Caffeine induces concentration-dependent biphasic or hormetic effects in insects, yet its impact on Drosophila ananassae remains unexplored. We evaluated adult physiological traits (survival, fecundity, lipid content) under adult-only exposure and developmental traits under combined short-term parental adult and continuous offspring developmental exposure across a caffeine concentration gradient (0.6-4.8 mg/ml). Low concentrations (0.6-1.8 mg/ml) increased survival (LT50) approximately 1.6-fold over control (Kaplan-Meier; log-rank P < 0.01), moderately increased fecundity and adult lipid content. Proportions of pupae eclosion were near control, and eggs hatched were slightly but significantly higher than control (P < 0.05) at lower concentrations. Higher concentrations (≥ 3.0 mg/ml) were detrimental, decreasing survival (̴2.5-folds), fecundity, and lipid content, and progressively impairing performance. The proportion of pupae eclosion declined significantly beyond ≥3.6 mg/ml. Developmental duration increased for 2nd and 3rd larvae and pupae as concentration increased, indicating inhibition of post-embryonic development, whereas early embryonic and first-instar durations were unaffected. Mixed-model ANCOVA indicated significant treatment, isofemale line, and treatment × line interaction (P < 0.001), whereas dry body weight remained a non-significant covariate. After body size standardization, lipid content remained positively associated with fecundity across isofemale lines (R2 = 0.88-0.91, P < 0.001). Hormesis Index demonstrated stimulation for adult traits at low concentrations and inhibition at higher concentrations, with transition near 1.8 mg/ml. API showed improved integrated adult performance at lower concentrations, whereas DPI remained near control-equivalent levels or was slightly higher before both indices declined beyond 3.6 mg/ml. These findings suggest concentration-dependent caffeine hormesis, with lower concentrations increasing adult traits and maintaining near biological-maximum developmental performance under combined exposure, whereas higher concentrations impair physiological and developmental traits.

This study presents a novel approach combining stimulated Raman scattering (SRS) microscopy with mechanistic modelling to quantify the disposition and permeation of topically applied compounds in skin. The dermal delivery of 4-cyanophenol and caffeine was investigated using SRS microscopy, generating high-resolution images resolving their distribution within the stratum corneum (SC) lipid matrix and corneocytes. The imaging data revealed distinct permeation pathways, with 4-cyanophenol preferentially localising within the intercellular lipid matrix and caffeine within the corneocyte-rich regions. Depth-resolved SRS imaging provided concentration profiles across the SC, showing a monotonic decrease in 4-cyanophenol concentration, whereas caffeine exhibited depth-dependent transport behaviour. These experimental concentration profiles were modelled using a two-dimensional mechanistic model with calibration to reveal the diffusion, partition and deposition behaviour within the lipid and corneocyte domains. For 4-cyanophenol, the optimised permeability was consistent with literature-reported values and baseline model predictions, while for caffeine, optimisation substantially improved permeability predictions. Simulations further captured formulation-dependent effects predicting 1.3-fold and 1.5-fold increases in SC uptake of 4-cyanophenol and caffeine, respectively, in propylene glycol relative to aqueous vehicles. Overall, this work demonstrates the potential of combining SRS microscopy with inverse mechanistic modelling to derive transport parameters directly from skin imaging data and reveal dermal drug disposition and permeation. To our knowledge, this represents the first application of SRS-derived depth profiles to inform mechanistic modelling of skin permeation.

Pu-erh tea occupies an important position in tea consumption because of its distinctive flavor and potential health benefits; however, its flavor acceptability still has room for improvement. To enhance sensory quality and diversify product forms, this study investigated a blending system of American ginseng powder and ripe Pu-erh tea powder and compared the quality and chemical composition of samples with different blending ratios by integrating sensory evaluation, physicochemical analysis, flavoromics, and untargeted metabolomics. The results showed that SP2, consisting of 75% ripe Pu-erh tea powder and 25% American ginseng powder, achieved the highest overall sensory score among the experimental blends (SP1-SP3) and was characterized by an aged aroma accompanied by a chrysanthemum-like note, a mellow and full-bodied taste, and a pronounced sweet aftertaste. As the proportion of American ginseng increased, the contents of caffeine and esterified catechins decreased, whereas the soluble sugar content increased. Tentatively identified 2-methylbutanal and (E)-2-octenal in SP2 were considered potential aroma-active candidates. A total of 1,171 tentatively annotated non-volatile metabolic features were obtained, with representative differential features involving flavonoids, phenylpropanoid-related compounds, and ginsenoside-related components. These compositional differences mainly reflected the respective contributions of the two raw materials and changes in their blending proportions, providing a reference for formulation optimization and quality evaluation of blended products.

