This paper presents a potential approach to settle the problem of surviving major safety accidents in Submerged Floating Tunnel (SFT) that detachable emergency escape devices are set up outside SFT. ...The Computational Fluid Dynamics (CFD) technology is used to investigate the effect of emergency escape devices on the hydrodynamic load acting on SFT in uniform and oscillatory flows and water waves by numerical test. The governing equations, i.e., the Reynolds-Averaged Navier-Stokes (RANS) equations and k – ɛ standard turbulence equations, are solved by the Finite Volume Method (FVM). Analytic solutions for the Airy wave are applied to set boundary conditions to generate water wave. The VOF method is used to trace the free surface. In uniform flow, hydrodynamic loads, applied to SFT with emergency escape device, reduce obviously. But, in oscillatory flow, it has little influence on hydrodynamic loads acting on SFT. Horizontal and vertical wave loads of SFT magnify to some extend due to emergency escape devices so that the influence of emergency escape devices on hydrodynamic loads of SFT should be taken into consideration when designed.
This paper presents a potential approach to settle the problem of surviving major safety accidents in Submerged Floating Tunnel （SFT） that detachable emergency escape devices are set up outside SFT. ...The Computational Fluid Dynamics （CFD） technology is used to investigate the effect of emergency escape devices on the hydrodynamic load acting on SFT in uniform and oscillatory flows and water waves by numerical test. The governing equations, i.e., the Reynolds-Averaged Navier-Stokes （RANS） equations and k - ε standard turbulence equations, are solved by the Finite Volume Method （FVM）. Analytic solutions for the Airy wave are applied to set boundary conditions to generate water wave. The VOF method is used to trace the free surface. In uniform flow, hydrodynamic loads, applied to SFT with emergency escape device, reduce obviously. But, in oscillatory flow, it has little influence on hydrodynamic loads acting on SFT. Horizontal and vertical wave loads of SFT magnify to some extend due to emergency escape devices so that the influence of emergency escape devices on hydrodynamic loads of SFT should be taken into consideration when designed.
During pond culture of Eriocheir sinensis, a high limb-impairment rate restricts the industry development and quality. Therefore, research on limb autotomy and regeneration has important practical ...significance for the industrial development and basic biology of E. sinensis. This study evaluated the changes in bud morphology, growth-related gene expression and nutritional status during cheliped regeneration in E. sinensis. The study found that the new cheliped was pre-formed in the bud and then regenerated with the completion of molting of E. sinensis. The new cheliped was similar in morphology to the normal cheliped after the first molting but smaller in size. The qRT-PCR results of growth-related genes showed that the expression levels of EcR-mRNA (ecdysteroid receptor) and Chi-mRNA (chitinase) were significantly up-regulated, whereas the expression of MIH-mRNA (molt-inhibiting hormone) was significantly down-regulated (P < 0.05). The nutritional status during the regeneration process showed that the hepatopancreas total lipid content decreased significantly within 28 days and was significantly lower in the autotomy group than in the control group at 14 d and 21 d (P < 0.05). The hepatopancreas fatty acid composition results showed that saturated fatty acids (SFA), highly unsaturated fatty acids (HUFA) and n-3/n-6 were significantly higher in the autotomy group than in the control group at 21 d (P < 0.05), whereas the ∑ n-6 PUFA and ∑ n-3 PUFA at 1 d and 7 d, and the monounsaturated fatty acid (MUFA) at 28 d in the autotomy group were significantly lower than in the control group (P < 0.05). Moreover, the levels of eicosatetraenoic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed that DHA was significantly lower at 7 d and significantly higher at 21 d in the autotomy group than in the control group (P < 0.05), whereas ARA and EPA were not significantly different between the two groups. Muscle L-tryptophan content was significantly lower at 1 d and significantly higher at 7 d in the autotomy group than in the control group (P < 0.05). These results indicate that during the cheliped regeneration process, crabs could accelerate molting and regeneration by regulating growth-related gene expression (e.g., EcR-mRNA and MIH-mRNA) and nutrient metabolism (e.g., lipid metabolism).
Aim
Regorafenib is a tyrosine kinase inhibitor that is mainly metabolized by CYP3A4. The genetic polymorphism of CYP3A4 would contribute to differences in metabolism of regorafenib. Previously, we ...had discovered several novel CYP3A4 variants. However, the catalytic characteristics of these 27 CYP3A4 variants on oxidizing regorafenib have not being determined. The purpose of this study was to investigate the catalytic characteristics of 27 CYP3A4 protein variants on the oxidative metabolism of regorafenib in vitro.
Method
Wild‐type CYP3A4.1 or other variants was incubated with 0.5‐20 μmol/L regorafenib for 30 minutes. After sample processing, regorafenib‐N‐oxide, a primary metabolite, was detected by ultra‐performance liquid chromatography‐tandem mass spectrometry system.
Result
CYP3A4.20 had no detectable enzyme activity compared with wild‐type CYP3A4.1; five variants (CYP3A4.5, .16, .19, .24, .29) exhibited similar clearance value with CYP3A4.1; four variants (CYP3A4.14, .15, .28, .31) displayed increased enzymatic activities, while remaining variants showed markedly decreased intrinsic clearance values.
Conclusion
This study is the first to investigate the function of 27 CYP3A4 protein variants on the metabolism of regorafenib in vitro, and it may provide some valuable information for further research in clinic.
Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated ...that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses. Nevertheless, the underlying molecular mechanisms largely remained elusive.
To determine the hepatoprotective effects of SHE on ethanol-triggered liver damage and further elucidate its potential mechanisms.
