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PubMed2026

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66 years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans↗

PubMed2026

Effects of adjunctive memantine on executive function and global cognition in bipolar disorder (BD): A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Cognitive impairment contributes substantially to disability in bipolar disorder (BD), but effective pharmacologic options remain limited. This trial evaluated whether adjunctive memantine improves global cognition and executive function in BD. METHODS: In this double-blind, placebo-controlled randomized trial, patients with bipolar I disorder (B1D) receiving lithium and olanzapine were assigned to memantine or placebo. Memantine was titrated to 20 mg/day over 6 weeks. Cognitive outcomes were assessed at baseline, week 6, and week 18. Global cognition was measured with the Neurocognitive Assessment Battery (NuCog), and executive function with the Frontal Assessment Battery (FAB). Data were analyzed using generalized estimating equations and Bonferroni-adjusted post-hoc tests. RESULTS: Sixty-three participants were randomized (memantine, n = 31; placebo, n = 32), and all completed follow-up. Groups were comparable at baseline for demographic and clinical variables and for most cognitive measures. Both groups improved over time (P < 0.001), but improvement was greater with memantine for global cognition at week 6 (MD = 9.32; 95% CI, 4.84-13.81; P < 0.001) and week 18 (MD = 12.69; 95% CI, 8.67-16.71; P < 0.001). FAB total scores favored memantine at week 18 (MD = 2.68; 95% CI, 1.76-3.61; P < 0.001), but not at week 6. Domain analyses showed significant benefits for NuCog attention, visuoconstructional ability, memory, and executive function, and for several FAB subscales by week 18. CONCLUSIONS: Adjunctive memantine improved global cognition and, over longer follow-up, executive function in BD. These findings support NMDA receptor modulation as a potential strategy for cognitive dysfunction in BD.

Humans↗

PubMed2026

Dissociable neural mechanisms of cognitive enhancement through transcranial stimulation and behavioral training.

BACKGROUND: Transcranial direct current stimulation (tDCS) and adaptive working memory (WM) training are promising cognitive enhancement approaches; however, their neural mechanisms and potential synergies remain poorly understood. OBJECTIVE: We directly compared how tDCS and WM training modulate neural oscillations during WM performance and examined whether combining both interventions produces additive effects. METHODS: We randomized 112 healthy adults into four groups: control (sham tDCS + non-adaptive 1-back), tDCS-only (active tDCS + non-adaptive 1-back), training-only (sham tDCS + adaptive n-back training), or combined (active tDCS + adaptive training). Participants underwent five daily intervention sessions. We recorded high-density EEG during transfer n-back tasks at baseline, post-intervention, and one-week follow-up. RESULTS: All active interventions improved WM performance relative to the control group, with the combined group showing the largest gains (n-back accuracy: +15.6% vs. + 10.1% tDCS-only, +9.7% training-only, +0.7% control; all p < 0.001). Critically, tDCS selectively increased gamma-band (30-50 Hz) power in the frontal and parietal regions (cluster p = 0.018, d > 1.0), whereas WM training enhanced frontal theta-band (4-8 Hz) power and theta-gamma phase-amplitude coupling (both cluster p < 0.012, d > 0.85). The combined group exhibited both neural signatures. Brain-behavior correlations revealed dissociable relationships: gamma increases predicted n-back accuracy improvements (r = 0.61, p < 0.001), whereas theta enhancements correlated with operation span gains (r = 0.58, p = 0.002). CONCLUSIONS: tDCS and WM training enhance cognition through distinct yet complementary neural mechanisms: tDCS via gamma-mediated cortical excitability and WM training via theta-mediated cognitive control. These findings provide neurophysiological evidence for multimodal enhancement strategies that target parallel pathways within WM networks.

Humans↗

PubMed2026

Effectiveness of transcranial direct current stimulation with and without positive mood induction on worry and transdiagnostic cognitive-emotional processes: A randomized controlled trial.

