Maple (Acer spp.) seeds are potential sources of fat-soluble nutrients and bioactive compounds, yet they remain comparatively understudied. This study compared six market-derived Acer seed types by quantifying phospholipids (PLs), fatty acids, carotenoids, and phytosterols, and by evaluating total phenolic content (TPC) and DPPH radical scavenging activity in methanolic extracts. Total phospholipid contents varied markedly among samples (17.94-295.87 mg/100 g), with phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) as the predominant classes. Fatty acid profiles were dominated by oleic acid (C18:1) and linoleic acid (C18:2), and nervonic acid (NA; C24:1) was consistently detected in all samples at 0.17-1.88 g/100 g (4.55-7.89% of total fatty acids). β-Sitosterol ranged from 16.58 ± 1.41 to 37.46 ± 1.62 mg/100 g. Carotenoid composition varied among the tested samples, and Jeju red maple showed the highest provitamin A potential, including the exclusive detection of α-carotene and the highest retinol activity equivalent. Antioxidant indices also differed significantly among samples (TPC: 317.89-897.12 mg GAE/100 g; DPPH: 81.37-93.27%), but TPC was not consistently proportional to DPPH activity, suggesting contributions from non-phenolic constituents. Pearson correlation analysis further showed exploratory co-variation patterns among the measured variables across the tested samples. Overall, the tested market-derived Acer seed materials exhibited marked compositional diversity and antioxidant potential, supporting their further evaluation as candidate functional food, nutraceutical, and value-added plant lipid resources.
Early detection of the Asian longhorned beetle (Anoplophora glabripennis, ALB), a destructive wood-boring pest, remains challenging in living trees. Volatile organic compounds (VOCs) have gained increasing attention as potential detection cues due to their key roles in plant-insect interactions, yet trunk-based volatile responses to wood-boring herbivores are still poorly understood. Here, we present a detailed case study characterizing constitutive and herbivore-induced plant volatiles (HIPVs) emitted from a living Acer platanoides trunk infested by ALB. Over six months, trunk emissions were monitored and analyzed noninvasively using thermal desorption gas chromatography mass spectrometry (TD-GC-MS). Constitutive emissions were dominated by aldehydes and were primarily influenced by abiotic factors such as temperature and light, whereas ALB infestation had only minor effects on their emission rates. In contrast, HIPVs were characterized mainly by terpenoids and exhibited infestation-stage-specific dynamics: monoterpenoids - dominated by p-cymene, (E)-4,8-dimethylnona-1,3,7-triene, and γ-terpinene - prevailed during oviposition, whereas sesquiterpenoids dominated during larval feeding, particularly cyclosativene, α-longipinene, α-copaene, zingiberene, and α-curcumene. In addition, nitrogen- and oxygen-containing volatiles were identified as previously unreported components of the ALB-induced trunk volatile blend. Several induced terpenoids are known to elicit electrophysiological or behavioral responses in ALB and its natural enemies, and therefore represent valuable key compounds that can be utilized for olfactory detection purposes. Though requiring validation with replications and analogous experiments with further plant and insect species, the findings of this study provide valuable mechanistic insights in tritrophic interactions between plant, wood-boring insect and its enemies.
The genus Diaporthe (asexual synonym: Phomopsis) encompasses pathogenic, endophytic, and saprophytic species with a broad host range, where certain species can readily migrate between hosts. As pathogens, some species of Diaporthe (asexual synonym Phomopsis) can infect a variety of host plants, resulting in severe fungal diseases. However, the species occurring on Acer palmatum has never been systematically studied. In this study, a total of 251 Diaporthe isolates were obtained from the foliage of A. palmatum showing leaf blight symptoms. Phylogenetic analyses based on five loci (ITS, CAL, HIS3, TEF, and TUB), the species delimitation analysis (ABGD, bPTP, and GMYC method), and morphology revealed that the 70 representative isolates belonged to 10 known species (including Diaporthe arecae, Diaporthe biconispora, Diaporthe caryae, Diaporthe discoidispora, Diaporthe eres, D.ganjae, Diaporthe hongkongensis, Diaporthe sackstonii, Diaporthe sojae, and Diaporthe unshiuensis). Molecular clock analyses suggested that the ancestor of Diaporthe emerged in the late Eocene, with a mean stem age of 52.37 Mya (95% HPD of 50.44-54.33 Mya) and a mean crown age of 43.95 Mya (95% HPD of 36.21-51.01 Mya). Although Koch's postulates confirmed all isolates as being pathogenic, a high degree of variation in pathogenicity was observed. Such a high diversity of Diaporthe on one single host, A. palmatum, raised questions in fungal evolution, ecology, population dynamics, and phytopathology of Diaporthe for future studies. And this provides new evidence for extrapolating global fungal diversity based on the ratio of plants to fungi.
