Association of hyperuricemia combined with sarcopenia on ASCVD risk.

BACKGROUND: Hyperuricemia and sarcopenia are both strongly linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD), and this study was designed to look into the interactive effects of hyperuricemia on ASCVD risk. METHODS: This study collected information from patients (N = 2647) who underwent health check-ups at the Health Care Building of Wuhan Union Hospital between January 2019 and December 2020. Skeletal muscle mass was measured using bioelectrical impedance methods. The Asian Working Group on Sarcopenia diagnostic criteria were used to classify patients with sarcopenia. ASCVD risk was calculated using the Framingham Heart Study, and ASCVD risk ≥ 20% was considered high risk ASCVD. IBM SPSS 25.0 and GraphPad prism 8.0 software were used for data analysis and graphing. RESULTS: The prevalence of hyperuricemia and sarcopenia was 23.57% and 15.34%, respectively. The occurrence of cardiovascular risk factors such as obesity, hypertension, diabetes mellitus, chronic kidney disease, and low HDL-Cemia was significantly higher in subjects with hyperuricemia combined with sarcopenia (OR = 1.734, 3.064, 1.61, 8.77 and 1.691 respectively, p < 0.05); Hyperuricemia and high-risk ASCVD were independently associated (OR = 1.355, 95% CI = 1.000-1.838, p = 0.04). Although there was no significant association between sarcopenia and high-risk ASCVD after controlling for confounders (OR = 1.274, 95% CI = 0.828-1.959, p = 0.271), sarcopenia combined with hyperuricemia significantly increased high-risk ASCVD (OR = 3.229, 95% CI 1.544-6.751, p = 0.002). CONCLUSION: Hyperuricemia is independently associated with high-risk ASCVD; Sarcopenia and high-risk ASCVD did not show an independent relationship, but there was a synergistic effect of the two on ASCVD risk, which may imply that managing both hyperuricemia and sarcopenia may have a greater cardiovascular benefit.

The ZJU index is associated with the risk of obstructive sleep apnea syndrome in Chinese middle-aged and older people: a cross-sectional study.

BACKGROUND: The ZJU index, a novel calculation that combines body mass index, triglycerides, fasting blood glucose and the ratio of alanine aminotransferase to aspartate aminotransferase, is a closely related measure of obesity and insulin resistance. Studies of the ZJU index in relation to obstructive sleep apnea syndrome (OSAS) have not been reported. This study assessed the correlation between the ZJU values and OSAS risk. METHODS: A total of 2,130 participants who underwent polysomnographic monitoring were included in the study. The participants' basic information and laboratory biochemical indicators were collected, and the ZJU index was computed. The ZJU index was divided into quartiles. The correlation between the different ZJU index levels and OSAS risk was assessed using logistic regression. Drew a receiver operating characteristic (ROC) relationship curve, with prediction efficacy judged by the area under the curve (AUC), and found the optimum cut-off point for ZJU index to predict OSAS. Relative risks were presented as odds ratios (OR). The range of OR values is expressed in the form of 95% confidence intervals (95% CI). RESULTS: The number of patients diagnosed with OSAS increased progressively with increasing ZJU index (T1: 9.4%; T2: 20.6%; T3: 28.3%; T4: 41.7%; P < 0.001). The additional confounders were adjusted by the logistic regression models, the study revealed an independent correlation between ZJU index and OSAS. (P < 0.001). The OSAS risk was notably higher at the highest ZJU index levels. (OR = 2.046 [95% CI: 1.057 to 3.964]). The ROC curve for the ZJU index showed an AUC of 0.64 (P < 0.001) for males and 0.75 (P < 0.001) for females, with a specificity of 64% and 55% and a sensitivity of 60% and 92% for males and females, respectively, with the optimum cut-off values of 36.568 and 34.722, respectively. CONCLUSION: A high ZJU index was significantly associated with an increasing risk of OSAS. The ZJU is expected to be a meaningful index for detecting OSAS in the general population.