Glyphosate is the most extensively applied herbicide and can be absorbed by non-target plants potentially altering their chemical profile. Coffee, the second most consumed beverage worldwide, relies on glyphosate use to sustain productivity. However, limited evidence exists regarding absorption of soil-applied glyphosate, its possible translocation into coffee beans, and chemical changes. This study investigated the impact of different glyphosate application techniques on chemical composition and residue accumulation in Coffea arabica and Coffea canephora beans. Plants were subjected to seven treatments varying in spray nozzle types (flat-fan and cone) and application schedules (October and December; October and February; and October, December and February). Glyphosate residues were quantified by LC-MS/MS, while gravimetric analyses assessed moisture, ash, and soluble extract yield; chlorogenic acids and caffeine were determined by UHPLC-PDA. Results demonstrated that glyphosate is absorbed and translocated to beans, with residue levels ranging from 0.0 to 0.5 mg/kg. Nonetheless, applications performed in October and December resulted in lower residues levels compared to schedules performed until February, with no significant alterations related to the negative control. Contrary to expectations, chlorogenic acids levels were not affected by glyphosate application. Similarly, despite isolated differences, none of the evaluated parameters were significantly influenced by glyphosate use. These findings were supported by PCA and PERMANOVA, which revealed that sample discrimination was influenced exclusively by species and crop year. Further studies investigating additional coffee bean compounds, particularly from a food safety perspective, are needed to provide a more comprehensive understanding of the effects of glyphosate on coffee beans.

Guarana is a fruit native to the Amazon and is widely recognized for its stimulant properties and economic importance in Brazil, the world's leading producer. However, guarana processing utilizes only the seeds, generating substantial amounts of residues, particularly seed coats. Despite being treated as waste, these residues may constitute valuable sources of nutrients and bioactive compounds, offering opportunities for upcycling and sustainable valorization. This study comprehensively characterized guarana seed coats (PR1, PR2, and PR3) sourced from producers in Amazonas State, Brazil, through integrated physicochemical, compositional, chromatographic, and multivariate analyses. The samples evaluated exhibited high dietary fiber (61.96-64.42%) and protein contents (15.93-17.33%), alongside relevant concentrations of structural carbohydrates (total lignin: 27.59-39.98%; cellulose: 17.19-31.52%; hemicellulose: 9.45-26.27%) and essential minerals, particularly Ca, Mg, K, Cu, and Mn. The residues also showed high concentrations of bioactive compounds, mainly caffeine (16.96-28.88 mg/g) and epicatechin (0.50-12.53 mg/g). Multivariate analyses (PCA and ComDim) revealed distinct compositional profiles among the evaluated production sources, with PR1 as being associated with the highest levels of bioactive compounds, PR2 with elevated structural carbohydrate contents, and PR3 with higher concentrations of essential minerals. Overall, the findings provide a comprehensive compositional basis to support the sustainable valorization of guarana seed coats and future studies evaluating their technological functionality, safety, and food applications, contributing to circular economy strategies.

This study examines acute and delayed adverse reactions reported in naturalistic psychedelic use, focusing on their associations with substance-use patterns, contextual variables, and user motivations. Using an online survey incorporating the Psychedelic Use Scale, data were collected from a large naturalistic sample (N = 1022) to analyze patterns of self-reported adverse reactions. Acute adverse reactions were consistently associated with similar delayed adverse reactions, suggesting continuity between immediate and subsequent self-reported adverse experiences. Furthermore, most acute adverse reactions, with the exception of vomiting, which showed an opposite pattern, were associated with higher current psychopathology and lower well-being. Self-reported lifetime use of individual psychedelics (e.g., DMT, MDMA, and LSD) and combined substances (e.g., alcohol, caffeine, and cannabis) showed participant-level associations with specific self-reported adverse-reaction categories, while MDMA use was also associated with poorer current psychological indicators. Adverse reactions were also associated with contextual variables, including setting, type of companionship, and user motivations. Younger age and higher current frequency of psychedelic consumption were associated with higher odds of reporting adverse reactions. Because the study is cross-sectional and retrospective, and adverse reactions were not linked to specific substances or psychedelic episodes, the findings should be interpreted as correlational, hypothesis-generating co-reporting patterns rather than as substance-specific attribution. Nevertheless, they provide an empirical basis for future prospective, longitudinal, and clinical studies aimed at clarifying temporal relationships and informing harm reduction strategies.

