A dynamic nomogram for predict individual risk of malignant brain edema after endovascular thrombectomy in acute ischemic stroke.

The aim of this study was to develop a dynamic nomogram combining clinical and imaging data to predict malignant brain edema (MBE) after endovascular thrombectomy (EVT) in patients with large vessel occlusion stroke (LVOS). We analyzed the data of LVOS patients receiving EVT at our center from October 2018 to February 2023, and divided a 7:3 ratio into the training cohort and internal validation cohort, and we also prospectively collected patients from another stroke center for external validation. MBE was defined as a midline shift or pineal gland shift > 5 mm, as determined by computed tomography (CT) scans obtained within 7 days after EVT. A nomogram was constructed using logistic regression analysis, and its receiver operating characteristic curve (ROC) and calibration were assessed in three cohorts. A total of 432 patients were enrolled in this study, with 247 in the training cohort, 100 in the internal validation cohort, and 85 in the external validation cohort. MBE occurred in 24% (59) in the training cohort, 16% (16) in the internal validation cohort and 14% (12) in the external validation cohort. After adjusting for various confounding factors, we constructed a nomogram including the clot burden score (CBS), baseline neutrophil count, core infarct volume on CTP before EVT, collateral index, and the number of retrieval attempts. The AUCs of the training cohorts were 0.891 (95% CI 0.840-0.942), the Hosmer-Lemeshow test showed good calibration of the nomogram (P = 0.879). And our nomogram performed well in both internal and external validation data. Our nomogram demonstrates promising potential in identifying patients at elevated risk of MBE following EVT for LVOS.

Genetically identified mediators associated with increased risk of stroke and cardiovascular disease in individuals with autism spectrum disorder.

Growing evidence suggested that individuals with autism spectrum disorder (ASD) associated with stroke and cardiovascular disease (CVD). However, the causal association between ASD and the risk of stroke and CVD remains unclear. To validate this, we performed two-sample Mendelian randomization (MR) and two-step mediation MR analyses, using relevant genetic variants sourced from the largest genome-wide association studies (GWASs). Two-sample MR evidence indicated causal relationships between ASD and any stroke (OR = 1.1184, 95% CI: 1.0302-1.2142, P < 0.01), ischemic stroke (IS) (OR = 1.1157, 95% CI: 1.0237-1.2160, P = 0.01), large-artery atherosclerotic stroke (LAS) (OR = 1.2902, 95% CI: 1.0395-1.6013, P = 0.02), atrial fibrillation (AF) (OR = 1.0820, 95% CI: 1.0019-1.1684, P = 0.04), and heart failure (HF) (OR = 1.1018, 95% CI: 1.0007-1.2132, P = 0.05). Additionally, two-step mediation MR suggested that type 2 diabetes mellitus (T2DM) partially mediated this effect (OR = 1.14, 95%CI: 1.02-1.28, P = 0.03). The mediated proportion were 10.96% (95% CI: 0.58%-12.10%) for any stroke, 11.77% (95% CI: 10.58%-12.97%) for IS, 10.62% (95% CI: 8.04%-13.20%) for LAS, and 7.57% (95% CI: 6.79%-8.36%) for HF. However, no mediated effect was observed between ASD and AF risk. These findings have implications for the development of prevention strategies and interventions for stroke and CVD in patients with ASD.

Silver nanoparticles induced synaptic degeneration via Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells.

