Maintenance of protein homeostasis and organelle integrity and function is critical for cellular homeostasis and cell viability. Autophagy is the principal mechanism that mediates the delivery of ...various cellular cargoes to lysosomes for degradation and recycling. A myriad of studies demonstrate important protective roles for autophagy against disease. However, in cancer, seemingly opposing roles of autophagy are observed in the prevention of early tumour development versus the maintenance and metabolic adaptation of established and metastasizing tumours. Recent studies have addressed not only the tumour cell intrinsic functions of autophagy, but also the roles of autophagy in the tumour microenvironment and associated immune cells. In addition, various autophagy-related pathways have been described, which are distinct from classical autophagy, that utilize parts of the autophagic machinery and can potentially contribute to malignant disease. Growing evidence on how autophagy and related processes affect cancer development and progression has helped guide efforts to design anticancer treatments based on inhibition or promotion of autophagy. In this Review, we discuss and dissect these different functions of autophagy and autophagy-related processes during tumour development, maintenance and progression. We outline recent findings regarding the role of these processes in both the tumour cells and the tumour microenvironment and describe advances in therapy aimed at autophagy processes in cancer.
Li‐alloying materials such as Si and Ge nanowires have emerged as the forerunners to replace the current, relatively low‐capacity carbonaceous based Li‐ion anodes. Since the initial report of ...binder‐free nanowire electrodes, a vast body of research has been carried out in which the performance and cycle life has significantly progressed. The study of such electrodes has provided invaluable insights into the cycling behavior of Si and Ge, as the effects of repeated lithiation/delithiation on the material can be observed without interference from conductive additives or binders. Here, some of the key developments in this area are looked at, focusing on the problems encountered by Li‐alloying electrodes in general (e.g., pulverization, loss of contact with current collector etc.) and how the study of nanowire electrodes has overcome these issues. Some key nanowire studies that have elucidated the consequences of the alloying/dealloying process on the morphology of Si and Ge are also considered, in particular looking at the impact that effects such as pore formation and lithium‐assisted welding have on performance. Finally, the challenges for the practical implementation of nanowire anodes within the context of the current understanding of such systems are discussed.
The study of silicon and germanium nanowire anodes for lithium‐ion batteries provides invaluable insight into the fundamental cycling behavior of Li‐alloying materials. Key studies of nanowire anodes are reviewed, looking in particular at those that have elucidated the effect of repeated lithiation and delithiation on the Si and Ge morphology. A critical analysis of the current status of Li‐alloying nanowire electrodes is also presented, along with the challenges still faced before their practical implementation can be realized.
This review captures the synthesis, assembly, properties, and applications of copper chalcogenide NCs, which have achieved significant research interest in the last decade due to their compositional ...and structural versatility. The outstanding functional properties of these materials stems from the relationship between their band structure and defect concentration, including charge carrier concentration and electronic conductivity character, which consequently affects their optoelectronic, optical, and plasmonic properties. This, combined with several metastable crystal phases and stoichiometries and the low energy of formation of defects, makes the reproducible synthesis of these materials, with tunable parameters, remarkable. Further to this, the review captures the progress of the hierarchical assembly of these NCs, which bridges the link between their discrete and collective properties. Their ubiquitous application set has cross-cut energy conversion (photovoltaics, photocatalysis, thermoelectrics), energy storage (lithium-ion batteries, hydrogen generation), emissive materials (plasmonics, LEDs, biolabelling), sensors (electrochemical, biochemical), biomedical devices (magnetic resonance imaging, X-ray computer tomography), and medical therapies (photochemothermal therapies, immunotherapy, radiotherapy, and drug delivery). The confluence of advances in the synthesis, assembly, and application of these NCs in the past decade has the potential to significantly impact society, both economically and environmentally.
Cell death is part of the lifecycle of every multicellular organism. Nineteenth-century pathologists already recognised that organised forms of cell death must exist to explain the demise and ...turnover of cells during metamorphosis (of insects), embryogenesis and normal tissue homoeostasis 1. Nevertheless, Kerr, Wyllie and Currie in their seminal paper of 1972, were the first to collate and define the distinct morphological features of controlled cell death in different contexts 2. To describe the processes of cell deletion observed under both physiological and pathological conditions, they coined the term 'Apoptosis' (derived from the Greek word 'ἀπόπτωσις', meaning 'dropping off or falling off' of petals from flowers). Kerr, Wyllie and Currie defined apoptosis as a mechanism 'complementary to mitosis in the regulation of animal cell populations'. In addition, they already recognised the potential to use this programmed form of cell death for cancer therapy, but they also emphasised the occurrence of apoptosis during cancer development. In this article, some 50 years after its initial publication in The British Journal of Cancer, we revaluate and put the authors initial assumptions and general concepts about apoptosis into the context of modern-day biology.
