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*

OBJECTIVE To analyze the peak wideband acoustic immittance(WAI)values reflecting the tympanic membrane absorption characteristics during the measurement process in patients with congenital middle ear malformation.METHODS We selected 36 patients diagnosed with congenital middle ear malformation by CT as subjects and evaluated their tympanic membrane absorption characteristics by measuring their acoustic impedance peak pressure.Then,we divided these data into two groups based on the pathological malformation obseved during the surgical process,namely the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group.Calculate the absorption rate values of the tympanic membrane at each frequency corresponding to the peak pressure value of the tympanogram,and the relative area of absorption rate.By conducting independent t-tests,we compared two groups-normal children and patients who had undergone ossicular chain fixation surgery-to analyze the absorption area and peak absorption rate of their tympanic peak pressure values.RESULTS Under peak pressure,there were significant differences(P<0.001)in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with fixed ossicular chain and the normal group.However,there was no difference in the full frequency range tympanic membrane absorption rate and peak absorption rate between the group with soft ossicular chain and the normal group.Under peak pressure,the absorption area of the ossicular chain fixation group was significantly lower than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001),while the absorption area of the ossicular chain soft connection group was significantly higher than that of the normal group in the low frequency range of 226-1 000 Hz(P<0.001).CONCLUSION When conducting broadband acoustic impedance test,there is a significant difference in the relative area of tympanic membrane absorption rate of acoustic impedance peak pressure between the auditory ossicular chain soft connection group and the auditory ossicular chain fixation group across 226-1 000 Hz.It has application value as a clinical rapid screening and diagnostic tool for middle ear malformations.

Objective: To examine the associations between peer bullying and parental phubbing with executive function and their combined effect among primary and secondary school students, so as to provide scientific evidence for promoting healthy development of executive function among primary and secondary school students. Methods: In November 2024, a combining convenience with clustering method was used to select 3 547 primary and secondary school students in Shenzhen City. The Chinese versions of the Delaware Bullying Victimization Scale-Student (DBVS-S), the Parental Phubbing Scale (PPS), and the Teenage Executive Functioning Inventory (TEXI) were used to assess peer bullying, parental phubbing, and executive function, respectively. Generalized linear regression models were applied to analyze the associations of peer bullying and parental phubbing with executive function, and to assess their joint effects. Subgroup analyses were performed by ages and genders, and multiplicative interaction terms were used to test for interactions. Results: The score for peer bullying among primary and secondary school students was (15.27± 5.67 ), with verbal bullying, physical bullying, and relational bullying scores being (5.64±2.77) (4.70±1.62) (4.93±2.07), respectively. The score for parental phubbing was (13.98±5.00). Executive function score was (47.35±15.89), while inhibitory control and working memory scores were (26.44±9.00) (20.91±7.49), respectively. After adjusting for confounding factors such as age, gender, self reported family relationship, self reported family economic status, parental education level, both peer bullying ( β= 0.75, 95%CI =0.67-0.84), verbal bullying( β=1.41, 95%CI =1.23-1.58), physical bullying ( β=2.18, 95%CI =1.87- 2.49 ), relational bullying ( β=1.78, 95%CI =1.54-2.01) and parental phubbing ( β=0.88, 95%CI =0.79-0.98) were significantly positively associated with the degree of executive function impairment (all P <0.01). Joint effect analysis showed that, compared with the "no bullying low phubbing" group, the total executive function scores in other combined exposure groups were all higher ( β = 6.78-15.96, all P <0.01). Among them, the "bullying high phubbing" group exhibited the highest level of executive function impairment ( β=14.17, 95%CI=12.61-15.73, P <0.01). Subgroup analysis indicated significant interactions between verbal bullying and age on total executive function, inhibitory control, and working memory (all P interaction <0.01). The association of verbal bullying with executive function was slightly higher in primary and secondary school students younger than 13 years ( β=1.80, 95%CI = 1.45-2.16) than in those aged 13 years or older ( β=1.25, 95%CI =1.05-1.45) (both P <0.01). Other types of bullying and parental phone neglect showed no statistically significant interaction with age or gender in executive function, inhibitory control, and working memory(all P interaction >0.05). Conclusion Both peer bullying and parental phubbing are significantly associated with impaired executive function among primary and secondary school students, and there is a combined effect between them; among these, the association between verbal bullying and executive function impairment in younger primary and secondary school students is more pronounced.

