Esophageal squamous cell carcinoma(ESCC) is known for its rapid progression and poor outcomes. China has the highest incidence and mortality in the world. Diagnoses made at early stages and accurate ...staging are associated with better outcomes, all of which can play a significant role in the selection of treatment protocols. ESCC is staged according to the widely accepted TNM system. Common imaging modalities used in staging ESCC before treatment include endoscopy, computed tomography(CT), positron emission tomography(PET) and magnetic resonance imaging(MRI). Endoscopic ultrasound is useful for staging tumor depth and nodal status. Narrow band imaging is valuable for early stage disease assessment. CT and PET provide additional valuable information regarding node and metastasis staging. The ability of MRI to delineate ESCC is continuously being improved and adds information regarding locoregional status to routine examinations.
Basalt fiber reinforced concrete (BFRC) has been widely utilized in various constructions such as buildings, large industrial floors, and highways, due to its excellent physical and mechanical ...properties, as well as low production cost. In order to address the influence of basic parameters such as fiber volume fraction (0.05∼0.40%), fiber length (12∼36 mm) of BF, and compressive strength (30, 40, and 50 MPa) of concrete on both physical and mechanical properties of BFRC including compressive strength, tensile and flexural strength, workability, and anti-dry-shrinkage cracking properties, a series of standard material tests were conducted. Experimental results indicated that clumping of fibers may occur at relatively higher fiber volume fraction resulting in mixing and casting problems. Based on experimental values of mechanical properties and anti-dry-shrinkage cracking resistance of BFRC, the reasonable basalt fiber length and fiber volume fractions are identified. The addition of a small amount of short basalt fibers can result in a considerable increase in both compressive strength and modulus of rupture (MoR) of BFRC and that the proposed fiber length and content are 12.0 mm and 0.10%∼0.15%, respectively. As the length of basalt fibers increases, the development of early shrinkage cracks decreases initially and then increases slowly and the optimal fiber length is 18.0 mm. Results of the study also indicated that early shrinkage cracks decrease with the increase of fiber volume fraction, and when the volume fraction of 0.20% is used, no cracks were observed. All the findings of the present study may provide reference for the material proportion design of BFRC.
Cystic echinococcosis is a global parasitic disease caused by infection with Echinococcus granulosus larvae with potentially life-threatening complications in humans. To date, the status of the ...immune cells believed to be associated with the pathogenicity of E. granulosus infection has not been demonstrated clearly.
In this study, we developed a multiplex flow cytometry assay to investigate the systemic immune status of innate and adaptive immunity at 30, 180, 360 days post-infection (dpi) in mice infected with E. granulousus. At 30 dpi, an increase in the number of CD11b(+) and CD11c(+) antigen-presenting cells (APCs) was observed. This was accompanied by the slight down-regulated expression of the co-stimulatory molecule MHC-II, indicating the impairment of APCs in early infection through the release of secretory-excretory products. In all infected groups, we observed a significant increase in innate immune cells, including APCs and GR-1(+) cells, and a dramatic increase in the myeloid-derived suppressor cells (MDSC) expressing CD11b(+)/GR-1(+). Moreover, the upregulation of the activated markers CD69, CD44, CD40L, and the downregulation of CD62L were observed in the CD4(+) and CD8(+) T cells following infection. Regulatory T cells expressing CD4(+)/CD25(+)/FoxP3 (+) increased significantly over the course of infection.
Our findings demonstrate that the microenvironment in the peripheral immune system after E. granulosus infection changes in subtle but detectably ways, especially during the persistent period of infection. We found that T cells were activated following infection, but observed that the significant increase of immunosuppressive cells such as MDSC and Treg cells could inhibit T cell response to E. granulosus antigens. We suggest these cells may play a neglected but key role in the downregulation of the immune response in long-term parasitic infection. Understanding the basic functions and temporal interactions of these immunosuppressive cells will pave the way for new strategies of parasite vaccine design.
To build and assess a pre-treatment dual-energy CT-based clinical-radiomics nomogram for the individualized prediction of clinical response to systemic chemotherapy in advanced gastric cancer (AGC).
...A total of 69 pathologically confirmed AGC patients who underwent dual-energy CT before systemic chemotherapy were enrolled from two centers in this retrospective study. Treatment response was determined with follow-up CT according to the RECIST standard. Quantitative radiomics metrics of the primary lesion were extracted from three sets of monochromatic images (40, 70, and 100 keV) at venous phase. Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used to select the most relevant radiomics features. Multivariable logistic regression was performed to establish a clinical model, three monochromatic radiomics models, and a combined multi-energy model. ROC analysis and DeLong test were used to evaluate and compare the predictive performance among models. A clinical-radiomics nomogram was developed; moreover, its discrimination, calibration, and clinical usefulness were assessed.
Among the included patients, 24 responded to the systemic chemotherapy. Clinical stage and the iodine concentration (IC) of the tumor were significant clinical predictors of chemotherapy response (all
< 0.05). The multi-energy radiomics model showed a higher predictive capability (AUC = 0.914) than two monochromatic radiomics models and the clinical model (AUC: 40 keV = 0.747, 70 keV = 0.793, clinical = 0.775); however, the predictive accuracy of the 100-keV model (AUC: 0.881) was not statistically different (
= 0.221). The clinical-radiomics nomogram integrating the multi-energy radiomics signature with IC value and clinical stage showed good calibration and discrimination with an AUC of 0.934. Decision curve analysis proved the clinical usefulness of the nomogram and multi-energy radiomics model.
The pre-treatment DECT-based clinical-radiomics nomogram showed good performance in predicting clinical response to systemic chemotherapy in AGC, which may contribute to clinical decision-making and improving patient survival.
