Sesquiterpenes are natural terpenes containing 15 carbon atoms. They are widely used in the perfume, pharmaceutical, and biofuel industries due to their remarkable biological activities. The traditional production of sesquiterpenes relies on chemical synthesis or plant extraction, which has the disadvantages of low yields and waste of resources. The construction of microbial cell factories for the efficient synthesis of sesquiterpenes by means of synthetic biology provides a new option. In recent years, with the development of metabolic engineering and synthetic biology, the heterologous synthesis of a variety of sesquiterpenes has been successfully achieved by metabolic engineering of the oleaginous yeast, Yarrowia lipolytica. In this paper, we review the research progress in the heterologous synthesis of different sesquiterpenes by Y. lipolytica, discuss the synthetic biology strategies commonly used in this field, and make an outlook on the research directions and engineering approaches to further enhance the sesquiterpene yield in this host. This paper provides a reference for strategies such as synergistic optimization of synthetic biology and metabolic engineering, enhanced precursors, and opens up new directions for the application of synthetic biology in green chemistry and sustainable production.
Yarrowia/genetics* ; Sesquiterpenes/metabolism* ; Metabolic Engineering/methods* ; Synthetic Biology/methods*

BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

Objective:To explore the impact of noise and dust exposure in the mechanical manufacturing industry on the risk of hypertension and abnormal electrocardiogram in workers, and their combined effects, in order to provide support for the prevention and treatment of occupational related diseases among workers.Methods:In January 2024, A convenience sampling method was used to study 2802 on-the-job workers who underwent occupational health check-ups from January 2023 to December 2023 at a machinery manufacturing enterprise in Baotou, Inner Mongolia. Blood pressure and electrocardiogram results were analyzed in the noise group, dust group, dust noise group and control group according to the exposure factors. For count data, the chi-square test was employed to analyze differences among groups. Additionally, a binary logistic regression model was utilized to assess the impact of dust and noise exposure on the prevalence of hypertension and electrocardiogram abnormalities.Results:The stratified analysis results showed that the differences in hypertension prevalence among the four groups were statistically significant ( P<0.001) in males, age groups >30-40 years, >40-50 years, >50 years, different exposure durations, and different enterprise sizes. For ECG abnormalities, significant differences were observed among the four groups ( P<0.001) in males, the age group >30-40 years, different enterprise sizes, and those with exposure durations ≤15 years. The trend test for hypertension prevalence across different age groups revealed that as age increased, the prevalence of hypertension showed an upward trend in the noise-exposed group, dust-exposed group, and combined dust-noise-exposed group ( χ2=10.76, 4.25, 6.60, P<0.001, 0.039, 0.010) . Binary regression model analyses revealed that the the risk of hypertension in the noise group, dust group and dust noise group was 2.63 times ( OR=2.63, 95% CI: 1.89~3.67, P<0.001) , 2.36 times ( OR=2.36, 95% CI: 1.76~3.16, P<0.001) and 2.69 times ( OR=2.69, 95% CI: 2.14~3.38, P<0.001) . Using ECG abnormalities as the dependent variable and incorporating the statistically significant variables from Table 1 as independent variables into the binary logistic regression model, the results showed no statistically significant differences in the risk of ECG abnormalities in the dust-exposed, noise-exposed, and combined dust-noise-exposed groups compared to the control group ( P> 0.05) . Conclusion:Combined exposure to dust and noise increases the risk of hypertension in workers and has a combined effect.

