N-degrons recognized by UBR box-containing N-recognins that induce substrate ubiquitination and proteasomal degradation. Recent studies led to the discovery of the autophagic Arg/N-degron pathway, in which the autophagic receptor p62/SQSTM1/Sequestosome-1 acts as an N-recognin that binds the Nt-Arg and other destabilizing residues as N-degrons. Upon binding to Nt-Arg, p62 undergoes self-polymerization associated with its cargoes, accelerating the macroautophagic delivery of p62-cargo complexes to autophagosomes leading to degradation by lysosomal hydrolases. This autophagic mechanism is emerging as an important pathway that modulates the lysosomal degradation of various biomaterial ranging from protein aggregates and subcellular organelles to invading pathogens. Chemical mimics of the physiological N-degrons were developed to exert therapeutic efficacy in pathophysiological processes associated with neurodegeneration and other related diseases. Here, we describe the methods to monitor the activities of p62 in a dual role as an N-recognin and an autophagic receptor. The topic includes self-polymerization (for cargo condensation), its interaction with LC3 on autophagic membranes (for cargo targeting), and the degradation of p62-cargo complexes by lysosomal hydrolases. We also discuss the development and use of small molecule mimics of N-degrons that modulate p62-dependent macroautophagy in biological and pathophysiological processes.

Temperature-dependent development of Helicoverpa armigera (Lepidoptera: Noctuidae) at constant temperatures: instar pathways and stage transition models with semifield validation.

Temperature-dependent development of Helicoverpa armigera (Hüber) fed with an artificial diet was studied at different temperatures. The instar pathway (IPW) defined as the number of instars prior to pupation significantly affected larval development time, with higher IPW leading to longer larval development time. The IPW was determined at the fifth instar to proceed to 6-7 IPW, when the development time of fifth instar was largely shortened. Accordingly, the development time after the fourth instar was combined (i.e., the fifth-seventh instar) as a single stage to simplify the various IPW and applied to develop phenology models. In linear models, the lower threshold temperature (LT) and thermal constant (degree-days, DD) for each stage were estimated. DD based on the common LT of 10.7 °C were 43, 287, and 191 DD for eggs, larvae, and pupae, respectively. DD model (253.6 DD with LT 10.3 °C for larvae and 181.5 DD with 11.6 °C for pupae) showed good performance in predicting the 50% occurrences of pupae and adults. In nonlinear models, stage transition (ST) models were constructed using the development rate and distribution models to simulate the proportion of individuals shifted from one stage to the next stage. The ST model showed good performance, indicating an average discrepancy of 1.74 days at 25%, 50%, 75%, and 90% adult emergence. Our models developed here will be useful to predict the phenology of H. armigera in the field and to construct a deterministic population model in the future.

Theranostic Surrogacy of [123I]NaI for Differentiated Thyroid Cancer Radionuclide Therapy.

Precise dosimetry has gained interest for interpreting the response assessments of novel therapeutic radiopharmaceuticals, as well as for improving conventional radiotherapies such as the "one dose fits all" approach. Although radioiodine as same-element isotope theranostic pairs has been used for differentiated thyroid cancer (DTC), there are insufficient studies on the determination of its dosing regimen for personalized medicine and on extrapolating strategies for companion diagnostic radiopharmaceuticals. In this study, DTC xenograft mouse models were generated after validating iodine uptakes via sodium iodine symporter proteins (NIS) through in vitro assays, and theranostic surrogacy of companion radiopharmaceuticals was investigated in terms of single photon emission computed tomography (SPECT) imaging and voxel-level dosimetry. Following a Monte Carlo simulation, the hypothetical energy deposition/dose distribution images were produced as [123I]NaI SPECT scans with the use of 131I ion source simulation, and dose rate curves were used to estimate absorbed dose. For the tumor, a peak concentration of 96.49 ± 11.66% ID/g occurred 2.91 ± 0.42 h after [123I]NaI injection, and absorbed dose for 131I therapy was estimated as 0.0344 ± 0.0088 Gy/MBq. The absorbed dose in target/off-target tissues was estimated by considering subject-specific heterogeneous tissue compositions and activity distributions. Furthermore, a novel approach was proposed for simplifying voxel-level dosimetry and suggested for determining the minimal/optimal scan time points of surrogates for pretherapeutic dosimetry. When two scan time points were set to Tmax and 26 h and the group mean half-lives were applied to the dose rate curves, the most accurate absorbed dose estimates were determined [-22.96, 2.21%]. This study provided an experimental basis to evaluate dose distribution and is expected hopefully to improve the challenging dosimetry process for clinical use.

Monitoring the Activation of Selective Autophagy via N-Terminal Arginylation.

In addition to generating N-degron-carrying substrates destined for proteolysis, N-terminal arginylation can globally upregulate selective macroautophagy via activation of the autophagic N-recognin and archetypal autophagy cargo receptor p62/SQSTM1/sequestosome-1. To evaluate the macroautophagic turnover of cellular substrates, including protein aggregates (aggrephagy) and subcellular organelles (organellophagy) mediated by N-terminal arginylation in vivo, we report here a protocol for assaying the activation of the autophagic Arg/N-degron pathway and degradation of cellular cargoes via N-terminal arginylation. These methods, reagents, and conditions are applicable across a wide spectrum of different cell lines, primary cultures, and/or animal tissues, thereby providing a general means for identification and validation of putative cellular cargoes degraded by Nt-arginylation-activated selective autophagy.

Analyzing the Interaction of Arginylated Proteins and Nt-Arg-Mimicking Chemical Compounds to N-Recognins.

Characterizing and measuring the interactome of N-degrons and N-recognins are critical to the identification and verification of putative N-terminally arginylated native proteins and small-molecule chemicals that structurally and physiologically mimic the N-terminal arginine residue. This chapter focuses on in vitro and in vivo assays to confirm the putative interaction, and measure the binding affinity, between Nt-Arg-carrying natural (or Nt-Arg-mimicking synthetic) ligands and proteasomal or autophagic N-recognins carrying the UBR box or the ZZ domain. These methods, reagents, and conditions are applicable across a wide spectrum of different cell lines, primary cultures, and/or animal tissues, allowing for the qualitative analysis and quantitative measurement of the interaction of arginylated proteins and N-terminal arginine-mimicking chemical compounds to their respective N-recognins.

The N-degron pathway: From basic science to therapeutic applications.

The N-degron pathway is a degradative system in which single N-terminal (Nt) amino acids regulate the half-lives of proteins and other biological materials. These determinants, called N-degrons, are recognized by N-recognins that link them to the ubiquitin (Ub)-proteasome system (UPS) or autophagy-lysosome system (ALS). In the UPS, the Arg/N-degron pathway targets the Nt-arginine (Nt-Arg) and other N-degrons to assemble Lys48 (K48)-linked Ub chains by UBR box N-recognins for proteasomal proteolysis. In the ALS, Arg/N-degrons are recognized by the N-recognin p62/SQSTSM-1/Sequestosome-1 to induce cis-degradation of substrates and trans-degradation of various cargoes such as protein aggregates and subcellular organelles. This crosstalk between the UPS and ALP involves reprogramming of the Ub code. Eukaryotic cells developed diverse ways to target all 20 principal amino acids for degradation. Here we discuss the components, regulation, and functions of the N-degron pathways, with an emphasis on the basic mechanisms and therapeutic applications of Arg/N-degrons and N-recognins.