(+)-Borneol, the main component of "Natural Borneol" in the Chinese Pharmacopoeia, is a high-end spice and precious medicine. Plant extraction cannot meet the increasing demand for (+)-borneol, while microbial biosynthesis offers a sustainable supply route. However, its production was extremely low compared with other monoterpenes, even with extensively optimizing the mevalonate pathway. We found that the key challenge is the complex and unusual dephosphorylation reaction of bornyl diphosphate (BPP), which suffers the side-reaction and the competition from the cellular dephosphorylation process, especially lipid metabolism, thus limiting (+)-borneol synthesis. Here, we systematically optimized the dephosphorylation process by identifying, characterizing phosphatases, and balancing cellular dephosphorylation metabolism. For the first time, we identified two endogenous phosphatases and seven heterologous phosphatases, which significantly increased (+)-borneol production by up to 152%. By engineering BPP dephosphorylation and optimizing the MVA pathway, the production of (+)-borneol was increased by 33.8-fold, which enabled the production of 753 mg/L under fed-batch fermentation in shake flasks, so far the highest reported in the literature. This study showed that rewiring dephosphorylation metabolism was essential for high-level production of (+)-borneol in Saccharomyces cerevisiae, and balancing cellular dephosphorylation is also helpful for efficient biosynthesis of other terpenoids since all whose biosynthesis involves the dephosphorylation procedure.

Background Pneumoconiosis is a chronic inflammatory disease that cannot be completely cured. Therefore, how to control lung inflammation and delay of the body aging is one of the keys to treating pneumoconiosis. The studies in past two decades suggested that many small molecule drugs are able to enhance cardiopulmonary function. Objective To explore the effects of homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine on experimental silicosis in rats. Methods Seventy-two SD specific pathogen-free rats were randomized into 4 groups (18 mice in each group): negative control group (ultrapure water, without dust), positive control group, homeopathic treatment group, co-administered treatment group. One mL of quartz dust suspension was injected into the rat trachea by disposable non-exposed tracheal injection method (50 mg·mL⁻¹) to establish a rat silicosis model. Rats were administered by gavage since the 4th day after dust exposure. The homeopathic treatment group rats received taurine solution (0.03 g·mL⁻¹) in the morning and β-nicotinamide mononucleotide (0.03 g·mL⁻¹) in the afternoon; the co-administered treatment group rats received a mixed solution (0.015 g·mL⁻¹ β-nicotinamide mononucleotide + 0.015 g·mL⁻¹ taurine) twice, in the morning and afternoon respectively. The positive and negative control groups received equivalent of ultrapure water in the morning and afternoon. All groups of rats were administered 5 d a week for a total of 6 weeks. The rats were neutralized after 6 weeks of administration. Organ coefficient, lung hydroxyproline content, whole lung dry and wet weights, whole lung free silica content, and cell count and classification in lung lavage fluid were measured and calculated, and lung histopathological changes in lung samples were observed. Results Compared with the positive control group, the whole lung wet weight, whole lung dry weight , total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were reduce in the homeopathic treatment group, and the co-administered treatment group (P＜0.05). Compared with the negative control group, the total cell count, neutrophil rate, lung organ coefficient, lung hydroxyproline content, and whole lung free silica content were elevated in the homeopathic treatment group and the co-administered treatment group, the whole lung dry weight was elevated in the co-administered treatment group, and those differences were all statistically significant (P＜0.05). The rat lung histopathological results showed that, in the positive control group, round or oval nodules were formed in the lung tissue, which were phagocytic cellular nodules, and the alveolar structures in some areas still existed. The histopathological changes in the homeopathic treatment group and the co-administered treatment group were similar to those of the positive group, but less severe. No pathological change was observed in the lung tissue of the negative control group. Conclusion Some improvement and dust removal in experimental silicosis rats by homeopathic dosing and combined dosing of β-nicotinamide mononucleotide and taurine are observed.

Objective To construct a global model of cardiac surface motion based on average intensity projection(AIP)image.Methods The cine magnetic resonance imaging data were divided into training set and test set for model construction and validation.The datum points were obtained on the AIP surface point cloud,and the corresponding points of each cardiac phase surface point cloud were found based on surface features.Principal component analysis was used to extract feature information,establish the mapping relationship between the datum points and the corresponding points,and construct a model for predicting each temporal phase surface point cloud from the AIP surface point cloud.Results The RMSE of the model on test set for corresponding point prediction ranged from(0.209±0.020)mm to(0.841±0.074)mm,while the Euclidean distance for each time phase surface point cloud prediction ranged from(1.399±0.029)mm to(1.658±0.100)mm.Conclusion The proposed global model exhibit high accuracy and can provide a reference for image segmentation and clinical treatments.

With the rapid advancements in minimally invasive spine surgery and the increasingly sophisti-cated concept of visualization,transforaminal endoscopic lumbar discectomy(TELD)has become a primary treatment for lumbar disc herniation.Among the critical preoperative steps in TELD,foraminalplasty plays a pivotal role,as its quality directly impacts surgical outcomes and postoperative recurrence rates.This article systemati-cally reviews the evolution of foraminalplasty techniques,evaluates the selection and application of plasty sites,examines factors influencing stability after lumbar foraminalplasty,and highlights recent advancements in computer-assisted navigation.The goal is to serve as a comprehensive reference for clinicians.

