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Quo vadis, BGA? A collaborative EDNAP exercise on the challenges and progress in forensic biogeographical ancestry inference.

There is a broad consensus that forensic tests for the prediction of externally visible characteristics (EVC) and analysis of biogeographic ancestry (BGA) of an individual are technically reliable. However, interpretation of the results and population-specific genotype distribution patterns remains challenging. EVC and BGA analyses provide valuable information for population genetics studies and as investigative leads for criminal cases, as well as for historical and contemporary identification tests. However, inaccurate or incorrect predictions, for example, from subjective bias in the interpretations made, have the potential to misdirect police investigations. The legal situation regarding EVC and BGA testing varies by country: ranging from countries where it is explicitly prohibited, to those without specific regulations on biogeographic ancestry prediction, and others that have already enacted laws governing its use. The reluctance to utilize these analyses is not only due to legal restrictions and data protection concerns, but also to initial limited sets of sufficiently comprehensive forensic DNA assays. Forensic BGA marker panels typically contain up to ∼300 SNPs. This relatively small number of genetic markers, along with limited reference population data, complicates the interpretation of results from donors of unknown origin. This paper presents the results of a collaborative EDNAP study, which, for the first time, evaluated the approach to reporting EVC and BGA data between international laboratories. For the study, DNA from nine individuals with self-reported ancestry was collected and analysed using various forensic panels differing in the number and composition of ancestry-informative markers genotyped, comprising: the Precision ID mtDNA Whole Genome Panel, the VISAGE Basic Tool and the VISAGE Enhanced Tool for Appearance and Ancestry Prediction, and the Ion AmpliSeq™ PhenoTrivium Panel. To ensure full data protection, all SNP genotypes and uniparental marker haplotypes obtained were not shared with third parties. Instead, the genetic data were analysed using a range of commonly used population analysis software packages. These analysis outcomes were then distributed to twelve European forensic laboratories (both academic and law enforcement institutions), who were asked to prepare reports based on their interpretation of the phenotypes and ancestry they inferred from the analysis data. A questionnaire sent alongside the genetic information, aimed to evaluate which difficulties were encountered by the participants in processing the BGA analysis data they were given.

Humans

ScRNA-seq analysis reveals the effects of nitrite stress on the endocrine system of the eyestalk in Litopenaeus vannamei.

Nitrite is a harmful substance generated in Litopenaeus vannamei farming systems, largely originating from the inadequate breakdown of surplus feed and shrimp feces. Its accumulation in the water can affect the growth and physiological functions of shrimp, damage the immune system, and even cause mass mortality, thus becoming a key environmental factor restricting the green development of the industry. Under nitrite stress, the eyestalk, as an important neuroendocrine regulatory center in crustaceans, participates in the stress adaptation of the organism and exerts a protective effect by regulating energy metabolism and immune function. However, the molecular regulatory mechanism of the eyestalk in response to nitrite stress remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) technology was used to analyze the heterogeneity of eyestalk cells in L. vannamei under nitrite stress. A total of 18, 394 high-quality cells were obtained, and six major cell subpopulations, including Neurosecretory cell, Motor neuron, Sensory neuron, Interneuron, Neurogliocyte, and Support cell, were identified. Differential expression analysis identified 839 differentially expressed genes, and different cell types showed distinct specific responses to nitrite stress. Functional enrichment analysis indicated that pathways such as glycolysis, oxidative phosphorylation, ribosome function, and endoplasmic reticulum protein processing were significantly activated, while signal transduction and DNA repair-related pathways were inhibited. Further analysis revealed that nitrite stress could induce mitochondrial function changes and trigger oxidative stress, thereby affecting the neuroendocrine system function of the eyestalk. This study provided insights into transcriptomic responses of the eyestalk to nitrite stress at the single-cell level, laying a theoretical foundation for the management of aquaculture environments.

Animals

Revealing potential biomarkers and metabolic mechanisms of ovarian aging in hens during late laying period based on machine learning and metabolomics.