Silver nanoparticles (AgNPs) have been widely used in biomedicine and cosmetics, increasing their potential risks in neurotoxicity. But the involved molecular mechanism remains unclear. This study aims to explore molecular events related to AgNPs-induced neuronal damage by RNA-seq, and elucidate the role of Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells synaptic degeneration induced by AgNPs. This study found that cell viabilities were decreased by AgNPs in a dose/time-dependent manner. AgNPs also increased protein expression of PINK1, Parkin, synaptophysin, and inhibited PGC-1α, MAP2 and APP protein expression, indicating AgNPs-induced synaptic degeneration involved in disturbance of mitophagy and mitochondrial biogenesis in HT22 cells. Moreover, inhibition of AgNPs-induced Ca2+/CaMKII activation and Drp1/ROS rescued mitophagy disturbance and synaptic degeneration in HT22 cells by reserving aforementioned protein express changes except for PGC-1α and APP protein. Thus, AgNPs-induced synaptic degeneration was mediated by Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells, and mitophagy is the sensitive to the mechanism. Our study will provide in-depth molecular mechanism data for neurotoxic evaluation and biomedical application of AgNPs.

Hemodynamic predictors of early neurological deterioration and clinical outcome after endovascular treatment in large artery occlusion.

Objective: Half of the patients with acute large artery occlusion (LAO) have poor outcomes after endovascular treatment (EVT). Early complications such as cerebral edema and symptomatic intracranial hemorrhage (sICH) can lead to early neurological deterioration (END), which correlates with hemodynamics. This study aimed to identify the hemodynamic predictors of END and outcomes in LAO patients after EVT. Methods: A total of 76 patients with anterior circulation LAO who underwent EVT and received transcranial Doppler (TCD) monitoring were included. Bilateral middle cerebral artery (MCA) blood flow velocities (BFVs) were measured repeatedly within 1 week. Mean flow velocities (MFV) and MFV index (ipsilateral MFV/contralateral MFV) were calculated. The primary outcome was the incidence of END within 72 h. The secondary outcome was the functional outcome at 90 days-a good outcome was defined as a modified Rankin scale (mRS) score of 0-2, while a poor outcome was defined as an mRS score of 3-6. Results: A total of 13 patients (17.1 %) experienced END within 72 h, including 5 (38.5 %) with cerebral edema, 5 (38.5 %) with sICH, and 3 (23.0 %) with infarct progression. Multivariable logistic regression analysis showed that a higher 24 h MFV index was independently associated with END (aOR 10.5; 95 % CI 2.28-48.30, p = 0.003) and a poor 90-day outcome (aOR 5.10; 95 % CI 1.38-18.78, p = 0.014). The area under the receiver operating characteristic (ROC) curve (AUC) of the 24 h MFV index for predicting END was 0.807 (95 % CI 0.700-0.915, p = 0.0005), the sensitivity was 84.6 %, and the specificity was 66.7 %. At the 1-week TCD follow-up, patients who had poor 90-day outcomes showed significantly higher 1-week iMFV [73.5 (58.4-99.0) vs. 57.7 (45.3-76.3), p = 0.004] and MFV index [1.24 (0.98-1.57) vs.1.0 (0.87-1.15) p = 0.007]. A persistent high MFV index (PHMI) was independently associated with a poor outcome (aOR 7.77, 95 % CI 1.81-33.3, p = 0.006). Conclusion: TCD monitoring within 24 h after EVT in LAO patients can help predict END, while dynamic follow-up within 1 week is valuable in predicting clinical outcomes.

Inferring the genetic effects of serum homocysteine and vitamin B levels on autism spectral disorder through Mendelian randomization.

