Fatty acid oxidation drives mitochondrial hydrogen peroxide production by α-ketoglutarate dehydrogenase.

In the present study, we examined the mitochondrial hydrogen peroxide (mH2O2) generating capacity of α-ketoglutarate dehydrogenase (KGDH) and compared it to components of the electron transport chain using liver mitochondria isolated from male and female C57BL6N mice. We show for the first time there are some sex dimorphisms in the production of mH2O2 by electron transport chain complexes I and III when mitochondria are fueled with different substrates. However, in our investigations into these sex effects, we made the unexpected and compelling discovery that 1) KGDH serves as a major mH2O2 supplier in male and female liver mitochondria and 2) KGDH can form mH2O2 when liver mitochondria are energized with fatty acids but only when malate is used to prime the Krebs cycle. Surprisingly, 2-keto-3-methylvaleric acid (KMV), a site-specific inhibitor for KGDH, nearly abolished mH2O2 generation in both male and female liver mitochondria oxidizing palmitoyl-carnitine. KMV inhibited mH2O2 production in liver mitochondria from male and female mice oxidizing myristoyl-, octanoyl-, or butyryl-carnitine as well. S1QEL 1.1 (S1) and S3QEL 2 (S3), compounds that inhibit reactive oxygen species generation by complexes I and III, respectively, without interfering with OxPhos and respiration, had a negligible effect on the rate of mH2O2 production when pyruvate or acyl-carnitines were used as fuels. However, inclusion of KMV in reaction mixtures containing S1 and/or S3 almost abolished mH2O2 generation. Together, our findings suggest KGDH is the main mH2O2 generator in liver mitochondria, even when fatty acids are used as fuel.

Mitochondrial hydrogen peroxide production by pyruvate dehydrogenase and α-ketoglutarate dehydrogenase in oxidative eustress and oxidative distress.

Pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) are vital entry points for monosaccharides and amino acids into the Krebs cycle and thus integral for mitochondrial bioenergetics. Both complexes produce mitochondrial hydrogen peroxide (mH2O2) and are deactivated by electrophiles. Here, we provide an update on the role of PDH and KGDH in mitochondrial redox balance and their function in facilitating metabolic reprogramming for the propagation of oxidative eustress signals in hepatocytes and how defects in these pathways can cause liver diseases. PDH and KGDH are known to account for ∼45% of the total mH2O2 formed by mitochondria and display rates of production several-fold higher than the canonical source complex I. This mH2O2 can also be formed by reverse electron transfer (RET) in vivo, which has been linked to metabolic dysfunctions that occur in pathogenesis. However, the controlled emission of mH2O2 from PDH and KGDH has been proposed to be fundamental for oxidative eustress signal propagation in several cellular contexts. Modification of PDH and KGDH with protein S-glutathionylation (PSSG) and S-nitrosylation (PSNO) adducts serves as a feedback inhibitor for mH2O2 production in response to glutathione (GSH) pool oxidation. PSSG and PSNO adduct formation also reprogram the Krebs cycle to generate metabolites vital for interorganelle and intercellular signaling. Defects in the redox modification of PDH and KGDH cause the over generation of mH2O2, resulting in oxidative distress and metabolic dysfunction-associated fatty liver disease (MAFLD). In aggregate, PDH and KGDH are essential platforms for emitting and receiving oxidative eustress signals.

A Commentary on Fasting of Nonclinical Research Animals.

This commentary discusses the implementation of fasting in nonclinical animal experimental subjects. The short-term removal of food from cages of experimental animals is in all respects innocuous. The term "stress" is ill-defined and the statutes and regulations governing animal research laboratories that exert their authority in the performance of their operations do so without substantive grounds to base compliance. The legislative and administrative history of the implementation of the Animal Welfare Act (AWA) has evolved into the development of laboratory management strategies that focus on the reduction of the biological cost of stress to the animals and the determination of when subclinical stress (eustress) becomes distress. Animal welfare is based on the tenet that in laboratories conducting animal research in compliance with Good Laboratory Practices (Title 21 USC, Chapter 13,§58), it is the study protocol and the study director that establish procedures and processes that are approved by each Institutional Animal Care and Use Committee to ensure the humane care and use of animals in research, teaching, and testing and to ensure compliance with guidelines and regulations. This approval process establishes the justification of eustress in the environment that do not rise to the threshold of distress under the AWA.

Radiation Hormesis in Barley Manifests as Changes in Growth Dynamics Coordinated with the Expression of PM19L-like, CML31-like, and AOS2-like.

