Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significa...Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects.Nanomedicines hold tremendous theranostic potential for treating,monitoring,diagnosing,and controlling various diseases and are attracting an unfathomable amount of input of research resources.Against the backdrop of an exponentially growing number of publications,it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines.Herein,this review elaborates on the development trends of nanomedicines,emerging nanocarriers,in vivo fate and safety of nanomedicines,and their extensive applications.Moreover,the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed.The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.展开更多
Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced a...Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.展开更多
A cDNA clone encoding an ABA-responsiveprotein HVA1,was isolated by differentialscreening from barley aleurone layers(Hong etal.).Expression of the HVA1 gene is shownto be developmentally regulated,organ-specif-ic,an... A cDNA clone encoding an ABA-responsiveprotein HVA1,was isolated by differentialscreening from barley aleurone layers(Hong etal.).Expression of the HVA1 gene is shownto be developmentally regulated,organ-specif-ic,and ABA-and stress-induced(Hong et展开更多
Hydrophilic silica/copolymer nanoparticles of SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) are prepared by silica surface-initiating atom transfer radical polymerization (SI-ATRP) of poly (ethylene glycol) methyl e...Hydrophilic silica/copolymer nanoparticles of SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) are prepared by silica surface-initiating atom transfer radical polymerization (SI-ATRP) of poly (ethylene glycol) methyl ether methacrylate (PEGMA) and poly(ethylene glycol) methacrylate (PEG), by using Three molar ratios of SiO<sub>2</sub>-Br/PEGMA/PEG as 1/42.46/19.44, 1/42.46/38.88 and 1/42.46/77.76. Their temperature sensitive behaviour, pH response and surface properties as protein-resistance coatings are characterized. 220 nm core-shell nanoparticles as P(PEGMA)-b-P(PEG) shell grafted on SiO2 core are formed in water solution, which gained LCST at 60<sup>。</sup>C - 77<sup>。</sup>C and good dispersion in water when pH > 5.0. The water-casted films by SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) obtain a little rough surface (Ra = 26.8 - 29.7 nm). While, the introduction of P(PEG) segments could slight increase the protein-repelling adsorption of SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) films (△f = ?6.96 Hz ~ ?7.25 Hz) compared with SiO2-g-P(PEGMA) films (△f = ?9.5 Hz). Therefore, SiO2-g-P(PEGMA)-b-P(PEG) could be used as protein-resistance coatings.展开更多
Genetically encoded covalent peptide tagging tools such as the SpyTag/SpyCatcher reactive pair,have been demonstrated versatile and useful for protein modification.Herein,we present a superpositively charged SpyCatche...Genetically encoded covalent peptide tagging tools such as the SpyTag/SpyCatcher reactive pair,have been demonstrated versatile and useful for protein modification.Herein,we present a superpositively charged SpyCatcher bearing a theoretical net charge of+21 capable of accomplishing multiple unrelated independent tasks to enrich this toolbox and cultivate new functions.The SpyCatcher(+21)possessed stimuli-responsive reactivity toward SpyTag and could serve as a potent and general platform for the delivery of proteins,including RNaseAinto HeLa cells.Remarkably,the delivered RNase A caused substantial proliferation inhibition toward HeLa cells.In addition,the superpositively charged SpyCatcher could form coacervate with plasmid DNA for further study of gene delivery and liquid–liquid phase separation.These findings demonstrate the robustness of the SpyTag/SpyCatcher structure against surface mutation and the prospect of applying supercharging technology on diverse functional proteins to create moonlighting proteins.展开更多