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Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug molecules. ...Though nanosizing of drug particles has been proven to greatly enhance drugs dissolution rate and apparent solubility, nanosized materials have presented significant challenges for their formulation as solid dosage forms (e.g. tablets, capsules). This is due to the strong Van der Waals attraction forces between dry nanoparticles leading to aggregation, cohesion, and consequently poor flowability. In this review, the broad area of nanomedicines is overviewed with the primary focus on drug nanocrystals and the top-down and bottom-up methods used in their fabrication. The review also looks at how nanosuspensions of pharmaceutical drugs are generated and stabilised, followed by subsequent strategies for isolation of the nanoparticles. A perspective on the future outlook for drug nanocrystals is also presented.
Both autophagy, a cellular recycling process, and the innate immune response can have different effects on tumour formation at different stages. Interestingly, autophagy and the innate immune ...response interact during tumorigenesis to have both tumour‐promoting and tumour‐inhibiting affects. By dissecting the interaction between autophagy and the innate immune response during tumour formation, novel therapeutic strategies may be identified.
Autophagy is a cellular degradation and recycling system, which can interact with components of innate immune signalling pathways to enhance pathogen clearance, in both immune and nonimmune cells. Whilst this interaction is often beneficial for pathogen clearance, it can have varying outcomes in regard to tumorigenesis. Autophagy and the innate immune response can have both pro‐ and antitumorigenic effects at different stages of tumorigenesis due to the plastic nature of the tumour microenvironment (TME). Although both of these components have been studied in isolation as potential therapeutic targets, there has been less research concerning the interaction between autophagy and the innate immune response within the TME. As the innate immune response is critical for the formation of an effective antitumour adaptive immune response, targeting autophagy pathways in both tumour cells and innate immune cells could enhance tumour clearance. Within tumour cells, autophagy pathways are intertwined with pattern recognition receptor (PRR), inflammatory and cell death pathways, and therefore can alter the immunogenicity of the TME and development of the antitumour immune response. In innate immune cells, autophagy components can have autophagy‐independent roles in functional pathways, and therefore could be valuable targets for enhancing immune cell function in the TME and immunotherapy. This review highlights the individual importance of autophagy and the innate immune response to tumorigenesis, and also explains the complex interactions between these pathways in the TME.
Nearly 60 years ago, lysosomes were first described in the laboratory of Christian de Duve, a discovery that significantly contributed to him being awarded a share of the 1974 Nobel Prize in ...Physiology or Medicine for elucidating ‘the structural and functional organization of the cell’. Initially thought of as a simple waste degradation facility of the cell, these organelles recently emerged as signalling centres with connections to major cellular processes. This review provides an overview of the many roles of lysosomal proteins in two of these processes: cell death and autophagy. We discuss both resident lysosomal proteins as well those that temporarily associate with lysosomes to influence autophagy and cell death pathways. Particular focus is given to studies in mammalian cells and in vivo systems.
Whether ignited by lightning or by Native Americans, fire once shaped many North American ecosystems. Euro-American settlement and 20th-century fire suppression practices drastically altered historic ...fire regimes, leading to excessive fuel accumulation and uncharacteristically severe wildfires in some areas and diminished flammability resulting from shifts to more fire-sensitive forest species in others. Prescribed fire is a valuable tool for fuel management and ecosystem restoration, but the practice is fraught with controversy and uncertainty. Here, we summarize fire use in the forests and woodlands of North America and the current state of the practice, and explore challenges associated with the use of prescribed fire. Although new scientific knowledge has reduced barriers to prescribed burning, societal aversion to risk often trumps known, long-term ecological benefits. Broader implementation of prescribed burning and strategic management of wildfires in fire-dependent ecosystems will require improved integration of science, policy, and management, and greater societal acceptance through education and public involvement in land-management issues.
The quaternary copper chalcogenide Cu2ZnSnS4 is an important emerging material for the development of low-cost and sustainable solar cells. Here we report a facile solution synthesis of ...stoichiometric Cu2ZnSnS4 in size-controlled nanorod form (11 nm × 35 nm). The monodisperse nanorods have a band gap of 1.43 eV and can be assembled into perpendicularly aligned arrays by controlled evaporation from solution.
Controlling pharmaceutical polymorphism in crystallization processes represents a major challenge in pharmaceutical science and engineering. For instance, CO2-antisolvent crystallization typically ...favors the formation of metastable forms of carbamazepine (CBZ), a highly polymorphic drug, with impurities of other forms. This work demonstrates for the first time that a supercritical CO2-antisolvent crystallization process in combination with certain molecular additives allows control of the polymorphic outcome of CBZ. We show herein that in the presence of sodium stearate and Eudragit L-100, needle-shaped crystals of CBZ form II are obtained, while blocky-shaped crystals of CBZ form III are obtained in the presence of Kollidon VA64, sodium dodecyl sulfate, ethyl cellulose, and maltitol. This selectivity for pure forms in this supercritical set up contrasts to the results when the same set of additives where used in a solvent evaporation method that yielded mixtures of form I, II, and III. The type of additive used in the CO2-antisolvent crystallization process impacted both the product crystal polymorphic form and size. A detailed molecular-level analysis along with density functional theory calculations allowed us to give a mechanistic insight into the role of sodium stearate and Eudragit L-100 in facilitating nucleation of the metastable form II.
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