Ovarian function decline during the late laying period represents a major bottleneck for the economic efficiency of the global poultry industry. However, the underlying metabolic mechanisms and reliable early-warning biomarkers for ovarian aging remain poorly understood. In this study, we performed the first untargeted LC-MS/MS metabolomics analysis of ovarian tissues from Taihe silky fowls at peak laying (30 weeks) and late laying (50 weeks) stages, and employed an ensemble machine learning strategy integrating LASSO, random forest, and support vector machine (SVM) algorithms to identify high-confidence core biomarkers of ovarian aging. Gene expression analysis was further conducted to validate the potential molecular mechanisms. Our results showed that the metabolic profiles of ovarian tissues differed significantly between the two groups. A total of 6 core biomarkers were identified, 4 of which were long-chain acylcarnitines. Mechanistic analysis revealed that downregulation of key genes in the carnitine shuttle system led to impaired mitochondrial fatty acid β-oxidation, which in turn triggered excessive oxidative stress and compromised ovarian endocrine function. In conclusion, this study identifies long-chain acylcarnitines as potential metabolic biomarkers for ovarian aging in Taihe silky fowls. These findings provide novel insights into the metabolic basis of poultry ovarian aging and lay a theoretical foundation for the precise regulation of reproductive performance in indigenous poultry breeds.

Animals

Early hepatic protein responses to dietary restriction-refeeding in Japanese quail: A proteomic investigation.

Feed intake and refeeding after nutrient scarcity induce rapid metabolic adaptations in the poultry liver; however, hepatic proteomic recovery pathways in the early hours post-refeeding remain poorly defined. This study aimed to characterize early liver protein signatures in Japanese quail (Coturnix japonica) recovering from nutritional stress under two refeeding conditions. Eighteen 12-week-old male quails (245.20 ± 0.213 g) were assigned to three groups (n = 6): control fed ad libitum (12.13 MJ/kg), 24 h feed deprivation followed by 6 h refeeding, and 24 h low metabolizable energy (6.30 MJ/kg) diet followed by 6 h refeeding. In total, 854 proteins were identified, of which 515 met the filtering criteria. The low metabolizable energy refeeding showed higher abundance of proteins linked to ATP binding and carbohydrate/carboxylic acid metabolism, alongside detoxification-related proteins, while suppressing translation/RNA-binding machinery and antioxidant pathways. Feed-deprived refeeding enriched in oxidative phosphorylation and mitochondrial complex I assembly with reduced cytoplasmic translation, NMD-related components, and sulfur compound metabolism. A direct comparison indicated divergent recovery strategies: low metabolizable energy refeeding mainly reflected oxidoreductase activity and translation initiation, whereas feed-deprived refeeding potentially enriched mitochondrial ATP production and glutathione-based defenses. Our analysis indicate that 6 h of refeeding initiates an early, incomplete recovery toward hepatic homeostasis, with the severity of prior nutritional restriction dictating distinct liver metabolic priorities. Collectively, these findings might provide a preliminary understanding of the hepatic mechanisms involved in recovery from nutrient deprivation and may help in the development of feeding strategies for managing metabolic recovery in poultry. However, these findings should be considered hypothesis-generating pending further validation.

Animals

Proteomic responses of the oil palm pest Metisa plana (Psychidae) to farnesyl acetate exposure.

Metisa plana Walker (Lepidoptera: Psychidae) is a major defoliator of oil palm in Malaysia, causing substantial economic losses. Farnesyl acetate (FA), a sesquiterpenoid compound, has been proposed as a potential insecticidal agent against M. plana, yet its molecular impact on larval physiology remains poorly understood. Here, we employed label-free quantitative proteomics, functional enrichment analysis, and targeted transcript assessment to characterize the temporal proteomic response of M. plana larvae at 7 and 14 days after treatment (DAT) with FA. Principal component analysis revealed robust separation between treated and control samples at both time points, indicating sustained treatment-driven proteomic restructuring. Early exposure (7 DAT) elicited a heterogeneous response involving stress-associated proteins, redox enzymes, and cytoskeletal regulators, whereas later exposure (14 DAT) produced a consolidated profile characterized by metabolic reprogramming, downregulation of ribosomal proteins, induction of heat shock proteins, and enrichment of RNA surveillance and mitochondrial pathways. Targeted transcript analysis qualitatively supported proteomic trends for HSP83 and aldehyde dehydrogenase X, although limited amplification precluded quantitative inference. Collectively, these findings demonstrate that FA exposure drives a shift from acute proteomic perturbation toward a maintenance-oriented physiological state, prioritizing proteostasis, energy management, and stress adaptation over growth and development. This integrated molecular perspective provides mechanistic insight into the chronic effects of FA, highlighting its potential to suppress larval performance and informing the development of biorational, physiology-based pest management strategies in non-model insects.

