Adaptive Response Research Articles

Passive Heat Therapy for Cardiovascular Disease: Current Evidence and Future Directions

Passive heat therapy is gaining popularity as an intervention to promote cardiovascular, physiological, and to a lesser degree, thermoregulatory, adaptations in patients with cardiovascular disease. Despite this, the efficacy of heat therapy to elicit these adaptations remains unknown. We searched 5 databases for original research, screening 2,913 studies and identifying 18 eligible studies. Heat therapies included Waon therapy, balneotherapy, water perfused trousers, Finnish sauna, and foot immersion. Interventions were administered across various time frames (20- to 90-min) and performed 3 to 7 times per week, for durations of 2- to 8-weeks. The studies collectively involved a diverse population (mean age: 67 (10) years) with cardiovascular diseases. Heat therapy was consistently shown to improve ejection fraction, flow-mediated dilation, brain natriuretic peptide levels, New York Heart Association classification, and six-minute walk distance. However, positive effects on resting heart rate and blood pressure were infrequently observed, and thermoregulatory responses scarcely reported. Heat therapy may increase sweat rate during heat exposure and reduce resting core temperature, but adaptive skin blood flow responses were not observed. Passive heat therapy shows promising utility in patients with cardiovascular disease, while secondary benefits such as markers of thermoregulatory adaptation may also be observed, these require further investigation.

Resilience Informatics in Public Health: Qualitative Analysis of Conference Proceedings

Background In recent years, public health has confronted 2 formidable challenges: the devastating COVID-19 pandemic and the enduring threat of climate change. The convergence of these crises underscores the urgent need for resilient solutions. Resilience informatics (RI), an emerging discipline at the intersection of informatics and public health, leverages real-time data integration from health systems, environmental monitoring, and technological tools to develop adaptive responses to multifaceted crises. It offers promising avenues for mitigating and adapting to these challenges by proactively identifying vulnerabilities and fostering adaptive capacity in public health systems. Addressing critical questions regarding target audiences, privacy concerns, and scalability is paramount to fostering resilience in the face of evolving health threats. Objective The University of Arizona held a workshop, titled Resilience Informatics in Public Health, in November 2023 to serve as a pivotal forum for advancing these discussions and catalyzing collaborative efforts within the field. This paper aims to present a qualitative thematic analysis of the findings from this workshop. Methods A purposive sampling strategy was used to invite 40 experts by email from diverse fields, including public health, medicine, weather services, informatics, environmental science, and resilience, to participate in the workshop. The event featured presentations from key experts, followed by group discussions facilitated by experts. The attendees engaged in collaborative reflection and discussion on predetermined questions. Discussions were systematically recorded by University of Arizona students, and qualitative analysis was conducted. A detailed thematic analysis was performed using an inductive approach, supported by MAXQDA software to manage and organize data. Two independent researchers coded the transcripts; discrepancies in coding were resolved through consensus, ensuring a rigorous synthesis of the findings. Results The workshop hosted 27 experts at the University of Arizona, 21 (78%) of whom were from public health–related fields. Of these 27 experts, 8 (30%) were from the field of resilience. In addition, participants from governmental agencies, American Indian groups, weather services, and a mobile health organization attended. Qualitative analysis identified major themes, including the potential of RI tools, threats to resilience (eg, health care access, infrastructure, and climate change), challenges with RI tools (eg, usability, funding, and real-time response), and standards for RI tools (eg, technological, logistical, and sociological). The attendees emphasized the importance of equitable access, community engagement, and iterative development in RI projects. Conclusions The RI workshop emphasized the necessity for accessible, user-friendly tools bridging technical knowledge and community needs. The workshop’s conclusions provide a road map for future public health resilience, highlighting the need for scalable, culturally sensitive, community-driven interventions. Future directions include focused discussions to yield concrete outputs such as implementation guidelines and tool designs, reshaping public health strategies in the face of emerging threats.

