Common in nature and artificial systems,quasi-liquid represents a special phase under specific conditions,where precise regulations can be conducted to accommodate various applications,such as material,biology,life an...Common in nature and artificial systems,quasi-liquid represents a special phase under specific conditions,where precise regulations can be conducted to accommodate various applications,such as material,biology,life and manufacture.展开更多
Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the production.However,promoters in nonconventional yeasts such as Ogataea polymorpha are always limited,which res...Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the production.However,promoters in nonconventional yeasts such as Ogataea polymorpha are always limited,which results in incompatible gene modulation.Here,we expanded the promoter library in O.polymorpha based on transcriptional data,among which 13 constitutive promoters had the strengths ranging from 0–55%of PGAP,the commonly used strong constitutive promoter,and 2 were growth phase-dependent promoters.Subsequently,2 hybrid growth phase-dependent promoters were constructed and characterized,which had 2-fold higher activities.Finally,promoter engineering was applied to precisely regulate cellular metabolism for efficient production ofβ-elemene.The glyceraldehyde-3-phosphate dehydrogenase gene GAP was downregulated to drive more flux into pentose phosphate pathway(PPP)and then to enhance the supply of acetyl-CoA by using phosphoketolase-phosphotransacetylase(PK-PTA)pathway.Coupled with the phase-dependent expression of synthase module(ERG20∼LsLTC2 fusion),the highest titer of 5.24 g/L with a yield of 0.037 g/(g glucose)was achieved in strain YY150U under fed-batch fermentation in shake flasks.This work characterized and engineered a series of promoters,that can be used to fine-tune genes for constructing efficient yeast cell factories.展开更多
Quantum dot(QD)-based memristors enable precise and energy-efficient neuromorphic computing through atomic-level control over electrical synapse performance.However,the stochastic nature of QD structures results in th...Quantum dot(QD)-based memristors enable precise and energy-efficient neuromorphic computing through atomic-level control over electrical synapse performance.However,the stochastic nature of QD structures results in the poor reliability of resistive switching in neuromorphic computing,limiting its practical applications.Here,we present a data-driven QD synthesis optimization loop to precisely engineer QD structures for reliable neuromorphic computing.By deeply integrating high-throughput density functional theory with machine learning,we establish a cross-scale screening platform for precise synthesis of QDs,enabling multi-dimension predictions from atomic-level structures to macroscopic electrical synaptic behaviors.Through the minimization of structural disorder,achieved by pure phase,uniform size distribution,and highly preferred orientation,QD-based memristors demonstrate a 57%reduction in switching voltage,a two-order-of-magnitude increase in the ON/OFF ratio,and endurance and retention degradation as low as 0.1%over 8.4×10^(7)s of continuous operation and 10^(5)rapid read cycles.Furthermore,the dynamic learning range and neuromorphic computing accuracy are improved by 477%and 27.8%(reaching 92.23%),respectively.These findings establish a scalable,data-driven strategy for rational design of QD-based memristors,advancing the development of next-generation reliable neuromorphic computing systems.展开更多
Amplification of biosynthetic gene clusters is important to increase secondary metabolite production.However,the copy number of amplified gene clusters is difficult to control precisely.In this study,the tandem amplif...Amplification of biosynthetic gene clusters is important to increase secondary metabolite production.However,the copy number of amplified gene clusters is difficult to control precisely.In this study,the tandem amplification of a 70 kb bleomycin biosynthetic gene cluster was precisely regulated through the combined strategy of a Zou A-dependent DNA amplification system and double-reporter-guided recombinant selection in Streptomyces verticillus ATCC15003.The production of bleomycin in the recombinant strain containing six copies of the bleomycin gene cluster was 9.59-fold higher than that in the wild-type strain.The combined strategy used in this study is powerful and applicable for precisely regulating the amplification of gene clusters and improving the corresponding secondary metabolite production.展开更多
Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of or...Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of organisms.In the past decades,cell–cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology,and bioengineering.People have developed a series of strategies to artificially regulate cell–cell aggregation through chemical–biological approaches.To date,not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids,are employed as the“cell glue”to achieve the control of the cell aggregation.So it is meaningful to review the recent advances of the chemical–biological approaches in cell–cell aggregation manipulation.In this review,we discuss the mechanisms and features of recently developed strategies to control cell–cell aggregation.We introduce molecules and designs relying on chemical reactions and biological conjugations respectively,and talk about their advantages and suitable applications.A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also proposed.We expect this review could inspire innovative work on manipulating cell–cell aggregation and further modulate cell–cell interactions in the research of bio/chemical fields.展开更多
Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA...Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA”is its accessibility.In cancer cells,aberrant chromatin accessibility is recognized as one of the major hallmarks.Understanding such events requires high-throughput screening,such as Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq),which generates large-scale data that are puzzling for biologists.However,existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes.Here,we developed Shiny Pan-cancer Accessible Chromatin Explorer(SPACE)as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types.展开更多
基金financially supported by the National Natural Science Foundation of China(91434203,21776278,and 51674234)
文摘Common in nature and artificial systems,quasi-liquid represents a special phase under specific conditions,where precise regulations can be conducted to accommodate various applications,such as material,biology,life and manufacture.