Biologics play an essential role in treating various indications from cancers to the metabolic diseases,while the current development of new classes of intracellular-acting protein drugs is still hindered because of h...Biologics play an essential role in treating various indications from cancers to the metabolic diseases,while the current development of new classes of intracellular-acting protein drugs is still hindered because of high molecular mass and overall hydrophilicity of proteins creating extremely poor permeability across cell membrane.Hence,there remains an unmet need to develop safe,potent approaches to augment intracellular protein delivery efficiency.Here,we described a facile multicomponent reaction system for generating a small library of redox-responsive cationic polypeptoids with high biocompatibility.The co-assembly of optimized polymer with protein leads to the formation of compacted nanocomplexes with smaller size and high encapsulation efficiency,thus improving cellular internalization via the macropinocytosis and/or caveolae-mediated endocytosis mainly.After endo-lysosomal escape,the nanocomplexes can be disassociated to efficiently release cargo proteins into the cytosol,owing to the intracellular glutathione(GSH)-triggered rapid cleavage of disulfide bonds in polymers backbone.As a result,we screened a promising platform reagent for efficient cytosolic protein delivery application.展开更多
BACKGROUND Patients with lipopolysaccharide(LPS)-responsive beige-like anchor protein(LRBA)deficiency have a variety of clinical symptoms,but there is no apparent genotype–phenotype correlation,and patients carrying ...BACKGROUND Patients with lipopolysaccharide(LPS)-responsive beige-like anchor protein(LRBA)deficiency have a variety of clinical symptoms,but there is no apparent genotype–phenotype correlation,and patients carrying the same mutations may have different phenotypes.Therefore,it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation(HSCT)for LRBA-deficient patients.We hypothesized that there may be a protein–phenotype correlation to indicate HSCT for LRBA-deficient patients.AIM To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes.METHODS Clinical data of three Chinese LRBA-deficient patients were collected,and protein levels were detected by Western blot analysis.In addition,LRBA mutation information of another 83 previously reported patients was summarized.RESULTS All the major clinical findings indicated enteropathy,but patients 1 and 3 presented with more severe symptoms than patient 2.Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2.Compound heterozygous mutations in LRBA were found in patient 1,and homozygous mutations in LRBA were found in patient 2 and patient 3.Only patient 2 responded well to traditional immunosuppressive treatment.Residual expression of the LRBA protein in patients 1 and 3 was very low,but in patient 2,a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control.After HSCT,patient 1 had increased LRBA protein expression.We summarized the genetic information of 86 patients,and the mutations in patients 1 and 3 were novel mutations.CONCLUSION We described three Chinese LRBA-deficient patients,two of whom carried novel mutations.These patients had no genotype-phenotype correlations,but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.展开更多
A non-destructive, safe and practical strategy to produce high quality graphene in high yield is urgently required, since this would pave the way for a wide range of applications of graphene in the future. Here we pre...A non-destructive, safe and practical strategy to produce high quality graphene in high yield is urgently required, since this would pave the way for a wide range of applications of graphene in the future. Here we present a pH-responsive water-dispersible method for the exfoliation and functionalization of graphene by using lysozyme. The pH-responsive dispersion of graphene may be useful for the reversible assembly of multicomponent/multifunctional nanohybrid materials and nanoscale electronic devices. More importantly, composites can be easily constructed through the interactions between disulphide groups in lysozyme and gold nanoparticles （AuNPs）. The resulting graphene-AuNPs composites show excellent catalytic activity towards reduction of o-nitroaniline by NaBH4. Since lysozyme is low cost and has antibacterial properties, and has been widely used in food preservation, medicine and the pharmaceutical industry, our approach may open a new scalable route for the manufacture of high-quality, nondestructive graphene for practical applications.展开更多
In this study, we identified a defense-related major latex protein （MLP） from upland cotton （designated GhMLP28） and investigated its functional mechanism. GhMLP28 transcripts were ubiquitously present in cotton p...In this study, we identified a defense-related major latex protein （MLP） from upland cotton （designated GhMLP28） and investigated its functional mechanism. GhMLP28 transcripts were ubiquitously present in cotton plants, with higher accumulation in the root. Expression of the GhMLP28 gene was induced by Verticillium dahliae inoculation and was responsive to defense signaling molecules, including ethylene, jas- monic acid, and salicylic acid. Knockdown of GhMLP28 expression by virus-induced gene silencing re- sulted in increased susceptibility of cotton plants to V. dahliae