The level of seed dormancy regulates germination timing, which is an adaptive differentiation that hedges risks against unpredictable and variable environments across a species's geographic range. The adaptive differentiation is significantly influenced by a combination of local environmental and intraspecific variation in seed traits. However, the relative importance of these influencing factors varies considerably among various geographic provenances of the same species. The objective of this study is to assess the association between level of dormancy and key environmental factors and intraspecific seed traits for the same species from different geographic provenances (climatic regions), and consequently, to predict how the species may react in the future climate change. Seeds of widely distributed species Acer mono were collected from six geographic provenances along a latitudinal gradient in China. We employed a multi-factorial experimental design, treating seeds with gibberellin (multiple concentrations), cold/warm stratification (varying durations), dry after-ripening, and isolated embryo culture. Key morphometric (e.g., size, weight) and quality traits of seeds were measured. Germination responses were analyzed using Generalized linear models (binomial distribution) and Kruskal-Wallis. Multivariate relationships between seed traits and environmental factors were examined using Principal component analysis. Seeds from higher-latitude geographic provenances (cold/dry) were larger and exhibited nondeep physiological dormancy (PD) broken by shortened stratification (40-120 days of cold (5 °C) or warm (15 °C) stratification), gibberellin, dry after-ripening, or embryo isolation, consistent with adaptive differentiation for rapid germination in the short growing season. Seeds from lower-latitude geographic provenances (warm/wet) displayed intermediate PD, requiring 150 days of cold stratification (5 °C) for release. This study provides empirical evidence that environmental gradients shape intraspecific variation in seed dormancy and traits in Acer mono, thereby enhancing our capacity to predict the species' regenerative potential via seeds under global climate change.
Climate change threatens global forest biodiversity, particularly affecting long-lived, endangered tree species. However, the molecular mechanisms underlying their population evolution and environmental adaptation remain unclear. Here, we employed multi-omics analyses, including pan-genomes, transcriptomics, metabolomics, population genomics, and epigenomics, to decipher nervonic acid biosynthesis and population evolutionary history of the endangered tree Acer miaotaiense. A high-quality, chromosome-level genome of A. miaotaiense was first assembled (645.94 Mb). Pan-genome characterization showed that core genes and structural variation of seven Acer species were enriched in long-chain fatty acid metabolism. Metabolomic and transcriptomic analyses identified AmiaKCS7 and AmiaKCS9 as key regulators of nervonic acid biosynthesis. Population genomics demonstrated east-west divergence, with eastern populations showing elevated inbreeding and deleterious mutations. Especially, the eastern marginal populations represented priority conservation units under global warming due to their heightened genomic vulnerability. Landscape genomics revealed 747 candidate genes involved in local adaptation, particularly to temperature fluctuations and drought stress (e.g., heat shock protein 20 and major intrinsic protein). Integrated epigenomic analyses further confirmed transposon-associated methylation and lncRNAs modulated heat-responsive environmental adaptation. Our findings establish a foundational resource for understanding the adaptive evolution of A. miaotaiense and pinpoint critical genes and populations essential for its future conservation.
