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 study the diagnostic value of artificial intelligence B-ultrasound image computer-aided diagnosis system (hereinafter referred to as intelligent ultrasound system) in adult goiter.Methods:In June 2022 and March 2023, two phases of thyroid disease survey were carried out in 4 cities in Anhui Province. One village was selected in each city, and 250 adults were selected as survey subjects in each village. Adult bilateral thyroid area was scanned by both intelligent ultrasound system and conventional ultrasound scanning equipment, and the effectiveness of intelligent ultrasound system in the diagnosis of goiter was analyzed based on the results of conventional ultrasound examination. Receiver operating characteristic (ROC) curve was drawn, and Kappa test was used to analyze the consistency between intelligent ultrasound system and conventional ultrasound examination in the diagnosis of goiter. At the same time, Spearman correlation analysis and Bland-Altman method were used to evaluate the consistency of the two methods in measuring thyroid volume.Results:After screening and removing outliers and missing values, a total of 910 adults were included, including 253 males (27.80%) and 657 females (72.20%). The age was (45.92 ± 10.20) years old, ranging from 18 to 60 years old. The sensitivity, specificity, and accuracy of the intelligent ultrasound system for diagnosing adult goiter were 80.00%, 99.67%, and 99.56%, respectively. The area under the ROC curve (AUC) was 0.996, which was consistent with the results of conventional ultrasound examination for diagnosing goiter ( κ = 0.67, P < 0.001). After controlling for variables such as gender, thyroid function, and thyroid nodules, the intelligent ultrasound system showed good consistency with conventional ultrasound examination in the diagnosis of goiter in females, adults with thyroid dysfunction, and adults without thyroid nodules ( κ = 0.66, 0.80, 0.80, P < 0.001). The consistency in the diagnosis of goiter in adults with thyroid nodules was moderate ( κ = 0.56, P < 0.001). Spearman correlation analysis showed a highly positive correlation between the measurement results of adult thyroid volume by intelligent ultrasound system and conventional ultrasound examination ( r = 0.88, P < 0.001). The Bland-Altman method results showed that only 4.62% (42/910) of points in adults were outside the 95% consistency limit, indicating good consistency between intelligent ultrasound system and conventional ultrasound examination in measuring thyroid volume (< 5%). The proportion of points outside the 95% consistency limit in males, adults with thyroid dysfunction, and adults with thyroid nodules was 6.72% (17/253), 5.83% (12/206), and 6.45% (12/186), respectively. Conclusions:The intelligent ultrasound system has certain diagnostic value for adult goiter and has good consistency with conventional ultrasound examination for thyroid volume measurement. However, the accuracy of diagnosis for males and adults with thyroid nodules still needs to be improved.

Odontogenic maxillary sinusitis(OMS)is a subtype of maxillary sinusitis(MS).It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion.Due to the lack of unique clinical features,OMS is difficult to distinguish from other types of rhinosinusitis.Besides,the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis.Its current diagnosis and treatment are thus facing great difficulties.The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS.However,this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality.Based on systematically reviewed literature and practical experiences of expert members,our consensus focuses on characteristics,symptoms,classification and diagnosis of OMS,and further put forward multi-disciplinary treatment decisions for OMS,as well as the common treatment complications and relative managements.This consensus aims to increase attention to OMS,and optimize the clinical diagnosis and decision-making of OMS,which finally provides evidence-based options for OMS clinical management.

