The present study provides molecular insight into the mechanisms underlying energy dissipation and lubrication of a smooth contact lubricated by an ionic liquid. We have performed normal and lateral force measurements with a surface forces apparatus and by colloidal probe atomic force microscopy on following model systems: 1-ethyl-3-methyl imidazolium bis-(trifluoro-methylsulfonyl)imide, in dry state and in equilibrium with ambient (humid) air; the surface was either bare mica or functionalized with a polymer brush. The velocity-dependence of the friction force reveals two different regimes of lubrication, boundary-film lubrication, with distinct characteristics for each model system, and fluid-film lubrication above a transition velocity V*. The underlying mechanisms of energy dissipation are evaluated with molecular models for stress-activated slip and flow, respectively. The stress-activated slip assumes that two boundary layers (composed of ions/water strongly adsorbed to the surface) slide pass each; the bond dynamics and the strength of the interaction at the slip plane dictate the change in friction -decreasing, increasing or remaining constant- with velocity in the boundary-film lubrication regime. Above a transition velocity V*, friction monotonically increases with velocity in the three model systems. Here, layers of ions slide past each (“flow”) under a shear stress and friction depends on a shear-activation volume that is significantly affected by confinement. The proposed friction model provides a molecular perspective of the lubrication of smooth contacts by ionic liquids and allows identifying the physical parameters that control friction.

Smoking is a pervasive global health concern associated with a myriad of diseases, but its impact on cellular aging, particularly in relation to telomeres, is increasingly recognized. Telomeres, protective caps at the ends of chromosomes, play a crucial role in maintaining genomic integrity. This review critically examines the existing evidence on the association between smoking and telomere atrophy, exploring the molecular mechanisms involved and the implications for accelerated aging and heightened disease risk. The comprehensive analysis encompasses both cross-sectional and longitudinal studies, elucidating potential gender and age disparities. Insights into the molecular pathways linking smoking to telomere shortening are discussed, along with the broader implications for public health. The review concludes by outlining potential interventions and suggesting future research directions in this critical area.

Weeds are a permanent component of anthropogenic ecosystems, which requires strict control to avoid the accumulation of their long–lasting seeds in the soil. With high crop infestation, many elements of crop production technologies (fertilization, productive varieties, growth stimulators, etc.) turn out to be practically meaningless due to high yield losses. Intensive use of chemical herbicides (CH) has led to undesirable consequences: contamination of soil and wastewater, accumulation of their residues in the crop, the emergence of CH-resistant populations of weeds. In this regard, the development of environmentally friendly CH with new mechanisms of action is relevant. Natural phytotoxins of plant or microbial origin may be directly explored in herbicidal formulations (biorational CH) or indirectly as scaffolds for nature-derived CH. This review considers: 1) the main current trends in the development of CH that may be important for enhancement of biorational herbicides; 2) advances in the development and practical application of natural compounds for weed control; 3) the use of phytotoxins as prototypes of synthetic herbicides. Some modern approaches such as computational methods of virtual screening and design herbicidal molecules, development of modern formulations, determination of molecular targets are stressed as important to make exploration of natural compounds more effective.

The formability and failure behavior of TRIP steel blanks were investigated through various stress states. The forming limit diagram (FLD) at fracture is constructed both experimentally and numerically. Numerical studies are performed to evaluate the applicability of different damage criteria in predicting the FLD as well as complex cross-die deep drawing process. The fracture surface and numerical results revealed that the material failed in a different mode for different strain path. Therefore, Tresca model which is based on shear stress accurately predicted the conditions where shear had the profound effect on the damage initiation, whereas Situ localized necking criterion was able to calculate the conditions which localization was dominant.

This work aims to explore the impact of side loads, drill-pipe tool-joint (DP-TJ) speed (RPM), and mud type on the austenitic stainless steel SM2535-110 casing wear characteristics. Actual field drill pipe tool joints, casings, and drilling muds are used in this study. The results of the study show that under both types of lubrication, the wear volume increased with radial load and DP-TJ speed. SM2535-110 casing specimens tested under oil-based mud (OBM) lubrication had higher casing wear volumes than those obtained under water-based mud (WBM) lubrication. This unexpected behavior is mainly due to the increase in the surface hardness of the casing specimens tested under WBM. The results also show that the specific wear factor (K) values of specimens tested under WBM are in general 2 to 4 times higher than those obtained under OBM. While K values under WBM increase with both the side load and RPM, those under OBM show a sharp decrease with RPM. This behavior under OBM is due to this lubricant’s higher viscosity and the change of lubrication regime from thin film to thick film lubrication at higher RPM. Scanning electron microscopy (SEM) and the digital microscopic imaging (DMI) of SM235-110 casing specimens show that an aggressive combination of adhesive, abrasive, and plastic deformation was observed under WBM, while the dominant wear mechanism under OBM is abrasive wear.

Uncontrolled chronic inflammation results in cardiovascular disease and early death. In this review, we studied the impact of rheumatoid arthritis on the cardiovascular system, including the early and accelerated development of atherosclerosis, and its clinical manifestations, focusing on the inflammatory mechanisms leading to arterial wall damage, rapid atherosclerotic plaque formation, and thrombosis. Furthermore, the influence of medications used to treat rheumatoid arthritis on the cardiovascular system. The influence of chronic inflammation and medicaments on traditional cardiovascular risk factors is not the main subject of this review. We found that uncontrolled chronic inflammation and some medications directly impact all stages of atherosclerosis. In conclusion, reducing inflammation and maintaining long-term remission in rheumatoid arthritis may pre-vent early atherosclerosis. We believe that this review will encourage a better interdisciplinary approach for these patients and further research in this field.

