The effect of the normal stress and joint persistency on the mechanical behavior of granite samples containing discontinuous joints was investigated in the laboratory through direct shear tests. The ...test results revealed three different failure modes occurring at the rock bridge: (a) shear failure, (b) compressive-shear failure, and (c) tensile failure. The failure mode depends on the joint persistency and normal stress level and influences the peak shear strength. Moreover, the joint persistency and normal stress level were also found to have a considerable influence on the post-failure behavior such as the fracture roughness and residual shear strength based on rock bridge area. The conducted investigation provided better understanding of the effect of a rock bridge on mechanical behavior of granitic discontinuous joints towards estimating the resistance capacity of rock bridges and hence to allow evaluation of stability of rock masses in both surface and underground excavations in rock engineering.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The increasing natural or man-made space debris could pose a serious threat to orbital space-based systems and their operators. Consequently, their detection, reorganization, and tracking are of ...considerable significance. However, the traditional solutions, including ground-based radar and optical telescope, cannot exactly observe the debris with small diameter. Imaging with space-based terahertz (THz) radar in combination with inverse synthetic aperture radar (ISAR) technique enables us to obtain high-resolution 3-D image. In this paper, we have developed a high-resolution THz radar that operates at 340 GHz with a bandwidth of 28.8 GHz and the output peak power of 5 mW for proof-of-concept. In addition, using the characteristic that space debris rotates about its main axis, we have established a 3-D ISAR imaging geometry as well as its corresponding signal model. Then, a 3-D wavenumber-domain image formation algorithm is presented and has been validated by point target simulation. The experimental results have confirmed that the THz radar can effectively achieve high-resolution 3-D imaging of the spinning space debris.
This paper investigates the strong convergence of a fully discrete numerical method for the stochastic partial differential equations driven by multiplicative noise. The fully discrete space–time ...approximation consists of the symmetric interior penalty discontinuous Galerkin method for the spatial discretization and the implicit Euler method for the temporal discretization. Rather than the usual semi group analysis techniques, in this paper, we present an analysis framework in the variational formulation by introducing new weak variational approximation techniques. Some error estimates in a strong sense are established for the proposed fully discrete scheme. The optimal convergence rates are then obtained in both space and time. Numerical results for the nonlinear stochastic partial differential equations are finally presented to confirm the theoretical results.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Levels of HIF-1α increase in psoriatic lesions and serum of psoriatic patients.•HIF-1α in epithelial keratinocytes promote angiogenesis and skin inflammation.•HIF-1α works in association with IL-6, ...VEGF, mRNA and ROS.•BMP6, TREM-1, PI3K/Akt are also associated with HIF-1α-induced skin inflammation.
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcriptional factor and is composed of HIF-1α and HIF-1β subunits. An increase in the levels of HIF-1α in the psoriatic lesions and the serum of psoriatic patients has been reported. An increase in the HIF-1α in the epithelial keratinocytes may contribute in promoting angiogenesis and skin inflammation. Accordingly, the drug therapy directed to control HIF-1α levels may effectively manage the disease. An increase in HIF-1α may participate in the pathogenesis of psoriasis in association with IL-6, vascular endothelial growth factor (VEGF), microRNA-150, microRNA-270, reactive oxygen species, bone morphogenetic protein 6 (BMP6), triggering receptor expressed on myeloid cells 1 (TREM-1) and phosphoinositide 3-kinases (PI3K)/Akt pathway. An increase in the levels of IL-6, free radicals, and reduction in miR-150 may increase the expression of HIF-1α, which may act to induce angiogenesis via VEGF-ERK2 signaling pathway. An increase in HIF-1α may attenuate the expression of BMP6 to inhibit the terminal differentiation and increase the proliferation of keratinocytes. Moreover, HIF-1α may increase the expression of miR-210 to decrease the levels of STAT-6 and LYN, which in turn is manifested in the form of excessive activation of immune system. An increase in keratinocyte proliferation, excessive angiogenesis along with abnormal activation of the immune system play a key role in the pathogenesis of psoriasis. The present review discusses the evidence showing the crucial role of HIF-1α in psoriasis along with interrelationship with other mediators/signaling pathways that may contribute to the development of psoriasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Low temperature is an important abiotic stress in plant growth and development, especially for thermophilic plants. Eggplants are thermophilic vegetables, although the molecular mechanism of their ...response to cold stress remains to be elucidated. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play an essential role during plant development and stress responses. Although the role of many plant miRNAs in facilitating chilling tolerance has been verified, little is known about the mechanisms of eggplant chilling tolerance.