Diagnostic value of combined pelvic floor ultrasound parameters for pelvic floor dysfunction and risk factors.

OBJECTIVE: To investigate the diagnostic value of pelvic floor ultrasound parameters in combination for pelvic floor dysfunction (PFD), and to explore the risk factors. METHODS: Forty PFD patients treated from April2019to December 2020(case group) and another 40 healthy women (control group) were enrolled. Their clinical data were collected, and both groups received three-dimensional (3D) ultrasound of the pelvic floor. The diagnostic value of pelvic floor ultrasound parameters for PFD was assessed by receiver operating characteristic (ROC) curves. The risk factors of PFD were evaluated by multivariate logistic regression analysis. RESULTS: The area under the ROC curve (AUC), sensitivity, and specificity of the parameters in combination for predicting PFD were 0.851 [95% confidence interval (CI): 0.743-0.959], 0.901, and 0.812, respectively, indicating acceptable accuracy. Results of logistic regression analysis revealed that spontaneous delivery, lateral episiotomy/laceration, and large bladder neck rotation angle, posterior urethrovesical angle (PUA), bladder neck tilt angle, bladder neck distance (BND), levator hiatus area (LHA) (at anal contraction), R-LHA and V-LHA were risk factors for PFD (p < 0.05), while physical exercise was a protective factor (p < 0.05). ROC curve analysis revealed that the AUC, sensitivity, and specificity of the forest map model were 0.822 (95% CI: 0.759-0.885), 0.942, and 0.601, respectively, indicating acceptable accuracy of the model. Internal data validation of the model demonstrated consistence of the predicted occurrence of PFD with the actual one. CONCLUSIONS: Spontaneous delivery, lateral episiotomy/laceration, and large bladder neck rotation angle, PUA, bladder neck tilt angle, BND, LHA (at anal contraction), R-LHA and V-LHA were risk factors for PFD.

In Silico Investigation of the Molecular Mechanism of PARP1 Inhibition for the Treatment of BRCA-Deficient Cancers.

The protein PARP1, which plays a crucial role in DNA repair processes, is an attractive target for cancer therapy, especially for BRCA-deficient cancers. To overcome the acquired drug resistance of PARP1, PARP1 G-quadruplex (G4) identified in the PARP1-promotor region is gaining increasing attention. Aiming to explore the molecular mechanism of PARP1 inhibition with PARP1 G4 and PARP1 as potential targets, a comparative investigation of the binding characteristics of the newly identified G4 stabilizer MTR-106, which showed modest activity against talazoparib-resistant xenograft models and the FDA-approved PARP1 inhibitor (PARPi) talazoparib, were performed through molecular simulations. Combined analyses revealed that, relative to the groove binding of talazoparib, MTR-106 induced the formation of a sandwich framework through stacking with dT1 and the capping G-pair (dG2 and dG14) of PARP1 G4 to present largely enhanced binding affinity. For the binding with PARP1, although both were located in the catalytic pocket of PARP1, MTR-106 formed more extensive interactions with the surrounding PARP1 residues compared to talazoparib, in line with its increased binding strength. Importantly, vdW interaction was recognized as a decisive factor in the bindings with PARP1 G4 and PARP1. Collectively, these findings demonstrated the ascendancy of MTR-106 over talazoparib at the atomic level and revealed that the dual targeting of PARP1 G4 and PARP1 might be pivotal for PARPi that is capable of overcoming acquired drug resistance, providing valuable information for the design and development of novel drugs.

Hsa-miR-599 inhibits breast cancer progression via BRD4/Jagged1/Notch1 axis.

