Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Lung cancer has the highest incidence and mortality among malignant tumors in China.Persistent subsolid nodules(SSNs)are closely associated with early-stage lung adenocarcinoma.Artificial intelligence(AI),as an emerging technology,is capable of performing in-depth analysis of large-scale imaging data through autonomous learning and possesses the ability to predict outcomes from new data,demonstrating great potential and application prospects in the assessment of SSNs.AI can not only effectively assist radiologists in diagnosis and treatment,but also improve work efficiency while reducing misdiagnosis and missed diagnosis rates.This review summarizes the recent applications and research progress of AI in the assessment of SSNs,to provide new insights for the diagnosis and treatment of SSNs.

Bone defect repair is an urgent problem in the field of orthopedics,and numerous researchers are working to develop more effective treatment plans.The accurate evaluation of bone repair after surgery is a crucial step.In line with the development of computed tomography(CT)imaging,dual-energy CT imaging has shown significant advantages in analyzing bone composition and reducing metal artifacts.This article reviews the application of dual-energy CT imaging for the evaluation of bone repair in animals.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective:This study aimed to evaluate the value of CT-based radiomics machine learning models in predicting spread through air spaces(STAS)in lung adenocarcinoma(LUAD)and to determine the optimal peritumoral analysis region.Methods:Data from 378 pa-tients who underwent non-small cell lung cancer surgery at Zhejiang Cancer Hospital between January 2013 to January 2017 were retro-spectively analyzed.Logistic regression,random forest,and XGBoost models were constructed using regions extending 0,3,6,9,and 12 mm outward from the tumor margin.Results:The XGBoost model using the 6 mm peritumoral region performed best on the test set,with an AUC-ROC of 0.855(95%CI:0.756-0.950),followed by the XGBoost model using the 9 mm region.Decision curve analysis(DCA)indicated that the XGBoost models for the 6 mm and 9 mm regions had higher net clinical benefits.Feature analysis revealed that some wavelet trans-form features significantly contributed to STAS prediction.Conclusions:This preliminary study suggests that CT-based radiomics machine learning models have predictive value for STAS.The XGBoost model based on the 6 mm peritumoral region demonstrated the best perform-ance,and holds promise in assisting preoperative assessment.

Bone defect repair is an urgent problem in the field of orthopedics,and numerous researchers are working to develop more effective treatment plans.The accurate evaluation of bone repair after surgery is a crucial step.In line with the development of computed tomography(CT)imaging,dual-energy CT imaging has shown significant advantages in analyzing bone composition and reducing metal artifacts.This article reviews the application of dual-energy CT imaging for the evaluation of bone repair in animals.

Objective:To assess the effect of using different thicknesses of reconstruction layer and different thicknesses of region of interest (ROI) on the results of vertebral bone mineral density (BMD) values that were measured by quantitative computed tomography (QCT). Methods:A total of 100 patients who underwent QCT screening for opportunistic osteoporosis between May and September 2021 at the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Images that the thicknesses of QCT reconstruction layer were respectively 1 and 5 mm were transferred to the QCT Pro workstation,and ROI thicknesses were adjusted to 5,7,and 9 mm,respectively. The average BMD values of QCT measurements were recorded under different thicknesses of reconstruction layer and different ROI thicknesses. Then,the effects of the choose of different thicknesses of reconstruction layer and the different ROI thicknesses on BMD values that were measured by QCT were analyzed. Results:The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (117.41±45.97) mg/cm3 and (118.77±44.84) mg/cm3 when ROI thickness was 5 mm,with a statistically significant difference (t=-2.283,P<0.05). The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (116.38±46.06) mg/cm3 and (119.06±44.55) mg/cm3 when the ROI thickness was 7mm,and the difference was statistically significant (t=-3.280,P<0.05). The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (116.25±45.36) mg/cm3 and (120.12±44.10) mg/cm3 when the ROI thickness was 9 mm,and the difference was statistically significant (t=-5.841,P<0.001). The differences in BMD measurement values among 5,7 and 9 mm ROI thicknesses were not statistically significant when the thicknesses of reconstruction layer were respectively 1 and 5 mm. Conclusion:There is an effect of the thickness of QCT reconstruction layer on average BMD measurement values,and 1 mm thickness of reconstruction layer is more suitable to clinical application,while there is not significant effect in ROI thickness on average BMD measurement value of QCT. In clinical application,it is feasible to adjust ROI thickness according to actual situation so as to avoid the effect caused by some factors such as fracture or vertebral implants.

