We study analytically quantum tunneling of relativistic and non-relativistic particles at both Killing and universal horizons of Einstein–Maxwell-aether black holes, after high-order curvature ...corrections are taken into account, for which the dispersion relation of the particles becomes nonlinear. Our results at the Killing horizons confirm the previous ones, i.e., at high frequencies the corresponding radiation remains thermal and the nonlinearity of the dispersion does not alter the Hawking radiation significantly. In contrary, non-relativistic particles are created at universal horizons and are radiated out to infinity. The radiation also has a thermal spectrum, and the corresponding temperature takes the form, TUHz=2κUH(z−1)/(2πz), where z (z≥2) denotes the power of the leading term in the nonlinear dispersion relation, κUH is the surface gravity of the universal horizon, defined by peering behavior of ray trajectories at the universal horizon. We also study the Smarr formula by assuming that: (a) the entropy is proportional to the area of the universal horizon, and (b) the first law of black hole thermodynamics holds, whereby we derive the Smarr mass, which in general is different from the total mass obtained at infinity. This indicates that one or both of these assumptions must be modified.
Immunogenic cell death (ICD) has been classified as a form of regulated cell death (RCD) that is sufficient to activate an adaptive immune response. Accumulating evidence has demonstrated the ability ...of ICD to reshape the tumor immune microenvironment through the emission of danger signals or DAMPs, which may contribute to the immunotherapy. Currently, identification of ICD-associated biomarkers that stratify patients according to their benefit from ICD immunotherapy would be of great advantage. Here, we identified two ICD-associated subtypes by consensus clustering. ICD-high subtype was associated with the favorable clinical outcomes, abundant immune cell infiltration, and high activity of immune response signaling. Besides, we established and validated an ICD-related prognostic model that predicted the survival of HNSCC and was associated with tumor immune microenvironment. In conclusion, we established a new classification system of HNSCC based on ICD signatures. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of HNSCC patients.
Granulomatous inflammation (GI) diseases are a group of chronic inflammation disorders characterized by focal collections of multinucleated giant cells, epithelioid cells and macrophages, with or ...without necrosis. GI diseases are closely related to microbes, especially virulent intracellular bacterial infections are important factors in the progression of these diseases. They employ a range of strategies to survive the stresses imposed upon them and persist in host cells, becoming the initiator of the fighting. Microbe-host communication is essential to maintain functions of a healthy host, so defense capacity of hosts is another influence factor, which is thought to combine to determine the result of the fighting. With the development of gene research technology, many human genetic loci were identified to be involved in GI diseases susceptibility, providing more insights into and knowledge about GI diseases. The current review aims to provide an update on the most recent progress in the identification and characterization of bacteria in GI diseases in a variety of organ systems and clinical conditions, and examine the invasion and escape mechanisms of pathogens that have been demonstrated in previous studies, we also review the existing data on the predictive factors of the host, mainly on genetic findings. These strategies may improve our understanding of the mechanisms underlying GI diseases, and open new avenues for the study of the associated conditions in the future.
Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen ...challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.
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•karst drainage soil DOM was characterized by EEMs-PARAFAC.•Different vegetation restoration types affect soil DOM quality.•Karst hydrodynamic processes control the migration and loss ...of DOM.
Dissolved organic matter (DOM) has strong reactivity and migration ability, which affects biogeochemical processes such as nutrient cycling. Karst ecological vulnerability has been widely discussed. However, the characteristics of soil DOM, the main energy matrix of the soil, in the process of rocky desertification control have rarely been reported. This study examined the characteristics of DOM in shallow soil after vegetation restoration in a karst area. Soil samples of 5 vegetation restoration types (abandoned land, AL; grassland, GL; peanut cultivated land, PCL; Zanthoxylum bungeanum land, ZBL; forest, FS) and water samples from the drainage were collected. DOM in soils of different vegetation restoration types was characterized by UV–Vis absorption spectroscopy and fluorescence excitation emission matrix (EEM)-parallel factor analysis (PARAFAC), and the fluorescent components of DOM in the soil and water samples were identified. Redundancy analysis (RDA) was used to identify the controlling factors of optical soil DOM characteristics. The results showed the following: (1) the DOC/SOC < 0.40 ± 0.04%, most HIX values < 3.0, most BIX values < 1 and the protein-like component ranged from 40 ± 0.03% to 54 ± 0.02%. These results indicate that the DOM content in the study area is low, and the soil has weak aromaticity and low humification. (2) Karst hydrodynamic processes control the migration and loss of DOM (the explanatory degree accounts for 23.53%). (3) In AL, the DOC/SOC is the lowest, and C3 (the molecular weight is the highest among the three components) accounted for the highest proportion compared to the other vegetation restoration types. Taken together, our results indicate that environmental and vegetation factors have important impacts on DOM migration. In rocky desertification areas with weak aromaticity and a low degree of humification, there is great potential for the soil to lose lightweight DOM. These results can help predict future changes in carbon allocation across landscapes due to changes in land use and hydrodynamic processes.
Previous expression quantitative trait loci (eQTL) studies have identified thousands of genetic variants to be associated with gene expression at the mRNA level in the human liver. However, protein ...expression often correlates poorly with mRNA levels. Thus, protein quantitative trait loci (pQTL) study is required to identify genetic variants that regulate protein expression in human livers.
