Data_Sheet_1_Association between intracranial and extracranial atherosclerosis and white matter hyperintensities: a systematic review and meta-analysis.PDF

BackgroundWhite matter hyperintensities (WMHs) are key neuroimaging markers of cerebral small vessel diseases. This study aimed to investigate whether intracranial and extracranial atherosclerotic stenosis is associated with WMHs.MethodsFollowing a previously registered protocol (PROSPERO protocol: CRD42023407465), PubMed, Web of Science, and Embase were systematically searched for relevant literature published until March 2023. Cross-sectional studies examining the association between intracranial and extracranial atherosclerotic stenosis and WMHs were included. Random effects models were used to calculate the pooled estimates.ResultsTwenty-one eligible studies, including 10,841 participants, were identified. Intracranial and extracranial atherosclerotic stenosis was associated with an increased risk of WMHs (OR 1.80, 95% CI 1.25–2.57, I2 = 75%) and increased WMH volumes (SMD 0.40, 95% CI 0.18–0.63, I2 = 63%). Heterogeneity resulted from the WMHs rating method and the location. Extracranial atherosclerotic stenosis (ECAS) was significantly associated with WMHs (OR 2.10, 95% CI 1.22–3.62, I2 = 71%), but intracranial atherosclerotic stenosis (ICAS) was insignificantly associated with WMHs (OR 1.75, 95% CI 0.97–3.15, I2 = 84%). The association was stable in the subgroup analysis based on WMHs location, which included deep WMHs and periventricular WMHs.ConclusionIntracranial and extracranial atherosclerotic stenosis is associated with WMHs. This association is significant in ECAS, but attenuated in ICAS.</p

Facile Synthesis of Alkali Metal Polyhedral Oligomeric Silsesquioxane Salt and Its Application in Flame-Retardant Epoxy Resins

A series of metal polyhedral oligomeric silsesquioxane salts (POSS-M, M = Li or Na or K) were facilely synthesized using the click reaction and neutralization reaction. The chemical structure of POSS-M was confirmed by FT-IR, 1H, 13C, 29Si NMR, and XRD patterns. The well-characterized POSS-M was introduced into epoxy resins. The epoxy composites containing POSS-Na achieved the UL-94 V1 rating, and the highest LOI value also came from EP/POSS-Na, which was 27.4%. A dramatical decrease in pHRR was observed in all three composites. With 3 wt % POSS-M, the pHRR of epoxy composites dropped by up to 64.2%. Notably, compact char layers with sodium silicate on the surface were clearly observed for the first time, extending the silicon-containing flame retardant mechanism

Reprogramming Tumor-Associated Macrophages To Reverse EGFR^T790M Resistance by Dual-Targeting Codelivery of Gefitinib/Vorinostat

Gefitinib is a first-line therapy in the EGFR-mutated nonsmall cell lung cancer (NSCLC). However, the development of drug resistance is almost unavoidable, thus leading to an unsustainable regimen. EGFR^T790M mutation is the major cause responsible for the molecular-targeting therapy failure in NSCLC. Although the recently approved osimertinib is effective for the EGFR^T790M-positive NSCLC, the osimertinib-resistant EGFR mutation is rapidly developed, too. In this study, we proposed a tumor-associated macrophage (TAM) reprogramming strategy for overcoming the EGFR^T790M-associated drug resistance via a dual-targeting codelivery system of gefitinib/vorinostat that acted on both TAM with overexpression of mannose receptors and the HER-2 positive NSCLC cells. The trastuzumab-modified, mannosylated liposomal system was able to repolarize the protumor M2 phenotype to the antitumor M1 and cause the elevating ROS in the cancer cells, consequently modulating the intracellular redox balance via ROS/NOX3/MsrA axis. The suppressed MsrA facilitated the EGFR^T790M degradation through 790M oxidation by ROS, thus resensitizing the EGFR^T790M-positive cells to gefitinib. The dual-targeting codelivery and TAM-reprogramming strategies provided a potential method for rescuing the EGFR^T790M-caused resistance to tyrosine kinase inhibitor treatment

Additional file 1 of Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model

Additional file 1: Note S1. Sample preparation. Note S2. Mass spectrometry analysis. Note S3. Bioinformatics tools and databases. Figure S1. Cerebral microvascular extraction and identification in CFA and EAMG rats. The cerebral microvascular was confirmed by the tubular structure via A optical microscope and B HE staining. C the absence of the neuronal markers (Syp and Tubb3 genes) via qPCR. Statistical analysis was performed using t test, ***P < 0.001, ****P < 0.0001. Figure S2. The leakage of BBB in EAMG rats. The brain, spleen and kidney fluorescence, “ + ” and “−” indicated with or without Alexa flour 488 cadaverine injection (40 × magnification). Figure S3. The expression of DRD1-DRD5 and Scl6a3 genes in T cells (A) and B cells (B) of CFA and EAMG groups. Statistical analysis was conducted using t test, *P < 0.05, **P < 0.01, ns = no significance. Figure S4. The impact of SCH23390 (dopamine D1 receptor antagonist) and Haloperidol (dopamine D2 receptor antagonist) on bEnd.3 cells was investigated. A, B The proliferative effects of SCH23390 and Haloperidol on bEnd.3 cell line were assessed using CCK-8 assays. (C-D) The expression of CD31 was significantly increased upon incubation with both SCH23390 and Haloperidol, while Claudin5 remained unchanged. Additionally, the expression levels of Wnt3a in bEnd.3 cell line were examined through western blot, showing no significant changes in SCH23390 and Haloperidol treated cell lines. However, the results examined through western blot also showed elevated levels of p-GSK3β and active-β-catenin in SCH23390-treated cell line. Statistical analysis was conducted using one-way ANOVA, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns = no significant difference. Figure S5. The effects of dopamine on T and B cells were examined. A Upon dopamine incubation, the mean fluorescence intensity (MFI) level of Th17 cells were significantly increased, whereas the MFI of Th1 and Treg cells exhibited no significant changes. B The dopamine exposure resulted in a significant increase in the MFI of CD86+ B cells and CD69+ B cells. Conversely, the MFI of CD80+ B cells decreased, and MHC II+ B cells remained unsignificant. Statistical analysis was conducted using t test, *P < 0.05, **P < 0.01, ns = no significant difference. Figure S6. Diaphragm samples were analyzed using immunofluorescence and HE staining. We performed A α-BTX and DAPI staining and B HE staining in the CFA group. We also performed C α-BTX and DAPI staining and D HE staining in the EAMG group. Blue staining represents DAPI, and α-BTX is the red staining highlighted by the white arrow. Figure S7. The effect of SCH23390 (dopamine D1 receptor antagonist) on EAMG rats was investigated by gavage every other day after the first immunization in vivo. A Clinical scores. B Survival probability and number at risk. Table S1. The criterion for each EAMG score is listed below. Table S2. The rat primer sequences are listed below. Table S3. The mouse primer sequences are listed below. Table S4. The detailed statistical results