This Special Issue of Cancers focuses on new advances in the treatment of renal cell carcinoma, both surgical and pharmacological (and combinations of these), and novel approaches to tackle treatment resistance and improve our understanding of this phenomenon.

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This book focuses on the recent advancements in both fundamental and clinical research, focusing on identifying, developing, and applying new and improved biological markers for specific neurologic disorders in the future. The original research work and review articles published here highlight some unique mechanisms underlying the most prevalent pathophysiological conditions affecting human health. Other areas covered in the book include emerging treatment options and correct diagnoses using different biochemical and imaging techniques.

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The high importance of free radical chemistry for a variety of biological events, including ageing and inflammation, has attracted considerable interest in understanding the related mechanistic steps at the molecular level. Modelling the free radical chemical reactivity of biological systems is an important research area. When studying free-radical-based chemical mechanisms, biomimetic chemistry and the design of established biomimetic models come into play to perform experiments in a controlled environment, suitably designed to be a similar as possible to cellular conditions. This Special Issue provides readers with a wide overview of biomimetic radical chemistry, where molecular mechanisms have been defined and molecular libraries of products are developed to be used as traces for the discoveries of some relevant biological processes. Several subjects are presented, with five articles and five reviews written by specialists in the fields of DNA, proteins, lipids, biotechnological applications and bioinspired synthesis, with “free radicals” as the common denominator.

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Professor Hong-Yuan Chen is a full-time professor of analytical chemistry at Nanjing University, China. He graduated from Nanjing University in 1961 and became a professor in 1988. He worked as a visiting scholar at Mainz University from 1981 to 1984 and was elected to the Chinese Academy of Sciences in 2001. Professor Chen is well known as a pioneer in the field of electrochemistry and biosensors. He has authored numerous papers and reviews on chemical sensors, probes, labels, and bioassays; microchips, single-cell and single-particle imaging; and spectroscopic methods, including fluorescence and electrochemiluminescence imaging. Professor Chen also has experience in live cell analysis using microneedles, and his group first described microelectrodes in 1987. This work has been adopted in IUPAC. Professor Chen has published >1,100 papers with over >55000 citations and an h-index of 114. He received National Natural Science Award (2nd Class) from the Chinese Government (2007), the Scientific and Technological Progress Award from Ho Leung Hdo Lee Foundation (2007) and the Nature’s 2015 Lifetime Award for South China, among others. This Special Issue is dedicated to celebrating the career of Professor Hong-Yuan Chen in honor of his contributions to the fields of bionic recognition and biosensors.

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This book provides new and in-depth insights into molecular aspects of plant cell signaling in response to biotic, such as aphid- and grey mold disease-resistance, and abiotic stresses, such as soil salinity and drought stress, and additionally, functional analysis on signaling components involved in flowering, juvenility, GA signaling, and biosynthesis, and miRNA-regulated gene expression. Furthermore, plant acclimation was reported, with emphasis on mechanistic insights into the roles of brassinosteroids, cyclic AMP, and hydrogen sulfide, and the recent advances of transmembrane receptor-like kinases were refined. Clearly, plant cell signaling is an intensive topic and whether it is now or in the future, the emerging technology in functional analysis such as genome editing technologies, high-throughput technologies, integrative multiple-omics as well as bioinformatics can assist researchers to reveal novel aspects of the regulatory mechanisms of plant growth and development, and acclimation to environmental and biotic stresses. The achievement of such research will be useful in improving crop stress tolerances to increase agricultural productivity and sustainability for the food supply of the world.

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This book collects 17 original research papers and 9 reviews that are part of the Special Issue “Cellular Oxidative Stress”, published in the journal Antioxidants. Oxidative stress on a cellular level affects the function of tissues and organs and may eventually lead to disease. Therefore, a precise understanding of how oxidative stress develops and can be counteracted is of utmost importance. The scope of the book is to emphasize the latest findings on the cellular targets of oxidative stress and the potential beneficial effect of antioxidants on human health.

