Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness ...the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC
values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.
Abstract
Introducing additional elements into Ni‐rich cathodes is an essential strategy for addressing the instability of the cathode material. Conventionally, this doping strategy considers only the ...incorporation of additional elements into the bulk structure of the cathode in terms of fortifying the crystal structure. However, high‐valence elements such as Nb
5+
, Ta
5+
, and Mo
6+
are likely to be insoluble in the crystal structure, resulting in accumulation along the interparticle boundaries. Herein, a new mechanism for doping high‐valence elements into Ni‐rich cathodes and their effects on the morphology and crystal structure are investigated by calcining LiNiO
2
(LNO) and X‐doped LNO cathodes (X = Al, Nb, Ta, and Mo) at various temperatures. Operando X‐ray diffraction analysis reveals that the temperature at which the content of Li‐X‐O compounds declines is higher for the dopants with high oxidation states, reinforcing segregation at the grain boundary and widening the calcination temperature range. Thus, the highly aligned microstructure and high crystallinity of the LNO cathode are maintained over a wide calcination temperature range after doping with high‐valence elements, enhancing the electrochemical performance. As next‐generation dopants, high‐valence elements can fortify not only the crystal structure, but also the microstructure, to maximize the electrochemical performance of Ni‐rich cathodes.
To explore the career decisions and aspirations of early-career registered nurses in New Brunswick, Canada.
A qualitative study using an interpretive description approach was conducted.
...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.
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.
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.
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.
Standards for Reporting Qualitative Research (SRQR).
No patient or public contribution.
A high fraction of reactive Ni4+ ions at the cathode–electrolyte interfaces lead to capacity fading of Ni‐rich cathodes. Therefore, a core–shell (CS) design encapsulating the Ni‐rich region by a ...Ni‐less shell is an effective approach for improving the cycling stability of the cathodes. However, with increasing average Ni content to increase the capacity, the thickness of the shell should be reduced or the Ni fraction of the shell will be inevitably higher, making it susceptible to interdiffusion, which flattens the concentration gradient during the lithiation process. Herein, the limit of the average Ni composition in the CS‐type cathode is pushed to 94% via Ta doping, which suppresses interdiffusion by segregating the Ta‐rich phases at the particle boundaries. Ta doping allows the maintenance of the highly aligned microstructure and the ordered intermixing structure of Li and transition metal ions, as well as the concentration gradient, over a wide lithiation temperature range. The Ta‐doped CS‐type cathode retains 92.6% of its initial capacity after 1000 cycles and exhibits resistance to damage from fast charging. Multifunctional Ta doping in the CS‐type cathode provides a simple and all‐around solution to maximize the electrochemical performance of Ni‐rich cathodes, providing flexibility in the lithiation process.
The Ni composition in core–shell‐type cathodes is brought to 94% via Ta doping, which suppresses interdiffusion by segregating the Ta‐rich phases at the particle boundaries. Ta doping allows the maintenance of the highly aligned microstructure and the ordered intermixing structure of Li and transition metal ions, as well as the concentration gradient, over a wide lithiation temperature range.
Human exposure to microplastics contained in food has become a significant concern owing to the increasing accumulation of microplastics in the environment. In this paper, we summarize the presence ...of microplastics in food and the analytical methods used for isolation and identification of microplastics. Although a large number of studies on seafood such as fish and shellfish exist, estimating the overall human exposure to microplastics via food consumption is difficult owing to the lack of studies on other food items. Analytical methods still need to be optimized for appropriate recovery of microplastics in various food matrices, rendering a quantitative comparison of different studies challenging. In addition, microplastics could be added or removed from ingredients during processing or cooking. Thus, research on processed food is crucial to estimate the contribution of food to overall human microplastic consumption and to mitigate this exposure in the future.
Substantial endeavors are dedicated to advance the electrochemical performance of Ni‐rich LiNi1−x−yCoxMnyO2 (NCM) and LiNi1−x−yCoxAlyO2 (NCA) cathode, with a particular focus on doping, aimed at ...addressing cycling durability and thermal stability of the cathodes. Mn is widely considered an attractive dopant because of its abundance and considerably lower cost than other dopant candidates. However, despite the long history of research, the role of Mn doping remains poorly understood, confined to the historical level, and associated with crystal structural and chemical aspects. Herein, the role of Mn doping beyond its classical role is redefined, particularly in terms of cathode microstructure. Introducing excess Mn during calcination significantly engineers the nano‐ and micro‐level structural features of the peripheral grains of the LiNi0.910Co0.079Al0.011O2 cathode. The microstructural modification achieved by doping with 4 mol% Mn significantly improves the electrochemical cycling performance of the cathode, extending the capacity retention up to 76.5% after 1000 cycles under fast charging conditions (3 C and 45 °C). Hence, by providing an alternative approach to redesign the structural features of the cathode, Mn doping offers a significant step toward the sustainable development of high‐performance Ni‐rich LiNi1−x−y−zCoxMnyAlzO2 (NCMA) cathodes for next‐generation lithium‐ion batteries.
