Objective To investigate the effects of low-dose ionizing radiation on the thyroid status and hormone levels of radiation workers. Methods Radiation workers who underwent occupational health examinations at a hospital in Guangzhou from 2015 to 2022 were selected as the subjects of this study. The levels of FT3, FT4 and TSH were analyzed, and the thyroid abnormality status of radiation workers in different groups were compared. Results A total of 1152 participants were included in this study, consisting of 885 (76.82%) males and 267 (23.18%) females, with an average age of (35.26 ± 10.16) years. The prevalence of thyroid abnormalities was 9.38%, which was significantly higher in females (13.86%) than in males (8.02%) (P < 0.05). The TSH level of females [(2.15 ± 1.29) mIU/L] was higher than that of males [(1.85 ± 1.20) mIU/L], while the levels of FT3 [(5.10 ± 0.64) pmol/L] and FT4 [(15.84 ± 2.32) pmol/L] in females were lower than those in males [(5.23 ± 0.63) pmol/L and (16.61 ± 2.75) pmol/L, P < 0.05]. The FT3 of industrial workers [(5.25 ± 0.63) pmol/L] was higher than that of medical workers [(5.10 ± 0.63) pmol/L], while the TSH of industrial workers [(1.80 ± 1.12) mIU/L] was lower than that of medical workers [(2.15 ± 1.37) mIU/L]. FT4 levels decreased with increasing age and duration of occupational exposure. Multivariable logistic regression analysis revealed that sex was a significant independent predictor of thyroid abnormalities among radiation workers. Female workers were more likely to experience thyroid abnormalities (β = −0.62, P < 0.05). Conclusion Low-dose ionizing radiation may have a certain impact on the thyroid status of radiation workers, especially for female workers, which requires further attention and research.

Objective To compare the efficacy of tegoprazan and esomeprazole in treatment of reflux esophagitis(RE)and analyze the influencing factors for treatment failure.Methods A total of 120 RE patients were selected as study subjects and divided into control group(treated with esome-prazole)and observation group(treated with tegoprazan)using random number table method,with 60 cases in each group.The clinical efficacy and gastroscopic efficacy of the two groups were com-pared.Based on the gastroscopic assessment results,the patients were divided into failure group(26 cases)and success group(94 cases).The clinical data of the failure group and the success group were collected and compared.Multivariate Logistic regression analysis was used to screen the influen-cing factors for treatment failure in RE patients.Results The total clinical effective rate in the ob-servation group was 93.33％(56/60),which was higher than 76.67％(46/60)in the control group(P＜0.05).The total effective rate under gastroscopy in the observation group was 88.33％(53/60),which was higher than 68.33％(41/60)in the control group,and the difference was statistically significant(P＜0.05).The proportions of patients with body mass index(BMI)＞28 kg/m2,diabe-tes,a family history,Helicobacter pylori(Hp)infection,Los Angeles classification(LA classifica-tion)of gastroesophageal reflux disease(GERD)grade C to D,and treated with esomeprazole in the failure group were all higher than those in the success group,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that BMI＞28 kg/m2,con-comitant diabetes,LA classification grade C to D,and treatment with esomeprazole were all inde-pendent risk factors for treatment failure in RE patients(P＜0.05).Conclusion Tegoprazan has a significant clinical effect in treatment of RE,and its efficacy is superior to that of esomeprazole.BMI＞28 kg/m2,concomitant diabetes,LA classification grade C to D,and treatment with esome-prazole are all risk factors for treatment failure in RE patients.

Transcriptional regulation based on transcription factors is an effective regulatory method widely used in microbial cell factories. Currently, few naturally transcriptional regulatory elements have been discovered from Saccharomyces cerevisiae and applied. Moreover, the discovered elements cannot meet the demand for specific metabolic regulation of exogenous compounds due to the high background expression or narrow dynamic ranges. There are abundant transcriptional regulatory elements in plants. However, the sequences and functions of most elements have not been fully characterized and optimized. Particularly, the applications of these elements in microbial cell factories are still in the infancy stage. In this study, natural regulatory elements from Medicago truncatula were selected, including the transcription factors MtTASR2 and MtTASR3, along with their associated promoter P_roHMGR1, for functional characterization and engineering modification. We constructed an inducible transcriptional regulation tool and applied it in the regulation of heterologous β-carotene synthesis in S. cerevisiae, which increased the β-carotene production by 7.31 folds compared with the original strain. This study demonstrates that plant-derived transcriptional regulatory elements can be used to regulate the expression of multiple genes in S. cerevisiae, providing new strategies and ideas for the specific regulation and application of these elements in microbial cell factories.
Medicago truncatula/metabolism* ; Saccharomyces cerevisiae/metabolism* ; Transcription Factors/genetics* ; beta Carotene/biosynthesis* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Metabolic Engineering/methods* ; Regulatory Elements, Transcriptional/genetics* ; Plant Proteins/genetics*

