Identification of key drivers and new therapeutic targets is important given the poor prognosis for hepatocellular carcinoma (HCC) patients, particularly those ineligible for surgical resection or ...liver transplant. However, the approach to identify such driver genes is facing significant challenges due to the genomically heterogenous nature of HCC. Here we tested whether the integrative genomic profiling of a well-defined HCC subset that is classified by an extreme EpCAM super(+) AFP super(+) gene expression signature and associated with poor prognosis, all attributes of a stem cell-like phenotype, could uncover survival-related driver genes in HCC. Following transcriptomic analysis of the well-defined HCC cases, a Gene Set Enrichment Analysis coupled with genomic copy number alteration assessment revealed that YY1-associated protein 1 (YY1AP1) is a critical oncoprotein specifically activated in EpCAM super(+) AFP super(+) HCC. YY1AP1 silencing eliminates oncogene addiction by altering the chromatin landscape and triggering massive apoptosis in vitro and tumor suppression in vivo. YY1AP1 expression promotes HCC proliferation and is required for the maintenance of stem cell features. We revealed that YY1AP1 cooperates with YY1 to alter the chromatin landscape and activate transcription of stemness regulators. Thus YY1AP1 may serve as a key molecular target for EpCAM super(+) AFP super(+) HCC subtype. Our results demonstrate the feasibility and power of a new strategy by utilizing well-defined patient samples and integrative genomics to uncover critical pathways linked to HCC subtypes with prognostic impact.
Two novel metal−organic frameworks (MOFs) Zn(TITMB)(OAc)(OH)·8.5H2O (1) and Ag(TITMB)N3·H2O (2) TITMB = 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene, OAc = acetate anion were synthesized ...and their structures were determined by X-ray crystallography. Complex 1 crystallizes in tetragonal space group P4̄ with a = 23.2664(7) and c = 11.9890(3) Å and Z = 8. 1 has a one-dimensional tubelike structure with large inner pore size of ∼17 Å. Complex 2 crystallizes in monoclinic space group C2 with a = 20.7193(10), b = 11.5677(8), and c = 12.2944(6) Å, β = 125.5770(10)°, and Z = 4. 2 consists of two-dimensional honeycomb networks that interpenetrate each other to generate a polycatenated structure. In these two complexes, both zinc(II) and silver(I) atoms are four-coordinated with the same tetrahedral coordination geometry. The topologies of 1 and 2 are predominated by the conformations of TITMB, which are cis, trans, trans in 1 and cis, cis, cis in 2, respectively.
To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19).
Minimally ...invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV.
Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs.
The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.
▶ First report about the influence of emulsifier content of sizing agent. ▶ The emulsifier content of sizing agent has an important influence to carbon fibres. ▶ The sizing agent has an important ...influence to the carbon fibres composites. ▶ This research has concluded that E-3 sized carbon fibres showed better properties. ▶ The sizing agent E-2 sized carbon fibre has better ageing resistant properties.
In this work, carbon fibres were sized with different emulsifier content sizing agent in order to improve the performances of carbon fibres and the interface of carbon fibres composites. The surface characteristic changing after modification was investigated by scanning electron microscopy (SEM), atomic force microscopy (AFM). Wetting and surface energy along with contact angles were determined by the dynamic contact angle analysis test (DCAT). At the same time, the single fibre strengths and weibull distributions were also studied in order to understand the effect of the emulsifier content of sizing agent on the carbon fibres. The interfacial shear strength and hygrothermal ageing of the composites were measured which showed a different enhancement, respectively. The results revealed that sizing agent E-3 showed better interface adhesion between fibres and matrix and sizing agent E-2 sized carbon fibre has better ageing resistant properties.
Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in glutamatergic function in brain regions associated with reinforcement. Previous studies have examined ...ionotropic glutamate receptor (iGluR) subunit protein level changes following acute and chronic experimenter‐administered cocaine or after withdrawal periods from experimenter‐administered cocaine. To evaluate whether alterations in expression of iGluRs are associated with cocaine reinforcement, protein levels were assessed after binge (8 h/day, 15 days; 24‐h access, days 16–21) cocaine self‐administration and following 2 weeks of abstinence from this binge. Western blotting was used to compare levels of iGluR protein expression (NR1–3B, GluR1–7, KA2) in the ventral tegmental area (VTA), substantia nigra (SN), nucleus accumbens (NAc), striatum and prefrontal cortex (PFC) of rats. iGluR subunits were altered in a time‐dependent manner in all brain regions studied; however, selective alterations in certain iGluR subtypes appeared to be associated with binge cocaine self‐administration and withdrawal in a region‐specific manner. In the SN and VTA, alterations in iGluR protein levels compared with controls occurred only following binge access, whereas in the striatum and PFC, iGluR alterations occurred with binge access and following withdrawal. In the NAc, GluR2/3 levels were increased following withdrawal compared with binge access, and were the only changes observed in this region. Because subunit composition determines the functional properties of iGluRs, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long‐term biochemical and behavioral effects of cocaine.
Exosomes are a kind of membrane vesicle with a diameter of 30-150 nm. It is formed by the budding of multiple vesicles in cells, which can fuse with the cell membrane and be released into the ...extracellular matrix. Adipose derived stem cells (ADSCs) have the potential of self-renewal and multi-directional differentiation. They can transport the active substance, regulate the inflammatory response, cell migration, proliferation, differentiation and angiogenesis via the action of paracrine exosomes, so as to enhance the ability of wound repair, promote wound healing, and inhibit the formation of scars. Chronic wounds refer to the wounds that can not reach the anatomic and functional integrity through the normal, orderly, and timely repair process, and the course of the wound healing is more than 4 weeks. At present, there are various treatment methods for chronic wounds, among which ADSCs, although showing a good application prospect, have some limitations due to ethical issues, while exosomes can avoid this pro
► Pure zinc oxide (ZnO) particles were fabricated by a simple aqueous solution route. ► Hydrogen peroxide (H2O2) treatment was used to reduce the negative influences of oxygen vacancies and promote ...the proportion of oxygen interstitials. ► There is an enhancement in the ferromagnetism of ZnO after H2O2 treatment. ► Oxygen interstitials may have some close connections with the ferromagnetism of ZnO.
Pure zinc oxide (ZnO) particles fabricated by a simple aqueous solution route were treated with hydrogen peroxide (H2O2) solution. X-ray diffraction (XRD) and scanning electron microscopy (SEM) showed the homogeneous growth of particles throughout the substrate with the wurtzite phase. Magnetic properties were measured and a correlation between immersion time and ferromagnetism (FM) was observed. X-ray photoemission spectroscopy (XPS) and photoluminescence (PL) were then performed to investigate the influence of hydrogen peroxide (H2O2) treatment on oxygen-related defects. It is revealed that oxygen interstitials (IO) may be considered to be playing an important role in tailoring the magnetic properties of ZnO.
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