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The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands of Toll-like receptors (TLRs) have been suggested to activate adaptive immune responses by modulating the function of antigen-presenting cells (APCs). Despite their therapeutic potential, the development of TLR ligands for immunotherapy is often hampered due to rapid systemic toxicity. Regarding the safety concerns of currently available TLR ligands, finding a new TLR agonist with potent efficacy and safety is needed. A unique structural domain (UNE-C1) was identified as a novel TLR2/6 in the catalytic region of human cysteinyl-tRNA synthetase 1 (CARS1) using comprehensive approaches, including RNA sequencing, the human embryonic kidney (HEK)-TLR Blue system, pull-down, and ELISA. The potency of its immunoadjuvant properties was analyzed by assessing antigen-specific antibody and CTL responses. In addition, the efficacy of tumor growth inhibition and the presence of the tumor-infiltrating leukocytes were evaluated using E.G7-OVA and TC-1 mouse models. The combined effect of UNE-C1 with an immune checkpoint inhibitor, anti-CTLA-4 antibody, was also evaluated in vivo. The safety of UNE-C1 immunization was determined by monitoring splenomegaly and cytokine production in the blood. Here, we report that CARS1 can be secreted from cancer cells to activate immune responses via specific interactions with TLR2/6 of APCs. A unique domain (UNE-C1) inserted into the catalytic region of CARS1 was determined to activate dendritic cells, leading to the stimulation of robust humoral and cellular immune responses in vivo. UNE-C1 also showed synergistic efficacy with cancer antigens and checkpoint inhibitors against different cancer models in vivo. Further, the safety assessment of UNE-C1 showed lower systemic cytokine levels than other known TLR agonists. We identified the endogenous TLR2/6 activating domain from human cysteinyl-tRNA synthetase CARS1. This novel TLR2/6 ligand showed potent immune-stimulating activity with little toxicity. Thus, the UNE-C1 domain can be developed as an effective immunoadjuvant with checkpoint inhibitors or cancer antigens to boost antitumor immunity.

Although it has been suggested that social network site (SNS) use motives are one of important determinants of SNS addiction, there has not been yet a scale to assess them. The aim of this study was to examine psychological properties of a newly developed Social Network Site Use Motives Scale (SUMS) in a college student sample. The SUMS was administered to 481 nonclinical participants. Exploratory factor analysis, internal consistency analysis, and correlation analysis were undertaken to examine its validity and reliability. Results of factor analysis indicated that the SUMS consisted of four factors. Indices of internal consistency reliability, test-retest reliability, and criterion validity of SUMS were acceptable. Our study suggested that SUMS could be used as an effective tool to assess SNS use motives. The usage of SUMS should be encouraged in future studies of SNS use motives. Future research using this measure could provide a more comprehensive model of the relationship between SNS use motives and SNS addiction.

Key Points: Question: Does early intensive blood pressure management improve outcomes after successful reperfusion with endovascular thrombectomy in acute ischemic stroke? Findings: In this randomized clinical trial that included 306 patients, 39.4% of patients with intensive blood pressure management (systolic blood pressure target <140 mm Hg) and 54.4% of those with conventional blood pressure management (systolic blood pressure target 140-180 mm Hg) achieved functional independence (modified Rankin Scale score ≤2) at 3 months; this represented a significant difference. Meaning: Intensive blood pressure lowering during the first 24 hours after successful reperfusion may be harmful in patients with acute ischemic stroke who have undergone endovascular thrombectomy. Importance: Optimal blood pressure (BP) control after successful reperfusion with endovascular thrombectomy (EVT) for patients with acute ischemic stroke is unclear. Objective: To determine whether intensive BP management during the first 24 hours after successful reperfusion leads to better clinical outcomes than conventional BP management in patients who underwent EVT. Design, Setting, and Participants: Multicenter, randomized, open-label trial with a blinded end-point evaluation, conducted across 19 stroke centers in South Korea from June 2020 to November 2022 (final follow-up, March 8, 2023). It included 306 patients with large vessel occlusion acute ischemic stroke treated with EVT and with a modified Thrombolysis in Cerebral Infarction score of 2b or greater (partial or complete reperfusion). Interventions: Participants were randomly assigned to receive intensive BP management (systolic BP target <140 mm Hg; n = 155) or conventional management (systolic BP target 140-180 mm Hg; n = 150) for 24 hours after enrollment. Main Outcomes and Measures: The primary outcome was functional independence at 3 months (modified Rankin Scale score of 0-2). The primary safety outcomes were symptomatic intracerebral hemorrhage within 36 hours and death related to the index stroke within 3 months. Results: The trial was terminated early based on the recommendation of the data and safety monitoring board, which noted safety concerns. Among 306 randomized patients, 305 were confirmed eligible and 302 (99.0%) completed the trial (mean age, 73.0 years; 122 women [40.4%]). The intensive management group had a lower proportion achieving functional independence (39.4%) than the conventional management group (54.4%), with a significant risk difference (−15.1% [95% CI, −26.2% to −3.9%]) and adjusted odds ratio (0.56 [95% CI, 0.33-0.96]; P =.03). Rates of symptomatic intracerebral hemorrhage were 9.0% in the intensive group and 8.1% in the conventional group (risk difference, 1.0% [95% CI, −5.3% to 7.3%]; adjusted odds ratio, 1.10 [95% CI, 0.48-2.53]; P =.82). Death related to the index stroke within 3 months occurred in 7.7% of the intensive group and 5.4% of the conventional group (risk difference, 2.3% [95% CI, −3.3% to 7.9%]; adjusted odds ratio, 1.73 [95% CI, 0.61-4.92]; P =.31). Conclusions and Relevance: Among patients who achieved successful reperfusion with EVT for acute ischemic stroke with large vessel occlusion, intensive BP management for 24 hours led to a lower likelihood of functional independence at 3 months compared with conventional BP management. These results suggest that intensive BP management should be avoided after successful EVT in acute ischemic stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT04205305 This randomized trial assesses the effect of intensive blood pressure management vs conventional management on functional independence at 3 months among patients with large vessel occlusion acute ischemic stroke treated with endovascular thrombectomy. [ABSTRACT FROM AUTHOR]