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.

Doxorubicin-loaded poly(ε-caprolactone)-Pluronic micelle for targeted therapy of esophageal cancer.

There is still lack of effective treatment of esophageal cancer, and it is urgently necessary to develop a new programs to treat this disease. More and more evidence suggests that the combination of 2 or more treatment strategies can enhance the antitumor activity in cancer treatment. We have established a new therapeutic strategy that combines doxorubicin-loaded poly(ε-caprolactone) (PCL)-Pluronic micelles and miR-34a to better combat esophageal cancer. Doxorubicin was loaded into PCL-Pluronic micelle to achieve better uptake. Confocal microscopy was used to assess in vitro cellular uptake of PCL-Pluronic micelle. Finally, the in vivo effect of this new combination therapy strategy was also studied. The results showed that PCL-Plannick micelles significantly enhanced the uptake of doxorubicin in esophageal cancer cells in vitro, thereby improving the accumulation of doxorubicin in the cells. In vitro and in vivo combination of doxorubicin-loaded PCL-Pluronic micelles and miR-34a, achieving a significantly synergistic therapeutic effect over the corresponding single treatment. These results suggested that the combinational therapy based on doxorubicin-loaded PCL-Pluronic micelle and miR-34a may provide a reasonable strategy for improving the outcome of esophageal cancer treatment.

Qiliqiangxin Protects against Renal Injury in Rat with Cardiorenal Syndrome Type I through Regulating the Inflammatory and Oxidative Stress Signaling.

Cardiorenal syndrome (CRS) is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. CRS remains a major global health problem. Qiliqiangxin (QLQX) is a traditional Chinese herbs medication, which can improve cardiac function, urine volume, and subjective symptoms in patients with chronic heart failure. In the present study, we aim to investigate the role of QLQX in the treatment of CRS type I and the possible mechanism through establishment of a rat model of myocardial infarction. Rats in CRS-Q group were orally treated with QLQX daily for 2 weeks or 4 weeks, while in sham group and CRS-C group were treated with saline at the same time. Enzyme-linked immunosorbent assay (ELISA) analysis showed that QLQX significantly reduced the levels of angiotensin II (AngII), brain natriuretic peptides (BNP), creatinine (CRE), cystatin C (CysC), tumor necrosis factor (TNF)-α, interleukin (IL)-6, microalbuminuria (MAU), and neutrophil gelatinase-associated lipocalin (NGAL) in plasma induced by myocardial infarction. Western blot analysis showed that QLQX significantly reduced the expressions of AngII, non-phagocytic cell oxidase (NOX)2, and B-cell lymphoma (Bcl)2 associated X protein (Bax), and increased the expressions of Bcl2 and Angiotensin II Type 1 receptor (ATR) in the kidney as compared with the CRS-C group. Fluorescence microscopy showed that the content of reactive oxygen species (ROS) was significantly reduced in the kidney as compared with the CRS-C group. We also examined the apoptosis level in kidney by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, and the result showed that QLQX significantly reduced the apoptosis level in kidney induced by myocardial infarction. Taken together, we suggest that QLQX may be a potentially effective drug for the treatment of CRS by regulating inflammatory/oxidative stress signaling.

HSP60 overexpression increases the protein levels of the p110α subunit of phosphoinositide 3-kinase and c-Myc.

Heat shock protein 60 (HSP60) is a chaperone protein which plays an essential role in facilitating the folding of many newly synthesized proteins to reach their native forms. Increased HSP60 expression is observed in various types of human cancers. However, proteins induced by HSP60 to mediate transformation remain largely unknown. Here we show that HSP60 overexpression increases the protein levels of the p110α subunit of phosphoinositide 3-kinase (PI3K). The amino acid domain 288-383 of HSP60 is used to increase the protein levels. Overexpression of HSP60 also induces the levels of phosphorylated Akt. In addition, the amino acid domain 288-383 of HSP60 is used to induce c-Myc expression. Finally, a mono-ubiquitinated form of ß-catenin has a higher activity to activate ß-catenin downstream targets compared to wild-type ß-catenin. These results indicate that HSP60 overexpression induces the levels or activity of multiple oncogenic proteins to mediate transformation.

Prediction of fishing intensity and trends across South China Sea biogeographic zones.

The volume of industrial fishing in the South China Sea ranks among the top global sustainable fisheries concerns of the Food and Agriculture Organization (FAO). To better understand the scale of management challenges, biogeographic zones of the SCS were characterized, and within each a multivariate GAM (General Additive Model) was fitted to predict and map the complete fishing activities from 2017 to 2020. Model variables, some incomplete or with gaps, included: VIIRS DNB night-time light imagery; Global Fisheries Watch (GFW) data; satellite Ocean Colour; Sea Surface Temperature; and bathymetry data. Four biogeographic zones with differing fishing patterns and trends were identified. We used cross-validation and the GAM model's own tuning method for model prediction accuracy determination, which performed well in four biogeographic zones (R2 respectively: 0.62, 0.68, 0.74 and 0.71). High-intensity fishing grounds are mainly distributed in offshore continental shelf areas. From 2017 to 2019, high-intensity fishing grounds were located near the Beibu Gulf of Vietnam, south Vietnam, part of the Gulf of Thailand and the central Java Sea, where fishing effort greater than 50 h exceeded average annual SCS fishing intensity for several years. By season, intensity and extent of fishing in Spring were largest. In 2020, due to the impact of COVID-19, except for Spring, fishing volume generally decreased. Our experimental results provide new insights and an adaptable biogeographic modelling methodology to map the scale and intensity of regional fishing activities more accurately and completely. This more comprehensive database, that takes account of intrinsic biogeographic fishery context, will help improve and strengthen the regulation of fishing activities around the world.