The stimulation of growth and development of crops using ionising radiation (radiation hormesis) has been reported by many research groups. However, specific genes contributing to the radiation stimulation of plant growth are largely unknown. In this work, we studied the impact of the low-dose γ-irradiation of barley seeds on the growth dynamics and gene expression of eight barley cultivars in a greenhouse experiment. Our findings confirmed that candidate genes of the radiation growth stimulation, previously established in barley seedlings (PM19L-like, CML31-like, and AOS2-like), are significant in radiation hormesis throughout ontogeny. In γ-stimulated cultivars, the expression of these genes was aligned with the growth dynamics, yield parameters, and physiological conditions of plants. We identified contrasting cultivars for future gene editing and found that the γ-stimulated cultivar possessed some specific abiotic stress-responsive elements in the promotors of candidate genes, possibly revealing a new level of radiation hormesis effect execution. These results can be used in creating new productive barley cultivars, ecological toxicology of radionuclides, and eustress biology studies.

Predicting Office Workers' Productivity: A Machine Learning Approach Integrating Physiological, Behavioral, and Psychological Indicators.

This research pioneers the application of a machine learning framework to predict the perceived productivity of office workers using physiological, behavioral, and psychological features. Two approaches were compared: the baseline model, predicting productivity based on physiological and behavioral characteristics, and the extended model, incorporating predictions of psychological states such as stress, eustress, distress, and mood. Various machine learning models were utilized and compared to assess their predictive accuracy for psychological states and productivity, with XGBoost emerging as the top performer. The extended model outperformed the baseline model, achieving an R2 of 0.60 and a lower MAE of 10.52, compared to the baseline model's R2 of 0.48 and MAE of 16.62. The extended model's feature importance analysis revealed valuable insights into the key predictors of productivity, shedding light on the role of psychological states in the prediction process. Notably, mood and eustress emerged as significant predictors of productivity. Physiological and behavioral features, including skin temperature, electrodermal activity, facial movements, and wrist acceleration, were also identified. Lastly, a comparative analysis revealed that wearable devices (Empatica E4 and H10 Polar) outperformed workstation addons (Kinect camera and computer-usage monitoring application) in predicting productivity, emphasizing the potential utility of wearable devices as an independent tool for assessment of productivity. Implementing the model within smart workstations allows for adaptable environments that boost productivity and overall well-being among office workers.

Homeostatic control of redox status and health.

Research on oxidants and electrophiles has shifted from focusing on damage to biomolecules to the more fine-grained physiological arena. Redox transitions as excursions from a steady-state redox set point are continually ongoing in maintenance of redox balance. Current excitement on these topics results from the fact that recent research provided mechanistic insight, which gives rise to more concrete and differentiated questions. This Commentary focuses on redox eustress and the feedback restoration of steady state as concepts in active maintenance of physiological health, with brief discussion of redox stress response to viral infection, exemplified by COVID-19.

Eustress and Distress: Neither Good Nor Bad, but Rather the Same?

The terms "eustress" and "distress" are widely used throughout the scientific literature. As of February 2020, 203 items in the Web of Science show up in a search for "eustress," however, there are almost 16 400 items found in a search for the term "distress." Based on the reasoning in this article, however, it is believed there is no such thing as eustress or distress. The adaptation reaction of an organism under stress is not intrinsically good or bad, and its effect on health or performance depends on a plethora of other interactions of the body with the environment as well as on the history of such interactions. The vagueness of the terms "eustress/distress" has historically led to vast differences in the perception and application of the terms across disciplines. While psychology or sociology perceive eustress as something inextricably linked to positive perception and enhanced cognition, biomedicine perceives eustress as generally associated with better survival, health, or increased longevity, no matter how the event is perceived. In this paper, the authors review the current understanding of the term "eustress" in different fields, discuss possible implications of its misleading use, and suggest that the term may be replaced by "stress" only.

Findings in redox biology: From H2O2 to oxidative stress.

