(+)-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.

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.

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 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 gene expression profile in paraspinal muscle degeneration(PMD)and identify key ferroptosis genes.Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes.Through protein-protein interaction(PPI)and gene functional enrichment analysis,the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis.The diagnostic value for PMD disease was analyzed by receiver operating characteristic(ROC)curves.Results A total of 292 differentially expressed genes were identified in PMD.Among them,125 genes were significantly downregulated and 167 genes were significantly upregulated.Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis.Among them,ferroptosis genes MUC1,ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD.Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis,ferroptosis and skeletal muscle tissue development and differentiation.Conclusion Ferroptosis genes MUC1,ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD,providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.