Objective:To investigate the effects of dagliprazin combined with olmesartan ester on the expression of Plin and miR-26a in renal tissues of diabetic nephropathy rats.Methods:Sixty male SD rats were selected and fed adaptively for 1 week, then fed high-fat and high-sugar diet for 2 months, and then injected streptozotocin (STZ) 30 mg/kg for modeling. They were given 10 mg/kg daaglizin intragastric administration as daglizin group, 10 mg/kg olmesartan ester intragastric administration as olmesartan ester group, 5 mg/kg daaglizin and 5 mg/kg olmesartan ester intragastric administration as daglizin and olmesartan ester combination group, respectively. Twenty rats were given 10 mg/kg normal saline intragastric administration as normal control group. After 3 months, the serum samples of rats were taken to detect the levels of fasting blood glucose, blood creatinine, urea nitrogen, 24h urinary microalbumin and other renal function indicators and the levels of C-reactive protein (CRP), tumor necrosis factor (TNF-α), cell surface specific marker antigen (ED-1) and other inflammatory responses. Then the rats were killed and their kidney tissues were taken. The protein and gene expression of vascular endothelial growth factor (VEGF), perilipin (Plin), Nephlrin, miR-26a were detected by Western blot and real-time fluorescence quantitative PCR.Results:The levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05). The difference between groups was statistically significant ( P<0.05). The levels of serum CRP, TNF-αand ED-1 in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of CRP, TNF-αand ED-1 in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05). The expression of serum VEGF, Plin and Nephlrin protein in dagliprazin group, olmesartan ester group and combined group were lower than those in normal control group ( P<0.05), while the protein and gene of Plin and Nephlrin in combined group were lower than those in dagliprazin group and olmesartan ester group. The mRNA and protein expressions of miR-26a and VEGF were higher than those of Daglipzin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05) . Conclusion:Dagliprazin combined with olmesartan ester can reduce kidney injury and delay the progression of diabetic nephropathy by regulating the expression of Plin and miR-26a protein and gene in renal tissue of diabetic nephropathy rats.

Objective:To investigate the effects of dagliprazin combined with olmesartan ester on the expression of Plin and miR-26a in renal tissues of diabetic nephropathy rats.Methods:Sixty male SD rats were selected and fed adaptively for 1 week, then fed high-fat and high-sugar diet for 2 months, and then injected streptozotocin (STZ) 30 mg/kg for modeling. They were given 10 mg/kg daaglizin intragastric administration as daglizin group, 10 mg/kg olmesartan ester intragastric administration as olmesartan ester group, 5 mg/kg daaglizin and 5 mg/kg olmesartan ester intragastric administration as daglizin and olmesartan ester combination group, respectively. Twenty rats were given 10 mg/kg normal saline intragastric administration as normal control group. After 3 months, the serum samples of rats were taken to detect the levels of fasting blood glucose, blood creatinine, urea nitrogen, 24h urinary microalbumin and other renal function indicators and the levels of C-reactive protein (CRP), tumor necrosis factor (TNF-α), cell surface specific marker antigen (ED-1) and other inflammatory responses. Then the rats were killed and their kidney tissues were taken. The protein and gene expression of vascular endothelial growth factor (VEGF), perilipin (Plin), Nephlrin, miR-26a were detected by Western blot and real-time fluorescence quantitative PCR.Results:The levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of fasting blood glucose, urea nitrogen, creatinine and 24h urinary microalbumin in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05). The difference between groups was statistically significant ( P<0.05). The levels of serum CRP, TNF-αand ED-1 in dagliprazin group, olmesartan ester group and combined group were higher than those in normal control group ( P<0.05), while the levels of CRP, TNF-αand ED-1 in combined group were lower than those in dagliprazin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05). The expression of serum VEGF, Plin and Nephlrin protein in dagliprazin group, olmesartan ester group and combined group were lower than those in normal control group ( P<0.05), while the protein and gene of Plin and Nephlrin in combined group were lower than those in dagliprazin group and olmesartan ester group. The mRNA and protein expressions of miR-26a and VEGF were higher than those of Daglipzin group and olmesartan ester group ( P<0.05), and the differences between groups were statistically significant ( P<0.05) . Conclusion:Dagliprazin combined with olmesartan ester can reduce kidney injury and delay the progression of diabetic nephropathy by regulating the expression of Plin and miR-26a protein and gene in renal tissue of diabetic nephropathy rats.

Objective To construct a global model of cardiac surface motion based on average intensity projection(AIP)image.Methods The cine magnetic resonance imaging data were divided into training set and test set for model construction and validation.The datum points were obtained on the AIP surface point cloud,and the corresponding points of each cardiac phase surface point cloud were found based on surface features.Principal component analysis was used to extract feature information,establish the mapping relationship between the datum points and the corresponding points,and construct a model for predicting each temporal phase surface point cloud from the AIP surface point cloud.Results The RMSE of the model on test set for corresponding point prediction ranged from(0.209±0.020)mm to(0.841±0.074)mm,while the Euclidean distance for each time phase surface point cloud prediction ranged from(1.399±0.029)mm to(1.658±0.100)mm.Conclusion The proposed global model exhibit high accuracy and can provide a reference for image segmentation and clinical treatments.

