RESUMEN
A zinc-mediated cross-electrophile coupling of benzyl sulfonium salts with thiosulfonates via C-S bond cleavage was achieved. The reductive thiolation proceeded well under transition metal-free conditions to afford the desired benzyl sulfides in good yields, exhibiting both broad substrate scope and good functionality tolerance. In addition, the reaction could be applied to the use of selenosulfonate as an effective selenylation agent and be subjected to scale-up synthesis.
RESUMEN
Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.
RESUMEN
A straightforward cross-coupling of aryl thioether with aryl bromide with the aid of nickel salt, magnesium, and lithium chloride in tetrahydrofuran at ambient temperature was accomplished. The one-pot reactions proceeded efficiently via C-S bond cleavage to produce the desired biaryls in modest to good yields, avoiding the use of pregenerated or commercial organometallic reagents.
RESUMEN
Background: The difference of patients' baseline characteristics such as sex, age, Eastern Cooperative Oncology Group performance status (ECOG PS), and smoking status may influence the immune response. However, little is known about whether these factors affect the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we performed this systematic review and meta-analysis to investigate the relationship between patients' baseline characteristics and survival benefits in immunotherapy-treated NSCLC. Materials and Methods: We performed a systematic search of PubMed, the Cochrane Library, and Embase for randomized controlled trials (RCTs) of NSCLC immunotherapy. We also searched abstracts and presentations from the proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology to identify unpublished studies. These studies have available data based on patients' baseline characteristics (such as sex, age, ECOG PS, and smoking status). We take the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) as the effect index and use the random effect model to pool the results. Results: We included 18 phase II/III RCTs with a total of 14,189 participants. The benefits of ICIs were found for both male (pooled OS-HR 0.77, 95% CI 0.72-0.82, P < 0.05) and female patients (pooled OS-HR 0.77, 95% CI 0.67-0.87, P < 0.05); for both younger (<65 y: pooled OS-HR 0.74, 95% CI 0.68-0.81, P < 0.05) and older patients (≥65 y: pooled OS-HR 0.80, 95% CI 0.75-0.86, P < 0.05); and for both patients with ECOG PS = 0 (pooled OS-HR 0.77, 95% CI 0.71-0.84, P < 0.05) and ECOG PS ≥ 1 (pooled OS-HR 0.76, 95% CI 0.70-0.82, P < 0.05). Moreover, there was no significant difference in the efficacy of ICIs among different sex (P value for interaction = 0.955), age (P value for interaction = 0.17), or ECOG PS (P value for interaction = 0.765). However, in patients with different smoking status, the application of ICIs significantly prolonged the OS of smokers (pooled OS-HR 0.77, 95% CI 0.71-0.83, P < 0.05) but could not significantly improve the OS of never smokers (pooled OS-HR 0.85, 95% CI 0.70-1.03, P > 0.05). Conclusions: ICIs could significantly improve prognosis in patients with advanced NSCLC, regardless of sex, age, or ECOG PS. But among patients with different smoking status, the survival benefits of never smokers treated with ICIs were no better than that of controls. The impact of these factors on immunotherapy should be considered in the future clinical practice and guidelines.
RESUMEN
Rehabilitation therapy is beneficial for patients with ischemic stroke. Our previous study showed that treadmill training is conducive to neurological function in rats that underwent middle cerebral artery occlusion (MCAO). However, whether exercise benefits cerebral edema and the underlying mechanism remain unclear. This study investigated the influence of treadmill exercise on brain edema and the mechanism of its formation and elimination. The MCAO model was established with Sprague-Dawley (SD) rats, and lentivirus-mediated caveolin-1 shRNA was used to investigate the role of caveolin-1 in brain edema. As expected, we found that treadmill exercise has a beneficial effect on brain edema after stroke. Training led to a significant increase in the expression of caveolin-1 and TRPV4; and reduced brain water content and blood-brain barrier (BBB) damage. This treatment also changed the localization of aquaporin-4 (AQP4). Moreover, the effect of treadmill training on the polar expression of AQP4 differed over time. The results showed that early treadmill training inhibited the polar expression of AQP4, and later promoted its expression. However, the rats that were injected with the caveolin-1 shRNA lentivirus exhibited enhanced edema. Caveolin-1 shRNA eliminated the protective effect induced by exercise, which is consistent with the downregulation of TRPV4 expression. The findings indicate that treadmill training improves brain edema through the caveolin-1/TRPV4/AQP4 pathway.