Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a propo...Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a proportion in which a gene mutation can be the cause of the predisposition for breast cancer. A careful assessment of family and clinical history should be performed in these women in order to determine if a genetic counseling referral is indicated. In cases of hereditary breast cancer, genetic testing with a multigene panel can identify specific genetic mutations in over 100 genes. The most common genes mutated in hereditary breast cancer are the high-penetrance BRCA1 and BRCA2 genes. In addition, other mutations in high-penetrance genes in familial cancer syndromes and mutations in DNA repair genes can cause hereditary breast cancer. Mutations in low-penetrance genes and variants of uncertain signifcance may play a role in breast cancer development, but the magnitude and scope of risk in these cases remain unclear, thus the clinical utility of testing for these mutations is uncertain. In women with high-penetrance genetic mutations or lifetime risk of breast cancer 〉 20%, risk-reducing interventions, such as intensive screening, surgery, and chemoprevention, can decrease the incidence and mortality of breast cancer.展开更多
Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 pa...Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.展开更多
Microorganisms are often likened to complex production workshops.In Saccharopolyspora spinosa(S.spinosa),the biosynthesis of spinosad is a production line within its intricate workshop.Optimizing the entire production...Microorganisms are often likened to complex production workshops.In Saccharopolyspora spinosa(S.spinosa),the biosynthesis of spinosad is a production line within its intricate workshop.Optimizing the entire production environment and reducing unnecessary metabolic flow is essential to increasing spinosad yield.Pyruvate serves as a crucial precursor for spinosad biosynthesis.Previous studies revealed that the pyc gene is highly expressed in the gluconeogenic pathway,leading to a pyruvate shunt.By downregulating pyc,we enhanced spinosad yield,although the improvement was below expectations.We speculated that most of the accumulated pyruvate following the pyc knockdown entered some synthetic pathways unrelated to spinosad.Through metabolic pathway and qRT-PCR analyses,we found that the expression levels of gltA1 and atoB3 within the pyruvate metabolic tributary,including the TCA cycle and ethylmalonyl-CoA pathway,were significantly increased in the pyc knockdown strain.The combined knockdown of these three genes optimized the spinosad production line,increasing its yield to 633.1±38.6 mg/L,representing a 199.4%increase.This study identifies three key genes for optimizing spinosad biosynthesis and offers insights into gene screening and the efficient construction of Spinosad-producing strains.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
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
Understanding scale-up effects on the hydrodynamics of a liquid-solid circulating fluidized bed(LSCFB)unit requires both experimental and theoretical analysis.We implement multigene genetic programming(MGGP)to investi...Understanding scale-up effects on the hydrodynamics of a liquid-solid circulating fluidized bed(LSCFB)unit requires both experimental and theoretical analysis.We implement multigene genetic programming(MGGP)to investigate the solid holdup and distribution in three LSCFB systems with different heights.In addition to data obtained here,we also use a portion of data sets of LSCFB systems developed by Zheng(1999)and Liang et al.(1996).Model predictions are in good agreement with the experimental data in both radial and axial directions and at different normalized superficial liquid and solid velocities.The radial profiles of the solid holdup are approximately identical at a fixed average cross-sectional solid holdup for the three LSCFB systems studied.Statistical performance indicators including the mean absolute percentage error(6.19%)and correlation coefficient(0.985)are within an acceptable range.The results suggest that a MGGP modeling approach is suitable for predicting the solid holdup and distribution of a scaled-up LSCFB system.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
文摘Approximately 1 in 8 women will develop breast cancer during their lifetime and the risk factors include age, family history, and reproductive factors. In women with a family history of breast cancer, there is a proportion in which a gene mutation can be the cause of the predisposition for breast cancer. A careful assessment of family and clinical history should be performed in these women in order to determine if a genetic counseling referral is indicated. In cases of hereditary breast cancer, genetic testing with a multigene panel can identify specific genetic mutations in over 100 genes. The most common genes mutated in hereditary breast cancer are the high-penetrance BRCA1 and BRCA2 genes. In addition, other mutations in high-penetrance genes in familial cancer syndromes and mutations in DNA repair genes can cause hereditary breast cancer. Mutations in low-penetrance genes and variants of uncertain signifcance may play a role in breast cancer development, but the magnitude and scope of risk in these cases remain unclear, thus the clinical utility of testing for these mutations is uncertain. In women with high-penetrance genetic mutations or lifetime risk of breast cancer 〉 20%, risk-reducing interventions, such as intensive screening, surgery, and chemoprevention, can decrease the incidence and mortality of breast cancer.