Here, we used high-throughput sequencing to extract the miRNA and target genes expression profiles of Solanum aculeatissimum (S. aculeatissimum) under low temperature stress at different time periods(0 h, 2 h, 6 h, 12 h, 24 h). Differentially regulated miRNAs and their target genes were analyzed by comparing the small RNA (sRNA) and miRBase 20.0 databases using BLAST or BOWTIE, respectively. Fifty-six down-regulated miRNAs and 28 up-regulated miRNAs corresponding to 220 up-regulated mRNAs and 94 down-regulated mRNAs, respectively, were identified in S. aculeatissimum. Nine significant differentially expressed miRNAs and twelve mRNAs were identified by quantitative Real-time PCR and association analysis, and analyzed for their GO function enrichment and KEGG pathway association.
In summary, numerous conserved and novel miRNAs involved in the chilling response were identified using high-throughput sequencing, which provides a theoretical basis for the further study of low temperature stress-related miRNAs and the regulation of cold-tolerance mechanisms of eggplant at the miRNA level.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Liver injury is usually caused by different sources (such as drugs, food, and alcohol), which is regarded as a serious threat to human health. Since the current indicators are not well defined, it is ...crucial to develop novel probes to characterize the kinetic process of liver injury. In this paper, a novel probe with fluorescence signals, Lyso-ONOO, was synthesized to detect the fluctuating peroxynitrite (ONOO−) level in various acute injury model mice. With the addition of ONOO−, the fluorescence response of Lyso-ONOO exhibited a large Stokes shift of 105 nm under 450 nm excitation. The reaction had the merits of high sensitivity, high selectivity, rapid reaction, and stability under various pH conditions. In addition, Lyso-ONOO had prominent lysosome-targeting ability. It achieved monitoring the exogenous and endogenous ONOO− in human hepatic stellate cells. Further, Lyso-ONOO could display endogenous ONOO− in models of 4T1-xenograft and inflammation in mice. More importantly, Lyso-ONOO could gauge the changing levels of ONOO− in three types (induced by CCl4, APAP, and alcohol) of acute liver injury models and treatments (silybin and bicyclol) of CCl4-induced liver injury mice. Both in vivo imaging and depth-of-penetration fluorescence imaging demonstrated that Lyso-ONOO could characterize the developmental and therapeutic status during the liver injury process by measuring the dynamic change of ONOO−. The monitoring of Lyso-ONOO appeared to be useful in inferring the order of severity in diverse acute liver injury processes and taking into account the efficacy of treatment regimens, which might provide important information for corresponding research.
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•A multifunctional lysosome-targetable fluorescent probe for ONOO− was constructed.•Determining the endogenous level of ONOO− in living cells, 4T1-xenograft tumor, and inflammation model.•Characterizing the situation of acute liver injury, and evaluate the efficacy of liver injury drugs for the first time.•Accompanied by the checking with optical signals, serum indexes, and histopathological staining.
Liver injury is usually caused by different sources (such as drugs, food, and alcohol), which is regarded as a serious threat to human health. Since the current indicators are not well defined, it is crucial to develop novel probes to characterize the kinetic process of liver injury. In this paper, a novel probe with fluorescence signals, Lyso-ONOO, was synthesized to detect the fluctuating peroxynitrite (ONOO−) level in various acute injury model mice. With the addition of ONOO−, the fluorescence response of Lyso-ONOO exhibited a large Stokes shift of 105 nm under 450 nm excitation. The reaction had the merits of high sensitivity, high selectivity, rapid reaction, and stability under various pH conditions. In addition, Lyso-ONOO had prominent lysosome-targeting ability. It achieved monitoring the exogenous and endogenous ONOO− in human hepatic stellate cells. Further, Lyso-ONOO could display endogenous ONOO− in models of 4T1-xenograft and inflammation in mice. More importantly, Lyso-ONOO could gauge the changing levels of ONOO− in three types (induced by CCl4, APAP, and alcohol) of acute liver injury models and treatments (silybin and bicyclol) of CCl4-induced liver injury mice. Both in vivo imaging and depth-of-penetration fluorescence imaging demonstrated that Lyso-ONOO could characterize the developmental and therapeutic status during the liver injury process by measuring the dynamic change of ONOO−. The monitoring of Lyso-ONOO appeared to be useful in inferring the order of severity in diverse acute liver injury processes and taking into account the efficacy of treatment regimens, which might provide important information for corresponding research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acinetobacter baumannii is considered the prototypical example of a multi- or pan- drug-resistant bacterium. It has been increasingly implicated as a major cause of nosocomial and ...community-associated infections. This study proposed to evaluate the efficacy of immunological approaches to prevent and treat A. baumannii infections.