My interest in biological chemistry proceeded from enzymology in vitro to the study of physiological chemistry in vivo Investigating biological redox reactions, I identified hydrogen peroxide (H2O2) as a normal constituent of aerobic life in eukaryotic cells. This finding led to developments that recognized the essential role of H2O2 in metabolic redox control. Further research included studies on GSH, toxicological aspects (the concept of "redox cycling"), biochemical pharmacology (ebselen), nutritional biochemistry and micronutrients (selenium, carotenoids, flavonoids), and the concept of "oxidative stress." Today, we recognize that oxidative stress is two-sided. It has its positive side in physiology and health in redox signaling, "oxidative eustress," whereas at higher intensity, there is damage to biomolecules with potentially deleterious outcome in pathophysiology and disease, "oxidative distress." Reflecting on these developments, it is gratifying to witness the enormous progress in redox biology brought about by the science community in recent years.

The short-term stress response - Mother nature's mechanism for enhancing protection and performance under conditions of threat, challenge, and opportunity.

Our group has proposed that in contrast to chronic stress that can have harmful effects, the short-term (fight-or-flight) stress response (lasting for minutes to hours) is nature's fundamental survival mechanism that enhances protection and performance under conditions involving threat/challenge/opportunity. Short-term stress enhances innate/primary, adaptive/secondary, vaccine-induced, and anti-tumor immune responses, and post-surgical recovery. Mechanisms and mediators include stress hormones, dendritic cell, neutrophil, macrophage, and lymphocyte trafficking/function and local/systemic chemokine and cytokine production. Short-term stress may also enhance mental/cognitive and physical performance through effects on brain, musculo-skeletal, and cardiovascular function, reappraisal of threat/anxiety, and training-induced stress-optimization. Therefore, short-term stress psychology/physiology could be harnessed to enhance immuno-protection, as well as mental and physical performance. This review aims to provide a conceptual framework and targets for further investigation of mechanisms and conditions under which the protective/adaptive aspects of short-term stress/exercise can be optimized/harnessed, and for developing pharmacological/biobehavioral interventions to enhance health/healing, and mental/cognitive/physical performance.

Field study of a web service for stimulating the positive side of stress: entrepreneurs' experiences and design implications.

BACKGROUND: Digital services have been found promising in managing different aspects of health, also stress. We developed a web service for cultivating the positive side of stress based on the stress experiences of entrepreneurs. In this paper, we present a field study conducted to evaluate the user acceptance and the user experience of the developed service. METHODS: Twenty-two participants, working as entrepreneurs or having an entrepreneurial-type job description, used the web service for 6 weeks. User experiences were collected from all participants with electronic questionnaires, and 10 participants were interviewed to gain deeper understanding and to formulate design implications. In addition, usage logs of the web service were analysed to assess how actively the participants used the service and a pre and post questionnaires on stress and work engagement were conducted to evaluate the preliminary effectiveness of the service. RESULTS: The usage activity of the service was relatively low, on average, the service was used on 3 days and a total of 101 min. During the usage period, the participants' negative stress measured by the perceived stress scale decreased and their self-reported positive stress experiences had increased. The participants considered the positive perspective to stress useful. In the Eustress Toolbox service, the users appreciated especially the off-line and reflection exercises, as well as the quotations from peers, but the design should have supported more active triggering to use the service. CONCLUSIONS: Based on user experience, we propose four design implications: Integrate the service into the daily hassle of entrepreneurs, Provide personal guidance while maintaining a possibility to explore, Recognise the user's progress and accomplishments in a meaningful way and Support implicit learning from peer entrepreneurs. TRIAL REGISTRATION: ISRCTN14739582 , Sept 3 2019, retrospectively registered.

Macronutrient deprivation eustress elicits differential secondary metabolites in red and green-pigmented butterhead lettuce grown in a closed soilless system.

BACKGROUND: Through precise control of the nutrient solution (NS), closed soilless systems enable targeted manipulation of plant secondary metabolites, which constitute health-promoting components of the human daily diet. A nutrient film technique (NFT) system was employed to assess the effect of NS macronutrient-based concentration (full, half-, and quarter-strength corresponding to electrical conductivity (EC) of 1.5, 0.75, and 0.5 dS m-1 ) on the bioactive profile of red and green-pigmented Salanova® butterhead lettuce. RESULTS: Half-strength NS reduced fresh biomass of both cultivars by 14%, whereas quarter-strength NS reduced the fresh biomass of green and red Salanova by 24% and 38%, respectively. However, moderate nutrient stress (half-strength NS) boosted red Salanova total ascorbic acid, chlorogenic, chicoric, caffeoyl-meso-tartaric, total phenolic acids, and anthocyanins concentrations by 266%, 199%, 124%, 251%, 162%, and 380%, respectively compared with the control, full-strength NS. CONCLUSIONS: Nutritional eustress and appropriate cultivar selection are effective means to increase phytochemical content and optimize year-round production of lettuce in closed soilless systems. © 2019 Society of Chemical Industry.