This study introduces a fruit harvesting mechanism powered by a single motor, designed for integration with unmanned aerial vehicles (UAVs). The mechanism performs reciprocating motion by converting linear motion into rotational motion. Consequently, the end-effector can execute multi-dimensional kinematic trajectories, including biaxial and rotational movements, synchronized with the motor's position. These axial and rotational motions facilitate the gripper's ability to reach, retrieve, and detach fruit from branches during the harvesting process. Notably, a critical consideration in designing this fruit harvesting mechanism is to generate the necessary torque at the end-effector while minimizing reaction forces and torque that could destabilize the UAV during flight. With these considerations in mind, this preliminary study aimed to harvest a Fuji apple and conducted dynamic analysis. We constructed a prototype of the single motor-driven fruit harvesting mechanism using a suitable servo motor. To assess its mechanical performance and evaluate its impact on the hexacopter, we developed both a specific test platform featuring a six-spherical-prismatic-spherical parallel structure and a virtual environmental flight simulator. Overall, the results demonstrate the successful harvesting of a Fuji apple weighing approximately 300 g by the single motor-driven fruit harvesting mechanism, with no adverse effects observed on the hexacopter's operation.

Given the significant role of the Ningxia Urban Agglomeration along the Yellow River in reshaping the urban network and promoting coordinated development in the upper Yellow River region of China, this paper takes enterprise flow as the explicit manifestation of the regional urban network. Based on the data of registered enterprises from 2005 to 2021, combined with the interlocking network model, social network analysis method, and spatial panel econometric model, this paper interprets the evolution of the regional urban network structure and its influencing mechanisms through the different types of enterprise flow. The results indicate the following: (1) The external network is primarily focused on outflow investments towards North China, East China, and Northwest China. The overall inflow sources form a multi-origin structure dominated by North China and East China. The Jinfeng and Xingqing serve as core hubs for enterprise exports in the external network and destinations for incoming enterprises. However, in the Productive manufacturing connections, a spatial organizational pattern driven by multiple cities has formed. (2) In the internal network, a concentric connection structure centered around the Jinfeng and Xingqing has formed. The Productive service connections are relatively active, while the Productive manufacturing connections are relatively concentrated between the Jinfeng, Xingqing, Ningdong, and Lingwu. However, there is an imbalance in the spatial connections within the urban agglomeration network and an incomplete hierarchical system of network nodes. (3) In the external network, the main feature is the absorption of external elements to foster development momentum. In the internal network, the Jinfeng and Xingqing serve as contact and radiation sources, influencing various nodes. However, their driving capacity is weak. (4) The market demand and coordinated development both demonstrate significant promoting effects on the connections within the external and internal networks. The sluggish adjustment and transformation of regional industrial structure have resulted in a temporary negative inhibitory effect on the development of transformation. The negative impact of urban investment activities and the positive impact of government management are reflected within the internal network. (5) The improvement of urban management and service functions, as well as external borrowing, can promote the connection in different network. However, the borrowing economic activity can have a negative impact in different networks. (6) Industrial agglomeration can promote enterprises connections in different networks and generate significant spatial spillover effects.

Poa crymophila is a perennial, cold-tolerant, native grass species, widely distributed to the Qing-hai-Tibet Plateau. However, the molecular mechanism behind the cold stress tolerance and role of key regulatory genes and pathways of P. crymophila are poorly understood yet. Therefore, the present study investigated the physiological and transcriptome responses of P. crymophila’s roots, stems, and leaves under cold stress to explore the molecular mechanism of cold tolerance. Results of the present study suggested that cold stress significantly changed the physiologic characteristics of roots, stems, and leaves of P. crymophila. In addition, the transcriptome results showed that 4434, 8793, and 14942 differentially expressed genes (DEGs) were identified in roots, stems, and leaves, respectively; however, 464 DEGs were commonly identified in these three tissues. The Gene On-tology (GO) results showed that a large numbers of DEGs were significantly enriched in the pho-tosynthetic related categories in leaves. In addition, the “response to stimulus” category was sig-nificantly enriched in roots and stems. The Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that DEGs involved in “phenylpropanoid biosynthesis” were significantly enriched in roots, “photosynthesis” and “circadian rhythm-plant” pathways significantly enriched in stems and leaves, starch and sucrose metabolism, and galactose metabolism were pathways significantly enriched in three tissues. Weighted gene coexpression network analysis (WGCNA) identified Hub genes involved in P. crymophila cold response. This study provides new insights into the molecular mechanisms underlying the cold tolerance of P. crymophila belowground and aboveground tissues. In addition, specific genes involved in Ca2+ signaling, ROS scavenging system, hormones, circadian clock, photosynthesis, and transcription factors (TFs) were identified in P. crymophila. The identi-fication of key genes may provide valuable resources for further functional genomic and breeding studies.

Farmers and seed companies constantly require high-quality seeds with excellent agronomic performance. However, faced with environmental adversity, limited natural resources and increasing food demand around the globe, more attention has turned to improving crop plant production by implementing efficient strategies. Seed priming technology has shown promising biological improvements leading to suitable agronomic performance in crop plants under adverse environmental conditions. Seeds are subjected to controlled conditions that are conducive to complex physiological, biochemical, and molecular changes, conferring specific stress tolerance to subsequent germination and growth conditions. In this review paper, we aimed to study the recent approaches in the efficiency of hydropriming, osmopriming, chemopriming, hormopriming, nanopriming, matrix priming, biopriming, physical priming and hybrid priming procedures in the production of crop plants under environmental adversity, as well as their biological mechanism changes. All priming methods demonstrated relevant changes in the biological mechanism related to crop plant production by mitigating salinity effects, heavy metals, and flooding stress and enhancing chilling, heat, drought and phytopathogen tolerance. We strongly recommend that researchers combine multiple priming methods, known as hybrid priming, in their investigations to provide novel technologies and additional biological approaches to enhance the knowledge of crop plant science. Thus, the findings shed light on the use of seed priming technology as a key strategy to increase crop plant production under environmental adversity by acquiring stress tolerance and enhancing agronomic traits to meet the global food demand.