文摘Objective:To study the clinical effects of multigene combination test to guide chemotherapy combined with targeted therapy in patients with advanced gastrointestinal tumors.Methods:The samples were selected from 60 patients with advanced gastrointestinal tumors admitted to our hospital from March 2019 to July 2020,and were divided into a study group and a control group using a random number table model;patients in the control group did not undergo genetic testing and FOLLOX4+PD-1 chemotherapy,while patients in the study group underwent TYMS,ERCC1,EGFR,and KRAS and VEGF gene expression levels test,and the sensitive treatment plan was determined based on the test results,and the clinical indexes were compared between the two groups.Results:By comparing the total effective rate,survival time,and time to disease progression of chemotherapy in the two groups,the study group has a significant advantage(P<0.05).Conclusion:The combination of chemotherapy and targeted therapy for advanced gastrointestinal tumor patients can improve the efficiency of chemotherapy and prolong the time of disease progression and survival,which is worthy of comprehensive promotion.
基金supported by funding from the National Natural Science Foundation of China(31770106,32200062)the Natural Science Foundation of Hunan Province(2024JJ5258).
文摘Microorganisms are often likened to complex production workshops.In Saccharopolyspora spinosa(S.spinosa),the biosynthesis of spinosad is a production line within its intricate workshop.Optimizing the entire production environment and reducing unnecessary metabolic flow is essential to increasing spinosad yield.Pyruvate serves as a crucial precursor for spinosad biosynthesis.Previous studies revealed that the pyc gene is highly expressed in the gluconeogenic pathway,leading to a pyruvate shunt.By downregulating pyc,we enhanced spinosad yield,although the improvement was below expectations.We speculated that most of the accumulated pyruvate following the pyc knockdown entered some synthetic pathways unrelated to spinosad.Through metabolic pathway and qRT-PCR analyses,we found that the expression levels of gltA1 and atoB3 within the pyruvate metabolic tributary,including the TCA cycle and ethylmalonyl-CoA pathway,were significantly increased in the pyc knockdown strain.The combined knockdown of these three genes optimized the spinosad production line,increasing its yield to 633.1±38.6 mg/L,representing a 199.4%increase.This study identifies three key genes for optimizing spinosad biosynthesis and offers insights into gene screening and the efficient construction of Spinosad-producing strains.
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 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support provided by King Abdulaziz City for Science and Technology(KACST)through the Science&Technology Unit at King Fahd University of Petroleum&Minerals(KFUPM)for funding of this work,project No.NSTIP#13-WAT96-04,as part of the National Science,Technology and Innovation Plan.
文摘Understanding scale-up effects on the hydrodynamics of a liquid-solid circulating fluidized bed(LSCFB)unit requires both experimental and theoretical analysis.We implement multigene genetic programming(MGGP)to investigate the solid holdup and distribution in three LSCFB systems with different heights.In addition to data obtained here,we also use a portion of data sets of LSCFB systems developed by Zheng(1999)and Liang et al.(1996).Model predictions are in good agreement with the experimental data in both radial and axial directions and at different normalized superficial liquid and solid velocities.The radial profiles of the solid holdup are approximately identical at a fixed average cross-sectional solid holdup for the three LSCFB systems studied.Statistical performance indicators including the mean absolute percentage error(6.19%)and correlation coefficient(0.985)are within an acceptable range.The results suggest that a MGGP modeling approach is suitable for predicting the solid holdup and distribution of a scaled-up LSCFB system.
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.