infection, while ectopic overexpression of GhMLP28 in tobacco improved the disease tolerance of the transgenic plants. Further analysis revealed that GhMLP28 interacted with cotton ethylene response factor 6 （GhERF6） and facilitated the binding of GhERF6 to GCC-box element. Transient expression assay demonstrated that GhMLP28 enhanced the tran- scription factor activity of GhERF6, which led to the augmented expression of some GCC-box genes. GhMLP28 proteins were located in both the nucleus and cytoplasm and their nuclear distribution was dependent on the presence of GhERF6. Collectively, these results demonstrate that GhMLP28 acts as a positive regulator of GhERF6, and synergetic actions of the two proteins may contribute substantially to protection against V. dahliae infection in cotton plants.展开更多
In flowering plants, photoperiodic flowering is controlled by a complicated network. Light is one of the most important environmental stimuli that control the timing of the transition from vegetative growth to reprodu...In flowering plants, photoperiodic flowering is controlled by a complicated network. Light is one of the most important environmental stimuli that control the timing of the transition from vegetative growth to reproductive development. Several photoreceptors, including PHYA, PHYB, CRY2, and FKF1 in Arabi- dopsis and their homologs （OsPHYA, OsPHYB, OsPHYC, and OsCRY2） in rice, have been identified to be related to flowering. Our previous study suggests that OsHAL3, a flavin mononucleotide-binding protein, may function as a blue-light sensor. Here, we report the identification of OsHAL3 as a positive regulator of flowering in rice. OsHAL3 overexpression lines exhibited an early flowering phenotype, whereas down- regulation of OsHAL3 expression by RNA interference delayed flowering under an inductive photoperiod （short-day conditions）. The change in flowering time was not accompanied by altered I-Idl expression but rather by reduced accumulation of Hd3a and MADS14 transcripts. OsHAL3 and Hdl colocalized in the nucleus and physically interacted in vivo under the dark, whereas their interaction was inhibited by white or blue light. Moreover, OsHAL3 directly bound to the promoter of Hd3a, especially before dawn. We conclude that OsHAL3, a novel light-responsive protein, plays an essential role in photoperiodic control of flowering time in rice, which is probably mediated by forming a complex with Hdl. Our findings open up new perspectives on the photoperiodic flowering pathway.展开更多
神经系统疾病由于其发病机制的复杂性已成为威胁人类健康的主要原因之一,给社会和患者家庭带来了沉重的经济负担。至今,人们对绝大部分神经系统疾病的病因及发病机制尚未得以完全阐述清楚。因此,神经系统疾病相关蛋白分子的研究对疾病...神经系统疾病由于其发病机制的复杂性已成为威胁人类健康的主要原因之一,给社会和患者家庭带来了沉重的经济负担。至今,人们对绝大部分神经系统疾病的病因及发病机制尚未得以完全阐述清楚。因此,神经系统疾病相关蛋白分子的研究对疾病的诊断和治疗就显得尤为重要。cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)是细胞内cAMP变化的转录转导因子,其主要功能是调节基因的转录和蛋白质的合成。CREB作为一种重要的细胞核内调控因子,通过自身的磷酸化和去磷酸化作用实现调节转录的功能。目前,已有大量的研究表明CREB在神经系统如突触的可塑性、学习与记忆及早期脑损伤等方面都具有重要的调节作用。CREB在神经系统中的作用是作为许多信号通路的终止与交汇点,其调控的上下有信号分子及其靶基因和CREB一起参与了神经干细胞的增殖、细胞周期调控、神经元诱导分化、学习记忆等正常生理活动。这使得CREB信号通路相关的分子成为较受关注的神经系统疾病潜在的药物干预靶点。本文概述了CREB结构及其转录因子家族、CREB相关信号通路在神经系统中的调节机制及CREB在记忆障碍、癫痫发作、脑缺血再灌注损伤、出血性脑血管病、酒精成瘾、帕金森病等多种神经系统疾病中的调节作用,以期为理解神经系统疾病的发病机制和临床治疗靶点的选择提供新的思路。展开更多
Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional me...Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2 DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract(MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance(IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1 c(SREBP-1 c) and carbohydrate-responsive element binding protein(Ch REBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and m RNA expression levels of SREBP-1 c and Ch REBP. In conclusion, down-regulation of SREBP-1 c and Ch REBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2 DM associated with NAFLD.展开更多
基金financially supported by the Science and Technology Commission of Shanghai Municipality (No.21430760800,China)the National Natural Science Foundation of China (Nos.82273867,82030107,82241002,and 82073782)。
文摘Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects.Nanomedicines hold tremendous theranostic potential for treating,monitoring,diagnosing,and controlling various diseases and are attracting an unfathomable amount of input of research resources.Against the backdrop of an exponentially growing number of publications,it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines.Herein,this review elaborates on the development trends of nanomedicines,emerging nanocarriers,in vivo fate and safety of nanomedicines,and their extensive applications.Moreover,the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed.The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.