Happy to co­create: the influence of product co­creation over consumer hedonic adaptation

Purpose Researchers have been exploring the consequences of the hedonic adaptation process at length. This phenomenon is characterized by the reduction of pleasure with consumption experiences over time. Meanwhile, co-creation initiatives seem to be gaining traction in brand strategies. However, little is known about how individuals experience the co-creation effects in consumption. The purpose of this study is to analyse the impact of consumer co-creation experiences on predicting hedonic adaptation. Also, it aims to provide insights into the emotional aspects of consumption. Design/methodology/approach Three mixed-design experimental studies were conducted to explore the effects of co-creation on consumer hedonic adaptation, affective forecasting and emotional responses. Study 1 and Study 2 were conducted online with American participants. Study 3 was conducted in a laboratory setting in Brazil. Findings The research demonstrated that individuals predict that the path to consumption adaptation will be longer when co-creating their products co-create. However, this effect varies depending on the type of product. As for the emotional aspect, consumers attribute more positive emotions than negative ones in the context of co-creation. Research limitations/implications This study manipulated different conditions considering specific product types. Future research should apply this framework to other products and services to confirm the generalization of the study’s findings. Also, the authors encourage future studies that explore emotions in different co-creation scenarios. Practical implications Elucidating how co-creation impacts consumers’ hedonic adaptation empowers companies to leverage co-creation to cultivate positive consumer attitudes and brand loyalty. Marketing campaigns can highlight the emotional benefits of ownership and personalization. It also provides a sustainable perspective for companies, which seeks consumers who remain present over time and trust the company. Furthermore, co-creation can be used strategically for innovation management. By co-creating limited-edition trial products, companies can involve new customers, foster a sense of ownership and potentially mitigate hedonic adaptation, while gathering valuable insights for new product development. Originality/value This research advances the limited literature on co-creation and customer hedonic adaptation, which lies at the interface between consumer behaviour and product development. It explores how product co-creation affects consumers’ predictions and shopping experiences concerning pleasure decrease, including product value and company feedback. Additionally, it examines the role of emotions in co-creation and hedonic adaptation. This research contributes by demonstrating the impact of co-creation on adaptation, affective forecasting and emotional responses during consumption.

"A place to call home": A process of liberation for Rohingya Refugees in the United States.

This study explores the experiences of Rohingya refugees in the United States following their forced migration and years as stateless refugees. Qualitative strengths-based phenomenological analysis was applied to individual interviews with eight key informants, all identified as Rohingya refugees. Interviews focused on experience and meaning-making concerning the complexities of Rohingya identity and belonging, rights and liberation in the United States, and the impact of generational, gender, and migration patterns. Five superordinate themes were initially identified. The first theme focused on the adaptive and resilient responses to institutionalized discrimination, emphasizing changes in Rohingya identity and values. The second theme examined how these adaptive responses influenced participants' perceptions of American culture and society. The final three themes underscored participants' reflections on their sense of agency, efforts to preserve Rohingya culture, and their journey to find belonging. These themes were further analyzed and discussed through a liberation framework. The findings demonstrate how Rohingya diaspora communities are impacted by their pre-, intermediary, and post-migration experiences as they create cultural roots and establish permanency, actively claim their agency, and promote liberation.

Regulation of Stress-Induced Immunosuppression in the Context of Neuroendocrine, Cytokine, and Cellular Processes

Understanding the regulatory mechanisms of stress-induced immunosuppression and developing reliable diagnostic methods are important tasks in clinical medicine. This will allow for the development of effective strategies for the prevention and treatment of conditions associated with immune system dysfunction induced by chronic stress. The purpose of this review is to conduct a comprehensive analysis and synthesis of existing data on the regulatory mechanisms of stress-induced immunosuppression. The review is aimed at identifying key neuroendocrine, cytokine, and cellular processes underlying the suppression of the immune response under stress. This study involved a search of scientific literature covering the neuroendocrine, cellular, and molecular mechanisms of stress-induced immunosuppression regulation, as well as modern methods for its diagnosis. Major international bibliographic databases covering publications in biomedicine, psychophysiology, and immunology were selected for the search. The results of the analysis identified key mechanisms regulating stress-induced immunosuppression. The reviewed publications provided detailed descriptions of the neuroendocrine and cytokine processes underlying immune response suppression under stress. A significant portion of the data confirms that the activation of the hypothalamic–pituitary–adrenal (HPA) axis and subsequent elevation of cortisol levels exert substantial immunosuppressive effects on immune cells, particularly macrophages and lymphocytes, leading to the suppression of innate and adaptive immune responses. The data also highlight the crucial role of cortisol and catecholamines (adrenaline and noradrenaline) in initiating immunosuppressive mechanisms under chronic stress.

