HIV Protease Inhibitors Sensitize Human Head and Neck Squamous Carcinoma Cells to Radiation by Activating Endoplasmic Reticulum Stress

Background Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that HIV PIs induce cell apoptosis via activation of endoplasmic reticulum (ER) stress. The aim of this study was to examine the role of ER stress in HIV PI-induced radiosensitivity in human HNSCC. Methodology and Principal Findings HNSCC cell lines, SQ20B and FaDu, and the most commonly used HIV PIs, lopinavir and ritonavir (L/R), were used in this study. Clonogenic assay was used to assess the radiosensitivity. Cell viability, apoptosis and cell cycle were analyzed using Cellometer Vision CBA. The mRNA and protein levels of ER stress-related genes (eIF2α, CHOP, ATF-4, and XBP-1), as well as cell cycle related protein, cyclin D1, were detected by real time RT-PCR and Western blot analysis, respectively. The results demonstrated that L/R dose-dependently sensitized HNSCC cells to irradiation and inhibited cell growth. L/R-induced activation of ER stress was correlated to down-regulation of cyclin D1 expression and cell cycle arrest under G0/G1 phase. Conclusion and Significance HIV PIs sensitize HNSCC cells to radiotherapy by activation of ER stress and induction of cell cycle arrest. Our results provided evidence that HIV PIs can be potentially used in combination with radiation in the treatment of HNSCC

Experimental Research about Thermal Capacity Difference between Domestic and Foreign Plate Heat Exchangers

Because of the noticeable advantages of plate heat exchangers compared with tube heat exchangers, it has been widely applied and researched. However, in the process of practical application, it is easy to find that the performance of heat exchangers produced domestically and from developed countries are quite different, which is one of the key factors that restrict the wide application of domestic plate heat exchangers, there are few studies on this subject yet. Thus, the paper analyzed the main difference of thermal capacity between a domestic and foreign plate heat exchangers through experimental researches, and the results all show that, foreign plate heat exchangers has a more superior thermal capacity and heat exchange efficiency than domestic one, which is in purpose of offering some guidance on technical improvements and applications in the future

Experimental Research about Thermal Capacity Difference between Domestic and Foreign Plate Heat Exchangers

Because of the noticeable advantages of plate heat exchangers compared with tube heat exchangers, it has been widely applied and researched. However, in the process of practical application, it is easy to find that the performance of heat exchangers produced domestically and from developed countries are quite different, which is one of the key factors that restrict the wide application of domestic plate heat exchangers, there are few studies on this subject yet. Thus, the paper analyzed the main difference of thermal capacity between a domestic and foreign plate heat exchangers through experimental researches, and the results all show that, foreign plate heat exchangers has a more superior thermal capacity and heat exchange efficiency than domestic one, which is in purpose of offering some guidance on technical improvements and applications in the future

Carbon-supported Fe catalysts with well-defined active sites for highly selective alcohol production from Fischer-Tropsch synthesis

International audienc

Selective biosorption of thorium (IV) from aqueous solutions by ginkgo leaf.

Low-cost biosorbents (ginkgo leaf, osmanthus leaf, banyan leaf, magnolia leaf, holly leaf, walnut shell, and grapefruit peel) were evaluated in the simultaneous removal of La3+, Ce3+, Pr3+, Nd3+, Sm3+, Eu3+, Gd3+, Yb3+, Lu3+, UO22+, Th4+, Y3+, Co2+, Zn2+, Ni2+, and Sr2+ from aqueous solutions. In single metal systems, all adsorbents exhibited good to excellent adsorption capacities toward lanthanides and actinides. In a simulated multicomponent mixed solution study, higher selectivity and efficiency were observed for Th4+ over other metal cations, with ginkgo leaves providing the highest adsorptivity (81.2%) among the seven biosorbents. Through optimization studies, the selectivity of Th4+ biosorption on ginkgo leaf was found to be highly pH-dependent, with optimum Th4+ removal observed at pH 4. Th4+ adsorption was found to proceed rapidly with an equilibrium time of 120 min and conform to pseudo-second-order kinetics. The Langmuir isotherm model best described Th4+ biosorption, with a maximum monolayer adsorption capacity of 103.8 mg g-1. Thermodynamic calculations indicated that Th4+ biosorption was spontaneous and endothermic. Furthermore, the physical and chemical properties of the adsorbent were determined by scanning electron microscopy, Brunauer-Emmett-Teller, X-ray powder diffraction, and Fourier transform infrared analysis. The biosorption of Th from a real sample (monazite mineral) was studied and an efficiency of 90.4% was achieved from nitric acid at pH 4 using ginkgo leaves