PURPOSE: The previous studies have suggested that serum homocysteine (Hcy) and vitamin B levels are potentially related to autism spectrum disorder (ASD). However, the causality between their concentrations and ASD risk remains unclear. To elucidate this genetic association, we used a Mendelian randomization (MR) design. METHODS: For this MR analysis, 47 single-nucleotide polymorphisms (SNPs)-13 related to Hcy, 13 to folate, 14 to vitamin B6, and 7 to vitamin B12-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). Our study used three approaches to calculate the MR estimates, including inverse-variance weighted (IVW) method, MR-Egger method, and weighted median (WM) method. Among these, the IVW method served as our primary MR method. False discovery rate (FDR) was implemented to correct for multiple comparisons. We also performed a series of sensitivity analyses, including Cochran's Q test, MR-Egger's intercept, MR-PRESSO, leave-one-out analysis, and the funnel plot. RESULTS: Univariable Mendelian randomization (UVMR) analysis revealed a statistical association between serum vitamin B12 levels and ASD risk (OR = 1.68, 95% CI 1.12-2.52, P = 0.01) using the IVW method. However, neither the WM method (OR = 1.57, 95% CI 0.93-2.66, P = 0.09) nor the MR-Egger method (OR = 2.33, 95% CI 0.48-11.19, P = 0.34) was significantly association with higher levels of serum vitamin B12 and ASD risk. Additionally, we found no evidence of causal relationships between serum levels of vitamin B6, folate, Hcy, and ASD risk. After correcting for the FDR, the causality between serum vitamin B12 levels and ASD risk remained significant (q value = 0.0270). Multivariate Mendelian randomization (MVMR) analysis indicated an independent association between elevated serum vitamin B12 levels and the risk of ASD (OR = 1.74, 95% CI 1.03-2.95, P = 0.03) using the IVW method, but this finding was inconsistent when using the WM method (OR = 1.73, 95% CI 0.89-3.36, P = 0.11) and MR-Egger method (OR = 1.60, 95% CI 0.95-2.71, P = 0.08). Furthermore, no causal associations were observed for serum levels of vitamin B6 and folate in MVMR analysis. Sensitivity analyses confirmed that these results were reliable. CONCLUSION: Our study indicated that elevated serum vitamin B12 levels might increase the risk of ASD. The potential implications of our results for ASD risk warrant validation in randomized clinical trials.

Neuroprotective effect of plasmalogens on AlCl3-induced Alzheimer's disease zebrafish via acting on the regulatory network of ferroptosis, apoptosis and synaptic neurotransmission release with oxidative stress as the center.

Plasmalogens (Pls) are considered to play a potential role in the treatment of neurodegenerative diseases. In the present study, an Alzheimer's disease (AD) model of zebrafish induced by AlCl3 was established to investigate whether the marine-derived Pls could alleviate cognitive impairments of AD zebrafish. Behavioral tests were carried out to assess the athletic ability. The transcriptional profiles of zebrafish in the control, AD model and AD_PLS group were compared and analyzed to determine the potential mechanisms of dietary Pls on AD. The study found that Pls could reverse athletic impairment in the AD zebrafish model, and the expression levels of genes related to ferroptosis, synaptic dysfunction and apoptosis were significantly altered between experimental groups. Further analysis showed that all of these genes were associated with oxidative stress (OS). These data suggest that healthy protective role of marine-derived Pls on AD zebrafish may result from inhibition of ferroptosis and neuronal apoptosis, restoring synaptic neurotransmission release, and reducing neuroinflammation. Among them, Oxidative stress is acted as the center to connect different regulation pathways. This study provides evidence to support the essential roles of OS in pathogenesis of AD, and the application of Pls in relieving AD.

Blood-brain barrier permeability by CT perfusion predicts parenchymal hematoma after recanalization with thrombectomy.

BACKGROUND AND PURPOSE: Parenchymal hematoma is a dreaded complication of mechanical thrombectomy after acute ischemic stroke. This study evaluated whether blood-brain barrier permeability measurements based on CT perfusion could be used as predictors of parenchymal hematoma after successful recanalization and compared the predictive value of various permeability parameters in patients with acute ischemic stroke. METHODS: We enrolled 53 patients with acute ischemic stroke who underwent mechanical thrombectomy and achieved successful recanalization. Each patient underwent CT, CT angiography, and CT perfusion imaging before treatment. We used relative volume transfer constant (rKtrans ) values, relative permeability-surface area product (rP·S), and relative extraction fraction (rE) to evaluate preoperative blood-brain barrier permeability in the delayed perfusion area. RESULTS: Overall, 22 patients (37.7%) developed hemorrhagic transformation after surgery, including 10 patients (16.9%) with hemorrhagic infarction and 11 patients (20.8%) with parenchymal hematoma. The rP·S, rKtrans , and rE of the hypoperfusion area in the parenchymal hematoma group were significantly higher than those in the hemorrhagic infarction and no-hemorrhage transformation groups (p < .01). We found that rE and rP·S were superior to rKtrans in predicting parenchymal hematoma transformation after thrombectomy (P·S area under the curve [AUC] .844 vs. rKtrans AUC .753, z = 2.064, p = .039; rE AUC .907 vs. rKtrans AUC .753, z = 2.399, p = .017). CONCLUSIONS: Patients with parenchymal hematoma after mechanical thrombectomy had higher blood-brain barrier permeability in hypoperfusion areas. Among blood-brain barrier permeability measurement parameters, rP·S and rE showed better accuracy for parenchymal hematoma prediction.