The immunomodulatory behaviour of the CCR6/CCL20 axis in multi -system pathophysiology and molecular signalling was investigated at two clinically significant time points, using a Ccr6 - deficient mouse model of spontaneous colitis. Four groups of mice, (C57BL/6J, Ccr6^-/- of C57BL/6J, Winnie x Ccr6 ^-/- and Winnie) were utilized and (I) colonic clinical parameters (2) histology of colon, spleen, kidney and liver (3) T and B lymphocyte distribution in the spleen and MLN by flowcytometry (5) colonic CCL20, phosphorylated PI3K and phosphorylated Akt expression by immunohistochemistry and (6) colonic cytokine expression by RT-PCR were evaluated. CCR6 deficiency was shown to attenuate inflammation in the spleen, liver and gut while renal histology remained unaffected. Marked focal lobular inflammation with reactive nuclear features were observed in hepatocytes and a significant neutrophil infiltration in red pulp with extra medullary hemopoiesis in the spleen existed in Winnie. These changes were considerably reduced in Winnie x Ccr6^-/- with elevated goblet cell numbers and mucus production in the colonic epithelium. Results indicate that Ccr6- deficiency in the colitis model contributes towards resolution of disease. Our findings demonstrate an intricate networking role for CCR6 in immune activation, which is downregulated by Ccr6 deficiency, and could provide newer clinical therapies in colitis.

Causality is the most important topic in the history of Western Science, and since the beginning of the statistical paradigm, it meaning has been reconceptualized many times. Causality entered into the realm of multi-causal and statistical scenarios some centuries ago. Despite of widespread critics, today Deep Learning and Machine Learning advances are not weakening causality but are creating a new way of finding indirect factors correlations. This process makes possible us to talk about approximate causality, as well as about a situated causality.

Rice production, owing to its high-water requirement for cultivation, is very vulnerable to the threat of changing climate, particularly prolonged drought and high temperature. Such threats heighten the need for abiotic stress-resilient rice varieties with better yield potential. This review examines the physiological and molecular mechanisms of rice varieties to cope with stress conditions of drought (DS), high temperature (HTS) and their combination (DS-HTS). It appraises research studies in rice about its various phenotypic traits, genetic loci and response mechanisms to stress conditions to help craft new breeding strategies for rice varieties with improved resilience to abiotic stresses. This review consolidates available information on promising rice cultivars with desirable traits as well as advocates synergistic and complementary approaches in molecular and systems biology to develop new rice breeds that favorably respond to climate-induced abiotic stresses. The development of new breeding and cultivation strategies for climate-resilient rice varieties is a challenging task. It requires a comprehensive understanding of the various morphological, biochemical, physiological, and molecular components governing yield under drought and high temperature, but possible by implementing cohesive approaches involving molecular and systems biology approaches in genomics and molecular breeding, including genetic engineering.

With the emergence of COVID-19 pandemic in 2019, the world saw a humungous loss of human life and economic resources globally but also the rapid appearance of SARS-CoV-2 variants which have exhibited a higher transmissibility and/or virulence and which also evade immune system to such an extent that it raises a big question mark on the efficacy of current diagnostics, vaccines and convalescent plasma and mAb therapies. This has been attributed to the emergence of huge spectrum of mutations, especially in the virus’s spike (S) protein, occurring in regions harboring high concentration of B cell epitopes thus allowing neutralizing antibody escape. The mutations resulting in ACE 2 receptor recognition failure (T19R), unfavorable electrostatic interactions (E484K), structural change (∆69-70), disruption of hydrogen bonds, salt bridges or hydrophobic interactions (K417N, N501Y, ∆Y145) and change in orientation (N501Y) cause strong immune evasion by these variants. Further, the recent emergence of Omicron with more than 30 mutations in the S protein VOC allows it to escape and fail diagnosis as well as immune system and the protection generated by different vaccination regimes. Yet Omicron may not be the end of the story. This review presents an insight of the immunity escape and its mechanisms followed by different SARS-CoV-2 variant of concerns.

Understanding how plants change their root foraging strategy in the presence of neighbors is of paramount importance for plant ecology and agriculture. The root tragedy of the common (RToC) is a plant behavior predicted by game theory models in which competing plants forage for soil resources inefficiently. The RToC is generally assumed to be induced by non-self root recognition, and researchers consider root overproliferation and reduced fitness with respect to a plant growing solo as the trace left by plants engaging in an RToC in experiments and model results. Herein, I first challenge both notions, and argue that the RToC is a suboptimal phenotypically plastic response of plants that is based in soil resource information exclusively. Second, I discuss how this new perspective carries important implications for the design of experiments investigating the physiological mechanisms underlying observable plant root responses. Finally, I discuss why placing the RToC theory in the context of more general root research is fundamental: The RToC represents a mechanistic foundation for understanding the belowground behavior of plants interacting with neighbors, and a spatially explicit approach to RToC may produce more comprehensive results.

During the last years, epigenetic processes have emerged as important factors for many neurodegenerative diseases, such as Alzheimer’s diseases (AD). These complex diseases seem to have a heritable component; however, genome-wide association studies failed to identify the genetic loci involved in the eatiology. So, how can these changes be transmitted from one gen-eration to the next? Answering this question would allow us to understand how the environ-ment can affect human populations for multiple generations and explain the high prevalence of neurodegenerative diseases, such as AD. This review pays particular attention to the relationship among epigenetics, cognition, and neurodegeneration across generations, deepening the under-standing of the relevance of heritability in neurodegenerative diseases. In fact, we highlight some recent examples of EI induced by experiences, focusing on their contribution of processes in learning and memory, to point out new targets for therapeutic interventions. Here, we first describe the prominent role of epigenetic factors in memory processing. Then, we briefly discuss aspects of EI. And ends, we summarize evidence of how epigenetic marks inherited by experi-ence and/or environmental stimuli contribute to cognitive status offspring, since better knowledge of EI can provide clues in the appearance and development of age-related cognitive decline and AD.

Compliant amplifying mechanisms are used widely in high-precision instruments driven by piezoelectric actuators, and the dynamic and static characteristics of these mechanisms are closely related to instrument performance. Although the majority of existing research has focused on analysis of their static characteristics, the dynamic characteristics of the mechanisms affect their response speeds directly. Therefore, this paper proposes a comprehensive theoretical model of compliant amplifying mechanisms based on the multi-body system transfer matrix method to analyze the dynamic and static characteristics of these mechanisms. The effects of the main amplifying mechanism parameters on the displacement amplification ratio and the resonance frequency are analyzed comprehensively using the control variable method. An iterative optimization algorithm is also used to obtain specific parameters that meet the design requirements. Finally, simulation analyses and experimental verification tests are performed. The results indicate the feasibility of using the proposed theoretical compliant amplifying mechanism model to describe the mechanism’s dynamic and static characteristics, which represents a significant contribution to the design and optimization of compliant amplifying mechanisms.

