Apigenin suppresses epithelial-mesenchymal transition in high glucose-induced retinal pigment epithelial cell by inhibiting CBP/p300-mediated histone acetylation.

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.

Melatonin, a potentially effective drug for the treatment of infected bone nonunion.

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.

Prediction of lymph node metastasis in patients with papillary thyroid cancer based on radiomics analysis and intraoperative frozen section analysis: A retrospective study.

INTRODUCTION: To evaluate the diagnostic efficiency among the clinical model, the radiomics model and the nomogram that combined radiomics features, frozen section (FS) analysis and clinical characteristics for the prediction of lymph node (LN) metastasis in patients with papillary thyroid cancer (PTC). METHODS: A total of 208 patients were randomly divided into two groups randomly with a proportion of 7:3 for the training groups (n = 146) and the validation groups (n = 62). The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for the selection of radiomics features extracted from ultrasound (US) images. Univariate and multivariate logistic analyses were used to select predictors associated with the status of LN. The clinical model, radiomics model and nomogram were subsequently established by logistic regression machine learning. The area under the curve (AUC), sensitivity and specificity were used to evaluate the diagnostic performance of the different models. The Delong test was used to compare the AUC of the three models. RESULTS: Multivariate analysis indicated that age, size group, Adler grade, ACR score and the psammoma body group were independent predictors of lymph node metastasis (LNM). The results showed that in both the training and validation groups, the nomogram showed better performance than the clinical model, albeit not statistically significant (p > .05), and significantly outperformed the radiomics model (p < .05). However, the nomogram exhibits a slight improvement in sensitivity that could reduce the incidence of false negatives. CONCLUSION: We propose that the nomogram holds substantial promise as an effective tool for predicting LNM in patients with PTC.

Seven-layer analysis model of an optical waveguide excitation fluorescence microscopy.

In this paper, an optical waveguide evanescent field fluorescence microscopy is studied. Based on Maxwell's equation, a seven-layer theoretical analysis model is developed for the evaluation of an optical waveguide excitation fluorescence microscopy. The optical waveguide excitation fluorescence microscopy structure is systematically and comprehensively analysed at the wavelengths of 488, 532 and 646 nm for fluorescent dyes. The analysis results provide some useful suggestions, which will be beneficial to the research of an optical waveguide evanescent field fluorescence microscopy.

Solute carrier family 11 member 1 genetic polymorphisms rs17235409 and rs3731865 associate with susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population.

Genetic variations in the solute carrier family 11 member 1 (SLC11A1) gene have been implicated in developing inflammatory disorders. However, it is still unclear whether such polymorphisms contribute to the pathogenesis of post-traumatic osteomyelitis (PTOM). Therefore, this study investigated the roles of genetic variations of the SLC11A1 gene (rs17235409 and rs3731865) in PTOM development in a Chinese Han cohort. The SNaPshot method was used for genotyping 704 participants (336 patients and 368 controls) for rs17235409 and rs3731865. Outcomes revealed that rs17235409 increased the risk of PTOM occurrence by dominant (p = .037, odds ratio [OR] = 1.44) and heterozygous models (p = .035, OR = 1.45), implying AG genotype as a risk factor for PTOM development. In addition, patients with AG genotype had relatively higher levels of inflammatory biomarkers than those with AA and GG genotypes, especially for the white blood cell count and C-reactive protein. Despite no statistically significant differences achieved, rs3731865 may reduce the PTOM susceptibility, suggested by the results of dominant (p = .051, OR = 0.67) and heterozygous (p = .068, OR = 0.69) models. In short, rs17235409 confers an elevated chance of developing PTOM, with AG genotype as a risk factor. Whether rs3731865 involves in the pathogenesis of PTOM requires further investigations.

Structure-dependent of 3-fluorooxindole derivatives interacting with ctDNA: Binding effects and molecular docking approaches.

3-Fluorooxindole has been shown to be a biologically active structural unit, novel derivative containing 3-fluorooxindole unit has been successfully constructed using 3-fluorooxindole as a substrate in previous work. Here, the interactions between novel 3-fluorooxindole derivatives and ctDNA were explored through molecular docking, multi-spectral and NMR methods, and the dependence of the binding mechanism on the structure was revealed by combined physical chemistry and organic chemistry. Firstly, molecular docking indicated that the planarity of the molecule enhances the binding strength to ctDNA. UV absorption result showed a weak binding effect. Fluorescence spectroscopy suggested the binding mechanism of 3-fluorooxindoles and ctDNA via groove binding. Moreover, the binding mechanism of 3-fluorooxindoles to ctDNA was further confirmed by 1H NMR spectroscopy, viscometry, and CD spectroscopy as groove binding. FT-IR spectroscopy reflected a more obvious disturbance of the phosphate group in the groove region of ctDNA. Electrochemistry was also used to probe the binding strength of 3-fluorooxindoles to ctDNA, and it showed a weak binding strength. From the above study, we concluded that 3-fluorooxindoles bind mainly in the groove region of ctDNA with weak binding strength. This study provides an idea for the activity screening aspect of 3-fluorooxindole derivatives from molecular planarity consideration and relevant information on biophysical and bioorganic aspects for drug development.