Acer truncatum is a tree species of the genus Acer, within the Sapindaceae family. Traditionally, it has functioned as a medicinal, edible, and ornamental plant in northern China. The oil content of A. truncatum seed can reach up to 48 %, and contains approximately 92 % unsaturated fatty acids, including a substantial amount of nervonic acid (NA), which constitutes 5.8 % of its composition. To use eggs as a carrier to develop a daily nutritional product enriched with NA and high nutritional value, A. truncatum seed was supplemented in feed of laying hens. A total of 120 healthy 42-week-old Hy-Line White laying hens were randomly assigned to two groups. The control group (Control, CON) was fed basal diet, whereas the experimental group (A. truncatum seed, ATS) received basal diet supplemented with 10 % A. truncatum seed. The experimental period lasted 2 weeks. The results showed that, compared with the CON group, the ATS group exhibited increased egg weight and overall egg quality, elevated serum HDL-C levels, and no adverse effects on liver or kidney function. Lipidomics analysis further demonstrated that the ATS group exhibited significant reduction in glycerolipids particularly TG content, accompanied by increased levels of glycerophospholipids particularly PC, PE and sphingolipid subclasses particularly Hex2Cer, Hex3Cer, GD3, GM2, LSM, and GT3 content in egg yolk. In addition, dietary supplementation with A. truncatum seed increased the contents of NA, DHA, EA, cis-11-eicosenoic acid, and LA in egg yolk. No significant difference was observed between the two groups in the levels of essential or nonessential amino acids in egg white. In addition, A. truncatum seed modulated cecal microbiota structure, by increasing the relative abundance of p_Firmicutes, f_Turicibacteraceae, and g_Turicibacter, while decreasing the relative abundance of p_Bacteroidetes, f_Bacteroidaceae, and g_Bacteroides. In conclusion, dietary supplementation with A. truncatum seed enhanced egg quality, improved egg yolk lipid profiles, optimized the unsaturated fatty acid content, and regulated egg white amino acid content, thereby enhancing the nutritional and functional value of eggs. This study provides scientific basis for the future application of A. truncatum seed in laying hen production.
Wild trees have a long prematuration period before flowering. Threshold tree size and light conditions are suspected to trigger the reproductive maturation, though genetic evidence is needed to confirm this. We investigated the genetic mechanisms underlying the onset of reproduction using two wild maple species, Acer amoenum var. amoenum (Aa) and A. mono var. glabrum (Am). We performed RNA-seq on leaves and buds sampled from the canopy tops of wild juvenile and mature trees to capture RNA expression during bud formation. We identified genes whose expression levels were highly correlated with FLOWERING LOCUS T (FT) as well as with tree size and/or light conditions; such genes were designated as differentially expressed genes (DEGs). Genes significantly correlated with light were further examined through a light manipulation experiment. Most DEGs were correlated with both tree size and light conditions, demonstrating clear expression changes between saplings and adult trees. In Am, DEG expression patterns in adult trees further relied on tree size and light conditions, unlike Aa, the shade-adapted species. DEGs included mRNA of several flowering pathway transcription factors, including SQUAMOSA promoter-binding protein-like, FRIGIDA-like, and COP1, indicating their involvement in the lifetime reproductive schedule of Acer trees. Some of these genes responded to light manipulation, demonstrating light-dependent adjustments. Overall, our results reveal a synchronous shift in flowering-related gene expression across tree size, along with interspecific differences correlated with their different light requirements.
Urban air quality degradation, driven by intensified urbanization and traffic, presents a critical public health challenge in most cities worldwide, such as Guelma, Algeria, where concentrations of fine particulate matter (PM2.5, PM10) and carbon dioxide (CO2) often exceed health standards. This study evaluates the efficacy of conventional greening by suggesting that the air purification potential of public gardens may be limited by suboptimal initial design. It is an exploratory modeling framework to propose a shift from qualitative landscaping to quantitative, performance-driven biophilic design. By simulating six parameterized intervention scenarios, this research indicates that simplistic canopy densification may be an insufficient strategy under high pollutant loads. Based on a specific summer field campaign and a limited temporal scope, the results identify a proposed design configuration protocol, where significant pollutant mitigation is achieved by a specific arrangement: a 60% urban forest index composed of high-efficiency species (Platanus × acerifolia, Acer saccharinum, Quercus spp.), combined with a 10% shrub layer and 40% grass cover to form a multilayered filter. This vegetative system is integrated with complementary engineered systems: linear water features covering 15% of the surface for particle wash-down, soil engineered to an aerodynamic roughness length (z0) of 0.15 m across 65% of the site to enhance deposition, and pollutant-absorbing paving on 20% of the surface. This study suggests that enhancing the functional efficiency of urban gardens requires precise, multimechanism integration of biomass, water, and engineered surfaces, providing an exploratory framework for designing public spaces as potential infrastructure for sustainable air quality improvement.