Hsa-miR-599 was identified as a tumor suppressor against cancer. This study aimed to explore possible mechanisms of antitumor effect of hsa-miR-599 against breast cancer. Tissue specimens were collected from 106 breast cancer cases, and breast cancer cell line MCF-7 was cultured for in vitro experiments. The expression pattern of hsa-miR-599 was measured via quantitative real-time polymerase chain reaction. Lipofectamine® 2000 reagent was used for cell transfection. Cell viability, motility and apoptosis were detected using MTT assay, transwell assay, and flow cytometer, respectively. Protein analysis was performed via western blot. Hsa-miR-599 expression was decreased in breast cancer tissues and cells. Moreover, its expression was negatively correlated with TNM stage (p = 0.004) and lymph node metastasis (p = 0.001). Enhanced hsa-miR-599 expression in breast cancer cells could induce the inhibition against cell proliferation, migration and invasion, and strengthen cell apoptosis. BRD4 might be a target of hsa-miR-599. Hsa-miR-599 combined with BRD4 inhibited breast cancer progression through targeting Jagged1/Notch1 pathway. Hsa-miR-599 expression is downregulated in breast cancer. Hsa-miR-599 may inactivate BRD4/Jagged1/Notch1 axis, thus suppressing malignant progression of breast cancer.

Identification of new hypoxia-regulated epithelial-mesenchymal transition marker genes labeled by H3K4 acetylation.

Hypoxia-induced epithelial-mesenchymal transition (EMT) involves the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5. The histone mark histone 3 lysine 4 acetylation (H3K4Ac) is observed in the promoter regions of various EMT marker genes (eg, CDH1 and VIM). To further define the genome-wide location of H3K4Ac, a chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) analysis was performed using a head and neck squamous cell carcinoma (HNSCC) FaDu cell line under normoxia and hypoxia. H3K4Ac was found to be located mainly around the transcription start site. Coupled with analysis of gene expression by RNA sequencing and using a HDAC3 knockdown cell line, 10 new genes (BMI1, GLI1, SMO, FOXF1, SIRT2, etc) that were labeled by H3K4Ac and regulated by HDAC3 were identified. Overexpression or knockdown of GLI1/SMO increased or repressed the in vitro migration and invasion activity in OECM-1/FaDu cells, respectively. In HNSCC patients, coexpression of GLI1 and SMO in primary tumors correlated with metastasis. Our results identify new EMT marker genes that may play a significant role in hypoxia-induced EMT and metastasis and further provide diagnostic and prognostic implications.

ERK1/2-PPARγ pathway is involved in Chlamydia pneumonia-induced human umbilical vein endothelial cell apoptosis through increased LOX-1 expression.

Chlamydia pneumonia (C.pn) is a common respiratory pathogen that is involved in human cardiovascular diseases and promotes the development of atherosclerosis in hyperlipidemic animal models. C.pn reportedly up-regulated lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Recently, the anti-atherosclerotic activity of peroxisome proliferator-activated receptor γ (PPARγ) has been documented. In the present study, we investigated the effect of C.pn on LOX-1 expression in human umbilical vein endothelial cells (HUVECs) and identified the involvement of the PPARγ signaling pathway therein. The results showed that C.pn increased the expression of LOX-1 in HUVECs in a dose- and time-dependent manner. C.pn-induced up-regulation of LOX-1 was mediated by ERK1/2, whereas p38 MAPK and JNK had no effect on this process. C.pn induced apoptosis, inhibited cell proliferation, and decreased the expression PPARγ in HUVECs. Additionally, LOX-1 activity and cell injury caused by C.pn through activation of ERK1/2 was completely inhibited by rosiglitazone, a PPARγ agonist. In conclusion, we inferred that activation of PPARγ in HUVECs suppressed C.pn-induced LOX-1 expression and cell damage by inhibiting ERK1/2 signaling.

Large-Scale Marsh Loss Reconstructed from Satellite Data in the Small Sanjiang Plain since 1965: Process, Pattern and Driving Force.

