Ergothioneine is a natural antioxidant known for its potent anti-inflammatory and antioxidative properties. It has been applied in various sectors such as food, cosmetics, and pharmaceuticals. Edible fungi, both wild and cultivated, stand as the primary natural sources capable of synthesizing ergothioneine. This paper reviews the research progress in the content, physiological functions, extraction and detection methods, synthetic genes and pathways, mycelium fermentation, and engineering strain construction for ergothioneine production. The aim is to provide a comprehensive reference for advancing the research and industrial development related to ergothioneine in edible fungi.
Ergothioneine/isolation & purification* ; Fungi/genetics* ; Antioxidants/metabolism* ; Fermentation

Objective To investigate the predictive value of PCSK9 gene rs562556 polymorphism for major adverse cardiovascular events(MACE)after percutaneous coronary intervention(PCI)in patients with type 2 diabetes mellitus(T2DM)complicated by acute myocardial infarction(AMI).Methods A total of 97 patients were involved in this study with T2DM complicated by AMI,who underwent PCI at The Third Affiliated Hospital of Qiqihar Medical University between January 2019 and December 2021.Based on MACE occurrence during a 2-year follow-up period,patients were divided into non-MACE group and MACE group(n=57 and 40,respectively).Clinical biochemical parameters,including blood glucose and lipid levels,were recorded.Plasma PCSK9 levels were assessed using enzyme-linked immunosorbent assay.Plasma PCSK9 gene rs562556 polymorphism was detected through sequencing.Kaplan-Meier curve analysis was performed to assess how rs562556 polymorphism impacts MACE incidence post-PCI.Multivariate logistic regression was applied to identify independent MACE-associated risk factors.ROC curve analysis was performed to evaluate the predictive value of rs562556 poly-morphism and key clinical variables for MACE occurrence post-PCI.Results Compared to the non-MACE group,patients in the MACE group exhibited significantly higher age,heart rate,creatinine,NT-proBNP,LDL-C,and plasma PCSK9 levels,along with higher hyper-tension and coronary atherosclerotic heart disease prevalence,and lower diastolic blood pressure(all P＜0.05).In patients with T2DM and AMI,the rs562556 genotype AA of the PCSK9 gene positively correlated with plasma PSCK9 levels(r=0.61,P＜0.000 1).The frequen-cies of the rs562556 genotype AA and allele A were significantly higher in the MACE compared to the non-MACE group(P＜0.05).The AA genotype of the PCSK9 gene rs562556 was associated with an increased risk of MACE during follow-up in patients with T2DM and AMI(P＜0.05).After adjusting for other confounding variables,advanced age,increased NT-proBNP and PCSK9 levels,and the rs562556 AA genotype were identified as independent risk factors for MACE post-PCI in this patient population.Combined analysis of these factors demonstrated superior predictive value for MACE occurrence compared to individual markers.Conclusion The PCSK9 gene rs562556 genotype AA is associated with a significantly increased risk of MACE within two years post-PCI in patients with T2DM and AMI,sug-gesting that it could serve as a promising predictive biomarker for post-PCI MACE in the given population.

Objective To investigate the predictive value of PCSK9 gene rs562556 polymorphism for major adverse cardiovascular events(MACE)after percutaneous coronary intervention(PCI)in patients with type 2 diabetes mellitus(T2DM)complicated by acute myocardial infarction(AMI).Methods A total of 97 patients were involved in this study with T2DM complicated by AMI,who underwent PCI at The Third Affiliated Hospital of Qiqihar Medical University between January 2019 and December 2021.Based on MACE occurrence during a 2-year follow-up period,patients were divided into non-MACE group and MACE group(n=57 and 40,respectively).Clinical biochemical parameters,including blood glucose and lipid levels,were recorded.Plasma PCSK9 levels were assessed using enzyme-linked immunosorbent assay.Plasma PCSK9 gene rs562556 polymorphism was detected through sequencing.Kaplan-Meier curve analysis was performed to assess how rs562556 polymorphism impacts MACE incidence post-PCI.Multivariate logistic regression was applied to identify independent MACE-associated risk factors.ROC curve analysis was performed to evaluate the predictive value of rs562556 poly-morphism and key clinical variables for MACE occurrence post-PCI.Results Compared to the non-MACE group,patients in the MACE group exhibited significantly higher age,heart rate,creatinine,NT-proBNP,LDL-C,and plasma PCSK9 levels,along with higher hyper-tension and coronary atherosclerotic heart disease prevalence,and lower diastolic blood pressure(all P＜0.05).In patients with T2DM and AMI,the rs562556 genotype AA of the PCSK9 gene positively correlated with plasma PSCK9 levels(r=0.61,P＜0.000 1).The frequen-cies of the rs562556 genotype AA and allele A were significantly higher in the MACE compared to the non-MACE group(P＜0.05).The AA genotype of the PCSK9 gene rs562556 was associated with an increased risk of MACE during follow-up in patients with T2DM and AMI(P＜0.05).After adjusting for other confounding variables,advanced age,increased NT-proBNP and PCSK9 levels,and the rs562556 AA genotype were identified as independent risk factors for MACE post-PCI in this patient population.Combined analysis of these factors demonstrated superior predictive value for MACE occurrence compared to individual markers.Conclusion The PCSK9 gene rs562556 genotype AA is associated with a significantly increased risk of MACE within two years post-PCI in patients with T2DM and AMI,sug-gesting that it could serve as a promising predictive biomarker for post-PCI MACE in the given population.