Adolescent suicide remains a major public health concern, with recent increases observed, particularly among females in Japan. However, the toxicological characteristics in forensic settings have not yet been sufficiently described. This study examined the toxicological patterns in adolescent suicide cases before and after the onset of the coronavirus disease 2019 (COVID-19) pandemic, using forensic autopsy data from three institutions in metropolitan Japan (2015-2024). A total of 41 cases (10 males, 31 females) were included in the study. Toxicological findings were compared between the pre-2020 (n = 9) and post-2020 (n = 32) periods, with additional analyses by sex. Over-the-counter (OTC) medication-related components, excluding caffeine, were detected in 33.3% of pre-2020 cases and 53.1% of post-2020 cases. Relevant drugs other than caffeine were detected in 44.4% and 68.8% of cases in the two periods, respectively. Overall, relevant drug detection was more frequent among females than males. Benzodiazepines and Z-drugs were detected predominantly in the post-2020 period. No illicit drugs were identified. These findings indicate that OTC-related components were commonly detected among adolescent suicide decedents undergoing forensic autopsy and suggest possible sex-related differences in toxicological patterns. Comprehensive toxicological assessment may provide additional information for understanding drug exposure associated with adolescent suicide.

Cocaine stands out due to its significant social problems stemming from trafficking, leading to increased violence and detrimental effects on the physical and mental health of its users. Brazil serves as a transit route for cocaine produced in Colombia, Peru, and Bolivia to Europe, with Paraná being a strategic region due to its border with Paraguay and the second-largest port in Brazil. Cocaine is gradually adulterated with cutting agents along the distribution chain, altering its chemical profile. Paradoxically, these components can create a unique chemical signature, enabling the tracing of the drug's origin and distribution routes. This study analysed 298 mid-infrared spectra of cocaine samples seized in Paraná and applied Multivariate Curve Resolution with Alternating Least Squares (MCR-ALS) to identify and characterise the main adulterants and diluents present. MCR-ALS was chosen due to its ability to decompose overlapping spectra into individual component contributions, making it ideal for analysing complex mixtures. Five distinct chemical profiles were identified, and based on their spectral interpretation and the most reported adulterants and diluents in cocaine samples, the five components were defined as: cornstarch, cocaine, caffeine, sodium bicarbonate, and creatine. The concentration profiles of the components were clustered using Hierarchical Cluster Analysis, and seven profiles of cocaine samples were identified based on the amount of cocaine and the presence of adulterants and diluents. The MCR-ALS method proved effective in identifying cocaine cutting agents via ATR-FTIR, offering a fast and reliable approach for forensic analysis that can help to identify commercial routes.

BackgroundRed Bull (RB) is widely consumed by athletes in an effort to enhance performance through its stimulant content, primarily caffeine and taurine. Although its potential ergogenic effects have been studied, evidence regarding the impact of commercially available servings of RB on short-term anaerobic performance remains inconsistent.AimThis study examined whether acute ingestion of a standard commercially available serving of RB influences anaerobic power, handgrip strength, and jumping ability in female sub-elite volleyball players.MethodsFifteen female sub-elite volleyball players (mean age 21.3 ± 2.4 years) participated in a randomized, double-blind, placebo-controlled crossover study. Each athlete completed three physical tests (Wingate anaerobic test, jump test, and handgrip strength test) on two occasions, separated by 1 week, after consuming either RB or a placebo designed to mimic its taste and appearance. Participants ingested 250.7 ± 28.2 mL of RB, providing 80.3 ± 9.0 mg of caffeine (1.143 mg·kg[-1]). Performance testing began 33 min after ingestion. Performance outcomes were compared between conditions using paired t-tests.SummaryNone of the 13 measured performance variables showed statistically significant differences (p > 0.05) between RB and placebo trials. Eight participants reported mild nausea following RB consumption. Under the conditions of this study, consumption of a standard commercially available serving of RB (∼1.143 mg·kg[-1] caffeine) did not produce measurable improvements in anaerobic performance, handgrip strength, or jump ability, suggesting that a single serving does not confer meaningful performance benefits for short-duration, high-intensity exercise in female sub-elite volleyball players.