We conducted a genome-wide pQTL study in 287 normal human liver samples and identified 900 local pQTL variants and 4026 distant pQTL variants. We further discovered 53 genome hotspots of pQTL variants. Transcriptional region mapping analysis showed that 1133 pQTL variants are in transcriptional regulatory regions. Genomic region enrichment analysis of the identified pQTL variants revealed 804 potential regulatory interactions among 595 predicted regulators (e.g., non-coding RNAs) and 394 proteins. Moreover, pQTL variants and trait-variant integration analysis implied several novel mechanisms underlying the relationships between protein expression and liver diseases, such as alcohol dependence. Notably, over 2000 of the identified pQTL variants have not been reported in previous eQTL studies, suggesting extensive involvement of genetic polymorphisms in post-transcriptional regulation of protein expression in human livers.
We have partially established protein expression regulation networks in human livers and generated a wealth of pQTL data that could serve as a valuable resource for the scientific community.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human hepatic cell lines are widely used as an in vitro model for the study of drug metabolism and liver toxicity. However, the validity of this model is still a subject of debate because the ...expressions of various proteins in the cell lines, including drug-metabolizing enzymes (DMEs), can differ significantly from those in human livers. In the present study, we first conducted an untargeted proteomics analysis of the microsomes of the cell lines HepG2, Hep3B, and Huh7, and compared them to human livers using a sequential window acquisition of all theoretical mass spectra (SWATH) method. Furthermore, high-resolution multiple reaction monitoring (MRM-HR), a targeted proteomic approach, was utilized to compare the expressions of pre-selected DMEs between human livers and the cell lines. In general, the SWATH quantifications were in good agreement with the MRM-HR analysis. Over 3000 protein groups were quantified in the cells and human livers, and the proteome profiles of human livers significantly differed from the cell lines. Among the 101 DMEs quantified with MRM-HR, most were expressed at substantially lower levels in the cell lines. Thus, appropriate caution must be exercised when using these cell lines for the study of hepatic drug metabolism and toxicity.
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Forkhead transcription factor 3 (FOXA3) has been shown to regulate metabolism and development. Hepatic FOXA3 is reduced in obesity and fatty liver disease. However, the role of hepatic FOXA3 in ...regulating obesity or steatohepatitis remains to be investigated. In this work, C57BL/6 mice were i.v. injected with AAV8-ALB-FOXA3 or the control virus. The mice were then fed a chow or Western diet for 16 weeks. The role of hepatic FOXA3 in energy metabolism and steatohepatitis was investigated. Plasma bile acid composition and the role of Takeda G protein–coupled receptor 5 (TGR5) in mediating the metabolic effects of FOXA3 were determined. Overexpression of hepatic FOXA3 reduced hepatic steatosis in chow-fed mice and attenuated Western diet–induced obesity and steatohepatitis. FOXA3 induced lipolysis and inhibited hepatic genes involved in bile acid uptake, resulting in elevated plasma bile acids. The beneficial effects of hepatic FOXA3 overexpression on Western diet–induced obesity and steatohepatitis were abolished in Tgr5−/− mice. Our data demonstrate that overexpression of hepatic FOXA3 prevents Western diet–induced obesity and steatohepatitis via activation of TGR5.
Vibrating flip-flow screens (VFFS) are widely used to separate high-viscosity and fine materials. The most remarkable characteristic is that the vibration intensity of the screen frame is only 2–3 g ...(g represents the gravitational acceleration), while the vibration intensity of the screen surface can reach 30–50 g. This effectively solves the problem of the blocking screen aperture in the screening process of moist particles. In this paper, the approximate state of motion of the sieve mat is realized by setting the discrete rigid motion at multiple points on the elastic sieve mat of the VFFS. The effects of surface energy levels between particles separated via screening performance were compared and analyzed. The results show that the flow characteristics of particles have a great influence on the separation performance. For 8 mm particle screening, the particle’s velocity dominates its movement and screening behavior in the range of 0–8 J/m2 surface energy. In the feeding end region (Sections 1 and 2), with the increase in the surface energy, the particle’s velocity decreases, and the contact time between the particles and the screen surface increases, and so the passage increases. When the surface energy level continues to increase, the particles agglomerate together due to the effect of the cohesive force, and the effect of the particle’s agglomeration is greater than the particle velocity. Due to the agglomeration of particles, the difficulty of particles passing through the screen increases, and the yields of various size fractions in the feeding end decrease to some extent. In the transporting process, the agglomerated particles need to travel a certain distance before depolymerization, and the stronger the adhesive force between particles, the larger the depolymerization distance. Therefore, for the case of higher surface energy, the screening percentage near the discharging end (Sections 3 and 4) is greater. The above research is helpful to better understand and optimize the screening process of VFFS.
Development of Small‐Diameter Vascular Grafts Wang, Xinwen; Lin, Peter; Yao, Qizhi ...
World journal of surgery,
April 2007, Letnik:
31, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Introduction
Cardiovascular disease, including coronary artery and peripheral vascular pathologies, is the leading cause of mortality in the United States and Western countries. There is a pressing ...need to develop small‐diameter vascular vessels for bypass surgery and other vascular reconstructive procedures. Tissue engineering offers the prospect of being able to meet the demand for replacement of diseased vessels. Significant advances have been made in recent studies and provide confidence that success is attainable. For instance, a completely cellular approach culturing cells into tissue sheets and wrapping these layers was able to form a layered cellular vascular graft with impressive strength.
Methods/Results
In our experiments, decellularization and heparin immobilization grafts from porcine tissues implanted in a canine model could be repopulated from the host cells, indicating the grafts’ potential to develop into living tissues that can adapt and respond to changes in the body.
Conclusions
This review summarizes the current status of vascular grafts used clinically, updates the most recent developments on vascular tissue engineering, and discusses the challenges for the future.
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