Tumor initiation and progression are highly intricate biolog-ical processes,and mutation-driven tumorigenesis is a pri-mary underlying cause.Personalized cancer vaccines have been developed to exploit these specific m...Tumor initiation and progression are highly intricate biolog-ical processes,and mutation-driven tumorigenesis is a pri-mary underlying cause.Personalized cancer vaccines have been developed to exploit these specific mutations,particu-larly in the form of tumor neoantigens,to induce immune responses,particularly the activation of CD8+T cells,which can attack malignant cells.Since tumor mutations result in protein sequence alterations distinct from those in normal tissues,therapies that precisely target these alterations could,in principle,confer effective tumor control while minimizing off-target effects.展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade.However,due to comp...Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade.However,due to complexity of cellular metabolism,the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering.Recently,cell-free protein synthesis system(CFPS)has been emerging as an enabling alternative to address challenges in biomanufacturing.This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits(biosensors)to speed up design-build-test(DBT)cycles of metabolic engineering and synthetic biology.展开更多
Saccharomyces cerevisiae is an excellent microbial cell factory for producing valuable recombinant proteins because of its fast growth rate,robustness,biosafety,ease of operability via mature genomic modification tech...Saccharomyces cerevisiae is an excellent microbial cell factory for producing valuable recombinant proteins because of its fast growth rate,robustness,biosafety,ease of operability via mature genomic modification technologies,and the presence of a conserved post-translational modification pathway among eukaryotic organisms.However,meeting industrial and market requirements with the current low microbial production of recombinant proteins can be challenging.To address this issue,numerous efforts have been made to enhance the ability of yeast cell factories to efficiently produce proteins.In this review,we provide an overview of recent advances in S.cerevisiae engineering to improve recombinant protein production.This review focuses on the strategies that enhance protein production by regulating transcription through promoter engineering,codon optimization,and expression system optimization.Additionally,we describe modifications to the secretory pathway,including engineered protein translocation,protein folding,glycosylation modification,and vesicle trafficking.Furthermore,we discuss global metabolic pathway optimization and other relevant strategies,such as the disruption of protein degradation,cell wall engineering,and random mutagenesis.Finally,we provide an outlook on the developmental trends in this field,offering insights into future directions for improving recombinant protein production in S.cerevisiae.展开更多
基金supported by the National Natural Science Foundation of China(82341042 and 32270993)the PhD program of the Interdisciplinary Research Center,Sun Yat-sen University.
文摘Tumor initiation and progression are highly intricate biolog-ical processes,and mutation-driven tumorigenesis is a pri-mary underlying cause.Personalized cancer vaccines have been developed to exploit these specific mutations,particu-larly in the form of tumor neoantigens,to induce immune responses,particularly the activation of CD8+T cells,which can attack malignant cells.Since tumor mutations result in protein sequence alterations distinct from those in normal tissues,therapies that precisely target these alterations could,in principle,confer effective tumor control while minimizing off-target effects.
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
基金This work was financially supported by the National Natural Science Foundation of China(Grant No.21606205,21576232&21506185)the Fundamental Research Funds for the Central Universities,and the Startup Fund from Zhejiang University.
文摘Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade.However,due to complexity of cellular metabolism,the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering.Recently,cell-free protein synthesis system(CFPS)has been emerging as an enabling alternative to address challenges in biomanufacturing.This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits(biosensors)to speed up design-build-test(DBT)cycles of metabolic engineering and synthetic biology.
基金supported by supported by the Key innovation Project of Qilu University of Technology(Shandong Academy of Sciences)(2022JBZ01-06)the Shandong Provincial Technical Innovation Boot Program(02055183)the Shandong Provincial Natural Science Foundation(ZR2020MC016).
文摘Saccharomyces cerevisiae is an excellent microbial cell factory for producing valuable recombinant proteins because of its fast growth rate,robustness,biosafety,ease of operability via mature genomic modification technologies,and the presence of a conserved post-translational modification pathway among eukaryotic organisms.However,meeting industrial and market requirements with the current low microbial production of recombinant proteins can be challenging.To address this issue,numerous efforts have been made to enhance the ability of yeast cell factories to efficiently produce proteins.In this review,we provide an overview of recent advances in S.cerevisiae engineering to improve recombinant protein production.This review focuses on the strategies that enhance protein production by regulating transcription through promoter engineering,codon optimization,and expression system optimization.Additionally,we describe modifications to the secretory pathway,including engineered protein translocation,protein folding,glycosylation modification,and vesicle trafficking.Furthermore,we discuss global metabolic pathway optimization and other relevant strategies,such as the disruption of protein degradation,cell wall engineering,and random mutagenesis.Finally,we provide an outlook on the developmental trends in this field,offering insights into future directions for improving recombinant protein production in S.cerevisiae.
