Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These ...three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro‐survival or pro‐death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti‐cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis‐related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.
Abstract
A large repulsion between particles in a quantum system can lead to their localization, an effect responsible for the Mott insulator phases in strongly correlated materials. In a system with ...multiple orbitals, an orbital-selective Mott insulator can form, where electrons in some orbitals are predicted to localize while others remain itinerant. Here we demonstrate a more general version of this phenomenon by observing flavour-selective localization in an atom-based quantum simulator. Our experiment realizes Fermi–Hubbard models with an SU(3) symmetry that can be broken using a tunable coupling between flavours. We observe an enhancement of the localization associated with a selective Mott transition and the emergence of flavour-dependent correlations. Our realization of flavour-selective Mott physics demonstrates the potential of cold atoms to simulate interacting multicomponent materials such as superconductors and topological insulators.
The Hall effect, which originates from the motion of charged particles in magnetic fields, has deep consequences for the description of materials, extending far beyond condensed matter. Understanding ...such an effect in interacting systems represents a fundamental challenge, even for small magnetic fields. In this work, we used an atomic quantum simulator in which we tracked the motion of ultracold fermions in two-leg ribbons threaded by artificial magnetic fields. Through controllable quench dynamics, we measured the Hall response for a range of synthetic tunneling and atomic interaction strengths. We unveil a universal interaction-independent behavior above an interaction threshold, in agreement with theoretical analyses. The ability to reach hard-to-compute regimes demonstrates the power of quantum simulation to describe strongly correlated topological states of matter.
Reactive oxygen species (ROS) are chemically reactive molecules that are naturally produced within biological systems. Research has focused extensively on revealing the multi‐faceted and complex ...roles that ROS play in living tissues. In regard to the good side of ROS, this article explores the effects of ROS on signalling, immune response and other physiological responses. To review the potentially bad side of ROS, we explain the consequences of high concentrations of molecules that lead to the disruption of redox homeostasis, which induces oxidative stress damaging intracellular components. The ugly effects of ROS can be observed in devastating cardiac, pulmonary, neurodegenerative and other disorders. Furthermore, this article covers the regulatory enzymes that mitigate the effects of ROS. Glutathione peroxidase, superoxide dismutase and catalase are discussed in particular detail. The current understanding of ROS is incomplete, and it is imperative that future research be performed to understand the implications of ROS in various therapeutic interventions.
Three-dimensional printing (3DP) is a computer-controlled additive manufacturing technique which is able to repeatedly and accurately fabricate objects with complicated geometry and internal ...structures. After 30 years of fast development, 3DP has become a mainstream manufacturing process in various fields. This study focuses on identifying the most suitable 3DP material from five targeted available 3DP materials, i.e. ceramics, gypsum, PMMA (poly(methyl methacrylate)), SR20 (acrylic copolymer) and resin (Accura
®
60), to simulate brittle and hard rocks. Firstly, uniaxial compression tests were performed to determine the mechanical properties and failure patterns of the 3DP samples fabricated by those five materials. Experimental results indicate that among current 3DP techniques, the resin produced via stereolithography (SLA) is the most suitable 3DP material for mimicking brittle and hard rocks, although its brittleness needs to be improved. Subsequently, three methods including freezing, incorporation of internal macro-crack and addition of micro-defects were adopted to enhance the brittleness of the 3DP resin, followed by uniaxial compression tests on the treated samples. Experimental results reveal that 3DP resin samples with the suggested treatments exhibited brittle properties and behaved similarly to natural rocks. Finally, some prospective improvements which can be used to facilitate the application of 3DP techniques to rock mechanics were also discussed. The findings of this paper could contribute to promoting the application of 3DP technique in rock mechanics.
Magnetic skyrmions are two-dimensional non-collinear spin textures characterized by an integer topological number. Room-temperature skyrmions were recently found in magnetic multilayer stacks, where ...their stability was largely attributed to the interfacial Dzyaloshinskii-Moriya interaction. The strength of this interaction and its role in stabilizing the skyrmions is not yet well understood, and imaging of the full spin structure is needed to address this question. Here, we use a nitrogen-vacancy centre in diamond to measure a map of magnetic fields produced by a skyrmion in a magnetic multilayer under ambient conditions. We compute the manifold of candidate spin structures and select the physically meaningful solution. We find a Néel-type skyrmion whose chirality is not left-handed, contrary to preceding reports. We propose skyrmion tube-like structures whose chirality rotates through the film thickness. We show that NV magnetometry, combined with our analysis method, provides a unique tool to investigate this previously inaccessible phenomenon.
