Metabolic engineering of erythritol production from glycerol by Yarrowia lipolytica

Ya-Ting Wang,Ling-Xuan Zhao,Liu-Jing Wei,Jun Chen,Zhijie Liu,Feng Liu,Qiang Hua 한국생물공학회 2024 Biotechnology and Bioprocess Engineering Vol.29 No.1

Erythritol as a four-carbon polyol has been widely used in food, pharmaceutical and daily chemical industries with characteristics of low caloric value and high chemical stability. Here, a system metabolic engineering strategy was used to increase the yield of erythritol from glycerol in Yarrowia lipolytica by enhancing the substrate transformation and restricting the by-product synthesis. Specifi cally, we determined that over-expression of a newly identifi ed erythrose reductase YPR1 was able to improve the erythritol production as same as the well-known erythrose reductase ER27. Instead of its up-regulation, knockout of erythrose reductase ER10 was eff ective to improve erythritol synthesis. Moreover, both over-expression of YPR1 and deletion of ER10 signifi cantly accelerated the glycerol utilization in response to high osmotic stress. To further decrease the by-product accumulation, a restriction and recycling strategy was implemented by knockout of mannitol dehydrogenase MDH2 and enhancement of arabitol dehydrogenase ADH1 and fructokinase HXK1. The engineered strain YL13 produced a titer of 25 g/L erythritol and less than 0.5 g/L mannitol and arabitol. By over-expression of transketolase TKL1, the fi nal strain YL14 produced 28.5 g/L erythritol and none of mannitol and arabitol. This study provides a new idea for reducing the production of by-products and improving the glycerol conversion to erythritol.

An Investigation Into the Relationship Between Metabolic Responses and Energy Regulation in Antibody-Producing Cell

Ya Ting Sun,Liang Zhao,Zhao Yang Ye,Li Fan,Xu Ping Liu,Wen Song Tan 한국미생물생명공학회(구 한국산업미생물학회) 2013 Journal of microbiology and biotechnology Vol.23 No.11

Energy-efficient metabolic responses were often noted in high-productive cultures. To better understand these metabolic responses, an investigation into the relationship between metabolic responses and energy regulation was conducted via a comparative analysis among cultures with different energy source supplies. Both glycolysis and glutaminolysis were studied through the kinetic analyses of major extracellular metabolites concerning the fast and slow cell growth stages, respectively, as well as the time-course profiles of intracellular metabolites. In three cultures showing distinct antibody productivities, the amino acid metabolism and energy state were further examined. Both the transition of lactate from production to consumption and steady intracellular pools of pyruvate and lactate were observed to be correlated with efficient energy regulation. In addition, an efficient utilization of amino acids as the replenishment for the TCA cycle was also found in the cultures with upregulated energy metabolism. It was further revealed that the inefficient energy regulation would cause low cell productivity based on the comparative analysis of cell growth and productivity in cultures having distinct energy regulation.

Evidence for the Presence of Long-Lived Plasma Cells in Nasal Polyps

Ya-Na Zhang,Jia Song,Guan-Ting Zhai,Hai Wang,Ren-Zhong Luo,Jing-Xian Li,Bo Liao,Jin Ma,Heng Wang,Xiang Lu,Da-Bo Liu,Zheng Liu 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.2

Purpose: Plasma cells and immunoglobulins (Igs) play a pivotal role in the induction and maintenance of chronic inflammation in nasal polyps. During secondary immune responses, plasma cell survival and Ig production are regulated by the local environment. The purpose of the present study was to investigate the presence of long-lived plasma cells (LLPCs) and specific survival niches for LLPCs in human nasal polyps. Methods: Nasal mucosal samples were cultured with an air-liquid interface system and the Ig levels in culture supernatants were analyzed by enzyme-linked immunosorbent assay. The characteristics of LLPCs in nasal polyps were determined by immunohistochemistry and immunofluorescence. The expression of neurotrophins as well as their receptors was detected by quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blotting. Results: The numbers of CD138+ total plasma cells and BCL2+ plasma cells were increased in both eosinophilic and non-eosinophilic nasal polyps compared with those in normal tissues. The production of IgG, IgA, and IgE was detected in culture supernatants even after a 32-day culture of nasal polyps. Although the total numbers of plasma cells were decreased in nasal polyps after culture, the numbers of BCL2+ plasma cells remained stable. The expression of nerve growth factor (NGF) as well as tropomyosin receptor kinase (Trk) A, a high-affinity receptor for NGF, was upregulated in both eosinophilic and non-eosinophilic nasal polyps. In addition, BCL2+ plasma cell numbers were positively correlated with NGF and TrkA mRNA expression in nasal mucosal tissues. Polyp plasma cells had the expression of TrkA. Conclusions: Human nasal polyps harbor a population of LLPCs and NGF may be involved in their prolonged survival. LLPCs may be a novel therapeutic target for suppressing the local Ig production in nasal polyps.

