Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Objective:To analyze the prevalence of chronic kidney disease (CKD) and influencing factors of adults in Hebei Province, and provide scientific evidence for the development of comprehensive CKD prevention and control strategies.Methods:In China Adult Chronic Disease and Nutrition Surveillance in Hebei in 2018, a total of 7 562 permanent residents aged ≥18 years were selected by multi-stage stratified cluster random sampling from 13 surveillance points in Hebei for questionnaire survey, medical examination and laboratory test.Results:A total of 1 067 CKD patients were detected in the adults aged ≥18 years in this survey, with a weighted prevalence rate of 12.10%. The results of multivariate analysis showed that the daily total static behavior time ( OR=1.07, 95% CI: 1.04-1.09), living in rural area ( OR=1.50, 95% CI: 1.14-1.97), coal use ( OR=1.37, 95% CI: 1.16-1.61), coal gas/liquefied gas/natural gas/biogas use ( OR=2.92, 95% CI: 2.40-3.54) and solar energy/electricity use ( OR=1.75, 95% CI: 1.36-2.25), insufficient fruit intake ( OR=1.39, 95% CI: 1.06-1.83), insufficient physical activity ( OR=1.35, 95% CI: 1.11-1.64), suffering from hypertension ( OR=1.80, 95% CI: 1.44-2.24) and suffering from diabetes ( OR=1.77, 95% CI: 1.27-2.45) were risk factors for CKD in adults in Hebei. High education level ( OR=0.41, 95% CI: 0.19-0.91), excessive drinking ( OR=0.53, 95% CI: 0.28-0.99), central obesity ( OR=0.75, 95% CI: 0.58-0.97), history of allergic diseases ( OR=0.44, 95% CI: 0.27-0.72) were protective factors for CKD. Conclusions:The prevalence of CKD in adults in Hebei was relatively high, especially in those who had too long average daily static behavior, lived in rural area, used coal, gas/liquefied gas/natural gas/biogas, solar energy/electricity, had inadequate intake of fruits, lacked physical activity and suffered from hypertension and diabetes. It is necessary to pay attention to the early prevention and treatment of CKD, strengthen the health education about healthy lifestyle and improve the management of patients with chronic disease, such as hypertension and diabetes, to further reduce the risk for CKD.

Objective To investigate the clinical efficacy of fasting nasogastric administration of sesame oil combined with multi-frequency vibrational abdominal massage in stroke patients with consti-pation undergoing nasogastric feeding.Methods A total of 50 stroke patients with nasogastric feeding were selected as study subjects and randomly divided into control group and study group,with 25 pa-tients in each group.The control group received routine nursing care plus multi-frequency vibrational abdominal massage,while the study group received fasting nasogastric administration of 20 mL of sesa-me oil on the basis of the control group's treatment.After 15 days of intervention,the defecation condi-tions[constipation clinical symptom score(CSS),stool consistency(Bristol stool scale),and stool volume]were compared between the two groups.Results After treatment,the CSS score in the study group was lower than that in the control group[(6.52±2.52)versus(12.64±3.32),P＜0.05].The normal stool consistency(types Ⅳ and Ⅴ on the Bristol stool scale)in the study group was higher than that in the control group(76.0％versus 8.0％,P＜0.05).The stool volume in the study group was higher than that in the control group[(303.00±93.79)g versus(196.40±60.27)g,P＜0.05].The total effective rate of defecation in the study group was 96.0％,which was higher than 32.0％in the control group(P＜0.05).The Patient Assessment of Constipation-Quality of Life(PAC-QOL)score in the study group was lower than that in the control group[(40.07±5.67)versus(63.07±7.46),P＜0.05].Conclusion Fasting nasogastric administration of sesame oil com-bined with multi-frequency vibrational abdominal massage can promote the recovery of intestinal function and improve constipation symptoms in stroke patients with nasogastric feeding.

GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To observe the clinical value of neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),C-reactive protein(CRP)to albumin(ALB)ratio(CAR)dynamic monitoring in the acute phase of Kawasaki disease(KD).Methods:This study was a single-center prospective study,146 in the acute phase of KD patients who were admitted to The Third Affiliated Hospital of Guangdong Medical University from June 2022 to September 2024 were selected as the study subjects(KD group).Hospitalized patients with fever ≥ 3 days received during the same period(fever control group,n=146)and healthy children underwent physical examination(healthy control group,n=146)were seleted.According to the differences in response to intravenous immunoglobulin treatment,KD patients were divided into two subgroups:immunoglobulin insensitive group(n=21)and immunoglobulin sensitive group(n=125).According to the presence or absence of coronary artery injury(CAL),KD patients were divided into two subgroups:non CAL group(n=97)and CAL group(n=49).According to alanine aminotransferase(ALT)expression level,KD patients were divided into two subgroups:non liver injury group(ALT value＜80 U/L,n=110)and liver injury group(ALT value ≥ 80 U/L,n=36).NLR,PLR,and CAR of KD group,fever control group,and healthy control group were compared.NLR,PLR,and CAR were compared at admission,before and 3 d after immunoglobulin infusion between the immunoglobulin sensitive group and immunoglobulin insensitive group,liver injury group and non liver injury group,CAL group and non CAL group.Receiver operating characteristic(ROC)curve was used to evaluate diagnostic efficacy.Result:NLR,PLR,and CAR of the KD group and fever control group were higher than those of the healthy control group,and the KD group were higher than those of the fever control group(P＜0.05).NLR,PLR,and CAR of the immunoglobulin insensitive group were higher than those of the immunoglobulin sensitive group at admission,before and 3 d after immunoglobulin infusion(P＜0.05).NLR,PLR,and CAR of the liver injury group were higher than those of non liver injury group at admission,before and 3 d after immunoglobulin infusion(P＜0.05).NLR,PLR,and CAR of the CAL group were higher than those of the non CAL group at admission,before and 3 days after immunoglobulin infusion(P＜0.05).When NLR,PLR,and CAR were used alone or in combination at admission,the area under curve(AUC)(95％CI)of ROC values were 0.798(0.715～0.869),0.802(0.717～0.871),0.833(0.752～0.896),and 0.935(0.873～0.973),respectively,among them,the combination had the highest diagnostic efficacy.Conclusion:NLR,PLR,and CAR are all abnormally elevated in KD patients,and which are associated with patient immunoglobulin sensitivity,liver injury and CAL.The combination detection of the above three indicators has better diagnostic efficacy for KD.

Objective To summarize and analyze the clinicopathological characteristics,imaging manifestations,treatment and prognosis of anaplastic lymphoma kinase(ALK)-positive histiocytosis(APH)involving the central nervous system(CNS),so as to enhance understanding of this rare disease.Methods A retrospective analysis was conducted on 5 cases of CNS-involved APH diagnosed in Huashan Hospital,Fudan University between 2019 and 2023.Clinical,imaging and pathological data were collected,and supplemented by immunohistochemical staining(IHC),fluorescence in situ hybridization(FISH)and high-throughput sequencing for auxiliary diagnosis and molecular characterization.The findings were summarized and integrated with previous literature for a comprehensive analysis.Results All five patients were male,with a mean age of 27.6 years,in which 2 cases exhibited multi-system involvement,while 3 cases exhibited single system involvement.Imaging revealed multiple intracranial lesions in multi-system cases and solitary lesions in single system cases,with well-defined boundaries and homogeneous enhancement.Histologically,tumor cells were intermingled with lymphocytes,displaying an alternating"light and dark"pattern in 1 case.Granuloma-like structures were observed in 4 cases,along with frequent nuclear grooves,indentations and convolutions.Tumor cells usually infiltrated surrounding tissues.IHC demonstrated that tumors expressed histiocytic markers(CD68/CD163)and ALK predominantly expressed in the cytoplasm.FISH confirmed ALK gene rearrangements in all patients,while high-throughput sequencing identified KIF5B-ALK fusions in 2 cases.All single system CNS cases achieved complete remission after surgical resection with or without adjuvant chemotherapy/ALK inhibitors.Among multi-system cases,one achieved partial remission,and one experienced relapse and progression.Conclusion CNS APH is prone to preoperative misdiagnosis.Its histopathological features,ALK immunohistochemical expression,and ALK gene fusions are critical for diagnosis.Patients with single system involvement demonstrate overall superior outcomes compared to multi-system cases.Total resection is effective for localized disease,while multi-system cases require systemic therapy.Multidisciplinary collaboration is crucial for precise diagnosis and treatment.

