Cell line models are essential tools to study the molecular mechanisms underlying tumor initiation and progression. There are limited treatment options for penile squamous cell carcinoma (PSCC), ...accounting for 1-2% of male tumors in developing countries, and limited progress in preclinical research in PSCC due to lacking available models with identified genomic characteristics. Here, biological and molecular characteristics and whole-genomic alterations were analyzed in a panel of PSCC cell lines newly established in our laboratory. These cell lines were all human papillomavirus (HPV)-negative, epithelial-like, immortalized, and tumorigenic in nude mice, whereas they displayed different proliferation, migration and invasion capacities in vitro, and tumorigenic ability in nude mice. They were all cisplatin sensitive, anti-EGFR therapy resistant, and androgen irresponsive. Whole-genomic sequecing analysis revealed that transition mutations (C:G>T:A and T:A>C:G) were the most common substitution types in these cell lines, whereas ERCC5, TP53, PTH1, CLTCL1, NOTCH2, MAP2K3, CDK11A/B, USP6, ADCH5, BCLAF1, CDKN2A, FANCD2, HRAS, and NOTCH1 were the most frequently altered genes. Amplifications of MYC, PLAG1, NCOA2, RUNX1T1, COX6C, and EGFR and losses of FBXW7, TET2, XPC, and FANCE were frequently observed in cell lines. The exomic variations between cell lines and their corresponding cancer tissues were highly consistent. Genetic variations were mainly involved in the MAPK, Jak-STAT, TGF-beta, Notch, and apoptosis signaling pathways. Conclusively, these panel of PSCC cell lines established in our laboratory harbor some common or specific biological characteristics and genomic variations, and they may serve as optimal models to investigate the molecular mechanisms underlying the progression, metastasis, relapses, and treatment resistance of PSCC and to develop effective treatment strategy.
Deciphering the regulatory network for human naive and primed pluripotency is of fundamental theoretical and applicable significance. Here, by combining quantitative proteomics, phosphoproteomics, ...and acetylproteomics analyses, we revealed RNA processing and translation as the most differentially regulated processes between naive and primed human embryonic stem cells (hESCs). Although glycolytic primed hESCs rely predominantly on the eukaryotic initiation factor 4E (eIF4E)-mediated cap-dependent pathway for protein translation, naive hESCs with reduced mammalian target of rapamycin complex (mTORC1) activity are more tolerant to eIF4E inhibition, and their bivalent metabolism allows for translating selective mRNAs via both eIF4E-dependent and eIF4E-independent/eIF4A2-dependent pathways to form a more compact naive proteome. Globally up-regulated proteostasis and down-regulated post-translational modifications help to further refine the naive proteome that is compatible with the more rapid cycling of naive hESCs, where CDK1 plays an indispensable coordinative role. These findings may assist in better understanding the unrestricted lineage potential of naive hESCs and in further optimizing conditions for future clinical applications
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•RNA processing and translation are most different between naive and primed hESCs•Glycolytic primed hESCs mainly rely on eIF4E-dependent translation•Bivalent metabolism in naive hESCs promotes eIF4E-independent translation•CDK1 is required for naive pluripotency partially by activating E-cadherin signaling
Molecular biology; Stem cells research; Proteomics
This paper presents experimental tests, numerical simulations, and design methods on steel equal-leg angles subjected to compression. In the experimental programme, a total of 30 steel angles, with ...different depths of local defects produced at the mid-height, were loaded by a compression force on one leg. Two slendernesses of steel angles were selected in the design of specimens, and the location of local defects were placed at the inner face of the loaded leg and the inner and outer faces of the unloaded leg. The applied compression force and the associated deflections at the mid-height of steel angles were measured during testing. Besides, longitudinal strains of sections at the mid-height, top and bottom ends of steel angles were also measured to gain insight into the development of failure pattern. Comparisons were made among steel angles in terms of the ultimate load and the associated deflection to investigate the effects of slenderness, the location and depth of local defects. Numerical models are also developed for steel equal-leg angles in compression, in which residual stresses and initial geometric imperfections are considered. The validated numerical model is then used to conduct parametric studies on slenderness and local defect on the load capacity of steel angles. Based on the results of the parametric study, a design equation to calculate the ultimate load-carrying capacity of corroded steel angle is proposed. Comparisons with experimental results show that the design equation can calculate the ultimate load-carrying capacity of steel angle with local defects with good accuracy.
•Ten groups of steel angles with local defects at the mid-height were tested under compression on one leg.•Numerical models are developed for steel angles in which residual stresses and initial geometric imperfections are considered.•Design equations are developed to calculate the load capacity of steel angles.