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Chloroplasts are at the front line of many advancements in molecular biology, ranging from evolutionary biology to the mechanism of energy transduction, also including stress responses and programmed leaf death. In addition to the relevance of basic knowledge, advances are unveiling promising insights to improve plant productivity, disease resistance, and environmental control. The production of secondary metabolites and proteins by transformed chloroplasts adds further excitement to applied investigations on chloroplasts.The comparison of the sequences of the chloroplast DNA of different plants provides valuable information on gene content, reordering in the circular chloroplast DNA, and mutational genetic-derive, relevant to the evolution of the chloroplast. Increasing facilities for intense genome sequencing have prompted many laboratories to focus on the chloroplast DNA. Reflecting these efforts, more than half of the articles in this book deal with functional or evolutionary investigations based on sequence analyses of chloroplast DNA. Additional topics treated in the issue include post-transcriptional control, the processing of nuclear encoded preproteins of chloroplasts, the response of photosynthetic machinery to water deficit, turn-over of chloroplast proteins, mechanism of chloroplast division, and chloroplast movements.

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Chronic kidney disease (CKD) is a worldwide public health problem that must be addressed. The global increase in CKD prevalence is associated with an increase in conventional disease risk factors (e.g., diabetes and hypertension), which may be exacerbated by additional variables such as environmental and occupational exposure to toxic compounds. Authors contributed to this Special Issue by highlighting the finding of potential novel biomarkers of the disease and more effective therapy alternatives, as well as works that enhance the understanding of CKD pathogenesis and its related complications.

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The huge prevalence of type 2 diabetes is a leading human and economic concern worldwide. The diagnosis code of type 2 diabetes includes multiple clinical phenotypes showing different degrees of obesity, fat distribution patterns, types of dyslipidemia, and characteristics of insulin resistance syndrome. In addition, subjects with type 2 diabetes could develop different clinical trajectories, with age being a critical factor in progression. The chronic complications of type 2 diabetes are a major cause of mortality and disability, and are ranked in the top places in western countries’ scores. The pathophysiological heterogeneity of type 2 diabetes is not captured by the current classifications and guidelines. The potential for diabetes progression and complications developing is different depending on the type 2 diabetes cluster, which is mostly regardless of the degree of glycemic control. However, the impact on quality and life expectancy with the current therapeutic approach is not always the same for every individual. Clinical research is the key to reducing the burden of diabetes. New basic, digital, and clinical approaches are obtaining useful knowledge and designing more individualized interventions to prevent, track, and treat diabetic complications. This Special Issue is a clear reflection of this methodological evolution.

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Creatine plays a critical role in cellular metabolism, primarily by binding with phosphate to form phosphocreatine (PCr) as well as shuttling high-energy phosphate compounds in and out of the mitochondria for metabolism. Increasing the dietary availability of creatine increases the tissue and cellular availability of PCr, and thereby enhances the ability to maintain high-energy states during intense exercise. For this reason, creatine monohydrate has been extensively studied as an ergogenic aid for exercise, training, and sport. Limitations in the ability to synthesize creatine and transport and/or store dietary creatine can impair metabolism and is a contributor to several disease states. Additionally, creatine provides an important source of energy during metabolically stressed states, particularly when oxygen availability is limited. Thus, researchers have assessed the role of creatine supplementation on health throughout the lifespan, as well as whether creatine availability may improve disease management and/or therapeutic outcomes. This book provides a comprehensive overview of scientific and medical evidence related to creatine's role in metabolism, health throughout the lifespan, and our current understanding of how creatine can promote brain, heart, vascular and immune health; reduce the severity of musculoskeletal and brain injury; and may provide therapeutic benefits in glucose management and diabetes, cancer therapy, inflammatory bowel disease, and post-viral fatigue.