Objective:To assess the effect of using different thicknesses of reconstruction layer and different thicknesses of region of interest (ROI) on the results of vertebral bone mineral density (BMD) values that were measured by quantitative computed tomography (QCT). Methods:A total of 100 patients who underwent QCT screening for opportunistic osteoporosis between May and September 2021 at the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Images that the thicknesses of QCT reconstruction layer were respectively 1 and 5 mm were transferred to the QCT Pro workstation,and ROI thicknesses were adjusted to 5,7,and 9 mm,respectively. The average BMD values of QCT measurements were recorded under different thicknesses of reconstruction layer and different ROI thicknesses. Then,the effects of the choose of different thicknesses of reconstruction layer and the different ROI thicknesses on BMD values that were measured by QCT were analyzed. Results:The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (117.41±45.97) mg/cm3 and (118.77±44.84) mg/cm3 when ROI thickness was 5 mm,with a statistically significant difference (t=-2.283,P<0.05). The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (116.38±46.06) mg/cm3 and (119.06±44.55) mg/cm3 when the ROI thickness was 7mm,and the difference was statistically significant (t=-3.280,P<0.05). The average BMD values of 1 mm and 5 mm thicknesses of reconstruction layer were respectively (116.25±45.36) mg/cm3 and (120.12±44.10) mg/cm3 when the ROI thickness was 9 mm,and the difference was statistically significant (t=-5.841,P<0.001). The differences in BMD measurement values among 5,7 and 9 mm ROI thicknesses were not statistically significant when the thicknesses of reconstruction layer were respectively 1 and 5 mm. Conclusion:There is an effect of the thickness of QCT reconstruction layer on average BMD measurement values,and 1 mm thickness of reconstruction layer is more suitable to clinical application,while there is not significant effect in ROI thickness on average BMD measurement value of QCT. In clinical application,it is feasible to adjust ROI thickness according to actual situation so as to avoid the effect caused by some factors such as fracture or vertebral implants.

AIM To explore the clinical effects of Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation on patients with mild to moderate bronchial asthma in chronic and persistent period.METHODS One hundred and eighteen patients were randomly assigned into control group(59 cases)for 4-week administration of Budesonide and Formoterol Fumarate Powder for Inhalation,and observation group(59 cases)for 4-week administration of both Jiawei Yanghe Decoction and Budesonide and Formoterol Fumarate Powder for Inhalation.The changes in clinical effects,ACT score,bronchial asthma control rate,pulmonary function indices(FEV1,PEF,FEV1％,PEF％),inflammatory indices(EOS,EOS％,FeNO),TCM syndrome score and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed increased bronchial asthma control rate,ACT score,PEF(P＜0.05),and decreased TCM syndrome score(P＜0.05),especially for the observation group(P＜0.05);the observation group exhibited increased FEV1,FEV1％,PEF％(P＜0.05),among which FEV1,PEF％were higher than those in the control group(P＜0.05);the observation group showed decreased inflammatory indices(P＜0.05),among which FeNO was lower than that in the control group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with mild to moderate bronchial asthma in chronic and persistent period,Jiawei Yanghe Decoction combined with Budesonide and Formoterol Fumarate Powder for Inhalation can safely and effectively alleviate clinical symptoms,improve pulmonary functions,airway inflammatory reactions,and enhance bronchial asthma control rate.

Objective:This study aimed to evaluate the value of CT-based radiomics machine learning models in predicting spread through air spaces(STAS)in lung adenocarcinoma(LUAD)and to determine the optimal peritumoral analysis region.Methods:Data from 378 pa-tients who underwent non-small cell lung cancer surgery at Zhejiang Cancer Hospital between January 2013 to January 2017 were retro-spectively analyzed.Logistic regression,random forest,and XGBoost models were constructed using regions extending 0,3,6,9,and 12 mm outward from the tumor margin.Results:The XGBoost model using the 6 mm peritumoral region performed best on the test set,with an AUC-ROC of 0.855(95%CI:0.756-0.950),followed by the XGBoost model using the 9 mm region.Decision curve analysis(DCA)indicated that the XGBoost models for the 6 mm and 9 mm regions had higher net clinical benefits.Feature analysis revealed that some wavelet trans-form features significantly contributed to STAS prediction.Conclusions:This preliminary study suggests that CT-based radiomics machine learning models have predictive value for STAS.The XGBoost model based on the 6 mm peritumoral region demonstrated the best perform-ance,and holds promise in assisting preoperative assessment.