The Pingbei area is the main accumulation area of oil and gas in the Xihu Sag. The phase characteristics of oil and gas in this area are complex, and the understanding of their genesis is still unclear. In this paper, based upon discussions of crude oil and natural gas geochemical data, integrated with local geological features, we discuss the sources, migration, and phase state characteristics of oil and gas in the Pingbei area of the Xihu Sag. The study results showed that the crude oil and natural gas in the Pingbei area are coal-derived and the oil and gas produced by the humic organic matter during the maturity stage. The oil and gas source correlation showed that crude oil and natural gas have good affinity with the Eocene Pinghu Formation (PF) coal-bearing source rocks. Crude oil has the characteristics of near-source accumulation and short-distance migration while natural gas is supplied from a dual source: the coal-derived hydrocarbon rocks of PH in the deep part of the study area, supplemented by the coal-derived hydrocarbon rocks of PH on the bottom of the slope, and adjacent hydrocarbon-bearing sub sag. The distribution characteristics and geochemical migration indices of hydrocarbon showed that the oil generated from the hydrocarbon source rocks of PH in the deep Pingbei area mainly migrates vertically along the fault connecting the reservoir and the source rocks to the trap, where it accumulates, while the natural gas exhibits deep and large faults that mainly migrate vertically, supplemented by its lateral migration along the composite transport system composed of faults and sandstone layers in the slope zone. The mechanisms of produced, exhausted, and geochromatographic effects (PGE), as well as evaporative fractionation (EF) and phase-controlled migration fractionation (PMF), result in the obvious discrepancy of hydrocarbon’s properties on the vertical profiles.

Parasitic diseases are among the most serious public health problems in developing countries, causing high mortality and economic burdens. The Trypanosomatidae family includes Leishmania spp. and Trypanosoma cruzi, which cause leishmaniasis and Chagas disease, respectively. Both these parasites are among the major agents of neglected tropical diseases (NTDs). Leishmaniasis is currently the second most widespread vector-borne parasitic disease after malaria. The World Health Organization (WHO) records approximately 0.7-1 million newly diagnosed leishmaniasis cases each year, resulting in approximately 20,000-30,000 deaths. Also, 25 million people worldwide are at risk of Chagas disease and an estimated 6 million people are infected with Trypanosoma cruzi. Despite the similarity of the parasites, the evolution of the disease and the clinical indexes are explicitly different in African, Asian, and American forms of infection. Clinical therapies are associated with drug resistance and side effects. As a result, the discovery of novel therapeutic agents has emerged as a top priority and a promising alternative. Peptide-based drugs are an attractive class of therapeutic agents. They are recognized for being highly selective and effective, as well as safe and well tolerated. Moreover, they are now being explored in the development of novel therapeutics for a variety of health disorders, including oncology, endocrinology, metabolic, cardiovascular, and bone diseases. In addition, they are being explored in tropical diseases such as leishmaniasis and Chagas disease. We will discuss current knowledge regarding the parasite life cycle, signs and symptoms, diagnosis, and treatment options for leishmaniasis and Chagas disease.

In crank presses, an important role is played by the presence of actuators with dwell, in which, with continuous movement of the input links, the output working link remains stationary at some part of the work. The use of a high-class structural group (fourth class) expands the functionality of the crank press, including it can ensure the link dwell of the working link on a given section of movement during the required period of time. As a result of the conducted research, four variants of actuators of the crank knee press were designed. Due to the rational choice of the positions of racks and crosshead guide, the best layout of the dimensions of the press mechanism has been achieved, changing the coordinates of the racks accordingly allows to design a mechanism with upper or lower dwells of the working links. When synthesizing (selecting) parameters such as: l_2 and h, it is possible to obtain a height of different duration. All this is shown on the basis of a numerical experiment based on kinematic analysis. In addition, the complex structure of the mechanism makes it possible to ensure the exact link dwell, which cannot be achieved due to the well-known knee presses based on the second-class mechanism [21].

Postoperative headaches (POH) following retrosigmoid microsurgery for ves-tibular schwannoma (VS) can significantly diminish patients' perceived health benefits (PHB). A survey of 101 VS patients, utilizing the Rostock Headache Compendium, Glasgow Benefit Inventory, Ten-Item Personality Inventory (TI-PI-G), and German pain processing questionnaire (FESV), revealed that almost half experienced POH, leading to a markedly reduced overall PHB compared to those without POH. This decrease in PHB was linked to higher levels of pain-related helplessness, depression, anxiety, and anger. Positive associations were found between PHB and action-planning competence, cognitive restruc-turing, and experience of competence. Personality traits, particularly low emo-tional stability and openness, were associated with pain-related psychological impairment. Interestingly, hearing loss and facial paresis did not impact PHB. The study underscores the influence of pain-related mental interference and coping strategies on PHB in long-term POH patients, suggesting a role for personality traits in their pain management. The findings advocate for short-term psychological interventions, emphasizing adaptive coping mecha-nisms like cognitive restructuring, to enhance PHB in VS patients post-microsurgery.

Astronauts in space are subject to a continuous bombardment of ionizing radiation. The Earth's magnetic field and the ISS shield some biologically damaging particles traveling through. Still, travel beyond low-Earth orbit and extravehicular activities are exceedingly more dangerous and there is a concern for the acute and late-occurring adverse health effects befalling astronauts. So, it is vital to consider the current tools and models used to describe and study the organic consequences of ionizing radiation exposure. It is equally important to see where these models may improve. This article reviews the historical development and current state of knowledge of radiation effects impacting astronauts in orbit. We explain the space radiation environment, cellular microenvironment, and how these may be incorporated in radiobiological models to aid in our understanding of the influence space travel may have on astronaut health. The topics discussed in this paper include a review of DNA damage and repair mechanisms and the numerical models that aim to explain the biological effects resulting from ionizing radiation damage. Historically, radiobiological models focused on how radiation damages nuclear DNA, built upon the hypotheses of Crowther and Lea in the 1940s and 1960s, and neglected other sub-cellular targets outside of nuclear DNA.