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MicroRNAs (miRNAs) are small noncoding RNAs that are 19–24 nucleotides in length, following maturation. Recent evidence has demonstrated their key role as post-transcriptional regulators of gene expression through the binding of specific sequences within target messenger RNA (mRNA). miRNAs are involved in the synthesis of a very large number of proteins, and it is speculated that they could regulate up to 30% of the human genome. They control virtually every cellular process and are essential for animal development, cell differentiation, and homeostasis. Altered miRNA expression has been linked to such pathological events as inflammatory, degenerative, or autoimmune processes and have been associated with several diseases, including cancer, cardiovascular diseases, diabetes mellitus, and rheumatic and neurological disorders. Recently, miRNAs have been found in many different biological fluids, and this observation suggests the potential of miRNAs as new candidate biomarkers for diagnosis, classification, prognosis, and responsiveness in the treatment of different pathological conditions. Furthermore, the development of therapeutic strategies that involve either restoring or repressing miRNAs expression and activity has attracted much attention. Significant progress has been made in the systems for delivery of miRNAs, even if substantial improvements in this area are still necessary. Although they have been extensively studied, a number of interesting questions regarding the physiological and pathological role of miRNAs have been postulated, and their potential diagnostic and therapeutic role remain yet unanswered. Reactive oxygen species (ROS) are free radical-containing oxygen molecules derived from cellular oxidative metabolism, including enzyme activities and mitochondrial respiration, and play a pivotal role in many cellular functions. Whereas ROS are essential for normal cellular processes, their aberrant production, or failure of the capacity to scavenge excessive ROS, induces an altered redox status with excessive synthesis of free radicals, leading to an imbalance in the redox environment of the cell. The loss of normal ROS levels causes lipid, protein, and DNA damage, which contribute to the development of various pathologies including neurological disorders, rheumatic and cardiovascular diseases, diabetes, and cancer. Increasing evidence highlights that there is crosstalk between miRNAs and components of redox signaling, even if this complex and the characteristics of mutual interaction need to be amply elucidated. Hence, both miRNAs and oxidative stress are involved in the multifactorial development and progression of acute and chronic diseases by influencing numerous signaling and metabolic pathways. The Special Issue entitled "Crosstalk between MicroRNA and Oxidative Stress in Physiology and Pathology" of the International Journal of Molecular Sciences includes original articles and reviews that provide new insights into the interaction between miRNAs and oxidative stress under normal and pathological conditions which can assist in the development of new therapeutic strategies. Finally, I would like to thank all the authors for their excellent contribution. I hope this Special Issue will provide readers with updated knowledge about the role of miRNAs and oxidative stress in physiology and pathology.

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Supporting initiation, development and resolution of appropriate immune responses is key to survival. Many nutrients and dietary components have been purported to have a role in supporting optimal immune function. This is vital throughout the life course, from the development and programming of the immune system in early life, to supporting immunity and reducing chronic inflammation in older people. In this special issue of Nutrients, we examine the evidence for the role of diet and dietary components in promoting protective immunity.

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This Special Issue begins with two preclinical studies on bergamot fruit extract (Citrus bergamia) showing reductions in oxidative stress and dyslipidemia both in vitro and in vivo. Additionally, a review explores the potential therapeutic use of combining SGLT2 inhibitors with plant extracts. In another in vivo study, humanized mice supplemented with L-carnitine and essential oil emulsions exhibited prebiotic effects on gut microbiota, reducing plasma trimethylamine N-oxide (TMAO) levels and increasing fecal short-chain fatty acids (SCFAs). Preclinical studies also examined the impact of copper nanoparticles on oxidative stress and vascular relaxation, and assessed the quality of herbal teas and dietary supplements, revealing deficiencies in their nutraceutical content. Two reviews highlight the health benefits of astaxanthin and taurine. Clinical studies include a retrospective analysis linking glucosamine usage to increased cardiovascular risk in osteoarthritis patients, and a trial demonstrating the efficacy of L-Arginine plus vitamin C supplementation in long-COVID patients. The issue concludes with three placebo-controlled trials: one showing Coenzyme Q10 plus NADH benefits on fatigue and quality of life in chronic fatigue syndrome patients, another revealing the antioxidant effects of water-soluble tomato concentrate in healthy adults, and a third highlighting the positive impact of bergamot polyphenolic fraction phytosome, artichoke extracts, Q10 phytosome, and zinc on lipid profiles, inflammation, NAFLD, and endothelial reactivity in hypercholesterolemic individuals.

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Computational fluid dynamics (CFD), which uses numerical analysis to predict and model complex flow behaviors and transport processes, has become a mainstream tool in engineering process research and development. Complex chemical processes often involve coupling between dynamics at vastly different length and time scales, as well as coupling of different physical models. The multiscale and multiphysics nature of those problems calls for delicate modeling approaches. This book showcases recent contributions in this field, from the development of modeling methodology to its application in supporting the design, development, and optimization of engineering processes.

