Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.

Objective:To systematically screen and identify long noncoding RNA(lncRNA)associated with bone marrow adiposity changes in aplastic anemia(AA).Methods:The PPARγ and C/EBPα ChIP-Seq data in ChIPBase was analyzed by bioinformatics and the potential lncRNA co-transcriptionally regulated by PPARγ and C/EBPα was screened.The expression of candidate lncRNA was verified by qRT-PCR in the in vitro adipogenic differentiation model of BM-MSC,BM-MSC infected with lenti-shPPARγ and lenti-shC/EBPα as well as clinical BM-MSC samples derived from AA and controls.Results:PPARγ and C/EBPα were significantly highly expressed in AA BM-MSC,and knock-down of PPARγ and C/EBPα impaired the adipogenic capacity of AA BM-MSC.PPARγ and C/EBPα cotranscriptionally activate LINC01230 promoter activity in binding sites dependant manner.The LINC01230 was also aberrantly highly expressed in AA BM-MSC compared with controls.Conclusion:PPARγ and C/EBPα are aberrantly expressed in AA BM-MSC and may promote the adipogenic differentiation of AA BM-MSC,and to a certain extent mediate the bone marrow adiposity alteration by transcriptionally activating LINC01230 expression.

This study was aimed at understanding the etiological and genetic characteristics of Yersinia enterocolica isolated in Jiangsu Province between 2005 and 2019.All 110 identified strains of Y.enterocolica were from patients with foodborne diar-rhea in Jiangsu Province,or from pigs,dogs,cattle,sheep,poultry,flies,or food.Virulence genes,biological serotypes,drug resistance,multilocus sequence typing(MLST),and core genome multilocus sequence typing(cgMLST)based on whole-genome sequencing were performed.The strains included 27 pathogenic strains(24.5％)and 83 non-pathogenic strains(75.5％).Non-pathogenic strains accounted for a high proportion,particularly among strains from patients(15/16,93.8％).The biological serotypes of pathogenic strains were mainly type 3/O∶3(26/27,96.3％).Non-pathogenic strains included 1A/O∶8 type(23/83,27.7％),1 A/O∶5 type(14/83,16.9％),and the other four biological serotypes(excluding unknown se-rotypes).Pathogenic strains were dominated by type 3/O∶3(26/27,96.3％),and more than 80％of these strains were sensi-tive to 19 antibiotic types.Whole-genome sequencing indicated that the pathogenic strains were all ST135 type,whereas the non-pathogenic strains were more diverse and scattered.HierCC clustering analysis grouped all strains into three clus-ters:pathogenic strains were in one cluster,and strains from patients were found in all three clusters.In conclusion,the Y.enterocolica strains from patients were primarily non-patho-genic.Non-pathogenic strains showed richer epigenetic and ge-netic diversity than pathogenic strains.The monitoring of these strains should be strengthened to decrease the risk of human infection.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Cardiac cephalalgia is a rare disease caused by underlying coronary artery disease that presents as headache with or without chest symptoms.Headache symptoms are often caused by referred pain,increased intracranial pressure and release of large amounts of pain-causing neurochemicals due to myocardial ischemia,and cortical hypoperfusion.Due to the low overall prevalence of the disease,the lack of chest pain typical of coronary heart disease,and the fact that it may be difficult to distinguish from headaches caused by neurological diseases,accurate diagnosis and treatment of the disease are often delayed.We report a case of acute coronary syndrome with headache only.Revascularization was achieved through percutaneous coronary intervention therapy,followed by standard secondary prevention pharmacotherapy.Follow-up six months postoperatively showed a significant improvement in exercise tolerance,with no further headache episodes.The purpose is to improve the understanding of patients with cardiac cephalalgia,with a view to early identification and timely intervention,and ultimately improve the symptoms and prognosis.

Objective To investigate the influence of different delivery techniques,treatment sites and dose-volume algorithms on the results of three-dimensional dosimetric verification for intensity-modulated radiation therapy(IMRT)plans and the importance of individualized quality assurance(QA)evaluation standard for radiotherapy plans.Methods Totally 350 tumor patients receiving radiotherapy at some hospital from January 2017 to February 2022 had their three-dimensional dosimetric verification results of IMRT plans selected retrospectively and underwent data collection with COMPASS system,and then were grouped in terms of delivery technique(fixed-beam IMRT and volumetric modulated arc therapy),treatment site(neck,chest and abdomen)and dose-volume algorithm(anisotropic analytical algorithm and collapsed cone convolution algorithm).All the groups were compared based on the 3％/2 mm criterion with regard to the Gamma pass rate of 10％prescription dose area(GP10％),Gamma pass rate(GP50％)and mean Gamma index(μGI5o％)of 50％prescription dose area,dose of 95％target volume(D95％)and its mean dose(Dmean),parotid gland mean dose(Dmean),dose of 1％spinal cord volume(D1％),dose of 1％brain stem volume(D1％)of head and neck radiotherapy plan,heart and lung mean dose(Dmean)and dose of 1％spinal cord volume(D1％)of chest radiotherapy plan and bladder,rectum and femur mean dose of abdomen radiotherapy plan(Dmean).SPSS 26.0 software was used for statistical analysis.Results For different delivery techniques,significant differences were found in all the QA results except GP50％of abdomen radiotherapy plan(P＜0.05).For different treatment sites,the differences were statistically significant between the QA results of head and neck radiotherapy plan and abdomen plan and between those of chest radio-therapy plan and abdomen radiotherapy plan(P＜0.05),while were not significant between the QA results of head and neck radiotherapy plan and chest radiotherapy plan(P＞0.05).For different dose-volume algorithms,the QA results had significant differences except D5％of abdomen radiotherapy planning target volume and Dmean and D1％of chest radiotherapy PTV(P＜0.05).Conclusion Dosimetric verification results vary depending on the delivery technique,treatment site and dose-volume algorithm.Statistical process control recommended by AAPM TG-218 report may be involved in to establish individualized QA standard for radiotherapy plans in case universal action limits are not appropriate.[Chinese Medical Equipment Journal,2024,45(11):54-59]

