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.

AIM:To investigate the association between long noncoding RNA(lncRNA)growth arrest-specific transcript 5(GAS5)genetic polymorphism and the onset of polycystic ovary syndrome(PCOS).METHODS:The case-control study was performed,selecting 236 PCOS patients diagnosed at the Reproductive Medicine Center of the Affiliated Hospital of Guangxi Youjiang University for Nationalities from May 2018 to May 2019 as the case group,while 277 healthy women matched in sex and age during the same period were selected as the control group.The iMLDR single nucleotide polymorphism(SNP)was used to detected the genotypes of rs145204276 I/D,rs55829688 C/T and rs6790 G/A in GAS5 gene.The correlation between GAS5 gene polymorphism and PCOS was analyzed using logistic regression.RESULTS:The difference of GAS5 gene rs145204276 I/D polymorphism had statistical significance between control group and PCOS group.Logistic regression analysis showed that compared with the I/I genotype,the I/D and D/D genotypes,as well as the dominant model I/D+D/D,had a reduced risk of PCOS[I/D vs I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002].Compared with the I allele,the D allele significantly reduced the risk of PCOS[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001).There was no statistically significant difference in the polymorphism of rs55829688 C/T and rs6790 G/A between control group and PCOS group(P＞0.05).The combined analysis of haplotypes showed that the difference of D-T-A haplo-type distribution was statistically significant between control group and PCOS group[OR(95%CI)=0.61(0.45,0.84),P=0.002].CONCLUSION:The polymorphism of GAS5 gene rs145204276 I/D may be associated with genetic suscepti-bility to PCOS,and individuals carrying the D allele may have a reduced risk of developing PCOS.

Objective To establish a high-throughput HPLC method for the simultaneous determination of 11 common antibacterial agents in acyclovir eye drops and to evaluate the quality and safety of the antibacterial agents in 42 batches of national drug inspection samples.Methods Gradient elution was performed on a Kromasil 100-5-C18(4.6 mm×250 mm,5 μm)column with acetonitrile-5 mmol·L-1 ammonium acetate aqueous solution(containing 1%triethylamine,pH adjusted to 4.5 by acetic acid)as the mobile phase.The detection wavelength was 262 nm.Results Good linear relationships were obtained for 11 antibacterial agents(r≥0.999 9).The average recovery range was 98.2%-101.8%,and the RSD was 0.7%-2.7%(n=9).As revealed by the systematic analysis of 42 batches of national drug inspection samples,some batches of samples were detected with out-of-prescription antibacterial agents 4-hydroxybenzoic acid and ethylparaben,and the results were 0.02-49 μg·mL-1.This indicated that ethylparaben degradation and colinear production pollution were the two major risk sources.Conclusions The method is accurate,sensitive,and specific and can be used for the qualitative and quantitative detection of antibacterial agents in acyclovir eye drops.Besides,some products have degradation of antibacterial agents and incomplete cleaning during co-linear production.It is still essential to further reinforce product quality control.

Objective To establish a high-throughput HPLC method for the simultaneous determination of 11 common antibacterial agents in acyclovir eye drops and to evaluate the quality and safety of the antibacterial agents in 42 batches of national drug inspection samples.Methods Gradient elution was performed on a Kromasil 100-5-C18(4.6 mm×250 mm,5 μm)column with acetonitrile-5 mmol·L-1 ammonium acetate aqueous solution(containing 1%triethylamine,pH adjusted to 4.5 by acetic acid)as the mobile phase.The detection wavelength was 262 nm.Results Good linear relationships were obtained for 11 antibacterial agents(r≥0.999 9).The average recovery range was 98.2%-101.8%,and the RSD was 0.7%-2.7%(n=9).As revealed by the systematic analysis of 42 batches of national drug inspection samples,some batches of samples were detected with out-of-prescription antibacterial agents 4-hydroxybenzoic acid and ethylparaben,and the results were 0.02-49 μg·mL-1.This indicated that ethylparaben degradation and colinear production pollution were the two major risk sources.Conclusions The method is accurate,sensitive,and specific and can be used for the qualitative and quantitative detection of antibacterial agents in acyclovir eye drops.Besides,some products have degradation of antibacterial agents and incomplete cleaning during co-linear production.It is still essential to further reinforce product quality control.

