D-pinitol is a natural compound related to the important family of inositols. It can be found and isolated from many plants, being the active component of ayurvedic remedies such as Talisa patra (Abies webbiana, A. pindrow) or antidiabetic as Bougainvillea (Bougainvillea spectabilis). Although many synthetic and semi-synthetic methods have been reported for D-pinitol and its derivatives, through chemical and biochemical transformations, Ceratonia siliqua L. (Carob), a Mediterranean tree now in decline, known because of its environmental advantages, is the only raw material from which D-pinitol can be isolated in quantities enough for a viable commercial exploitation. Fortunately, the pharmacological interest in this compound has risen enormously in the last years owing to their established multifunctional properties through a variety of signalling pathways: ⅰ) anti-cancer, through inhibition of TNF-ᾳ and suppression of NF-ⱪB pathway; ⅱ) insulinomimetic and metabolic regulator in type 2 diabetes mellitus, via a post-receptor pathway of insulin action; ⅲ) antioxidant; ⅳ) hepatoprotective; ⅴ) immuno-modulator, balancing Th1/Th2 cytokines; ⅵ) osteoporosis preventive, through p38/JNK and NF-ⱪB pathways; ⅶ) anti-aging, via reduction of the insulin/IGF-1 signaling (IIS) pathway; ⅷ) improver of creatine retention; ⅸ) preventive and ameliorative of Alzheimer's disease through selective g-secretase modulation. Thus, the present review compress the literature reported to date in relation to the health-promoting effects and metabolic pathways of this naturally occurring super-food ingredient and its derivatives, providing an extensive guide for a future utilization of all of its potentialities, aiming a positive impact in the promotion and recovery of carob crops.

There is little doubt that increases in thermal load beyond the thermo-neutral state prove progressively stressful to all living organisms. Increasing temperatures across the globe represent in some locales, and especially for outdoors workers, a significant source of such chronic load increase. However, increases in thermal load affect cognition as well as physical work activities. Such human cognition has perennially been viewed as the primary conduit through which to solve many of the iatrogenic challenges we now face. Yet, thermal stress degrades the power to think. Here, we advance and refine the isothermal description of such cognitive decrements, founded upon a synthesis of extant empirical evidence. We report a series of mathematical functions which describe task-specific patterns of performance deterioration, linking such degrees of decrement to the time/temperature conditions in which they occur. Further, we provide a simple, free software tool to support such calculations so that adverse thermal loads can be monitored, assessed and (where possible) mitigated to preserve healthy cognitive functioning.

Over the last 15 years, mixture risk assessment for food xenobiotics has evolved from conceptual discussions and simple screening tools, such as the Hazard Index (HI), towards operational, component-based and probabilistic frameworks embedded in major food-safety institutions. This review synthesizes methodological and regulatory advances in cumulative risk assessment for dietary “cocktails” of pesticides, contaminants and other xenobiotics, with a specific focus on food-relevant exposure scenarios. At the toxicological level, the field is now anchored in concentration/dose addition as the default model for similarly acting chemicals, supported by extensive experimental evidence that most environmental mixtures behave approximately dose-additively at low effect levels. Building on this paradigm, a portfolio of quantitative metrics has been developed to operationalize component-based mixture assessment: HI as a conservative screening anchor; Relative Potency Factors (RPF) and Toxic Equivalents (TEQ) to express doses within cumulative assessment groups; the Maximum Cumulative Ratio (MCR) to diagnose whether risk is dominated by one or several components; and the combined Margin of Exposure (MOET) as a point-of-departure-based integrator that avoids compounding uncertainty factors. Regulatory frameworks developed by EFSA, the U.S. EPA and FAO/WHO converge on tiered assessment schemes, biologically informed grouping of chemicals and dose addition as the default model for similarly acting substances, while differing in scope, data infrastructure and legal embedding. Implementation in food safety critically depends on robust exposure data streams. Total Diet Studies provide population-level, “as eaten” exposure estimates through harmonized food-list construction, home-style preparation and composite sampling, and are increasingly combined with conventional monitoring. In parallel, human biomonitoring quantifies internal exposure to diet-related xenobiotics such as PFAS, phthalates, bisphenols and mycotoxins, embedding mixture assessment within a dietary-exposome perspective. Across these developments, structured uncertainty analysis and decision-oriented communication have become indispensable. By integrating advances in toxicology, exposure science and regulatory practice, this review outlines a coherent, tiered and uncertainty-aware framework for assessing real-world dietary mixtures of xenobiotics, and identifies priorities for future work, including mechanistically and data-driven grouping strategies, expanded use of physiologically based pharmacokinetic modelling and refined mixture-sensitive indicators to support public-health decision-making.