1.Engineering yeast for high-efficiency isoliquiritigenin production via synthetic biology approaches
Yan YIN ; Shucan LIU ; Ting LI ; Ying HUANG ; Xianan ZHANG ; Guangxi REN ; Wei GAO ; Xinghong GUO ; Dan JIANG ; Chunsheng LIU
Science of Traditional Chinese Medicine 2025;3(4):356-365
Background: Isoliquiritigenin, a key pharmacologically active compound derived from the traditional Chinese medicine Glycyrrhizae Radix et Rhizoma, can be further modified into various high-value 5-deoxyflavones, demonstrating significant potential for pharmaceutical development. Currently, the supply of isoliquiritigenin primarily depends on plant extraction. However, heterologous synthesis using microbial cell factories presents a promising alternative, offering a solution to resource limitations caused by the dwindling availability of Glycyrrhiza uralensis. Objective: This study aimed to employ heterologous synthesis in yeast strains for the stable and high-efficiency production of isoliquiritigenin. Methods: First, a stable chassis strain for isoliquiritigenin production was constructed by integrating optimized biosynthetic pathway enzyme genes. A type IV noncatalytic chalcone isomerase-like protein and a synthetic protein scaffold system were employed to enhance the metabolic channeling of key pathway enzymes. Subsequently, yeast metabolism was fine-tuned to balance precursor supply, and cofactor engineering strategies were implemented to increase nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) availability, thereby ensuring the catalytic efficiency of the key enzyme chalcone reductase. Results: The engineered strain Y21-2 achieved a 24.4-fold increase in isoliquiritigenin titer compared to the original strain. Additionally, the proportion of the by-product naringenin chalcone was reduced by 67.8%, marking the first instance in which the ratio of C-5 hydroxylated by-products was minimized to 10.4% during the microbial synthesis of 5-deoxyflavones. Conclusion: This work provides a valuable reference for the efficient and sustainable production of isoliquiritigenin, laying a solid foundation for further pathway optimization and the biotechnological synthesis of other high-value natural 5-deoxyflavones.
2.The effect and mechanism of exposure to polystyrene nanoplastics on lipid metabolism in mice liver
Xianan ZHANG ; Qingtao MENG ; Hongwei ZHANG ; Chao WANG ; Shuyi ZHANG ; Hanqing CHEN ; Xiaobo LI ; Rui CHEN
Chinese Journal of Preventive Medicine 2024;58(10):1524-1533
Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.
3.The effect and mechanism of exposure to polystyrene nanoplastics on lipid metabolism in mice liver
Xianan ZHANG ; Qingtao MENG ; Hongwei ZHANG ; Chao WANG ; Shuyi ZHANG ; Hanqing CHEN ; Xiaobo LI ; Rui CHEN
Chinese Journal of Preventive Medicine 2024;58(10):1524-1533
Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.
4.New techniques and methods for study of environmental health effects
Xianan ZHANG ; Shenshen WU ; Qingtao MENG ; Xiaobo LI ; Rui CHEN ; Hanqing CHEN
Journal of Environmental and Occupational Medicine 2024;41(10):1083-1086
The health effects associated with environmental pollutants remain one of the major public health issues at present. The research method focusing on the population as the research subjects is limited by reliable cohorts, and the research method targeting individual molecules cannot fully reflect the biological health effects under environmental pollutant stress. Using high-throughput multi-omics, machine learning, and epigenetic detection to conduct targeted research and joint analysis on cells, organoids, organs, animals, and humans in different biological dimensions will help provide data support for the study of potential targets and biological effects of environmental pollutants, providing a theoretical basis for the risk assessment and safety evaluation of environmental pollutants.