Objective To explore the effect of cognitive behavioral therapy(CBT)on improving anxiety,depression,sleep,and fatigue in patients with post-intensive care syndrome(PICS).Methods Sixty PICS patients transferred from the department of respiratory intensive care unit(RICU)of Puyang Oilfield General Hospital from September 2022 to February 2023 were selected as the study subjects.Patients were divided into a control group and an intervention group using a random number table method,with 30 cases in each group.The control group only received routine health education,while the intervention group received CBT on the basis of routine health education.After 3 months of intervention,the changes in hospital anxiety and depression scale(HADS),Pittsburgh sleep quality index(PSQI),and fatigue assessment scale(FAS)before and after intervention were observed in both groups of patients.Results There was no statistically significant difference in anxiety,depression,PSQI,and FAS scores between the two groups of patients before intervention.The scores gradually decreased over time and reached the lowest level at 3 months after intervention.After intervention,the above scores in the intervention group were significantly lower than those in the control group(anxiety score:5.06±1.76 vs.9.33±1.42,depression score:6.93±1.64 vs.7.63±1.61,PSQI score:5.27±1.37 vs.8.43±2.56,FAS score:5.67±0.47 vs.9.97±0.21,all P<0.05).Conclusion Implementing CBT for PICS patients can alleviate anxiety and depression,improve their sleep quality and fatigue symptoms,thereby enhancing their quality of life.

OBJECTIVE To explore the changes of serum Toll-like receptor(TLR)2,TLR4 and 25 hydroxyvitamin D[25(OH)D]in the general anesthesia orthopedic surgery patients with postoperative pulmonary infections and analyze the distribution and drug resistance of pathogens.METHODS A total of 59 general anesthesia orthopedic surgery patients with postoperative pulmonary infections who were treated in Tianjin Fifth Central Hospital from Jul.2019 to Jul.2024 were chosen as the infection group,meanwhile,65 patients who underwent the same surger-y but did not have postoperative pulmonary infection or other acute and chronic infections were chosen as the non-infection group.The etiological characteristics of the postoperative pulmonary infections and the drug re-sistance rates were analyzed.The clinical data and the levels of serum TLR2,TLR4 and 25(OH)D were observed and compared between the two groups of patients.The values of the above indicators in diagnosis of the postopera-tive pulmonary infections in the general anesthesia orthopedic surgery were analyzed.RESULTS Totally 63 strains of pathogens were isolated from the 59 general anesthesia orthopedic surgery patients with postoperative pulmona-ry infections,36(57.14％)of which were gram-negative bacteria.3 of 15 Pseudomonas aeruginosa strains were resistant to meropenem;4 of 12 Klebsiella pneumoniae strians were resistant to meropenem;all of the 11 Staph-ylococcus aureus strains were methicilin-resistant S.aureus.The proportions of patients with age,hypoproteine-mia and diabetes mellitus,the serum TLR2 and TLR4 levels were higher in the infection group than in the non-infection group(P＜0.05),while the 25(OH)D level of the infection group was lower than that of the no in-fection group(P＜0.05).The area under the curves(AUCs)of serum TLR2,TLR4,25(OH)D and the joint de-tection of the above indicators were respectively 0.817,0.801,0.787 and 0.917 in diagnosis of postoperative pul-monary infections in the general anesthesia orthopedic surgery patients,and the AUC of the joint detection of the indicators was greater than that of the single detection(P＜0.05).CONCLUSIONS The general anesthesia or-thopedic surgery patients with postoperative pulmonary infections show high expressions of serum TLR2 and TLR4 and the low expression of 25(OH)D.The joint detection of the above indexes has higher diagnostic value.The gram-negative bacteria are dominant among the pathogens causing the infections.The pathogens vary in the drug resistance.

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 characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.