The therapeutic effect of granulocyte colony stimulating factor (G-CSF) on potential biochemical pregnancy in patients with unexplained repeated transplantation failure (RIF): a case series and literature review.

BACKGROUND: Biochemical pregnancy is a type of embryo transfer failure, patients with unexplained repeated implantation failure (RIF) also have higher biochemical pregnancy rate. Our study intends to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) in patients with unexplained RIF with low hCG levels in early pregnancy. METHODS: Unexplained RIF patients with low hCG levels after embryo transfer were allocated. G-CSF were administrated from the ninth days after embryo transfer. Clinical pregnancy, miscarriage and live birth rates were evaluated. RESULTS: The clinical pregnancy and live birth rates were 52.5% and 30%. CONCLUSION: G-CSF is an effective treatment for potential biochemical pregnancy in unexplained RIF patients.

Implant surface culture may be a useful adjunct to standard tissue sampling culture for identification of pathogens accounting for fracture-device-related infection: a within-person randomized agreement study of 42 patients.

BACKGROUND AND PURPOSE: Identification of pathogens causing fracture-device-related infection (FDRI) is always a challenge as the positive rate of standard tissue sampling culture (TSC) remains unsatisfactory. This study evaluates the efficiency of implant surface culture (ISC) as an adjunct to standard TSC for identification of FDRI-associated microorganisms. PATIENTS AND METHODS: Between November 2020 and March 2022, patients diagnosed with FDRI defined by the International Fracture-Related Infection (FRI) Consensus Group, and indicated for implant removal, underwent both methods for bacteria detection. The test order of ISC and TSC was randomly selected for each patient included, as a within-person randomized design. For ISC, the recovered implants were gently covered with tryptic soy agar after rinsing with normal saline twice, and then incubated at 37℃ 5% CO2 for up to 14 days. For TSC, 5 specimens were sampled and sent to the Clinical Laboratory of Southern Medical University Nanfang Hospital, Guangzhou, for culture and identification. RESULTS: 42 consecutive patients were included, with a mean age of 46 years. The most frequent infection site and implant type were the tibia (21 cases) and plates with screws (30 cases), respectively. Altogether 21 patients were found with positive outcomes by both methods, and the identified pathogens were consistent. ISC found an additional 15 patients showing positive results, which were negative by TSC. Furthermore, the mean culture time of ISC was shorter than that of TSC (1.5 days vs. 3.2 days). INTERPRETATION: ISC may be a useful adjunct to TSC for detection of bacteria causing FDRI, with a relatively higher positive rate and a shorter culture time.

Interactions between Two Kinds of Gold Nanoclusters and Calf Thymus Deoxyribonucleic Acid: Directions for Preparations to Applications.

Gold nanoclusters (AuNCs) have shown promising applications in biotherapy owing to their ultrasmall size and unique molecular-like properties. In order to better guide the preparations and applications of AuNCs, dihydrolipoic acid-protected AuNCs (DHLA-AuNCs) and glutathione-protected AuNCs (GSH-AuNCs) were selected as models and the interactions between them and calf thymus DNA (ctDNA) were studied in detail. The results showed that there was a small difference in the binding mechanisms and forces between both AuNCs and ctDNA. The quenching mechanisms of both AuNCs to (ctDNA-HO) were completely different. The binding constants indicated that the binding strength between DHLA-AuNCs and ctDNA was greater than those of GSH-AuNCs. The conformation investigations showed that GSH-AuNCs had a greater impact on the conformation of ctDNA, and both AuNCs were more inclined to interact with the A-T base pairs of ctDNA. These results indicate that the surface ligand had a significant effect on the interactions between AuNCs and DNA and might also further affect the applications of AuNCs, and these results could guide the preparations of AuNCs. For DHLA-AuNCs, their good biocompatibility made them a potential candidate for application in imaging, drug treatment, sensing, and so on. The resulting base accumulation of ctDNA and weak interactions made GSH-AuNCs have great potential for application in gene therapy, which was consistent with the current reports on the applications of these two AuNCs. This work has pointed out the directions for the preparations and applications of AuNCs.

Preparation of graphene quantum dots with glycine as nitrogen source and its interaction with human serum albumin.

Graphene quantum dots (GQDs) could be regarded as graphene with a lateral dimension less than 100 nm. Compared with graphene, GQDs not only possess the excellent properties of graphene but also have been proven to have low toxicity, high fluorescence stability, strong water solubility, as well as better biocompatibility. In this work, an amide bond-based, N-doped graphene quantum dot was synthesized using a simple hydrothermal method. When the reaction time was 4 h and the temperature was 180°C, fluorescence excitation and emission peaks of the product were 340 nm and 450 nm, respectively. Its interaction with human serum albumin (HSA) was investigated using spectroscopy, gel electrophoresis, and molecular simulation. Gel electrophoresis showed that the product did not cause complete scission of the peptide chain in HSA, indicating good biocompatibility. The results of molecular docking showed that the product tended to bind to site III of HSA. This paper provides a meaningful reference for design and development in nanomedicine.