Animals

Transcranial Photobiomodulation Variables Assessment Battery: Development and Validation.

Transcranial photobiomodulation (tPBM) response variability is partly driven by biophysical characteristics such as skin tone and hair properties that attenuate photon penetration, and by lifestyle factors including sleep quality, alcohol use, and nicotine consumption that disrupt the mitochondrial and vascular pathways on which tPBM acts. To date, no validated self-report tool exists to capture these moderators systematically. To address this gap, the tPBM Variables Assessment Battery was developed and psychometrically evaluated. It integrates adapted versions of established measures (Brief Pittsburgh Sleep Quality Index, E-cigarette Dependence Scale, Hair Scale Assessment PRO, Monk Skin Tone Scale, and Heaviness of Smoking Index), validated wellbeing evaluators (Ryff's Psychological Wellbeing), and custom measures (Hairstyle Classification, Hair Color Classification). Face and content validity met recommended expert thresholds, internal consistency was acceptable across adapted subscales, and criterion validity analyses confirmed meaningful associations between the lifestyle components and PROMIS-10 global health outcomes. The battery is low-burden, digitally deployable, and psychometrically defensible, offering a practical tool for characterizing the variables most likely to moderate tPBM response in home-use studies.

Humans

Genome-wide insights into the evolutionary and demographic history of the red alga Mazzaella laminarioides: Evidence for speciation with ancient migration along the southeast Pacific coast.

The mechanisms driving lineage divergence in red algae remain unexplored, despite the group's remarkable diversity and ancient evolutionary history. The red alga Mazzaella laminarioides, a Chilean intertidal species complex composed of three parapatric cryptic lineages (North, Center, South), offers a valuable system to evaluate these processes, as its life history combines severe dispersal limitation with a haploid-diploid cycle that may influence the emergence of reproductive barriers. We reconstructed its evolutionary history using whole-genome sequencing and nuclear genome assembly of representative individuals from each lineage. Phylogenomic analyses based on 1,507 single-copy orthologs recovered three deeply divergent lineages with limited nuclear discordance consistent with incomplete lineage sorting. For both splits, demographic modelling was most consistent with an Ancient Migration scenario, although support over strict isolation was moderate, suggesting that divergence may have begun with low asymmetric ancestral gene flow followed by subsequent loss of connectivity, demographic bottlenecks, and later population expansion. Coding sequence analyses revealed lineage-specific dN/dS heterogeneity; only one South-lineage locus passed FDR correction (metaxin-1, mitochondrial protein import), with two further South-lineage candidates in chlorophyll and heme biosynthesis falling below the FDR threshold. Together, these signals suggest that divergent selective pressures on energy acquisition may have contributed to divergence at the southern end of the distribution. These results add to the small but growing body of whole-genome data for red algae and, alongside recent macroalgal studies, suggest that ancestral connectivity could be a recurrent feature of lineage divergence even in marine organisms with extremely restricted dispersal.

Rhodophyta

Proteomic insights into hepatic responses to high soybean meal inclusion with citric acid supplementation in hybrid grouper (Epinephelus fuscoguttatus × Epinephelus lanceolatus) juveniles.