Mice were immunized with outer membrane vesicles (OMVs) prepared from a clinically isolated multidrug-resistant strain of A. baumannii. Pneumonia and sepsis models were used to evaluate the efficacy of active and passive immunization with OMVs. The probable effective mechanisms and the protective potential of clonally distinct clinical isolates were investigated in vitro using an opsonophagocytic assay.
Intramuscular immunization with OMVs rapidly produced high levels of OMV-specific IgG antibodies, and subsequent intranasal challenge with A. baumannii elicited mucosal IgA and IgG responses. Both active and passive immunization protected the mice from challenges with homologue bacteria in a sepsis model. Bacterial burden in bronchoalveolar lavage fluids (BALF), lung, and spleen, inflammatory cell infiltration in BALF and lung, and inflammatory cytokine accumulation in BALF was significantly suppressed in the pneumonia model by both active and passive immunization strategies. The antisera from immunized mice presented with significant opsonophagocytic activities in a dose-dependent manner against not only homologous strains but also five of the other six clonally distinct clinical isolates.
Utilizing immunological characteristics of outer membrane proteins to elevate protective immunity and circumvent complex multidrug-resistance mechanisms might be a viable approach to effectively control A. baumannii infections.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, we performed a comprehensively analysis of gene expression and DNA methylation data to establish diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC).
: We ...collected gene expression and DNA methylation datasets for over 1,200 clinical samples. Integrated analyses of RNA-sequencing and DNA methylation data were performed to identify DNA methylation-driven genes. These genes were utilized in univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to build a prognostic model. Recurrence and diagnostic models for HCC were also constructed using the same genes.
: A total of 123 DNA methylation-driven genes were identified. Two of these genes (SPP1 and LCAT) were chosen to construct the prognostic model. The high-risk group showed a markedly unfavorable prognosis compared to the low-risk group in both training (HR = 2.81; P < 0.001) and validation (HR = 3.06; P < 0.001) datasets. Multivariate Cox regression analysis indicated the prognostic model to be an independent predictor of prognosis (P < 0.05). Also, the recurrence model successfully distinguished the HCC recurrence rate between the high-risk and low-risk groups in both training (HR = 2.22; P < 0.001) and validation (HR = 2; P < 0.01) datasets. The two diagnostic models provided high accuracy for distinguishing HCC from normal samples and dysplastic nodules in the training and validation datasets, respectively.
: We identified and validated prognostic, recurrence, and diagnostic models that were constructed using two DNA methylation-driven genes in HCC. The results obtained by integrating multidimensional genomic data offer novel research directions for HCC biomarkers and new possibilities for individualized treatment of patients with HCC.
Resonant modular multilevel converters (RMMCs) have been proposed for high-voltage dc-dc applications. Using different modulation strategies, RMMC operates in different modes and achieves flexible ...step ratio. To provide a comprehensive study of RMMCs, this paper presents the modulation method achieving a wide range of step ratio with the ability of inherent-balancing. The conditions for guaranteeing the inherent-balancing ability are provided. The operation principle and performance of the RMMC are presented in this paper, which have been explored in a case study. The experimental results are obtained from a bench-scale setup, which have verified the theoretical analysis.
Cardiac fibrosis is one of the major pathological characteristics of diabetic cardiomyopathy (DCM). MicroRNAs (miRNAs, miRs) have been identified as key regulators in the progression of cardiac ...fibrosis. This study aimed to investigate the role of miR-30a-5p in DCM and the underlying mechanism. The rat model of diabetes mellitus (DM) was established by streptozotocin injection, and the rat primary cardiac fibroblasts (CFs) were isolated from cardiac tissue and then treated with high glucose (HG). MTT assay was performed to assess the viability of CFs. Dual-luciferase reporter gene assay was conducted to verify the interaction between miR-30a-5p and Smad2. The expression of miR-30a-5p was downregulated in the myocardial tissues of DM rats and HG-stimulated CFs. Overexpression of miR-30a-5p reduced Smad2 levels and inhibited collagen formation in HG-stimulated CFs and DM rats, as well as decreased the proliferation of CFs induced by HG. Smad2 was a target of miR-30a-5p and its expression was inhibited by miR-30a-5p. Furthermore, the simultaneous overexpression of Smad2 and miR-30a-5p reversed the effect of miR-30a-5p overexpression alone in CFs. Our results indicated that miR-30a-5p reduced Smad2 expression and also induced a decrease in proliferation and collagen formation in DCM.
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DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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