基金This research was supported by the National Key Research and Development Project(2023YFC3503900)Liaoning Distinguished Scholar Program(2023JH6/100500001)。
文摘Precisely controlling gene expression is beneficial for optimizing biosynthetic pathways for improving the production.However,promoters in nonconventional yeasts such as Ogataea polymorpha are always limited,which results in incompatible gene modulation.Here,we expanded the promoter library in O.polymorpha based on transcriptional data,among which 13 constitutive promoters had the strengths ranging from 0–55%of PGAP,the commonly used strong constitutive promoter,and 2 were growth phase-dependent promoters.Subsequently,2 hybrid growth phase-dependent promoters were constructed and characterized,which had 2-fold higher activities.Finally,promoter engineering was applied to precisely regulate cellular metabolism for efficient production ofβ-elemene.The glyceraldehyde-3-phosphate dehydrogenase gene GAP was downregulated to drive more flux into pentose phosphate pathway(PPP)and then to enhance the supply of acetyl-CoA by using phosphoketolase-phosphotransacetylase(PK-PTA)pathway.Coupled with the phase-dependent expression of synthase module(ERG20∼LsLTC2 fusion),the highest titer of 5.24 g/L with a yield of 0.037 g/(g glucose)was achieved in strain YY150U under fed-batch fermentation in shake flasks.This work characterized and engineered a series of promoters,that can be used to fine-tune genes for constructing efficient yeast cell factories.
基金supported by the National Natural Science Foundation of China(51572205,52372159)the Natural Science Foundation Innovation Research Team of Hainan Province(524CXTD431)+1 种基金the National Science Fund for Distinguished Young Scholars of Hubei Province(201CFA067)the National Innovation and Entrepreneurship Training Program for College Students(S202510497020,202510497003,and S202510497010)。
文摘Quantum dot(QD)-based memristors enable precise and energy-efficient neuromorphic computing through atomic-level control over electrical synapse performance.However,the stochastic nature of QD structures results in the poor reliability of resistive switching in neuromorphic computing,limiting its practical applications.Here,we present a data-driven QD synthesis optimization loop to precisely engineer QD structures for reliable neuromorphic computing.By deeply integrating high-throughput density functional theory with machine learning,we establish a cross-scale screening platform for precise synthesis of QDs,enabling multi-dimension predictions from atomic-level structures to macroscopic electrical synaptic behaviors.Through the minimization of structural disorder,achieved by pure phase,uniform size distribution,and highly preferred orientation,QD-based memristors demonstrate a 57%reduction in switching voltage,a two-order-of-magnitude increase in the ON/OFF ratio,and endurance and retention degradation as low as 0.1%over 8.4×10^(7)s of continuous operation and 10^(5)rapid read cycles.Furthermore,the dynamic learning range and neuromorphic computing accuracy are improved by 477%and 27.8%(reaching 92.23%),respectively.These findings establish a scalable,data-driven strategy for rational design of QD-based memristors,advancing the development of next-generation reliable neuromorphic computing systems.
基金supported by the National Key Research and Development Program of China (2021YFC2100600)the National Natural Science Foundation of China (30970072 and 31170088)+1 种基金Biological Resources ProgrammeChinese Academy of Sciences (KFJBRP-009)。
文摘Amplification of biosynthetic gene clusters is important to increase secondary metabolite production.However,the copy number of amplified gene clusters is difficult to control precisely.In this study,the tandem amplification of a 70 kb bleomycin biosynthetic gene cluster was precisely regulated through the combined strategy of a Zou A-dependent DNA amplification system and double-reporter-guided recombinant selection in Streptomyces verticillus ATCC15003.The production of bleomycin in the recombinant strain containing six copies of the bleomycin gene cluster was 9.59-fold higher than that in the wild-type strain.The combined strategy used in this study is powerful and applicable for precisely regulating the amplification of gene clusters and improving the corresponding secondary metabolite production.
基金Nankai University,Grant/Award Number:63211050NationalNatural Science Foundation of China,Grant/Award Numbers:21874075,22074068,591859123。
文摘Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of organisms.In the past decades,cell–cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology,and bioengineering.People have developed a series of strategies to artificially regulate cell–cell aggregation through chemical–biological approaches.To date,not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids,are employed as the“cell glue”to achieve the control of the cell aggregation.So it is meaningful to review the recent advances of the chemical–biological approaches in cell–cell aggregation manipulation.In this review,we discuss the mechanisms and features of recently developed strategies to control cell–cell aggregation.We introduce molecules and designs relying on chemical reactions and biological conjugations respectively,and talk about their advantages and suitable applications.A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also proposed.We expect this review could inspire innovative work on manipulating cell–cell aggregation and further modulate cell–cell interactions in the research of bio/chemical fields.
基金supported by the National Natural Science Foundation of China(31770935,81873531,31970616)the Distinguished Professorship Program of Jiangsu Province to YF+2 种基金the Distinguished Professorship Program of Jiangsu Province to RMthe National Undergraduate Training Programs for Innovation(201710304030Z)the National Undergraduate Training Programs for Innovation(201810304026Z).
文摘Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA”is its accessibility.In cancer cells,aberrant chromatin accessibility is recognized as one of the major hallmarks.Understanding such events requires high-throughput screening,such as Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq),which generates large-scale data that are puzzling for biologists.However,existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes.Here,we developed Shiny Pan-cancer Accessible Chromatin Explorer(SPACE)as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types.
