Construction and characterization of a humanized SLCO1B1 rat model with its application in evaluating the uptake of different statins

Organic anion-transporting polypeptides IB1(OATPIB1)plays a crucial role in the transport of statins.However,there are too few animal models related to OATPIB1,especially humanized animal models.In this study,the human SLCOIB1 cDNA was inserted into the second exon of the rat Slcolb2 gene using CRISPR/Cas9 technology.Pharmacokinetic characteristics of statins were conducted in wild-type(WT),humanized OATPIB1(hOATPIB1),and OATPIB2 knockout(OATPIB2 KO)rats,respec-tively.The results showed that human OATPIB1 was successfully expressed in rat liver and exhibited transport function.Furthermore,the pharmacokinetic results revealed that OATPIB1 exhibited varying uptake levels of pivastatin,rosuvastatin,and fluvastatin,leading to different levels of exposure within the body.These results were consistent with those obtained from in vitro experiments using overexpressed cell lines.In conclusion,we established a novel humanized SLCOIBI transgenic rat model to assess the role of human OATPIB1 in the uptake of different statins.The different uptake mediated by OATPIB1 may be an important reason for the different efficacy of statins.The hOATPIB1 rat is a promising model for improving the prediction of human drug transport.

Transcription factor OsWRKY11 induces rice heading at low concentrations but inhibits rice heading at high concentrations

The heading date of rice is a crucial agronomic characteristic that influences its adaptability to different regions and its productivity potential.Despite the involvement of WRKY transcription factors in various biological processes related to development,the precise mechanisms through which these transcription factors regulate the heading date in rice have not been well elucidated.The present study identified OsWRKY11 as a WRKY transcription factor which exhibits a pivotal function in the regulation of the heading date in rice through a comprehensive screening of a clustered regularly interspaced palindromic repeats(CRISPR)-CRISPR-associated nuclease 9 mutant library that specifically targets the WRKY genes in rice.The heading date of oswrky11 mutant plants and OsWRKY11-overexpressing plants was delayed compared with that of the wild-type plants under short-day and long-day conditions.Mechanistic investigation revealed that OsWRKY11 exerts dual effects on transcriptional promotion and suppression through direct and indirect DNA binding,respectively.Under normal conditions,OsWRKY11 facilitates flowering by directly inducing the expression of OsMADS14 and OsMADS15.The presence of elevated levels of OsWRKY11 protein promote formation of a ternary protein complex involving OsWRKY11,Heading date 1(Hd1),and Days to heading date 8(DTH8),and this complex then suppresses the expression of Ehd1,which leads to a delay in the heading date.Subsequent investigation revealed that a mild drought condition resulted in a modest increase in OsWRKY11 expression,promoting heading.Conversely,under severe drought conditions,a significant upregulation of OsWRKY11 led to the suppression of Ehd1 expression,ultimately causing a delay in heading date.Our findings uncover a previously unacknowledged mechanism through which the transcription factor OsWRKY11 exerts a dual impact on the heading date by directly and indirectly binding to the promoters of target genes.

抗污染薄层复合聚酰胺膜的结构设计及改性策略

由活性层和支撑层组成的薄层复合(TFC)聚酰胺(PA)膜,是目前广泛应用于纳滤、反渗透、正渗透和压力延迟渗透过程中的高性能脱盐膜,具有水通量大和截盐率高等优异性能。然而,由于TFC-PA膜存在活性层疏水性强、支撑层孔径大等特点,致使TFC-PA膜在实际使用过程中极易受到膜污染,制约了TFC-PA膜的进一步推广和使用。本文讨论分析了TFC-PA膜的结构特点和表面性质,总结归纳了在不同膜过程中TFC-PA膜污染形成的原因及特点,详细论述了国内外抗污染TFC-PA膜的研究进展。本文重点介绍了活性层抗污染改性和支撑层抗污染改性方法,并对其抗污染机理以及存在的问题进行了阐述与分析,最后对抗污染TFC-PA膜的结构设计与表面改性策略进行了总结及展望。