Development and utilization of“liquid sunshine”could be one of key solutions to deal with the issues of fossil fuel depletion and increasing carbon dioxide.Cyanobacteria are the only prokaryotes capable of performin...Development and utilization of“liquid sunshine”could be one of key solutions to deal with the issues of fossil fuel depletion and increasing carbon dioxide.Cyanobacteria are the only prokaryotes capable of performing oxygenic photosynthesis,and their activity accounts for~25%of the total carbon fixation on earth.More importantly,besides their traditional roles as primary producers,cyanobacteria could be modified as“photosynthetic cell factories”to produce renewable fuels and chemicals directly from CO_(2) driven by solar energy,with the aid of cutting-edging synthetic biology technology.Towards their large-scale biotechnological application in the future,many challenges still need to be properly addressed,among which is cyanobacterial cell factories inevitably suffer from high light(HL)stress during large-scale outdoor cultivation,resulting in photodamage and even cell death,limiting their productivity.In this review,we critically summarized recent progress on deciphering molecular mechanisms to HL and developing HL-tolerant chassis in cyanobacteria,aiming at facilitating construction of HLresistant chassis and promote the future application of the large-scale outdoor cultivation of cyanobacterial cell factories.Finally,the future directions on cyanobacterial chassis engineering were discussed.展开更多
AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate...AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole "viral surface" induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cellsdirected against HCV. Furthermore, T-cell responses confi rmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further.展开更多
Stern et al. have developed a mathematical model describing pseudo-plateau bursting of pituitary cells. This model is formulated based on the Hodgkin-Huxley scheme and described by a system of nonlinear ordinary diffe...Stern et al. have developed a mathematical model describing pseudo-plateau bursting of pituitary cells. This model is formulated based on the Hodgkin-Huxley scheme and described by a system of nonlinear ordinary differential equations. In the present study, computer simulation analysis of this model was performed to evaluate the correlation between the dynamic states of the model and two system parameters: long-lasting external stimulation (Iapp) and the time constant of delayed-rectifier potassium conductance activation (τn). Computer simulation results revealed that the model showed four different dynamic states: a hyperpolarized steady state, a depolarized steady state, a repetitive spiking state, and a bursting state. An increase in Iapp changed the dynamic states from the hyperpolarized steady state to bursting state to depolarized steady state when τn was fixed at smaller values, whereas it changed the dynamic states from the hyperpolarized steady state to bursting state to repetitive spiking state when τn was fixed at larger values. An increase in τn 1) did not change the dynamic states when Iapp was fixed at a very small value, 2) changed the dynamic states from the depolarized steady state to repetitive spiking state when Iapp was fixed at a very large value, and 3) changed the dynamic states from the depolarized steady state to bursting state to repetitive spiking state when Iapp was fixed at an intermediate value.展开更多
Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthoo...Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.展开更多
Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic s...Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic significance for building a carbon-neutral,sustainable economic and industrial system.With the rapid advancement of RNA sequencing technology and mass spectrometer analysis,researchers have used these quantitative microbiology methods extensively,especially isotope-based metabolic flux analysis,to study the metabolic processes initiating from C1 feedstocks in natural C1-utilizing bacteria and synthetic C1 bacteria.This paper reviews the use of advanced quantitative analysis in recent years to understand the metabolic network and basic principles in the metabolism of natural C1-utilizing bacteria grown on methane,methanol,or formate.The acquired knowledge serves as a guide to rewire the central methylotrophic metabolism of natural C1-utilizing bacteria to improve the carbon conversion efficiency,and to engineer non-C1-utilizing bacteria into synthetic strains that can use C1 feedstocks as the sole carbon and energy source.These progresses ultimately enhance the design and construction of highly efficient C1-based cell factories to synthesize diverse high value-added products.The integration of quantitative biology and synthetic biology will advance the iterative cycle of understand–design–build–testing–learning to enhance C1-based biomanufacturing in the future.展开更多
基金This research was supported by grants from the National Key Research and Development Program of China(No.2019YFA0904600,2018YFA0903600,2020YFA0906800 and 2018YFA0903000)the National Natural Science Foundation of China(No.31770035,31972931,91751102,31770100,31901017,31901016,32070083 and 21621004)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(No.TSBICIP-KJGG-007).
文摘Development and utilization of“liquid sunshine”could be one of key solutions to deal with the issues of fossil fuel depletion and increasing carbon dioxide.Cyanobacteria are the only prokaryotes capable of performing oxygenic photosynthesis,and their activity accounts for~25%of the total carbon fixation on earth.More importantly,besides their traditional roles as primary producers,cyanobacteria could be modified as“photosynthetic cell factories”to produce renewable fuels and chemicals directly from CO_(2) driven by solar energy,with the aid of cutting-edging synthetic biology technology.Towards their large-scale biotechnological application in the future,many challenges still need to be properly addressed,among which is cyanobacterial cell factories inevitably suffer from high light(HL)stress during large-scale outdoor cultivation,resulting in photodamage and even cell death,limiting their productivity.In this review,we critically summarized recent progress on deciphering molecular mechanisms to HL and developing HL-tolerant chassis in cyanobacteria,aiming at facilitating construction of HLresistant chassis and promote the future application of the large-scale outdoor cultivation of cyanobacterial cell factories.Finally,the future directions on cyanobacterial chassis engineering were discussed.