文摘Objective:To investigate the regulatory role of cyclic adenosine monophosphate responsive element binding protein(CREB)/brain-derived neurotrophic factor(BDNF)signaling pathway in acute sleep deprivation(SD)-induced anxiety-like behavior mice(SD group)to study the mechanism of anxiety-like behavior better.Methods:The SD chamber was used to deprive the mice of sleep,and the anxiety-like behavior of the mice was verified using an open field test(OFT),elevated plus maze(EPM),forced swim test(FST),and tail suspension test(TST).Finally,proteins were detected by Western blotting.Result:OFT showed that the active distance and the time of stay in the central area were significantly reduced(P<0.05).EPM showed that the time and number of open arms in the SD group were significantly lower than in the control group(P<0.05).The FST showed that the forced swimming immobility time of the SD group was significantly lower than that of the control(P<0.05).Moreover,the TST showed that the immobility time of the tail suspension experiment in the SD group was significantly higher than that in the control group(P<0.05).Conclusion:Acute SD can regulate anxiety-like behavior in mice through the CREB/BDNF signaling pathway.
文摘 A cDNA clone encoding an ABA-responsiveprotein HVA1,was isolated by differentialscreening from barley aleurone layers(Hong etal.).Expression of the HVA1 gene is shownto be developmentally regulated,organ-specif-ic,and ABA-and stress-induced(Hong et
文摘Hydrophilic silica/copolymer nanoparticles of SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) are prepared by silica surface-initiating atom transfer radical polymerization (SI-ATRP) of poly (ethylene glycol) methyl ether methacrylate (PEGMA) and poly(ethylene glycol) methacrylate (PEG), by using Three molar ratios of SiO<sub>2</sub>-Br/PEGMA/PEG as 1/42.46/19.44, 1/42.46/38.88 and 1/42.46/77.76. Their temperature sensitive behaviour, pH response and surface properties as protein-resistance coatings are characterized. 220 nm core-shell nanoparticles as P(PEGMA)-b-P(PEG) shell grafted on SiO2 core are formed in water solution, which gained LCST at 60<sup>。</sup>C - 77<sup>。</sup>C and good dispersion in water when pH > 5.0. The water-casted films by SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) obtain a little rough surface (Ra = 26.8 - 29.7 nm). While, the introduction of P(PEG) segments could slight increase the protein-repelling adsorption of SiO<sub>2</sub>-g-P(PEGMA)-b-P(PEG) films (△f = ?6.96 Hz ~ ?7.25 Hz) compared with SiO2-g-P(PEGMA) films (△f = ?9.5 Hz). Therefore, SiO2-g-P(PEGMA)-b-P(PEG) could be used as protein-resistance coatings.
基金support fromthe National Key R&D Program of China(grant nos.2020YFA0908100,2020AAA0105200)the National Natural Science Foundation of China(NSFC,grant nos.21991132,21925102,92056118,8200907120,8200907121)Beijing National Laboratory for Molecular Sciences(BNLMS,grant no.BNLMS-CXXM-202006).
文摘Genetically encoded covalent peptide tagging tools such as the SpyTag/SpyCatcher reactive pair,have been demonstrated versatile and useful for protein modification.Herein,we present a superpositively charged SpyCatcher bearing a theoretical net charge of+21 capable of accomplishing multiple unrelated independent tasks to enrich this toolbox and cultivate new functions.The SpyCatcher(+21)possessed stimuli-responsive reactivity toward SpyTag and could serve as a potent and general platform for the delivery of proteins,including RNaseAinto HeLa cells.Remarkably,the delivered RNase A caused substantial proliferation inhibition toward HeLa cells.In addition,the superpositively charged SpyCatcher could form coacervate with plasmid DNA for further study of gene delivery and liquid–liquid phase separation.These findings demonstrate the robustness of the SpyTag/SpyCatcher structure against surface mutation and the prospect of applying supercharging technology on diverse functional proteins to create moonlighting proteins.
基金This work was supported by the National Natural Science Foundation of China(51803243,51820105004)the Guangdong Basic and Applied Basic Research Foundation(2020A1515011285)the Guangdong Innovative and Entrepreneurial Research Team Program(2013S086).