Examining the impact of surgical coaching on trainee physiologic response and basic skill acquisition.

BACKGROUND: We examined how problem-solving coaching impacts trainee skill acquisition and physiologic stress as well as how trainee sensitivity to feedback, known as self-monitoring ability, impacts coaching effectiveness. METHODS: Medical students completed a pre-training demographics questionnaire, a 12-item self-monitoring ability scale (1 = always false, 5 = always true), and baseline FLS Task 5 with physiologic sensors. After watching a laparoscopic suturing instructional video, students practiced the task for 30 min, either with a surgical coach, or alone, depending on condition. The coach logged frequency of coaching behaviors according to a task-specific coaching script. Trainees then completed FLS Task 5 with physiologic sensors, a post-training questionnaire, and a 12-item coaching quality evaluation (1 = poor, 5 = very good). RESULTS: Twenty-four students (age 24.5 ± 1.4; 54% men; 58% MS4) participated in the study. All were fairly high self-monitors (3.8 ± 0.76). No differences in baseline suturing skills between the groups emerged. Improvement in the coaching group's suturing (N = 12; 285.0 ± 79.9) was significantly higher than the control group (N = 12; 200.9 ± 110.3). One measure of physiologic stress (rMSSD) was significantly higher in the coaching group. Trainees who received more coaching demonstrated larger improvements (r = 0.7, p < 0.05). Overall ,perceived quality of the coaching relationship was high (4.4 ± 0.6). There was no correlation between trainee self-monitoring ability and skill improvement. CONCLUSIONS: This work suggests that coaching may increase heart rate variability of trainees, indicating coping well with training. Trainee disposition toward feedback did not play a role in this relationship.

Exploring the link between eustress and adolescent health in India: An empirical study.

BACKGROUND: Modern psychological research challenges the conventional view of stress as solely detrimental by introducing the concept of eustress versus distress, emphasizing the potentially positive aspects of stress. In the context of India, limited studies have investigated the distinct effects of eustress and distress on adolescents, a group prone to stress-related health issues. This study aims to bridge this gap by examining the correlation between eustress and both mental and physical well-being among adolescents attending government schools in two districts of Haryana, India. MATERIALS AND METHODS: A non-experimental quantitative research approach was adopted to achieve this objective. The study involved a sample of 400 adolescent students, equally split between genders, aged 15 to 18 years, enrolled in grades 10 to 12. Participants were selected through systematic random sampling from two districts in Haryana. The assessment tools employed in the study included the Post Graduate Institute Health Questionnaire and the Eustress Scale, which were utilized to evaluate the participants' mental, physical, and eustress levels. RESULTS: In our study involving Indian adolescents, we discovered a substantial positive correlation (r = 0.563, P < 0.01) between eustress and mental health, underlining the valuable role of positive stress in enhancing psychological well-being. Notably, male participants exhibited significantly higher eustress scores (mean = 26.63) than their female counterparts (mean = 22.82, P < 0.01), indicating gender-specific variations in stress responses. Furthermore, our findings emphasized the influence of cultural nuances inherent to the Indian context on how adolescents perceived and experienced eustress. These outcomes emphasize the urgency of culturally sensitive interventions to promote adolescents' well-being. CONCLUSION: This investigation contributes valuable insights into the nexus between eustress and adolescent health in the Indian context. The study accentuates the potential advantages of leveraging eustress to foster positive development by underlining the differential influence of eustress and distress on adolescent health. Future research endeavors and policy formulation could delve into the mechanisms underpinning eustress and distress, thus guiding strategies to enhance adolescents' health and overall well-being.

Relationships between mental toughness, eustress-distress, and mindfulness in adolescents: A network analysis and mediator model testing.

The main aim of this study was to investigate adolescents' eustress-distress and mindfulness by examining mental toughness (MT) using network and mediator analyses. The study included 414 adolescents. The results showed that MT was positively related to eustress and mindfulness, but distress was negatively related to MT. Based on the network analysis findings, we tested mindfulness' mediating role in the relationship between eustress-distress and MT. The findings showed that mindfulness played a significant mediating role. However, the mediating role of mindfulness was negative for the relationship between distress and toughness and positive for eustress. These findings advance eustress, distress, and mindfulness as mechanisms for understanding the effects of MT. Considering current knowledge of MT, eustress, distress, and mindfulness, the results are discussed.