5.Association between ambient air pollution and pregnancy outcomes in women undergoing in vitro fertilization
Hongxiu ZHANG ; Huidi DU ; Minglei WANG ; Xianan LI ; Yan ZHAO ; Bin LIU
Chinese Journal of Reproduction and Contraception 2024;44(1):51-58
Objective:To investigate the association between exposure to ambient air pollutants and pregnancy outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to clarify the susceptible windows of exposure. Methods:A retrospective cohort study was conducted on 2 071 infertile women aged ≤40 years who underwent the first fresh cleavage stage embryo transfer in the Department of Reproductive Medicine of the First Affiliated Hospital of Harbin Medical University from January 2014 to December 2021. Patients were divided into heating season group and non-heating season group based on whether the start date of gonadotropin (Gn) was during the heating season or not, and baseline data and pregnancy outcomes were compared between the two groups. Daily average levels of six criteria air pollutants [fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), sulfur dioxide (SO 2), carbon monoxide (CO), ozone (O 3) max-8 h] in four discrete periods were obtained. The four discrete periods included period 1, 75 d prior to Gn start to Gn start; period 2, Gn start to oocyte retrieval; period 3, oocyte retrieval to day 3 embryo transfer; period 4, embryo transfer to serum human chorionic gonadotropin test. The primary outcome was ongoing pregnancy. A multiple logistic regression model was used to investigate the association between air pollutant exposure and pregnancy outcomes, adjusted for important confounders. Results:The biochemical pregnancy rate [51.7% (465/900)], the clinical pregnancy rate [45.2% (407/900)], the ongoing pregnancy rate [38.2% (344/900)], and the live birth rate [36.1% (325/900)] in the heating season group were significantly lower than those in the non-heating season group [56.3% (659/1 171), P=0.037; 51.2% (599/1 171), P=0.007; 44.3% (519/1 171), P=0.005; 41.3% (484/1 171), P=0.016]. A significant negative correlation was observed between SO 2 and NO 2 exposure and ongoing pregnancy in all four time windows. SO 2 increased by one interquartile range (IQR), corresponding to adjusted OR (a OR) and 95% CI were 0.92 (0.85-0.99), 0.92 (0.87-0.99), 0.93 (0.87-0.99) and 0.93 (0.87-0.99), respectively. An IQR increase in NO 2 was also significantly associated with decreased odds of ongoing pregnancy (a OR=0.83, 95% CI: 0.72-0.95; a OR=0.87, 95% CI: 0.77-0.97; a OR=0.90, 95% CI: 0.81-1.00; a OR=0.85, 95% CI: 0.77-0.95, respectively). During period 1 and period 4, we observed adverse effects of PM 10 exposure on ongoing pregnancy (a OR=0.86, 95% CI: 0.75-0.98; a OR=0.89, 95% CI: 0.80-1.00, respectively). In Period 1, PM 2.5 exposure was significantly associated with reduced odds for ongoing pregnancy with a OR=0.86, 95% CI: 0.75-0.99. In addition, NO 2 exposure was associated with a decreased likelihood of achieving clinical pregnancy across all exposure windows except for period 3. However, no associations were noted with CO and O 3. Conclusion:Ambient air pollution has detrimental effects on pregnancy outcomes in patients undergoing fresh embryo transfer. Notably, the adverse impacts were also observed during preantral-antral follicle transition stage before IVF/ICSI treatment. A significant negative association between NO 2 exposure and pregnancy outcomes was observed in almost all exposure windows, indicating that NO 2 may be the main air pollutant associated with adverse pregnancy outcomes.
6.Association between ambient air pollution and pregnancy outcomes in women undergoing in vitro fertilization
Hongxiu ZHANG ; Huidi DU ; Minglei WANG ; Xianan LI ; Yan ZHAO ; Bin LIU
Chinese Journal of Reproduction and Contraception 2024;44(1):51-58
Objective:To investigate the association between exposure to ambient air pollutants and pregnancy outcomes in patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to clarify the susceptible windows of exposure. Methods:A retrospective cohort study was conducted on 2 071 infertile women aged ≤40 years who underwent the first fresh cleavage stage embryo transfer in the Department of Reproductive Medicine of the First Affiliated Hospital of Harbin Medical University from January 2014 to December 2021. Patients were divided into heating season group and non-heating season group based on whether the start date of gonadotropin (Gn) was during the heating season or not, and baseline data and pregnancy outcomes were compared between the two groups. Daily average levels of six criteria air pollutants [fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), nitrogen dioxide (NO 2), sulfur dioxide (SO 2), carbon monoxide (CO), ozone (O 3) max-8 h] in four discrete periods were obtained. The four discrete periods included period 1, 75 d prior to Gn start to Gn start; period 2, Gn start to oocyte retrieval; period 3, oocyte retrieval to day 3 embryo transfer; period 4, embryo transfer to serum human chorionic gonadotropin test. The primary outcome was ongoing pregnancy. A multiple logistic regression model was used to investigate the association between air pollutant exposure and pregnancy outcomes, adjusted for important confounders. Results:The biochemical pregnancy rate [51.7% (465/900)], the clinical pregnancy rate [45.2% (407/900)], the ongoing pregnancy rate [38.2% (344/900)], and the live birth rate [36.1% (325/900)] in the heating season group were significantly lower than those in the non-heating season group [56.3% (659/1 171), P=0.037; 51.2% (599/1 171), P=0.007; 44.3% (519/1 171), P=0.005; 41.3% (484/1 171), P=0.016]. A significant negative correlation was observed between SO 2 and NO 2 exposure and ongoing pregnancy in all four time windows. SO 2 increased by one interquartile range (IQR), corresponding to adjusted OR (a OR) and 95% CI were 0.92 (0.85-0.99), 0.92 (0.87-0.99), 0.93 (0.87-0.99) and 0.93 (0.87-0.99), respectively. An IQR increase in NO 2 was also significantly associated with decreased odds of ongoing pregnancy (a OR=0.83, 95% CI: 0.72-0.95; a OR=0.87, 95% CI: 0.77-0.97; a OR=0.90, 95% CI: 0.81-1.00; a OR=0.85, 95% CI: 0.77-0.95, respectively). During period 1 and period 4, we observed adverse effects of PM 10 exposure on ongoing pregnancy (a OR=0.86, 95% CI: 0.75-0.98; a OR=0.89, 95% CI: 0.80-1.00, respectively). In Period 1, PM 2.5 exposure was significantly associated with reduced odds for ongoing pregnancy with a OR=0.86, 95% CI: 0.75-0.99. In addition, NO 2 exposure was associated with a decreased likelihood of achieving clinical pregnancy across all exposure windows except for period 3. However, no associations were noted with CO and O 3. Conclusion:Ambient air pollution has detrimental effects on pregnancy outcomes in patients undergoing fresh embryo transfer. Notably, the adverse impacts were also observed during preantral-antral follicle transition stage before IVF/ICSI treatment. A significant negative association between NO 2 exposure and pregnancy outcomes was observed in almost all exposure windows, indicating that NO 2 may be the main air pollutant associated with adverse pregnancy outcomes.