This study evaluated the growth performance and hepatic proteomic responses of juvenile hybrid grouper (Epinephelus fuscoguttatus&#xa0;&#xd7;&#xa0;Epinephelus lanceolatus) juveniles fed diets containing 30% or 40% soybean meal (SBM), with or without 3% citric acid supplementation, and compared with a fishmeal (FM) control diet over a 10-week feeding trial. Fish fed 30% SBM (LSBM) showed a final body weight comparable to the FM group, whereas fish fed 40% SBM (HSBM) recorded significantly reduced growth and net protein utilization (NPU) (p&#xa0;<&#xa0;0.05). Supplementation of citric acid in the 40% SBM diet (HSBM + CA) significantly improved NPU and partially restored growth relative to HSBM. LC-MS/MS based quantitative proteomics identified 1544 hepatic proteins and showed clear dietary segregation. Differentially expressed proteins were predominantly associated with reduced abundance of proteins involved in lipid metabolism, amino acid metabolism, pyruvate metabolism, and the tricarboxylic cycle across all SBM diets, suggesting a shift in oxidative metabolic capacity. In contrast, LSBM induced upregulation of spliceosome-associated proteins and RNA processing components, suggesting adaptive post-transcriptional regulation under moderate SBM inclusion. In contrast, HSBM exhibited greater reduction in metabolic protein abundance without comparable upregulation of adaptive regulatory components, coinciding with reduced nutrient retention. Protein-protein interaction analysis further confirms the correlation between the regulation of spliceosomal clusters and mitochondrial lipid-catabolic modules. Citric acid supplementation did not markedly reverse hepatic metabolic protein changes but improved protein retention. Data are available via ProteomeXchange with identifier PXD081994. These findings suggest a tolerance limit between 30% and 40% SBM inclusion, with 30% inducing adaptive hepatic proteomic responses compatible with maintained growth performance.

Animals

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

The impact of supernormal lung function on mortality risk in adults with and without sleep-disordered breathing.

BACKGROUND: In the general population, supernormal lung function is associated with a lower risk of all-cause mortality. RESEARCH QUESTION: It remains unclear whether sleep-disordered breathing (SDB) affects this relationship. METHODS: This cohort analysis included 4,839 adults. Lung function was categorised as supernormal (FEV1&#x2009;>&#x2009;ULN), normal (LLN&#x2009;&#x2264;&#x2009;FEV1&#x2009;&#x2264;&#x2009;ULN), and below normal (FEV1&#x2009;<&#x2009;LLN). SDB severity was classified using apnoea-hypopnoea index categories: no SDB (<5 events/hour), mild SDB (5-<15 events/hour), moderate SDB (15-<30 events/hour), and severe SDB (&#x2265;30 events/hour). The association between lung function and all-cause mortality was assessed using Cox proportional hazards models with subgroup analyses according to SDB severity and formal testing for interaction. Analyses were repeated using FVC-defined lung function groups as an alternative definition of supernormal lung function. RESULTS: Among the included participants, 4,068 (84.1%) had normal lung function, 369 (7.6%) had supernormal lung function, and 402 (8.3%) had below normal lung function. During 52 421.5 person-years of follow-up (median 11.72&#x2009;years; IQR, 10.46-12.56), 1,188 deaths occurred. Compared with the normal lung function group, the supernormal lung function group had a lower prevalence of baseline hypertension and cardiovascular disease. The association between lung function and all-cause mortality varied across SDB severity strata (P for interaction&#x2009;=&#x2009;0.034). A lower mortality risk associated with supernormal lung function was observed in participants without SDB (HR: 0.24, 95% CI: 0.06-0.97), whereas this association was not statistically significant in the mild, moderate, or severe SDB strata. Below normal lung function was generally associated with an increased all-cause mortality risk. Sensitivity analyses using FVC-defined lung function groups yielded broadly consistent findings. CONCLUSION: Supernormal lung function was associated with lower all-cause mortality primarily among individuals without SDB. These findings underscore the importance of considering SDB severity when assessing the health implications of lung function.

Humans

Peripheral inflammation and executive function among community samples across the lifespan: A systematic review and meta-analysis.