Characterizing the patient experience of physical restraint in psychiatric settings via a linguistic, sentiment, and metaphor analysis

Physical Restraint (PR) is a coercive procedure used in emergency psychiatric care to ensure safety in life-threatening situations. Because of its traumatic nature, studies emphasize the importance of considering the patient’s subjective experience. We pursued this aim by overcoming classic qualitative approaches and innovatively applying a multilayered semiautomated language analysis to a corpus of narratives about PR collected from 99 individuals across seven mental health services in Italy. Compared to a reference corpus, PR narratives were characterized by reduced fluency and lexical density, yet a greater use of emotional and cognitive terms, verbs, and first-person singular pronouns. Sadness was the most represented emotion, followed by anger and fear. One-third of the PR narratives contained at least one metaphor, with Animals and War/Prison as the most distinctive source domains. The quality and length of the PR experience impacted both the structure and the sentiment of the narratives. Findings confirm the distressful nature of PR but also point to the use of various linguistic mechanisms which might serve as an early adaptive response toward healing from the traumatic experience. Overall, the study highlights the importance of Natural Language Processing as an unobtrusive window into subjective experience, offering insights for therapeutic choices.

The edaphic factor and orchids: Gymnadenia conopsea from contrasting geologies in the Central Balkans.

Two different strategies for the distribution of macro- and trace elements can be observed in the terrestrial orchid Gymnadenia conopsea. Most trace elements are not translocated to the above-ground parts, whereas for macro-elements the trend was reversed, with the highest accumulation in the distal parts of the plants. Edaphic stress is one of the main factors affecting plant fitness, but it is still poorly understood, even in rare plants such as orchids. Gymnadenia conopsea is a terrestrial orchid that grows on different geological substrates, making it a model species for the study of adaptive responses to edaphic factors, including metals in soil. The samples of plant tissues of G. conopsea growing on carbonate, ultramafic and siliceous substrates in Serbia and the associated rhizosphere soil were collected and analysed for elemental concentrations. Two different strategies for the distribution of macro- and trace elements were found, corresponding to the trend generally observed in orchids. Trace elements (As, B, Cr, Co, Fe, Mn, and Ni) remain mainly in the underground organs and only a small proportion is transferred to the shoots. It was the opposite for the macroelements (Ca, Mg, K and P) with the highest accumulation occurred in the leaves and inflorescences. The tolerance of G. conopsea to the different geological substrates results from the moderate metal concentrations in the soils analysed and the exclusion strategy of the species, which is the most common response to metal induced stress in orchids.

Post Farmer-herder Conflict Management and Relief Strategies of Farmers in Nigeria

Purpose: This study shed light on the self-relief strategy employed by farmers after their experience in farmer-herder conflict.Research Method: The survey was carried out among 150 farm households headed in four farming communities. Frequency and logistic regression statistics were employed to analyze data.Findings: Findings showed that farmer-herder conflict resulted in the destruction of farm crops and insufficient food for household consumption among affected rural households. Affected rural households decided to adopt coping strategies that reduce their vulnerability by tightening farm security, preventing future huge farm loss by sowing less, and completely avoiding of risk of conflict effects with no intention to continue crop farming by borrowing money and shifting to off-farm jobs. Education/literacy of the people and causes of conflict were found to be the behavioral control factors of the farmers.Practical Implication: The study provided recommendations for rural development advisors and policymakers to inform post-conflict management and relief strategies for effective coping and adaptation responses to farmer-herders conflict victims in Africa and other developing countries experiencing similar nature of conflict.Originality/ Value: The study is novel for reporting, for the first time, the post-farmer-herder conflict behavior of farmers in Nigeria

