Although both protein arginine methylation(PRMT)and jasmonate(JA)signaling are crucial for regulating plant development,the relationship between these processes in the control of spikelet development remains unclear.I...Although both protein arginine methylation(PRMT)and jasmonate(JA)signaling are crucial for regulating plant development,the relationship between these processes in the control of spikelet development remains unclear.In this study,we used the CRISPR/Cas9 technology to generate two OsPRMT6a loss-of-function mutants that exhibit various abnormal spikelet structures.Interestingly,we found that OsPRMT6a can methylate arginine residues in JA signal repressors OsJAZ1 and OsJAZ7.We showed that arginine methylation of OsJAZ1 enhances the binding affinity of OsJAZ1 with the JA receptors OsCOI1a and OsCOI1b in the presence of JAs,thereby promoting the ubiquitination of OsJAZ1 by the SCF^(OsCOI1a/OsCOI1b) complex and degradation via the 26S proteasome.This process ultimately releases OsMYC2,a core transcriptional regulator in the JA signaling pathway,to activate or repress JA-responsive genes,thereby maintaining normal plant(spikelet)development.However,in the osprmt6a-1 mutant,reduced arginine methylation of OsJAZ1 impaires the interaction between OsJAZ1 and OsCOI1a/OsCOI1b in the presence of JAs.As a result,OsJAZ1 proteins become more stable,repressing JA responses,thus causing the formation of abnormal spikelet structures.Moreover,we discovered that JA signaling reduces the OsPRMT6a mRNA level in an OsMYC2-dependent manner,thereby establishing a negative feedback loop to balance JA signaling.We further found that OsPRMT6a-mediated arginine methylation of OsJAZ1 likely serves as a switch to tune JA signaling to maintain normal spikelet development under harsh environmental conditions such as high temperatures.Collectively,our study establishes a direct molecular link between arginine methylation and JA signaling in rice.展开更多
Inspired by the success of CH-series acceptors, a small-molecular acceptor, CH-Tz was reported by adopting a new conjugationextended electron-deficient unit([1,2,5]thiadiazolo[3,4-b]pyrazine) on the central core. Owin...Inspired by the success of CH-series acceptors, a small-molecular acceptor, CH-Tz was reported by adopting a new conjugationextended electron-deficient unit([1,2,5]thiadiazolo[3,4-b]pyrazine) on the central core. Owing to the enhanced inter-/intramolecular interactions, CH-Tz exhibited near-infrared absorption and an effective three-dimensional molecular packing network in its single crystal. When blended with polymer donor PM6, the binary device achieved a high power conversion efficiency(PCE) of 18.54%, with a notable short-circuit current density(J_(sc)) of 27.54 m A cm-2and an excellent fill factor(FF) over 80%,which can be partly ascribed to the balanced charge transport properties in the blend film. After employing D18-Cl as the third component, an enhanced PCE of 18.85% was achieved due to a more obvious fiber network. Impressively, the CH-Tz-based OSC devices show excellent thermal stability and thickness insensitivity. Record-breaking Jscof 28.92 m A cm-2was reached for PM6:D18-Cl:CH-Tz ternary device with a thickness of 560 nm. Besides, CH-Tz shows potential in fabricating multicomponent high-performance organic solar cells, where over 19% efficiency could be realized in the quaternary device. Our work advances the strong influence of electron-deficient central units on molecular photovoltaic properties and guides the design of acceptors for stable and large-thickness organic solar cells.展开更多
Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 ...Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells,the weights of the two arms contributing to apoptosis inhibition have not been explored.This study analyzed the best combination ratio for different Bcl-2 selective inhibitors.Methods:We used a previously established mathematical model to study the weights of Bcl-2(representing both Bcl-2 and BcI-xL in this study)and myeloid cell leukemia-1(Mcl-1).Correlation and single-parameter sensitivity analysis were used to find the major molecular determinants for Bcl-2 and Mcl-1 dependency,as well as their weights.Biological experiments were used to verify the mathematical model.Results:Bcl-2 protein level and Mcl-1 protein level,production,and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency.The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231.Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1,respectively.Conclusions:The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment.展开更多
基金We thank Prof.Qiang Cai(College of Life Sciences,Wuhan University)and Prof.Zheng Yuan(School of Life Sciences and Biotechnology,Shanghai Jiao Tong University)for providing morphology data for the eg1-1 and eg2-1D mutants.This work was supported by grants from the National Key R&D Program of China(2022YFD1200100)STI2030-Major Projects(2023ZD0406802)the National Natural Science Foundation of China(no.92035301 and no.31771765).
