The glymphatic system and meningeal lymphatic vessels: from physiology to pathophysiology, with insights into visualization.

Vestibular brainstem impairment following in utero exposure to high dose paracetamol.

Comorbid depression is greatly predominant among COPD patients. Nevertheless, comorbid depression associated with COPD is frequently unidentified, and pathogenic exploration is too inadequate. Exposure to cigarette smoke (CS) contributes to inflammation and oxidative stress (OS), which are basic components in the pathogenesis of lung disorders of COPD. Robinin (RB), a kaempferol derivative of flavonoid glycoside, possesses neuroprotective, antioxidative, and anti-inflammatory properties. Hence, our research has evaluated the neuroprotective effect of RB on the CS-induced COPD mouse model. C57BL/6J mice were randomly assigned to 5 groups, each comprising 6 mice. Normal control (NC), CS, CS + RB (25mg/kg bw), CS + RB (50mg/kg bw), and CS + Dexamethasone (DEX, 5mg/kg bw). CS was exposed to the COPD development to assess the mice's body weight, neurological dysfunction, depression-interrelated behaviours, blood cellularity, oxidative stress, neuroinflammation, cytokines, immune cells, neurotransmitters, inflammatory signalling cascade, and histopathology of lungs, as well as the hippocampus. RB could attenuate body weight loss, oxidative stress, neuroinflammation, neurological impairments, immune cell infiltration, cytokine levels, and histopathological alterations, as well as immunohistochemistry, in a concentration-dependent manner by enhancing neurotransmitter levels. Our findings established that the neuroprotective and anti-inflammatory activities of RB against CS-exposed COPD with comorbid depression are achieved by suppressing PI3K/AKT-mediated NF-κB/NLRP3 signalling pathways.

Cerebrotendinous xanthomatosis (CTX) is rare, autosomal recessive inborn error of metabolism caused by biallelic pathogenic variants in CYP27A1, which encodes sterile 27 hydroxylase, a key enzyme in bile acid biosynthesis. Enzyme deficiency results in reduced cholic and chenodeoxycholic acid synthesis with accumulation of cholestanol, bile acid intermediates, and bile alcohols, producing a progressive multisystem disorder characterized by chronic diarrhea, juvenile-onset cataracts, tendons xanthomas, and neurological dysfunction. Although CTX typically begins in childhood, diagnosis is frequently delayed until adulthood, limiting the benefit of effective disease modifying therapy with chenodeoxycholic acid. Since the identification of CYP27A1, more than 200 pathogenic variants have been reported, including canonical loss of function alleles and missense variants with variable residual enzyme activity. In this review, we summarize the medical genetics, population genetics and genotype phenotype relationships of CTX. We highlight insights from large population databases that refine global incidence estimates, revealing population-specific enrichment of pathogenic variants and persistent underdiagnosis. We further review functional and clinical data demonstrating that stratification of CYP27A1 variants by functional effect,complete loss of function versus hypomorph alleles,correlates with clinical severity and biochemical phenotype. Finally, we discuss emerging advances in biochemical testing and newborn screening strategies that offer the potential for presymptomatic diagnosis, enabling timely initiation of therapy and prevention of irreversible disease manifestations. Integrating molecular, functional, and population genetic data provides a framework for improved variant interpretation, earlier diagnosis, and optimized therapeutic intervention in CTX.

Intranasal administration of geniposide-baicalin treats ischemic stroke reperfusion conjugated with pneumonia by inhibiting HMGB1-mediated pyroptosis via NLRP3/Caspase-1/GSDMD pathway.

Dynamic ROS-responsive injectable hydrogel incorporating nanozymes for spinal cord repair by alleviating oxidative stress and neuronal ferroptosis.

Mechanistic insights into glufosinate-ammonium (GLA)-Induced brain injury revealed by LC-MS/MS-based metabolomics.

Pediatric tracheotomy: A 25-year experience at a portuguese tertiary children's hospital.

