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

Alveolar bone reconstruction simulation is an effective means for quantifying orthodontics, but currently, it is not possible to directly obtain human alveolar bone material models for simulation. This study introduces a prediction method for the equivalent shear modulus of three-dimensional random porous materials, integrating the first-order Ogden hyperelastic model to construct a computed tomography (CT) based porous hyperelastic Ogden model (CT-PHO) for human alveolar bone. Model parameters are derived by combining results from micro-CT, nanoindentation experiments, and uniaxial compression tests. Compared to previous predictive models, the CT-PHO model shows a lower root mean square error (RMSE) under all bone density conditions. Simulation results using the CT-PHO model parameters in uniaxial compression experiments demonstrate more accurate prediction of the mechanical behavior of alveolar bone under compression. Further prediction and validation with different individual human alveolar bone samples yield accurate results, confirming the generality of the CT-PHO model. The study suggests that the CT-PHO model proposed in this paper can estimate the material properties of human alveolar bone and may eventually be used for bone reconstruction simulations to guide clinical treatment.
Humans ; Tomography, X-Ray Computed/methods* ; Porosity ; Alveolar Process/physiology* ; Bone Density ; Computer Simulation ; Elasticity ; X-Ray Microtomography ; Stress, Mechanical ; Finite Element Analysis ; Models, Biological

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength

Objectives:To analyze the consistency of evaluating left ventricular hemodynamics (HDF) based on single plane and multi plane cine sequences of magnetic resonance mitral valve orifice.Methods:A prospective study was conducted on 48 healthy adults, and two methods were used to measure the mitral valve diameter and calculate HDF parameters. The first method was to measure the diameter of the mitral valve opening in the left ventricular three chamber cine sequence; The second method is to measure the mitral valve diameter using cine sequences of two chamber, three chamber, and four chamber hearts, and then take the average value. Paired t-tests were used to compare the differences in HDF measured by two methods, and Pearson correlation coefficient ( r), intra group correlation coefficient ( ICC), and Bland-Altman analysis were used to test the consistency and reproducibility of the two methods. Results:The root mean square (RMS) of longitudinal HDF calculated using single plane and multi plane mitral valve diameters were [(17.28±4.41)% vs (17.21±4.61)%] ( P=0.379) for the entire cardiac cycle, [(21.45±5.54)% vs (21.49±5.68)%] ( P=0.646) for systolic phase, and [(12.78±4.10)% vs (12.54±4.24)%] ( P=0.106) for diastolic phase, respectively. The difference in the calculation results of HDF parameters related to ventricular function was not statistically significant (all P>0.05), and there was good consistency ( r=0.924-0.996, ICC=0.924-0.995). The two HDF parameters related to atrial function were sensitive to the measurement method of mitral valve orifice diameter [RMS of longitudinal HDF during active atrial emptying: (3.26±1.51)% vs (3.32±1.55)%, P=0.006; longitudinal HDF pulse during active atrial emptying: (-2.60±1.28)% vs (-2.76±1.30)%, P<0.001]. Conclusions:The ventricular function related HDF parameters obtained from the analysis of mitral valve orifice diameter using single plane and multi plane methods have good consistency, and can be evaluated using relatively simple single plane methods for left ventricular HDF.

The operating room was the core department of a hospital,and its operational efficiency had a significant impact on the high-quality development of a hospital.An analysis has revealed that low efficiency and irrational allocation in the operating room were mainly due to the lack of operational regulations and norms,the unreasonable arrangement of surgical specialties,and the unbalanced allocation of supporting resources.To address these issues,the First Affiliated Hospital of Zhengzhou University has taken into account the overall allocation of resources for the central operating room and the central operating room,and formulated strategies to improve operational efficiency,including adjusting the operational mechanism,optimizing the structure of surgical specialties,and providing corresponding supporting resources.Based on the adjustment of surgical structure,the implementation effect of the program was measured and evaluated,which provided practical strategies for optimizing operating room efficiency in hospitals.

The operating room was the core department of a hospital,and its operational efficiency had a significant impact on the high-quality development of a hospital.An analysis has revealed that low efficiency and irrational allocation in the operating room were mainly due to the lack of operational regulations and norms,the unreasonable arrangement of surgical specialties,and the unbalanced allocation of supporting resources.To address these issues,the First Affiliated Hospital of Zhengzhou University has taken into account the overall allocation of resources for the central operating room and the central operating room,and formulated strategies to improve operational efficiency,including adjusting the operational mechanism,optimizing the structure of surgical specialties,and providing corresponding supporting resources.Based on the adjustment of surgical structure,the implementation effect of the program was measured and evaluated,which provided practical strategies for optimizing operating room efficiency in hospitals.

The operating room was the core department of a hospital,and its operational efficiency had a significant impact on the high-quality development of a hospital.An analysis has revealed that low efficiency and irrational allocation in the operating room were mainly due to the lack of operational regulations and norms,the unreasonable arrangement of surgical specialties,and the unbalanced allocation of supporting resources.To address these issues,the First Affiliated Hospital of Zhengzhou University has taken into account the overall allocation of resources for the central operating room and the central operating room,and formulated strategies to improve operational efficiency,including adjusting the operational mechanism,optimizing the structure of surgical specialties,and providing corresponding supporting resources.Based on the adjustment of surgical structure,the implementation effect of the program was measured and evaluated,which provided practical strategies for optimizing operating room efficiency in hospitals.

The operating room was the core department of a hospital,and its operational efficiency had a significant impact on the high-quality development of a hospital.An analysis has revealed that low efficiency and irrational allocation in the operating room were mainly due to the lack of operational regulations and norms,the unreasonable arrangement of surgical specialties,and the unbalanced allocation of supporting resources.To address these issues,the First Affiliated Hospital of Zhengzhou University has taken into account the overall allocation of resources for the central operating room and the central operating room,and formulated strategies to improve operational efficiency,including adjusting the operational mechanism,optimizing the structure of surgical specialties,and providing corresponding supporting resources.Based on the adjustment of surgical structure,the implementation effect of the program was measured and evaluated,which provided practical strategies for optimizing operating room efficiency in hospitals.

The operating room was the core department of a hospital,and its operational efficiency had a significant impact on the high-quality development of a hospital.An analysis has revealed that low efficiency and irrational allocation in the operating room were mainly due to the lack of operational regulations and norms,the unreasonable arrangement of surgical specialties,and the unbalanced allocation of supporting resources.To address these issues,the First Affiliated Hospital of Zhengzhou University has taken into account the overall allocation of resources for the central operating room and the central operating room,and formulated strategies to improve operational efficiency,including adjusting the operational mechanism,optimizing the structure of surgical specialties,and providing corresponding supporting resources.Based on the adjustment of surgical structure,the implementation effect of the program was measured and evaluated,which provided practical strategies for optimizing operating room efficiency in hospitals.