Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

Modifications of Pyridine-3,5-dicarbonitrile Acceptor for Highly Efficient Green-to-Red Organic Light-Emitting Diodes.

The strategy of acceptor modification is a powerful technique for tuning the emission color of thermally activated delayed fluorescence (TADF) emitters. In this study, we have successfully designed and synthesized three TADF emitters with donor-acceptor (D-A) structures using a 4-(diphenylamino)-2,6-dimethylphenyl (TPAm) donor and various pyridine-3,5-dicarbonitrile (PC) acceptor units. As a result, three compounds named TPAmbPPC, TPAm2NPC, and TPAmCPPC exhibited greenish-yellow to orange-red emissions with high photoluminescent quantum yields (76-100%) in thin films. Remarkably, a greenish-yellow device based on TPAmbPPC and TPAm2NPC showed a high maximum external quantum efficiency (EQEmax) of 39.1 and 39.0%, respectively. Furthermore, benefiting from the suitable steric hindrance between the acceptor and donor, the nondoped organic light-emitting diodes (OLEDs) based on TPAmbPPC demonstrated an exceptional EQEmax of 21.6%, indicating its promising potential as an efficient emitter for the application of OLED applications. Furthermore, orange-red OLED devices based on TPAmCPPC exhibited a high EQEmax of 26.2%, a CE of 50.1 cd A-1, and a PE of 52.4 lm W-1.

The condensed tannin chemistry and astringency properties of fifteen Vitis davidii Foex grapes and wines.

This study sought to determine the effects of variety on the astringency and chemistry of condensed tannins of spine grapes and wines. Fifteen varieties of red spine grape (Vitis davidii Foex) were used. Condensed tannin content, composition, and wine astringency were determined. The condensed tannin profiles were assessed by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The condensed tannin content highly depended on the variety ranging from 0.30 mg/g to 7.80 mg/g (in skins), from 3.12 mg/g to 8.82 mg/g (in seeds), and from 62.60 mg/L to 225.90 mg/L (in wines). There were significant differences in proportions of certain constitutive subunits (as mole%) and mean degree of polymerization (mDp) among the varieties. Correlation analysis revealed that condensed tannin concentration and composition had a significant effect on the sensory evaluation and quantitative analysis of astringency. A positive correlation between mDp and astringency was also observed. The present results expand knowledge of the characterization of spine grape and wine condensed tannin chemistry and astringency.

A Tumor-Specific Tissue-Penetrating Peptide Enhances the Efficacy of Chemotherapy Drugs in Gastric Cancer.

PURPOSE: C-end rule (CendR) peptides are found to enhance the penetration of chemotherapeutic agents into tumor cells, while GX1 is a peptide that homes to gastric cancer (GC) vasculature. This study aimed to synthesize a novel peptide GX1-RPAKPAR (GXC) and to explore the effect of GXC on sensitizing GC cells to chemotherapeutic agents. MATERIALS AND METHODS: Intracellular Adriamycin concentration analysis was applied to conform whether GXC peptide increases the penetration of chemotherapeutic agents into GC cells in vitro. The effect of GXC peptide on sensitizing GC cells to chemotherapeutics was validated by apoptosis assay and in vitro/vivo drug sensitivity assay. The specificity of GXC to GC tissue was validated by ex vivo fluorescence imaging. RESULTS: In vitro, administration of GXC significantly increased Adriamycin concentrations inside SGC-7901 cells, and enhanced the efficacy of chemotherapeutic agents by decreasing the IC50 value. In vivo, FITC-GXC specifically accumulated in GC tissue. Moreover, systemic co-injection with GXC peptide and Adriamycin statistically improved the therapeutic efficacy in SGC-7901 xenograft models, surprisingly, without obviously increasing side effects. CONCLUSION: These results demonstrated that co-administration of the novel peptide GXC with chemotherapeutic agents may be a potential way to enhance the efficacy of anticancer drugs in GC treatment.