Electroacupuncture Improves Insulin Resistance by Reducing Neuroprotein Y/ Agouti-Related Protein Levels and Inhibiting Expression of Protein Tyrosine Phosphatase 1B in Diet-induced Obese Rats

Xia Liu,Jun-Feng He,Ya-Ting Qu,Zhi-Jun Liu,Qing-Yang Pu,Shengtong Guo,Jia Du,Peng-Fei Jiang 사단법인약침학회 2016 Journal of Acupuncture & Meridian Studies Vol.9 No.2

Electroacupuncture (EA) has been shown to exert beneficial effects on obesity, but the mechanism is unclear. This study investigated the effects of EA on diet-induced obese (DIO) rats. Fifty male SpragueeDawley rats were randomly divided into low-fat diet (LFD, 10 rats) and high-fat diet (HFD, 40 rats) groups. After the DIO models had been established, successful model rats were randomly divided into HFD, EA, and orlistat (OLST) groups. The EA group received EA at Zusanli (ST36) and Quchi (LI11) for 20 minutes once per day for 28 days. The OLST group was treated with orlistat by gavage. The body weight, homeostasis model assessment-insulin resistance index, adipocyte diameters, and neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B levels were significantly lower in the EA group than in the HFD group. The rats of the OLST group showed watery stools and yellow hairs whereas those of the EA group had regular stools and sleek coats. The effect of EA on weight loss may be related to improved insulin resistance caused by changes in the adipocyte size and by reductions in the expressions of neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B. This study indicates that EA may be a better method of alternative therapy for treating obesity and other metabolic diseases.

Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease

Xiong Liu-Lin,Xue Lu-Lu,Du Ruo-Lan,Niu Rui-Ze,Chen Li,Chen Jie,Hu Qiao,Tan Ya-Xin,Shang Hui-Fang,Liu Jia,Yu Chang-Yin,Wang Ting-Hua 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

Comprehensive Expression Analysis Suggests Functional Overlapping of Human FOX Transcription Factors in Cancer

Zhang, Ya-Li,Sun, Feng-Ting,Zhang, Ze,Chen, Xiao-Xu,Liu, Ai-Xiang,Pan, Jing-Jing,Peng, Fei,Zhou, Shuai,Sun, Li-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Forkhead-box (FOX) transcription factors comprise a large gene family that contains more than 50 members in man. Extensive studies have revealed that they not only have functions in control of growth and development, but also play important roles in different diseases, especially in cancer. However, biological functions for most of the members in the FOX family remain unknown. In the present study, the expression of 39 FOX genes in 48 kinds of cancer was mined from the Gene Expression Atlas database of European Bioinformatics Institute. The analysis results showed that some FOX genes demonstrate overlapping expression in various cancers, which suggests particular biological functions. The pleiotropic features of the FOX genes make them excellent candidates in efforts aimed to give medical treatment for cancers at the genetic level. The results also indicated that different FOX genes may have the synergy or antagonistics effects in the same cancers. The study provides clues for further functional analysis of FOX genes, especially for the pleiotropic biological functions and crosstalk of FOX genes in human cancers.

High Levels of Malic Acid Production by the Bioconversion of Corn Straw Hydrolyte Using an Isolated Rhizopus Delemar Strain

Xingjiang Li,Ya Liu,Ying Yang,Hua Zhang,Hualin Wang,Yue Wu,Min Zhang,Ting Sun,Jieshun Cheng,Xuefeng Wu,Lijun Pan,Shaotong Jiang,Hongwei Wu 한국생물공학회 2014 Biotechnology and Bioprocess Engineering Vol.19 No.3

The microbial fermentation of malic acid,which is one of the most important organic acid platformsused widely in food and chemical engineering, hasattracted considerable interest. A malate production strainwas isolated, a mutation was induced, and regulation of themetabolic network was then conducted. The identificationresults showed that the malic acid production strain, HF-119, belonged to Rhizopus delemar. An analysis of themetabolic pathway showed that the malic acid flux of thisstrain occurred through three main pathways, and manybyproducts, such as succinic acid, fumaric acid andethanol, were produced. Although corn straw hydrolytewas used, the metabolism of xylose was not as rapid as thatof glucose. Subsequently, breeding of the strains andregulation of the metabolic network resulted in an increasein malate yield, and the strain HF-121 produced more than120 g/L malic acid within 60 h. The ability to producemalic acid from biomass hydrolyte highlights the industrialdevelopment potential of this strain.