Objective:To utilize single-nucleus RNA sequencing(snRNA-seq) technology to investigate the primary cell subpopulations in human limb venous malformations (VMs) tissue and the role of the key gene RhoJ.Methods:Surgical resection specimens of VMs tissues and surrounding normal vein tissues were collected from 100 clinically diagnosed and screened patients with limb VMs at the Department of Hemangioma Surgery of the Third Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. (1) Transcriptome analysis: Three patient samples were randomly selected for snRNA-seq studies, with the surgically removed VMs tissue serving as the experimental group and the surrounding normal vein tissue as the control group. A gene expression matrix for cell nuclei was established, followed by data quality control, dimensionality reduction, clustering, and cell type annotation. Cell-to-cell communication analysis was performed using the R language CellChat package to identify dominant cell subpopulations. The FindMarkers function was utilized to screen for differentially expressed genes (DEGs) between the dominant cell subpopulations of the experimental and control groups, and functional enrichment analysis was conducted. (2) Tissue experiments: An additional 35 patient samples from both the experimental and control groups were randomly selected. The mRNA and protein expression levels of the RhoJ gene were measured using real-time quantitative PCR (RT-qPCR) and Western blotting, respectively. (3) Validation experiments with human umbilical vein endothelial cells (HUVECs): HUVECs were transfected with pcDNA3.1-NC (blank control) and pcDNA3.1-RhoJ (plasmid expression vector carrying the RhoJ gene), respectively. The biological behavior differences between the two groups of cells were examined using the CCK-8 cell proliferation assay, Transwell invasion assay, and Matrigel angiogenesis assay. Measurement data conforming to a normal distribution were expressed as Mean±SD, and comparisons between the two groups were performed using an independent samples t-test. Results:Through CellChat intercellular communication analysis, it was discovered that endothelial cells were the predominant cell subpopulation in both the experimental and control groups, exhibiting strong communication links with other cell subpopulations. In the analysis of DEGs, it was found that the RhoJ gene in endothelial cells was significantly involved in the biological processes of angiogenesis and regulation. In tissue experiments, RT-qPCR and Western bloting results indicated that the relative expression levels of RhoJ mRNA (4.48±1.29 vs. 1.01±0.17) and protein (1.22±0.03 vs. 0.51±0.20) in the experimental group were significantly higher than those in the control group, with statistically significant differences ( P<0.01 for both). The results of the HUVECs validation experiment showed that the cell proliferation, invasion, and angiogenesis abilities of the pcDNA3.1-RhoJ group were significantly enhanced compared to the pcDNA3.1-NC group. Conclusion:Endothelial cells represent the dominant cell subpopulation during the occurrence and locally invasive progression of VMs, playing a crucial role in this process. The RhoJ gene is significant in regulating the biological behavior of VMs endothelial cells.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Objectives:This study aimed to observe the disintegration of clopidogrel and ticagrelor in vitro solution with different pH levels and in human digestive tract.Methods:(1)In vitro study:0.9% normal saline was mixed with hydrochloric acid and sodium bicarbonate respectively to mimic fasting gastric fluid,postprandial gastric fluid,gastric fluid after taking acid-inhibiting agent,acid-free gastric fluid and small intestine fluid.The disintegration of clopidogrel and ticagrelor in different pH solutions was observed.(2)In vivo study:12 patients who were admitted to the Department of Geriatric,Peking University First Hospital from 2022.11 to 2023.6 were included and underwent magnetic controlled capsule endoscopy.We observed the disintegration of clopidogrel(n=6)and ticagrelor(n=6)in the digestive tract.Results:(1)In vitro study:clopidogrel began to disintegrate earlier than ticagrelor([21.67±7.53]s vs.[40.00±6.33]s,P=0.001),but clopidogrel disintegrated more slowly than ticagrelor([23.00±9.38]min vs.[8.33±1.97]min,P=0.011).Clopidogrel disintegrated faster in alkaline solution than in acidic and neutral solution([11.50±4.95]min vs.[28.75±2.50]min,P=0.004),and the disintegration rate of ticagrelor in alkaline solutions is comparable to that in acidic and neutral solutions([7.00±1.41]min vs.[9.00±2.00]min,P=0.285).(2)In vivo study:In the study population,the morphology of clopidogrel and ticagrelor began to change after passing through the esophagus,of which 3 cases(clopidogrel 1 case,ticagrelor 2 cases)were in powder state when passing through the cardia,and the remaining 9 cases were basically intact when entering the stomach and completely disintegrated in the stomach.The complete disintegration time of Clopidogrel varied significantly among individuals,ranging from 8 to 33 min,with an average of(18.80±10.38)min,while the complete disintegration time of ticagrelor ranged from 3 to 6 min,with an average of(4.25±1.26)min.Clopidogrel disintegrated slower than ticagrelor(P=0.034).Conclusions:In vitro study,clopidogrel disintegrated more slowly than ticagrelor in solutions at different pH levels.Compared with clopidogrel,the disintegration rate of ticagrelor was less affected by pH.After oral administration of clopidogrel and ticagrelor,clopidogrel disintegrated more slowly than ticagrelor.The difference of complete disintegration time between individuals of ticagrelor was smaller and the disintegration rate was faster.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL