Olefin skeletal rearrangement enabling access to multiarylated N-sulfonyl amidines.

A base-promoted olefin skeletal rearrangement strategy from para-quinone methides (p-QMs) and N-fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated (Z)-N-sulfonyl amidines with complete stereoselectivity and generally good yields. Using p-QMs without o-hydroxy substituents gave triarylated N-sulfonyl amidines, whereas tetraarylated N,N'-disulfonyl amidines were synthesized with the existence of o-hydroxy groups.

Utility of CT Radiomics and Delta Radiomics for Survival Evaluation in Locally Advanced Nasopharyngeal Carcinoma with Concurrent Chemoradiotherapy.

BACKGROUND: A high incidence rate of nasopharyngeal carcinoma (NPC) has been observed in Southeast Asia compared to other parts of the world. Radiomics is a computational tool to predict outcomes and may be used as a prognostic biomarker for advanced NPC treated with concurrent chemoradiotherapy. Recently, radiomic analysis of the peripheral tumor microenvironment (TME), which is the region surrounding the gross tumor volume (GTV), has shown prognostic usefulness. In this study, not only was gross tumor volume (GTVt) analyzed but also tumor peripheral regions (GTVp) were explored in terms of the TME concept. Both radiomic features and delta radiomic features were analyzed using CT images acquired in a routine radiotherapy process. METHODS: A total of 50 patients with NPC stages III, IVA, and IVB were enrolled between September 2004 and February 2014. Survival models were built using Cox regression with clinical factors (i.e., gender, age, overall stage, T stage, N stage, and treatment dose) and radiomic features. Radiomic features were extracted from GTVt and GTVp. GTVp was created surrounding GTVt for TME consideration. Furthermore, delta radiomics, which is the longitudinal change in quantitative radiomic features, was utilized for analysis. Finally, C-index values were computed using leave-one-out cross-validation (LOOCV) to evaluate the performances of all prognosis models. RESULTS: Models were built for three different clinical outcomes, including overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). The range of the C-index in clinical factor models was (0.622, 0.729). All radiomics models, including delta radiomics models, were in the range of (0.718, 0.872). Among delta radiomics models, GTVt and GTVp were in the range of (0.833, 0.872) and (0.799, 0.834), respectively. CONCLUSIONS: Radiomic analysis on the proximal region surrounding the gross tumor volume of advanced NPC patients for survival outcome evaluation was investigated, and preliminary positive results were obtained. Radiomic models and delta radiomic models demonstrated performance that was either superior to or comparable with that of conventional clinical models.

In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is a common sensorineural hearing impairment that lacks U.S. Food and Drug Administration-approved drugs. To fill the gap in effective screening models, we used an in silico transcriptome-based drug screening approach, identifying 22 biological pathways and 64 potential small molecule treatments for NIHL. Two of these, afatinib and zorifertinib [epidermal growth factor receptor (EGFR) inhibitors], showed efficacy in zebrafish and mouse models. Further tests with EGFR knockout mice and EGF-morpholino zebrafish confirmed their protective role against NIHL. Molecular studies in mice highlighted EGFR's crucial involvement in NIHL and the protective effect of zorifertinib. When given orally, zorifertinib was found in the perilymph with favorable pharmacokinetics. In addition, zorifertinib combined with AZD5438 (a cyclin-dependent kinase 2 inhibitor) synergistically prevented NIHL in zebrafish. Our results underscore the potential for in silico transcriptome-based drug screening in diseases lacking efficient models and suggest EGFR inhibitors as potential treatments for NIHL, meriting clinical trials.

Mediating role of physical activity in the relationship between psychological distress and intimate relationships among stroke patients.

BACKGROUND: Stroke patients often experience psychological distress, which can impact their intimate relationships with spouses, subsequently influencing their treatment and recovery. Physical activity is considered a key rehabilitation method for stroke patients. This paper aims to analyze whether psychological distress affects intimate relationship between spouses through physical activity. AIM: To explore the mediating effect of physical activity between psychological distress and intimate relationship in stroke patients. METHODS: A total of 256 stroke patients who underwent treatment at the First People's Hospital of Shangqiu between July 2021 and July 2022 were enrolled in this study. The participants completed questionnaires, including the Kessler Psychological Distress Scale (K10), the Quality of Relationship Index (QRI), International Physical Activity Questionnaire, and a general information questionnaire. Data analysis were performed using SPSS 23.0. The Harman test was employed to detect common method deviations, and Spearman correlation was used for correlation analysis. The mediating effect was assessed using Process 3.4.1, with significance testing of the regression coefficients conducted using the bias-corrected percentile Bootstrap method (5000 iterations, 95% confidence interval). Statistical significance was set at P < 0.05. RESULTS: The results showed that patients scored an average of 21.61 ± 6.44 points on the K10, 32.40 ± 6.19 points on the QRI; the median physical activity level according to the International Physical Activity Questionnaire was 1861 (566, 2846) MET·min/w. The level of physical activity (the physical activity intensity of the patients reflected by the International Physical Activity Questionnaire-Long Form scale) negatively correlated with psychological distress and intimacy (P < 0.05), and positively correlated with each other (P < 0.05), with the correlation stronger at lower physical activity levels compared to higher ones. The mediating effect of physical activity between psychological distress and intimate relationship was calculated to be 40.23%. Bootstrap analysis further validated the results. The mediating effect of psychological distress on intimate relationships through physical activity level was -0.284, with a confidence interval of -0.409 to -0.163, excluding 0, confirming a significant mediating effect of psychological distress on intimate relationships. CONCLUSION: Physical activity significantly affects relationship between psychological distress and intimate relationships among stroke patients. Addressing the role of physical activity may have implications for improving patient outcomes and rehabilitation strategies.