In the service period, some engineering structures may have cracks or other nonlinear damages. The nonlinear damages are the major influence to the safety of engineering structures, which should be ...detected as early as possible. Currently, the effective nonlinear damage detection method is still lacking. Therefore, a penalty conversion index based on generalized autoregressive conditional heteroskedasticity (GARCH) model is presented to identify the nonlinear damage. First, an exact expression of GARCH model is described, the bilinear stiffness characteristic of nonlinear damage is given, and acceleration responses are used to establish the GARCH model. Then, through the GARCH model analysis of nonlinear damages responses, it can be found that the variance of conditional variance are sensitive to the nonlinear damage information of acceleration responses, so a basic conversion index based on the variance of conditional variance is proposed. Finally, a penalty conversion index based on GARCH model is presented, which can reduce the interference induced by the adjacent unrelated factors. Numerical and experimental examples show that the identification results of the proposed penalty conversion index based on GARCH model are superior to those of the basic conversion index and the cepstral metric (CM) index.
Background
Hepatic steatosis that occasionally results in nonalcoholic steatohepatitis (NASH) is related to obstructive sleep apnea (OSA). Many studies have shown that autophagy exerts protective ...effects on liver damage caused by various diseases and melatonin exhibits hepatoprotective properties. However, the mechanisms of liver injury induced by chronic intermittent hypoxia (CIH) and the effect of melatonin on the regulation of liver injury remain unclear.
Purpose
This study was aimed to evaluate the role of CIH in steatohepatitis progression and the regulatory function of melatonin on fatty liver sensitivity to CIH injury, mainly focusing on autophagy signaling.
Methods
A high-fat diet (FD)-induced obesity mouse model was subjected to intermittent hypoxia/normoxia events for approximately 8 h per day using an autophagy agonist, rapamycin, or an inhibitor, 3-methyladenine (3-MA), and SRT1720, a sirtuin 1 (SIRT1) activator, or sirtinol, a SIRT1 inhibitor, with or without melatonin for a total of six successive weeks, followed by assessment of expression of autophagy-related genes and activity of serum aminotransferase as well as histological evaluation of tissue morphology.
Results
Neither FD nor CIH alone causes significant liver injury; however, the combination yielded higher serum aminotransferase activities and more severe histological changes, accompanied by a decrease in autophagy activity. Melatonin markedly inhibited FD/CIH-stimulated liver injury by enhancing autophagy. In contrast, SIRT1 inhibition resulted in a decrease in the expression of melatonin-induced autophagy-related genes as well as diminished its protective effects on FD/CIH-induced liver injury.
Conclusion
These results suggest that melatonin could ameliorate FD/CIH-induced hepatocellular damage by activating SIRT1-mediated autophagy signaling.
The failure of plasma-sprayed thermal barrier coating (TBC) is often caused by the coating spallation due to crack propagation. In this study, a new model with stacking lamellae is developed based on ...the cross-section micrograph to explore crack propagation behavior within the ceramic top coat (TC) during isothermal cycling. The dynamic growth process of thermally grown oxide (TGO) is simulated via material properties change step by step. The stress profiles in the lamellar model are first evaluated, and the pore and lamellar interface crack effects on the stress state are further explored. Then, the successive crack growth, linkage, and ultimate coating spallation process is simulated. The results show that the stress intensity in TC enhances with thermal cycling. Large stress concentration always occurs near the pore and lamellar interface crack, which can result in the incipient crack growth. Moreover, the lamellar interface crack also changes the stress distribution within the TC and at the TC/bond coat interface. The multiple crack propagation upon temperature cycling is explored, and the possible coalescence mechanism is proposed. The lamellar crack steadily propagates at the early stage. The crack length sharply increases before the occurrence of coating spallation. The simulated coat spalling path is in line with the experimental result. Therefore, the new lamellar model developed in this work is beneficial to further reveal coating failure mechanism and predict coating lifetime.
Somatic embryogenesis (SE) plays a vital role in genetic transformation and massive propagation of important agronomical and economical crops. Here, we conducted a systematic assessment of the ...morphological, cytochemical, and cytogenetical characteristics of six culture strains with various embryogenic/regenerative potential during SE process in cotton. Results indicated that the six cell culture strains had stable ploidy levels, and did not reveal any relationship between the cytogenetic state and their morphogenetic potential. Moreover, the six culture strains were compared via double staining with Evans blue and Acetocarmine to efficiently distinguish embryogenic and non-embryogenic cells and determine the embryogenic nature of the calli. In addition, the kind of auxins added in medium affected not only growth property, color, size of cell clumps but also ploidy level and regeneration ability. By combining analysis of morphological, cytochemical, and cytogenetical characteristics of the cell cultures, we are able to obtain and maintain homogeneous cell population with high morphogenic and regeneration ability and establish efficient somatic embryogenesis and regeneration system from short-term cell cultures in upland cotton, which highlight the application of biotechnological approaches in crop breeding, and above all, to better understand totipotency of cells in higher plants.
