Metabolic effects of gender-affirming hormone therapy
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Consensus on the key characteristics of metabolism disruptors
Metabolism-disrupting agents (MDAs) are chemical, infectious or physical agents that increase the risk of metabolic disorders. Examples include pharmaceuticals, such as antidepressants, and environmental agents, such as bisphenol A. Various types of studies can provide evidence to identify MDAs, yet a systematic method is needed to integrate these data to help to identify such hazards. Inspired by work to improve hazard identification of carcinogens using key characteristics (KCs), we developed 12 KCs of MDAs based on our knowledge of processes underlying metabolic diseases and the effects of their causal agents: (1) alters function of the endocrine pancreas; (2) impairs function of adipose tissue; (3) alters nervous system control of metabolic function; (4) promotes insulin resistance; (5) disrupts metabolic signalling pathways; (6) alters development and fate of metabolic cell types; (7) alters energy homeostasis; (8) causes inappropriate nutrient handling and partitioning; (9) promotes chronic inflammation and immune dysregulation in metabolic tissues; (10) disrupts gastrointestinal tract function; (11) induces cellular stress pathways; and (12) disrupts circadian rhythms. In this Consensus Statement, we present the logic that revealed the KCs of MDAs and highlight evidence that supports the identification of KCs. We use chemical, infectious and physical agents as examples to illustrate how the KCs can be used to organize and use mechanistic data to help to identify MDAs.
What makes a man unmanly? The global concept of ‘unmanliness’
This paper presents the findings of a multi-national study that led to the development of a new analytical framework in masculinity research—the Global Concept of ‘Unmanliness’ (GCU). Drawing on three key theories—hegemonic masculinity, precarious manhood and masculinity threat, and emasculation—we conducted an innovative study across 15 countries (selected from an initial pool of 62) to examine cultural perceptions of ‘unmanliness.’ Participants provided open-ended responses to identify traits and behaviors considered unmanly within their cultural contexts. By analyzing common themes expressed by young men, we propose the Global Concept of ‘Unmanliness’ as a framework for understanding how societies define and enforce masculinity norms. Furthermore, comparing these findings with the Global Gender Gap Index (GGGI) revealed a key distinction in how ‘unmanliness’ is characterized across different levels of gender emancipation. In countries with high GGGI rankings (e.g., Norway, Ireland, Germany), ‘unmanliness’ is more often associated with physical traits and behaviors linked to femininity (e.g., clothing, makeup). Conversely, in countries with low GGGI rankings (e.g., Pakistan, Morocco, Nigeria), it is more commonly defined by acts such as violence against women. Our study highlights how cultural and structural gender dynamics shape the boundaries of masculinity and offers a new lens for cross-cultural research on gender norms.
Exploring metabolic reprogramming in esophageal cancer: the role of key enzymes in glucose, amino acid, and nucleotide pathways and targeted therapies
Esophageal cancer (EC) is one of the most common malignancies worldwide with the character of poor prognosis and high mortality. Despite significant advancements have been achieved in elucidating the molecular mechanisms of EC, for example, in the discovery of new biomarkers and metabolic pathways, effective treatment options for patients with advanced EC are still limited. Metabolic heterogeneity in EC is a critical factor contributing to poor clinical outcomes. This heterogeneity arises from the complex interplay between the tumor microenvironment and genetic factors of tumor cells, which drives significant metabolic alterations in EC, a process known as metabolic reprogramming. Understanding the mechanisms of metabolic reprogramming is essential for developing new antitumor therapies and improving treatment outcomes. Targeting the distinct metabolic alterations in EC could enable more precise and effective therapies. In this review, we explore the complex metabolic changes in glucose, amino acid, and nucleotide metabolism during the progression of EC, and how these changes drive unique nutritional demands in cancer cells. We also evaluate potential therapies targeting key metabolic enzymes and their clinical applicability. Our work will contribute to enhancing knowledge of metabolic reprogramming in EC and provide new insights and approaches for the clinical treatment of EC.
Fasting appetite-related gut hormone responses after weight loss induced by calorie restriction, exercise, or both in people with overweight or obesity: a meta‐analysis
Altered appetite-related gut hormone concentrations may reflect a physiological adaptation facilitating weight regain after weight loss. This review investigates hormonal changes after weight loss achieved through calorie restriction (CR), exercise (EX), or both combined (CREX).
Emotions and individual differences shape human foraging under threat
A common behavior in natural environments is foraging for rewards. However, this is often in the presence of predators. Therefore, one of the most fundamental decisions for humans, as for other animals, is how to apportion time between reward-motivated pursuit behavior and threat-motivated checking behavior. To understand what affects how people strike this balance, we developed an ecologically inspired task and looked at both within-participant dynamics (moods) and between-participant individual differences (questionnaires about real-life behaviors) in two large internet samples (n = 374 and n = 702) in a cross-sectional design. For the within-participant dynamics, we found that people regulate task-evoked stress homeostatically by changing behavior (increasing foraging and hiding). Individual differences, even in superficially related traits (apathy–anhedonia and anxiety–compulsive checking) reliably mapped onto unique behaviors. Worse task performance, due to maladaptive checking, was linked to gender (women checked excessively) and specific anxiety-related traits: somatic anxiety (reduced self-reported checking due to worry) and compulsivity (self-reported disorganized checking). While anhedonia decreased self-reported task engagement, apathy, strikingly, improved overall task performance by reducing excessive checking. In summary, we provide a multifaceted paradigm for assessment of checking for threat in a naturalistic task that is sensitive to both moods as they change throughout the task and clinical dimensions. Thus, it could serve as an objective measurement tool for future clinical studies interested in threat, vigilance or behavior–emotion interactions in contexts requiring both reward seeking and threat avoidance.
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