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Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca 2+ entry (SOCE) is the predominant Ca 2+ entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca 2+ sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.

Nanometer-thick passive films on metals usually impart remarkable resistance to general corrosion but are susceptible to localized attack in certain aggressive media, leading to material failure with pronounced adverse economic and safety consequences. Over the past decades, several classic theories have been proposed and accepted, based on hypotheses and theoretical models, and oftentimes, not sufficiently nor directly corroborated by experimental evidence. Here we show experimental results on the structure of the passive film formed on a FeCr 15 Ni 15 single crystal in chloride-free and chloride-containing media. We use aberration-corrected transmission electron microscopy to directly capture the chloride ion accumulation at the metal/film interface, lattice expansion on the metal side, undulations at the interface, and structural inhomogeneity on the film side, most of which had previously been rejected by existing models. This work unmasks, at the atomic scale, the mechanism of chloride-induced passivity breakdown that is known to occur in various metallic materials. Collecting experimental evidence of chloride ion attack on protective passive metallic films due to corrosion remains challenging. Here, the authors show that the boundaries between nanocrystals and amorphous regions in the passive film ease chloride transport even as they do not coincide with areas of high chloride concentration.

In Alzheimer’s disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer’s patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.

Abstract Crack repair is crucial since cracks are the main cause for the decreased service life of concrete structures. An original and promising way to repair cracks is to pre-incorporate healing agents inside the concrete matrix to heal cracks the moment they appear. Thus, the concrete obtains self-healing properties. The goal of our research is to apply bacterially precipitated CaCO3 to heal cracks in concrete since the microbial calcium carbonate is more compatible with the concrete matrix and more environmentally friendly relative to the normally used polymeric materials. Diatomaceous earth (DE) was used in this study to protect bacteria from the high-pH environment of concrete. The experimental results showed that DE had a very good protective effect for bacteria. DE immobilized bacteria had much higher ureolytic activity (12–17 g/l urea was decomposed within 3 days) than that of un-immobilized bacteria (less than 1 g/l urea was decomposed within the same time span) in cement slurry. The optimal concentration of DE for immobilization was 60% (w/v, weight of DE/volume of bacterial suspension). Self-healing in cracked specimens was visualized under light microscopy. The images showed that cracks with a width ranging from 0.15 to 0.17 mm in the specimens containing DE immobilized bacteria were completely filled by the precipitation. Scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) were used to characterize the precipitation around the crack wall, which was confirmed to be calcium carbonate. The result from a capillary water absorption test showed that the specimens with DE immobilized bacteria had the lowest water absorption (30% of the reference ones), which indicated that the precipitation inside the cracks increased the water penetration resistance of the cracked specimens.

The amyloid-β protein (Aβ) protein plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD). It is believed that Aβ deposited in the brain originates from the brain tissue itself. However, Aβ is generated in both brain and peripheral tissues. Whether circulating Aβ contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aβ originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aβ plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aβ accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aβ can enter the brain, form the Aβ-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aβ metabolism in both the brain and the periphery.

Synthesizing isotopes located far away from the line of β -stability is the core research topic in nuclear physics. However, it remains a challenge due to their tiny production cross sections and short half-lives. Here, we report on the observation of a very neutron-deficient isotope 210 Pa produced via the fusion-evaporation reaction 175 Lu( 40 Ca, 5n) 210 Pa at a newly constructed China Accelerator Facility for Superheavy Elements. The measured α -particle energy of E α = 8284(15) keV and half-life of T 1 / 2 = 6 . 0 − 1.1 + 1.5 ms of 210 Pa allow us to extend the α -decay systematics and test the predictive power of theoretical models for heavy nuclei near the proton drip line. Based on its unhindered α -decay character, the spin and parity of 210 Pa is proposed to be (3 + ), supported by the large-scale shell model and cranked shell model calculations. This isotope is discovered with substantial statics within  ∼ 3 days using intensive 2 p μ A beam, demonstrating the tremendous capability of the facility for the study of heavy and superheavy nuclei. The study of isotopes away from the beta stability valley is crucial for the understanding of nuclear structure, especially for neutron-deficient heavy nuclei. Here, the authors report the observation of the alpha-decay isotope 210-protactinium (Pa), extending the alpha-decay systematics of underexplored regions of the nuclides chart.