Animal-assisted interventions (AAI) are a unique class of complementary medical treatments that can improve a patient’s quality of life, both physically and psychologically. Part I of this two-paper systematic literature review series focused on the study methods and quantitative results of researchers in this field. We continue this in-depth review here in Part II by discussing the common theories associated with AAI in the context of cancer. Of all the factors at work in human-animal interactions, researchers explicitly cite compatible animal personality, physical touch, physical movement, distraction/entertainment, and increased human interaction as the mechanisms responsible for the positive clinical outcomes observed in AAI. In various combinations, these mechanisms group under broader theoretical frameworks that attempt to fully explain the AAI context as it relates to cancer care. The social support hypothesis and the conception of a human-animal bond are the most referenced overarching frameworks. The cognitive activation theory of stress, the science of unitary human beings, and the self-object hypothesis are also referenced. We briefly consider other relevant theories commonly noted in the human-animal interactions literature that have the potential to clarify aspects of cancer-related AAI. We also discuss the neurobiological transduction mechanisms needed to connect theoretical frameworks and their mechanisms directly to the observed clinical outcomes. To advance the field, researchers should consider overarching theories with testable hypotheses when designing studies, and use consistent terminology when reporting results. This review lays a foundation for progress towards a unified theoretical framework and for effective treatment of the whole cancer patient.

Heavy metals and metalloids (HMs) are environmental pollutants, most notably cadmium, lead, arsenic, mercury, and chromium. When HMs accumulate to toxic levels in agricultural soils, these non-biodegradable elements adversely affect crop health and productivity. The toxicity of HMs on crops depends upon factors including crop type, growth condition, and developmental stage; nature of toxicity of the specific elements involved; soil physical and chemical properties; occurrence and bioavailability of HM ions in the soil solution; and soil rhizosphere chemistry. HMs can disrupt normal structure and function of cellular components and impede various metabolic and developmental processes. This review evaluates: (1) HM contamination in arable lands through agricultural practices, particularly due to chemical fertilizers, pesticides, livestock manures and compost, sewage-sludge based biosolids, and irrigation; (2) factors affecting the bioavailability of HM elements in the soil solution, and their absorption, translocation, and bioaccumulation in crop plants; (3) mechanisms by which HM elements directly interfere with the physiological, biochemical, and molecular processes in plants with particular emphasis on the generation of oxidative stress, inhibition of photosynthetic phosphorylation, enzyme/protein inactivation, genetic modifications, and hormonal deregulation, and indirectly through inhibition of soil microbial growth, proliferation, and diversity; and (4) visual symptoms of highly toxic non-essential HM elements in plants with an emphasis on crop plants. Finally, suggestions and recommendations are made to minimize crop losses from suspected HM contamination in agricultural soils.

Pediatric obstructive sleep apnea (OSA) has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. Recently, much attention has been paid to the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric OSA and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly. It is associated with aging and hair cell death due to oxidative stress-induced mitochondrial dysfunction. Although transgenic mice and long-term cultures for induction of aging have been used to study ARHL, there are presently no ARHL animal models stimulated by intermittent environmental change for aging. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined based on the expression of the hearing loss-induced phenotype and aging related factors in the short term. The incidence of hearing loss was significantly different among the groups subjected to intermittent hypoxic environment, high-fat diet (HFD), and injection with D-galactose. Continuous oxidative stress and HFD were factors that accelerated cellular aging. Increase in UCP2 affected oxidative stress and mitochondrial dysfunction. CDH23, SLC26A4, KCNQ4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in cells of the hearing organ. We found that intermittent hypoxic, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects intermittent environmental changes, will benefit future research on ARHL.

Anthracnose stands as the primary obstacle to lupin cultivation, impeding development despite the considerable agronomic, ecological, and economic potential of such legume crops. This review explores recent efforts to unravel the complexities of anthracnose in domesticated lupins, focusing on both the plant perspective and the causative pathogenic agent, Colletotrichum lupini. Leveraging cutting-edge technologies has yielded crucial insights into various facets of this devastating disease, encompassing plant and pathogen biology, genetic and molecular regulations of the interaction, fungal diversity and population dynamics, and screening of plant genetic resources for anthracnose resistance. The lack of effective disease control measures, relying primarily on the use of disease-free seeds, highlights the need to develop anthracnose-resistant varieties. However, challenges arise from the intricacy of lupin's response to the disease, influenced by polygenic inheritance, in spite of loci with major effects, and environmental factors. The slow pace of genetic improvement underscores the need for more efficient breeding processes, including biotechnological approaches. This review offers a comprehensive overview of current progress and knowledge gaps, stressing the urgent need to further enhance understanding of C. lupini pathogenic mechanisms and lupin‘s resistance. Integrating advanced technologies and accelerated research efforts is paramount for achieving efficient disease management and sustainable lupin cultivation in the face of anthracnose challenges.

Extracorporeal shock wave therapy (ESWT) is a safe and effective treatment option for various pathologies of the musculoskeletal system. Many studies addressed the molecular and cellular mechanisms of action of ESWT. However, no uniform concept could be established in this matter until now. We performed a systematic review of the effects of exposure of musculoskeletal tissue to extracorporeal shock waves (ESWs) reported in the literature. The key results were as follows: (i) compared to the effects of many other forms of therapy, the clinical benefit of ESWT does not appear to be based on a single mechanism; (ii) different tissues respond to the same mechanical stimulus in different ways; (iii) just because a mechanism of action of ESWT was described in a study does not automatically mean that this mechanism was relevant to the observed clinical effect; (iv) focused ESWs and radial ESWs seem to act in a similar way; and (v) even the most sophisticated research into the effects of exposure of musculoskeletal tissue to ESWs cannot substitute clinical research in order to determine the optimum intensity, treatment frequency and localization of ESWT.