In the present study, the Sprague-Dawley rats were fed with the Lieber–DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without SHE (300 and 600 mg/kg/d bw) for 8 weeks. The levels of serum biomarkers (ALT, AST and LDH) and LPS were detected by biochemical assay kits and endotoxin detection LAL kit, respectively. The histopathological changes of liver and intestinal tissues were observed by hematoxylin and eosin (H&E) staining and Transmission electron microscope (TEM). The expressions of CD14, TLR4, MyD88, NF-κB, Iκ-B, P-Iκ-B and TNF-α in liver, and ZO-1 and occludin in intestine were determined by western blot. The faecal microbial composition was determined by16S rRNA Gene Sequencing Analysis.
Biochemical and histopathological analysis revealed that SHE significantly alleviated the lipid deposition and inflammation response in liver induced by ethanol. SHE remarkably inhibited the TLR4 pathway and its downstream inflammatory mediators, and up-regulated the expressions of ZO-1 and occludin in the intestine. The further investigations suggested SHE dramatically reversed ethanol-induced alterations in the intestinal microbial flora and decreased the generation of gut-derived endotoxin.
In summary, SHE probably modulated abnormalities of gut-liver axis and inhibited TLR4-associated inflammatory mediators activation to exert its hepatoprotective properties. These findings suggested that SHE as a traditional therapeutic options which may play an essential role in protecting against the chronic ethanol-triggered liver injury.
Hepatoprotective mechanisms of SHE was mediated via modulating the perturbations of gut-liver axis to alleviate chronic ethanol-induced liver injury. Mechanistically, SHE administration remarkably enriched the beneficial microbiota abundance and decreased potential detrimental bacteria and gut-derived endotoxin to enter the enterohepatic circulation. Simultaneously, restoration of the intestinal barrier function in response to SHE was capable of decreasing gut-derived endotoxin absorption, which synergistically inhibited TLR4 signaling pathway and its downstream inflammatory mediators production in liver. Display omitted
Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we ...prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6−510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85−7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.
Quantum dots, which are made from semiconductor materials, possess tunable physical dimensions and outstanding optoelectronic characteristics, and they have aroused widespread interest in recent ...years. In addition to applications in biomolecular analysis, sensors, organic photovoltaic devices, fluorescence, solar cells, photochemical reagents, light‐emitting diodes, and catalysis, quantum dots have attracted mounting attention in the field of electrochemical energy storage owing to their size confinement and anisotropic geometry. In this review, a comprehensive summary is given and the research progress of the study of quantum dots for batteries and electrochemical capacitors in recent years, including their synthesis methods, micro/nanostructural features, and electrochemical performance, is appraised.
Quantum dots represent one promising kind of power materials for electrochemical energy storage. Synthesis strategies, tailored material properties, and different electrochemical performances are prominent characteristics of batteries and electrochemical capacitors. A comprehensive summary and evaluation of the electrode material are provided in this review.
Purpose
CD8
+
T cells are primarily cytotoxic cells that provide immunological protection against malignant cells. Considerable evidence suggests that the T-cell repertoire is closely associated with ...the host immune response and the development of cancer. In this study, we explored the characteristics of the circulating CD8
+
T-cell repertoire and their potential value in predicting the clinical response of breast cancer patients to chemotherapy.
Experimental design
We applied a high-throughput TCR β-chain sequencing method to characterize the CD8
+
T-cell repertoire of the peripheral blood from 26 breast cancer patients. In addition, changes in the circulating CD8
+
T-cell repertoire during chemotherapy were analyzed.
Results
We found that the HEC ratios of the CD8
+
T-cell repertoires from HER2
+
breast cancer patients were significantly higher than those of HER2
−
patients, suggesting that the HER2 protein is released into circulation where it is targeted by CD8
+
T cells. Several Vβ and CDR3 motifs preferentially used in HER2
+
patients were identified. Besides, we found that the circulating CD8
+
T-cell repertoires evolved during chemotherapy and correlated with patient clinical responses to chemotherapy. Increased CD8
+
T-cell repertoire heterogeneity during chemotherapy was associated with a better clinical response.
Conclusions
Although functional studies of clonally expanded CD8
+
T-cell populations are clearly required, our results suggest that the circulating CD8
+
T-cell repertoire reflects the characteristics of the tumor-associated biomolecules released into the blood and correlates with the clinical responses of the patients to chemotherapy which might assist in making treatment decisions.
Cataracts are a significant public health problem with no proven methods for prevention. Discovery of novel disease mechanisms to delineate new therapeutic targets is of importance in cataract ...prevention and therapy. Herein, we report that mutations in the RagA GTPase (RRAGA), a key regulator of the mechanistic rapamycin complex 1 (mTORC1), are associated with autosomal dominant cataracts. We performed whole exome sequencing in a family with autosomal dominant juvenile-onset cataracts, and identified a novel p.Leu60Arg mutation in RRAGA that co-segregated with the disease, after filtering against the dbSNP database, and at least 123,000 control chromosomes from public and in-house exome databases. In a follow-up direct screening of RRAGA in another 22 families and 142 unrelated patients with congenital or juvenile-onset cataracts, RRAGA was found to be mutated in two unrelated patients (p.Leu60Arg and c.-16G>A respectively). Functional studies in human lens epithelial cells revealed that the RRAGA mutations exerted deleterious effects on mTORC1 signaling, including increased relocation of RRAGA to the lysosomes, up-regulated mTORC1 phosphorylation, down-regulated autophagy, altered cell growth or compromised promoter activity. These data indicate that the RRAGA mutations, associated with autosomal dominant cataracts, play a role in the disease by acting through disruption of mTORC1 signaling.
PDF