The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity

The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice. We further investigate tPA’s potential role in SN pathology in an α-synuclein mouse model of Parkinson’s disease (PD). To characterize the mechanism of tPA action in α-synuclein-mediated pathology in the SN and to identify possible therapeutic pathways, we performed RNA-seq analysis of the SN and used multiple transgenic mouse models. These included tPA deficient mice and two newly developed transgenic mice, a knock-in model expressing endogenous levels of proteolytically inactive tPA (tPA Ala-KI) and a second model overexpressing proteolytically inactive tPA (tPA Ala-BAC). Our findings show that striatal GABAergic neurons send tPA+ projections to dopaminergic (DA)-neurons in the SN and that tPA is released from SN-derived synaptosomes upon stimulation. We also found that tPA levels in the SN increased following α-synuclein overexpression. Importantly, tPA deficiency protects DA-neurons from degeneration, prevents behavioral deficits, and reduces microglia activation and T-cell infiltration induced by α-synuclein overexpression. RNA-seq analysis indicates that tPA in the SN is required for the upregulation of genes involved in the innate and adaptive immune responses induced by α-synuclein overexpression. Overexpression of α-synuclein in tPA Ala-KI mice, expressing only proteolytically inactive tPA, confirms that tPA-mediated neuroinflammation and neurodegeneration is independent of its proteolytic activity. Moreover, overexpression of proteolytically inactive tPA in tPA Ala-BAC mice leads to increased neuroinflammation and neurodegeneration compared to mice expressing normal levels of tPA, suggesting a tPA dose response. Finally, treatment of mice with glunomab, a neutralizing antibody that selectively blocks tPA binding to the N-methyl-D-aspartate receptor-1 (NMDAR1) without affecting NMDAR1 ion channel function, identifies the tPA interaction with NMDAR1 as necessary for tPA-mediated neuroinflammation and neurodegeneration in response to α-synuclein-mediated neurotoxicity. Thus, our data identifies a novel pathway that promotes DA-neuron degeneration and suggests a potential therapeutic intervention for PD targeting the tPA-NMDAR1 interaction.

The influence of interleukin-27 on metabolic fitness in a murine neonatal model of bacterial sepsis.

Human neonates are predisposed to an increased risk of mortality from infection due to fundamental differences in the framework of innate and adaptive immune responses relative to those in the adult population. As one key difference in neonates, an increase in the immunosuppressive cytokine, IL-27, is responsible for poor outcomes in a murine neonatal model of bacterial sepsis. In our model, the absence of IL-27 signaling during infection is associated with improved maintenance of body mass, increased bacterial clearance with reduced systemic inflammation, and decreased mortality rates that correlate to preservation of glucose homeostasis and insulin production. To further elucidate the mechanisms associated with IL-27 signaling and metabolic fitness, we analyzed global transcriptomes from spleen, liver, pancreas, and hindlimb muscle during Escherichia coli-induced sepsis in wild-type (WT) and IL-27Rα-deficient (KO) mice. Metabolically important tissues such as the liver, pancreas, and hindlimb muscle exhibit a shift in differential gene expression of pathways involved in oxidative phosphorylation, glycolysis, gluconeogenesis, lipid metabolism, and fatty acid beta oxidation. The hindlimb muscle of KO pups demonstrated a significant reduction in all of these pathways during infection. The KO liver showed a significant down-regulation in gluconeogenesis and glycolytic pathways. Collectively, these findings suggest a negative influence of IL-27 on the metabolic profile during early life infection. This is an important consideration for antagonization of IL-27 as a potential host-directed therapeutic opportunity as our findings point to an overall improvement in infectious disease parameters and metabolic fitness.

Insights of cellular and molecular changes in sugarcane response to oxidative signaling

Main conclusionSignificant changes in the proteome highlight essential metabolic adaptations for development and oxidative signaling induced by the treatment of young sugarcane plants with hydrogen peroxide. These adaptations suggest that hydrogen peroxide acts not only as a stressor but primarily as a signaling molecule, triggering specific metabolic pathways that regulate growth and plant resilience.Sugarcane is a crucial crop for sugar and ethanol production, often influenced by environmental signals. Hydrogen peroxide (H2O2) is increasingly recognized as an important signaling molecule that regulates plant development and adaptation. In this study, two-month-old sugarcane plants were treated with varying concentrations of H2O2 to investigate how this molecule acts as a signal at the cellular, biochemical, and proteomic levels. Antioxidant enzyme activity exhibited fluctuations, suggesting a dynamic response to oxidative signaling. Lipid peroxidation, observed through TBARs and scanning electron microscopy, highlighted early membrane modifications. Proteomic analysis (ProteomeXchange PXD048142) identified 2,699 proteins, with 155 showing significant expression changes in response to H2O2 signaling. Bioinformatics, including Principal Component Analysis, revealed distinct proteomic profiles in roots and leaves, indicating tissue-specific metabolic reprogramming. Functional annotation through Gene Ontology and KEGG pathway enrichment showed that oxidative signaling led to the repression of photosynthesis-related pathways in leaves, while promoting pathways related to protein processing, glycolysis, and carbon metabolism in roots. Additionally, bioinformatic tools identified proteins involved in amino acid metabolism, the TCA cycle, and carbohydrate metabolism as critical components of sugarcane's adaptive signaling response. The data suggest that sugarcane plants responded to oxidative signals by adjusting their metabolic networks, promoting sustained development and potential pathways for targeted plant breeding.