The rational design of nano and microstructure in Ni‐rich layered cathode achieved via introducing an excess amount of Mn during the calcination process provides an alternative approach for redesigning the cathode for the sustainable development of high‐performance Ni‐rich cathodes for next‐generation electric vehicles.
For decades, plastic has been a valuable global product due to its convenience and low price. For example, polyethylene terephthalate (PET) was one of the most popular materials for disposable ...bottles due to its beneficial properties, namely impact resistance, high clarity, and light weight. Increasing demand of plastic resulted in indiscriminate disposal by consumers, causing severe accumulation of plastic wastes. Because of this, scientists have made great efforts to find a way to biologically treat plastic wastes. As a result, a novel plastic degradation enzyme, PETase, which can hydrolyze PET, was discovered in Ideonella sakaiensis 201-F6 in 2016.
A green algae, Chlamydomonas reinhardtii, which produces PETase, was developed for this study. Two representative strains (C. reinhardtii CC-124 and CC-503) were examined, and we found that CC-124 could express PETase well. To verify the catalytic activity of PETase produced by C. reinhardtii, cell lysate of the transformant and PET samples were co-incubated at 30 °C for up to 4 weeks. After incubation, terephthalic acid (TPA), i.e. the fully-degraded form of PET, was detected by high performance liquid chromatography analysis. Additionally, morphological changes, such as holes and dents on the surface of PET film, were observed using scanning electron microscopy.
A PET hydrolyzing enzyme, PETase, was successfully expressed in C. reinhardtii, and its catalytic activity was demonstrated. To the best of our knowledge, this is the first case of PETase expression in green algae.
In recent years, the development of energy storage devices has received much attention due to the increasing demand for renewable energy. Supercapacitors (SCs) have attracted considerable attention ...among various energy storage devices due to their high specific capacity, high power density, long cycle life, economic efficiency, environmental friendliness, high safety, and fast charge/discharge rates. SCs are devices that can store large amounts of electrical energy and release it quickly, making them ideal for use in a wide range of applications. They are often used in conjunction with batteries to provide a power boost when needed and can also be used as a standalone power source. They can be used in various potential applications, such as portable equipment, smart electronic systems, electric vehicles, and grid energy storage systems. There are a variety of materials that have been studied for use as SC electrodes, each with its advantages and limitations. The electrode material must have a high surface area to volume ratio to enable high energy storage densities. Additionally, the electrode material must be highly conductive to enable efficient charge transfer. Over the past several years, several novel materials have been developed which can be used to improve the capacitance of the SCs. This article reviews three types of SCs: electrochemical double-layer capacitors (EDLCs), pseudocapacitors, and hybrid supercapacitors, their respective development, energy storage mechanisms, and the latest research progress in material preparation and modification. In addition, it proposes potentially feasible solutions to the problems encountered during the development of supercapacitors and looks forward to the future development direction of SCs.
Genome editing has been harnessed through the development of CRISPR system, and the CRISPR from Prevotella and Francisella 1 (Cpf1) system has emerged as a promising alternative to CRISPR-Cas9 for ...use in various circumstances. Despite the inherent multiple advantages of Cpf1 over Cas9, the adoption of Cpf1 has been unsatisfactory because of target-dependent insufficient indel efficiencies. Here, we report an engineered CRISPR RNA (crRNA) for highly efficient genome editing by Cpf1, which includes a 20-base target-complementary sequence and a uridinylate-rich 3'-overhang. When the crRNA is transcriptionally produced, crRNA with a 20-base target-complementary sequence plus a U
AU
3'-overhang is the optimal configuration. U-rich crRNA also maximizes the utility of the AsCpf1 mutants and multiplexing genome editing using mRNA as the source of multiple crRNAs. Furthermore, U-rich crRNA enables a highly safe and specific genome editing using Cpf1 in human cells, contributing to the enhancement of a genome-editing toolbox.
Genome editing took a dramatic turn with the development of the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins (Cas) system. The CRISPR-Cas system is ...functionally divided into classes 1 and 2 according to the composition of the effector genes. Class 2 consists of a single effector nuclease, and routine practice of genome editing has been achieved by the development of the Class 2 CRISPR-Cas system, which includes the type II, V, and VI CRISPR-Cas systems. Types II and V can be used for DNA editing, while type VI is employed for RNA editing. CRISPR techniques induce both qualitative and quantitative alterations in gene expression via the double-stranded breakage (DSB) repair pathway, base editing, transposase-dependent DNA integration, and gene regulation using the CRISPR-dCas or type VI CRISPR system. Despite significant technical improvements, technical challenges should be further addressed, including insufficient indel and HDR efficiency, off-target activity, the large size of Cas, PAM restrictions, and immune responses. If sophisticatedly refined, CRISPR technology will harness the process of DNA rewriting, which has potential applications in therapeutics, diagnostics, and biotechnology.
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