With the rapid advancements in minimally invasive spine surgery and the increasingly sophisti-cated concept of visualization,transforaminal endoscopic lumbar discectomy(TELD)has become a primary treatment for lumbar disc herniation.Among the critical preoperative steps in TELD,foraminalplasty plays a pivotal role,as its quality directly impacts surgical outcomes and postoperative recurrence rates.This article systemati-cally reviews the evolution of foraminalplasty techniques,evaluates the selection and application of plasty sites,examines factors influencing stability after lumbar foraminalplasty,and highlights recent advancements in computer-assisted navigation.The goal is to serve as a comprehensive reference for clinicians.

Objective: To explore the association between physical activity levels and depressive symptoms among college students, so as to provide evidence for promoting physical and mental health of college students. Methods: Using a cohort study design,a baseline survey of 1 415 college students in Shenyang Normal University in 2017 followed for three years from 2018 to 2020. The International Physical Activity Questionnaire-Short Form (IPAQ-SF) and Selfrating Depression Scale (SDS) were used to evaluate the physical activity levels and depressive symptoms of college students. According to the level of physical activity at baseline (MET ·h/week), participants were divided into three groups [T1 (≤36.4), T2 (>36.4-89.3) and T3 (>89.3)]. Logistic regression analysis was used to examine the association between baseline physical activity levels and the incidence of depressive symptoms during the school years. Results: In the 3year followup (2018-2020), 852 (60.2%) participants exhibited depressive symptoms. The numbers of individuals with depressive symptoms in the T1, T2, and T3 groups were 324, 268, and 260, respectively. Logistic regression analysis showed that college students who participated in higher levels of physical activity decreased the risk of depressive symptoms by 34.2% [T2: OR(95%CI) = 0.658 (0.500-0.866)] and 38.9% [T3:OR(95%CI)=0.611(0.465-0.804)] compared with T1 group after adjusting for demographic, lifestyle, healthrelated factors, and baseline depressive symptoms as covariates. The sexstratified analysis showed a negative correlation between physical activity levels and the incidence of depressive symptoms in female college students. Compared with T1 group, higher levels of physical activity reduced the incidence of depressive symptoms by 39.6% [T2: OR(95%CI)=0.604(0.445-0.820)] and 37.7% [T3: OR(95%CI)=0.623(0.459-0.846)], respectively (P<0.01). However, there was no significant correlation between physical activity levels and depressive symptoms in male college students (P>0.05). Conclusions There is an inverse relationship between physical activity levels and depressive symptoms. The findings suggest that schools should reduce the risk of depressive symptoms by promoting physical activity levels among college students.

BACKGROUND:The landing error scoring system test is a standard for assessing the risk of non-contact injuries and has not yet been developed for Chinese college soccer programs. OBJECTIVE:To establish a test evaluation standard for the landing error scoring system to provide a basis for evaluating the risk of non-contact injuries in college soccer students. METHODS:A prospective cohort study was designed in which 219 athletes from 10 college soccer teams were tested with the standard landing error scoring system,and the subjects were followed up by questionnaires and medical examinations for non-contact injuries of the lower extremities and trunk for 1 year after testing to determine sex differences and assessment criteria for the landing error scoring system test indicators. RESULTS AND CONCLUSION:The total score of the landing error scoring system was(8.22±1.65)points for 219 subjects,(8.29±1.74)for males and(8.07±1.44)for females,with no significant difference between males and females(P>0.05).Within 1 year after the test,the overall injury rate of 219 subjects was 10.05%and the morbidity rate was 15.98%;the injury rate of male subjects with non-contact injury of the lower limbs and trunk was 12.75%and the morbidity rate was 20.13%;the injury rate of female subjects with non-contact injury of the lower limbs and trunk was 4.29%and the morbidity rate was 7.14%.There were no significant differences in the injury rate between men and women(P<0.05).The total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.50±1.14)vs.(8.08±1.64),P<0.01];for male subjects,the total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.63±1.12)vs.(8.09±1.73),P<0.01].The area under the curve for the total score of the landing error scoring system was 0.773(P=0.000),which had a diagnostic value for the risk of non-contact injury of the lower extremities and trunk in male subjects,with a best cut-off point of 8.5,sensitivity of 0.842,specificity of 0.623,positive likelihood ratio of 2.233,negative likelihood ratio of 0.254,relative risk factor of 8.400,and odds ratio of 8.816;the total score of the landing error scoring system was not applicable for assessing the risk of non-contact injury of the lower extremities and trunk in female subjects.To conclude,the landing error scoring system test can be used as a criterion to assess the risk of non-contact injury to the lower extremity and trunk in Chinese college male soccer players,with an optimal cut-off point of 8.5.The risk of non-contact injury to the lower extremity and trunk is 8.40 times higher in male athletes with a landing error scoring system test score of≥8.5 than in male athletes with a score of<8.5.