Educational Strategies for Teaching Metabolic Profiles Across Three Endurance Training Zones.

This article explores an innovative educational approach using a metabolic board designed to enhance understanding of muscle metabolism across three endurance training zones: Z1 (light intensity), Z2 (moderate intensity), and Z3 (intense/severe intensity). The aerobic threshold marks the transition from light to moderate domains, and the anaerobic threshold separates moderate from intense domains, with both thresholds adapting to training. Exercises within each training zone elicit specific adaptive responses through distinct signaling pathways, but the metabolic profile induced remains relatively constant across these intensity domains. The assembly of the metabolic board is guided by interpretative questions derived from recent incremental exercise studies. By interacting with the board, students gain clear insights into the rationale for choosing between continuous and interval exercises. This interactive tool simplifies complex physiological processes into understandable components, clarifying the relationships among motor unit types and its metabolism and principal energy sources at each intensity level. By assembling the board, students demystify muscle metabolism as a continuum of responses crucial for sustaining various exercise intensities. This integration of theoretical knowledge with practical application empowers students and professionals to make informed decisions about training prescriptions, a critical element of training periodization.

Adaptive evolution of stress response genes in parasites aligns with host niche diversity

BackgroundStress responses are key the survival of parasites and, consequently, also the evolutionary success of these organisms. Despite this importance, our understanding of the evolution of molecular pathways dealing with environmental stressors in parasitic animals remains limited. Here, we tested the link between adaptive evolution of parasite stress response genes and their ecological diversity and species richness. We comparatively investigated antioxidant, heat shock, osmoregulatory, and behaviour-related genes (foraging) in two model parasitic flatworm lineages with contrasting ecological diversity, Cichlidogyrus and Kapentagyrus (Platyhelminthes: Monopisthocotyla), through whole-genome sequencing of 11 species followed by in silico exon bait capture as well as phylogenetic and codon analyses.ResultsWe assembled the sequences of 48 stress-related genes and report the first foraging (For) gene orthologs in flatworms. We found duplications of heat shock (Hsp) and oxidative stress genes in Cichlidogyrus compared to Kapentagyrus. We also observed positive selection patterns in genes related to mitochondrial protein import (Hsp) and behaviour (For) in species of Cichlidogyrus infecting East African cichlids—a host lineage under adaptive radiation. These patterns are consistent with a potential adaptation linked to a co-radiation of these parasites and their hosts. Additionally, the absence of cytochrome P450 and kappa and sigma-class glutathione S-transferases in monogenean flatworms is reported, genes considered essential for metazoan life.ConclusionsThis study potentially identifies the first molecular function linked to a flatworm radiation. Furthermore, the observed gene duplications and positive selection indicate the potentially important role of stress responses for the ecological adaptation of parasite species.

Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates.

The recent outbreak of Marburg virus (MARV) in Rwanda underscores the need for effective countermeasures against this highly fatal pathogen, with case fatality rates reaching 90%. Currently, no vaccines or approved treatments exist for MARV infection, distinguishing it from related viruses like Ebola. Our research demonstrates that the oral drug obeldesivir (ODV), a nucleoside analog prodrug, shows promising antiviral activity against filoviruses in vitro and offers significant protection in animal models. In this study with cynomolgus macaques (n=6), a 10-day regimen of once-daily ODV, initiated 24 hours post-exposure, provided 80% protection against a thousand-fold lethal MARV challenge, delaying viral replication and disease onset. Transcriptome analysis revealed that early adaptive responses correlated with successful outcomes. Compared to intravenous options, oral antivirals like ODV offer logistical advantages in outbreak settings, enabling easier administration and broader contact coverage. Our findings support ODV's potential as a broad-spectrum, oral postexposure prophylaxis for filoviruses.

Long-term fasting induces a remodelling of fatty acid composition in erythrocyte membranes.