Radio loud active galactic nuclei are composed of different spatial features, each one characterized by different spectral properties in the radio band. Among them, blazars are the most common class of sources detected at gamma-rays by \fermi, and their radio emission is dominated by the flat spectrum compact core. In this contribution, we explore the connection between emission at high energy revealed by \fermi\ and at radio frequency. Taking as a reference the strong and very highly significant correlation found between gamma rays and cm-$\lambda$ radio emission, we explore different behaviours found as we change the energy range in gamma rays and in radio, therefore changing the physical parameters of the zones involved in the radiation emission. We find that the correlation weakens when we consider (1) gamma rays of energy above 10 GeV (except for high synchrotron peaked blazars) or (2) low frequency radio data taken by the Murchison Widefield Array; on the other hand, the correlation strengthens when we consider mm-$\lambda$ data taken by ALMA.

This paper aims to provide the smart grid research community with an open and accessible general mathematical framework to develop and implement optimal flexibility mechanisms in large-scale network applications. The motivation of this paper is twofold. On the one hand, flexibility mechanisms are currently a hot topic of research, which is aimed to mitigate variation and uncertainty of electricity demand and supply in decentralised grids with a high aggregated share of renewables. On the other hand, a large part of such related research is performed by heuristic methods, which are generally inefficient (such methods do not guarantee optimality) and difficult to extrapolate for different use cases. Alternatively, this paper presents an MPC-based (Model Predictive Control) framework explicitly including a generic flexibility mechanism which is easy to particularise to specific strategies such as Demand Response, Flexible Production and Energy Efficiency Services. The proposed framework is benchmarked with other non-optimal control configurations to better show the advantages it provides. The work of this paper is completed by the implementation of a generic use case which aims to further clarify the use of the framework and thus, to ease its adoption by other researchers in their specific flexibility mechanisms applications.

Forensic anthropologists play a key role in skeletal trauma analysis and commonly use macroscopic features to distinguish between trauma types. However, this approach can be challenging, particularly in cases of highly comminuted or incompletely recovered fractures. Histological analysis of microscopic fracture characteristics in fractured bones may thus help provide additional information on trauma type and bone fracture biomechanics in general. This study analysed the extent of microcrack damage to osteons in long bones with blunt force trauma (BFT) and gunshot trauma (GST), from both traumatic death cases and post-mortem experimental fractures. We identified four types of osteonal damage (OD). In traumatic death cases, OD affecting the inside of the osteon and compromising the Haversian canal (type 1) was found to be indicative of BFT. Moreover, OD affecting the cement line (type 3) and interstitial lamellae (type 4) was more common in the GST samples. OD affecting the inside of the osteon without compromising the Haversian canal (type 2) was not found to be indicative of either trauma type. In cases of experimental fractures, our study revealed that post-mortem fractures in dry bone samples featured the highest amount of OD, particularly of type 4. This study also found that the experimentally produced GST featured similar OD pattern to GST death cases. These findings support our hypothesis that there are distinct osteonal damage patterns in human long bones with BFT and GST, which are of relevant value for trauma analysis in forensic anthropology.

Cyclic vomiting syndrome (CVS) is a frequently disabling condition defined by severe, discrete, stereotypical episodes of nausea and vomiting. In our previous report [1], a candidate gene list was evaluated in a group of 80 unrelated participants with CVS with extensive genetic sequencing (whole exome/genome). Twenty-two good candidate genes for CVS association were identified, from which a cellular model of aberrant cation transport and energy metabolism was proposed. Herein, we present additional clinical information on those 80 participants, including eight case reports to highlight general principles and clinical practices. Our participants demonstrate substantial phenotypic and genotypic heterogeneity in CVS, including a propensity for specific co-morbidities in the participants and relatives, evolution towards episodes in which vomiting is less apparent, labeling with “non-organic” diagnoses, multiple genes, polygenic inheritance, and association with variants not designated as Pathogenic. Our case reports illustrate how genetic information can guide clinical management and argue to the high clinical utility of appropriate genetic testing and analysis in CVS. Expression profiling of our 22 candidate genes suggests an anatomical model in a unit defined by vagal afferents and adjacent cells. Our models are consistent with multiple current hypotheses of CVS and the efficacy of commonly-recommended treatments.

Brine-dependent recovery process has seen much global research efforts in the past two decades because of their benefits over other oil recovery methods. The process involves the tweaking of the ionic composition and strength of the injected water to improve oil production. In recent years, several studies ranging from laboratory coreflood experiments by many researchers to field trials by several companies admit to the potential of recovering additional oil in sandstone and carbonate reservoirs. Sandstone and carbonate rocks are composed of completely different minerals, with varying degree of complexity and heterogeneity, but wettability alteration has been widely considered as the consequence rather than the cause of brine-dependent recovery. However, there is no consensus on the cause as several mechanisms have been proposed to relate the wettability changes to the improved recovery. This review paper aims to provide a state-of-the-art development in published research and various efforts of the industry. This review outlines an overview of laboratory and field observations, descriptions of underlying mechanisms and their validity, the complexity of the oil-brine-rock interactions, modelling works, and comparison between sandstone and carbonate rocks. The provided information is intended to provide the reader with up-to-date information, point to relevant studies for those who are new and those implementing either laboratory- or field-scale projects to speed up the process of further investigations in this research area. Overall, the outcome of this review would potentially be of immense benefit to the oil industry.

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. However, while the binding mechanisms of L-17 to the SERT and 5-HT1A receptor were similar to fluoxetine and WAY100135, its interacting with 5-HT3 receptor might be substantially different from this of granisetron. Acute administration of L-17 led to dose-dependent inhibition of firing activity of 5-HT neurons of the dorsal raphe nucleus. This inhibition was partially reversed by subsequent administration of WAY100135. Based on both in silico and in vivo electrophysiology assessments, we suggest that L-17 is a potent 5-HT reuptake inhibitor and a putative partial agonist of 5-HT1A receptors. As such, L-17 in particular and thiadiazine derivatives, in general, might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardioprotective properties, it can be useful in affective illness developing due to the general medical condition, such as post-stroke and post-myocardial infarction (MI) depression.