文摘Biologics play an essential role in treating various indications from cancers to the metabolic diseases,while the current development of new classes of intracellular-acting protein drugs is still hindered because of high molecular mass and overall hydrophilicity of proteins creating extremely poor permeability across cell membrane.Hence,there remains an unmet need to develop safe,potent approaches to augment intracellular protein delivery efficiency.Here,we described a facile multicomponent reaction system for generating a small library of redox-responsive cationic polypeptoids with high biocompatibility.The co-assembly of optimized polymer with protein leads to the formation of compacted nanocomplexes with smaller size and high encapsulation efficiency,thus improving cellular internalization via the macropinocytosis and/or caveolae-mediated endocytosis mainly.After endo-lysosomal escape,the nanocomplexes can be disassociated to efficiently release cargo proteins into the cytosol,owing to the intracellular glutathione(GSH)-triggered rapid cleavage of disulfide bonds in polymers backbone.As a result,we screened a promising platform reagent for efficient cytosolic protein delivery application.
文摘BACKGROUND Patients with lipopolysaccharide(LPS)-responsive beige-like anchor protein(LRBA)deficiency have a variety of clinical symptoms,but there is no apparent genotype–phenotype correlation,and patients carrying the same mutations may have different phenotypes.Therefore,it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation(HSCT)for LRBA-deficient patients.We hypothesized that there may be a protein–phenotype correlation to indicate HSCT for LRBA-deficient patients.AIM To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes.METHODS Clinical data of three Chinese LRBA-deficient patients were collected,and protein levels were detected by Western blot analysis.In addition,LRBA mutation information of another 83 previously reported patients was summarized.RESULTS All the major clinical findings indicated enteropathy,but patients 1 and 3 presented with more severe symptoms than patient 2.Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2.Compound heterozygous mutations in LRBA were found in patient 1,and homozygous mutations in LRBA were found in patient 2 and patient 3.Only patient 2 responded well to traditional immunosuppressive treatment.Residual expression of the LRBA protein in patients 1 and 3 was very low,but in patient 2,a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control.After HSCT,patient 1 had increased LRBA protein expression.We summarized the genetic information of 86 patients,and the mutations in patients 1 and 3 were novel mutations.CONCLUSION We described three Chinese LRBA-deficient patients,two of whom carried novel mutations.These patients had no genotype-phenotype correlations,but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.
基金Acknowledgements Financial support was provided by the National Basic Research Program （973 Program） of China （Nos. 2011CB936004 and 2012CB720602）, and theNational Natural Science Foundation of China （NSFC）, Nos. （21210002 and 91213302）.
文摘A non-destructive, safe and practical strategy to produce high quality graphene in high yield is urgently required, since this would pave the way for a wide range of applications of graphene in the future. Here we present a pH-responsive water-dispersible method for the exfoliation and functionalization of graphene by using lysozyme. The pH-responsive dispersion of graphene may be useful for the reversible assembly of multicomponent/multifunctional nanohybrid materials and nanoscale electronic devices. More importantly, composites can be easily constructed through the interactions between disulphide groups in lysozyme and gold nanoparticles （AuNPs）. The resulting graphene-AuNPs composites show excellent catalytic activity towards reduction of o-nitroaniline by NaBH4. Since lysozyme is low cost and has antibacterial properties, and has been widely used in food preservation, medicine and the pharmaceutical industry, our approach may open a new scalable route for the manufacture of high-quality, nondestructive graphene for practical applications.
文摘In this study, we identified a defense-related major latex protein （MLP） from upland cotton （designated GhMLP28） and investigated its functional mechanism. GhMLP28 transcripts were ubiquitously present in cotton plants, with higher accumulation in the root. Expression of the GhMLP28 gene was induced by Verticillium dahliae inoculation and was responsive to defense signaling molecules, including ethylene, jas- monic acid, and salicylic acid. Knockdown of GhMLP28 expression by virus-induced gene silencing re- sulted in increased susceptibility of cotton plants to V. dahliae infection, while ectopic overexpression of GhMLP28 in tobacco improved the disease tolerance of the transgenic plants. Further analysis revealed that GhMLP28 interacted with cotton ethylene response factor 6 （GhERF6） and facilitated the binding of GhERF6 to GCC-box element. Transient expression assay demonstrated that GhMLP28 enhanced the tran- scription factor activity of GhERF6, which led to the augmented expression of some GCC-box genes. GhMLP28 proteins were located in both the nucleus and cytoplasm and their nuclear distribution was dependent on the presence of GhERF6. Collectively, these results demonstrate that GhMLP28 acts as a positive regulator of GhERF6, and synergetic actions of the two proteins may contribute substantially to protection against V. dahliae infection in cotton plants.