Home-based traditional Chinese medicine nursing interventions for discharged patients with COVID-19: a rapid review of Chinese guidelines

Xiao Xu,Ya-Nan Shi,Rong-Yun Wang,Ting Liu,Jingming Xu,Wen Mao,Qiu-Hua Sun 한국한의학연구원 2020 Integrative Medicine Research Vol.9 No.3

Background: The aim of this review was to comprehensively summarize and analyze the current guidelines on home-based traditional Chinese medicine (TCM) nursing interventions for discharged patients with COVID-19. Methods: Eight data sources were searched until June 28, 2020. The frequency of home-based TCM nursing interventions and the use of specific acupuncture points recommended in Chinese guidelines for discharged COVID-19 patients were computed and analyzed. Results: In total, we identified 5 Chinese guidelines that provide for home-based TCM nursing interventions for discharged patients with COVID-19. Moxibustion and acupressure were singled out as the most frequently used intervention of the 11 home-based TCM nursing interventions recommended by these guidelines. RN12 and ST36 were the 2 most promoted acupuncture points for moxibustion and acupressure interventions for these patients. Conclusions: The present review showed the important role of home-based TCM nursing interventions for discharged COVID-19 patients. However, direct evidence of their efficacy is still insufficient.

Active Distribution System Planning Considering Battery Swapping Station for Low-carbon Objective using Immune Binary Firefly Algorithm

Shi, Ji-Ying,Li, Ya-Jing,Xue, Fei,Ling, Le-Tao,Liu, Wen-An,Yuan, Da-Ling,Yang, Ting The Korean Institute of Electrical Engineers 2018 Journal of Electrical Engineering & Technology Vol.13 No.2

Active distribution system (ADS) considering distributed generation (DG) and electric vehicle (EV) is an effective way to cut carbon emission and improve system benefits. ADS is an evolving, complex and uncertain system, thus comprehensive model and effective optimization algorithms are needed. Battery swapping station (BSS) for EV service is an essential type of flexible load (FL). This paper establishes ADS planning model considering BSS firstly for the minimization of total cost including feeder investment, operation and maintenance, net loss and carbon tax. Meanwhile, immune binary firefly algorithm (IBFA) is proposed to optimize ADS planning. Firefly algorithm (FA) is a novel intelligent algorithm with simple structure and good convergence. By involving biological immune system into FA, IBFA adjusts antibody population scale to increase diversity and global search capability. To validate proposed algorithm, IBFA is compared with particle swarm optimization (PSO) algorithm on IEEE 39-bus system. The results prove that IBFA performs better than PSO in global search and convergence in ADS planning.

Active Distribution System Planning Considering Battery Swapping Station for Low-carbon Objective using Immune Binary Firefly Algorithm

Ji-Ying Shi,Ya-Jing Li,Fei Xue,Le-Tao Ling,Wen-An Liu,Da-Ling Yuan,Ting Yang 대한전기학회 2018 Journal of Electrical Engineering & Technology Vol.13 No.2

Active distribution system (ADS) considering distributed generation (DG) and electric vehicle (EV) is an effective way to cut carbon emission and improve system benefits. ADS is an evolving, complex and uncertain system, thus comprehensive model and effective optimization algorithms are needed. Battery swapping station (BSS) for EV service is an essential type of flexible load (FL). This paper establishes ADS planning model considering BSS firstly for the minimization of total cost including feeder investment, operation and maintenance, net loss and carbon tax. Meanwhile, immune binary firefly algorithm (IBFA) is proposed to optimize ADS planning. Firefly algorithm (FA) is a novel intelligent algorithm with simple structure and good convergence. By involving biological immune system into FA, IBFA adjusts antibody population scale to increase diversity and global search capability. To validate proposed algorithm, IBFA is compared with particle swarm optimization (PSO) algorithm on IEEE 39-bus system. The results prove that IBFA performs better than PSO in global search and convergence in ADS planning.