The present study investigated the effectiveness of transcranial direct current stimulation (tDCS), with and without positive mood induction, on worry and key transdiagnostic cognitive-emotional processes, including attentional bias, working memory, problem solving, and emotion regulation, in individuals with high levels of worry. This single-blind randomized controlled trial included 45 individuals with high levels of worry. After a structured clinical interview, participants were randomly assigned, with gender balancing, to one of three groups: (1) tDCS alone, (2) tDCS combined with positive mood induction, or (3) a sham control group. Outcome measures were administered at three time points (pretest, posttest, and one-month follow-up) and assessed attentional bias (Dot Probe Task), working memory (1-back task), problem solving (Tower of London task), emotion regulation (Gross's Emotion Regulation Questionnaire), and worry severity (Penn State Worry Questionnaire; PSWQ). Repeated-measures ANOVA showed that both active groups (tDCS alone and tDCS + positive mood induction) significantly improved attentional bias, worry, working memory, problem solving, and emotion regulation compared to controls (p < 0.05). The combined intervention produced significantly greater gains than tDCS alone in working memory, problem solving, emotion regulation (p < 0.05), and reductions in attentional bias and worry (p < 0.001). All effects persisted at one-month follow-up (p < 0.05). tDCS reduces worry and attentional bias and enhances cognition and emotion regulation in individuals with high levels of worry. The combined intervention produced larger and more sustained improvements than tDCS alone across the assessed behavioral outcomes. These findings support further investigation of combining tDCS with structured positive mood induction while the mechanisms underlying the additional benefits remain to be established.

Humans↗

PubMed2026

Does high fructose consumption trigger microglia activation and neuroinflammation? A systematic review.

This systematic review evaluated the effects of fructose intake on neuroinflammatory markers in rodent models. The search terms Fructose AND neuroinflammation OR Neurodegeneration OR chemokines OR interleukins OR microglia OR behaviour OR memory OR cognition were used in Google Scholar, Scopus and Web of Science. Thirteen animal studies investigating fructose-induced neuroinflammation that matched the eligibility criteria were included in the study. Across the studies, 16 inflammatory markers were identified and significantly altered following exposure to fructose. The findings consistently demonstrated elevated expression of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1β, following fructose administration. Fructose consumption also dysregulated MCP-1, fractalkine, and CX3CR1 levels, thereby promoting inflammatory signalling and microglial activation. Furthermore, fructose exposure significantly increased IBA-1 and CD11b, indicating sustained neuroimmune activation. Alterations in important inflammatory pathways involving TLR4, NLRP3, NF-κB, MyD88, iNOS, and cyclooxygenases (COX-1 and COX-2) were also observed. In contrast, expression of the anti-inflammatory regulator peroxisome proliferator-activated receptor gamma (PPARγ) was reduced after fructose treatment. Overall, the findings suggest that chronic fructose consumption induces neuroinflammation through multiple inflammatory and immune-related mechanisms in the brain. These effects appear to be dose- and duration-dependent and may contribute significantly to neurodegeneration and cognitive impairment.

Microglia↗

PubMed2026

Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.

BACKGROUND: Guanidinoacetic acid (GAA) supplementation has been reported to increase brain creatine content more effectively than creatine monohydrate (CrM). However, the effects on cognitive function are unclear. PURPOSE: The purpose of this proof-of-concept exploratory clinical trial was to determine whether GAA supplementation with and without CrM affects cognitive function and/or markers of health. METHODS: In a double-blind, randomized, and counterbalanced manner, 58 healthy and active adults (33 females, 35.5 ± 14 years, 76.2 ± 14 kg) ingested a PLA (PLA, 2 × 6 g/d maltodextrin), GAA (2 × 1 g/d) + PLA (2 × 5 g/d), or GAA (2 × 1 g/d) + CrM (2 × 5 g/d) for six weeks. The participants donated fasting blood samples and completed a battery of tests and questionnaires assessing various aspects of function, mood, stress, sleep quality, and markers of health at baseline and after six weeks of supplementation. Data were analyzed using General Linear Model (GLM) multivariate and univariate with repeated measures, and mean changes from baseline with 95% confidence intervals, and Chi-squared analysis, and considered significant when the probability of error was 0.05 or less, and approaching significance (p > 0.05-p < 0.10). RESULTS: GAA supplementation tended to improve overall reaction time (-241.8 ms [-533, 50], p = 0.10) while significant interaction effects were observed in overall reaction time (p = 0.031-330 ms [-629, -31]) and YES reaction time (-290 ms [-484, -96], p = 0.004) while recalled correct reaction time (-178 ms [-374, 21], p = 0.078) and recalled correct YES (7.4 % [-1, 15.8], p = 0.084) approached significance compared to PLA. Limited to no effects were observed on the Delayed Picture Recognition Task Test, Digit Vigilance Task Test, Corsi Block Task Test, or Stroop Color-Word Task Test. The amount of time engaged in moderate physical activity was significantly greater (p < 0.05) in the GAA group compared to PLA. Participants in the GAA group reported a lower frequency of controlling irritations (p = 0.036), and feeling like difficulties are mounting (p = 0.053) on the Perceived Stress Scale. Some positive and potentially undesirable effects were observed in sleep quality assessments. The quality of life assessment revealed that participants in the GAA group reported less frequent feelings of being worn out (p = 0.068) and that their health was excellent (p = 0.092) while those in the GAA + CrM group reported more frequent limitations when bending, kneeling, or stooping (p = 0.053), more often feeling full of life (p = 0.081), and less frequency in feeling downhearted and depressed (p = 0.066). No clinically meaningful changes were observed in blood markers or self-reported side effects among the groups. CONCLUSION: Dietary supplementation with GAA (2 g/d) and the combination of CrM (10 g/d + GAA 2 g/d) for six weeks improved delayed verbal episodic recognition memory and retrieval speed and some measures of perceived stress, sleep quality, and quality of life. However, most cognitive tests were not affected, particularly when comparing the GAA to the PLA group; there were some inconsistencies in the findings, and several differences only approached significance. Additional research is needed before conclusions can be drawn. Clinical trial registration: ISRCTN68542582.

