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Background: There is an increase in the use of cigarettes and e-cigarettes worldwide, and the similar trends may be observed in young adults. Since 2014, e-cigarettes have become the most commonly used nicotine products among young adults (Sun et al., JAMA Netw Open 4:e2118788, 2021). With the increase in e-cigarette use and the decrease in use of cigarettes and other tobacco products, however, there is limited information about Chinese smokers, e-cigarettes users and trends in cigarettes and e-cigarettes use among university students. Therefore, our objective was to investigate the using status of cigarettes, e-cigarettes and smoking behavior among the students from 7 universities in Guangzhou, China. Methods: Students at 7 different universities in Guangzhou were investigated online in 2021 through a cross-sectional survey. A total of 10,008 students were recruited and after screening, 9361 participants were adopted in our statistics. Descriptive analysis, Chi-square analysis, and multiple logistic regression analysis were used to explore the smoking status and influencing factors. Results: The average age of the 9361 university students was 22.4 years (SD = 3.6). 58.3% of participants were male. 29.8% of the participants smoked or used e-cigarettes. Among the smokers and users of e-cigarettes, 16.7% were e-cigarettes only users, 35.0% were cigarettes only users, and 48.3% were dual users. Males were more likely to smoke or use e-cigarettes. Medical students, students from prestigious Chinese universities, and students with higher levels of education were less likely. Students with unhealthy lifestyles (e.g., drinking alcohol frequently, playing video games excessively, staying up late frequently) were more likely to smoke or use e-cigarettes. Emotion can have significant impacts on both cigarettes and e-cigarettes dual users when choosing cigarettes or e-cigarettes to use. More than half of dual users said they would choose cigarettes when they were depressed and e-cigarettes when they were happy. Conclusion: We identified factors influencing the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Gender, education level background, specialization, lifestyle habits and emotion all influenced the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Male, low education level, from non-prestigious Chinese universities or vocational schools, non-medical specialization, and presence of unhealthy lifestyles were influencing factors for the use of cigarettes and e-cigarettes among university students in Guangzhou and students with these factors were more likely to smoke or use e-cigarettes. Besides, emotions can influence dual users' choice of products. This study provides more information to better understand young people's preferences for cigarettes and e-cigarettes by elucidating the characteristics of cigarettes and e-cigarettes use, as well as related influencing factors, among university students in Guangzhou. Further research involving more variables connected to the use of cigarettes and e-cigarettes will be required in our future study. [ABSTRACT FROM AUTHOR]

Cysteine protease ATG4B, a key autophagy protein, is an attractive target for colorectal cancer therapy. However, ATG4B inhibitors with higher efficiency, safety, and clear mechanism are still limited. In this study, we discovered ATG4B inhibitors based on the FDA-approved drug library through FRET-based high-throughput screening and gel-based analysis. Among the nine hits, compound Ebselen showed the most potent ATG4B inhibitory activity (IC50 = 189 nM) and exhibited controllable selectivity and structural optimizable possibility against ATG4A and caspases. We then performed mass spectrometry assay and cysteine mutations to confirm that Ebselen could covalently bind to ATG4B at Cys74. Moreover, Cys292 and Cys361 instead of Cys74 are responsible for the redox-oligomerization and efficient activity inhibition of ATG4B. Ultimately through cell culture and mouse xenograft tumor models, we established the impact of Ebselen on autophagy and tumor suppression via ATG4B inhibition other than apoptosis. These results suggest that old drug Ebselen as an ATG4B inhibitor through oxidative modification may be repurposed as a promising anti-colorectal cancer drug. Highlights: High-throughput screening of ATG4B inhibitors based on FDA-approved drug library Ebselen can covalently bind to ATG4B at Cys74 Ebselen can promote ATG4B oligomerization at Cys292 and Cys361 Ebselen suppresses the growth of colorectal cancer cells and xenograft tumors via ATG4B inhibition [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein encoded from extra tracts of CAG repeats in exon 1 of the HTT gene. mHTT proteins are neurotoxic to render the death of neurons and a series of disease-associated phenotypes. The mHTT is degraded through autophagy pathway and ubiquitin–proteasome system (UPS). This study identified a small molecule, J3, as an autophagy inducer by high-content screening. The results revealed that J3 could inhibit mTOR, thus promoting autophagic flux and long-lived protein degradation. Further, J3 selectively lowered the soluble and insoluble mHTT but not wild type HTT levels in cell models. The HdhQ140 mice showed reduced HD-associated activity and loss of motor functions. However, administration of J3 showed increased activity and a slight improvement in the motor function in the open-field test, balance beam test, and rotarod tests. Furthermore, in vivo studies revealed that J3 decreased T-HTT and misfolded protein levels in the striatum and increased the levels of the medium spiny neuron marker DARPP-32. In addition, J3 showed good permeability across the brain-blood barrier efficiently, suggesting that J3 was a promising candidate for the treatment of HD. [ABSTRACT FROM AUTHOR]