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The unmet clinical needs of patients with rare diseases persist. Many rare diseases lack effective treatments, and drug development for rare diseases faces greater challenges than that for common multiple diseases. In recent years, the concept of " patient-centered" drug development has been widely adopted. The Center for Drug Evaluation(CDE) of the National Medical Products Administration has successively issued a series of relevant guiding principles, such as the Technical Guidelines for the Implementation of Patient-Centered Clinical Trials, to promote a " patient-centered" drug development model. The implementation of the " patient-centered" approach in rare disease drug research and development, with a focus on patient perspectives and active engagement, can effectively facilitate a comprehensive understanding of rare diseases and patient needs among drug research and development enterprises, researchers, and regulatory agencies. This approach also enhances the accuracy and efficiency of rare disease drug research and development. The CDE will continue to prioritize the integration of the " patient-centered" concept into rare disease drug research and development, effectively enhance the involvement of rare patients in the drug research and development process, and leverage the guiding role of patients′ perspectives on drug research and development.

Clinical trials of drugs for rare diseases face special challenges such as a limited number of patients, difficult recruitment, long trial period, and frequent video interviews during the trial. Therefore, in the clinical operation of rare diseases, a decentralized clinical trials (DCT) model based on the " patient-centred" research and development concept is implemented. With the help of decentralized elements and digital health technology, the barriers of geographical restrictions can be overcome and subjects do not have to be limited to traditional clinical trial sites (hospitals/research centers), which can significantly reduce the burden on subjects, increase their representation, and obtain a wider range of scientific research data. To guide the industry′s scientific and standardized application of DCT in the research and development of drugs for rare diseases, the Center for Drug Evaluation of the National Medical Products Administration (NMPA) organized the stake holders to draft the Technical Guideline for the Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases. This guideline provides scientific recommendations for the development and implementation of DCT for rare disease drugs. It aims to solve the difficult and key problems during rare disease drug research and development, improve the efficiency and optimize patient experience. This article, combining the research and development concepts in the guideline, explains the current research and development thinking on the application of DCT in the research and development of rare disease drugs, with a view of providing reference for the industry.

Zinc (Zn) is an essential mineral element for plant growth and development. Zn deficiency in crops frequently occurs in many types of soils. It is therefore crucial to identify genetic resources linking Zn acquisition traits and development of crops with improved Zn-use efficiency for sustainable crop production. In this study, we functionally identified a rice uncharacterized ABCG (ATP-binding cassette G-subfamily) gene encoding a PDR20 (pleiotropic drug resistance 20) metal transporter for mediation of rice growth, seed development and Zn accumulation. OsPDR20 was localized to the plasma membrane, but it was not transcriptionally induced under Zn deficiency, rather was sufficiently up-regulated under high level of Zn stress. Yeast (Saccharomyces cerevisiae) transformed with OsPDR20 displayed a relatively lower Zn accumulation with attenuated cellular growth, suggesting that OsPDR20 had an activity for Zn transport. Knocking-down OsPDR20 by RNA interference (RNAi) compromised rice growth with shorter plant height and decreased biomass in rice plantlets grown under hydroponic media. Zn concentration in the roots of OsPDR20 knocked-down rice lines declined under Zn deficiency, while they remained unchanged compared with the wild type under normal Zn supply. A rice lifelong field trial demonstrated that OsPDR20 mutation impaired the capacity of seed development, with shortened panicle and seed length, compromised spikelet fertility, and reduced grain number per plant or grain weight per unit area. Interestingly, OsPDR20 mutation elevated the accumulation of Zn in husk and brown rice over the wild type. Overall, this study pointed out that OsPDR20 is fundamentally required for rice growth and seed development through Zn transport and homeostasis.

Emerging multidrug resistance (MDR) in Clarireedia spp. is a huge challenge to the management of dollar spot (DS) disease on turfgrass. Insight into the molecular basis of resistance mechanisms may help identify key molecular targets for developing novel effective chemicals. Previously, a MDR isolate (LT586) of C. jacksonii with significantly reduced sensitivities to propiconazole, boscalid, and iprodione, and a fungicide-sensitive isolate (LT15) of the same species were isolated from creeping bentgrass (Agrostis stolonifera L.). The present study aimed to further explore the molecular mechanisms of resistance by using genome-wide transcriptional analyses of the two isolates. A total of 619 and 475 differentially expressed genes (DEGs) were significantly down and upregulated in the MDR isolate LT586, compared with the sensitive isolate LT15 without fungicide treatment. Three hundreds and six and 153 DEGs showed significantly lower and higher expression in the MDR isolate LT586 than those in the sensitive isolate LT15, which were commonly induced by the three fungicides. Most of the 153 upregulated DEGs were xenobiotic detoxification-related genes and genes with transcriptional functions. Fifty and 17 upregulated DEGs were also commonly observed in HRI11 (a MDR isolate of the C. jacksonii) compared with the HRS10 (a fungicide-sensitive isolate of same species) from a previous study without and with the treatment of propiconazole, respectively. The reliability of RNA-seq data was further verified by qRT-PCR method using a few select potentially MDR-related genes. Results of this study indicated that there were multiple uncharacterized genes, possibly responsible for MDR phenotypes in Clarireedia spp., which may have important implications in understanding the molecular mechanisms underlying MDR resistance.