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Cancer is a great challenge to efficient therapy due to biological diversity. Disturbed oxidative homeostasis in cancer cells certainly contributes to differential therapy response. Further, one of the hallmarks of cancer cells is adaptation which includes fine tuning of the cellular metabolic and signalling pathways as well as transcription profiles. There are several factors which contribute to the tumor diversity and therapy response, and oxidative stress is certainly one of them. Changes in oxygen levels due to hypoxia/reoxygenation during tumor growth modulate antioxidative patterns finally supporting increased cell diversity and adaptation to stressing conditions. Additionally, cancer chemotherapy based on ROS production can also induce also adaptation. To counteract these negative effects natural products are often used for their antioxidant activities as well as photodynamic therapy supported by novel chemosensitizers. Understanding of possible pathways which can trigger antioxidant defence at a certain time during cancer development can also provide possible strategies in fighting cancer.

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The general process of lipid peroxidation consists of three stages: initiation, propagation, and termination. The initiation phase of lipid peroxidation includes hydrogen atom abstraction. Several species can abstract the first hydrogen atom and include the radicals: hydroxyl, alkoxyl, peroxyl, and possibly HO* 2. The membrane lipids, mainly phospholipids, containing polyunsaturated fatty acids are predominantly susceptible to peroxidation because abstraction from a methylene group of a hydrogen atom, which contains only one electron, leaves at the back an unpaired electron on the carbon. The initial reaction of *OH with polyunsaturated fatty acids produces a lipid radical (L*), which in turn reacts with molecular oxygen to form a lipid hydroperoxide (LOOH). Further, the LOOH formed can suffer reductive cleavage by reduced metals, such as Fe++, producing lipid alkoxyl radical (LO*). Peroxidation of lipids can disturb the assembly of the membrane, causing changes in fluidity and permeability, alterations of ion transport and inhibition of metabolic processes. In addition, LOOH can break down, frequently in the presence of reduced metals or ascorbate, to reactive aldehyde products, including malondialdehyde (MDA), 4-hydroxy-2-nonenal (HNE), 4-hydroxy-2-hexenal (4-HHE) and acrolein. Lipid peroxidation is one of the major outcomes of free radical-mediated injury to tissue mainly because it can greatly alter the physicochemical properties of membrane lipid bilayers, resulting in severe cellular dysfunction. In addition, a variety of lipid by-products are produced as a consequence of lipid peroxidation, some of which can exert beneficial biological effects under normal physiological conditions. Intensive research performed over the last decades have also revealed that by-products of lipid peroxidation are also involved in cellular signalling and transduction pathways under physiological conditions, and regulate a variety of cellular functions, including normal aging. In the present collection of articles, both aspects (adverse and benefitial) of lipid peroxidation are illustrated in different biological paradigms. We expect this eBook may encourage readers to expand the current knowledge on the complexity of physiological and pathophysiological roles of lipid peroxidation.

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Fresh fruit and vegetables are considered as essential components of a healthy human diet, due to their pleasant taste and rich nutrients. However, fruits and vegetables are characterized by production seasonality, regionality, and perishability, which greatly affect the acceptance of consumers and increase the challenges of their post-harvest storage and preservation. A plurality of preservation technologies, including chemical treatment (calcium chloride, 1-methylcyclopropene, salicylic acid, etc.), physical methods (low-temperature conditioning, controlled atmosphere storage, ultraviolet-C irradiation, etc.), and biotechnology (such as genetic engineering technology) have been applied to maintain storage quality and to extend the storage life of fresh fruit and vegetables in recent years. Developing advanced preservation techniques to prolong the storage life of fruit and vegetables is of importance for improving social and economic benefits. Therefore, we invited authors to contribute original research articles and review articles focused on the innovative preservation technology of fresh produce, addressing storage problems, such as post-harvest quality deterioration caused by senescence, physiological disorders, and disease, to extend the shelf-life of fresh produce and reduce post-harvest loss.

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This topic focuses on distribution, synthesis, metabolism, and the in vivo roles of melatonin in plants, with 1 editorial, 3 reviews, 21 original research studies and 1 corrigendum.

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Mitochondria are subcellular organelles evolved by the endosymbiosis of bacteria with eukaryotic cells. They are the main source of ATP in the cell and engaged in other aspects of cell metabolism and cell function, including the regulation of ion homeostasis, cell growth, redox status, and cell signaling. Due to their central role in cell life and death, mitochondria are also involved in the pathogenesis and progression of human diseases/conditions, including neurodegenerative and cardiovascular disorders, cancer, diabetes, inflammation, and aging. However, despite the increasing number of studies, precise mechanisms whereby mitochondria are involved in the regulation of basic physiological functions, as well as their role in the cell under pathophysiological conditions, remain unknown. A lack of in-depth knowledge of the regulatory mechanisms of mitochondrial metabolism and function, as well as interplay between the factors that transform the organelle from its role in pro-survival to pro-death, have hindered the development of new mitochondria-targeted pharmacological and conditional approaches for the treatment of human diseases. This book highlights the latest achievements in elucidating the role of mitochondria under physiological conditions, in various cell/animal models of human diseases, and in patients.