Higher levels of peripheral inflammatory markers are proposed to disrupt cognitive processes; however, the extent to which this relationship applies to executive functions, specifically, has yet to be systematically evaluated. The current meta-analysis synthesizes all available literature measuring the association between peripheral inflammation and executive functions among community individuals across the lifespan. This systematic review searched Web of Science, PubMed, and PsycINFO for published and unpublished studies, in the English language, that assessed the association between markers of peripheral inflammation and self-report and behavioral measures of executive function. In addition to methodological and demographic information, correlation/beta coefficients were extracted from included studies to quantify the association between inflammation and executive functions. This review included 58 studies, 41 of which were included in the random-effects meta-analysis (N&#x202f;=&#x202f;255,539). Among community individuals, higher levels of CRP and IL-6 were associated with poorer executive functioning. These results did not differ when models accounted for potential confounding variables. Meta-regressions revealed that the relationship between inflammatory biomarkers and executive function did not differ as a function of age, adiposity, or percentage of the sample who identified as female. Results of the present review indicate that higher levels of specific inflammatory markers are associated with lower performance on executive function measures; however, we observed significant heterogeneity in the study design and measurement of both inflammation and executive functioning, suggesting important considerations for future research.

Humans

Repetitive transcranial magnetic stimulation in functional motor disorders: A systematic review of effects and targets.

OBJECTIVE: To evaluate the effectiveness, safety, and potential mechanistic implications of repetitive transcranial magnetic stimulation (rTMS) in adults with functional motor disorders (FMD), focusing on possible phenotype-specific responses and stimulation protocols. METHODS: Seven databases were searched from inception to July 2026. Randomised and non-randomised interventional studies were included. Risk of bias and evidence certainty were assessed using PEDro, RoB 2, JBI tools, and GRADE. Because of substantial clinical and methodological heterogeneity, findings were synthesised qualitatively. RESULTS: Fourteen studies were included. The primary motor cortex was targeted in 11 studies. Functional tremor showed the most consistent evidence with inhibitory stimulation: one small sham-controlled trial found a significant group-by-time effect on tremor severity (p&#xa0;=&#xa0;0.007), while an uncontrolled prospective series reported 40&#xa0;% reduction in postural tremor amplitude (p&#xa0;=&#xa0;0.05). Evidence for functional weakness was conflicting: excitatory M1 stimulation increased objective strength by 25&#xa0;% versus 10&#xa0;% with sham (p&#xa0;=&#xa0;0.004), whereas the largest inhibitory sham-controlled trial found no benefit (p&#xa0;=&#xa0;0.80). No severe adverse events were reported, but safety reporting was incomplete. GRADE certainty was moderate for tremor and very low for all other outcomes. CONCLUSIONS: Current evidence is insufficient to establish the efficacy of rTMS in FMD or to recommend phenotype-specific protocols. Preliminary findings support further investigation of inhibitory stimulation for functional tremor, whereas evidence for excitatory stimulation in functional weakness remains uncertain. SIGNIFICANCE: The possible interaction between phenotype and stimulation direction is hypothesis-generating. rTMS should currently be considered an experimental, context-sensitive adjunct within multidisciplinary care, pending adequately powered phenotype-stratified sham-controlled trials. Prospero Registration Number: CRD420251250969.

Humans

Sustained cognitive and functional effects of pro-cognitive interventions for bipolar disorder: A systematic review of randomised controlled trials.

A substantial proportion of individuals with bipolar disorder (BD) experience considerable cognitive deficits. Existing systematic reviews have evaluated the efficacy of pro-cognitive interventions in BD, but have not established whether any cognitive benefits translate into functional improvements, with evidence for sustained functional effects remaining limited. A systematic search was conducted on MEDLINE, EMBASE, PsycINFO and Cochrane Library from inception until 21 May 2026. Eligible studies were randomised controlled trials (RCTs) in BD reporting cognitive or functional outcomes at three or more months following a pro-cognitive intervention, or examining the translation of cognitive benefits into improvements in functional outcomes at any timepoint. Seven unique RCTs plus three secondary analyses of these trials (n&#xa0;=&#xa0;615) met the inclusion criteria. Approximately 13% (7/55) of RCTs identified in the search of pro-cognitive interventions in adult BD assessed cognitive or functional outcomes at least 3&#xa0;months after treatment end. Of the seven unique RCTs, most evaluated cognitive remediation (CR; k&#xa0;=&#xa0;4). The average follow-up length was 4&#xa0;months (range: 3-6&#xa0;months). Three of the four RCTs examining CR reported cognitive benefits at 3 to 6&#xa0;months, whereas only one CR RCT found consistent functional effects at 3&#xa0;months. Evidence on the translation of cognitive benefits to functional improvements is scarce and inconsistent. Most trials examining pro-cognitive interventions do not examine whether potential benefits are sustained or whether they translate into improvements in real-world functioning. CR appears to be a promising intervention for achieving durable cognitive gains in BD, although evidence for sustained effects of other interventions is limited.

