Although osteopontin (OPN) is expressed in the liver and pigment gallstones of patients with hepatolithiasis, its role in pigment gallstone formation remains unclear. This study aimed to explore the ...function of OPN in pigment gallstone formation.
Rats were fed a chow diet (CD) or lithogenic diet (LD) for 10 consecutive weeks; blocking tests were then performed using an OPN antibody (OPN-Ab). Incidence of gallstones and levels of several bile components, OPN, tumor necrosis factor alpha (TNF-α), and cholesterol 7 alpha-hydroxylase (CYP7A1) were analyzed. To determine TNF-α expression in hepatic macrophages and both CYP7A1 and bile acid (BA) expression in liver cells, recombinant rat OPN and recombinant rat TNF-α were used to treat rat hepatic macrophages and rat liver cells, respectively. Chi-square or Fisher exact tests were used to analyze qualitative data, Student t-test or one-way analysis of variance were used to analyze qualitative data.
Incidence of gallstones was higher in LD-fed rats than in CD-fed rats (80% vs. 10%, P < 0.05). BA content significantly decreased in bile (t = -36.08, P < 0.01) and liver tissue (t = -16.16, P < 0.01) of LD-fed rats. Both hepatic OPN protein expression (t = 9.78, P < 0.01) and TNF-α level (t = 8.83, P < 0.01) distinctly increased in the LD group; what's more, CYP7A1 mRNA and protein levels (t = -12.35, P < 0.01) were markedly down-regulated in the LD group. Following OPN-Ab pretreatment, gallstone formation decreased (85% vs. 25%, χ2 = 14.55, P < 0.01), liver TNF-α expression (F = 20.36, P < 0.01) was down-regulated in the LD group, and CYP7A1 expression (F = 17.51, P < 0.01) was up-regulated. Through CD44 and integrin receptors, OPN promoted TNF-α production in macrophage (F = 1041, P < 0.01), which suppressed CYP7A1 expression (F = 48.08, P < 0.01) and reduced liver BA synthesis (F = 119.4, P < 0.01).
We provide novel evidence of OPN involvement in pigmented gallstone pathogenesis in rats.
High fracture strength and fracture toughness are vital requirements for the Al2O3/Al2O3 composites. This advanced structural material is composed of two-dimensional alumina fiber fabrics with porous ...alumina matrices. However, the Al2O3/Al2O3 composites exhibit low delamination resistance under shear stress. In this study, an as-fabricated Al2O3/Al2O3 composite was densified through a slurry infiltration and sintering (SIS) process. The SIS-cycle-dependent mechanical properties of the Al2O3/Al2O3 composites were investigated. The results showed that the matrix was strengthened, and the fibers were unaffected after SIS process. With increasing SIS cycles, the flexural and interlaminar shear strengths increased, whereas the fracture toughness decreased. The best performance was reached after six SIS cycles, which had a flexural strength of 414.7 ± 41.6 MPa, an interlaminar shear strength of 25.6 ± 3.1 MPa, and a fracture toughness of 11.0 ± 0.3 MPa m1/2. The different changes in fracture strength and fracture toughness with the SIS cycles were attributed to matrix densification and enhanced interfacial bonding. The SIS process has the potential to improve the strength without sacrificing the damage tolerance.
Antiferroelectrics characterized by voltage-driven reversible transitions between antiparallel and parallel polarity are promising for cutting-edge electronic and electrical power applications. ...Wide-ranging explorations revealing the macroscopic performances and microstructural characteristics of typical antiferroelectric systems have been conducted. However, the underlying mechanism has not yet been fully unraveled, which depends largely on the atomistic processes. Herein, based on atomic-resolution transmission electron microscopy, the deterministic phase transition pathway along with the underlying lattice-by-lattice details in lead zirconate thin films was elucidated. Specifically, we identified a new type of ferrielectric-like dipole configuration with both angular and amplitude modulations, which plays the role of a precursor for a subsequent antiferroelectric to ferroelectric transformation. With the participation of the ferrielectric-like phase, the phase transition pathways driven by the phase boundary have been revealed. We provide new insights into the consecutive phase transformation in low-dimensional lead zirconate, which thus would promote potential antiferroelectric-based multifunctional devices.
