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Strain and process engineering toward continuous industrial fermentation

《化学科学与工程前沿（英文）》 2023年第17卷第10期页码 1336-1353 doi: 10.1007/s11705-022-2284-6

摘要： Most current biotechnology industries are based on batch or fed-batch fermentation processes, which often show low productivity and high production costs compared to chemical processes. To increase the economic competitiveness of biological processes, continuous fermentation technologies are being developed that offer significant advantages in comparison with batch/fed-batch fermentation processes, including: (1) removal of potential substrates and product inhibition, (2) prolonging the microbial exponential growth phase and enhancing productivity, and (3) avoiding repeated fermentation preparation and lowering operation and installation costs. However, several key challenges should be addressed for the industrial application of continuous fermentation processes, including (1) contamination of the fermentation system, (2) degeneration of strains, and (3) relatively low product titer. In this study, we reviewed and discussed metabolic engineering and synthetic biology strategies to address these issues.

关键词： continuous fermentation productivity contamination strain degeneration metabolic engineering

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New insights into different surfactants’ impacts on sludge fermentation: Focusing on the particular metabolic

《环境科学与工程前沿（英文）》 2022年第16卷第8期 doi: 10.1007/s11783-022-1527-6

摘要：

• The promoting effects for VFA generation follow the order of APG>SDBS>HTAB.

关键词： Waste activated sludge (WAS) Volatile fatty acids (VFA) Surfactant types Functional microorganisms Metabolic activity upregulation

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electron transfer and its application in dictating routes of biochemical processes associated with metabolic

《医学前沿（英文）》 2021年第15卷第5期页码 679-692 doi: 10.1007/s11684-021-0866-1

摘要： Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.

关键词： metabolic reprogramming potential of electron transfer cell proliferation aerobic glycolysis cancer metabolism

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Metabolic hypertension: concept and practice

null

《医学前沿（英文）》 2013年第7卷第2期页码 201-206 doi: 10.1007/s11684-013-0264-4

摘要：

Hypertension is a serious public health problem worldwide. More than 60% of the risk factors for hypertension are associated with metabolic disturbances. Metabolic abnormalities increase the risk for hypertension and cause high blood pressure. Improving metabolic disturbances is beneficial for hypertension treatment. Due to the importance of metabolic abnormalities in the pathogenesis of hypertension, we propose a concept of metabolic hypertension. In this review, we discuss and review the clinical types, pathogenesis, risk evaluation and management of metabolic hypertension. Elucidation of the mechanism of metabolic hypertension should facilitate the design of novel pharmacotherapeutics and dedicated antihypertensive manipulations.

关键词： hypertension cardiometabolic risk factors metabolic abnormalities

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Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

《医学前沿（英文）》 2015年第9卷第2期页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要：

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词： inflammation obesity cytokine energy expenditure insulin resistance

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Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology

null

《医学前沿（英文）》 2013年第7卷第1期页码 25-30 doi: 10.1007/s11684-013-0244-8

摘要：

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

关键词： FGF21 metabolism pharmacology physiology clinical relevance

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Water-dispersible nano-pollutions reshape microbial metabolism in type-specific manners: A metabolic

《环境科学与工程前沿（英文）》 2022年第16卷第9期 doi: 10.1007/s11783-022-1548-1

摘要：

• Water-dispersible nano-pollutions exhibit type-specific toxic effects on E. coli.

关键词： Nano-toxicity Nano-plastics Quantum dots Microbial metabolite Metabolic dysregulation

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Metformin and metabolic diseases: a focus on hepatic aspects

null

《医学前沿（英文）》 2015年第9卷第2期页码 173-186 doi: 10.1007/s11684-015-0384-0

摘要：

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.

关键词： metformin diabetes hepatic steatosis inflammatory response insulin resistance

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denitrification system with short-term pyridine exposure: Process capability, inhibition kinetics and metabolic

《环境科学与工程前沿（英文）》 2021年第15卷第6期 doi: 10.1007/s11783-021-1433-3

摘要：

• Short-term effect of the pyridine exposure on the SAD process was investigated.

关键词： Anammox Inhibition Metabolic pathway Microbial community Pyridine SAD

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The FGF metabolic axis

Xiaokun Li

《医学前沿（英文）》 2019年第13卷第5期页码 511-530 doi: 10.1007/s11684-019-0711-y

摘要： Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.