Most international guidelines recommend a two-step approach using the Fibrosis-4 index (FIB-4) and vibration-controlled transient elastography (VCTE) to identify advanced fibrosis, a key predictor of all-cause and liver-related mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, VCTE is not available in most primary care settings in Malaysia, and there is scarce data on the cost-effectiveness of different approaches. This study evaluated the cost-effectiveness of three referral pathways for identifying advanced fibrosis among type 2 diabetes mellitus(T2DM) patients with MASLD. We developed a decision-analytical model from the healthcare provider's perspective, using 1,000 simulated patients to compare: (i) Current Practice (direct referral based on elevated alanine transaminase), (ii) Clinical Practice Guidelines (CPG) Pathway using FIB-4 single-cutoff 1.3, and (iii) FIB-4 dual-cutoffs (1.3,3.25) followed by a gamma-glutamyl transferase (GGT) test for indeterminate cases (Sequential FIB-4/GGT Pathway). Current practice served as the reference comparator. The primary outcomes were the average cost-effectiveness ratio (ACER) and the incremental cost-effectiveness ratio (ICER). Model parameters were mainly derived from local studies. Direct medical costs were reported in 2024 Malaysian Ringgit (MYR). Sequential FIB-4/GGT pathway had the lowest ACER at MYR930 per advanced fibrosis case identified, compared to MYR1,299 for current practice and MYR1,581 for the CPG pathway. Sequential FIB-4/GGT pathway was potentially more effective and less costly, demonstrating dominance over current practice with a cost savings of MYR2,911/additional advanced fibrosis case identified. CPG pathway was more effective and more costly than current practice, with an ICER of MYR3,785. Sequential FIB-4/GGT pathway was cost-effective for identifying advanced fibrosis in T2DM patients with MASLD. This pragmatic approach could reduce tertiary care referrals, lower healthcare resource use and costs compared to current practice. CPG pathway was more effective than current practice, but incurred higher costs and required increased availability of VCTE within clinical practice.
Methanogenic and methane-oxidizing communities (i.e., the microbial communities involved in methane production and consumption) of the tree phyllosphere remain uncharacterized for most tree species despite increasing evidence of their role in regulating tree methane fluxes. Using 16S rRNA gene sequencing, we studied the methanogenic and methane-oxidizing communities of leaves, wood, and bark of five tree species (Acer saccharinum, Fraxinus nigra, Ulmus americana, Salix nigra, and Populus spp.) growing in the floodplain of Lake St-Pierre (Québec) and assessed their relationships with plant traits. Methane-cycling communities differed primarily between tree tissues (leaf, wood, and bark) but also between tree species according to different traits (e.g., leaf, heartwood and bark pH, leaf humidity). Methanogens were prevalent in wood, while methane-oxidizing taxa were found at higher proportions in leaves and bark. Tissue pH was a particularly important trait modulating methane-cycling community composition and the relative abundance of methanogens and methane-oxidizing taxa in the different phyllosphere compartments. Overall, our study shows that methanogens and methane-oxidizing taxa are prevalent in the phyllosphere of several tree species, suggesting a potential widespread role in the regulation of tree methane fluxes. Better understanding these microbial communities and their drivers can help assess their potential contribution to methane-flux regulation.