Identification of Two CDK5R1-Related Subtypes and Characterization of Immune Infiltrates in Alzheimer’s Disease Based on an Integrated Bioinformatics Analysis

Background. Alzheimer’s disease (AD) is a neurodegenerative disorder and the major cause of senile dementia. The Reelin pathway has been involved in both learning and AD pathogenesis. However, the specific Reelin-related gene signature during the pathological process remains unknown. Methods. Reelin-related gene (CDK5R1) expression was analyzed using the GEO datasets. The relevant genes of CDK5R1 were identified using differential expression analysis and weighted gene correlation network analysis (WGCNA) based on the GSE43850 dataset. ConsensusClusterPlus analysis was applied to identify subtypes (C1 and C2) of AD. The CIBERSORT algorithm was used to assess the immune cell infiltration between the two AD subtypes. Results. CDK5R1 was downregulated in AD. 244 differentially expressed CDK5R1-related genes (DECRGs) between the two subgroups were mainly enriched in GABAergic synapse, neuroactive ligand-receptor interaction, synapse organization, neurotransmitter transport, etc. Furthermore, the GSVA results indicated that immune-related pathways were significantly enriched in the C1 subgroup. Interestingly, 10 Reelin pathway-related genes (CRK, DAB2IP, LRP8, RELN, STAT5A, CDK5, CDK5R1, DAB1, FYN, and SH3KBP1) were abnormally expressed between the two subgroups. The proportion of T cell gamma delta, monocytes, macrophage M2, and dendritic cells activated decreased from C1 to C2, while the proportion of plasma cells, T cell follicular helper, and NK cells activated increased. Conclusion. Two CDK5R1-related subtypes of AD were identified, helping us to better understand the role of CDK5R1 in the pathological process of AD

Design of mesoporous ZnCoSiOx hollow nanoreactors with specific spatial distribution of metal species for selective CO2 hydrogenation

In heterogeneous catalysis, the precise placement of active components to perform unique functions in cooperation with each other is a tremendous challenge. The migration of matter on micro/nano-scale caused by diffusion is a promising pathway for design of catalytic nanoreactors with precise active sites location and controllable microenvironment through compartmentalization and confinement effects. Herein, we report two categories of mesoporous ZnCoSiOx&nbsp;hollow nanoreactors with different metal distributions and microenvironment engineered by the diffusion behavior of metal species in confined nanospace. Double-shelled hollow structures with well-distributed metal species were obtained by adopting core@shell structured ZnCo-zeolitic imidazolate framework (ZIF)@SiO2&nbsp;as a template and employing three stages of hydrothermal treatment including the decomposition of ZIF, diffusion of metal species into the silica shell, and Ostwald ripening. Additionally, the formation of yolk@shell structure with a collective (Zn-Co) metal oxide as the yolk was achieved by direct pyrolysis of ZnCo-ZIF@SiO2. In CO2&nbsp;hydrogenation, ZnCoSiOx&nbsp;with double-shelled hollow structures and yolk@shell structures respectively afford CO and CH4&nbsp;as main product, which is related with different dispersion and location of active sites in the two catalysts. This study provides an efficient method for the synthesis of catalytic nanoreactors on the basis of insights of the atomic diffusion in confined space at the mesoscale.</p