关键词： FGF19 FGF21 FGF23 FGFR metabolism endocrine Klotho

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Zinc homeostasis in the metabolic syndrome and diabetes

null

《医学前沿（英文）》 2013年第7卷第1期页码 31-52 doi: 10.1007/s11684-013-0251-9

摘要：

Zinc (Zn) is an essential mineral that is required for various cellular functions. Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome, diabetes and diabetic complications. The associations of Zn with metabolic syndrome, diabetes and diabetic complications, thus, stem from the multiple roles of Zn: (1) a constructive component of many important enzymes or proteins, (2) a requirement for insulin storage and secretion, (3) a direct or indirect antioxidant action, and (4) an insulin-like action. However, whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome, diabetes, or diabetic complications remains unclear. In fact, it is known that Zn deficiency is a common phenomenon in diabetic patients. Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism. Theoretically Zn supplementation should prevent the metabolic syndrome, diabetes, and diabetic complications; however, limited available data are not always supportive of the above notion. Therefore, this review has tried to summarize these pieces of available information, possible mechanisms by which Zn prevents the metabolic syndrome, diabetes, and diabetic complications. In the final part, what are the current issues for Zn supplementation were also discussed.

关键词： zinc zinc transporters metallothionein diabetes diabetic complications insulin resistance antioxidant

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Regulation of T cell immunity by cellular metabolism

null

《医学前沿（英文）》 2018年第12卷第4期页码 463-472 doi: 10.1007/s11684-018-0668-2

摘要：

T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.

关键词： T cell immunity metabolic pathways nutrient uptake metabolic checkpoints

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Low-temperature caproate production, microbial diversity, and metabolic pathway in xylose anaerobic fermentation

《环境科学与工程前沿（英文）》 2023年第17卷第3期 doi: 10.1007/s11783-023-1637-9

摘要：

● Converting xylose to caproate under a low temperature of 20 °C by MCF was verified.

关键词： Xylose fermentation Caproate Low temperature Bifidobacterium FAB pathway RBO pathway

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Profiling influences of gene overexpression on heterologous resveratrol production in

Duo Liu,Bingzhi Li,Hong Liu,Xuejiao Guo,Yingjin Yuan

《化学科学与工程前沿（英文）》 2017年第11卷第1期页码 117-125 doi: 10.1007/s11705-016-1601-3

摘要： Metabolic engineering of heterologous resveratrol production in faces challenges as the precursor L-tyrosine is stringently regulated by a complex biosynthetic system. We overexpressed the main gene targets in the upstream pathways to investigate their influences on the downstream resveratrol production. Single-gene overexpression and DNA assembly-directed multigene overexpression affect the production of resveratrol as well as its precursor -coumaric acid. Finally, the collaboration of selected gene targets leads to an optimal resveratrol production of 66.14±3.74 mg·L , 2.27 times higher than the initial production in YPD medium (4% glucose). The newly discovered gene targets expressing phosphoribosylanthranilate isomerase, expressing 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase, and expressing 4-coumaryl-CoA ligase show notable positive impacts on resveratrol production in .

关键词： resveratrol aromatic amino acid DNA assembly metabolic engineering gene overexpression

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Metabolic flux analysis on arachidonic acid fermentation

JIN Mingjie, HUANG He, ZHANG Kun, YAN Jie, GAO Zhen

《化学科学与工程前沿（英文）》 2007年第1卷第4期页码 421-426 doi: 10.1007/s11705-007-0077-6

摘要： The analysis of flux distributions in metabolic networks has become an important approach for understanding the fermentation characteristics of the process. A model of metabolic flux analysis of arachidonic acid (AA) synthesis in ME-1 was established and carbon flux distributions were estimated in different fermentation phases with different concentrations of N-source. During the exponential, decelerating and stationary phase, carbon fluxes to AA were 3.28%, 8.80% and 6.97%, respectively, with sufficient N-source broth based on the flux of glucose uptake, and those were increased to 3.95%, 19.21% and 39.29%, respectively, by regulating the shifts of carbon fluxes via fermentation with limited N-source broth and adding 0.05% NaNO at 96 h. Eventually AA yield was increased from 1.3 to 3.5 g · L. These results suggest a way to improve AA fermentation, that is, fermentation with limited N-source broth and adding low concentration N-source during the stationary phase.

关键词： AA different fermentation concentration N-source exponential metabolic