Objective To observe the clinical effect of PENG's tendon-separating tuina therapy combined with lateral needling technique for meridian sinew in the treatment of acute scapulohumeral periarthritis(referred to as frozen shoulder),and to provide therapeutic ideas and evidence for the treatment of acute scapulohumeral periarthritis.Methods Sixty patients with acute scapulohumeral periarthritis were randomly divided into treatment group and control group,with 30 cases in each group.The control group was treated with lateral needling technique for meridian sinew,and the treatment group was treated with PENG's tendon-seperating tuina therapy combined with lateral needling technique for meridian sinew.Both groups were treated for once a day,10 times as a course of treatment,and for a total of 2 courses of treatment.The changes of pain Visual Analogue Scale(VAS)score and Constant-Murley Scale(CMS)score of shoulder joint function in the two groups were observed before treatment and after one and two course(s)of treatment.Moreover,the clinical efficacy of the two groups was evaluated.Results(1)After two courses of treatment,the total effective rate of the treatment group was 90.00%(27/30),and that of the control group was 73.30%(22/30).The overall efficacy(tested by rank sum test)and total effective rate(tested by chi-square test)of the treatment group were significantly superior to those of the control group,and the differences were statistically significant(P＜0.05).(2)After one and two course(s)of treatment,the VAS scores of pain in the two groups were significantly decreased than those before treatment(P＜0.05 or P＜0.01);after two courses of treatment,VAS scores in the two groups were significantly lower than those after one course of treatment(P＜0.05).The decrease of VAS scores in the treatment group after one and two course(s)of treatment was significantly superior to that in the control group,and the difference were statistically significant(P＜0.05 or P＜0.01).(3)After one and two course(s)of treatment,the CMS scores of shoulder joint function in the two groups were significantly higher than those before treatment(P＜0.01);after two courses of treatment,the CMS scores in the two groups were higher than those after one course of treatment(P＜0.05).The increase of CMS scores in the treatment group after one and two course(s)of treatment was significantly superior to that in the control group,and the difference was statistically significant(P＜0.01).Conclusion PENG's tendon-separating tuina therapy combined with lateral needling technique for meridian sinew has a definite clinical effect in the treatment of patients with acute scapulohumeral periarthritis,which can effectively relieve the pain and discomfort of shoulder joint and improve the movement function of shoulder joint.

Objective To investigate the protective effect of placental mesenchymal stem cells(P-MSCs)on pancreatic trauma(PT)in rats.Methods Sixty healthy adult male SD rats were randomly divided into control group,pancreatic trauma group(inject 1 ml of PBS solution locally in the pancreatic injury area and around the trauma area),and P-MSCs group[inject 1 ml of P-MSCs(1×106/ml)locally in the pancreatic injury area and around the trauma area],with 20 rats in each group.The pancreatic trauma rat model was established using a traumatic pressure of 400 kPa.Five rats were sacrificed at 1,3,5,and 7 d after modeling in each group,and serum and pancreatic tissue were collected.HE staining was used to observe the pathological changes of pancreatic tissue and pathological scores were performed.The ELISA method was used to measure the concentrations of serum amylase(AMS),lipase(LPS),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-10,and transforming growth factor-β1(TGF-β1),as well as the activities of myeloperoxidase(MPO)and superoxide dismutase(SOD)in pancreatic tissue.The TUNEL method was used to observe the level of apoptosis in pancreatic tissue was observed by the TUNEL method.Results Compared with control group,pancreatic trauma group and P-MSCs group showed significant differences after pancreatic trauma,including the generation of peritoneal fluid increased(P<0.05),the ratio of pancreas to body weight and the total score of pancreatic tissue pathological damage increased(P<0.05),and serum levels of AMS,LPS,TNF-α,IL-6,and MPO activity increased early and showed a decreasing trend over time(P<0.05),while anti-inflammatory factors IL-10 and SOD activity showed an increasing trend over time(P<0.01),level of TGF-β1 in the early decline showed an upward trend over time(P<0.01),and the apoptosis index(AI)significantly increased(P<0.001).Compared with pancreatic trauma group,P-MSCs group showed an improvement in the overall morphology of pancreatic tissue,the generation of peritoneal fluid decreased(P<0.001),the pancreas to body weight ratio and the total score of pancreatic tissue pathological damage decreased(P<0.05),and serum levels of AMS,LPS,IL-6,TNF-α and MPO activity returned to normal levels faster(P<0.05);and the rate of anti-inflammatory factors IL-10,TGF-β1 and SOD activity elevation increased(P<0.05),the AI increased(P<0.001).Conclusion P-MSCs can achieve therapeutic effects on pancreatic trauma in rats by promoting pancreatic tissue repair,reducing local and systemic inflammation,improving tissue oxidative stress,and enhancing pancreatic acinar cell apoptosis.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

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.

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.
Male ; Female ; Humans ; Child ; Fanconi Anemia/genetics* ; Chromosome Breakage ; Retrospective Studies ; Exons ; China/epidemiology*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.