Differentiated response of Hypericum perforatum to foliar application of selected metabolic modulators: Elicitation potential of chitosan, selenium, and salicylic acid mediated by redox imbalance.

Plants plastically alter their metabolism in response to environmental stimuli, which induces changes in the accumulation of specialized metabolites. This ability can be utilized to manipulate plant phytochemistry in a desired direction. However, the abundance of secondary metabolites in the different plant species, especially medicinal, is enormous; therefore, it is difficult to establish a clear direction for the effects of metabolic modulators on phytochemical composition, especially given the possibility of using different types thereof. In order to gain insight into these changes, we investigated the effects of foliar-applied chitosan (ChL, 100 mg/L), selenium (Se, 10 mg/L), salicylic acid (SA, 150 mg/L), or an equal volume mixture thereof on Hypericum perforatum L. metabolism. Selenium and SA proved to be the more effective than ChL in enhancing the accumulation of phenolic compounds. The greatest increase was found in the concentration of neochlorogenic acid after Se-spraying. The treatment with the elicitors generally increased the concentration of identified flavonoids, but not the level of naphthodianthrone or phloroglucinol metabolites. The most pronounced response was observed on day 10 following the application of the compounds, and is likely the consequence of elevated levels of O2-˙, free proline, and modulated activity of enzymatic antioxidants.

Ozone Treatment as an Approach to Induce Specialized Compounds in Melissa officinalis Plants.

Plants are constantly subjected to environmental changes that deeply affect their metabolism, leading to the inhibition or synthesis of "specialized" compounds, small organic molecules that play a fundamental role in adaptative responses. In this work, Melissa officinalis L. (an aromatic plant broadly cultivated due to the large amounts of secondary metabolites) plants were exposed to realistic ozone (O3) dosages (80 ppb, 5 h day-1) for 35 consecutive days with the aim to evaluate its potential use as elicitor of specialized metabolite production. Ozone induced stomatal dysfunction throughout the whole experiment, associated with a low photosynthetic performance, a decrease in the potential energy conversion activity of PSII, and an alteration in the total chlorophyll content (-35, -36, -10, and -17% as average compared to the controls, respectively). The production of hydrogen peroxide at 7 days from the beginning of exposure (+47%) resulted in lipid peroxidation and visible injuries. This result suggests metabolic disturbance within the cell and a concomitant alteration in cell homeostasis, probably due to a limited activation of antioxidative mechanisms. Moderate accumulated doses of O3 triggered the accumulation of hydroxycinnamic acids and the up-regulation of the genes encoding enzymes involved in rosmarinic acid, phenylpropanoid, and flavonoid biosynthesis. While high accumulated doses of O3 significantly enhanced the content of hydroxybenzoic acid and flavanone glycosides. Our study shows that the application of O3 at the investigated concentration for a limited period (such as two/three weeks) may become a useful tool to stimulate bioactive compounds production in M. officinalis.

An antireductant approach ameliorates misfolded proinsulin-induced hyperglycemia and glucose intolerance in male Akita mice.

Protein folding in the endoplasmic reticulum (ER) requires a high ratio of oxidized to reduced glutathione (GSSG/rGSH). Since the GSSG/rGSH depends on total glutathione (tGSH = GSSG + rGSH) levels, we hypothesized that limiting GSH biosynthesis will ameliorate protein misfolding by enhancing the ER oxidative milieu. As a proof-of-concept, we used DL-buthionine-(S,R)-sulfoximine (BSO) to inhibit GSH biosynthesis in Akita mice, which are prone to proinsulin misfolding. We conducted a 2-week intervention to investigate if BSO was safe and a 6-week intervention to find its effect on glucose intolerance. In both cohorts, male heterozygous Akita (AK) and wild-type (WT) mice were continuously administered 15 mM BSO. No adverse effects were observed on body weight, food intake, and water intake in either cohort. Unaltered levels of plasma aspartate and alanine aminotransferases, and cystatin-C, indicate that BSO was safe. BSO-induced decreases in tGSH were tissue-dependent with maximal effects in the kidneys, where it altered the expression of genes associated with GSH biosynthesis, redox status, and proteostasis. BSO treatment decreased random blood glucose levels to 80% and 67% of levels in untreated mice in short-term and long-term cohorts, respectively, and 6-h fasting blood glucose to 82% and 74% ï»¿of levels in untreated mice, respectively. BSO also improved glucose tolerance by 37% in AK mice in the long-term cohort, without affecting insulin tolerance. Neither glucose tolerance nor insulin tolerance were affected in WT. Data indicate that BSO might treat misfolded proinsulin-induced glucose intolerance. Future studies should investigate the effect of BSO on proinsulin misfolding and if it improves glucose intolerance in individuals with Mutant Insulin Diabetes of Youth.