Monitoring wetland dynamics and related land-use changes over long-time periods is essential to understanding wetland evolution and supporting knowledge-based conservation policies. Combining multi-source remote sensing images, this study identifies the dynamics of marshes, a core part of wetlands, in the Small Sanjiang Plain (SSP), from 1965 to 2015. The influence of human activities on marsh patterns is estimated quantitatively by the trajectory analysis method. The results indicate that the marsh area decreased drastically by 53.17% of the total SSP area during the study period, which covered the last five decades. The marsh mostly transformed to paddy field and dry farmland in the SSP from 1965 to 2015, indicating that agricultural encroachment was the dominant contributor to marsh degradation in the area. Analysis of the landscape indexes indicates that marsh fragmentation was aggravated during the past five decades in the SSP. Trajectory analysis also indicated that human activities have acted as the primary driving force of marsh changes in the SSP since 1965. This study provides scientific information to better understand the evolution of the wetland and to implement ecological conservation and sustainable management of the wetlands in the future.

Comparison of land surface and air temperatures for quantifying summer and winter urban heat island in a snow climate city.

The urban heat island (UHI) effect is an increasingly consequential problem that confronts cities. The accurate characterization and quantification of UHI are crucial for sustainable urban development. Few UHI studies, however, compare data source, spatio-temporal variations, and indicators for the same city in parallel. This study uses Changchun, a snow climate city in China, as an example and compares five different indicators of the UHI based on land surface temperature (LST) derived from Landsat 8 TIRS and hourly air temperature (AT) collected from 41 meteorological weather stations to conduct a more comprehensive comparative study of the UHI. The results show the following. (1) The relationships between LST and AT are all statistically significant, and the surface urban heat island (SUHI) intensity characterized by the LST is considerably stronger than that of AT both in summer and winter. (2) The SUHI intensity is significantly stronger in summer (6.83 °C) than in winter (1.55 °C) based on the morning LST, whereas the UHI intensity (0.27 °C in summer and 0.40 °C in winter) that is simultaneously quantified by the AT has an opposite result. The mean whole-day and daytime UHI intensity difference, which is quantified hourly by the AT between summer and winter, is not significant. The difference between nighttime and daytime UHI intensities is evident in both summer (1.26 °C) and winter (0.76 °C). Additionally, the high temperatures for both LST and AT have a more concentrated distribution in winter than in summer. (3) The values of UHI/SUHI intensity considerably vary based on different indicators. The different choices among land covers to represent "urban" and "rural" areas would significantly affect the values of UHI/SUHI intensity. The selection of appropriate indicators and data sources to quantify the UHI remains a problem that has to be resolved in future studies.

Bioinformatic identification of candidate biomarkers and related transcription factors in nasopharyngeal carcinoma.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is rare, but a certain amount of mortality remains in NPC patients. Our study aimed to identify candidate genes as biomarkers for NPC screening, diagnosis, and therapy. METHODS: We investigated two microarray profile datasets GSE64634 and GSE12452 to screen the potential differentially expressed genes (DEGs) in NPC. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs were also performed. A protein-protein interaction (PPI) network of DEGs was constructed by STRING and visualized by Cytoscape software. The associated transcriptional factor regulatory network of the DEGs was also constructed. RESULTS: A total of 152 DEGs were identified from the GSE64634 and GSE12452 datasets, including 10 upregulated and 142 downregulated genes. Gene functional enrichment analysis indicated that these DEGs were enriched in the cilium movement, antimicrobial humoral response, O-glycan processing, mucosal immune response, carbohydrate transmembrane transporter activity, hormone biosynthetic process, neurotransmitter biosynthetic process, and drug metabolism-cytochrome P450 pathway. Five hub genes (DNALI1, RSPH4A, RSPH9, DNAI2, and ALDH3A1) and one significant module (score = 5.6) were obtained from the PPI network. Key transcriptional factors, such as SPI1, SIN3B, and GATA2, were identified with close interactions with these five hub DEGs from the gene-transcriptional factor network. CONCLUSIONS: With the integrated bioinformatic analysis, numerous DEGs related to NPC were screened, and the hub DEGs we identified may be potential biomarkers for NPC.