Humans↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

PubMed2026

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

Humans↗

PubMed2026

Fyn signaling in the medial prefrontal cortex regulates resistance to stress-induced object recognition impairments in male rats.

Genome-wide association studies on patients with depression have identified FYN and FYB, an FYN-binding protein, as being linked to depression. We have reported that experimental manipulations in gene expression in the medial prefrontal cortex (mPFC) alter stress-induced object recognition impairments in animals. Therefore, we examined the impact of alterations in FYN and FYB expression in the mPFC of adult male rats on resistance to stress-induced impairments in object recognition. Animals with virus-mediated knockdown or overexpression of Fyn in the mPFC were subjected to either a brief 20-min restraint with 20 intermittent tail shocks, which does not induce object recognition impairment, or a prolonged 60-min restraint with 60 intermittent tail shocks, which does. In an object recognition task, control rats maintained intact object recognition following a brief stress, whereas rats with Fyn knockdown or overexpression in the mPFC showed impaired object recognition. Prolonged stress impaired object recognition in both control rats and rats with Fyn knockdown or overexpression. Additionally, rats with Fyn knockdown in the mPFC exhibited fewer c-Fos-positive cells in the mPFC in response to brief stress, accompanied by a trend toward increased c-Fos in the amygdala compared with control rats. Fyn knockdown also reduced Fyb expression in the mPFC. Furthermore, Fyb knockdown in the mPFC impaired object recognition following brief stress, suggesting that the observed effects are consistent with involvement of a coupled Fyn-Fyb signaling axis rather than Fyn alone. These findings suggest that altered Fyn-related signaling in the mPFC may underlie the resistance to stress-induced object recognition impairments.

Animals↗

PubMed2026

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5 years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult↗

PubMed2026

Environmentally relevant concentrations of DCOIT impaired lifespan and healthspan in Caenorhabditis elegans.

DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is an antifouling biocide widely used as an alternative to organotin compounds. While previous studies had focused on its effects on energy production, endocrine disruption, and lipid metabolism, its impact on aging and underlying mechanisms remained unclear. Here, we demonstrated that environmentally relevant concentrations of DCOIT (37, 370 and 3700 ng/L) significantly impaired both lifespan and healthspan in Caenorhabditis elegans. RNA-seq and validation assays revealed that DCOIT upregulated comt-4, a key gene in dopamine metabolism, leading to dopamine depletion and subsequent induction of oxidative stress. This redox imbalance critically contributed to accelerated aging phenotypes. Importantly, both genetic (comt-4 RNAi) and pharmacological (opicapone) interventions restored dopamine levels, alleviated oxidative stress, and reversed DCOIT-induced aging deficits. Our study established the comt-4/dopamine/oxidative stress axis as a central mechanism in DCOIT toxicity, suggesting dopamine modulation as a potential countermeasure against environmental toxicant-induced aging.

Animals↗

PubMed2026

Post-intervention effectiveness of a computerized personalized cognitive stimulation program adapted according to cognitive reserve in older adults without cognitive impairment in Primary Care: A randomized clinical trial.