As the growing criterion of electromagnetic wave (EMW) absorption materials, micro/nano-scale magnetic materials are drawing more and more attention for their unique features compared to bulky ...absorbers. Generally, the complex permeability of micro/nano-scale magnetic absorbers varies in a relatively narrow range, whatever for the storage of magnetic energy or the dissipation of magnetic energy. If so, how the small variation of permeability affects the ultimate performances is still unclear. Here, a strategy of electromagnetic parameters regulation for the magnetic materials is applied to understand the loss contribution in micro/nanoscale magnetic absorbers. After analyzing the evolution of electromagnetic maps of ten ferrosoferric oxide samples, it can be found that the dissipation contribution of permeability for magnetic materials is weaker than that of permittivity, in spite of its significant role in determining the impedance matching characteristics. In summary, this work systematically explores the loss contribution in micro/nano-magnetic absorbers for the first time, which is of great importance in designing and optimizing the microwave absorption properties of magnetic absorbers.
Intrinsic or acquired chemoresistance represents a major obstacle in cancer treatment. Multiple mechanisms can contribute to cancer cells' resistance to chemotherapy. Among them, an aberrantly ...strengthened DNA repair mechanism is responsible for a large proportion of drug resistance to alkylating agents and radiation therapy. In cancer cells, damping overactivated DNA repair system can overcome survival advantages conferred by chromosomal translocations or mutations and lead to cytostatic effects or cytotoxic. Therefore, selectively targeting DNA repair system in cancer cells holds promise for overcoming chemoresistance.
In this study, we revealed that the endonuclease Flap Endonuclease 1 (FEN1), essential for DNA replication and repair, directly interacts with phosphatidylinositol 3-phosphate PI(3)P, and FEN1-R378 is the primary PI(3)P-binding site. PI(3)P-binding deficient FEN1 mutant (FEN1-R378A) cells exhibited abnormal chromosomal structures and were hypersensitized to DNA damage. The PI(3)P-mediated FEN1 functionality was essential for repairing DNA damages caused by multiple mechanisms. Furthermore, VPS34, the major PI(3)P synthesizing enzyme, was negatively associated with patients' survival in various cancer types, and VPS34 inhibitors significantly sensitized chemoresistant cancer cells to genotoxic agents.
These findings open up an avenue for counteracting chemoresistance by targeting VPS34-PI(3)P-mediated DNA repair pathway, and call for assessing the efficacy of this strategy in patients suffering from chemoresistance-mediated cancer recurrence in clinical trials.
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•.With R378 as its primary PI(3)P-binding site, FEN1 functions as a new PI(3)P-binding protein.•PI(3)P-FEN1 interaction contributes to FEN1-mediated DNA repair.•VPS34 can be an effective drug target in enhancing sensitivity to genotoxic agents and combating chemoresistance.
Cu (II) is a toxic heavy metal commonly identified in groundwater contaminants. Bentonite-based cutoff wall is the most used method in isolating and adsorbing contaminants, while the bentonite in it ...easily to fail due to Cu(II) exchange. This study synthesized a novel material through the modification of calcium bentonite (CaB) utilizing sodium hexametaphosphate (SHMP) and nano zero-valent iron (NZVI). The characteristics, adsorption performance, and mechanism of the NZVI/SHMP-CaB were investigated comprehensively. The results showed that SHMP can disperse CaB and reduce flocculation, while NZVI can be further stabilized without agglomeration. The best adsorption performance of NZVI/SHMP-CaB could be obtained at the dosage of 2% SHMP and 4% NZVI. The NZVI/SHMP-CaB exhibited an outstanding removal efficiency of over 60% and 90% at a high Cu(II) concentration (pH = 6, Cu(II) = 300 mg/L) and acidic conditions (pH = 3–6, Cu(II) = 50 mg/L), respectively. The adsorption of Cu(II) by NZVI/SHMP-CaB followed a pseudo-second-order kinetic model, and fitting results from the Freundlich isothermal model suggested that the adsorption process occurred spontaneously. Besides the rapid surface adsorption on the NZVI/SHMP-CaB and ion exchange with interlayer ions in bentonite, the removal mechanism of Cu(II) also involved the chemical reduction to insoluble forms such as Cu0 and Cu2O. The generated FePO4 covered the surface of the homogenized NZVI particles, enhancing the resistance of NZVI/SHMP-CaB to acidic and oxidative environments. This study indicates that NZVI/SHMP-CaB is a promising alternative material which can be used for heavy metal removal from contaminated soil and water.