Nasopharyngeal carcinoma (NPC) is the most common nasopharyngeal squamous cell carcinoma, and recurrence and metastasis are still difficult problems in its current treatment. This study aimed to ...investigate the effect of SUMO modification of STAT1 protein on the proliferation and invasion of NPC, and to reveal the underlying mechanism. Two gene expression profiles (GSE12452 and GSE53819) of 49 nasopharyngeal carcinomas and 28 normal controls were analyzed to identify differentially expressed genes. In total, 448 up-regulated genes and 622 down-regulated genes were identified. In addition, 16 SUMO-related molecules in the NPC dataset GSE102349 with survival data were analyzed, and it was found that the high expression of SENP1 and SENP2 was closely related to the poor prognosis of NPC. GO and GSEA analysis suggested that immune-related biological processes, IFN-γ-STAT signaling pathway and protein modification-related molecules were significantly enriched in NPC, resulting in poor survival prognosis. In order to verify the results of bioinformatics analysis and explore its underlying molecular mechanisms, western blot, Immunofluorescence, Immunoprecipitation and Immunohistochemistry are conducted in NPC cells, animals and clinical samples. SENP1 and STAT protein levels were increased in NPC tissues. SENP1 inhibited SUMOylation of STAT1, thereby promoting the protein level of STAT1 and the nuclear translocation. SENP1 promoted the proliferation and invasion of NPC by inducing STAT1. Overall, SENP1-induced deSUMOylation of STAT1, resulting in an increased proliferation and invasion of nasopharyngeal carcinoma.
•SENP1 and STAT were increased in NPC.•SENP1 inhibited SUMOylation of STAT1, promoting the protein level of STAT1 and the nuclear translocation.•SENP1 promotes the proliferation and invasion of NPC by STAT1
The North China Craton (NCC) is proposed to have formed by collision between the Western and Eastern blocks at ∼1.85
Ga. However, the detailed history of the individual blocks remains unsolved. In ...the Eastern block, the Paleoproterozoic volcano-sedimentary rocks are mainly exposed along its eastern margin, and are referred to as the Liaohe Group in the Liaodong Peninsula of Liaoning Province and as the Guanghua, Ji’an and Laoling Groups in the Tonghua area of southern Jilin Province. The Guanghua and Ji’an Groups are characterized by the occurrence of volcanic rocks, whereas the Laoling Group is composed of clastic sediments and carbonates. Zircon U–Pb isotopic dating by LA-ICP-MS and SHRIMP methods indicates that the Guanghua and Ji’an Groups were formed between 2.1 and 2.0
Ga, but that the rocks of the Laoling Group may have formed in two episodes at 2.5–2.2 and 2.0–1.9
Ga, respectively. The present data indicate that the Ji’an, Laoling and Liaohe Groups are chaotic, without a common stratigraphy, with intense deformation making it difficult to identify original layering and contact relationships. Combined with age data from rocks intrusive into the sequence, the Paleoproterozoic tectonic evolution of the Liaoning–Jilin area can be related to collision and extension between the Liaonan block to the south and the Longgang block to the north. Extension in the Longgang block occurred at 2.12–1.98
Ga and was represented by eruption of the Guanghua mafic volcanic rocks. However, extension in the Liaonan block is expressed by 2.16–2.09
Ga A-type granites and ∼2.12–1.98
Ga volcano-sedimentary rocks of the Ji’an Group. These two blocks collided at ∼1.93–1.90
Ga, resulting in a clockwise metamorphic
P–
T path recorded in the N. Liaohe–Laoling Groups, followed by ∼1.85
Ga post-collisional evolution expressed by anticlockwise metamorphic
P–
T paths and immense granitic intrusions in the S. Liaohe–Ji’an Groups. Therefore, it is suggested that the collision between the Longgang and Liaonan in the Eastern block of the NCC occurred a little earlier than ∼1.85
Ga, when the NCC amalgamated by collision of the Western and Eastern blocks.