We aimed to explore the value of personalized narrative intervention in the nursing care of elderly patients with stroke hemiplegia(SH).A total of 68 elderly patients with SH were selected and divided into two groups using the ball-rolling method,with 34 cases in each group.The control group received routine nursing care,while the observation group received routine care and personalized narrative nursing.The nursing outcomes of the two groups were compared.Compared with the control group,the observation group had lower scores in anxiety and depression(P<0.05),and higher scores in the Functional Evaluation of Cognitive State-Short Screening(FECS-SS)(P<0.05).The rehabilitation effects of normal rate in the observation group was higher than that in the control group(P<0.05).Personalized narrative nursing for SH patients can effectively relieve the patients'negative emotions,enhance their compliance with rehabilitation,and improve the outcomes of rehabilitation.

Objective:To analyze the prevalence of chronic kidney disease (CKD) and influencing factors of adults in Hebei Province, and provide scientific evidence for the development of comprehensive CKD prevention and control strategies.Methods:In China Adult Chronic Disease and Nutrition Surveillance in Hebei in 2018, a total of 7 562 permanent residents aged ≥18 years were selected by multi-stage stratified cluster random sampling from 13 surveillance points in Hebei for questionnaire survey, medical examination and laboratory test.Results:A total of 1 067 CKD patients were detected in the adults aged ≥18 years in this survey, with a weighted prevalence rate of 12.10%. The results of multivariate analysis showed that the daily total static behavior time ( OR=1.07, 95% CI: 1.04-1.09), living in rural area ( OR=1.50, 95% CI: 1.14-1.97), coal use ( OR=1.37, 95% CI: 1.16-1.61), coal gas/liquefied gas/natural gas/biogas use ( OR=2.92, 95% CI: 2.40-3.54) and solar energy/electricity use ( OR=1.75, 95% CI: 1.36-2.25), insufficient fruit intake ( OR=1.39, 95% CI: 1.06-1.83), insufficient physical activity ( OR=1.35, 95% CI: 1.11-1.64), suffering from hypertension ( OR=1.80, 95% CI: 1.44-2.24) and suffering from diabetes ( OR=1.77, 95% CI: 1.27-2.45) were risk factors for CKD in adults in Hebei. High education level ( OR=0.41, 95% CI: 0.19-0.91), excessive drinking ( OR=0.53, 95% CI: 0.28-0.99), central obesity ( OR=0.75, 95% CI: 0.58-0.97), history of allergic diseases ( OR=0.44, 95% CI: 0.27-0.72) were protective factors for CKD. Conclusions:The prevalence of CKD in adults in Hebei was relatively high, especially in those who had too long average daily static behavior, lived in rural area, used coal, gas/liquefied gas/natural gas/biogas, solar energy/electricity, had inadequate intake of fruits, lacked physical activity and suffered from hypertension and diabetes. It is necessary to pay attention to the early prevention and treatment of CKD, strengthen the health education about healthy lifestyle and improve the management of patients with chronic disease, such as hypertension and diabetes, to further reduce the risk for CKD.