Additive manufactured electrochemical platforms produced using bespoke conductive filaments are becoming increasingly established within modern electrochemical research; however, the latest developments within the field of additive manufacturing electrochemistry using fused filament fabrication technology have shown that it is constrained by the available material pool. Here, we introduce the first conductive high-density poly(ethylene) (HDPE) filament engineered for additive manufacturing implementation as a new alternative for conductive, chemically resilient filaments which is paramount to unlocking new applications. Using a thermal compounding process that avoids environmentally harmful chemical solvents, 40 wt% carbon black (CB) was incorporated into HDPE and extruded into a flexible, plasticizer-free filament with a low bulk resistivity of 16.4 (±1.0) Ω cm[‒] [1]. Following printing, electrochemical activation was required to expose the conductive carbon black phase and generate the functional electrode surface, particularly for inner-sphere electron transfer. Optimized additive manufacturing produced electrochemical platforms with reproducible performance and heterogeneous electron transfer kinetics corresponding to 2.93 (±0.19) × 10[-3] cm s[-1]. Electrochemical stability testing revealed that the CB/HDPE additive manufactured electrodes exhibited consistent voltammetric responses for over 60 scans, representing an improvement compared to other conductive polymer feedstocks. Over a 70-day period, the CB/HDPE electrodes also maintained chemical stability following immersion in six different solvents. The material's versatility was demonstrated through proof of concept for the electrosynthetic oxidation of chlorpromazine-to-chlorpromazine sulfoxide and the electroanalytical determination of caffeine in commercial energy and coffee beverages, which was validated against liquid chromatography mass spectroscopy, both in aqueous and organic media. This work establishes conductive HDPE as a new entrant to the additive manufacturing electrochemistry toolkit, expanding the material landscape and enabling applications previously inaccessible with existing polymers.

This study investigated the effect of caffeinated Arabica and decaffeinated coffee lyophilizate (0.6 g/100 g), incorporated either before or after fermentation, on the phenolic compound profile, caffeine and diterpene content, antioxidant activity, and physicochemical properties of yogurt during 20 d of refrigerated storage. Yogurts were produced from commercially available pasteurized and homogenized cow's milk (2.0% fat) using a thermophilic starter culture comprising Streptococcus thermophilus, Lactobacillus acidophilus, and Bifidobacterium animalis ssp. lactis (Lyofast SAB 440B). Total phenolic losses during lyophilization amounted to 14.0% and 19.0% for caffeinated and decaffeinated preparations, respectively, with feruloylquinic acid isomers showing the highest susceptibility to degradation (losses of 55-72%). Coffee enrichment resulted in an approximately 9-10-fold increase in total phenolic content relative to control yogurt, with overall phenolic retention reaching 73-85% of theoretical values. After-fermentation addition yielded higher extractable phenolic content, while before-fermentation addition was associated with lower extractable phenolics but superior hydroxyl radical scavenging capacity (OHSC), potentially reflecting the formation of polyphenol-protein complexes during fermentation. Oxygen radical absorbance capacity (ORAC) increased significantly during storage in before-fermentation variants, suggesting progressive release of bound phenolics through starter culture-mediated proteolysis. Decaffeinated lyophilizate added before fermentation produced the firmest yogurt gel, an effect potentially attributable to polyphenol-casein interactions and possible caffeine-mediated modification of starter culture activity. Addition timing rather than coffee type was the primary determinant of surface optical properties. The majority of bioactive compound profiles and physicochemical parameters showed no systematic changes during the 20-d storage period, although significant storage-related changes were observed for selected antioxidant activity indices, textural parameters, surface gloss, and diterpene content in specific treatment groups. These findings indicate that coffee lyophilizate is a promising functional ingredient for yogurt enrichment, with the timing of addition being a critical process parameter that influences bioactive compound availability, antioxidant functionality, and textural quality.