Antimicrobial resistance (AMR) poses a global One Health challenge, linking human, animal, and environmental health. Marine environments and organisms are increasingly recognized as reservoirs of antimicrobial-resistant bacteria and mobile genetic elements. This study investigates the prevalence of antibiotic non-susceptible bacteria and resistance genes in juvenile Glaucostegus cemiculus blackchin guitarfish along the Israeli Mediterranean coast. Between 2023 and 2024, 19 specimens were sampled from Ma'agan Michael, Acer, and Evtach. Swabs from skin, gills, and mouth were cultured on selective and chromogenic media, followed by identification using matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF MS) and antimicrobial susceptibility testing. Resistance genes were screened by quantitative PCR (qPCR), with CTX-M beta-lactamases (bla CTX-M) variants sequenced and phylogenetically analyzed. A total of 162 bacterial isolates were obtained, of which 54% were identified to 26 species across eight families, primarily Staphylococcaceae (39%) and Bacillaceae (36%). Several clinically relevant pathogens were detected, including Staphylococcus aureus, Pseudomonas spp., and Escherichia coli. Reduced susceptibilities were observed in 31 isolates from 10 specimens, with multidrug resistance identified in P. mendocina, P. stutzeri, and E. coli. Skin samples yielded the highest proportion of resistant isolates. Importantly, the bla CTX-M-185 extended-spectrum β-lactamase gene was detected in six individuals, with sequences closely related to those of human-associated strains, suggesting anthropogenic origins. These findings demonstrate that juvenile guitarfish harbor clinically significant resistant bacteria and genes, highlighting the marine environment as a potential reservoir of AMR. Integrating endangered species into AMR surveillance highlights the importance of for environmental monitoring and conservation strategies within a One Health framework. Our study applies a One Health perspective to investigate antimicrobial resistance in marine environments. Using the blackchin guitarfish (G. cemiculus) as a model, we sampled individuals along the Israeli Mediterranean coast and analyzed bacterial isolates from the gills, skin, and mouth. We detected multiple clinically relevant pathogens, including Staphylococcus spp., Pseudomonas spp., and E. coli, several of which exhibited resistance to key antibiotics such as β‐lactams, cephalosporins, and carbapenems. Notably, the bla CTX‐M‐185 gene was detected in multiple samples, highlighting the presence of mobile resistance elements and the potential for horizontal gene transfer. To our knowledge, this is the first study to evaluate AMR prevalence in G. cemiculus in the Eastern Mediterranean, providing novel insights into marine reservoirs of antimicrobial resistance. Our findings demonstrate that marine organisms can serve as reservoirs for AMR, linking human activity (e.g., wastewater discharge), wildlife health, and ecosystem stability. Furthermore, our findings provide valuable data relevant to global AMR surveillance, illustrating the interconnectedness of human, animal, and environmental health. This work underscores the importance of integrated environmental monitoring within a One Health framework for assessing public health risks and marine ecosystem integrity.
Rodent populations in agricultural environments serve as critical reservoirs for zoonotic diseases, posing significant risks to food security and public health. Transmission in these settings is complex, thereby occurring through both direct rodent-to-rodent contacts and indirect exposures to environmental contamination. In this paper, we formulate and analyze a deterministic model that integrates rodent population dynamics with an environmental pathogen compartment. To identify resource-efficient mitigation policies, we develop an optimal control framework that incorporates three time-dependent interventions: contact prevention, environmental sanitation, and treatment. By applying Pontryagin's Maximum Principle, we derive the Hamiltonian, the adjoint system, and the characterization of the optimal controls, and subsequently solve the optimality system using a forward-backward sweep algorithm. We evaluate the epidemiological impact and economic viability of seven distinct intervention strategies using the Average Cost-Effectiveness Ratio (ACER) and the Incremental Cost-Effectiveness Ratio (ICER). Numerical simulations demonstrate that while the full combination of controls yields the maximum reduction in infection, the prevention-only strategy emerges as the most economically attractive option under restricted budgets. These findings suggest that prioritizing contact-reduction measures provides the most cost-effective basis for disease management, while integrated sanitation and treatments should be scaled based on resource availability. This study provides a quantitative framework that may assist agricultural stakeholders in developing resource-efficient control policies.
Heatwaves are intensifying worldwide, often coinciding with high vapour pressure deficit (VPD) and soil drought. Yet, how temperate tree species tolerate these combined stresses remains elusive. Using single-tree gas-exchange chambers, we examined the response of leaf gas exchange and thermoregulation of three broadleaved tree species to a stepwise increase in air temperature (25°C-45°C) along with VPD (2.5-7.9 kPa) under well-watered and moderate drought conditions, followed by a 2-day recovery at 25°C. Across species, heat stress increased transpiration but reduced net assimilation, leading to sharp declines in water-use efficiency. Alongside, leaf cooling intensified, driving leaf temperatures below air temperature. Under moderate drought, restricted stomatal conductance reduced transpirational cooling, causing leaf temperatures to exceed air temperature and increasing heat-related damage. Species differed markedly in their heat responses along the isohydric-anisohydric spectrum. Isohydric Acer platanoides showed early stomatal closure, limited cooling, severe leaf damage, and poor recovery. Anisohydric Quercus robur maintained gas exchange, exhibited minimal leaf damage and recovered rapidly, while Fagus sylvatica showed intermediate responses. Together, these results highlight that the ability of temperate trees to withstand future heatwaves will depend on the interplay between water availability, transpirational cooling, as well as species-specific hydraulic strategy and heat tolerance.