Objective:To analyze the association between the rs562556 polymorphism of the proprotein convertase subtilisin/kexin type 9(PCSK9)gene and the degree of coronary artery stenosis in the patients with acute myocardial infarction(AMI).Methods:A total of 200 patients diagnosed with AMI from January 2021 to December 2022 were selected as AMI group,and 200 healthy individuals during the same period were selected as control group.According to the Gensini scoring standard,the patients in AMI group were divided into low risk group(Gensini score≤40,n=78)and medium-high risk group(Gensini score>40,n=122).The levels of lipid metabolism indicators in serum of the patients in two groups were detected by fully automatic biochemical analyzer;enzyme linked immunosorbent assay(ELISA)method was used to detect the PCSK9 levels in serum of the patients in two groups;ultraviolet spectrophotometry was used to detect the single nucleotide polymorphism(SNP)of PCSK9 gene of the patients in two groups;Spearman correlation analysis was used to detect the correlation between the rs562556 polymorphism of the PCSK9 gene and the degree of the disease and the levels of lipid metabolism indicators in serum of the patients.Results:Compared with control group,the percentage of smokers of the patients in AMI group was significantly increased(P<0.01).Compared with control group,the levels of low-density lipoprotein cholesterol(LDL-c)and PCSK9 in serum of the patients in AMI group were significantly increased(P<0.05).Compared with low risk group,the levels of LDL-c and PCSK9 in serum of the patients in medium-high risk group were significantly increased(P<0.05).The distribution of PCSK9 gene rs1800487 genotype in both control and AMI groups conformed to the Hardy-Weinberg(H-W)equilibrium(χ2=0.677,P=0.713;χ2=0.970,P=0.831).Compared with control group,the distribution frequencies of PCSK9 gene rs562556 genotype AA and allele A of the patients in AMI group were significantly increased(P<0.05).In the AMI patients,the distribution of PCSK9 gene rs562556 genotype in both low risk and medium-high risk groups conformed to the H-W equilibrium(χ2=0.045,P=0.978;χ2=1.290,P=0.525).Compared with low risk group,the distribution frequencies of genotype AA and allele A of PCSK9 gene rs562556 of the patients in medium-high risk group were significantly increased(P<0.05).The PCSK9 gene rs562556 genotype AA was positively correlated with the degree of AMI(r=0.193,P=0.006)and LDL-c level(r=0.301,P<0.01).Allele A was positively correlated with the LDL-c level(r=0.168,P=0.017).Conclusion:The PCSK9 gene rs562556 genotype AA is positively correlated with the degree of coronary artery stenosis of the AMI patients,and its polymorphism may promote the development of AMI by upregulating the LDL-c level.