BACKGROUND: Cognitive reserve may influence responsiveness to cognitive interventions, yet it is rarely used to tailor computerized stimulation. OBJECTIVE: To evaluate the effectiveness of a computerized cognitive stimulation program personalized according to cognitive reserve on cognition, reserve-related activities, and digital competence in community-dwelling older adults without cognitive impairment in Primary Care. METHODS: In this randomized clinical trial, 102 adults aged ≥65 years with normal cognitive performance were recruited from three primary care centers in Zaragoza, Spain, and stratified by cognitive reserve level before random allocation to intervention or control. The intervention comprised digital literacy sessions followed by 8 weeks of home-based computerized cognitive stimulation tailored to participants' cognitive reserve profiles and life history. Controls received a single group-based health education session focused on maintaining everyday cognitive activity. Outcomes were assessed at baseline and post-intervention using global cognition (MEC-35), the Cognitive Reserve Questionnaire, the Mobile Device Proficiency Questionnaire-16, and domain-specific neuropsychological tests. A total of 100 participants completed the final evaluation and were included in complete-case analyses. RESULTS: Compared with controls, the intervention group showed greater adjusted post-intervention improvements in global cognition (MEC-35 between-group difference: 1.8 points) and several cognitive measures, including temporal orientation, calculation, attention, praxis, verbal fluency, processing speed, executive functions, and verbal learning. CRQ scores and digital competence also improved, with small-to-large effect sizes. CONCLUSIONS: A computerized cognitive stimulation program adapted according to cognitive reserve appears feasible in Primary Care and may improve cognition, engagement in reserve-related activities, and digital competence in older adults without cognitive impairment.

Humans↗

PubMed2026

Norgestrel drives mitochondrial collapse and plasma membrane impairment in Pacific oyster (Crassostrea gigas) sperm by triggering premature acrosome reaction.

The toxic mechanisms of norgestrel (NGT), an emerging marine pollutant, on the sperm from externally fertilized invertebrates remain elusive. This study employed an integrated physiological and multi-omics framework to elucidate how NGT (10 and 1000 ng/L) disrupts acrosome reaction (AR) signaling machinery, thereby impairing the functional integrity of Pacific oyster (Crassostrea gigas, also known as Magallana gigas) sperm. Exposure to NGT triggered a significant, dose-dependent premature AR, characterized by elevated acrosin activity and a loss of acrosomal integrity. Multi-omics integration supports a model in which this premature exocytosis is linked to signaling disturbances, including disruption of calcium signaling and reduced transcript abundance of calmodulin (CaM) and the primary recognition protein zonadhesin (Zan). This signaling interference induced an premature AR, subsequently driving a cascade of bioenergetic and structural failures. At the mitochondrial level, NGT induced abnormal mitochondrial permeability transition pore (mPTP) opening and elevated the transcript levels of antioxidant defense genes (e.g., peroxiredoxin-5, PRDX5). These alterations indicate the occurrence of mitochondrial collapse. Concurrently, scanning electron microscopy verified localized plasma membrane wrinkling and pore formation in sperm. In addition, NGT exposure decreased the transcript abundance of cytoskeleton-related genes, including solute carrier family 26 member 6 (SLC26A6), actin (ACT), and tubulin polymerization promoting protein family member 3 (TPPP3). These molecular changes further disrupted membrane phospholipid homeostasis, as represented by altered glycerophospholipid metabolism. At the same time, cumulative cellular stress was associated with decreased transcript abundance of cytoprotective factors (e.g., baculoviral IAP repeat-containing proteins, birc2) and changes in apoptosis-related genes consistent with activation of a caspase-8-mediated apoptotic programme. In conclusion, NGT, as a representative synthetic progestin, exerts reproductive toxicity by interfering with signaling mediators to induce premature AR, which subsequently exhausts metabolic energy and triggers plasma membrane impairment. These findings provide a critical mechanistic basis for the aquatic ecological risk assessment of synthetic progestins.

Animals↗

PubMed2025

Uncovering parental exposure risks of TCPP: Impaired development and metabolic homeostasis in zebrafish offspring.