This study investigates the climate sensitivity and resilience of radial growth in eight coniferous and deciduous tree species in the Vienna Woods, Austria. Using dendrochronological methods, we analyzed tree-ring width data from 63 forest plots to assess growth responses to meteorological variability over the period 1933-2023. Historic climate records were used to develop a water balance model, from which we derived seasonal growth factors. Linear mixed effects models were applied to quantify species-specific relationships between tree-ring width and climatic conditions during the current and preceding two years. Tree-ring width responded not only to climatic conditions of the current growing season but also strongly to those of the previous year. Soil moisture and air temperature emerged as the principal drivers of radial growth, with soil moisture positively and temperature negatively affecting ring width. Climatic conditions during June-July of the current year exerted the strongest impact on ring formation. Using regional climate trends and projected air temperature and precipitation trajectories for Central Europe under RCP4.5 and RCP8.5, we forecast future growing conditions for the region. Both scenarios predict an extended growing season, increased transpiration demand, and heightened drought risk - more pronounced under RCP8.5. However, projected increases in precipitation partly offset the drought risk. By combining historical climate sensitivity of radial increment with future climate projections, we modelled expected tree-ring growth for eight tree species. Most species are predicted to experience notable declines in radial growth, with the strongest reductions in conifers, including European larch (Larix decidua), Norway spruce (Picea abies), Austrian pine (Pinus nigra) and Scots pine (Pinus sylvestris). Deciduous species - Sycamore maple (Acer pseudoplatanus), European beech (Fagus sylvatica), and sessile oak (Quercus petraea) - show moderate declines. In contrast, Turkey oak (Quercus cerris) is projected to increase radial growth under future climate scenarios. These findings suggest that forest management in the Vienna Woods and adjacent regions should prioritize the promotion of warm- and drought-tolerant tree species such as Quercus cerris to enhance forest resilience and sustainability in the face of climate change.
Phenylketonuria (PKU) is a rare, autosomal recessive inborn error of metabolism caused by genetic variants of the PAH gene, which encodes phenylalanine hydroxylase (PAH). In PKU, the PAH enzyme has reduced affinity for its substrate [phenylalanine (Phe)] or cofactor [tetrahydrobiopterin (BH4)], shows decreased substrate activation or becomes destabilized owing to protein misfolding. Approximately 3500 PAH variants have been identified that vary in residual PAH activity and thus disease severity and BH4 responsiveness. Burdensome, lifelong dietary restriction remains the standard of care for PKU. Until recently, only two pharmacological therapies were approved for PKU: sapropterin and pegvaliase; however, the need for additional treatment options remained. In 2025, sepiapterin (Sephience™), a novel oral treatment for children and adults with PKU, was approved in several countries, including the USA. Sepiapterin has pharmacological and clinical properties unique from existing therapies. A key differentiating factor is that it has two distinct mechanisms of action: it acts as an independent chaperone for PAH, stabilizing misfolded enzyme variants, and it serves as a bioavailable precursor to BH4, increasing intracellular BH4 levels. Preclinical studies demonstrate that sepiapterin increases PAH activity across a broad range of genetic variants, including those associated with severe phenotypes and BH4-nonresponsiveness. Clinical trials (e.g., phase 3 APHENITY, AMPLIPHY) show that sepiapterin can significantly lower blood Phe versus placebo and sapropterin, with efficacy observed in both classic PKU and BH4-nonresponsive participants. In clinical studies, sepiapterin is consistently well tolerated, with limited side effects and a convenient oral formulation. On the basis of its dual mechanism of action and favorable safety and tolerability profile, sepiapterin has the potential to treat a broad range of individuals with PKU across the spectrum of disease severities and ages. Thus, all individuals should be considered for an initial treatment trial with sepiapterin to establish responsiveness, regardless of genetic variant or phenotypic severity. Sepiapterin: how it works and its potential benefits for people with phenylketonuria Phenylketonuria is a rare genetic condition that causes changes in the enzyme phenylalanine hydroxylase, stopping it from working. As a result, the body cannot break down the amino acid phenylalanine, leading to a buildup of phenylalanine in the blood and brain. Without treatment, phenylketonuria can affect the way the brain develops and how people think or behave. Currently, the main treatment is a specialized, restrictive, low-protein diet. Two medicines, sapropterin and pegvaliase, are also available; however, they are not beneficial for many individuals with phenylketonuria because of age restrictions, side effects, or lack of effectiveness. So, new treatment options are needed. Sepiapterin (Sephience™) is a new treatment approved in 2025 in several countries for children and adults with phenylketonuria. Sepiapterin works differently from existing treatments. It works in two ways: it interacts directly with phenylalanine hydroxylase to make the enzyme work better, and it turns into a substance called tetrahydrobiopterin in the body, which also helps phenylalanine hydroxylase work better. Here, clinicians summarize how sepiapterin works and its demonstrated benefits across the full range of phenylketonuria disease severities. Clinical trials show that sepiapterin lowers phenylalanine levels, including in many individuals with “classic” phenylketonuria (the most severe type). In addition, sepiapterin is well tolerated with minimal potential side effects. Overall, these data suggest that all individuals with phenylketonuria should be considered for treatment with sepiapterin to assess potential benefits.