Nanometer-thick passive films, which impart superior corrosion resistance to metals, are degraded in long-term service; they are also susceptible to chloride-induced localized attack. Here we show, by engineering crystallographic configurations upon metal matrices adjacent to their passive films, we obtain great enhancement of corrosion resistance of FeCr15Ni15 single crystal in sulphuric acid, with activation time up to two orders of magnitude longer than that of the non-engineered counterparts. Meanwhile, engineering crystallography decreases the passive current density and shifts the pitting potential to noble values. Applying anodic polarizations under a transpassivation potential, we make the metal matrices underneath the transpassive films highly uneven with {111}-terminated configurations, which is responsible for the enhancement of corrosion resistance. The transpassivation strategy also works in the commercial stainless steels where both grain interior and grain boundaries are rebuilt into the low-energy configurations. Our results demonstrate a technological implication in the pretreatment process of anti-corrosion engineering. Passive films on metal surfaces provide better corrosion resistance, but they can degrade in long-term service. Here the authors demonstrate a strategy to engineer crystallographic configuration at the metal/film interface to further improve corrosion resistance.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death, reflecting the need for better understanding the oncogenesis, and developing new diagnostic and therapeutic targets for the malignancy. Emerging evidence suggests that small nucleolar RNAs (snoRNAs) have malfunctioning roles in tumorigenesis. Our recent study demonstrated that small nucleolar RNA 42 ( SNORA42 ) was overexpressed in lung tumors. Here, we investigate the role of SNORA42 in tumorigenesis of NSCLC. We simultaneously assess genomic dosages and expression levels of SNORA42 and its host gene, KIAA0907 , in 10 NSCLC cell lines and a human bronchial epithelial cell line. We then determine in vitro functional significance of SNORA42 in lung cancer cell lines through gain- and loss-of-function analyses. We also inoculate cancer cells with SNORA42-siRNA into mice through either tail vein or subcutaneous injection. We finally evaluate expression level of SNORA42 on frozen surgically resected lung tumor tissues of 64 patients with stage I NSCLC by using quantitative reverse transcriptase PCR assay. Genomic amplification and associated high expression of SNORA42 rather than KIAA0907 are frequently observed in lung cancer cells, suggesting that SNORA42 overexpression is activated by its genomic amplification. SNORA42 knockdown in NSCLC cells inhibits in vitro and in vivo tumorigenicity, whereas enforced SNORA42 expression in bronchial epitheliums increases cell growth and colony formation. Such pleiotropy of SNORA42 suppression could be achieved at least partially through increased apoptosis of NSCLC cells in a p53-dependent manner. SNORA42 expression in lung tumor tissue specimens is inversely correlated with survival of NSCLC patients. Therefore, SNORA42 activation could have an oncogenic role in lung tumorigenesis and provide potential diagnostic and therapeutic targets for the malignancy.

In this paper, an initial pressure adjustable explosion vessel was developed, and the effect of negative pressure, positive pressure (0.2–1.8 atm) different initial ambient pressure on the explosive shock wave generated by the explosion of explosives was studied. The relationships between the specific impulse, shock wave velocity, the amount of explosive gas products and the ambient pressure were analyzed for different initial pressure environments. It was found that: the overpressure of the blast shock wave decreases with the initial ambient pressure of the explosion, and there exists a negative pressure environment with a dramatic pressure decrease near 0.6 atm, defined as the super-sensitive negative pressure P cr . The propagation velocity of an explosive wave increases with a decrease in the ambient pressure, and the propagation velocity at a pressure of 1.8 atm is four times less than the velocity at a pressure of 0.2 atm. The production of explosive gas products did not change. The greater the initial pressure of the environment where the explosive is located, the smaller the ratio of the gas generated by the explosion to the initial force gas in the explosion vessel is, and the greater the impact on the propagation of shock waves is. The maximum attenuation of the first specific impulse i 1 is 72.97% and the maximum attenuation of the second specific impulse i 2 is 72.39%. The experiments provide reference data for high-altitude military confrontation, high-altitude weapons and ammunition development, and deep-earth protection engineering.

Although elastic strains, particularly inhomogeneous strains, are able to tune, enhance or create novel properties of some nanoscale functional materials, potential devices dominated by inhomogeneous strains have not been achieved so far. Here we report a fabrication of inhomogeneous strains with a linear gradient as giant as 10 6 per metre, featuring an extremely lower elastic energy cost compared with a uniformly strained state. The present strain gradient, resulting from the disclinations in the BiFeO 3 nanostructures array grown on LaAlO 3 substrates via a high deposition flux, induces a polarization of several microcoulomb per square centimetre. It leads to a large built-in electric field of several megavoltage per metre, and gives rise to a large enhancement of solar absorption. Our results indicate that it is possible to build up large-scale strain-dominated nanostructures with exotic properties, which in turn could be useful in the development of novel devices for electromechanical and photoelectric applications. Inherent elastic strains are useful to tune the physical properties of functional materials but it is difficult to build. Here, Tang et al . report a fabrication of inhomogeneous strains with a linear gradient as giant as 10 6 per meter in a BiFeO 3 nanostructure array grown on a LaAlO 3 substrate.