The dietary zinc consumed in Chinese households has decreased over the past decade. However, the national dietary zinc intake in the last five years has seldom been investigated. Using data from ...12,028 participants 18 to 64 years old (52.9% male) in the China Nutritional Transition Cohort Survey (CNTCS) 2015, we describe the intake of dietary zinc and the contributions of major foods and we examine the relationship between the level of dietary zinc intake and metabolic syndrome indicators, including blood pressure, fasting glucose, and triglycerides (TG), in Chinese adults. We assessed dietary zinc intake using 24 h recalls on three consecutive days. The mean daily dietary zinc intake for all participants was 10.2 milligrams per day (males 11.2 mg/day, females 9.4 mg/day,
< 0.001). The mean daily dietary zinc density for all participants was 5.2 mg/day per 1000 kilocalories. Among all participants, 31.0% were at risk of zinc deficiency, with dietary zinc intakes of less than the Estimated Average Requirement (EAR) (males 49.2%, females 14.8%,
< 0.050), and 49.9% had adequate dietary zinc intakes, equal to or greater than the recommended nutrient intake (RNI) (males 30.7%, females 67.0%,
< 0.050). We found substantial gender differences in dietary zinc intake and zinc deficiency, with nearly half of the men at risk of zinc deficiency. Males of younger age, with higher education and incomes, and who consumed higher levels of meat, had higher zinc intakes, higher zinc intake densities, and higher rates of meeting the EAR. Among all participants, grains, livestock meat, fresh vegetables, legumes, and seafood were the top five food sources of zinc, and their contributions to total dietary zinc intake were 39.5%, 17.3%, 8.9%, 6.4%, and 4.8%, respectively. The groups with relatively better dietary zinc intakes consumed lower proportions of grains and higher proportions of livestock meat. For males with adequate dietary zinc intake (≥RNI), TG levels increased by 0.219 millimoles per liter (mmol/L) compared with males with deficient dietary zinc intake (<EAR). For females in the ≥RNI group, diastolic blood pressure decreased by 0.963 millimeters of mercury (mmHg) and fasting glucose decreased by 0.187 mmol/L compared with females in the <EAR group; in addition, TG increased by 0.097 mmol/L in females in the ≥RNI group and by 0.120 mmol/L in females in the equal to or greater than the EAR and less than the RNI (EAR-RNI) group compared with females in the <EAR group. Adequate dietary zinc was associated with reduced diastolic blood pressure and fasting glucose levels in female Chinese adults, but with raised TG levels in all Chinese adults. We recommend strengthened nutrition interventions for Chinese males and lower socioeconomic subgroups.
Layout pattern classification, which groups similar layout clips into clusters, underlies a variety of design for manufacturability (DFM) applications, such as hotspot library generation, ...hierarchical data storage, and yield optimization speedup. The key challenges of layout pattern classification are clip representation and clip clustering. In this paper, we present a fast and general layout pattern classification algorithm considering clip shifting and centroid recreation. Our simple but general clip representation captures both topology and density; we can handle not only rigid area match or edge displacement constraints but also variant edge tolerances and don't care regions. For achieving a small cluster count, our clip clustering is guided by the natural grouping structure of layout clips. The clustering results are further improved by centroid recreation. Our experiments are conducted on 2016 CAD contest at ICCAD benchmark suite. Our results show that our algorithm outperforms the reference solution and all contest winning teams, delivering the smallest cluster count, fastest runtime, and 100% validity. Moreover, our algorithm with clip shifting and centroid recreation further reduces the cluster count effectively and efficiently. In addition to the good solution quality, the interplay between adopted data structures and our algorithm makes it fast and viable to be incorporated into practical DFM flows.
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (GWAS) loci explain only a fraction of disease risk. To identify novel ...susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, odds ratio (OR)=1.13, P=7.27 × 10(-10)), ACCS on 11p11.2 (rs2074038, OR=1.14, P=3.93 × 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR=1.13, P=1.41 × 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P=2.26 × 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P=1.15 × 10(-19); rs12716641, P=9.53 × 10(-9); rs9314614, P=4.25 × 10(-9), multivariate association). The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
Glioblastoma (GBM) patients have extremely poor prognoses, and currently no effective treatment available including surgery, radiation, and chemotherapy. MAPK-interacting kinases (MNK1/2) as the ...downstream of the MAPK-signaling pathway regulate protein synthesis in normal and tumor cells. Research has shown that targeting MNKs may be an effective strategy to treat GBM. In this study we investigated the antitumor activity of osimertinib, an FDA-approved epidermal growth factor receptor (EGFR) inhibitor, against patient-derived primary GBM cells. Using high-throughput screening approach, we screened the entire panel of FDA-approved drugs against primary cancer cells derived from glioblastoma patients, found that osimertinib (3 μM) suppressed the proliferation of a subset (10/22) of EGFR-negative GBM cells (>50% growth inhibition). We detected the gene expression difference between osimertinib-sensitive and -resistant cells, found that osimertinib-sensitive GBM cells displayed activated MAPK-signaling pathway. We further showed that osimertinib potently inhibited the MNK kinase activities with IC
values of 324 nM and 48.6 nM, respectively, against MNK1 and MNK2 kinases; osimertinib (0.3-3 μM) dose-dependently suppressed the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). In GBM patient-derived xenografts mice, oral administration of osimertinib (40 mg· kg
·d
, for 18 days) significantly suppressed the tumor growth (TGI = 74.5%) and inhibited eIF4E phosphorylation in tumor cells. Given the fact that osimertinib could cross the blood-brain barrier and its toxicity was well tolerated in patients, our results suggest that osimertinib could be a new and effective drug candidate for the EGFR-negative GBM patients.
