Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called ...intermittent hypoxia or IH). Cyclic hypoxia is mimicked
and
by periodic exposure to cycles of hypoxia and reoxygenation (H-R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in increasing the risk of cancer in obstructive sleep apnea (OSA) patients. Here, we first compare and contrast the effects of acute, chronic and intermittent hypoxia in terms of molecular pathways activated and the cellular processes affected. We highlight the underlying complexity of these differential effects and emphasize the need to investigate various combinations of factors impacting cellular adaptation to hypoxia: total duration of hypoxia, concentration of oxygen (O
), and the presence of and frequency of H-R cycles. Finally, we summarize the effects of cycling hypoxia on various hallmarks of cancer highlighting their dependence on the abovementioned factors. We conclude with a call for an integrative and rigorous analysis of the effects of varying extents and durations of hypoxia on cells, including tools such as mechanism-based mathematical modelling and microfluidic setups.
Antibiotic is one of the most significant discoveries and have brought a revolution in the field of medicine for human therapy. In addition to the medical uses, antibiotics have broad applications in ...agriculture and animal husbandry. In developing nations, antibiotics use have helped to increase the life expectancy by lowering the deaths due to bacterial infections, but the risks associated with antibiotics pollution is largely affecting people. Since antibiotics are released partially degraded and undegraded into environment creating antibiotic pollution, and its bioremediation is a challenging task. In the present review, we have discussed the primary antibiotic sources like hospitals, dairy, and agriculture causing antibiotic pollution and their innovative detection methods. The strong commitment towards the resistance prevention and participation, nations through strict policies and their implementations now come to fight against the antibiotic resistance under WHO. The review also deciphers the bacterial evolution based strategies to overcome the effects of antibiotics, so the antibiotic degradation and elimination from the environment and its health benefits. The present review focuses on the environmental sources of antibiotics, it's possible degradation mechanisms, health effects, and bacterial antibiotics resistance mechanisms.
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•Antibiotic contamination is a global threat.•Ecotoxicity of antibiotics and impact on bacteria has described.•Inefficiency of WWTP's for antibiotic removal.•Bacterial strategies for resistance development is covered.•Antibiotic elimination from the environment is discussed.
The quantification of the fuzzy fault tree analysis (FFTA) is based on fuzzy arithmetic operations. It is well known that the weakest t-norm (T
)-based fuzzy arithmetic operations have some ...advantages. The T
-based fuzzy arithmetic operations provide fuzzy results with less fuzziness and preserve the shape of fuzzy numbers. The purpose of this study is to develop a T
-based fuzzy fault tree analysis (TBFFTA) to assess system reliability when only qualitative data such as expert opinions or decisions are available and described in linguistic terms. The developed TBFFTA applies T
-based fuzzy arithmetic operations to evaluate the lower bound, best estimate, and upper bound top event probability of a system fault tree, where occurrence possibilities of basic events are characterized by triangular fuzzy membership functions. To demonstrate the applicability and feasibility of TBFFTA, a case study has been performed. The computed results have been compared with results analyzed by existing fuzzy approach. The comparative study concludes that TBFFTA reduces fuzzy spreads (uncertainty interval) and provides more exact fuzzy results.
Epithelial-mesenchymal heterogeneity implies that cells within the same tumor can exhibit different phenotypes-epithelial, mesenchymal, or one or more hybrid epithelial-mesenchymal phenotypes. This ...behavior has been reported across cancer types, both in vitro and in vivo, and implicated in multiple processes associated with metastatic aggressiveness including immune evasion, collective dissemination of tumor cells, and emergence of cancer cell subpopulations with stem cell-like properties. However, the ability of a population of cancer cells to generate, maintain, and propagate this heterogeneity has remained a mystifying feature. Here, we used a computational modeling approach to show that epithelial-mesenchymal heterogeneity can emerge from the noise in the partitioning of biomolecules (such as RNAs and proteins) among daughter cells during the division of a cancer cell. Our model captures the experimentally observed temporal changes in the fractions of different phenotypes in a population of murine prostate cancer cells, and describes the hysteresis in the population-level dynamics of epithelial-mesenchymal plasticity. The model is further able to predict how factors known to promote a hybrid epithelial-mesenchymal phenotype can alter the phenotypic composition of a population. Finally, we used the model to probe the implications of phenotypic heterogeneity and plasticity for different therapeutic regimens and found that co-targeting of epithelial and mesenchymal cells is likely to be the most effective strategy for restricting tumor growth. By connecting the dynamics of an intracellular circuit to the phenotypic composition of a population, our study serves as a first step towards understanding the generation and maintenance of non-genetic heterogeneity in a population of cancer cells, and towards the therapeutic targeting of phenotypic heterogeneity and plasticity in cancer cell populations.
Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties ...such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.
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The cancer stem cell (CSC) concept stands for undifferentiated tumor cells with the ability to initiate heterogeneous tumors. It is also relevant in metastasis and can explain how metastatic tumors ...mirror the heterogeneity of primary tumors. Cellular plasticity, including the epithelial-to-mesenchymal transition (EMT), enables the generation of CSCs at different steps of the metastatic process including metastatic colonization. In this review, we update the concept of CSCs and provide evidence of the existence of metastatic stem cells (MetSCs). In addition, we highlight the nuanced understanding of EMT that has been gained recently and the association of mesenchymal-to-epithelial transition (MET) with the acquisition of CSCs properties during metastasis. We also comment on the computational approaches that have profoundly influenced our understanding of CSCs and EMT; and how these studies and new experimental technologies can yield a deeper understanding of the biological aspects of metastasis.
The epithelial-mesenchymal transition (EMT) is a process by which cells lose epithelial traits, such as cell-cell adhesion and apico-basal polarity, and acquire migratory and invasive traits. EMT is ...crucial to embryonic development and wound healing. Misregulated EMT has been implicated in processes associated with cancer aggressiveness, including metastasis. Recent experimental advances such as single-cell analysis and temporal phenotypic characterization have established that EMT is a multistable process wherein cells exhibit and switch among multiple phenotypic states. This is in contrast to the classical perception of EMT as leading to a binary choice. Mathematical modeling has been at the forefront of this transformation for the field, not only providing a conceptual framework to integrate and analyze experimental data, but also making testable predictions. In this article, we review the key features and characteristics of EMT dynamics, with a focus on the mathematical modeling approaches that have been instrumental to obtaining various useful insights.
Abstract
Environmental degradation due to the carbon emissions from burning fossil fuels has triggered the need for sustainable and renewable energy. Hydrogen has the potential to meet the global ...energy requirement due to its high energy density; moreover, it is also clean burning. Photoelectrochemical (PEC) water splitting is a method that generates hydrogen from water by using solar radiation. Despite the advantages of PEC water splitting, its applications are limited by poor efficiency due to the recombination of charge carriers, high overpotential, and sluggish reaction kinetics. The synergistic effect of using different strategies with cocatalyst decoration is promising to enhance efficiency and stability. Transition metal-based cocatalysts are known to improve PEC efficiency by reducing the barrier to charge transfer. Recent developments in novel cocatalyst design have led to significant advances in the fundamental understanding of improved reaction kinetics and the mechanism of hydrogen evolution. To highlight key important advances in the understanding of surface reactions, this review provides a detailed outline of very recent reports on novel PEC system design engineering with cocatalysts. More importantly, the role of cocatalysts in surface passivation and photovoltage, and photocurrent enhancement are highlighted. Finally, some challenges and potential opportunities for designing efficient cocatalysts are discussed.
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