Objective To determine the effect of thrombus aspiration combined with intracoronary injection of recombinant human TNK tissue type plasminogen activator(rhTNK-tPA)on micro-circulation and cardiac function during primary PCI in elderly patients with acute myocardial in-farction(AMI).Methods A retrospective study was conducted on 90 elderly patients with STEMI undergoing primary PCI in Tianjin Third Central Hospital from January 2021 to October 2023.According to their treatment strategies,they were divided into simple suction group(n=46)and combination group(n=44).The suction group received a suction catheter for thrombus aspiration within the coronary artery,while the combined group got a suction catheter for thrombus aspira-tion within the infarct related blood vessels,and then received a local injection of rhTNK-tPA into the lesion through the suction catheter.Their general data,proportion of ST segment resolution(STR)≥70％at 90 min after surgery,postoperative TIMI blood flow grade,postoperative TIMI myocardial perfusion grade(TMPG),corrected TIMI frame count(CTFC)and cardiac ultrasound indicators as well as the incidence of adverse cardiac events during hospitalization were compared between the two groups.Results Larger proportions of postoperative STR ≥70％,postoperative TIMI blood flow grade 3 and TMPG grade 3,and lower CTFC were observed in the combination group than the suction group(P＜0.05).In 1 week after surgery,the simple suction group had lower left ventricular ejection fraction[LVEF,(52.5±6.2)％vs(58.3±6.4)％,P＜0.05],but larger left ventricular diameter(LVD,44.1±3.9 mm vs 51.9±2.5 mm,P＜0.05)than the com-bined group.The incidence of MACE during hospitalization was obviously lower in the combined group than the suction group(20.5％vs 37.0％,P＜0.05).Conclusion Combined intracoronary injection of rhTNK-tPA based on thrombotic aspiration can effectively reduce the coronary thrombus burden,improve myocardial microcirculation perfusion,reduce the incidence of MACE during hospitalization,and not increase the risk of bleeding in elderly STEMI patients.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment(TME),which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma(HNSCC)patients.This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology.The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing(scRNA-seq)profiles and validated through bulk transcriptomes.Serine-glycine-one-carbon(SGOC)metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients.A 4-SGOC gene prognostic signature,constructed by LASSO-COX regression analysis,demonstrated good predictive performance for overall survival and therapeutic responses.Patients in the low-risk group exhibited greater infiltration of exhausted CD8+T cells,and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy.Conversely,high-risk patients exhibited characteristics of cold tumors,with enhanced IMPDH1-mediated purine biosynthesis,resulting in poor responses to current therapies.IMPDH1 emerged as a potential therapeutic metabolic target.Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress.Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.
Humans ; Male ; Animals ; Mice ; Semen/metabolism* ; Dyneins/metabolism* ; Cilia/metabolism* ; Mutation ; Ciliary Motility Disorders/genetics*

Primary ciliary dyskinesia (PCD) is a hereditary disease characterized by airway mucociliary clearance dysfunction. The estimated prevalence of PCD is 1꞉10 000 to 1꞉20 000. The main respiratory manifestations in children are cough, expectoration, chronic rhinitis, sinusitis, and chronic otitis media, while the most common symptoms in adults are chronic sinusitis, bronchiectasis, and infertility. About 50% of patients with certain PCD-related gene variants are combined with situs inversus, and the incidence of congenital heart disease is also high. The pathogenesis behind PCD is that gene variants cause structural or functional disorders of respiratory cilia and motile cilia of other organs, leading to a series of heterogeneous clinical manifestations, which makes it difficult to identify and diagnose PCD. Combining different disease screening tools and understanding the relationship between genotypes and phenotypes may facilitate early diagnosis and treatment for PCD.
Chronic Disease ; Cilia/pathology* ; Humans ; Kartagener Syndrome/genetics* ; Phenotype ; Sinusitis

ObjectiveTo investigate the status of sleep insufficiency in children and adolescents with mental disorders and related influencing factors. MethodsA total of 131 children and adolescents who were admitted to the Third People's Hospital of Fuyang from February to June 2021 and met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） for schizophrenia， depression or childhood-onset mood disorders were selected as the research subjects. A self-compiled questionnaire was used to collect the general demographic information， sleep status， lifestyle habits， family and school status of the selected individuals. The demographic information was compared between sleep sufficiency group and sleep insufficiency group. Spearman rank correlation was used to screen the influencing factors. Results① Among 131 children and adolescents with mental disorders， 93 cases （71.0%） had sleep insufficiency. There were significant differences between sleep insufficiency group and sleep sufficiency group in terms of disease types （χ²=8.798， P=0.012）， experience of being beaten in recent 6 months （χ²=3.427， P=0.035）， being scolded in recent 6 months （χ²=4.145， P=0.031）， and cyberbullying over the past year （χ²=4.187， P=0.041）. ② Among patients with sleep insufficiency， 77 cases （82.8%） reported difficulty in falling asleep and 69 cases （74.2%） reported nocturnal awakenings. ③ Sleep insufficiency in children and adolescents with mental disorders was positively correlated with the experience of being scolded （r=0.210， P=0.037） or beaten （r=0.145， P=0.023） over the past 6 months and cyberbullying over the past year （r=0.179， P=0.041）. ConclusionChildren and adolescents with mental disorders suffer a high risk of sleep insufficiency， and is closely associated with depressive disorder， experience of being scolded or beaten over the past 6 months， and cyberbullying over the past year.