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•NZVI/SHMP-CaB, a novel material, was synthesized for the removal of heavy metals.•Adsorption performance and mechanism of NZVI/SHMP-CaB were investigated.•Optimal ratio of 2% SHMP and 4% NZVI to CaB provided best adsorption performance.•Cu(II) was removed by rapid adsorption, ion exchange, and chemical reduction.
Naive human embryonic stem cells (hESCs) that resemble the pre-implantation epiblasts are fueled by a combination of aerobic glycolysis and oxidative phosphorylation, but their mitochondrial ...regulators are poorly understood. Here we report that, proline dehydrogenase (PRODH), a mitochondria-localized proline metabolism enzyme, is dramatically upregulated in naive hESCs compared to their primed counterparts. The upregulation of PRODH is induced by a reduction in c-Myc expression that is dependent on PD0325901, a MEK inhibitor routinely present in naive hESC culture media. PRODH knockdown in naive hESCs significantly promoted mitochondrial oxidative phosphorylation (mtOXPHOS) and reactive oxygen species (ROS) production that triggered autophagy, DNA damage, and apoptosis. Remarkably, MitoQ, a mitochondria-targeted antioxidant, effectively restored the pluripotency and proliferation of PRODH-knockdown naive hESCs, indicating that PRODH maintains naive pluripotency by preventing excessive ROS production. Concomitantly, PRODH knockdown significantly slowed down the proteolytic degradation of multiple key mitochondrial electron transport chain complex proteins. Thus, we revealed a crucial role of PRODH in limiting mtOXPHOS and ROS production, and thereby safeguarding naive pluripotency of hESCs.
Synopsis
Downregulation of PRODH promotes oxidative phosphorylation and ROS production, which in turn impair pluripotency and proliferation of naive but not primed hESCs, revealing a crucial role of PRODH in safeguarding human naive pluripotency.
PRODH is expressed in naive hESCs at a higher level compared to their primed counterparts.
MEK inhibitor present in naive culture media upregulates PRODH by suppressing MYC.
PRODH depletion boosts mtOXPHOS and ROS production in naive hESCs.
PRODH promotes proteolytic degradation of the ETC complex components.
Downregulation of PRODH promotes oxidative phosphorylation and ROS production, which in turn impair pluripotency and proliferation of naive but not primed hESCs, revealing a crucial role of PRODH in safeguarding human naive pluripotency.
Man With Right Hand Pain Kang, Bo-Hwi; Sun, Jen-Tang; Huang, Chun-Yen ...
Annals of emergency medicine,
December 2022, 2022-12-00, 20221201, Letnik:
80, Številka:
6
Journal Article
The stipe of shiitake, a disposable byproduct in mushroom industry, was applied as a nitrogen source in alcoholic fermentation. Four yeast strains were screened by evaluating their fermentative ...efficiency and ethanol tolerance. The results showed that shiitake stipe extract could enable yeast cell proliferation and be sequent to good performance of sugar utilization and ethanol production, depended on strains. The ethanol production (mL/100 mL) of 13.7 ± 0.8, 14.1 ± 0.9, 11.9 ± 0.1 and 10.9 ± 0.3 was obtained from strains 20262, 22236, 21686 and 21992, respectively, at the end of fermentation. Ethanol tolerance of strain in term of glucose utilization rate was more consistent with the extent of ethanol production during fermentation than that of survival rate. Therefore, the evaluation of glucose utilization rate in external ethanol condition might help establish a simple and quick method to screen the strains capable of high ethanol production. The shiitake stipe alcoholic beverage would also provide comparable consumer acceptances with a commercial Taiwanese white wine.
Quenching of inclusive and tagged b-jets at the LHC Xing, Hongxi; Huang, Jinrui; Kang, Zhong-Bo ...
Nuclear and particle physics proceedings,
July-September 2016, 2016-07-00, Letnik:
276-278
Journal Article
Recenzirano
Odprti dostop
We present theoretical predictions for the nuclear-induced attenuation of the differential cross sections for inclusive and tagged b-jet production in heavy ion collisions at the LHC. We find that ...for inclusive b-jet production at high transverse momentum the mass effects are negligible, and that the attenuation is comparable to the one observed for light jets. On the other hand, for isolated-photon and B-meson-tagged b-jets the sample of events with heavy quarks produced at the early stages of the collision is greatly enhanced. Thus, these tagged b-jet final-states have a much more direct connection to the physics of b-quark energy loss. We present theoretical predictions for the quenching of such tagged b-jet events at the LHC and the QGP-induced modification of the related momentum imbalance and asymmetry. We demonstrate that these tagged processes can be used to accurately study the physics of heavy quark production and propagation in dense QCD matter.
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