A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synth...A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.展开更多
Betalain,an economically valuable water-soluble natural plant pigment,is prized for its strong antioxidant activity,making it popular as a dietary supplement and a visual marker for plant transformation.However,market...Betalain,an economically valuable water-soluble natural plant pigment,is prized for its strong antioxidant activity,making it popular as a dietary supplement and a visual marker for plant transformation.However,market demand significantly outstrips current production capacity.This study reports the development of an efficient push-and-pull multigene strategy based on polycistronic expression and metabolic flux regulation to enhance betalain biosynthesis in transgenic maize(Zea mays L.)endosperm.We engineered a novel enhanced RUBY(eRUBY)system derived from the original polycistronic RUBY construct(CYP76AD1P2ADODA1P2ADOPA5GT unit,abbreviated CDG)by introducing arogenate dehydrogenase(ADHα)to increase the L-tyrosine substrate supply.All the genes were driven by the endosperm-specific promoter.Fusion of ADHαinto a single polycistronic eRUBY construct(CDGA)produced significantly higher betanin(6.88 mg g−1 dry weight)and isobetanin(1.81 mg g−1 dry weight)levels than in CDG+A,which stacked the ADHαcassette independently with CDG.The high betalain accumulation in CDGA lines(which also exhibited higher transgene copy number)resulted in a 2.85–7.58-fold improvement in endosperm antioxidant capacity compared to WT(versus 2.48–2.80-fold in CDG+A).Importantly,transgenic plants maintained a normal phenotype.Transcriptome and metabolome analyses further indicated that metabolism of phenylalanine,alanine,aspartate,and glutamate contributes to betalain production.Hybridization with sweet corn successfully created a high-sugar eRUBY maize variety.Collectively,these results demonstrate the successful development of a novel maize germplasm with significantly enhanced nutritional value through high betalain accumulation.展开更多
Objective:Non-diagnostic thyroid nodules(Bethesda I)account for 5%-20%of all thyroid nodules.Accurate differentiation of benign and malignant nodules can reduce unnecessary surgeries and repeat biopsies.Herein we eval...Objective:Non-diagnostic thyroid nodules(Bethesda I)account for 5%-20%of all thyroid nodules.Accurate differentiation of benign and malignant nodules can reduce unnecessary surgeries and repeat biopsies.Herein we evaluated the diagnostic efficacy of multigene testing in non-diagnostic thyroid nodules and developed a predictive model integrating molecular and clinical data.Methods:In this prospective cohort study,1,175 patients with thyroid nodules were evaluated for inclusion,of which 218 patients with Bethesda I nodules met our inclusion criteria.The primary outcome was diagnostic accuracy of molecular testing,and the secondary outcome was the performance of a predictive model integrating molecular and clinical data.Results:Final histopathology identified 165 benign and 53 malignant nodules.Molecular testing detected 10distinct point mutations and seven gene fusions.Among benign nodules,147 tested negative and 18 tested positive,whereas 44 malignant nodules tested positive and nine tested negative.In nodules with ultrasound grades 4-5 and fine-needle aspiration cytology(FNAC)results categorized as non-diagnostic,molecular testing achieved sensitivity of 83.00%,specificity of 89.00%,positive predictive value(PPV)of 71.00%,negative predictive value(NPV)of94.20%,and overall accuracy of 87.60%.The predictive model incorporated 18 clinical and 19 molecular features.Eleven non-zero predictors were selected via least absolute shrinkage and selection operator(LASSO),and the model achieved area under curve(AUC)of 0.95 in the training set and 0.96 in the testing set.Decision curve analysis indicated greater net benefit compared with conventional diagnostic approaches.Conclusions:Molecular testing significantly improved diagnostic accuracy for Bethesda I thyroid nodules.Integrating molecular and clinical data enabled the development of a robust predictive model,facilitating precise,individualized patient management and reducing the need for repeat FNAC and unnecessary surgeries.展开更多
In present study,morphological observation and phylogenetic relationship analyses by using multiple loci DNA sequences,including the internal transcribed spacer(ITS)regions,the large subunit nuclear ribosomal RNA gene...In present study,morphological observation and phylogenetic relationship analyses by using multiple loci DNA sequences,including the internal transcribed spacer(ITS)regions,the large subunit nuclear ribosomal RNA gene(nLSU),and the translation elongation factor 1-αgene(tef1),result in discovery of Sicyoideibasidia yunnanensis sp.nov.of Agaricales.The species is characterized by resupinate basidiomata with smooth,cream to yellowish hymenial surface,a monomitic hyphal system,generative hyphae bearing simple septa,and ellipsoid basidiospores.Phylogenetic analysis based on ITS+nLSU+tef1 data shows that the new species is closely related with S.bambusicola and S.punctata.展开更多
基金supported by grants from the Guangxi Science and Technology Major Project(GKAA24206023)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Natural Science Foundation of China(32272120)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.