The boreal summer Asian monsoon has been evaluated in 25 Coupled Model Intercomparison Project-5 (CMIP5) and 22 CMIP3 GCM simulations of the late twentieth Century. Diagnostics and skill metrics have ...been calculated to assess the time-mean, climatological annual cycle, interannual variability, and intraseasonal variability. Progress has been made in modeling these aspects of the monsoon, though there is no single model that best represents all of these aspects of the monsoon. The CMIP5 multi-model mean (MMM) is more skillful than the CMIP3 MMM for all diagnostics in terms of the skill of simulating pattern correlations with respect to observations. Additionally, for rainfall/convection the MMM outperforms the individual models for the time mean, the interannual variability of the East Asian monsoon, and intraseasonal variability. The pattern correlation of the time (pentad) of monsoon peak and withdrawal is better simulated than that of monsoon onset. The onset of the monsoon over India is typically too late in the models. The extension of the monsoon over eastern China, Korea, and Japan is underestimated, while it is overestimated over the subtropical western/central Pacific Ocean. The anti-correlation between anomalies of all-India rainfall and Niño3.4 sea surface temperature is overly strong in CMIP3 and typically too weak in CMIP5. For both the ENSO-monsoon teleconnection and the East Asian zonal wind-rainfall teleconnection, the MMM interannual rainfall anomalies are weak compared to observations. Though simulation of intraseasonal variability remains problematic, several models show improved skill at representing the northward propagation of convection and the development of the tilted band of convection that extends from India to the equatorial west Pacific. The MMM also well represents the space–time evolution of intraseasonal outgoing longwave radiation anomalies. Caution is necessary when using GPCP and CMAP rainfall to validate (1) the time-mean rainfall, as there are systematic differences over ocean and land between these two data sets, and (2) the timing of monsoon withdrawal over India, where the smooth southward progression seen in India Meteorological Department data is better realized in CMAP data compared to GPCP data.
•We successfully produced resin-based artificial rock specimens with 3D internal flaws with the SLA 3DP technique.•The flaw geometry greatly affects volumetric and mechanical properties of samples ...with 3D internal flaws.•Wing and anti-wing cracks could only propagate for approximately 1–1.5times the length of the initial flaw.•The ratio of initial cracking stress to uniaxial compressive strength is independent on the number of pre-existing flaws.
In nature, rock discontinuities, e.g., cracks, voids and joints, are usually three-dimensional, which to a large extent control the volumetric fracturing behaviors of rock masses. Understanding their growth behaviors and effects on rock volumetric fracturing properties is crucial for the stability assessment of rock engineering. In this study, three-dimensional printing (3DP) method was adopted to fabricate resin-based artificial rocks containing single flaw and double pre-existing penny-shaped 3D internal flaws. Static uniaxial compression tests were, subsequently, conducted on these samples to investigate the influence of flaw number, flaw angle (α) and ligament angle (β) on the volumetric fracturing behaviors of the 3DP artificial rocks. The results indicate that flaw geometry has remarkable influence on the mechanical and fracture behaviors of the flawed samples. The single flawed sample with α equal to 60° has the lowest compressive strength (σc) and axial strain at the peak stress (εa). σc and εa of the double flawed sample generally increase when β changes from 45° to 105°. When the flaw number increases from one to two, the initiation stress of the first wing crack, σc and εa decrease. With the aid of high-speed cameras, we studied 3D crack growth inside the transparent 3DP resin samples in real-time for the first time. Wing and anti-wing cracks wrapped around the flaw edge could only propagate for approximately 1–1.5 times the length of the initial flaw. Wing cracks generated at the inner tips of the flaws cannot coalesce, except for the sample with β of 105°. The maximum crack propagation velocity in single flawed specimens is higher than that in double flawed samples. The continuous propagation of the secondary cracks developed after the peak stress lead to the burst-like failure of the flawed samples. This study could enhance our understanding of volumetric fracturing behaviors of rocks.
New iron selenide superconductors by intercalating smaller-sized alkali metals (Li, Na) and alkaline earths using high-temperature routes have been pursued ever since the discovery of ...superconductivity at about 30 K in KFe2 Se2 , but all have failed so far. Here we demonstrate that a series of superconductors with enhanced Tc = 30∼46 K can be obtained by intercalating metals, Li, Na, Ba, Sr, Ca, Yb, and Eu in between FeSe layers by the ammonothermal method at room temperature. Analysis on their powder X-ray diffraction patterns reveals that all the main phases can be indexed based on body-centered tetragonal lattices with a∼3.755-3.831 Å while c∼15.99-20.54 Å. Resistivities show the corresponding sharp transitions at 45 K and 39 K for NaFe2 Se2 and Ba0.8 Fe2 Se2 , respectively, confirming their bulk superconductivity. These findings provide a new starting point for studying the properties of these superconductors and an effective synthetic route for the exploration of new superconductors as well.
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