7.Research progress in epigenetic toxicity of diesel exhausts
Xianan ZHANG ; Xiaobo LI ; Rui CHEN
Journal of Environmental and Occupational Medicine 2023;40(5):520-523
Diesel exhaust (DE) can enter the organism body and cause multiple organ damage. DE contains particles that can be suspended in the air for a long time. Epigenetic regulation is a post transcriptional regulation change that does not involve DNA sequence changes. Many evidences showed that DE can affect the normal physiological functions of multiple organs and systems through epigenetic changes, thus regulating the occurrence and development of multiple diseases. This paper reviewed the research progress of DNA methylation and non-coding RNA in the biological harmful effects of DE. This will provide a basis for the safety evaluation, health risk assessment, and management of DE.
8.Physical activity among senior primary school students on weekends in Beijing
LONG Xin, ZHANG Hongwei, JI Ying, ZHANG Xianan, XIE Lijing
Chinese Journal of School Health 2022;43(2):190-193
Objective:
To analyze the duration and influencing factors of moderate and vigorous physical activity(MVPA) on weekends for primary school students in grades 4 to 6 in Beijing, and to provide a reference for formulating health education and promotion measures.
Methods:
Multi stage stratified cluster sampling method was used to randomly select 2 515 students from grades 4-6 in 14 primary schools in Beijing, and a self administered questionnaire was used to record MVPA on weekend, social demographic characteristics, other related health behaviors and knowledge. Multivariate Logistic regression analysis was used to explore the influencing factors of MVPA on weekends.
Results:
The prevalence of insufficient MVPA on weekends in Beijing was 63.54 %, and the prevalence was higher among girls (69.92%) than boys (57.81%) ( χ 2=39.65, P <0.01). Multiple Logistic regression analysis revealed that girls ( OR =1.74), living in rural areas ( OR =1.41), participants attending general schools ( OR = 1.34 ), from divorced family ( OR =1.46), and short sleep duration ( OR =1.50) were more likely to fail to meet the MVPA recommendations( P <0.05).
Conclusion
It is quite common that no sufficient weekend MVPA among senior primary school students, among them, the outer suburbs and schools with relatively weak teaching resources are the key places that need attention, and girls are the key groups that need attention.
9.Research progress on the accessibility and promotion strategies of prenatal care services for urban migrant women
Ronghuang GUO ; Li SUN ; Xianan ZHU ; Ping WU ; Xuyuan LI ; Jing ZHANG
Chinese Journal of Modern Nursing 2021;27(28):3911-3915
Prenatal care services are an important part of my country's public health services, and play an important role in enhancing the pregnancy and childbirth experience of urban migrant women and improving their pregnancy and childbirth outcomes. The accessibility of prenatal care services is an important indicator for evaluating the equalization of basic public services. This paper outlines the concept and measurement dimensions of the accessibility of prenatal care services. This paper also analyzes the factors affecting the accessibility of prenatal care services for urban migrant women in my country from the perspectives of service providers, demanders, and both parties, and proposes strategies to improve the accessibility of prenatal care services for urban migrant women.
10.Prevalence and associated factors of electronic products usage among primary school students of grade 4-6 in Beijing
LONG Xin, ZHANG Xianan, ZHANG Hongwei, JI Ying, XIE Lijing
Chinese Journal of School Health 2020;41(5):673-675
Objective:
To explore the prevalence and associated factors of non learning-based screen time of 4-6 grade school students in Beijing, and to provide a basic data for further research on hazard control measures such as myopia, overweight and obesity among children and adolescents in Beijing.
Methods:
Multistage stratified random cluster sampling method was adopted. A total of 2 515 primary school students were randomly selected in from schools in Beijing, self-developed questionnaire was used to investigate on the time for each electronic products usage for non-learning purpose, the total of electronic products usage every day and other information.
Results:
The rates of screen time >15 minutes each time and ≥1 h daily were 48.43%, 22.90%, respectively. Multiple Logistic regression analysis showed that ordinary school, 6 th grade, male, single-parent family and other types of family, and lack of moderate-to-vigorous physical activity at weekend were associated with the students’ non learning-based screen time (OR=1.66, 2.28, 1.27, 1.44, 1.87, 2.20, P<0.05).
Conclusion
The situation of excessive screen time of primary school students was improved in Beijing, but still be prevelent, male students of grade 4 should be given more attention, and more importance should be attached to the offect of family in children.


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