An Empirical Study Analyzing the Moderating Effect of Supervisor Support and Mediating Effect of Presenteeism among Eustress, Distress, and Innovative Behavior.

PURPOSE: This article aims to illustrate that stress is not always a negative experience as it can have both positive and negative outcomes. The term "eustress" describes positive stress, while the term "distress" describes negative stress. To date, research on eustress is in the infancy stage. There are approximately 306 items that can be found in the Web of Science core collection for "eustress", while there are 184,714 items found for "distress". Few studies have examined the relationship between presenteeism, stress, and innovative behavior. Thus, the mechanism underlying this pathway still needs to be fully understood. MATERIALS AND METHODS: A survey was conducted among 350 medical healthcare professionals from Pakistan. With the help of SPSS and AMOS, the data were analyzed and the combined effects of the variables were also investigated. RESULTS: According to the current study, a mediation effect has been observed between innovative behavior and stress (eustress and distress). However, supervisor support moderates the relationship between stress and presenteeism and, likewise, between presenteeism and innovative behavior. CONCLUSION: Our analysis of variables establishes empirically robust relationships between the innovative behavior of medical healthcare professionals and the two different dimensions of stress. In addition, it describes a hypothetical alternative situation that explains how employees' innovative work behavior is affected by eustress and distress in the presence of supervisor support. This study could have implications for improving medical healthcare professionals' ability to incorporate innovative behavior into their practice in an effective manner in the future.

Cellular Functional, Protective or Damaging Responses Associated with Different Redox Imbalance Intensities: A Comprehensive Review.

Reactive species (RS) are produced in aerobic and anaerobic cells at different concentrations and exposure times, which may trigger diverse responses depending on the cellular antioxidant potential and defensive devices. Study searches were carried out using the PubMed database of the National Library of Medicine-National Institutes of Health. Cellular RS include reactive oxygen (ROS), nitrogen (RNS), lipid (RLS) and electrophilic species that determine either cell homeostasis or dysfunctional biomolecules. The complexity of redox signalling is associated with the variety of RS produced, the reactivity of the target biomolecules with RS, the multiplicity of the counteracting processes available, and the exposure time. The continuous distortion in the prooxidant/ antioxidant balance favoring the former is defined as oxidative stress, whose intensity determines (i) the basal not harmful unbalance (oxidative eustress) at RS levels in the pM to nM range that supports physiological processes (e.g., immune function, thyroid function, insulin action) and beneficial responses to external interventions via redox signalling; or (ii) the excessive, toxic distortion (oxidative distress) at RS levels exceeding those in the oxidative eustress zone, leading to the unspecific oxidation of biomolecules and loss of their functions causing cell death with associated pathological states. The cellular redox imbalance is a complex phenomenon whose underlying mechanisms are beginning to be understood, although how RS initiates cell signalling is a matter of debate. Knowledge of this aspect will provide a better understanding of how RS triggers the pathogenesis and progression of the disease and uncover future therapeutic measures.

Distress and eustress: an analysis of the stress experiences of offshore international students.

Introduction: The popularity of online learning provides higher education institutions with opportunities to deliver remote educational programs for international students who remain in their home countries but enroll in overseas universities. Yet the voices of offshore international students (OISs) have been rarely heard. This study focuses on the stress experiences of OISs, aiming to investigate the perception of stressors, specific responses, and stress management strategies pertaining to distress (negative stress) and eustress (positive stress). Methods: Semi-structured interviews were conducted in two phases with 18 Chinese postgraduate OISs enrolled in a range of institutions and disciplines. Interviews took place online and were analyzed thematically to explore participants' experiences. Results: Stress was found to originate from both socially- and task-based factors, closely related to participants' need to integrate into their on-campus community and gain useful knowledge and skills. Particular sources of stress were associated with distinct perceptions and subsequent responses and management strategies. Discussion: A summarizing theoretical model is offered to highlight the separate construct of distress and eustress, indicating tentative causal relationships to extend existing stress models to an educational context and provide new insights into OISs. Practical implications are identified and recommendations are provided for policy-makers, teachers, and students.