Vegetation-induced asymmetric diurnal land surface temperatures changes across global climate zones.

Unprecedented global vegetation greening during past decades is well known to affect annual and seasonal land surface temperatures (LST). However, the impact of observed vegetation cover change on diurnal LST across global climatic zones is not well understood. Using global climatic time-series datasets, we investigated the long-term growing season daytime and nighttime LST changes globally and explored associated dominant contributors including vegetation and climate factors including air temperature, precipitation, and solar radiation. Results revealed asymmetric growing season mean daytime and nighttime LST warming (0.16 °C/10a and 0.30 °C/10a, respectively) globally from 2003 to 2020, as a result, the diurnal LST range (DLSTR) declined at 0.14 °C/10a. The sensitivity analysis indicated the LST response to changes in LAI, precipitation, and SSRD mainly concentrated during daytime instead of nighttime, however, which showed comparable sensitivities for air temperature. Combining the sensitivities results and the observed LAI and climate trends, we found rising air temperature contributes to 0.24 ± 0.11 °C/10a global daytime LST warming and 0.16 ± 0.07 °C/10a nighttime LST warming, turns to be the dominant contributor to the LST changes. Increased LAI cooled global daytime LST (-0.068 ± 0.096 °C/10a) while warmed nighttime LST (0.064 ± 0.046 °C/10a); hence LAI dominates declines in DLSTR trends (-0.12 ± 0.08 °C/10a), despite some day-night process variations across climate zones. In Boreal regions, reduced DLSTR was due to nighttime warming from LAI increases. In other climatic zones, daytime cooling, and DLSTR decline, was induced by increased LAI. Biophysically, the pathway from air temperature heats the surface through sensible heat and increased downward longwave radiation during day and night, while the pathway from LAI cools the surface by enhancing energy redistribution into latent heat rather than sensible heat during the daytime. These empirical findings of diverse asymmetric responses could help calibrate and improve biophysical models of diurnal surface temperature feedback in response to vegetation cover changes in different climate zones.

Combining Fat-to-Muscle Ratio and Alanine Aminotransferase/Aspartate Aminotransferase Ratio in the Prediction of Cardiometabolic Risk: A Cross-Sectional Study.

Purpose: Altered body composition and liver enzymes are known to be related to cardiometabolic risk. Our study aimed to evaluate the association between fat-to-muscle ratio (FMR), alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio and cardiometabolic risk. Methods: In total, 1557 participants aged ≥40 years were included. A bioelectrical impedance analyzer (BIA) was used to measure fat mass and muscle mass. We created a cardiometabolic risk score with one point for each cardiometabolic risk factor, including elevated triglycerides (TGs), decreased high-density lipoprotein cholesterol (HDL-C), elevated blood pressure (BP), and abnormal blood glucose, yielding a score of 0-4 for each participant (≥2 for high-risk and <2 for low-risk). Logistic regression analyses were used to analyze the relationship between FMR, ALT/AST ratio and cardiometabolic risk. Results: FMR and ALT/AST ratio were significantly higher in the high-risk group than in the low-risk group (P<0.001). FMR and ALT/AST ratio were both positively correlated with a higher cardiometabolic risk score and the presence of each cardiometabolic risk factor. In subgroup analyses categorized according to FMR and ALT/AST ratio cutoffs, the high-FMR/high-ALT/AST group had the highest cardiometabolic risk (OR=8.51; 95% CI 4.46-16.25 in women and OR=5.09; 95% CI 3.39-7.65 in men) after adjusting for confounders. Conclusion: FMR and ALT/AST ratio were positively associated with cardiometabolic risk. Combining these two indicators improved the prediction of cardiometabolic risk.

Association of fat-to-muscle ratio with non-alcoholic fatty liver disease: a single-centre retrospective study.