Fruit detection and recognition has an important impact on fruit and vegetable harvesting, yield prediction and growth information monitoring in the automation process of modern agriculture, and the ...actual complex environment of orchards poses some challenges for accurate fruit detection. In order to achieve accurate detection of green fruits in complex orchard environments, this paper proposes an accurate object detection method for green fruits based on optimized YOLOX_m. First, the model extracts features from the input image using the CSPDarkNet backbone network to obtain three effective feature layers at different scales. Then, these effective feature layers are fed into the feature fusion pyramid network for enhanced feature extraction, which combines feature information from different scales, and in this process, the Atrous spatial pyramid pooling (ASPP) module is used to increase the receptive field and enhance the network's ability to obtain multi-scale contextual information. Finally, the fused features are fed into the head prediction network for classification prediction and regression prediction. In addition, Varifocal loss is used to mitigate the negative impact of unbalanced distribution of positive and negative samples to obtain higher precision. The experimental results show that the model in this paper has improved on both apple and persimmon datasets, with the average precision (AP) reaching 64.3% and 74.7%, respectively. Compared with other models commonly used for detection, the model approach in this study has a higher average precision and has improved in other performance metrics, which can provide a reference for the detection of other fruits and vegetables.
The RNA-binding protein Musashi-1 (MSI1) exerts essential roles in multiple cellular functions, such as maintenance of self-renewal and pluripotency of stem cells. MSI1 overexpression has been ...observed in several tumor tissues, including glioblastoma (GBM), and is considered as a well-established marker for tumor metastasis and recurrence. However, the molecular mechanisms by which MSI1 regulates cell migration are still undetermined. Here we reported that MSI1 alters cell morphology, promotes cell migration, and increases viscoelasticity of GBM cells. We also found that MSI1 directly binds to the 3'UTR of Tensin 3 (TNS3) mRNA, a negative regulator of cell migration, to inhibit its translation. Additionally, we identified that RhoA-GTP could be a potential regulator in MSI1/TNS3-mediated cell migration and morphological changes. In a xenograft animal model, high expression ratio of MSI1 to TNS3 enhanced GBM tumor migration. We also confirmed that MSI1 and TNS3 expressions are mutually exclusive in migratory tumor lesions, and GBM patients with MSI1
/TNS3
pattern tend to have poor clinical outcome. Taken together, our findings suggested a critical role of MSI1-TNS3 axis in regulating GBM migration and highlighted that the ratio of MSI1/TNS3 could predict metastatic and survival outcome of GBM patients.
Cadmium (Cd) is a toxic element that can accumulate in rice grains, presenting a threat to human health.
Indica
rice hybrid is dominant in southern China, and this genetic background is linked to ...high-level Cd accumulation in grains. Thus, lowering grain Cd levels in
indica
hybrids is a priority in the breeding programs. Previously, a locus on chromosome 7 was found to be associated with grain Cd variation in 617 rice hybrids and exhibited apparent
indica
–
japonica
differentiation. In this present study, a backcross population was generated to investigate the genetic control of this locus, as
qCd7
, on grain Cd performance in rice. Quantitative trait locus (QTL) analysis revealed
qCd7
as an incomplete dominant factor that has a major effect on grain Cd variation; the ‘NPB’ allele can reduce grain Cd content. Using a 3 × 13 NCII design population, we evaluated
qCd7
’s potential to decrease grain Cd content in
indica
hybrid combinations, and phenotypic comparisons indicated that introgression of
qCd7
-NPB effectively reduced grain Cd accumulation. Combining ability analysis revealed that parental lines carrying
qCd7
-NPB consistently displayed negative general combination ability (GCA) effects on grain Cd accumulation, which could be used to predict stable combiners in breeding programs. These results suggest that introgression of
qCd7
-NPB has great potential to decrease grain Cd content in
indica
hybrid breeding, which suggested that identifying allelic variation derived from
indica
–
japonica
genetic differences could facilitate genetic improvement in low grain Cd
indica
hybrid breeding programs.
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