Innovation has emerged as a critical driver of economic growth in the digital era, revolutionizing industries and reshaping economies worldwide. As traditional funding avenues continue to be dominated by risk-averse lenders and investors, entrepreneurs are increasingly turning to alternative funding mechanisms to fuel their innovative ideas and ventures. This article delves into the evolving landscape of financing innovation in the digital era, with a primary focus on the role of alternative funding mechanisms. By drawing on a comprehensive review of existing literature and empirical evidence, we aim to provide a conceptual framework that elucidates the interplay between alternative finance platforms, innovation ecosystems, and entrepreneurial activities. Moreover, this article examines the unique characteristics and challenges associated with financing innovation through crowdfunding, venture capital, and angel investing. The insights from this research contribute to a better understanding of how these alternative funding mechanisms can effectively support and catalyze innovation across industries and economies.

To understand lung damage caused by COVID-19, we deduced two-phase lung damage mechanisms. After the lungs are infected with SARS-CoV-2 virus, the affected lung tissue swells and surface properties of pulmonary capillaries change, resulting in an increased flow resistance of affected capillaries. If a sufficient number of capillaries are affected by the infection, the swelling and increased cell wall adhesion collectively raise pulmonary vascular resistance. The increased vascular resistance further increases the dwell times of WBCs in affected capillaries and nearly capillaries. When pulmonary pressure is sufficiently higher, WBCs are forced to squeeze into interstitial spaces or alveolar spaces when local pressures are higher than what the capillaries can withstand. When more and more WBCs are dynamically retained, the flow resistance of more capillaries rises, pulmonary vascular resistance rises, and pulmonary pressure rises. The rise in the pulmonary pressure in turn results in elevated capillary pressures. When capillary pressures around the alveoli are sufficiently high, they cause interstitial pressures to change from normally negative values to positive values. The positive pressures cause fluid leakage to the alveolar space and thus degrade lung function. Tissue swelling, and occupation of WBCs in interstitial spaces and alveolar spaces further reduce compressible volume, and thus cause further rise in the pulmonary vascular resistance and pulmonary pressure. When the pulmonary pressure has reached a critical point as in the second phase, the blood breaks capillary walls and squeezes through interstitial spaces to reach alveolar spaces, resulting in irreversible lung damages. The available free volume in the thorax cage, organ usable capacities, temperature and humid are expected to have great impacts on degree of lung damages. The free volume in the thorax cage, lung usable surplus capacity, and other organ usable capacities determine the arrival time of last-phase irreversible damage. The mechanisms imply that the top priority for protecting lungs is maintaining pulmonary micro-circulation and preserving organ functions in the entire disease course while controlling viral reproduction should be stressed in the earliest time possible. The mechanisms also explain leukecytes are recruited and migrated into inflamed tissues by increasing their dwell times caused by increased local flow resistance.

In this paper we describe many important aspects connected with lubricants, namely: the most cheapest organic lubricant in the word, how effectively save lubricant between pairs of friction, what kind of rational shapes for the lubricant must be, what it will be connected with wear and tear using the new organic lubricant (for this purpose formulas and curves are shown in computer program MathCad with calculation). Moreover, there is one physical model which helps to catch car exhausted gases. In conclusion, some recommendations will be given to realize them into the practice during the operation for the different mechanisms including ecology.

The electronic structure and the participation of the simplest azomethine imine (AI) in [3+2] cycloaddition (32CA) reactions have been analysed within the Molecular Electron Density Theory (MEDT) using DFT calculations at the MPWB1K/6-311G(d) level. Electron localisation function (ELF) topological analysis reveals that AI has a pseudoradical structure, while the conceptual DFT reactivity indices characterise this TAC as a moderate electrophile and a good nucleophile. The non-polar 32CA reaction of AI with ethylene takes place through a one-step mechanism with low activation energy, 5.3 kcal/mol-1. A bonding evolution theory (BET) study indicates that this reaction takes place through a non-concerted [2n+2τ] mechanism in which the C–C bond formation is clearly anticipated prior to the C–N one. On the other hand, the polar 32CA reaction of AI with dicyanoethylene takes place through a two-stage one-step mechanism. Now, the more favourable regioisomeric transition state structure (TS) is located 8.5 kcal•mol⁻¹ below the reagents, in complete agreement with the high polar character of the TS. The current MEDT study makes it possible to extend Domingo’s classification of 32CA reactions to a new pra-type of reactivity.

Product introductions play a pivotal role in the success and competitiveness of manufacturing, particularly in the context of new product development. Low-volume manufacturing companies exhibit distinct characteristics that significantly influence the product introduction process. Notably, the quality of information exchange between product design and production interfaces becomes paramount in this high-mix and low-volume industry. Consequently, there exists a pressing need to explore various methods for adapting and customizing management mechanisms and strategies to align with the unique requirements and characteristics of low-volume manufacturing and its associated product introduction processes. While the need for this knowledge is critical in the context of low-volume manufacturing, a majority of existing studies predominantly focus on the management aspects within high-volume manufacturing. Therefore, the primary aim of this study is to investigate the customization of product introduction management strategies to enhance the quality of information content within the realm of low-volume manufacturing. Drawing upon a longitudinal analysis of new product introductions within a low-volume manufacturing company, this study narratively elucidates how the examined company implemented product introduction management strategies to facilitate the enhancement of information content quality during the product introduction phase. The study presents its findings on management strategies across three key stages: pre-implementation, post-implementation, and subsequent modification and refinement of strategies following the initial round of implementation. By shedding light on these strategies, this study offers a comprehensive understanding of management approaches in the context of low-volume product introduction. As a result, it makes a valuable contribution to the discourse on information management and interface management in the high-mix, low-volume manufacturing literature.