文摘AIM: To explore dendritic cells (DCs) multiple functions in immune modulation. METHODS: We used bone-marrow derived dendritic cells from BALB/c mice pulsed with pseudo particles from the hepatitis C virus to vaccinate naive BALB/c mice. Hepatitis C virus (HCV) pseudo particles consist of the genotype 1b derived envelope proteins E1 and E2, covering a non-HCV core structure. Thus, not a single epitope, but the whole "viral surface" induces immunogenicity. For vaccination, mature and activated DC were injected subcutaneously twice. RESULTS: Humoral and cellular immune responses measured by enzyme-linked immunosorbent assay and interferon-gamma enzyme-linked immunosorbent spot test showed antibody production as well as T-cellsdirected against HCV. Furthermore, T-cell responses confi rmed two highly immunogenic regions in E1 and E2 outside the hypervariable region 1. CONCLUSION: Our results indicate dendritic cells as a promising vaccination model for HCV infection that should be evaluated further.
文摘Stern et al. have developed a mathematical model describing pseudo-plateau bursting of pituitary cells. This model is formulated based on the Hodgkin-Huxley scheme and described by a system of nonlinear ordinary differential equations. In the present study, computer simulation analysis of this model was performed to evaluate the correlation between the dynamic states of the model and two system parameters: long-lasting external stimulation (Iapp) and the time constant of delayed-rectifier potassium conductance activation (τn). Computer simulation results revealed that the model showed four different dynamic states: a hyperpolarized steady state, a depolarized steady state, a repetitive spiking state, and a bursting state. An increase in Iapp changed the dynamic states from the hyperpolarized steady state to bursting state to depolarized steady state when τn was fixed at smaller values, whereas it changed the dynamic states from the hyperpolarized steady state to bursting state to repetitive spiking state when τn was fixed at larger values. An increase in τn 1) did not change the dynamic states when Iapp was fixed at a very small value, 2) changed the dynamic states from the depolarized steady state to repetitive spiking state when Iapp was fixed at a very large value, and 3) changed the dynamic states from the depolarized steady state to bursting state to repetitive spiking state when Iapp was fixed at an intermediate value.
文摘Nigeria has a very high number of sickle cell disease (SCD) population with addition of 150,000 babies born annually with the disease. Early infant diagnosis and good care make many of these babies survive to adulthood. Severe pain requiring moderately strong or very strong analgesics is a common presentation of patients with Sickle Cell Anaemia. Paediatricians find ready usefulness of Opioids which are very useful for the painful episodes among these patients. Therefore, the chances of abuse and addiction to these medications become very high and constitute additional burden on the deficient manpower in the health sector. Opioid Use Disorder among Sickle Cell Disease patients has subtle presentation, so a high index of suspicion is required to make both the diagnosis and referral to treatment centres. In this review, the epidemiology, pain pathophysiology, behavioural and pharmacologic therapy have been re-examined.
基金National Key R&D Program of China,Grant Award Numbers:2018YFA0901500,2021YFC2103500National Natural Science Foundation of China,Grant/Award Numbers:22078169,32000003,31900004。
文摘Developing methylotrophic cell factories that can efficiently catalyze organic one-carbon(C1)feedstocks derived from electrocatalytic reduction of carbon dioxide into bio-based chemicals and biofuels is of strategic significance for building a carbon-neutral,sustainable economic and industrial system.With the rapid advancement of RNA sequencing technology and mass spectrometer analysis,researchers have used these quantitative microbiology methods extensively,especially isotope-based metabolic flux analysis,to study the metabolic processes initiating from C1 feedstocks in natural C1-utilizing bacteria and synthetic C1 bacteria.This paper reviews the use of advanced quantitative analysis in recent years to understand the metabolic network and basic principles in the metabolism of natural C1-utilizing bacteria grown on methane,methanol,or formate.The acquired knowledge serves as a guide to rewire the central methylotrophic metabolism of natural C1-utilizing bacteria to improve the carbon conversion efficiency,and to engineer non-C1-utilizing bacteria into synthetic strains that can use C1 feedstocks as the sole carbon and energy source.These progresses ultimately enhance the design and construction of highly efficient C1-based cell factories to synthesize diverse high value-added products.The integration of quantitative biology and synthetic biology will advance the iterative cycle of understand–design–build–testing–learning to enhance C1-based biomanufacturing in the future.