Objective:To investigate the status and influencing factors of substantial weight retention in patients with gestational diabetes mellitus (GDM) in early postpartum.Methods:This cross-sectional study employed a convenience sampling method to select 373 patients with GDM who underwent a 6-week postpartum health check at the Postpartum Health Clinic of Women′s Hospital of Nanjing Medical University from February to July in 2023. According to postpartum weight retention (PPWR) on the survey day, the participants were divided into a substantial PPWR group (≥5 kg, 139 cases) and a non-substantial PPWR group (<5 kg, 234 cases). Independent sample t-tests and χ2 tests were used to compare differences in demographic data, clinical data, and biochemical indicators between the two groups. Binary logistic regression was used to analyze the influencing factors of early substantial postpartum weight retention in patients with GDM. Results:A total of 37.27% (139/373) of GDM patients experienced substantial postpartum weight retention at 6 weeks postpartum. The rates of diabetes in family history, excessive gestational weight gain, gestational hypertension, and infant neonatal intensive care unit (NICU) admission in substantial PPWR group were all significantly higher than those in the non-substantial PPWR group (32.37% vs 23.08%, 73.38% vs 20.09%, 13.67% vs 5.56%, 21.58% vs 9.83%) (all P<0.05); but the proportion of overweight or obese before pregnancy and postpartum self-monitoring of blood glucose were both lower in the substantial PPWR group than those in the non-substantial PPWR group (25.18% vs 41.03%, 17.99% vs 27.78%)(all P<0.05). Binary logistic regression indicated that family history of diabetes ( OR=2.826, 95% CI: 1.517-5.265), excessive gestational weight gain ( OR=19.240, 95% CI: 10.360-35.732), and infant NICU admission ( OR=2.447, 95% CI: 1.150-5.205) were positively related to the occurrence of substantial weight retention in patients with GDM in early postpartum, whereas pre-pregnancy overweight or obesity ( OR=0.189, 95% CI: 0.100-0.360) was negatively correlated to substantial weight retention in patients with GDM in early postpartum (all P<0.05). Conclusion:Substantial weight retention is prevalent among GDM patients in early postpartum, which is significantly influenced by family history of diabetes, pre-pregnancy overweight or obesity, excessive gestational weight gain, and infant NICU admission history.

Palliative care is recognized as an effective measure to improve the quality of life for patients with end-stage diseases， and the significance and role of such patients participating in clinical trials to conquer major diseases has also become a broad consensus. However， due to the special physical， psychological， and social conditions of terminal trial participants， the ethical problems encountered in the trial process are more serious and complex. Drawing on ethical practice experience， these seemingly common phenomena and issues were deeply analyzed. Combined with the palliative care philosophy for end-stage patients， this paper proposed a series of improvement suggestions throughout the entire life cycle of clinical trials， hoping to promote the quality improvement of clinical research in which end-stage patients participate as subjects， while effectively protecting the safety and rights of the subjects and ensuring they receive appropriate palliative care during their participation in clinical trials or clinical-related scientific research.

Objective To develop a postoperative self-management question prompt list for adult liver transplant recipients and conduct preliminary application,aiming to provide an effective tool for facilitating their engagement in postoperative self-management.Methods From August to September 2024,the first draft of the postoperative self-management question prompt list for adult liver transplant recipients was developed through literature search and qualitative interviews,including 9 primary items and 50 secondary items.From October to November 2024,16 experts from Qingdao,Jinan,Beijing,and Fuzhou were interviewed on the Delphi method for 2 rounds to revise the question prompt list.From February to March 2025,19 patients after liver transplantation were selected for the preliminary application of the question prompt list.Results The response rates in the 2 rounds of consultations were both 100％and the authority coefficients of experts were both 0.88.The Kendall's W in the 2 rounds was 0.336 and 0.344(P＜0.001),respectively.The final question prompt list includes 9 primary items and 49 secondary items.The study showed that QPL demonstrated high clinical practicability in helping patients systematically understand the self-management framework after liver transplantation,promoting doctor-patient communication,and enhancing the initiative of self-management.Conclusion The question prompt list of postoperative self-management for adult liver transplant recipients established in this study is scientific,reliable,and practical,which is helpful for patients to obtain information about self-management from medical staff.

