Organocatalytic skeletal reorganization for enantioselective synthesis of S-stereogenic sulfinamides.

The enantioselective synthesis of S-stereogenic sulfinamides has garnered considerable attention due to their structural and physicochemical properties. However, catalytic asymmetric synthesis of sulfinamides still remains daunting challenges, impeding their broad application in drug discovery and development. Here, we present an approach for the synthesis of S-stereogenic sulfinamides through peptide-mimic phosphonium salt-catalyzed asymmetric skeletal reorganization of simple prochiral and/or racemic sulfoximines. This methodology allows for the facile access to a diverse array of substituted sulfinamides with excellent enantioselectivities, accommodating various substituent patterns through desymmetrization or parallel kinetic resolution process. Mechanistic experiments, coupled with density functional theory calculations, clarify a stepwise pathway involving ring-opening and ring-closing processes, with the ring-opening step identified as crucial for achieving stereoselective control. Given the prevalence of S-stereogenic centers in pharmaceuticals, we anticipate that this protocol will enhance the efficient and precise synthesis of relevant chiral molecules and their analogs, thereby contributing to advancements in drug discovery.

A redox-responsive nanosystem to suppress chemoresistant lung cancer through targeting STAT3.

Cancer stem cells (CSCs) have been demonstrated to be involved in tumor initiation and relapse, and the presence of CSCs in the tumor tissue often leads to therapeutic failure. BBI608 has been identified to eliminate CSCs by inhibiting signal transducer and activator of transcription 3 (STAT3). In this study, we confirm that BBI608 can efficiently suppress the proliferation and migration of non-small cell lung cancer (NSCLC) cells, and specifically kill the stemness-high population in chemoresistant NSCLC cells. To improve its bioavailability and tumor accumulation, BBI608 is successfully encapsulated into redox-responsive PEGylated branched N-(2-hydroxypropyl) methacrylamide (HPMA)-deoxy cholic acid (DA) polymeric nanoparticles (BBI608-SS-NPs). The BBI608-SS-NPs can release the drug in response to high concentrations of intracellular glutathione, and exhibit cytotoxicity against lung cancer cells and CSCs comparable to the free drug BBI608. Furthermore, the BBI608-SS-NPs preferentially accumulate in tumor sites, resulting in a superior anti-tumor efficacy in both cisplatin-resistant cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of NSCLC. Mechanistic studies demonstrate that BBI608-SS-NPs not only directly inhibit the downstream genes of the STAT3 pathway, but also indirectly inhibit the Wnt pathway. Overall, this stimuli-responsive polymeric nanoformulation of BBI608 shows great potential in the treatment of chemoresistant NSCLC by targeting CSCs.

Engineered extracellular vesicles-like biomimetic nanoparticles as an emerging platform for targeted cancer therapy.

Nanotechnology offers the possibility of revolutionizing cancer theranostics in the new era of precision oncology. Extracellular vesicles (EVs)-like biomimetic nanoparticles (EBPs) have recently emerged as a promising platform for targeted cancer drug delivery. Compared with conventional synthetic vehicles, EBPs have several advantages, such as lower immunogenicity, longer circulation time, and better targeting capability. Studies on EBPs as cancer therapeutics are rapidly progressing from in vitro experiments to in vivo animal models and early-stage clinical trials. Here, we describe engineering strategies to further improve EBPs as effective anticancer drug carriers, including genetic manipulation of original cells, fusion with synthetic nanomaterials, and direct modification of EVs. These engineering approaches can improve the anticancer performance of EBPs, especially in terms of tumor targeting effectiveness, stealth property, drug loading capacity, and integration with other therapeutic modalities. Finally, the current obstacles and future perspectives of engineered EBPs as the next-generation delivery platform for anticancer drugs are discussed.

Hope Levels and Resilience in Patients with Severe Novel Coronavirus Pneumonia: The Current Situation and a Correlation Analysis.

OBJECTIVE: The study aims to analyze the correlation between hope levels and resilience in patients with severe novel coronavirus pneumonia (COVID-19). METHODS: Fifty-six patients with severe COVID-19 were investigated, with the use of a general information questionnaire, the Herth Hope Index, and the Connor-Davidson resilience scale. RESULTS: There was a significant difference in patients' hope levels with respect to marital status and educational background (P < 0.05), and there was a significant difference in resilience scores depending on gender and family economic situation (P < 0.05). In the present study, the hope levels and resilience in the patients were moderate, with an average score of (34.93 ± 5.45) and (69.36 ± 15.52), respectively. There was a significant positive correlation between the hope level and the resilience score in these patients (P < 0.05). CONCLUSION: In patients with severe COVID-19, the higher the hope level, the higher the resilience score.

The Effect of Action Research on Neobladder Function Training in Patients with Orthotopic Ileal Neobladders: A Prospective Cohort Study.

PURPOSE: This study aims to evaluate the effects of action research on neobladder function training in patients with orthotopic ileal neobladders. METHODS: A total of 68 patients with orthotopic ileal neobladders were randomly divided into two groups: a control group (31 patients) and an experimental group (37 patients). Patients in the control group received neobladder function training, while patients in the experimental group received neobladder function training based on the action research method. The effects of neobladder function training in all patients were evaluated after three months. RESULTS: (1) The differences between the two groups in micturition time interval, urine volume per time, number of incidences of nocturia, and urinary continence rate (day time and night time) were statistically significant (P < 0.05). (2) Compared to the control group (241.6 ± 42.3 mL, 15.1 ± 4.9 mL/s, 23.1 ± 9.9 cmH2O, 63.6 ± 22.3 mL), the bladder capacity (292.6 ± 66.9 mL), maximum urinary flow rate (19.2 ± 6.5 mL/s), and bladder detrusor pressure (31.2 ± 11.4 cmH2O) of the experimental group increased, while the residual urine volume (47.2 ± 21.1 mL) decreased (P < 0.05). CONCLUSION: Neobladder function training based on the action research method can improve the neobladder function of patients with orthotopic ileal neobladders.

Effects of progressive muscle relaxation training on negative emotions and sleep quality in COVID-19 patients: A clinical observational study.

This study investigates the effect of progressive muscle relaxation training on negative mood and sleep quality in Coronavirus Pneumonia (COVID-19) patients.COVID-19 is an emerging infectious disease, and there is still uncertainty about when the outbreak will be contained and the effectiveness of treatments. Considering that this disease is highly contagious, patients need to be treated in isolation. This may lead to psychological symptoms such as anxiety and depression, and even sleep problems.This study is a clinical observation study.Participants included 79 COVID-19 patients admitted to a designated hospital for COVID-19 patients in Wuhan from February to March, 2020. Patients were selected and assigned to the control group and the observation group according to their wishes, with 40 and 39 cases in each group, respectively. The control group received routine treatment and nursing, and the observation group received progressive muscle relaxation training, in addition to the routine treatment and nursing. We compared scores of the Pittsburgh Sleep Quality Index Scale (PSQI), the Generalized Anxiety Disorder (GAD-7), and the Patient Health Questionnaire (PHQ-9) before and after the intervention.There was no significant difference in PSQI, GAD-7, and PHQ-9 scores between the control group and the observation group before the intervention (P > .05). After the intervention, the difference in scores of PSQI, GAD-7, and PHQ-9 in the 2 groups were statistically significant (P < .05).Progressive muscle relaxation training can significantly reduce anxiety and depression and improve sleep quality in COVID-19 patients during isolation treatment.Progressive muscle relaxation training was shown to improve the treatment effect of patients and is worthy of clinical promotion.