Long-term fasting (LF) activates an adaptative response to switch metabolic fuels from food glucose to lipids stored in adipose tissues. The increase in free fatty acid (FFA) oxidation during fasting triggers health benefits. We questioned if the changes in lipid metabolism during LF could affect lipids in cell membranes in humans. We thus analysed the FA composition in erythrocyte membranes (EM) during 12.6 ± 3.5 days of LF and 1 month after food reintroduction. A total of 98 subjects out of three single-arm interventional studies underwent a medical supervised long-term fasting (12.6 ± 3.5 days) programme. The distribution pattern of 26 FA as well as the HS-Omega-3 Index were assessed in the EM using gas chromatography. Eighteen of 26 FA showed significant changes. Within the group of saturated FA, myristic (14:0) and stearic acid (18:0) decreased while palmitic (16:0) and arachid acid (20:0) increased. While most monounsaturated FA increased, trans fatty acids decreased or remained unchanged. Within the polyunsaturated FA, arachidonic (20:4n6) and docosahexaenoic (22:6n3) acid increased, while linoleic (18:2n6), alpha-linolenic (18:3n3) and eicosapentaenoic acid (20:5n3) decreased. Consequently, the HS-Omega-3 Index increased. 11 out of the 18 FA with significant changes returned to baseline levels 1 month afterwards. Levels of linoleic and alpha-linolenic acid increased over baseline levels. Long-term fasting triggers changes in the FA composition of EM.

ANALYSIS OF THE USE OF ROY'S ADAPTATION NURSING THEORY IN HEART DISEASE PATIENTS

Background: The heart as an important organ cannot be protected from diseases that can attack it. One of the deadliest diseases in the world is heart attack. Objective: This research aims to determine the behavioral response of heart disease patients which gives rise to individual adaptive responses to maintain individual adaptation in heart disease patients. Method: This research uses a qualitative method with a qualitative descriptive approach. The sampling technique is purposive sampling. Data collection methods were in-depth interviews and observation sheets from Calista Roy. Data analysis using the content analysis method. The informants in this study with heart disease in the Siloam Hospital Palembang Inpatient Room were 4 people (2 men, 2 women) and 1 Key Informant. Results: The results of this study emerged 7 themes, namely lack of knowledge about heart disease, signs and symptoms felt by patients, heart patients' efforts to treat their disease, compliance with treatment regimens, healthy diet and lifestyle, obstacles in maintaining their health, and hospital facilities and actions for heart disease patients. The research results show that there is an adaptive response from heart disease patients which can improve patient integrity and be able to carry out activities that are favorable to survival. However, it was still found that participants lacked knowledge regarding their disease, so there was still non-compliance with the treatment regimen. Conclusions: The use of Roy's adaptive nursing theory in providing nursing care to patients with heart disease makes it easier for nurses to detect the patient's situation in adapting to heart disease.

Integrative molecular and physiological insights into the phytotoxic impact of liquid crystal monomer exposure and the protective strategy in plants.

Liquid crystal monomers (LCMs), the integral components in the manufacture of digital displays, have engendered environmental concerns due to extensive utilization and intensive emission. Despite their prevalence and ecotoxicity, the LCM impacts on plant growth and agricultural yield remain inadequately understood. In this study, we investigated the specific response mechanisms of tobacco, a pivotal agricultural crop and model plant, to four representative LCMs (2OdF3B, 5CB, 4PiMeOP, 2BzoCP) through integrative molecular and physiological approaches. The findings reveal specific impacts, with 4PiMeOP exerting the most pronounced effects, followed by 2BzoCP, 5CB, and 2OdF3B. LCM exposure disrupts the photosynthetic apparatus, exacerbating reactive oxygen species (ROS) levels in leaves, which in turn triggers the upregulation of antioxidative enzymes and the synthesis of antioxidant substances. Additionally, LCMs strongly stimulate the expression of genes involved in abscisic acid (ABA) biosynthesis and signalling pathways. The AI-assisted meta-analysis implicates ABA as a critical regulator in the tobacco response to LCMs. Notably, exogenous application of ABA alleviates LCM-induced toxicities, highlighting the pivotal role of ABA in stress amelioration. Our study provides novel insights into the toxicity and tolerance mechanisms of LCMs in plants, shedding light on both their harmful effects on the ecosystems and potential adaptation responses. This is crucial to develop sustainable agricultural systems by reducing the negative environmental impacts caused by emerging organic pollutants.

Nrf2 mediates mitochondrial and NADPH oxidase-derived ROS during mild heat stress at 40 °C.