As brominated flame retardants are phased out, tris (1‑chloro-2-propyl) phosphate (TCPP), a phosphorus-based flame retardant, has emerged as a prominent detectable flame retardant in the environment. However, TCPP has been found to exhibit endocrine-disrupting effects on organisms, raising significant safety concerns. In our study, we utilized the zebrafish model to explore the toxic effects of parental TCPP exposure on offspring and uncover its regulatory mechanisms through metabolomics analysis. Moreover, the impact on the nervous system and lipid metabolism was examined through behavioral analysis and specific staining. Our findings demonstrated that both embryonic and parental TCPP exposure induced developmental disorders in larvae, along with decreased locomotor activity and disordered lipid metabolism homeostasis. Parental exposure to TCPP, exhibiting stronger developmental toxicity than direct embryonic exposure, notably led to reductions in crucial energy substrates such as amino acids and carbohydrates. Meanwhile, embryonic TCPP exposure primarily affected the endogenous lipid-related metabolites including phospholipids, lipid-soluble vitamins, steroids and fatty acids, promoting lipid accumulation in larval liver and subcutaneous tissue. What's more, continuously parental and embryonic exposure showed the most pronounced effects on zebrafish development and metabolic regulation. Our study highlights the risk posed by parental exposure to TCPP on offspring zebrafish, underscoring the need for comprehensive consideration of the impact from parental exposure in pollutants regulation.

Animals↗

PubMed2026

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50 aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT×diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F = 4.322, P = 0.041); this interaction was driven by CCT specifically in aMCI (F = 4.465, P = 0.038). Significant CCT×diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F = 5.429, P = 0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F = 6.587, P = 0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F = 6.550, P = 0.013; F = 7.097, P = 0.010). No significant interaction effect on the change in hippocampal GMV was noted (P > 0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans↗

PubMed2026

Tranexamic acid in spontaneous intracerebral hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans↗

PubMed2026

Protein sorting and proteostasis mechanisms in CFTR-related exocrine pancreas dysfunction: A systematic narrative review.

The pancreas consists of exocrine and endocrine compartments. In the exocrine pancreas, cystic fibrosis transmembrane conductance regulator (CFTR) functions mainly in ductal epithelial cells as a chloride and bicarbonate channel. Its activity depends on proper protein folding, trafficking, and localization to the apical membrane. This systematic narrative review aims to synthesize the available evidence on the role of protein sorting machinery in CFTR channelopathies and its contribution to exocrine pancreatic dysfunction. A thorough search was conducted using PRISMA criteria on PubMed, Wiley Online Library, and Scopus for studies published in English between January 2000 and November 2025. Twenty studies that met the inclusion criteria were included in this review. Pathogenic CFTR variants impair protein folding, endoplasmic reticulum (ER) exit, and endosomal recycling, resulting in reduced apical membrane expression and stability. These defects disrupt the localization of associated transporters and secretory proteins, impair ductal bicarbonate secretion, alter zymogen handling, and promote acinar injury, although these claims are supported mainly by indirect experimental models and therefore require clinical confirmation. CFTR channelopathies in the exocrine pancreas encompass both ion transport defects and broader disruptions of protein sorting machinery. CFTR may contribute to the assembly, stabilization, or localization of selected apical transport complexes, and its loss can secondarily alter epithelial organization. Therapeutic approaches targeting both channel correction and intracellular trafficking may improve pancreatic function and mitigate disease progression.

Humans↗

PubMed2026

Parallel evolutionary trajectories rewire enteropathogenic Escherichia coli adhesion to restore host attachment.

Enteropathogenic Escherichia coli (EPEC) causes disease in children, presenting as chronic diarrhea that can impair physical and cognitive development. The attachment of typical EPEC (tEPEC) to the gut epithelium via bundle-forming pili (BFP) is a key factor in its virulence. Yet, infections by atypical EPEC (aEPEC), which lack BFP, have become increasingly common. To investigate how aEPEC recover host-attachment in the absence of BFP, we performed experimental evolution using a non-adherent E. coli, constructed to mimic the ancestor of aEPEC, and selected adherent progeny. Highly adherent variants evolved through phase-variable activation of type I fimbriae (T1F), followed by two alternative trajectories: bacterial filamentation, which increases T1F avidity, or point mutations in the T1F adhesin FimH that enhance ligand affinity. Extending our analysis to the genomes of 327 aEPEC strains isolated from infected patients revealed that similar FimH mutations are common. We further demonstrated experimentally that these naturally occurring variants often increase epithelial-attachment. Our findings implicate T1F in aEPEC pathogenesis and suggest it may be clinically relevant for anti-adhesion therapy. More broadly, these results indicate that impaired host-attachment can be rapidly compensated by upregulating and optimizing an alternative adhesin, and that combining experimental evolution with comparative genomics can reveal evolutionary trajectories occurring in nature.

Bacterial Adhesion↗