This study was aimed at understanding the etiological and genetic characteristics of Yersinia enterocolica isolated in Jiangsu Province between 2005 and 2019.All 110 identified strains of Y.enterocolica were from patients with foodborne diar-rhea in Jiangsu Province,or from pigs,dogs,cattle,sheep,poultry,flies,or food.Virulence genes,biological serotypes,drug resistance,multilocus sequence typing(MLST),and core genome multilocus sequence typing(cgMLST)based on whole-genome sequencing were performed.The strains included 27 pathogenic strains(24.5％)and 83 non-pathogenic strains(75.5％).Non-pathogenic strains accounted for a high proportion,particularly among strains from patients(15/16,93.8％).The biological serotypes of pathogenic strains were mainly type 3/O∶3(26/27,96.3％).Non-pathogenic strains included 1A/O∶8 type(23/83,27.7％),1 A/O∶5 type(14/83,16.9％),and the other four biological serotypes(excluding unknown se-rotypes).Pathogenic strains were dominated by type 3/O∶3(26/27,96.3％),and more than 80％of these strains were sensi-tive to 19 antibiotic types.Whole-genome sequencing indicated that the pathogenic strains were all ST135 type,whereas the non-pathogenic strains were more diverse and scattered.HierCC clustering analysis grouped all strains into three clus-ters:pathogenic strains were in one cluster,and strains from patients were found in all three clusters.In conclusion,the Y.enterocolica strains from patients were primarily non-patho-genic.Non-pathogenic strains showed richer epigenetic and ge-netic diversity than pathogenic strains.The monitoring of these strains should be strengthened to decrease the risk of human infection.

Objective:To investigate the prognostic value of 18F-FDG PET/CT in patients with locally recurrent nasopharyngeal carcinoma (NPC) receiving chemoradiotherapy, and relationships between different metabolic parameters and peripheral blood inflammation markers. Methods:From January 2013 to June 2016, the data of 56 patients (40 males, 16 females, age 27-81 years) with locally recurrent NPC receiving chemoradiotherapy in the First People′s Hospital of Foshan were retrospectively analyzed. The SUV max, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were determined by 18F-FDG PET/CT and peripheral blood inflammation markers within 1 week before treatment were measured. Spearman rank correlation analysis was used to estimate the correlations between metabolic parameters and inflammation markers. According to the ROC curve, the best cut-off values of the SUV max, MTV and TLG were obtained and used to group patients. The Kaplan-Meier method and Cox regression were used to conduct univariate analysis and multivariate analysis of 3-year locoregional failure-free survival (LRFFS) and 3-year overall survival (OS) in patients with locally recurrent NPC. The prognostic value of metabolic parameters in patients with early and advanced recurrent T(rT) stages were compared. Results:MTV was positively correlated with neutrophils, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and high-sensitivity C-reactive protein (hs-CRP) before treatment in patients with locally recurrent NPC ( rs values: 0.30, 0.30, 0.28, 0.27, all P<0.05); TLG was positively correlated with neutrophils, monocytes, NLR and PLR ( rs values: 0.30, 0.28, 0.32, 0.30, all P<0.05). But there were no correlations between SUV max and peripheral blood inflammation markers ( rs values: from -0.18 to 0.24, all P>0.05). SUV max was an factor affecting 3-year LRFFS of patients undergoing radiotherapy and chemotherapy (hazard ratio ( HR)=3.815(95% CI: 1.278-11.388), P=0.016), while rT stage and MTV were prognostic factors for 3-year OS ( HR values: 4.492(95% CI: 1.474-13.688), 7.238(95% CI: 1.653-31.688), P values: 0.008, 0.009). For patients with advanced rT (rT3-4), the 3-year OS of the MTV≥6.84 cm 3 group was significantly lower than that of MTV<6.84 cm 3 group ( χ2=6.99, P=0.008). Conclusions:SUV max of tumor and MTV before treatment have important prognostic values in patients with locally recurrent NPC receiving chemoradiotherapy, but their predictive effects on prognosis are not the same. The varying effects of local inflammation on metabolic parameters may be one of the important reasons lead to that difference.

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.
Rats ; Animals ; IgA Vasculitis/drug therapy* ; Monoterpenes ; Administration, Oral ; Liquid Chromatography-Mass Spectrometry

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.