Validation of different predictive scoring scales in patients with new-onset epileptic seizures or epilepsy related to neuronal surface antibody-mediated autoimmune encephalitis.

OBJECTIVE: To validate the different predictive scoring scales in the Chinese population with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface antibody (Ab)-mediated autoimmune encephalitis (AE). METHODS: We retrospectively reviewed the charts of 174 consecutive patients from October 2018 to December 2022, whose serum and cerebrospinal fluid samples were tested for neuronal surface Abs. The antibody prevalence in epilepsy and encephalopathy (APE2), antibodies contributing to focal epilepsy signs and symptoms (ACES), "obvious" indications for neural antibody testing in epilepsy or seizures (ONES) checklist, and the combinations were used to validate the predictive models of neuronal surface Ab-mediated AE. RESULTS: A total of 139 patients with new-onset epileptic seizures or epilepsy of unknown etiology were enrolled. Abs were detected in 37 patients (26.6%). The APE2/ONES reflex score had the highest sensitivity (89.2%) and lowest specificity (41.7%). The ACES score had the lowest sensitivity (67.5%) and highest specificity (64.7%). Variations in the performance were observed in the different types of AE. 100% of patients with anti-γ-aminobutyric acid B-B receptor encephalitis were predicted by ONES, APE2/ONES reflex, and ACES/ONES reflex scores. Only 75% of patients with anti-N-methyl-D-aspartate receptor encephalitis were predicted by the APE2/ONES and ACES/ONES reflex scores. CONCLUSION: Our study was the first to validate various predictive scoring scales in the Chinese cohort of patients with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface Ab-mediated AE. Based upon clinical suspicion, more than one scoring scale should be performed to predict the chance of AE in those patients.

Intracranial large artery embolism due to carotid thrombosis caused by a neck massager: A case report.

BACKGROUND: There are few reported cases of intracranial large artery embolism due to carotid thrombosis caused by a neck massager. Herein we report such a case. CASE SUMMARY: A 49-year-old woman presented with left limb weakness and dysarthria after a history of neck massage for 1 mo. Neurological examination showed left central facial paralysis and left hemiparesis with a National Institutes of Health Stroke Scale score of 12. Brain magnetic resonance imaging revealed restricted diffusion on diffusion-weighted imaging in the right parietal and temporal lobes. Computed tomography angiography (CTA) indicated M3 segment embolism of the right middle cerebral artery. Neck CTA revealed thrombosis of the bilateral common carotid arteries. Carotid ultrasound showed thrombosis in the bilateral common carotid arteries (approximately 2 cm below the proximal end of the carotid sinus), and contrast-enhanced ultrasound did not suggest enhancement. No hypertension, diabetes, heart disease, vasculitis, or thrombophilia was found after admission. After 1 wk of treatment with aspirin 200 mg and atorvastatin 40 mg, a carotid ultrasound reexamination showed that the thrombosis had significantly reduced. CONCLUSION: Neck massager may cause carotid artery thrombosis.

Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer's disease.

BACKGROUND: Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summarize the mechanisms through which ICA treats AD. METHODS: The PubMed and CNKI databases were utilized to review the advancements in ICA's role in AD prevention and treatment by analyzing literature published between January 2005 and April 2023. To further illustrate ICA's impact on AD development, tables, and images are included to summarize the relationships between various mechanisms. RESULTS: The study reveals that ICA ameliorates cognitive deficits in AD model mice by modulating Aß via multiple pathways, including BACE-1, NO/cGMP, Wnt/Ca2+, and PI3K/Akt signaling. ICA exhibits neuroprotective properties by inhibiting neuronal apoptosis through the suppression of ER stress in AD mice, potentially linked to NF-κB, MAPK, ERK, and PERK/Eif2α signaling pathways. Moreover, ICA may safeguard neurons by attenuating mitochondrial oxidative stress injury. ICA can also enhance learning, memory, and cognition by improving synaptic structure via regulation of the PSD-95 protein. Furthermore, ICA can mitigate neuroinflammation by inactivating microglial activity through the upregulation of PPARγ, TAK1/IKK/NF-κB, and JNK/p38 MAPK signaling pathways. CONCLUSION: This study indicates that ICA possesses multiple beneficial effects in AD treatment. Through the integration of pharmacological and molecular biological research, ICA may emerge as a promising candidate to expedite the advancement of TCM in the clinical management of AD.

Transcriptomics integrated with metabolomics reveals the ameliorating effect of mussel-derived plasmalogens on high-fat diet-induced hyperlipidemia in zebrafish.

Plasmalogens (Pls), a special group of phospholipids, are effective in ameliorating neurodegenerative disease. In the present study, the metabolic effects of seafood-derived Pls on high fat diet (HFD)-induced hyperlipidemia in zebrafish were evaluated, and the underlying mechanisms of dietary Pls against hyperlipidemia were explored through integrated analyses of hepatic transcriptomics and metabolomics. The results demonstrated that Pls supplementation could effectively alleviate HFD-induced obesity symptoms, such as body weight gain, and decrease total hepatic cholesterol and triglyceride levels. Integrated hepatic transcriptome and metabolome data suggested that Pls mainly altered lipid metabolism pathways (FA metabolism, primary bile acid biosynthesis, steroid hormone biosynthesis, and glycerolipid and glycerophospholipid metabolism) and the TCA cycle, induced the overexpression of anti-oxidation enzymes (Cat, Gpx4, Sod3a and Xdh), reduced disease biomarkers (such as glutarylcarnitine, gamma-glutamyltyrosine, and 11-prostaglandin f2) and gut microbiota-derived metabolites, and increased (±)12(13)-diHOME, EPA, lysoPC and PC levels. Moreover, 5 abnormally regulated metabolites were identified as potential biomarkers associated with hyperlipidemia according to the metabolomics results and suggested the involvement of gut microbiota in the anti-hyperlipidemic effects of Pls. Collectively, these findings suggest that the protective role of Pls is mainly associated with the promotion of unsaturated fatty acid biosynthesis and cholesterol efflux, lipid and phospholipid PUFA remodeling, and anti-oxidation and anti-inflammatory capabilities. This study provides valuable information for reasonably explaining the beneficial effects of seafood-derived Pls in alleviating hyperlipidemia and thus may contribute to the development and application of Pls as functional foods or dietary supplements to protect against obesity and hyperlipidemia.

Causal association between systemic lupus erythematosus and the risk of dementia: A Mendelian randomization study.

Introduction: It is well-documented that systemic lupus erythematosus (SLE) is associated with dementia. However, the genetic causality of this association remains unclear. Mendelian randomization (MR) was used to investigate the potential causal relationship between SLE and dementia risk in the current study. Methods: We selected 45 single nucleotide polymorphisms (SNPs) associated with SLE from publicly available genome-wide association studies (GWAS). Summary level statistics were obtained from the dementia GWAS database. MR estimates were performed using the inverse variance weighted (IVW) method, MR-Egger method and weighted median (WM) method. Cochran's Q test, the intercept of MR-Egger, MR-Pleiotropy Residual Sum and Outlier method, leave-one-out analysis and funnel plot were applied for sensitivity analyses. Results: No significant causal association was found between SLE and any type of dementia, including Alzheimer's disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. These findings were robust across several sensitivity analyses. Conclusion: Overall, our findings do not support a causal association between SLE and dementia risk.

Causal association between adiponectin and the risk of Alzheimer's disease: A Mendelian randomization study.

Background: Numerous observational studies have revealed that circulating adiponectin (ADPN) is associated with Alzheimer's disease (AD) risk. However, the causality remains unknown. We aimed to assess the causality of circulating ADPN on AD risk using Mendelian randomization (MR). Methods: Fourteen single nucleotide polymorphisms (SNPs) significantly associated with ADPN were selected from publicly available genetic abstract data. We applied these SNPs to two recent large-scale genome-wide association studies (GWAS) of AD, one from the FinnGen consortium and the other from a large meta-analysis. The inverse variance weighted method, MR-Egger method, the weighted median method, the Cochran Q statistic, the MR-Pleiotropy Residual Sum and Outlier methods, and the leave-one-out analysis were applied for MR analyses. Results: In MR analysis, no significant genetic association was found between plasma ADPN levels and AD risk by analyzing the FinnGen consortium GWAS database in the inverse variance weighted method [odds ratio (OR): 0.874, 95% confidence interval (CI): 0.701-1.089, p = 0.230], MR-Egger (OR: 0.944, 95% CI: 0.692-1.288, p = 0.721), and weighted median method (OR: 0.900, 95% CI: 0.678-1.194, p = 0.449). Additionally, the same analysis was conducted for the meta-analysis database, and we found no significant association (OR: 1.000, 95% CI: 0.999-1.001, p = 0.683). Conclusion: Our findings reveal no significant causal association between circulating ADPN and AD risk.

Real-time authentication of minced shrimp by rapid evaporative ionization mass spectrometry.

Minced shrimp is popular seafood due to its delicious flavor and nutritional value. However, the biological species of raw material of minced shrimp are not distinguished by naked eyes after processing. Thus, an in situ and real-time minced shrimp authentication method was established using iKnife rapid evaporative ionization mass spectrometry (REIMS) based lipidomics. The samples were analyzed under ambient ionization without any tedious preparation step. Seven economic shrimp samples were tested, whose phenotypes were used to develop a real-time recognition model. A total of 19 fatty acids and 45 phospholipid molecular species were efficiently identified and statistically analyzed by multivariate statistical analysis. The results showed that the seven shrimp species were well distinguished, and the most contributing ions at m/z 255.2, 279.2, 301.2, 327.2, 699.5, 742.5, etc., were revealed by variable importance in projection. The proposed iKnife REIMS showed excellent performance in minced shrimp authentication.

Rescue stenting after the failure of mechanical thrombectomy to treat acute intracranial atherosclerotic occlusion.

Background: Acute ischemic stroke (AIS) with intracranial large vessel occlusion (LVO) is refractory to reperfusion because of the underlying intracranial atherosclerosis (ICAS), and this condition often requires salvage methods such as balloon angioplasty and rescue stenting (RS). In this study, we investigated the short-term outcomes of RS after failed mechanical thrombectomy (MT) for the treatment of acute intracranial atherosclerotic occlusion. Methods: We retrospectively evaluated the clinical data of 127 patients who underwent MT for acute intracranial atherosclerotic occlusion in our hospital between August 2018 and January 2022. The degree of recanalization was evaluated immediately after the treatment by Modified Thrombolysis in Cerebral Infarction (mTICI). The modified Rankin Scale (mRS) was used 90 days after treatment to evaluate the neurological functions. In addition, the incidence of symptomatic intracranial hemorrhage (sICH) and postoperative mortality within 90 days of treatment were calculated. Results: Among the 127 patients, 86 patients (67.7%) had revascularization (mTICI 2b-3) immediately after MT (non-RS group), and RS was performed in 41 patients (32.3%) after MT failure (RS group). No difference in the sICH rate was observed between the two groups (17.1 vs. 16.3%, p = 0.91). There was a slightly higher mortality rate in the RS group (14.6 vs. 12.8%, p = 0.71); however, the difference was not significant. There was no difference in the proportion of patients in the RS and non-RS groups who had a 90-day mRS score of 0-2 (48.8 vs. 52.3%, p = 0.76). Conclusions: Rescue stenting after MT failure might be a feasible rescue modality for treating acute intracranial atherosclerotic occlusion.