AIM:To investigate the association between long noncoding RNA(lncRNA)growth arrest-specific transcript 5(GAS5)genetic polymorphism and the onset of polycystic ovary syndrome(PCOS).METHODS:The case-control study was performed,selecting 236 PCOS patients diagnosed at the Reproductive Medicine Center of the Affiliated Hospital of Guangxi Youjiang University for Nationalities from May 2018 to May 2019 as the case group,while 277 healthy women matched in sex and age during the same period were selected as the control group.The iMLDR single nucleotide polymorphism(SNP)was used to detected the genotypes of rs145204276 I/D,rs55829688 C/T and rs6790 G/A in GAS5 gene.The correlation between GAS5 gene polymorphism and PCOS was analyzed using logistic regression.RESULTS:The difference of GAS5 gene rs145204276 I/D polymorphism had statistical significance between control group and PCOS group.Logistic regression analysis showed that compared with the I/I genotype,the I/D and D/D genotypes,as well as the dominant model I/D+D/D,had a reduced risk of PCOS[I/D vs I:OR(95%CI)=0.61(0.42,0.88),P=0.009;D vs I/I:OR(95%CI)=0.44(0.23,0.84),P=0.013;I/D+D vs I/I:OR(95%CI)=0.57(0.40,0.81),P=0.002].Compared with the I allele,the D allele significantly reduced the risk of PCOS[D vs I:OR(95%CI)=0.62(0.47,0.82),P=0.001).There was no statistically significant difference in the polymorphism of rs55829688 C/T and rs6790 G/A between control group and PCOS group(P＞0.05).The combined analysis of haplotypes showed that the difference of D-T-A haplo-type distribution was statistically significant between control group and PCOS group[OR(95%CI)=0.61(0.45,0.84),P=0.002].CONCLUSION:The polymorphism of GAS5 gene rs145204276 I/D may be associated with genetic suscepti-bility to PCOS,and individuals carrying the D allele may have a reduced risk of developing PCOS.

Objective: To explore the relationship between septal myocardial metabolism and left ventricular mechanical synchronization in patients with dilated cardiomyopathy (DCM) and left bundle branch block (LBBB) by gated 18F-FDG myocardial metabolic imaging.
Methods: A total of 20 consecutive patients diagnosed for DCM with LBBB from 2010-10 to 2013-05 were enrolled, there were 11 male and 9 female at the mean age of (54±11) years. All patients received gated 18F-FDG myocardial metabolic PET imaging. TrueD software was used to determine the maximal standardized 18F-FDG uptake value (S-SUVmax) and the average standardized uptake value (S-SUVavg). QGS software was applied to conduct left ventricular phase analysis and to detect the cardiac function, left ventricular bandwidth (BW), standard deviation of bandwidth (SD), left ventricular end-diastolic volume (LVEDV), LVESV and LVEF. The relationship between 18F-FDG uptake in septal myocardium with the indexes of phase analysis and the indexes of cardiac function was analyzed.
Results: S-SUVmax and S-SUVavg were respectively negatively related to BW (r=-0.44, P<0.05 and r=-0.48, P<0.05);they were also respectively negatively related to SD (r=-0.57, P<0.01 and r=-0.51, P<0.05). While S-SUVmax and S-SUVavg were not really related to LVEDV, LVESV and LVEF, all P>0.05.
Conclusion: In patients of DCM with LBBB, reduced septal myocardial metabolism was closely related to left ventricular mechanical synchronization, gated 18F-FDG myocardial metabolic PET imaging may simultaneously detect both functions, which was important for prognostic evaluation and therapeutic monitoring in clinical practice;phase analysis.

Objective To explore the relationship between myocardial glucose metabolism in the right heart and cardiac function in patients with idiopathic dilated cardiomyopathy (IDCM).Methods From October 2010 to May 2013,64 consecutive patients (45 males,19 females; mean age:(53 ± 12) years) with IDCM were enrolled in this study.All patients underwent 18F-FDG myocardial PET imaging,late-gadolinium enhancement cardiac MRI (cMRI-LGE) and UCG.TrueD software was used to determine the SUVmax in right (SUV-R) and left (SUV-L) ventricular free wall,and the ratio of SUV-R to SUV-L (SUV-R/L) was calculated.The cMRI-LGE was used to evaluate LVEF,RVEF and LGE in left heart.Pulmonary artery systolic pressure (PASP) was measured by UCG.Two-sample t test and Pearson correlation analysis were used to analyze the data.Results Both SUV-R and SUV-R/L had negative correlation with LVEF (r=-0.48,-0.33; both P＜0.01) and also with RVEF (r=-0.45,-0.44; both P＜0.01).SUV-R/L positively correlated with PASP (r =0.58,P＜0.01).SUV-R/L of patients with and without LGE were statistically different (0.45±0.18 vs 0.36±0.12; t=2.50,P＜0.05).SUV-R and SUV-L of patients with LGE were 2.0±0.9 and 4.7±1.6,and those of patients without LGE were 1.7±0.9 and 5.0±2.8.Both differences of SUV-R and SUV-L between the two groups were not statistically significant (t=0.54 and 0.63,both P＞0.05).Conclusions Myocardial glucose metabolism in right heart is closely correlated with left and right ventricular function.The assessment of 18F-FDG uptake in right heart by PET imaging is potentially useful for evaluation of the severity and prognosis in IDCM patients.