Abstract Ferroptosis , a novel , non-apoptotic form of cell death discovered in 2012 , has garnered significant at- tention. It is implicated in the pathogenesis and progression of various intestinal diseases , including colorectal canc- er, intestinal ischemia-reperfusion injury , functional gastrointestinal disorders , and inflammatory bowel disease. These processes involve multiple pathological mechanisms such as inflammation , immune dysregulation , and intesti- nal epithelial dysfunction. By reviewing and summarizing recent literature on ferroptosis-related mechanisms in in- testinal diseases , this article explores the roles and effects of ferroptosis in different intestinal pathologies.

Objective:To investigate the impact of donor age on early postoperative liver function recovery in liver transplant recipients, as well as the incidence and risk factors for arterial complications following liver transplantation.Methods:A total of 518 patients who underwent liver transplantation at the Organ Transplantation Center of the Affiliated Hospital of Qingdao University between January 2021 and January 2024 were included in the study. Based on donor age, patients were classified into the elderly donor group (≥70 years, n=28) and the non-elderly donor group (<70 years, n=490). Liver function indicators—including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and direct bilirubin (DBIL)—were measured on postoperative days 1, 3, 7, and 14. The incidence of arterial complications, including hepatic artery thrombosis and hepatic artery stenosis, was recorded. Recipients were further categorized into the arterial complication group (n=26) and the non-arterial complication group (n=492) based on postoperative outcomes, and clinical characteristics of donors and recipients were compared. Binary logistic regression analysis was conducted to identify risk factors for arterial complications.Rusults:No significant differences were observed in baseline characteristics between the elderly and non-elderly donor groups ( P>0.05). However, the elderly donor group exhibited significantly higher AST, ALT, TBIL, and DBIL levels at all postoperative time points compared to the non-elderly donor group (all P<0.05). Specifically, on postoperative day 1, AST and ALT levels were (1,024.57±256.49) U/L and (756.24±145.89) U/L in the elderly donor group, compared to (895.23±225.19) U/L and (614.85±126.51) U/L in the non-elderly donor group. On day 3, AST and ALT levels were (402.46±71.61) U/L and (423.31±87.44) U/L versus (226.37±66.54) U/L and (256.79±70.25) U/L, respectively. On day 7, AST and ALT levels were (91.78±21.84) U/L and (92.36±21.62) U/L versus (68.41±18.38) U/L and (77.47±18.16) U/L. By day 14, AST and ALT levels were (67.52±10.35) U/L and (72.17±16.28) U/L versus (35.32±9.27) U/L and (48.56±14.10) U/L, respectively ( P<0.05 for all comparisons). For bilirubin indicators, TBIL and DBIL levels in the elderly donor group were also consistently higher than in the non-elderly donor group. On day 1, TBIL and DBIL were (95.76±21.93) μmol/L and (64.22±15.07) μmol/L, compared to (77.59±20.48) μmol/L and (51.18±12.96) μmol/L. By day 14, TBIL and DBIL levels had decreased to (41.26±8.30) μmol/L and (32.45±6.21) μmol/L, compared to (28.39±7.15) μmol/L and (20.58±5.04) μmol/L in the non-elderly donor group ( P<0.05 for all comparisons). The incidence of hepatic artery complications was 10.71% (3/28) in the elderly donor group and 4.69% (23/490) in the non-elderly donor group, with no statistically significant difference between the two groups ( P>0.05). Statistical analysis employing independent t-tests and χ2 tests demonstrated significant differences between the arterial complication group and non-arterial complication group in donor quality ratio ( P<0.05) and incidence of hepatic arterial hypoperfusion ( P<0.05). Multivariate binary logistic regression analysis, after adjusting for confounding factors (e.g., recipient gender, age, body mass index [BMI], primary disease, and donor-recipient blood type compatibility), identified recipient-to-donor mass ratio ( OR=1.352, P<0.05) and insufficient hepatic arterial blood flow ( OR=1.497, P<0.05) as independent risk factors for arterial complications following liver transplantation. Conclusion:Elderly liver donors can have a certain impact on early postoperative liver function recovery in liver transplant recipients, but have no significant impact on the occurrence of arterial complications after liver transplantation. The mass ratio of recipients to donors and insufficient hepatic arterial blood flow are independent risk factors for arterial complications after liver transplantation.

