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We have studied the effect of the absence of carotenoids on the organization of bacteriochlorophylls (BChls) in chlorosomes of Chlorobium (Chl.) phaeobacteroides strain CL1401. Carotenoid-depleted chlorosomes were obtained by means of 2-hydroxybiphenyl–supplemented cultures. In the presence of the inhibitor, isorenieratene (Isr) and β-Isr biosynthesis were inhibited to more than 95%, leading to an accumulation of the colorless precursor phytoene inside the chlorosomes. In addition, there was a 30–40% decrease in the baseplate BChl a content. The absorption spectrum of the carotenoid-depleted chlorosomes showed a 10 nm blue shift in the BChl e Qy absorption peak. Under reducing conditions, a decrease in the BChl a/BChl e fluorescence emission ratio was observed in carotenoid-depleted chlorosomes relative to that in control chlorosomes, caused mainly by the decrease in the BChl a content. The steady-state fluorescence emission anisotropy in the BChl e region dropped from ;0.24 for native chlorosomes to ;0.14 for carotenoid-depleted ones, indicating reorganization of BChl e. The circular dichroism (CD) signal of the carotenoid-depleted chlorosomes was increased two times in the BChl e Qy region. A simple model based on the structure proposed was used to explain the observed effects. Carotenoids might affect the angle between the direction of the BChl e Qy transition and the axis of the rod. The orientation of BChl a in the baseplate remains unchanged in carotenoid-depleted chlorosomes, although there is a partial loss of BChl a as a consequence of a decrease in the baseplate size. The carotenoids are most likely rather close to the BChls and appear to be important for the aggregate structure in Chl. phaeobacteroides. ; European Union (Contract FMRX-CT96-0081). Spanish Ministry of Education and Science (Ref. BIO96-1229-002-01). ; Peer reviewed

Jiuling Deng,1,* Ying Ma,2,* Yuqiong He,1,* Hong Yang,2 Yanhong Chen,2 Liang Wang,1 Doudou Huang,1 Shi Qiu,1,* Xia Tao,2 Wansheng Chen1 1Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of China*These authors contributed equally to this workCorrespondence: Wansheng ChenInstitute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of ChinaTel +64 021 81886182Email chenwansheng@shutcm.edu.cnXia TaoDepartment of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People's Republic of ChinaTel +64 021 81886182Email taoxia2003@126.comPurpose: Isatis indigotica (Ii) is a cruciferous herb that is widely distributed in China, and its roots and leaves have been used in two renowned antipyretic detoxicate crude drugs in Chinese Pharmacopoeia, Radix (R) and Folium (F) Isatidis. However, the pharmacodynamic material basis and underlying mechanisms of the herbal efficacy remained to be elucidated.Methods: Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was adopted for the chemical profiling of R and F Isatidis. The active ingredients were screened out through the prediction of gastrointestinal absorption and druglikeness analysis using SwissADME. A herb-ingredient-target network was constructed through target prediction of the herbal active ingredients and anti-inflammation or anti-viral properties, followed by protein–protein interaction analysis. Then, the potential relevant signaling pathways were predicted by pathway enrichment. Finally, for verification, RAW 264.7 cell line was adopted to examine the anti-inflammatory and anti-viral activities of 6 representative ingredients in Ii.Results: Seventy-three compounds have been identified from Ii through UPLC-Q-TOF-MS. A total of 17 potential active ingredients were screened through pharmacokinetics and drug-likeness evaluation using SwissADME. It was shown that key targets might include TNF, AKT1, SRC, IL2, CASP9, and CASP3 in our herb-ingredient-target network, and isovitexin, a flavonoid, tended to participate in the inflammatory response, indoles were more likely to affect the cell proliferation processes, and lignans might have a broader affinity to key targets than the other active ingredients, such as regulating immune system (targeting IL-2) and PI3K-Akt signaling pathway. In vitro, indigo and secoisolariciresinol diglucoside markedly reduced TNF-α expression in Poly (I: C)-incubated cells. Isovitexin significantly inhibited TNF-α expression, and isatin treatment markedly reduced IL-1β expression in LPS-incubated cells.Conclusion: As the pharmacodynamics material basis of Ii, indoles, lignans, and flavonoids are believed to confer beneficial properties through various cellular aspects with multiple signaling pathways involved.Keywords: Isatis indigotica, UPLC-Q-TOF-MS, network analysis, bioassay analysis

© 2020 The Authors. Published by American Medical Association. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher's website: 10.1001/jamanetworkopen.2020.6863 ; Importance: Both nonsuicidal self-injury (NSSI), defined as the direct, deliberate damage of one's body tissue without suicidal intent, and internet addiction among adolescents are public health concerns. However, the possible association of NSSI with internet addiction is not well understood. Objective: To examine the occurrence of internet addiction with NSSI and any sex differences among Chinese adolescents. Design, Setting, and Participants: A multicenter, cross-sectional, survey study was conducted from February 18 to October 15, 2015, among adolescents aged 11 to 20 years from 343 classes in 45 public high schools across 5 provinces of China. Data analysis was performed from August 1, 2018, to March 1, 2019. Exposures: Possible internet addiction and internet addiction. Main Outcomes and Measures: Less-frequent (1-4 times) NSSI and more-frequent (≥5 times) NSSI were surveyed using the Chinese version of the Functional Assessment of Self-Mutilation. Results: A total of 15 623 students (8043 male [51.5%] and 7580 female [48.5%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) participated. Of these, 4670 participants (29.9%) met the criteria for possible internet addiction and 509 participants (3.3%) met the criteria for internet addiction. A total of 2667 students (17.1%) engaged in less-frequent NSSI, while 1798 students (11.5%) engaged in more-frequent NSSI in the 12 months preceding the survey. Both possible internet addiction and internet addiction were associated with less-frequent or more-frequent NSSI. The adjusted odds ratios were 1.29 (95% CI, 1.17-1.42) for possible internet addiction and 1.41 (95% CI, 1.11-1.80) for internet addiction for less-frequent NSSI; for more-frequent NSSI, the adjusted odds ratios were 1.75 (95% CI, 1.56-1.96) for possible internet addiction and 2.66 (95% CI, 2.10-3.38) for internet addiction. These associations were similarly observed among age groups of 11 to 14, 15 to 17, and 18 to 20 years. No sex disparities were found in the associations of internet addiction with NSSI, except among adolescents aged 11 to 14 years, where the odds ratios for possible internet addiction with less-frequent NSSI were higher in male adolescents (1.53; 95% CI, 1.25-1.88) than female adolescents (1.13; 95% CI, 0.90-1.47). Conclusion and Relevance: Internet addiction appears to be associated with NSSI, and the findings of this study suggest that the association was similar between male adolescents and female adolescents. These data suggest that evaluation of the risk of NSSI for adolescents in association with internet addiction may help health care professionals in developing preventive interventions for NSSI. ; This study was supported by grants from National Natural Science Foundation of China (81773457, 81302445 [Dr Tang], and 81373022 [Dr Yu]), and a European Union grant from Horizon 2020 MSCA (DEMAIRPO 799247 [Drs Tang and Chen]). ; Published version