OBJECTIVES: Sarcopenia is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Studies evaluating the association between the fat-to-muscle ratio (FMR) and NAFLD are limited. Therefore, the aim of our study was to investigate the association between FMR and NAFLD. DESIGN: A retrospective study was conducted on individuals who underwent health examination at Wuhan Union Hospital between January 2020 and November 2021. Clinical data were collected from electronic medical records. SETTING: Wuhan Union Hospital, Wuhan, China. PARTICIPANTS: 1592 participants aged ≥40 years who underwent body composition analysis and liver ultrasonography were retrospectively reviewed. OUTCOME MEASURES: Liver ultrasonography was used to assess liver steatosis, and the fibrosis-4 index was used to calculate the risk scores for liver fibrosis. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction model was used to calculate ASCVD risk scores. RESULTS: The FMR was significantly higher in individuals with NAFLD than in those without NAFLD (p<0.001). The prevalence of NAFLD gradually increased from FMR tertile 1 (reference) to tertile 2 (OR=1.49, 95% CI 1.13 to 1.97) and tertile 3 (OR=2.85, 95% CI 2.08 to 3.90). In addition, patients with NAFLD in FMR tertile 3 had a significantly higher risk of liver fibrosis (OR=4.48, 95% CI 2.12 to 9.50) and ASCVD (OR=4.63, 95% CI 2.62 to 8.19) than those in FMR tertile 1 after adjustment for multiple confounders. CONCLUSION: In this study, we found a significant association between FMR and NAFLD. A higher FMR indicates a higher risk of NAFLD in the study population and a higher risk of liver fibrosis and ASCVD in NAFLD patients.

Restored vegetation is more resistant to extreme drought events than natural vegetation in Southwest China.

Large scale Ecosystem restoration projects (ERPs) have been implemented to restore vegetation and increase carbon stocks across China. However, whether restored vegetation is strongly resistant to Extreme drought events (EDEs) remains unclear, especially when compared to natural vegetation. Therefore, we used the standardized anomaly of 3-month Standard Precipitation-Evapotranspiration Index (SPEI) to characterize the spatial-temporal trends of EDEs, and figured out the capacity of restored vegetation to withstand the strongest EDE in Southwest China by analyzing their changes of Gross Primary Productivity (GPP) and Water Use Efficiency (WUE). The results showed that Southwest China had experienced six typical EDEs with increasing frequency and severity from 1982 to 2017, particularly the EDE during 2009-2010 (EDE 2009/2010) which had the longest duration and strongest severity. Overall, the EDE 2009/2010 substantially suppressed the vegetation GPP and ecosystem WUE in both restored and natural vegetation area. Compared with natural vegetation, the GPP and WUE of restored vegetation was relative higher and moreover, their GPP decreased more slowly during the EDE 2009/2010 and increased more quickly during the recovery period. This indicates that restored vegetation had a higher drought resistance to the EDE than natural vegetation. Additionally, karst landforms have a stronger negative impact on vegetation GPP and WUE during the EDE. Furthermore, the reduction in the afforestation areas was more obviously observed than that in natural forest areas. Therefore, we suggest that vegetation suitable for regional characteristics should be selected during vegetation restoration, such as afforestation in the non-karst areas.

Widespread global disparities between modelled and observed mid-depth ocean currents.

The mid-depth ocean circulation is critically linked to actual changes in the long-term global climate system. However, in the past few decades, predictions based on ocean circulation models highlight the lack of data, knowledge, and long-term implications in climate change assessment. Here, using 842,421 observations produced by Argo floats from 2001-2020, and Lagrangian simulations, we show that only 3.8% of the mid-depth oceans, including part of the equatorial Pacific Ocean and the Antarctic Circumpolar Current, can be regarded as accurately modelled, while other regions exhibit significant underestimations in mean current velocity. Knowledge of ocean circulation is generally more complete in the low-latitude oceans but is especially poor in high latitude regions. Accordingly, we propose improvements in forecasting, model representation of stochasticity, and enhancement of observations of ocean currents. The study demonstrates that knowledge and model representations of global circulation are substantially compromised by inaccuracies of significant magnitude and direction, with important implications for modelled predictions of currents, temperature, carbon dioxide sequestration, and sea-level rise trends.

Combination of tolvaptan and valsartan improves cardiac and renal functions in doxorubicin-induced heart failure in mice.

Heart failure (HF) is often complicated by renal dysfunction. Tolvaptan and valsartan are two well-known agents for the treatment of HF. However, the role of tolvaptan/valsartan combination on HF with renal dysfunction remains unclear. To establish a mice model with HF with renal dysfunction, mice were intraperitoneally injected with doxorubicin (Dox). Echocardiogram was applied to assess the left ventricular function. Additionally, serum aldosterone (ALD) and angiotensin II (Ang II) level in mice were determined by ELISA. Meanwhile, western blot assay was used to evaluate the expressions of B cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax) and cleaved caspase 3 in the heart and kidney tissues of mice. In this study, we found that compared to tolvaptan or valsartan alone treatment group, tolvaptan/valsartan combination obviously improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS), and reduced serum ALD and Ang II level in Dox-treated mice. Additionally, tolvaptan/valsartan combination significantly prevented the inflammation and fibrosis of heart and kidney tissues in Dox-treated mice. Meanwhile, tolvaptan/valsartan combination notably inhibited the myocardial and renal cell apoptosis in Dox-treated mice via upregulation of Bcl-2 and downregulation of Bax and cleaved caspase 3, compared to the single drug treatment. Collectively, tolvaptan/valsartan combination could improve cardiac and renal functions, as well as prevent the fibrosis, inflammation and apoptosis of heart and kidney tissues in Dox-treated mice. Taken together, combining tolvaptan with valsartan might be a promising approach to achieve enhanced therapeutic effect for treatment of HF with renal dysfunction.