文摘In flowering plants, photoperiodic flowering is controlled by a complicated network. Light is one of the most important environmental stimuli that control the timing of the transition from vegetative growth to reproductive development. Several photoreceptors, including PHYA, PHYB, CRY2, and FKF1 in Arabi- dopsis and their homologs （OsPHYA, OsPHYB, OsPHYC, and OsCRY2） in rice, have been identified to be related to flowering. Our previous study suggests that OsHAL3, a flavin mononucleotide-binding protein, may function as a blue-light sensor. Here, we report the identification of OsHAL3 as a positive regulator of flowering in rice. OsHAL3 overexpression lines exhibited an early flowering phenotype, whereas down- regulation of OsHAL3 expression by RNA interference delayed flowering under an inductive photoperiod （short-day conditions）. The change in flowering time was not accompanied by altered I-Idl expression but rather by reduced accumulation of Hd3a and MADS14 transcripts. OsHAL3 and Hdl colocalized in the nucleus and physically interacted in vivo under the dark, whereas their interaction was inhibited by white or blue light. Moreover, OsHAL3 directly bound to the promoter of Hd3a, especially before dawn. We conclude that OsHAL3, a novel light-responsive protein, plays an essential role in photoperiodic control of flowering time in rice, which is probably mediated by forming a complex with Hdl. Our findings open up new perspectives on the photoperiodic flowering pathway.
文摘神经系统疾病由于其发病机制的复杂性已成为威胁人类健康的主要原因之一,给社会和患者家庭带来了沉重的经济负担。至今,人们对绝大部分神经系统疾病的病因及发病机制尚未得以完全阐述清楚。因此,神经系统疾病相关蛋白分子的研究对疾病的诊断和治疗就显得尤为重要。cAMP应答元件结合蛋白(cAMP response element binding protein,CREB)是细胞内cAMP变化的转录转导因子,其主要功能是调节基因的转录和蛋白质的合成。CREB作为一种重要的细胞核内调控因子,通过自身的磷酸化和去磷酸化作用实现调节转录的功能。目前,已有大量的研究表明CREB在神经系统如突触的可塑性、学习与记忆及早期脑损伤等方面都具有重要的调节作用。CREB在神经系统中的作用是作为许多信号通路的终止与交汇点,其调控的上下有信号分子及其靶基因和CREB一起参与了神经干细胞的增殖、细胞周期调控、神经元诱导分化、学习记忆等正常生理活动。这使得CREB信号通路相关的分子成为较受关注的神经系统疾病潜在的药物干预靶点。本文概述了CREB结构及其转录因子家族、CREB相关信号通路在神经系统中的调节机制及CREB在记忆障碍、癫痫发作、脑缺血再灌注损伤、出血性脑血管病、酒精成瘾、帕金森病等多种神经系统疾病中的调节作用,以期为理解神经系统疾病的发病机制和临床治疗靶点的选择提供新的思路。
基金supported by Ningbo Science and Technology Innovation Team Program(No.2014B82002)the National Natural Science Foundation of China(Nos.81370165,81501421,and 31301068)+1 种基金the Natural Science Foundation of Ningbo(Nos.2013A610209 and 2015A610217)Fang Runhua Fund of Hong Kong and K.C.Wong Magna Fund of Ningbo University
文摘Nonalcoholic fatty liver disease(NAFLD) and type 2 Diabetes Mellitus(T2 DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2 DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2 DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract(MCE; 10 g·kg-1·d-1) lowered the blood lipid levels and reversed insulin resistance(IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1 c(SREBP-1 c) and carbohydrate-responsive element binding protein(Ch REBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and m RNA expression levels of SREBP-1 c and Ch REBP. In conclusion, down-regulation of SREBP-1 c and Ch REBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2 DM associated with NAFLD.