文摘Although both protein arginine methylation(PRMT)and jasmonate(JA)signaling are crucial for regulating plant development,the relationship between these processes in the control of spikelet development remains unclear.In this study,we used the CRISPR/Cas9 technology to generate two OsPRMT6a loss-of-function mutants that exhibit various abnormal spikelet structures.Interestingly,we found that OsPRMT6a can methylate arginine residues in JA signal repressors OsJAZ1 and OsJAZ7.We showed that arginine methylation of OsJAZ1 enhances the binding affinity of OsJAZ1 with the JA receptors OsCOI1a and OsCOI1b in the presence of JAs,thereby promoting the ubiquitination of OsJAZ1 by the SCF^(OsCOI1a/OsCOI1b) complex and degradation via the 26S proteasome.This process ultimately releases OsMYC2,a core transcriptional regulator in the JA signaling pathway,to activate or repress JA-responsive genes,thereby maintaining normal plant(spikelet)development.However,in the osprmt6a-1 mutant,reduced arginine methylation of OsJAZ1 impaires the interaction between OsJAZ1 and OsCOI1a/OsCOI1b in the presence of JAs.As a result,OsJAZ1 proteins become more stable,repressing JA responses,thus causing the formation of abnormal spikelet structures.Moreover,we discovered that JA signaling reduces the OsPRMT6a mRNA level in an OsMYC2-dependent manner,thereby establishing a negative feedback loop to balance JA signaling.We further found that OsPRMT6a-mediated arginine methylation of OsJAZ1 likely serves as a switch to tune JA signaling to maintain normal spikelet development under harsh environmental conditions such as high temperatures.Collectively,our study establishes a direct molecular link between arginine methylation and JA signaling in rice.
基金supported by the Ministry of Science and Technology of China (2022YFB4200400, 2019YFA0705900,2023YFE0210400)the National Natural Science Foundation of China(21935007, 52025033, 52303237, 22361132530)。
文摘Inspired by the success of CH-series acceptors, a small-molecular acceptor, CH-Tz was reported by adopting a new conjugationextended electron-deficient unit([1,2,5]thiadiazolo[3,4-b]pyrazine) on the central core. Owing to the enhanced inter-/intramolecular interactions, CH-Tz exhibited near-infrared absorption and an effective three-dimensional molecular packing network in its single crystal. When blended with polymer donor PM6, the binary device achieved a high power conversion efficiency(PCE) of 18.54%, with a notable short-circuit current density(J_(sc)) of 27.54 m A cm-2and an excellent fill factor(FF) over 80%,which can be partly ascribed to the balanced charge transport properties in the blend film. After employing D18-Cl as the third component, an enhanced PCE of 18.85% was achieved due to a more obvious fiber network. Impressively, the CH-Tz-based OSC devices show excellent thermal stability and thickness insensitivity. Record-breaking Jscof 28.92 m A cm-2was reached for PM6:D18-Cl:CH-Tz ternary device with a thickness of 560 nm. Besides, CH-Tz shows potential in fabricating multicomponent high-performance organic solar cells, where over 19% efficiency could be realized in the quaternary device. Our work advances the strong influence of electron-deficient central units on molecular photovoltaic properties and guides the design of acceptors for stable and large-thickness organic solar cells.
基金This research was supported by the National Natural Science Foundation of China(81430083,81903462 and 82073703)the China Postdoctoral Science Foundation(2018M641694)the Fundamental Research Funds for the Central Universities(DUT20LK28 and DUT20YG133).
文摘Background:Inhibitors of B-cell CLL/Iymphoma 2(Bcl-2)family proteins have shown hope as antitumor drugs.While the notion that it is efficient to coordinate,balance,and neutralize both arms of the anti-apoptotic Bcl-2 family has been validated in many cancer cells,the weights of the two arms contributing to apoptosis inhibition have not been explored.This study analyzed the best combination ratio for different Bcl-2 selective inhibitors.Methods:We used a previously established mathematical model to study the weights of Bcl-2(representing both Bcl-2 and BcI-xL in this study)and myeloid cell leukemia-1(Mcl-1).Correlation and single-parameter sensitivity analysis were used to find the major molecular determinants for Bcl-2 and Mcl-1 dependency,as well as their weights.Biological experiments were used to verify the mathematical model.Results:Bcl-2 protein level and Mcl-1 protein level,production,and degradation rates were the major molecular determinants for Bcl-2 and Mcl-1 dependency.The model gained agreement with the experimental assays for ABT-737/A-1210477 and ABT-737/compound 5 combination effect in MCF-7 and MDA-MB-231.Two sets of equations composed of Bcl-2 and Mcl-1 levels were obtained to predict the best combination ratio for Bcl-2 inhibitors with Mcl-1 inhibitors that stabilize and downregulate Mcl-1,respectively.Conclusions:The two sets of equations can be used as tools to bypass time-consuming and laborious experimental screening to predict the best drug combination ratio for treatment.