The Warden procedure effectively corrects partial anomalous pulmonary venous connection (PAPVC) draining into the superior vena cava (SVC), yet superior vena cava obstruction remains a serious potential complication. This report describes a rare case of acute prosthetic graft thrombosis in the SVC following Warden procedure, presenting primarily with rapid neurological deterioration and initially lacking typical signs of superior vena cava syndrome. A 51-year-old female patient underwent a Warden procedure with autologous pericardial tube reconstruction of the superior vena cava. Postoperatively, her central venous pressure (CVP) progressively increased from 12 mmHg to a peak of 28 mmHg. Concurrently, her level of consciousness deteriorated from mild coma to deep coma with brainstem reflex suppression. Emergency cranial CT revealed no hemorrhage or significant edema. The combination of elevated CVP and deteriorating neurological function suggested acute SVC obstruction, prompting emergency exploration. Intraoperatively, extensive thrombosis within the autologous pericardial graft was confirmed. After replacement with a large-bore bovine pericardial graft, venous return was restored. The patient regained consciousness 8h after the second surgery with no neurological sequelae. Acute superior vena cava (SVC) obstruction can directly cause severe neurological dysfunction due to impaired cerebral venous return and reduced cerebral perfusion pressure. During the perioperative period, even in the absence of facial/neck edema or positive cranial CT findings, immediate investigation of superior vena cava anastomotic patency is warranted upon detection of abnormally elevated central venous pressure (CVP) accompanied by altered mental status.

Mercury is one of the most toxic substances found in nature and can be harmful to both the environment and human health. The brain is a critical organ that is sensitive to mercury exposure, especially during development, when it can cause neurological dysfunction and abnormalities as well as other neurodevelopmental deficits. In this context, the identification of new biomarkers of mercury exposure and intoxication will provide valuable tools for the prevention, response, and treatment of environmental contamination. In this study, we propose biotinidase activity as a biomarker of effect, which may provide a direct measure of mercury intoxication, by performing a complete screening in silico, in vitro, and in vivo in human blood samples. Biotinidase is an enzyme that is responsible for the recycling of biocytin. A deficiency of biotinidase is an autosomal recessive disorder that has a variable clinical expression, including delays in development. We evaluated biotinidase activity in the blood of Amazonian riverine populations environmentally exposed to mercury compared to those not exposed. Also, in vitro, other metals were tested to verify the mercury specificity and selectivity for the inhibition of the biotinidase activity. An in silico molecular docking analysis of the target enzyme was performed to understand the preference of methylmercury for the catalytic site. We found that mercury exposure decreases serum biotinidase activity, while other metals do not change it. The molecular docking analysis of the active site indicated a high level of interaction with nucleophiles, with the thiol and selenic groups forming strong bonds with mercury, which implies that cysteine is a potential target for the inhibitory action of mercury. Overall, the evidence indicates that biotinidase activity may serve as a novel biomarker of effect for the assessment of mercury intoxication, which constitutes a persistent threat to both the environment and human populations in the Amazon region.

Excitotoxicity and PANoptosis are examined through endoplasmic reticulum stress of brain in the fat greenling (Hexagrammos otakii) under hypoxic stress.

Tethered cord syndrome and pediatric scoliosis: workup, natural history, and surgical timing.

