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 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 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 compare knowledge graphs (KGs) constructed from standardized clinical pathways and actual examination records within 24 hours of emergency care for acute gastrointestinal hemorrhage (AGH), acute myocardial infarction (AMI), and intracerebral hemorrhage (ICH), and to visually analyze discrepancies between guideline recommendations and real-world practice, thereby exploring a novel methodology for clinical pathway optimization.Methods:KGs were developed using clinical pathway standards and actual examination data collected within the first 24 hours of emergency treatment for AGH, AMI, and ICH. Entity attributes were weighted to visually represent the frequency and extent of examination usage through variable node sizes in the KG. The constructed KGs were used to compare and analyze the differences in type and frequency of examinations performed relative to pathway standards.Results:The proportion of examination items with >50% adherence to clinical pathway standards within 24 hours was 76.92% for AGH, 44.44% for AMI, and 78.57% for ICH. Items from the clinical pathways that were not performed in over 50% of patients accounted for 15.38%, 27.78%, and 21.43% of cases, respectively. Non-pathway examinations increased by 9, 7, and 4 items for each condition, of which 17 items (85%) were performed at least once in more than half of the patients. Visualization via KGs revealed a reduction in redundant examinations by 38.64% between AGH and AMI, 35.00% between AGH and ICH, and 37.50% between AMI and ICH. Overall, a 54.84% reduction in redundant examinations was achieved across all three critical conditions.Conclusions:The visual KG approach effectively integrates both guideline-recommended and experience-driven examinations, serving as a correlational analysis tool to assess deviations between actual clinical practice and standardized pathways. It provides a quantitative foundation for optimizing clinical pathways, with potential for greater efficiency gains as more critical conditions are incorporated into the graph.

Objective:To explore the clinical and genetic etiology of a Chinese pedigree affected with type 2 Long QT syndrome (LQTS).Methods:A pedigree with type 2 LQTS presented at Fuwai Central China Cardiovascular Hospital on August 23, 2019 was selected as the study subject. Peripheral blood samples were collected from the proband and her parents. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out for the proband, and candidate variant was screened through functional annotation and protein-protein interaction (PPI) analysis. Sanger sequencing was conducted to verify the pathogenicity of candidate variant. This study was approved by Medical Ethics Committee of the Fuwai Central China Cardiovascular Hospital (Ethics No. 2019-15).Results:WES revealed that the proband has harbored a missense variant of the KCNH2 gene, namely c. 1478A>G (p.Tyr493Cys), which was confirmed by Sanger sequencing to have inherited from her father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_supporting+ PM5+ PP3+ PP4). Conclusion:The KCNH2 gene c. 1478A>G (p.Tyr493Cys) variant probably underlay the type 2 LQTS in this pedigree.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Afferent baroreflex failure(ABF)is a rare disease.It refers to the clinical syndrome caused by the impairment of the afferent limb of the baroreflex or its central connections at the level of the medul-la.The recognized causes include trauma,surgery in related areas(radical neck tumor surgery,carotid endarterectomy),neck radiotherapy,brain stem stroke,tumor growth paraganglioma and hereditary diseases,among which the most common cause is extensive neck surgery or radiotherapy for neck cancer.The main manifestations are fluctuating hypertension,orthostatic hypotension,paroxysmal tachycardia and bradycardia.This case is a young man,whose main feature is blood pressure fluctuation,accom-panied by neurogenic orthostatic hypotension(nOH).After examination,the common causes of hyper-tension and nOH were ruled out.Combined with the previous neck radiotherapy and neck lymph node dissection,it was considered that the blood pressure regulation was abnormal due to the damage of carotid sinus baroreceptor after radiotherapy for nasopharyngeal carcinoma and neck lymph node dissection,which was called ABF.At the same time,the patient was complicated with chronic hyponatremia.Com-bined with clinical and laboratory examination,the final consideration was caused by syndrome of in-appropriate antidiuretic hormone(SIADH).Baroreceptors controlled the secretion of heart rate,blood pres-sure and antidiuretic hormone through the mandatory"inhibition"signal.We speculate that the carotid sinus baroreceptor was damaged after neck radiotherapy and surgery,which leads to abnormal blood pres-sure regulation and nOH,while the function of inhibiting ADH secretion was weakened,resulting in higher ADH than normal level and mild hyponatremia.The goal of treating ABF patients was to reduce the frequency and amplitude of sudden changes in blood pressure and heart rate,and to alleviate the on-set of symptomatic hypotension.At present,drug treatment is still controversial,and non-drug treatment may alleviate some patients'symptoms,but long-term effective treatment still needs further study.The incidence of ABF is not high,but it may lead to serious cardiovascular and cerebrovascular events,and the mechanism involved is extremely complicated,and there are few related studies.The reports of rele-vant medical records warn that patients undergoing neck radiotherapy or surgery should minimize the da-mage to the baroreceptor in the carotid sinus in order to reduce the adverse prognosis caused by complica-tions.

Emerging evidence suggests that ferroptosis,an iron-dependent form of regulated cell death,plays a criti-cal role in the genesis of liver fibrosis through inducing hepatic stellate cell(HSC)ferroptosis to inhibit liver fibrosis or inducing hepatic ferroptosis to potentiates liver fibrosis.Pharmacologically targeting at ferroptosis with its inducers can slow down the progression of liver fibrosis in vitro and in vivo model.This review suggests that pharmacological in-duction of HSC ferroptosis might be used as a potential novel targeted therapy for the treatment of liver fibrosis.