Protect Effects of Seafood-Derived Plasmalogens Against Amyloid-Beta (1-42) Induced Toxicity via Modulating the Transcripts Related to Endocytosis, Autophagy, Apoptosis, Neurotransmitter Release and Synaptic Transmission in SH-SY5Y Cells.

To investigate the underlying mechanisms of decreased plasmalogens (Pls) levels in neurodegenerative diseases, here the effects of seafood-derived Pls on undifferentiated and differentiated human SH-SY5Y neuroblastoma cells exposed to amyloid-ß1-42 was analyzed. Transcriptional profiles indicated that a total of 6,581 differentially expressed genes (DEGs) were significantly identified among different experimental groups, and KEGG analysis indicated that these DEGs were related to AD, endocytosis, synaptic vesicle cycle, autophagy and cellular apoptosis. After Pls treatment, the striking expression changes of ADORA2A, ATP6V1C2, CELF6, and SLC18A2 mRNA strongly suggest that Pls exerts a beneficial role in alleviating AD pathology partly by modulating the neurotransmitter release and synaptic transmission at the transcriptional level. Besides these, GPCRs are also broadly involved in Pls-signaling in neuronal cells. These results provide evidence for supporting the potential use of Pls as an effective therapeutic approach for AD.

Plasmalogens improve swimming performance by modulating the expression of genes involved in amino acid and lipid metabolism, oxidative stress, and ferroptosis in an Alzheimer's disease zebrafish model.

Plasmalogens (PLs) are critical to human health. Studies have reported a link between the downregulation of PLs levels and cognitive impairments in patients with Alzheimer's disease (AD). However, the underlying mechanisms remain to be clarified. In the present study, an AlCl3-induced AD zebrafish model was established, and the model was used to elucidate the neuroprotective effects of PLs on AD by analysing the transcriptional profiles of zebrafish in the control, AD model, AD_PL, and PL groups. Chronic AlCl3 exposure caused swimming performance impairments in the zebrafish, yet PLs supplementation could improve the dyskinesia recovery rate in the AD zebrafish model. Through transcriptional profiling, a total of 5413 statistically significant differentially expressed genes (DEGs) were identified among the groups. In addition to the DEGs involved in amino acid metabolism, we found that the genes related to iron homeostasis, lipid peroxidation, and oxidative stress, all of which contribute to ferroptosis, were dramatically altered among different groups. These results suggest that seafood-derived PLs, in addition to their role in eliminating oxidative stress, can improve the swimming performance in AlCl3-exposed zebrafish partly by suppressing neuronal ferroptosis and accelerating synaptic transmission at the transcriptional level. This study provides evidence for PLs to be developed as a functional food supplement to relieve AD symptoms.

In Situ Quality Assessment of Dried Sea Cucumber (Stichopus japonicus) Oxidation Characteristics during Storage by iKnife Rapid Evaporative Ionization Mass Spectrometry.