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The book starts with the editors’ preface summarizing the contributions of each of the following thirteen articles dealing with chemical and pharmacological aspects of the molecular modulators of the oxidative stress in regard to various therapeutic approaches in cardiovascular and neurodegenerative diseases, cancer, and diabetes. The seven articles present data from original research studies enlightening the roles and mechanisms of action of small molecular weight compounds (natural and synthetic; ascorbic acid/vitamin C, deferoxamine, N-acetylcysteine, MitoVitE, α-tocopherol, trolox, and ezetimibe) or proteins (SIRT3) in modulation of oxidative stress. In the six review papers, the authors present and discuss the possible therapeutic potential of novel approaches and compounds that are promising and deserve further investigation, in modulation of oxidative stress.

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This volume presents recent research achievements concerning the molecular genetic basis of agronomic traits in rice. Rice (Oryza sativa L.) is the most important food crop in the world, being a staple food for more than half of the world’s population. Recent improvements in living standards have increased the worldwide demand for high-yielding and high-quality rice cultivars. To achieve improved agricultural performance in rice, while overcoming the challenges presented by climate change, it is essential to understand the molecular basis of agronomically important traits. Recently developed techniques in molecular biology, especially in genomics and other related omics fields, can reveal the complex molecular mechanisms involved in the control of agronomic traits. As rice was the first crop genome to be sequenced, in 2004, molecular research tools for rice are well-established, and further molecular studies will enable the development of novel rice cultivars with superior agronomic performance.

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This reprint focuses on research concerning various types of nanoparticles in terms of their toxicity, removal of antibiotics, and behavior in natural environments. In addition, reviews on microplastics in the atmosphere and the possible health impacts of microplastics/nanoplastics on humans are included

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Cardiac biomarkers such as troponins and natiuretic peptides have made a great impact on clinical decision making as well as improving our understanding of molecular mechanisms of different disease conditions. However, the biomarkers that are currently in use do not reflect all the multiple disease pathways that are involved in a broad spectrum of cardiac disease conditions ranging from acute coronary syndrome, to heart failure (and heart failure with preserved ejection fraction, HFpEF), to pulmonary hypertension or arrhythmias. In this Special Issue, we will provide an overview of the current developments in the field of biomarker research, beginning with research on molecular pathways and cellular communication (e.g., microRNA) up to the clinical use of biomarkers.

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Parasitic infections pose a significant public health challenge, particularly in developing countries, and can lead to long-term illness, disability, and even death. This reprint focuses on parasitic diseases and how parasites respond to the oxidative and nitrosative stress generated by the host's immune system. The articles in this Special Issue cover various aspects of this topic, including the localization of parasites within the host, the impact of nutrition and drugs, and the role of the host's immune defense cells in the parasitic response to oxidative and nitrosative stress. Understanding the mechanisms underlying parasitic diseases is crucial for developing innovative treatments that can target parasites' defense against oxidative stress. This Special Issue serves as a valuable resource for researchers, students, and physicians interested in parasitic infections.

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ROS were long considered one of the key players in tissue injury. Indeed, overproduction of ROS results in oxidative stress, a process leading to the development of many pathological conditions. For the treatment of these conditions, the use of antioxidants was proposed. Over time, it was shown that ROS at low concentrations act as signaling molecules, leading to the regulation of physiological functions. Moreover, several interventions that increase ROS generation activate stress-adaptive responses that extend the lifespan. It was also shown that excessive use of antioxidants can counter the beneficial effects of ROS. Currently, much progress has been made in understanding the role of ROS in human diseases and aging, as well as in the regulation of physiological functions, and in identifying the signaling pathways involved in ROS. However, much remains to be understood about the mutual interactions among signaling pathways underlying organisms’ adaptive responses, their modifications (which occur during aging), and some disease states. The aim of this Special Issue is to underline the effects of ROS production and antioxidant treatment in living organisms, focusing on their impact on health, disease, and aging.

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