基金supported by grants from the Biological Breeding-National Science and Technology Major Project(2024ZD04077)the Invigorate the Seed Industry of Guangdong Province(2024-NPY-00-044)+3 种基金the National Natural Science Foundation of China(32272120)the Guangxi Science and Technology Major Project(GKAA24206023)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘Betalain,an economically valuable water-soluble natural plant pigment,is prized for its strong antioxidant activity,making it popular as a dietary supplement and a visual marker for plant transformation.However,market demand significantly outstrips current production capacity.This study reports the development of an efficient push-and-pull multigene strategy based on polycistronic expression and metabolic flux regulation to enhance betalain biosynthesis in transgenic maize(Zea mays L.)endosperm.We engineered a novel enhanced RUBY(eRUBY)system derived from the original polycistronic RUBY construct(CYP76AD1P2ADODA1P2ADOPA5GT unit,abbreviated CDG)by introducing arogenate dehydrogenase(ADHα)to increase the L-tyrosine substrate supply.All the genes were driven by the endosperm-specific promoter.Fusion of ADHαinto a single polycistronic eRUBY construct(CDGA)produced significantly higher betanin(6.88 mg g−1 dry weight)and isobetanin(1.81 mg g−1 dry weight)levels than in CDG+A,which stacked the ADHαcassette independently with CDG.The high betalain accumulation in CDGA lines(which also exhibited higher transgene copy number)resulted in a 2.85–7.58-fold improvement in endosperm antioxidant capacity compared to WT(versus 2.48–2.80-fold in CDG+A).Importantly,transgenic plants maintained a normal phenotype.Transcriptome and metabolome analyses further indicated that metabolism of phenylalanine,alanine,aspartate,and glutamate contributes to betalain production.Hybridization with sweet corn successfully created a high-sugar eRUBY maize variety.Collectively,these results demonstrate the successful development of a novel maize germplasm with significantly enhanced nutritional value through high betalain accumulation.
基金supported by Military Key Clinical Speciality(No.51561Z23612)Chongqing Talents Project(No.cstc2022ycjh-bgzxm0091)。
文摘Objective:Non-diagnostic thyroid nodules(Bethesda I)account for 5%-20%of all thyroid nodules.Accurate differentiation of benign and malignant nodules can reduce unnecessary surgeries and repeat biopsies.Herein we evaluated the diagnostic efficacy of multigene testing in non-diagnostic thyroid nodules and developed a predictive model integrating molecular and clinical data.Methods:In this prospective cohort study,1,175 patients with thyroid nodules were evaluated for inclusion,of which 218 patients with Bethesda I nodules met our inclusion criteria.The primary outcome was diagnostic accuracy of molecular testing,and the secondary outcome was the performance of a predictive model integrating molecular and clinical data.Results:Final histopathology identified 165 benign and 53 malignant nodules.Molecular testing detected 10distinct point mutations and seven gene fusions.Among benign nodules,147 tested negative and 18 tested positive,whereas 44 malignant nodules tested positive and nine tested negative.In nodules with ultrasound grades 4-5 and fine-needle aspiration cytology(FNAC)results categorized as non-diagnostic,molecular testing achieved sensitivity of 83.00%,specificity of 89.00%,positive predictive value(PPV)of 71.00%,negative predictive value(NPV)of94.20%,and overall accuracy of 87.60%.The predictive model incorporated 18 clinical and 19 molecular features.Eleven non-zero predictors were selected via least absolute shrinkage and selection operator(LASSO),and the model achieved area under curve(AUC)of 0.95 in the training set and 0.96 in the testing set.Decision curve analysis indicated greater net benefit compared with conventional diagnostic approaches.Conclusions:Molecular testing significantly improved diagnostic accuracy for Bethesda I thyroid nodules.Integrating molecular and clinical data enabled the development of a robust predictive model,facilitating precise,individualized patient management and reducing the need for repeat FNAC and unnecessary surgeries.
文摘In present study,morphological observation and phylogenetic relationship analyses by using multiple loci DNA sequences,including the internal transcribed spacer(ITS)regions,the large subunit nuclear ribosomal RNA gene(nLSU),and the translation elongation factor 1-αgene(tef1),result in discovery of Sicyoideibasidia yunnanensis sp.nov.of Agaricales.The species is characterized by resupinate basidiomata with smooth,cream to yellowish hymenial surface,a monomitic hyphal system,generative hyphae bearing simple septa,and ellipsoid basidiospores.Phylogenetic analysis based on ITS+nLSU+tef1 data shows that the new species is closely related with S.bambusicola and S.punctata.