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We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight <3 kDa) in alleviating liver and kidney injuries in aging mice induced by d-galactose ...(d-gal) and its underlying mechanism of action. First, we characterized TSCP. TSCP was passed through a 3-kDa ultrafiltration membrane, desalted in water by a solid-phase extraction column, purified further by reverse phase-high performance liquid chromatography, and analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. TSCP contained 17 types of amino acids (AAs) and 41 peptide chains of length 7 AAs to 22 AAs. The content of free AAs and total AAs of TSCP was 13.5% and 93.79%, respectively. Next, we undertook animal experiments. Mice were injected once-daily with D-gal (300 mg/kg body weight, s.c.) for 8 weeks, and TSCP was administered simultaneously once-daily by intragastric gavage. TSCP could visibly improve the decreased body weight, depressed appetite, and mental deterioration of mice triggered by d-gal. TSCP could also alleviate d-gal-induced damage to the liver and kidneys according to histopathology (especially high-dose TSCP). Consistent with these macroscopic and pathologic changes, TSCP could also prevent d-gal-induced increases in serum levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, lipid peroxidation, creatinine and uric acid, as well as decreases in serum levels of immunoglobulin (Ig)G and IgM. Moreover, TSCP improved the activities of superoxide dismutase, catalase, and glutathione peroxidase, but also inhibited the increases in the levels of malondialdehyde and inducible nitric oxide synthase expression in the liver and kidneys of d-gal-treated mice. These results suggest that TSCP can alleviate the injuries to the liver and kidneys in aging mice induced by d-gal, and that its mechanism of action might be, at least partially, associated with attenuation of oxidative stress and enhancement of immune function.
Src homology-2 domain-containing protein tyrosine phosphatase 1 (SHP1) is mainly restricted to hematopoietic and epithelial cells and widely accepted as a convergent node for oncogenic cell-signaling ...cascades. The development of efficient methods for rapidly tracing and inhibiting the SHP1 activity in complex biological systems is of considerable significance for advancing the integration of diagnosis and treatment of the related disease. With this aim, we designed and synthesized five 2-phenyl-1,3,4-thiadiazole derivatives (PT2, PT5, PT8, PT9 and PT10) here based on the reported SHP1 inhibitors (PT1, PT3, PT4, PT6 and PT7). The photophysical properties and inhibitory activities of these 2-phenyl-1,3,4-thiadiazole derivatives (PT1-PT10) against SHP1 were thoroughly studied from the theoretical simulation and experimental application aspects. The representative compound PT10 exhibited a larger quantum yield than the other molecules because of the smaller geometric relaxation and reorganization energy of the excited state, which was consistent with the results from the fluorescence experiments in organic solvents. In addition, PT10 showed a selective fluorescence response for SHP1 activity and low cytotoxicity in HeLa cells. Lastly, it indicated the potential application in two-photon cell fluorescence imaging in the future according to the calculated excellent two-photon absorption properties. In this contribution, firstly, we offered the fluorescent and activated molecule PT10 against SHP1, which achieved the integration of visualization and inhibitory activity of SHP1 preliminarily at the enzyme molecular level.
Abstract
Melanoma is a malignant tumor of melanocytes and is often considered immunogenic cancer. Toll-like receptor-related genes are expressed differently in most types of cancer, depending on the ...immune microenvironment inside cancer, and the key function of Toll-like receptors (TLRs) for melanoma has not been fully elucidated. Based on multi-omics data from TCGA and GEO databases, we first performed pan-cancer analysis on TLR, including CNV, SNV, and mRNA changes in TLR-related genes in multiple human cancers, as well as patient prognosis characterization. Then, we divided melanoma patients into three subgroups (clusters 1, 2, and 3) according to the expression of the TLR pathway, and explored the correlation between TLR pathway and melanoma prognosis, immune infiltration, metabolic reprogramming, and oncogene expression characteristics. Finally, through univariate Cox regression analysis and LASSO algorithm, we selected six TLR-related genes to construct a survival prognostic model, divided melanoma patients into the training set, internal validation set 1, internal validation set 2, and external validation set for multiple validations, and discussed the correlation between model genes and clinical features of melanoma patients. In conclusion, we constructed a prognostic survival model based on TLR-related genes that precisely and independently demonstrated the potential to assess the prognosis and immune traits of melanoma patients, which is critical for patients’ survival.
In this paper, we consider the following Schrödinger–Poisson system with perturbation:
where
,
and the radial general perturbation term
. By establishing a new abstract perturbation theorem based on ...the Bolle’s method, we prove the existence of infinitely many radial solutions of the above system. Moreover, we give the asymptotic behaviors of these solutions as
. Our results partially solve the open problem addressed in Y. Jiang, Z. Wang and H.-S. Zhou, Multiple solutions for a nonhomogeneous Schrödinger–Maxwell system in
, Nonlinear Anal. 83 2013, 50–57 on the existence of infinitely many solutions of the Schrödinger–Poisson system for
and a general perturbation term
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