Background
Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and ...cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up.
Methods
A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively.
Results
During a median follow-up of 7 years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan–Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs hazard ratio (95% confidence interval): 1.150 (1.063–1.244),
p
< 0.001 and 1.128 (1.026–1.240),
p
= 0.012.
Conclusion
The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs.
Clinical trials registration
None.
Graphic abstract
To solve the problems of the low energy efficiency and slow penetration rate of drilling, we took the geological data of adjacent wells, real-time logging data, and downhole engineering parameters as ...inputs; the mechanical specific energy and unit footage cost as multi-objective optimization functions; and the machine pump equipment limit as the constraint condition. A constrained Bayesian optimization algorithm model was established for the optimization solution, and drilling parameters such as weight-of-bit, revolutions per minute, and flowrate were optimized in real time. Through a comparison with NSGA-II, random search, and other optimization algorithms, and the application results of example wells, we show that the established Bayesian optimization algorithm has a good optimization effect while maintaining timeliness. It is suitable for real-time optimization of drilling parameters, can aid a driller in identifying the drilling rate and potential tapping area, and provides a decision-making basis for avoiding the low-efficiency rock-breaking working area and improving rock-breaking efficiency.
Nanoscale ZIF-8 had a high inhibitory effect on pyruvate kinase of M2.
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Tumor cells usually show abnormally high glycolysis rate to maintain the dynamic balance of energy. The growth ...of tumor cells can be affected by inhibiting the activity of pyruvate kinase (especially M2-type isozyme, PKM2), the rate limiting enzyme of glycolysis. This is helpful to the treatment of tumor. Herein, metal organic frameworks (MOFs) were found to inhibit the activity of PKM2. Nanoscale ZIF-8 was synthesized by standing and ultrasonic method, respectively. The ZIF-8 has the performance of inhibiting PKM2. Further research showed that the inhibition ability was attributed to zinc ion in ZIF-8. Interestingly, the IC50 of ZIF-8 on PKM2 was one percent of that of zinc ion. This novel enzyme inhibitor is expected to be used in cancer therapy.
Metabolomics, as an emerging technology, has been demonstrated to be a very powerful tool in the study of the host metabolic responses to infections by parasites. Schistosomiasis is a parasitic ...infection caused by schistosoma worm via the direct contact with the water containing cercaria, among which Schistosoma japonicum (S. japonicum) is endemic in Asia. In order to characterize the schistosome-induced changes in the host metabolism and further to develop the strategy for early diagnosis of schistosomiasis, we performed comprehensive LC-MS-based metabolomics analysis of serum from mice infected by S. japonicum for 5 weeks. With the developed diagnosis strategy based on our metabolomics data, we were able to successfully detect schistosomiasis at the first week post-infection, which was 3 weeks earlier than "gold standard" methods and 2 weeks earlier than the methods based on 1H NMR spectroscopy. Our metabolomics study revealed that S. japonicum infection induced the metabolic changes involved in a variety of metabolic pathways including amino acid metabolism, DNA and RNA biosynthesis, phospholipid metabolism, depression of energy metabolism, glucose uptake and metabolism, and disruption of gut microbiota metabolism. In addition, we identified seventeen specific metabolites whose down-regulated profiles were closely correlated with the time-course of schistosomiasis progression and can also be used as an indicator for the worm-burdens. Interestingly, the decrease of these seventeen metabolites was particularly remarkable at the first week post-infection. Thus, our findings on mechanisms of host-parasite interaction during the disease process pave the way for the development of an early diagnosis tool and provide more insightful understandings of the potential metabolic process associated with schistosomiasis in mice. Furthermore, the diagnosis strategy developed in this work is cost-effective and is superior to other currently used diagnosis methods.
Background Psoriasis's effect on diabetes onset is well documented, but its effect on course of diabetes is poorly understood. Objective We sought to compare risks of developing microvascular and ...macrovascular complications between diabetic patients with and without psoriasis. Methods Adults with 2 or more diabetes diagnoses selected from MarketScan databases (Truven Health Analytics Inc, Ann Arbor, MI) (2000-2006) were classified into 2 cohorts: 2 or more psoriasis diagnoses and without psoriasis diagnosis. Patients with psoriasis were matched using propensity score, and exactly matched using age, sex, and diabetes characteristics with patients without psoriasis. Outcomes were compared between cohorts using Cox regression models. Results In all, 6164 diabetic patients with psoriasis (27% moderate to severe) were matched to 6164 diabetic patients without psoriasis. Patients with psoriasis were significantly more likely to develop microvascular events than patients without psoriasis overall (hazard ratio HR 1.14, P < .001) and by psoriasis severity (mild: HR 1.13, P = .004; moderate to severe: HR 1.16, P = .038). Risk of macrovascular events was higher for patients without psoriasis overall (HR 1.13, P = .001) and those with mild psoriasis (HR 1.15, P = .003), but not for moderate to severe cases (HR 1.10, P = .210). Limitations Psoriasis to diabetes association may be underestimated. Conclusion Among diabetic patients, psoriasis is generally associated with higher rates of microvascular and macrovascular complications. Greater psoriasis severity did not increase risk of diabetic complications.
Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in ...coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms.
Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence.
Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1β and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway.
SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia.
The dismal prognosis of patients with glioma is largely attributed to cancer stem cells that display pivotal roles in tumour initiation, progression, metastasis, resistance to therapy, and relapse. ...Therefore, understanding how these populations of cells maintain their stem-like properties is critical in developing effective glioma therapeutics.
RNA sequencing analysis was used to identify genes potentially involved in regulating glioma stem cells (GSCs). Integrin β4 (ITGB4) expression was validated by quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) staining. The role of ITGB4 was investigated by flow cytometry, mammosphere formation, transwell, colony formation, and in vivo tumorigenesis assays. The reciprocal regulation between Integrin β4 and KLF4 was investigated by chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, immunoprecipitation, and in vivo ubiquitylation assays.
In this study, we found that ITGB4 expression was increased in GSCs and human glioma tissues. Upregulation of ITGB4 was correlated with glioma grades. Inhibition of ITGB4 in glioma cells decreased the self-renewal abilities of GSCs and suppressed the malignant behaviours of glioma cells in vitro and in vivo. Further mechanistic studies revealed that KLF4, an important transcription factor, directly binds to the promoter of ITGB4, facilitating its transcription and contributing to increased ITGB4 expression in glioma. Interestingly, this increased expression enabled ITGB4 to bind KLF4, thus attenuating its interaction with its E3 ligase, the von Hippel-Lindau (VHL) protein, which subsequently decreases KLF4 ubiquitination and leads to its accumulation.
Collectively, our data indicate the existence of a positive feedback loop between KLF4 and ITGB4 that promotes GSC self-renewal and gliomagenesis, suggesting that ITGB4 may be a valuable therapeutic target for glioma.
On the basis of daily observations data from 1984 to 2020, the spatiotemporal characteristics of extreme precipitation events in the Poyang Lake Basin (China) were analyzed using the ...intensity–area–duration method. With consideration of spatially distributed data on gross domestic product (GDP), population, and disaster losses related to historical extreme precipitation events, the exposure and vulnerability of the population and GDP of the study area to extreme precipitation events were systematically assessed. The results revealed the following. 1) The intensity and frequency of extreme precipitation, as well as the area affected, showed trends of increase, especially in the northeast of the basin. 2) Population exposure in the basin showed a trend of increase of 2.43 million/a. Change in population exposure was greatest in the most recent 10 years, with an average increase of 6.64 million/a. Change in extreme precipitation was the primary driver of the rapid increase in population exposure. 3) The average annual GDP exposure of the basin was ¥5.43 billion, and economic exposure has increased substantially at an average rate of ¥0.56 billion/a. Unlike population exposure, the increase in economic exposure was driven mainly by rapid economic growth. 4) By constructing vulnerability curves of economic losses in different decades, the trend of economic vulnerability was found to have clearly declined, i.e., economic vulnerability in 2010 was 13.3 (4.1) times lower than that in the 1990s (2000s). Effective disaster prevention and reduction measures should urgently be adopted in the study area to mitigate the effects of increase in extreme precipitation events.
Hydraulic fracturing may be induced easily in a cement-based structure in a sulfate-rich environment, which threatens engineering safety. In order to investigate the evolution of critical water ...pressure, a series of hydraulic fracturing tests and splitting tensile strength tests on the cement mortar under different sulfate-exposure periods are performed. The critical water pressure of the cement mortar under sulfate attack experiences an initial increase stage and a subsequent decrease stage. A stress intensity factor is modified by two proposed damage variables which are crack length and fracture stress. Then, the relationship between the critical water pressure and the tensile strength is established. Moreover, an evolution model of the critical water pressure is proposed, which reveals that the matrix tensile strength and porosity of cement mortar strongly affect the critical water pressure evolution. Additionally, an empirical formula is suggested to describe the critical water pressure evolution of the cement mortar under sulfate attack, and its validity is verified by experimental results.
MicroRNAs play an essential role in mammary gland development, and involution is a factor that limits lactation. Chi-miR-8516 is one of the validated microRNAs that regulates the expression of
and
, ...which surge during the involution of the mammary gland. This study aims to explore the direct or indirect regulation of
and
by chi-miR-8516 and the regulation of chi-miR-8516 by circ-140. In goat mammary epithelial cells, we found that chi-miR-8516 takes circ-140 as a sponge and regulates
expression by targeting
and promoting the phosphorylation of MAPK. The examination of αs1-/β-casein and lipid showed the modulation of the circ-140/chi-miR-8516/
-
axis in casein secretion and lipid formation, which was regulated by the phosphorylation of mTOR and STAT5. This study illustrates an axis that regulates the synthesis of milk components, and explores the pathways in which the axis participates.
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