Postoperative hepatic dysfunction is a frequent and severe complication in patients with acute type A aortic dissection (ATAAD) following emergency surgical repair, and it is strongly associated with adverse clinical outcomes and poor prognosis. The albumin-bilirubin (ALBI) score is an objective and well-validated indicator for evaluating hepatic function and reserve. Accumulating evidence has demonstrated its favorable prognostic value across a variety of clinical conditions, including cardiovascular diseases. Accordingly, this study was performed to comprehensively investigate the prognostic significance of the ALBI score in patients with ATAAD undergoing emergency surgical repair. A total of 306 patients with ATAAD who underwent emergent repair surgery were enrolled in this single-center retrospective study. The primary outcomes of interest included delayed extubation, reintubation, neurological dysfunction, requirement for continuous renal replacement therapy (CRRT), and 30-day mortality. Propensity score matching (PSM) was performed to balance baseline characteristics between low and high postoperative ALBI (postALBI) score groups, followed by comparison of adverse outcome incidences. Multivariate logistic regression analysis was used to identify independent risk factors for poor prognosis. After PSM, 191 matched pairs were obtained. The high postALBI group (≥-2.12) exhibited significantly higher rates of delayed extubation (40.34% vs. 18.48%, P < 0.001), CRRT requirement (31.93% vs. 10.92%, P < 0.01), and 30-day mortality (16.81% vs. 6.72%, P = 0.017) compared to the low postALBI group (<-2.12). Although the reintubation rate was higher in the high postALBI group (18.52% vs. 9.24%), the difference approached but did not reach statistical significance (P = 0.064). Multivariate analysis revealed that high postALBI was consistently identified as a common risk factor for all adverse outcomes, including delayed extubation (OR: 2.670; 95%CI: 1.080-6.601, P = 0.033), reintubation (OR: 3.071; 95%CI: 1.076-8.769, P = 0.036), neurological dysfunction (OR: 4.174; 95%CI: 1.354-12.868, P = 0.013), CRRT requirement (OR: 4.25; 95%CI: 1.544-11.699, P = 0.005), and 30-day mortality (OR: 3.215; 95%CI: 1.132-9.127, P = 0.028). The postALBI score exhibited superior discriminatory ability over individual liver function parameters (postoperative albumin and total bilirubin) for predicting multiple adverse clinical outcomes: its AUC and 95% CI were 0.668 (0.547-0.788, P = 0.006) for 30-day mortality, 0.737 (0.645-0.829, P < 0.001) for CRRT requirement, 0.730 (0.582-0.879, P = 0.002) for neurological dysfunction, 0.706 (0.588-0.824, P = 0.001) for reintubation, and 0.637 (0.548-0.725, P = 0.003) for delayed extubation. The postALBI score demonstrates independent prognostic potential for postoperative adverse events in patients with ATAAD undergoing emergent surgical repair. Owing to its simplicity and wide accessibility, this score may serve as a supportive tool for postoperative risk stratification and clinical decision-making in this high-risk population.

Resveratrol alleviates neurological disorders and motor dysfunction in 3-NP induced- Huntington Disease in rats: Role of activating AMPK/SIRT1/ULK1 autophagy pathway.

Marek’s disease (MD) is a highly contagious neoplastic disorder of poultry caused by MD virus (MDV; gallid alphaherpesvirus 2 [GaAHV2]). Infection results in profound immunosuppression, neurological dysfunction, and the development of malignant T‐cell lymphomas. Continued viral evolution has produced increasingly virulent strains capable of partially or fully evading current vaccines, leaving few options for controlling emerging variants. This highlights the importance of identifying new antiviral targets, particularly those involved in the nuclear trafficking events essential for GaAHV2 replication. The UL36 large tegument protein of alphaherpesviruses contains N‐terminal nuclear localization signals (NLSs) thought to guide capsid transport to the nuclear pore complex. However, the specific mechanism by which GaAHV2 UL36 engages the host nuclear import machinery remains unclear. In this work, we defined the NLS within the N‐terminal region of GaAHV2 UL36 and characterized its interaction with importin proteins. Through high‐resolution crystallography and quantitative binding assays, we pinpointed the residues and structural motifs within UL36 that mediate recognition by importin‐α (IMPα) and compared their affinities across different IMPα isoforms. Our structural and biochemical data show that the predicted N‐terminal NLS of GaAHV2 UL36 is essential for IMPα binding. These findings provide a detailed molecular framework for host–virus interactions during GaAHV2 nuclear entry and offer potential avenues for the development of targeted antiviral strategies.

Oligodendrocyte integrin-β1 regulates blood-brain barrier and remyelination in hemorrhagic brain.