One of the most rapidly advancing areas of deep learning research aims at creating models that learn to disentangle the latent factors of variation from a data distribution. However, modeling joint probability mass functions is usually prohibitive, which motivates the use of conditional models assuming that some information is given as input. In the domain of numerical cognition, deep learning architectures have successfully demonstrated that approximate numerosity representations can emerge in multi-layer networks that build latent representations of a set of images with a varying number of items. However, existing models have focused on tasks requiring to conditionally estimate numerosity information from a given image. Here we focus on a set of much more challenging tasks, which require to conditionally generate synthetic images containing a given number of items. We show that attention-based architectures operating at the pixel level can learn to produce well-formed images approximately containing a specific number of items, even when the target numerosity was not present in the training distribution.

Radio bursts provide important diagnostics of energetic phenomena of the Sun. In particular, bursts in decimetric and metric wavelengths probe the physical conditions and the energy release processes in the low corona as well as their association with heliospheric phenomena. The advent of spectral radio data with high time and high frequency resolution has provided a wealth of information on phenomena of short duration and narrow bandwidth. Of particular value are spectral data combined with imaging observations at specific frequencies. In this work we briefly review the results of a series of observations comprised from high-sensitivity, low-noise dynamic spectra obtained with the acousto-optic analyzer (SAO) of the ARTEMIS-IV/JLS solar radiospectrograph, in conjunction with high time-resolution images from the Nançay Radioheliograph (NRH). Our studies include fine structures embedded in type IV burst continua (mostly narrow-band "spikes" and intermediate drift "fiber" bursts) and spike-like structures detected near the front of type-II bursts. The implications of the observational results to theoretical models are discussed.

Familial Exudative Vitreoretinopathy (FEVR), Norrie disease, and persistent fetal vascular syndrome (PFVS) are extremely rare retinopathies that are clinically distinct but are unified by abnormal retinal endothelial cell function – and subsequent irregular retinal vascular development and/or aberrant inner blood-retinal-barrier (iBRB) function. The early angiogenesis of the retina and its iBRB is a delicate process that is mediated by the canonical Norrin Wnt-signaling pathway in retinal endothelial cells. Pathogenic variants in genes that play key roles within this pathway such as NDP, FZD4, TSPAN12, and LRP5, have been associated with the incidence of these retinal diseases. Recent efforts to further elucidate the etiology of these conditions have not only highlighted their multigenic nature but have also resulted in the discovery of pathological variants in additional genes such as CTNNB1, KIF11, and ZNF408, some of which operate outside of the Norrin Wnt-signaling pathway. Recent discoveries of FEVR-linked variants in two other Catenin genes (CTNND1, CTNNA1) and the Endoplasmic Reticulum Membrane Complex Subunit-1 gene (EMC1) suggest that we will continue to find additional genes that impact the neural retinal vasculature, especially in multi-syndromic conditions. The goals of this review are to briefly highlight the current understanding of the roles of their encoded proteins in retinal endothelial cells to understand the essential functional mechanisms that can be altered to cause these very rare pediatric retinal vascular diseases.

Throughout this paper the impact of anxiety on adolescent athlete’s is highlighted through analyzing neurological and psychological aspects involved in sports performance. The neuroanatomy and neuropsychology of the human brain plays a major role in developing athlete’s that has only begun to be analyzed within recent years. Especially in young athletes, there are numerous factors that affect performance on the field that originate from the environment and training the adolescent athlete is involved in. Sports performance is viewed as a major physical factor such as training and lifting weights, however the psychological aspect of sports performance often goes unnoticed. Athletes can begin to develop mental fatigue and anxiety which inevitably can decrease their ability to perform. The athlete’s internal suffering begins to go unnoticed, as the only tangible factor is watching their performance decrease. This causes the athlete to push themselves further in training resulting in greater mental fatigue. This paper emphasizes the numerous factors neurologically that play a role in athletic performance which should be focused on in adolescent athletes as they navigate the challenges and competition that are apparent within athletics. It is critical to understand the processes and hormonal changes the body undergoes with training and playing a sport, this information can change the way adolescent sports are approached and advanced.

Over recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimulus. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues or cells, and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved by light irradiation at different wavelengths, either in UV, visible or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics and material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the up-to-date phototriggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

The proliferation of deep learning in natural language processing (NLP) has led to the development and release of innovative technologies capable of understanding and generating human language with remarkable proficiency. Atinuke, a Transformer-based neural network, optimises performance across various language tasks by utilising a unique configuration. The architecture interweaves layers for processing sequential data with attention mechanisms to draw meaningful affinities between inputs and outputs. Due to the configuration of its topology and hyperparameter tuning, it can emulate human-like language by extracting features and learning complex mappings. Atinuke is modular, extensible, and integrates seamlessly with existing machine learning pipelines. Advanced matrix operations like softmax, embeddings, and multi-head attention enable nuanced handling of textual, acoustic, and visual signals. By unifying modern deep learning techniques with software design principles and mathematical theory, the system achieves state-of-the-art results on natural language tasks whilst remaining interpretable and robust.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

This comprehensive analysis thoroughly examines the topic of adversarial attacks in artificial intelligence (AI), providing a detailed overview of the various methods used to compromise machine learning models. It explores different attack techniques, ranging from the simple Fast Gradient Sign Method (FGSM) to the intricate Carlini and Wagner Attack (C&W), emphasising the wide range of adversarial approaches and their intended goals. The discussion also distinguishes between targeted and non-targeted attacks, highlighting the adaptability and versatility of these malicious efforts. Additionally, the study delves into the realm of black-box attacks, revealing the capability of adversarial strategies to compromise models even with limited knowledge. Real-life examples illustrate the tangible consequences and potential dangers of adversarial attacks in various fields such as self-driving cars, multimedia, and voice assistants. These cases highlight the difficulties in ensuring the legitimacy and dependability of AI-powered technologies and programs. The article stresses the importance of ongoing research and innovation to address the growing difficulties posed by advanced methods like deepfakes and disguised voice commands in preserving the security of AI systems. This study provides valuable insights on how different adversarial strategies and defence mechanisms interact within AI. The results emphasise the urgent need for stronger and more secure AI models to combat the increasing number of adversarial threats in today's AI landscape. These findings can guide future research and innovations in developing more resilient AI technologies that can better withstand various adversarial vulnerabilities and challenges.