Autistic people, including those without intellectual disability, face challenges during the transition to adulthood, and experience poor adult outcomes. We conducted a feasibility trial of a novel co-produced peer group intervention to support the transition to adulthood in autistic people. Autistic 16- to 25-year-olds were recruited to this feasibility randomised controlled trial via autism charities and research databases in England and Wales. Participants needed sufficient literacy abilities to be able to access the intervention materials. Participants were randomly assigned (1:1), via an online randomisation service, stratified by age (16-17 and 18-25 years) to the peer group intervention or care as usual (CAU). Participants in both arms could access CAU, which was the routine care offered to autistic 16-25 year-olds in their region, and so varied by participant. The intervention comprised six hour-long online peer group psychoeducation sessions to improve autism knowledge, autism social identity, and self-advocacy skills. The main outcomes of this feasibility trial were as follows: recruitment and retention rates; the acceptability of randomisation and outcome measurement procedures; CAU accessed by participants; acceptability of the interventions; and clinical outcome measure variances. Clinical outcome measures were collected at baseline, and 8-, 16-, and 24-weeks after randomisation. The primary clinical outcome measure was wellbeing at 16-weeks, using the Warwick Edinburgh Wellbeing Scale [WEMWBS], and all randomised participants were included in the analyses. A co-produced qualitative study investigated trial experiences. The trial is registered with the International Standard Randomised Controlled Trial Number [ISRCTN] registry, ISRCTN10513626. Seventy participants were recruited between 1st November 2023 and 10th June 2024 (n = 35 per arm). At 16-weeks, the primary clinical outcome measure (wellbeing score) was completed by 74% (n = 26) of the intervention group and 91% (n = 32) of the CAU group. In terms of CAU, across both arms, participants were most likely to have used medications and primary and community care. Adverse events were comparable between arms (intervention group: 6, CAU group: 7). Qualitative feedback indicated that both study procedures and the intervention itself were acceptable. A full trial appears to be feasible. Limitations including retention in the intervention arm and limited sample representativeness would need to be addressed for a full trial. National Institute of Health and Care Research (NIHR) Research for Social Care and Autistica.
Circadian rhythms are biological processes that occur in approximately 24-hour cycles in organisms. Disruption of circadian rhythms (CD) is thought to have adverse effects on many organs, including the eyes. The aim of this study was to evaluate the effects of circadian disruption on the cornea and conjunctiva, as well as the impact of two forms of omega-3 supplementation on the ocular surface, using a rat model of circadian disruption. This experimental study included 32 female Wistar albino rats, which were divided into four groups. The control group (Group 1) was maintained under normal feeding and sleeping conditions without any disruption. Circadian disruption was induced in the other three groups, which were administered saline (Group 2), fish oil (Group 3), or flaxseed oil (Group 4) via oral gavage. On the 31st day, all rats were euthanized, and corneal, conjunctival, and palpebral tissues were collected from both eyes through enucleation. Histological examination and immunohistochemical analysis of Caspase-3 (Cas-3), tumor necrosis factor-alpha (TNF-α), and PERIOD-2 (PER-2) were performed on the corneal and conjunctival tissues. Group 2 exhibited significantly thicker corneas compared to Group 1 (P < 0.001). Additionally, hyperemia, inflammatory cell infiltration in the conjunctiva, higher expression levels of Cas-3 and TNF-α, and decreased PER-2 expression were observed in the corneal and conjunctival tissues of Group 2. These pathological changes were minimal or absent in Groups 3 and 4. Notably, Group 3 showed better amelioration of these alterations compared to Group 4. Disruption of circadian rhythms can have a negative impact on the cornea and conjunctiva. Omega-3 supplementation demonstrated a significant protective effect against ocular tissue damage induced by circadian disruption. Fish oil was more effective than flaxseed oil in reducing corneal thickening, inflammation, and apoptotic marker expression, highlighting its potential as a therapeutic intervention for circadian rhythm-related ocular pathologies.