Humans

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with fragile brain function during the non-acute phase undergoing laparoscopic colorectal surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Older adults with non-acute fragile brain function (NFBF) may be particularly susceptible to perioperative disturbances in cerebral oxygenation and postoperative neurocognitive decline. Permissive hypercapnia (PHC) may enhance cerebral oxygenation, but its effects in this population remain unclear. We examined whether PHC-based ventilation improves intraoperative regional cerebral oxygen saturation (rSO2) and early postoperative cognitive outcomes in older patients with NFBF undergoing elective laparoscopic colorectal surgery. METHODS: In this single-center, single-blind randomized trial, 76 patients were assigned in a 1:1 ratio to PHC-based or conventional ventilation. The primary outcome was the absolute change in rSO2 from baseline (T0) to the end of surgery (T4). Analyses followed the intention-to-treat principle, with prespecified per-protocol sensitivity analysis. Secondary outcomes included intraoperative rSO2 trajectories, cerebral oxygen extraction-related indices, early postoperative cognitive screening, serum neuron-specific enolase and interleukin-6, and safety outcomes. RESULTS: PHC significantly increased rSO2 relative to conventional ventilation (left: adjusted mean difference [aMD] 10.64, 95% CI 8.96-12.33; right: aMD 10.16, 95% CI 8.22-12.11; both P&#xa0;<&#xa0;0.001), with consistent sensitivity results. Repeated-measures analyses showed persistently higher intraoperative rSO2 in the PHC group. Cerebral oxygen extraction-related indices were generally lower with PHC. However, early postoperative cognitive outcomes and serum biomarkers did not differ between groups. Emergence time was modestly longer with PHC, whereas adverse events were comparable. CONCLUSIONS: PHC-based ventilation favorably modified intraoperative cerebral oxygenation and oxygen-extraction profiles but did not translate into detectable early postoperative cognitive or biomarker benefits in older adults with NFBF.

Humans

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans

Short-term psychodynamic psychotherapy for functional neurological disorder: A pilot randomized controlled trial.

BACKGROUND: Evidence-based psychotherapeutic treatments for Functional Neurological Disorder (FND) remain limited. This pilot trial evaluated the preliminary efficacy of Short-term Psychodynamic Psychotherapy (STPP) plus Standard Medical Care (SMC) compared with SMC alone in reducing FND symptom frequency. METHODS: Adults with FND were randomized (1:1) to receive either SMC alone or 12 weekly sessions of STPP plus SMC. The primary outcome was symptom frequency (days with symptoms in the last 4 weeks) assessed at the end of treatment (3 months) and at 6-month follow-up. Secondary outcomes included treatment response (&#x2265;50% reduction in symptom frequency) and scores on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). RESULTS: Of 91 randomized patients (mean age 38.2 years, 75.8% female), 81.3% completed follow-up. Intention-to-treat analysis using Linear Mixed Models showed that STPP plus SMC significantly reduced symptom frequency compared with SMC alone (estimated mean difference -5.72 [95% CI -8.68 to -2.77]; Cohen's d = 0.77; p&#x202f;<&#x202f;0.001).Treatment response was achieved by 65.8% in the intervention group versus 16.7% in controls (OR 8.21 [95% CI 2.79-24.19]; p&#x202f;<&#x202f;0.001; NNT 2.0).Significant improvements were also observed for depression (HAM-D: estimated mean difference -10.80; d = 1.45), anxiety (HAM-A: -7.94; d = 1.06), and disability (WHODAS 2.0: -5.77; d = 0.74), all p&#x202f;<&#x202f;0.001. CONCLUSIONS: STPP was associated with clinically meaningful improvements in FND symptom frequency and all secondary outcomes, with large effect sizes and high treatment response rates. These findings support the preliminary efficacy of STPP for FND and justify larger, multicenter confirmatory trials.

Humans