Impact of closed management on gastrointestinal function and mental health of Chinese university students during COVID-19.

BACKGROUND: The innovative closed management of universities may have influenced the physical and mental health of students during the fourth stage of the COVID-19 pandemic in China. The study aimed to assess the gastrointestinal and mental health status of students in this stage and to explore the possible risk factors and mechanisms to provide a reference for future school responses to similar stressful events. METHOD: A multicenter, cross-sectional survey was administered to 598 college students from 10 Chinese universities. The study used the 7-item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), Fear of COVID-19 Scale (FCV-19 S), and the Diagnostic Tendency of Functional Bowel Disease Scale (DT-FBD) to evaluate anxiety, depression, fear of COVID-19 and likelihood of being diagnose diagnosed with functional bowel disease (FBD), respectively. RESULTS: A total of 516 college students completed the questionnaire. The proportions of students with more severe anxiety, more severe depression, greater fear of COVID-19, and a greater likelihood of being diagnosed with FBD were 49.8%, 57.0%, 49%, and 49%, respectively. These symptoms were significantly and positively correlated with the frequency of irregular sleep and eating (p < 0.05). Students in high-risk areas were more likely to experience anxiety and depression than students in areas with low/medium risk (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.12-3.24, p = 0.017; OR = 2.14, 95% CI: 1.11-4.11, p = 0.022). A high likelihood of being diagnosed with FBD was positively associated with the severity of anxiety and depression symptoms and fear of COVID-19 (all p < 0.001). Moreover, mediation analysis revealed the following pathway in college students: fear of COVID-19 → depression and anxiety → poor diet → likelihood of being diagnosed with FBD. CONCLUSION: College students generally exhibited higher more severe anxiety and depression symptoms and psychological symptoms with a greater higher propensity likelihood of being to be diagnosed with FBD. Good lifestyle habits, especially adequate sleep and a regular diet, can alleviate these problems. In addition, appropriate psychological intervention is very important.

Design, Synthesis and Biological Evaluation of Novel Rapamycin Benzothiazole Hybrids as mTOR Targeted Anti-cancer Agents.

The immunosuppressant drug rapamycin, was firstly identified as a mammalian target of rapamycin (mTOR) allosteric inhibitor, and its derivatives have been successfully developed as anti-cancer drugs. Therefore, finding rapamycin derivatives with better anti-cancer activity has been proved to be an effective way to discover new targeted anti-cancer drugs. In this paper, structure modification was performed at the C-43 position of rapamycin using bioisosterism and a hybrid approach: a series of novel rapamycin-benzothiazole hybrids 4a-e, 5a-c, and 9a, b have been designed, synthesized and evaluated for their anti-cancer activity against Caski, CNE-2, SGC-7901, PC-3, SK-NEP-1 and A-375 human cancer cell lines. Some of these compounds (4a-e, 9a, b) displayed good to excellent potency against the Caski and SK-NEP-1 cell line as compared with rapamycin. Compound 9b as the most active compound showed IC50 values of 8.3 (Caski) and 9.6 µM (SK-NEP-1), respectively. In addition, research on the mechanism showed that 9b was able to cause G1 phase arrest and induce apoptosis in the Caski cell line. Most importantly, it significantly decreased the phosphorylation of S6 ribosomal protein, p70S6K1 and 4EBP1, which indicated that 9b inhibited the cancer cell growth by blocking the mTOR pathway and may have the potential to become a new mTOR inhibitor.

Synthesis of Rapamycin Derivatives Containing the Triazole Moiety Used as Potential mTOR-Targeted Anticancer Agents.

Rapamycin, a potent antifungal antibiotic, was approved as immunosuppressant, and lately its derivatives have been developed into mTOR targeting anticancer drugs. Structure modification was performed at the C-42 position of rapamycin, and a novel series of rapamycin triazole hybrids (4a-d, 5a-e, 8a-e, and 9a-e) was facilely synthesized via Huisgen's reaction. The anticancer activity of these compounds was evaluated against the Caski, H1299, MGC-803, and H460 human cancer cell lines. Some of the derivatives (8a-e, 9a-e) appeared to have stronger activity than that of rapamycin; however, 4a-d and 5a-e failed to show potential anticancer activity. Compound 9e with a (2,4-dichlorophenylamino)methyl moiety on the triazole ring was the most active anticancer compound, which showed IC50 values of 6.05 (Caski), 7.89 (H1299), 25.88 (MGC-803), and 8.60 µM (H460). In addition, research on the mechanism showed that 9e was able to cause cell morphological changes and to induce apoptosis in the Caski cell line. Most importantly, 9e can decrease the phosphorylation of mTOR and of its downstream key proteins, S6 and P70S6K1, indicating that 9e can effectively inhibit the mTOR signaling pathway. Thus, it may have the potential to become a new mTOR inhibitor against various cancers.

Causal association between metabolic syndrome and cholelithiasis: a Mendelian randomization study.

Background: Metabolic syndrome (MetS) has been associated with digestive system diseases, and recent observational studies have suggested an association between MetS and cholelithiasis. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect of MetS on cholelithiasis using Mendelian randomization (MR) analysis. Methods: Single nucleotide polymorphisms (SNPs) of MetS and its components were extracted from the public genetic variation summary database. The inverse variance weighting method (IVW), weighted median method, and MR-Egger regression were used to evaluate the causal relationship. A sensitivity analysis was performed to ensure the stability of the results. Results: IVW showed that MetS increased the risk of cholelithiasis (OR = 1.28, 95% CI = 1.13-1.46, P = 9.70E-05), and the weighted median method had the same result (OR = 1.49, 95% CI = 1.22-1.83, P = 5.68E-05). In exploring the causal relationship between MetS components and cholelithiasis, waist circumference (WC) was significantly associated with cholelithiasis. IVW analysis (OR = 1.48, 95% CI = 1.34-1.65, P = 1.15E-13), MR-Egger regression (OR = 1.62, 95% CI = 1.15-2.28, P = 0.007), and weighted median (OR = 1.73, 95% CI = 1.47-2.04, P = 1.62E-11) all found the same results. Conclusion: Our study indicated that MetS increases the incidence of cholelithiasis, especially in MetS patients with abdominal obesity. Control and treatment of MetS can effectively reduce the risk of gallstone formation.