This narrative review evaluates glucagon-like peptide-1 receptor agonists (GLP-1RAs) as potential treatments for alcohol use disorder (AUD), a major public health problem with limited treatment options. We first briefly describe the development of GLP-1RAs for treating type 2 diabetes and obesity and then focus on recent studies of the drugs' effects on alcohol-related behaviors, both in animal models and clinical studies. We identified relevant literature by searching for studies of incretin-based therapies using PubMed, Google Scholar, and clinicaltrials.gov and reviewing the reference lists of published reviews. We limited our discussion of preclinical studies of alcohol-related effects to those that provide insights into the mechanism of effects. Clinical studies comprised both observational studies, including those using electronic health records and other real-world data, and randomized controlled clinical trials, including studies completed or in progress. Of the clinical studies, we include original, peer-reviewed research published in English and excluded case reports, commentaries, and preprints. This yielded a total of 13 preclinical studies, 14 clinical studies, 4 published interventional trials, and 19 interventional trials in progress or completed but unpublished. We found convergent evidence from animal and human studies that GLP-1RAs reduce alcohol consumption and improve alcohol-associated outcomes. Several randomized controlled trials (RCTs) in progress aim to test the effects of both established and novel compounds, and different drug formulations and combinations on alcohol consumption. Additional RCTs are needed to establish the efficacy of GLP-1RAs for treating AUD, with mechanistic studies needed to elucidate more fully their mode of action in reducing alcohol consumption.
Dementia is a neurocognitive disorder that involves deterioration in cognitive and daily functioning, leading to loss of independence and reduced quality of life. While pharmacological treatments offer limited symptomatic relief, non-pharmacological approaches such as exercise have shown promise in improving cognitive and functional outcomes. However, evidence from community-based structured exercise interventions remains limited, particularly in low-resource settings. This trial aims to evaluate the effects of a community-based structured group exercise program on cognitive and physical function among older adults with dementia. This assessor-blinded, community-based randomized controlled trial will be conducted from February to September 2026 in Bangladesh. A total of 120 older adults diagnosed with dementia will be randomly allocated (1:1) to either the experimental group (structured group exercise program with healthy lifestyle advice) or the control group (healthy lifestyle advice alone). The intervention will consist of supervised sessions three times a week for 12 weeks, followed by a 12-week follow-up period. The outcome will be measured on both cognitive and physical function bases. Cognitive function will be evaluated using the Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination Revised (ACE-R), Trail Making Test (TMT) A-B, and Digit Span Test (DST). Physical function will be measured using the Senior Fitness Test (SFT), Berg Balance Scale (BBS), Timed Up and Go (TUG) Test, and Instrumental Activities of Daily Living scale (IADLs). All outcomes will be measured at baseline, posttest (12 weeks), and follow-up period (12 weeks). Data will be analyzed using SPSS following the intention-to-treat principle. The findings are expected to support the integration of physiotherapist-led, community-based exercise into dementia care, offering a feasible, safe, and cost-effective approach for improving cognitive and physical function in older adults with dementia. Despite potential limitations in generalizability, the study's community implementation and follow-up design will contribute valuable insights into sustainable rehabilitation practices in resource-limited settings. This trial is registered prospectively in the Clinical Trial Registry India; ID: CTRI/2025/10/096618; Registered on: 29/10/2025. Link: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTQ0NDg3&Enc=&userName=.