Bio-distribution and deposition of wildfire smoke chemicals into olfactory bulb and brain of rats after intranasal instillation.

Ischemic stroke causes severe neurological disability, with some patients still presenting with residual neurological dysfunction. Aerobic exercise shows potential for post-stroke recovery. However, the mechanism behind its beneficial effects on the brain remains to be further explored. This study aimed to explore aerobic exercise's role in the neurological recovery of ischemic stroke mice and to clarify the specific protective mechanisms involved. A mouse model of ischemic stroke was employed in this study. Mice were subjected to aerobic exercise intervention, with additional exogenous lactate administration and RNA-sequencing (RNA-seq) analysis conducted to explore the molecular mechanisms. Results demonstrated that aerobic exercise significantly elevated protein lactylation levels in ischemic stroke mice and facilitated neurological recovery. In addition, aerobic exercise attenuated neuroinflammation in the ischemic penumbra and promoted neural cell proliferation in the subventricular zone. Mechanistically, aerobic exercise-induced lactylation of α-tubulin may enhance the dynamic properties of microtubules, thereby facilitating neural repair. Exogenous lactate intervention was found to augment α-tubulin lactylation, promote hippocampal neurogenesis, and increase dendritic spine density as well as synaptic plasticity in both the ischemic penumbra and hippocampus. Consistent with these findings, exogenous lactate administration improved neurological function in ischemic stroke mice. RNA-seq analysis further revealed that elevated lactate levels exerted a promotive effect on neural repair. Aerobic exercise promotes post-ischemic stroke neurological recovery via elevating protein lactylation (α-tubulin lactylation), attenuating neuroinflammation, and enhancing neural repair. These findings highlight the potential of targeting lactate metabolism and protein lactylation as therapeutic strategies for facilitating neural repair and improving neurological outcomes following ischemic stroke.

Ketogenic diet therapy in pyruvate dehydrogenase deficiency: Global clinical practice from literature and survey data.

Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common subtype of Ehlers-Danlos Syndrome, a group of connective tissue disorders caused by collagen abnormalities. While musculoskeletal features of hEDS are well characterized, its impact on visceral organs, including the bladder, remains underexplored. Despite frequent patient reports of urinary symptoms, a definitive link between hEDS and bladder pathology has not been established. This study aims to characterize lower urinary tract symptoms (LUTS) and urodynamic (UDS) findings in patients with hEDS to better understand potential mechanisms underlying bladder dysfunction in this population. A retrospective chart review was conducted on patients with hEDS who underwent video UDS at a single tertiary-care center between 2022 and 2025. Inclusion criteria included age > 18, confirmed hEDS diagnosis (2017 criteria), and completed UDS. Data were analyzed using Welch's t-test and Fisher's Exact Test. Among 27 patients, the mean age at hEDS diagnosis was 30.9 years (range 18-49), 92.6% (n = 25) were female, and 92.6% (n = 25) were white. Common LUTS seen in these patients included frequency in 74.1% (n = 20), incontinence in 14.8% (n = 4), frequent urinary tract infections in 25.9% (n = 7), bladder pain in 33.3% (n = 9), nocturia in 48.1% (n = 13), and weak stream in 51.8% (n = 14) of patients. UDS findings revealed no evidence of detrusor overactivity, stress urinary incontinence, or abnormalities in compliance. 1 patient had incomplete emptying with a pre-study post-void residual of 500 mL. Pelvic floor dysfunction was seen in 18.5% (n = 5) with active EMG noted during emptying. Pelvic floor physical therapy was the most common intervention recommended, followed by beta-3 agonists for overactive bladder symptoms. Our findings demonstrate that LUTS are prevalent in patients with hEDS, with evidence pointing to pelvic floor and neurologic dysfunction as key contributors rather than intrinsic bladder pathology. These results support prioritizing a pelvic floor-focused approach to evaluation and management of hEDS-related LUTS.