Objective:To investigate the effective ingredients and molecular mechanisms of Qizao oral liquid in the treatment of lead poisoning through network pharmacology and molecular docking technology.Methods:December 2023, the effective ingredients and their corresponding targets of Qizao oral liquid were searched from the TCM Systems Pharmacology database. Swiss Target Prediction was used to predict corresponding potential target genes of compounds. Targets associated with lead poisoning were obtained from GeneCards and OMIM databases. Cytoscape 3.10.1 software was employed to construct a components and corresponding target network as well as a components and corresponding target network, followed by visualization and cluster analysis. GO and KEGG enrichment analyses were conducted using the Metascape database, resulting in the generation of a signaling pathway-target network diagram. Molecular docking analysis between the principal compounds and target proteins was performed using Autodock 4.2.6 and Pymol 2.2.0 software to validate their underlying molecular mechanisms.Results:A total of 114 active chemical components, 361 potential targets, 2501 lead poisoning targets, and 191 intersection targets of "Qizao oral liquid and lead poisoning" were screened. Further analysis revealed that there were 2091 entries for GO biological processes and 202 KEGG signaling pathways. Enrichment analysis showed that the key targets were mainly enriched in cancer, lipid and atherosclerosis, PI3K-Akt signaling pathways. Molecular docking showed that there were 14 combinations with binding energy<-5 kcal/mol, among which PIK3R1-β-sitosterol binding energy was -9.71 kcal/mol.Conclusion:The primary active components found in Qizao oral liquid, such as β-sitosterol, nuciferine, stephanine, and stigmasterol, have the potential to modulate key targets including PIK3R1, AKT1, TP53, and NFKB1. These components are capable of influencing the PI3K-Akt signaling pathway as well as lipid and atherosclerosis pathways in order to mitigate the adverse effects of lead exposure.

Objective:To evaluate the clinical efficacy of endoclip papillaplasty (ECPP) for preventing recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP).Methods:A retrospective analysis was conducted on 1 941 patients who underwent ERCP for choledocholithiasis in Henan Provincial People's Hospital from January 2019 to December 2023. A total of 250 patients who received ECPP were assigned to the ECPP group, while 251 matched controls were selected via 1∶1 year-stratified sampling into the control group. After follow-up, 209 ECPP cases and 190 controls were ultimately included in the analysis. Stone removal success rate, incidence of perioperative complications, and postoperative choledocholithiasis recurrence were compared between the two groups. Univariate and multivariate logistic regression were used to determine the risk factors for choledocholithiasis recurrence after ERCP.Results:Both groups achieved 100.0% stone removal success rate. There was no significant difference in the incidence of intraoperative perforation [0.5% (1/209) VS 1.1% (2/190), χ2=0.01, P=0.934], postoperative hyperamylasemia [21.5% (45/209) VS 17.4% (33/190), χ2=1.10, P=0.295] or post-ERCP pancreatitis [3.8% (8/209) VS 8.1% (9/190), χ2=0.20, P=0.653] between the ECPP group and the control group. The ECPP group showed significantly lower bleeding rate [5.1% (11/209) VS 12.3% (23/190), χ2=5.98, P=0.014] and choledocholithiasis recurrence rate [10.5% (22/209) VS 18.9% (36/190), χ2=5.68, P=0.017] compared with the control group. The multivariate logistic regression identified dilated common bile duct diameter ( OR=1.881, 95% CI: 1.101-3.213, P=0.021) as an independent risk factor for choledocholithiasis recurrence, while being female ( OR=0.482, 95% CI: 0.266-0.875, P=0.016) and ECPP ( OR=0.497, 95% CI:0.278-0.887, P=0.018) were protective factors. Conclusion:ECPP effectively reduces choledocholithiasis recurrence rate and bleeding risk after ERCP. ECPP and being female serve as protective factors for choledocholithiasis recurrence, while dilated bile duct diameter is an independent risk factor.