Objective: To investigate the relationship between right ventricular (RV) glucose metabolism by18F-fludeoxyglucose positron emission tomography (18F-FDG PET) and right heart function in patients with dilated cardiomyopathy (DCM).
Methods: The18F-FDG PET imaging was performed in 34 consecutive DCM patients, with the reference of Herrero method, the corrected RV standard uptake value (cRVSUV), corrected left ventricular standard uptake value (cLVSUV) and the ratio of RV to LV SUV (cR/L) were obtained. And all 34 patients received cardiac magnetic resonance imaging (cMRI) examination within 7 days, the left ventricular ejection fraction (LVEF) and RVEF were automatically calculated with Simpson’s principle. The pulmonary arterial systolic pressure was measured by echocardiography.
Results: The corrected cRVSUV and cR/L by18F-FDG PET were negatively related to RVEF by cMRI, (r=-0.513, P<0.01) and (r=-0.463,P<0.01) respectively, and meanwhile, the corrected cRVSUV and cR/L were also negatively related to LVEF, (r=-0.387,P<0.01 andr=-0.362,P<0.01) respectively.
Conclusion: Increased RV glucose metabolism closely related to RV dysfunction, the18F-FDG uptake value by PET might be used as an index for assessing the right heart function and prognosis in DCM patients.

Radionuclide MPI is an important noninvasive modality for the diagnosis of coronary artery disease.The current clinically useful MPI tracers,201Tl and 99Tcm labeled agents,have limitations.Some known ligands bound with 99TcmN core might be promising MPI agents because of their high chemical stability.This review summarizes the structure,biodistribution and imaging characteristics of the 99TcmN core labelled MPI tracers with emphasis on several agents having promising prospects for future applications.

Objective To explore the relationship between hypothyroidism and myocardial injury in patients with idiopathic dilated cardiomyopathy (IDC) by 99Tcm-MIBI SPECT/18 F-FDG PET and late-gadolinium enhancement cardiac magnetic resonance imaging (cMRI-LGE).Methods Sixty-three consecutive patients (42 males and 21 females,(52±11) years) with IDC were enrolled from October 2010 to December 2012.Serum TT3,TT4,FT3,FT4 and TSH were determined using a fully automated chemiluminescence immunoassay.All patients underwent 99Tcm-MIBI myocardial perfusion SPECT/18F-FDG myocardial metabolism PET imaging and cMRI-LGE.Seventeen segments model was used for segmental analysis.Patterns of perfusion/metabolism were classified as normal,mismatch,mild-to-moderate match and complete match.cMRI-LGE was classified into 3 categories (non-LGE,mid-wall LGE and transmural LGE).x2 test was used for data analysis.Results All patients were divided into euthyroid group (n =53) and hypothyroidism group (n =10) according to the levels of serum thyroid hormones.The percentage of normal perfusion/metabolism segments in the euthyroid group was apparently higher than that in the hypothyroidism group:71.8％ (647/901) vs 57.6％ (98/170),x2 =13.50,P＜0.001 ; whereas the percentage of perfusion/metabolism mismatch segments in the euthyroid group was significantly lower than that in the hypothyroidism group:17.8％ (160/901) vs 31.2％ (53/170),x2=16.20,P＜0.001.The euthyroid group had a higher percentage of non-LGE segments (88.0％ (793/901) vs 69.4％ (118/170),x2 =35.70,P＜0.001) and a lower percentage of mid-wall LGE segments (4.8 ％ (43/901) vs 24.1％ (41 / 170),x2 =74.70,P＜ 0.001) compared to hypothyroidism group.Conclusions Hypothyroidism has a detrimental effect on myocardium.99Tcm-MIBI SPECT/18F-FDG PET imaging is sensitive in detecting viable/ischemia myocardium,and cMRI-LGE is good at detecting moderate fibrosis.Combining SPECT/PET imaging and cMRI-LGE for assessing myocardial injury would provide more comprehensive information.