TRPC1 participates in the HSV-1 infection process by facilitating viral entry

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1-induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1-induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1-infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.Fil: He, DongXu. Jiangnan University; ChinaFil: Mao, AiQin. Jiangnan University; ChinaFil: Li, YouRan. Jiangnan University; ChinaFil: Tam, SiuCheung. Chinese University Of Hong Kong; Hong KongFil: Zheng, YongTang. Kunming Institute Of Zoology Chinese Academy Of Sciences; ChinaFil: Yao, XiaoQiang. Chinese University Of Hong Kong; Hong KongFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ambudkar, Indu S.. National Institute Of Dental And Craniofacial Research ; Estados UnidosFil: Ma, Xin. Jiangnan University; Chin

Dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus and promotes viral replication leading to enhanced oncolysis in glioblastoma

Targeting reprogrammed energy metabolism such as aerobic glycolysis is a potential strategy for cancer treatment. However, tumors exhibiting low-rate glycolysis or metabolic heterogeneity might be resistant to such treatment. We hypothesized that a therapeutic modality that drove cancer cells to high-rate glycolysis might sensitize cancer cells to interference directed against metabolic flux. In this study, we found that attenuated oncolytic measles virus Edmonston strain (MV-Edm) caused glioblastoma cells to shift to high-rate aerobic glycolysis; this adaptation was blocked by dichloroacetate (DCA), an inhibitor of glycolysis, leading to profound cell death of cancer cells but not of normal cells. DCA enhanced viral replication by mitigating mitochondrial antiviral signaling protein (MAVS)-mediated innate immune responses. In a subcutaneous glioblastoma (GBM) xenograft mouse model, low-dose MV-Edm and DCA significantly inhibited tumor growth in vivo. We found that DCA impaired glycolysis (blocking bioenergetic generation) and enhanced viral replication (increasing bioenergetic consumption), which, in combination, accelerated bioenergetic exhaustion leading to necrotic cell death. Taken together, oncolytic MV-Edm sensitized cancer cells to DCA, and in parallel, DCA promoted viral replication, thus, improving oncolysis. This novel therapeutic approach should be readily incorporated into clinical trials

Interfacial Characterization and Bonding Properties of Copper/Aluminum Clad Sheets Processed by Horizontal Twin-Roll Casting, Multi-Pass Rolling, and Annealing

The copper/aluminum (Cu/Al) clad sheets were produced on a horizontal twin-roll caster and then were multi-pass rolled and annealed. The thickness of the as-cast clad sheet was 8 mm. Rolling was performed with total reductions of 12.5%, 25%, 37.5%, 50%, and 62.5%, separately. The effects of the rolling and annealing processes on the interface and peel strength of the Cu/Al clad sheets were investigated. The evolution of the interface and crack propagation were studied. The interface thickness of the as-cast clad sheet reached 9 μm to 10 μm. The average peel strength (APS) was only 9 N/mm. After multi-pass rolling, the peel strength first slightly increased and then gradually decreased with the increase of the rolling pass number. After annealing, the peel strength remarkably improved. The APS reached 25 N/mm when the rolled thickness was 7 mm. The improvement in the peel strength was due to the following three factors: (1) mechanical locking formed in the Cu/Al direct contact region after rolling, (2) the region of the Al matrix fracture, and (3) mechanical biting from the Cu/Al direct contact region

In-Situ Observation and Analysis of the Evolution of Copper Aluminum Composite Interface

To study the micromorphology and dynamic evolution law of copper aluminum composite interface evolution, ultra-high temperature laser Confocal microscopy (CLSM) was used to observe and analyze the evolution of copper aluminum interface in situ, and then SEM, EDS and other advanced material analysis methods were used to observe the micromorphology of the composite layer, and study the composition of the interface layer and the formation process of the copper aluminum composite interface. The results indicate that the formation of the copper aluminum composite interface layer is mainly related to the mutual diffusion of copper aluminum atoms and the interface reaction between copper and aluminum. The bonding of the copper aluminum composite interface is mainly related to the melting of the metal surface of the interface layer and the mutual diffusion of copper aluminum atoms, which is the main mechanism of the copper aluminum composite interface bonding. The intermetallic compound is mainly Al2Cu. In situ, observation of copper aluminum composite interface shows that there is a clear and relatively flat boundary between copper and the interface layer, while the boundary between aluminum and the interface layer is not straight, which is caused by the difference in thermal expansion coefficient, Lattice constant and hardness between intermetallic compounds and matrix and between intermetallic compounds. At the same time, it was found that there is a certain relationship between the visual changes of the copper aluminum composite interface image and reaction-diffusion migration during in-situ observation using a confocal laser scanning high-temperature microscope. Moreover, under no pressure, the oxide layer and interface inclusions can seriously affect the interface bonding

Effects of Heating Mode and Temperature on the Microstructures, Electrical and Optical Properties of Molybdenum Thin Films