Sea cucumber (Stichopus japonicus) is one of the most luxurious and nutritious seafoods in Asia. It is always processed into dried products to prevent autolysis, but its quality is easily destructed during storage. Herein, an extremely simplified workflow was established for real-time and in situ quality assessment of dried sea cucumbers (DSCs) during storage based on the lipid oxidation characteristics using an intelligent surgical knife (iKnife) coupled with rapid evaporative ionization mass spectrometry (REIMS). The lipidomic phenotypes of DSCs at different storage times were acquired successfully, which were then processed by multivariate statistical analysis. The results showed that the discrepancy in the characteristic ions in different DSCs was significant (p < 0.05) with high R2(Y) and Q2 values (0.975 and 0.986, respectively). The receiver operating characteristic curve revealed that the ions of m/z 739.5, m/z 831.5, m/z 847.6, and m/z 859.6 were the most specific and characteristic candidate biomarkers for quality assessment of DSCs during accelerated storage. Finally, this method was validated to be qualified in precision (RSDintraday ≤ 9.65% and RSDinterday ≤ 9.36%). In conclusion, the results showed that the well-established iKnife-REIMS method was high-throughput, rapid, and reliable in the real-time quality assessment of DSCs.

Increased Postoperative Fasting Glucose Is Associated With Unfavorable Outcomes in Patients Treated With Mechanical Thrombectomy Treatment.

Background and objective: Hyperglycemia on admission was associated with worse clinical outcomes after mechanical thrombectomy (MT) of acute ischemic stroke (AIS). We evaluated whether increased postoperative fasting glucose (PFG) was also related to poor clinical outcomes in patients who underwent MT treatment. Methods: Consecutive patients with large vessel occlusion underwent MT in our center were included. Admission glucose and fasting glucose levels after MT treatment were evaluated. Primary outcome was 90-day unfavorable outcomes (modified Rankin Scale score of 3-6). Secondary outcome was the rate of symptomatic intracranial hemorrhage (sICH) after MT treatment. The association of PFG and 90-day clinical outcome after MT treatment was determined using logistic regression analyses. Results: One hundred twenty seven patients were collected. The median postoperative fasting glucose level was 6.27 mmol/L (IQR 5.59-7.62). Fourteen patients (11.02%) had sICH, and fifty-eight patients (45.67%) had unfavorable outcomes at 90-day after MT. After adjustment for potential confounding factors, PFG level was an independent predictor of 90-day unfavorable outcome (OR 1.265; 95% CI 1.017-1.575; p = 0.035) and sICH (OR 1.523; 95% CI 1.056-2.195; p = 0.024) after MT. In addition, older age, higher baseline NIHSS score, and higher postoperative NLR were also associated with unfavorable outcomes at 90-day after MT treatment. Conclusions: Increased PFG is associated with unfavorable outcomes at 90-day and an increased risk of sICH in patients underwent MT treatment.

Number of Stent Retriever Passes Associated with Clinical Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke.

OBJECTIVE: To evaluate the association between the number of stent retriever (SR) passes and clinical outcome after mechanical thrombectomy (MT) in patients with acute ischemic stroke(AIS). METHODS: We retrospectively analyze data collected from consecutive patients with large vessel occlusion (LVO) in anterior circulation treated with MT. Baseline characteristics, number of SR passes, symptomatic intracranial hemorrhage (sICH), clinical outcome measured by modified Rankin Scale (mRS) at 90 days after MT were collected. Multivariate logistic regression analysis was performed to assess the association between number of SR passes and patients' clinical outcome. RESULTS: 134 patients with LVO achieved successful reperfusion (mTICI 2B/3) were enrolled. Univariate analysis showed that patients with favorable outcomes were less likely to need more than three passes of SR (9.8%vs39.7%, p = 0.001). In a multivariable analysis, baseline NIHSS score (OR 0.922, 95%CI 0.859∼0.990, p = 0.025), more than three passes of SR (OR 0.284, 95%CI0.091∼0.882, p = 0.030) and symptomatic intracranial hemorrhage (OR 0.116,95%CI0.021∼0.650, p = 0.014) each independently predicted poor outcome after MT at 90 days. CONCLUSION: The need for more than three passes of SR may be used as an independent predictor of poor outcome after MT in patients with acute ischemic stroke at 90 days.