Hyperthermia is an adjuvant to chemotherapy and radiotherapy and sensitizes tumors to these treatments. However, repeated heat treatments result in acquisition of heat resistance (thermotolerance) in tumors. Thermotolerance is an adaptive survival response that appears to be mediated by upregulated cellular defenses. However, the mechanisms of activation remain unclear. When HeLa cells were exposed to mild heat shock at 40 °C for 3 h, levels of superoxide and peroxides increased. Cells were treated with mitochondrial antioxidant MitoQ and NADPH oxidase (NOX) inhibitor apocynin to characterize the contribution of these two sources to the total reactive oxygen species (ROS) pool. We found that both mitochondria and NOX are sources of ROS during mild heat shock at 40 °C. Heat-derived ROS are thought to activate the adaptive survival response at 40 °C. Nrf2, the master regulator of the cellular antioxidant response, is thought to play a pivotal role in establishing the adaptive survival response. Nrf2 was overexpressed or knocked down to assess its role. Moreover, Nrf2 levels correlate with the cellular redox state, and do so via scavenging of mitochondria- and NOX-derived ROS. Knockdown of Nrf2 markedly increased levels of ROS that were scavenged by either apocynin or MitoQ. Finally, critical defense proteins such as DJ-1 and PGAM5 seemed to require a two-key activation system mediated by Nrf2 and mitochondrial ROS. Our study characterized mitochondrial and NOX-derived ROS as being essential in activating cellular defenses alongside Nrf2 and underlines potential therapeutic targets that may contribute to the acquisition of thermotolerance.

The Immune System: An Arrow to the Heart and Principles of Cardioimmunology as an Emerging Branch of Medicine.

Cardioimmunology is an emerging branch of medicine whose development has been facilitated by more sophisticated diagnostic procedures. Recent studies have mainly focused on the immune response during myocardial infarction (MI), and there is evidence that both resident and external immune cells participate in acute inflammatory disease, as well as tissue remodeling. Cardiac Innate Immune Cells: Following MI, macrophages, dendritic cells (DCs) and mast cells (MCs) are the main players in the heart. Under steady-state conditions, cardiac resident macrophages (CRMs) protect the heart against stress and infectious events, being involved in cell and matrix turnover, as well as phagocytosis of apoptotic cells. Moreover, CRMs contribute to the resolution of inflammation via release of interleukin (IL)-10, and efferocytosis of dying cells. Conversely, CCR2+ monocyte-derived macrophages promote inflammation in the acute phase of myocardial damage, with the release of pro-inflammatory cytokines. Conventional (c) DCs possess enhanced capacity to present antigens to T lymphocytes. In MI patient autopsies, massive infiltration of T helper (Th) cells and CDs has been detected in the myocardium. Cardiac MCs play a dual role during MI, with the production of cytokines for early inflammatory response, and the release of anti-inflammatory cytokines, IL10 and IL-13 during the resolution phase. Adaptive Immune Response: In experimental coronary artery ligation, the myocardium is infiltrated with Th1, Th2, Th17, and T regulatory (TREG) cells, which participate in the acute inflammation. In cardiac repair, T cell reparative response is mediated by TREG cells, with improved ventricular remodeling and function post-ischemia. In this review, emphasis will be placed on the innate and adaptive immune response during and post-MI. At the same time, immunotherapy-based cardiac failure following chimeric antigen receptor T-cell and immune checkpoint inhibitory therapy will be pointed out.

Transformer-based modeling of Clonal Selection and Expression Dynamics reveals resistance mechanisms in breast cancer

Understanding transcriptional heterogeneity in cancer cells and its implication for treatment response is critical to identify how resistance occurs and may be targeted. Such heterogeneity can be captured by in vitro studies through clonal barcoding methods. We present TraCSED (Transformer-based modeling of Clonal Selection and Expression Dynamics), a dynamic deep learning approach for modeling clonal selection. Using single-cell gene expression and the fitness of barcoded clones, TraCSED identifies interpretable gene programs and the time points at which they are associated with clonal selection. When applied to cells treated with either giredestrant, a selective estrogen receptor (ER) antagonist and degrader, or palbociclib, a CDK4/6 inhibitor, pathways dynamically associated with resistance are revealed. For example, ER activity is associated with positive selection around day four under palbociclib treatment and this adaptive response can be suppressed by combining the drugs. Yet, in the combination treatment, one clone still emerged. Clustering based on partial least squares regression found that high baseline expression of both SNHG25 and SNCG genes was the primary marker of positive selection to co-treatment and thus potentially associated with innate resistance — an aspect that traditional differential analysis methods missed. In conclusion, TraCSED enables associating features with phenotypes in a time-dependent manner from scRNA-seq data.