Glioblastoma is the most fatal and insidious malignancy, due to the existence of the blood-brain barrier (BBB) and the high invasiveness of tumor cells. Abnormal mitochondrial viscosity has been ...identified as a key feature of malignancies. Therefore, this study reports on a novel fluorescent probe for mitochondrial viscosity, called ZVGQ, which is based on the twisted intramolecular charge transfer (TICT) effect. The probe uses 3-dicyanomethyl-1,5,5-trimethylcyclohexene as an electron donor moiety and molecular rotor, and triphenylphosphine (TPP) cation as an electron acceptor and mitochondrial targeting group. ZVGQ is highly selective, pH and time stable, and exhibits rapid viscosity responsiveness.
experiments showed that ZVGQ could rapidly recognize to detect the changes in mitochondrial viscosity induced by nystatin and rotenone in U87MG cells and enable long-term imaging for up to 12 h in live U87MG cells. Additionally,
3D tumor spheres and
orthotopic tumor-bearing models demonstrated that the probe ZVGQ exhibited exceptional tissue penetration depth and the ability to penetrate the BBB. The probe ZVGQ not only successfully visualizes abnormal mitochondrial viscosity changes, but also provides a practical and feasible tool for real-time imaging and clinical diagnosis of glioblastoma.
Pyro-breaker, a fast-responding, highly reliable and explosive-driven circuit breaker, is utilized in several Quench Protection Systems (QPS). The commutation process and its parameters are the main ...technical considerations in the process of designing a new pyro-breaker. The commutation parameters, such as the commutation time and the current change rate, are not only determined by the electrical parameters of the commutation circuit but also the arc behavior during the operation. The arc behavior is greatly affected by the structure and the driving mechanism of the Commutation Section (CS) in the pyro-breaker. The arc model was developed decades ago and the black-box arc model is considered a valid method to study arc behavior. In this paper, the Schavemaker black-box arc model, an improved Mayr-type arc model, is applied to study the commutation process of a newly designed pyro-breaker. Unlike normal circuit breakers, the arc discussed in this paper is discharged in deionized water. A parameter selection method is proposed. The practicability of the method is verified by numerical calculation in Power Systems Computer Aided Design (PSCAD) and experimentally.
Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ...ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii.
Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 μM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis.
A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation.
Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii.
Two novel species of Lyophyllum are proposed based on morphological and phylogenetic investigations. Lyophyllum bulborhizum sp. nov. has abundant black scales on the surface, is a dry, dark grey at ...the center, grey at the margin, has a clear bulbous stipe base, and has a narrowly cylindrical or narrowly clavate pleurocystidia and cheilocystidia. Lyophyllum nigrum sp. nov. is tufted and has a dark grey pileus and subclavate, a greyish green-to-olive stipe, and a narrowly cylindrical or narrowly clavate pleurocystidia and cheilocystidia. In addition, L. rhombisporum is described with morphology and phylogeny and compared with the type species. Molecular analyses employing internal transcribed spacer (ITS) sequences strongly support the two new species to be unique in the genus Lyophyllum. Full descriptions, colour photos, illustrations, and phylogenetic analyses results of the two new taxa and the known taxon are presented in this study.
The aim of this study was to determine the effects of plant essential oil supplementation on growth performance, immune function and antioxidant activities in weaned pigs.
In the study, 24 weaned ...pigs were used to explore the effects of plant essential oil (PEO) on growth performance, immune properties and antioxidant activities. Pigs were fed with a basal diet (CON) or basal diet containing different concentrations of PEO (PEO50: 50 ppm; PEO100: 100 ppm; PEO200: 200 ppm). After 3 weeks, all pigs were slaughtered and blood and tissue samples were collected for biochemical analysis.
The results showed that PEO supplementation quadratically increased body weight gain (BWG) (P = 0.031), linearly (P < 0.05) and quadratically (P < 0.05) decreased F:G. In addition, IgG increased linearly (P < 0.05) and IgM increased linearly (P < 0.05) and quadratically (P < 0.05) as PEO supplementation. Similarly, MDA in serum, jejunal mucosa and pancreas were linearly decreased (P < 0.05) and GSH in serum (linear and quadratic, P < 0.05), duodenal mucosa (linear and quadratic, P < 0.05) and in ileal mucosa (linear and quadratic, P < 0.05) were notably increased. Futhermore, antioxidant-related genes expression levels of GST in spleen (linear and quadratic, P < 0.05), GPX1 (quadratic, P < 0.05) and SOD1 (linear, P < 0.05) in spleen and GST in liver (quadratic, P < 0.05) were markedly upregulated by PEO supplementation increasing.
These results suggest that PEO improves growth performance, immune function, and antioxidant activities in weaned pigs, and it may also relieve weaning stress if used as a feed additive in the livestock industry. And that supplementation 200 ppm PEO in diet would seem to be economically feasible.
Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous ...cell carcinoma (HNSC) is urgently required.
Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed.
We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR < 0.001) signaling pathways. CASEs enriched in immune-related pathways were closely associated with immune cell infiltration and cytolytic activity. AS regulatory networks suggested a significant association between splicing factor (SF) expression and CASEs and might be regulated by SF methylation. Eighteen CASEs were identified as independent prognostic factors for overall and disease-free survival. Unsupervised clustering analysis revealed distinct correlations between AS-based clusters and prognosis, molecular characteristics and immune features. Immunogenic features and immune subgroups cooperatively depict the immune features of AS-based clusters.
This comprehensive genome-wide analysis of the AS landscape in HNSC revealed novel AS events related to carcinogenesis and immune microenvironment, with implications for prognosis and therapeutic responses.
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