In this paper, molybdenum (Mo) thin films are deposited on soda-lime glass (SLG) substrates by direct current magnetron sputtering and heated in three different modes at different temperatures, including substrate heating, annealing treatment, and both substrate heating and annealing treatment. The effects of heating temperature and heating mode on the structures, morphology, optical and electrical properties of Mo thin films were systematically investigated by X-ray diffraction (XRD), Scanning electron microscopy (SEM), atomic force microscope (AFM) and UV-visible spectrophotometer (UV-vis spectra). It is shown that as the substrate and annealing temperature increase, the crystallinity of Mo thin films is improved, and the grain sizes become bigger. Especially in the mode of both substrate heating and annealing treatment at higher temperature, the obtained Mo thin films show higher crystallinity and conductivity. Moreover, with the increase of substrate and annealing temperature in different heating modes, both the surface compactness of Mo films and the optical reflectance increase correspondingly. Furthermore, the Mo film, prepared at the substrate heating temperature of 400 °C and annealed at 400 °C, showed excellent comprehensive performance, and the resistivity is as low as 1.36 × 10−5 Ω·cm. Using this optimized Mo thin film as an electrode, copper indium gallium selenium (CIGS) solar cells have a maximum photo-conversion efficiency of 12.8%

Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus

ABSTRACT Although apoptotic phenomena have been observed in malignant cells infected by measles virus vaccine strain Edmonston B (MV-Edm), the precise oncolytic mechanisms are poorly defined. In this study we found that MV-Edm induced autophagy and sequestosome 1-mediated mitophagy leading to decreased cytochrome c release, which blocked the pro-apoptotic cascade in non-small cell lung cancer cells (NSCLCs). The decrease of apoptosis by mitophagy favored viral replication. Persistent viral replication sustained by autophagy ultimately resulted in necrotic cell death due to ATP depletion. Importantly, when autophagy was impaired in NSCLCs MVEdm-induced cell death was significantly abrogated despite of increased apoptosis. Taken together, our results define a novel oncolytic mechanism by which mitophagy switches cell death from apoptosis to more efficient necrosis in NSCLCs following MV-Edm infection. This provides a foundation for future improvement of oncolytic virotherapy or antiviral therapy

Alterations in Cortical Thickness and White Matter Integrity in Mild-to-Moderate Communicating Hydrocephalic School-Aged Children Measured by Whole-Brain Cortical Thickness Mapping and DTI

Follow-up observation is required for mild-to-moderate hydrocephalic patients because of the potential damage to brain. However, effects of mild-to-moderate hydrocephalus on gray and white matter remain unclear in vivo. Using structural MRI and diffusion tensor imaging (DTI), current study compared the cortical thickness and white matter integrity between children with mild-to-moderate communicating hydrocephalus and healthy controls. The relationships between cortical changes and intelligence quota were also examined in patients. We found that cortical thickness in the left middle temporal and left rostral middle frontal gyrus was significantly lower in the hydrocephalus group compared with that of controls. Fractional anisotropy in the right corpus callosum body was significantly lower in the hydrocephalus group compared with that of controls. In addition, there was no association of cortical thinning or white matter fractional anisotropy with intelligence quota in either group. Thus, our findings provide clues to that mild-to-moderate hydrocephalus could lead to structural brain deficits especially in the middle temporal and middle frontal gyrus prior to the behavior changes

Effect of deep cryogenic treatment on the microstructure and mechanical properties of Al–Cu–Mg–Ag alloy

Effect of deep cryogenic treatment (DCT) on the aging behavior and tensile properties of Al–Cu–Mg–Ag alloy was investigated. Results show that DCT of Al–Cu–Mg–Ag alloy produces plastic deformation of about 0.2% and high-density dislocations in the α-Al matrix. These dislocations cut second-phase particles in under-aged Al–Cu–Mg–Ag alloy, resulting in a decrease in the size of Ω precipitates and an increase in the number density, thereby weakening the adverse effects of DCT on the tensile properties of the alloy

Effects of Thickness Ratios and Sputtering Mode on the Structural, Electrical and Optical Properties of Bilayer Molybdenum Thin Films

In this paper, the bilayer Mo films with a constant thickness were deposited by direct current and direct current (DC/DC), radio frequency and direct current mixed (RF/DC) magnetron sputtering, respectively. Changing thickness ratios of bottom layer to total thickness of bilayer film in the range from 10% to 50%, ten types of bilayer Mo thin films were deposited. The purpose is to improve the photo-conversion efficiency of Cu(In, Ga)Se2(CIGS) solar cells by changing the sputtering modes and thickness ratio. The microstructures, electrical and optical properties of the bilayer Mo thin films were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), atomic force microscope (AFM), Hall Effect measurement system, ultraviolet-visible spectrophotometer (UV-vis) and four-point probe resistance system. It was found that with the increase of thickness ratios in two sputtering modes, both the crystallinity and grain size decreased, while the reflectance increased. Especially, when the thickness ratio was 40%, the resistivity of Mo film prepared in RF/DC mode was as low as 3.365 ×10-5 Ω·cm and the highest reflectance was above 60%. Using this optimized Mo thin film as electrode, the highest photo-conversion efficiency for the CIGS thin film solar cells was as high as 11.5%