Different viral effectors hijack TCP17, a key transcription factor for host Auxin synthesis, to promote viral infection.

Auxin is an important class of plant hormones that play an important role in plant growth development, biotic stress response, and viruses often suppress host plant auxin levels to promote infection. However, previous research on auxin-mediated disease resistance has focused mainly on signaling pathway, and the molecular mechanisms of how pathogenic proteins manipulate the biosynthetic pathway of auxin remain poorly understood. TCP is a class of plant-specific transcription factors, of which TCP17 is a member that binds to the promoter of YUCCAs, a key rate-limiting enzyme for auxin synthesis, and promotes the expression of YUCCAs, which is involved in auxin synthesis in plants. In this study, we reported that Tomato spotted wilt virus (TSWV) infection suppressed the expression of YUCCAs through its interaction with TCP17. Further studies revealed that the NSs protein encoded by TSWV disrupts the dimerization of TCP17, thereby inhibit its transcriptional activation ability and reducing the auxin content in plants. Consequently, this interference inhibits the auxin response signal and promotes the TSWV infection. Transgenic plants overexpressing TCP17 exhibit resistance against TSWV infection, whereas plants knocking out TCP17 were more susceptible to TSWV infection. Additionally, proteins encoded by other RNA viruses (BSMV, RSV and TBSV) can also interact with TCP17 and interfere with its dimerization. Notably, overexpression of TCP17 enhanced resistance against BSMV. This suggests that TCP17 plays a crucial role in plant defense against different types of plant viruses that use viral proteins to target this key component of auxin synthesis and promote infection.

Cost-effectiveness analysis of fluticasone furoate/umeclidinium bromide/vilanterol and umeclidinium bromide/vilanterol in the management of moderate and severe COPD in China.

OBJECTIVE: A study has analyzed the long-term cost-effectiveness of fluticasone furoate/umeclidinium bromide/vilanterol combination therapy (FF/UMEC/VI) versus umeclidinium bromide/vilanterol dual therapy (UMEC/VI) in the treatment of moderate or severe chronic obstructive pulmonary disease (COPD), providing evidence for decision-making in COPD treatment. METHODS: From the perspective of the whole society, a Markov model based on the severity of COPD was established, consisting of four states: moderate, severe, very severe, and death. The cycle of the model is three months, and the time frame of the study is 20 years. Data such as initial states, transition probabilities, costs, and utilities were collected from published literature, the National Institute for Health and Care Excellence (NICE) COPD economic report, Yaozh database, and the National Statistics Office. The discount rate is 5 %, and the willingness to pay threshold is set at three times the per capita GDP of China in 2022. TreeAge Pro 2011 was used to obtain the results of multiplication analyses, and one-way factor analysis and probability sensitivity analysis were conducted. RESULTS: The study findings demonstrate that for patients treated with FF/UMEC/VI and UMEC/VI, the 20-year treatment costs amount to $10,126.46 and $10,685.74, respectively. Similarly, the effectiveness is 32.94 quality-adjusted life years (QALYs) and 32.19 QALYs, respectively. The incremental cost-effectiveness ratio is $-745.70/QALY, which is lower than the willingness to pay threshold. The tornado plot from one-way factor analysis indicates that the first two factors impacting the results are the utility values for severe COPD of UMEC/VI and FF/UMEC/VI. Probability sensitivity analysis indicates that FF/UMEC/VI compared to UMEC/VI can be considered a more cost-effective treatment at the willingness to pay threshold of $35,806.96. CONCLUSION: The triple therapy (FF/UMEC/VI) is more affordable than dual therapy (UMEC/VI) when compared to China's three times GDP per capita criterion.