Granular materials such as sand, powders and foams are ubiquitous in daily life and in industrial and geotechnical applications. These disordered systems form stable structures when unperturbed, but in the presence of external influences such as tapping or shear they 'relax', becoming fluid in nature. It is often assumed that the relaxation dynamics of granular systems is similar to that of thermal glass-forming systems. However, so far it has not been possible to determine experimentally the dynamic properties of three-dimensional granular systems at the particle level. This lack of experimental data, combined with the fact that the motion of granular particles involves friction (whereas the motion of particles in thermal glass-forming systems does not), means that an accurate description of the relaxation dynamics of granular materials is lacking. Here we use X-ray tomography to determine the microscale relaxation dynamics of hard granular ellipsoids subject to an oscillatory shear. We find that the distribution of the displacements of the ellipsoids is well described by a Gumbel law (which is similar to a Gaussian distribution for small displacements but has a heavier tail for larger displacements), with a shape parameter that is independent of the amplitude of the shear strain and of the time. Despite this universality, the mean squared displacement of an individual ellipsoid follows a power law as a function of time, with an exponent that does depend on the strain amplitude and time. We argue that these results are related to microscale relaxation mechanisms that involve friction and memory effects (whereby the motion of an ellipsoid at a given point in time depends on its previous motion). Our observations demonstrate that, at the particle level, the dynamic behaviour of granular systems is qualitatively different from that of thermal glass-forming systems, and is instead more similar to that of complex fluids. We conclude that granular materials can relax even when the driving strain is weak.

Glass transition is accompanied by a rapid growth of the structural relaxation time and a concomitant decrease of configurational entropy. It remains unclear whether the transition has a thermodynamic origin, and whether the dynamic arrest is associated with the growth of a certain static order. Using granular packing as a model hard-sphere glass, we show the glass transition as a thermodynamic phase transition with a ‘hidden' polytetrahedral order. This polytetrahedral order is spatially correlated with the slow dynamics. It is geometrically frustrated and has a peculiar fractal dimension. Additionally, as the packing fraction increases, its growth follows an entropy-driven nucleation process, similar to that of the random first-order transition theory. Our study essentially identifies a long-sought-after structural glass order in hard-sphere glasses.

Breast carcinoma is the most common malignant tumor in females, and lymph node (LN) status is one of the most important prognostic factors in patients with breast cancer. MiRNAs have been shown to have important role in oncogenesis, invasion, and metastasis via epigenetic posttranscriptional gene regulation. However, lymphatic metastasis-related miRNAs of breast cancer has not been well documented. The aim of this study was to identify and evaluate miRNAs related to breast cancer LN metastasis and to explore the clinical significance of the differentially expressed miRNAs in patients with breast cancer. The expression of miRNAs in patients with primary breast cancer with LN metastasis and that without LN metastases was compared by miRNA microarray. We further validated the miRNAs (miR-185-5p, miR-339-5p, miR-542-5p, and miR-3923) between LN (n 5 31) and nonlymph node (NLN; n 5 42) group using real-time reverse transcriptase polymerase chain reaction. Furthermore, the relationship between miRNA expression and clinical pathological features was analyzed. The miRNA microarray initially identified that eight miRNAs (miR-206, miR-3923, miR-181a, miR-92a, miR-421, miR-339-5p, miR-3196, and miR-29b) were downregulated in LN metastasis group, whereas five miRNAs (miR-542-5p, miR-200a, miR-564, miR-451, miR-30c, miR-200b, miR-191-3p, miR-142-5p, and miR-185-5p) were upregulated in LN group when compared with those in NLN group. In the validation cohort, the expression levels of miR-185-5p and miR-542-5p were significantly expressed higher in LN group (P 5 0.002 and P 5 0.001, respectively), and the expression levels of miR-339-5p and miR-3923 were significantly expressed lower in LN group (P 5 0.001 and P 5 0.001, respectively). Our results indicate the potential role of miR-185-5p, miR-542-5p, miR-339-5p, and miR-3923 in predicting metastasis to the LN and prognosis in breast cancers.

The dissipation behaviors of the two enantiomers of the organophosphorus pesticide malathion (MA) in environment samples were elucidated using a normal-phase high-performance liquid chromatography with a cellulose-tris(3,5-dimethylphenylcarbamate) (CDMPC) chiral column. A validated chiral residue analysis method in soil and water was established; the average recoveries for the two enantiomers were 88-102% in soil and 81-99% in water. Racemic and enantiopure R-(+)- and S-(-)-MA were incubated in five soil and water systems. The results of the degradation of racemate in all of the environment samples showed the inactive S-(-)-enantiomer degraded more rapidly than the active R-(+)-enantiomer, resulting in a relative enrichment of the R-form. Moreover, when the enantiopure S-(-)- and R-(+)-MA were incubated in three well-chosen soil and water samples, respectively, inversion from one enantiomer to another was found, indicating that using the optically pure enantiomer will not help to increase the bioactivity and reduce the environmental pollution.

The cinobufagin (CB) has a broad spectrum of cytotoxicity to inhibit cell proliferation of various human cancer cell lines, but the molecular mechanisms still remain elusive. Here we observed that CB inhibited the cell proliferation and tumor growth, but induced cell cycle arrest and apoptosis in a dose-dependent manner in non-small cell lung cancer (NSCLC) cells. Treatment with CB significantly increased the reactive oxygen species but decreased the mitochondrial membrane potential in NSCLC cells. These effects were markedly blocked when the cells were pretreated with N-acetylcysteine, a specific reactive oxygen species inhibitor. Furthermore, treatment with CB induced the expression of BAX but reduced that of BCL-2, BCL-XL and MCL-1, leading to an activation of caspase-3, chromatin condensation and DNA degradation in order to induce programmed cell death in NSCLC cells. In addition, treatment with CB reduced the expressions of p-AKTT308 and p-AKTS473 and inhibited the AKT/mTOR signaling pathway in NSCLC cells in a time-dependent manner. Our results suggest that CB inhibits tumor growth by inducing intrinsic apoptosis through the AKT signaling pathway in NSCLC cells.

To date, there is still no general consensus on the fundamental principle that governs glass transition. Colloidal suspensions are ordinarily utilized as model systems to study the dynamical arrest mechanisms in glass or gels. Here, we tackle the problem using athermal granular particles. Slow dynamics and structural evolution of granular packing upon tapping are monitored by fast X-ray tomography. When the packing are wet and short-range attractive interactions exist, we find a large amount of locally favoured structures with fivefold symmetry, which bear great structural similarity to colloidal gels. In addition, these structures are almost absent in dry packing with similar packing fractions. The study leads strong support for the geometrical frustration mechanism for dynamic arrest in both thermal and athermal systems with attractive interactions. It also suggests nontrivial structural mechanism, if exists, for dynamic arrest in systems with purely repulsive interactions.

Abstract. Distant migration and invasion is the main contributor to the death of cancer patients and miRNAs have been implicated in these processes. In the present study, we identified the role of microRNA-21 (miR-21) in hepatocellular carcinoma (HCC) migration and invasion and determined its underlying regulatory mechanism. miR-21 was significantly upregulated in HCC tissues and cell lines, compared with adjacent non-tumor tissues and normal hepatic cells. miR-21 upregulation was associated with the capacity of tumor migration and invasion in HCC. The expression level of miR-21 was inversely correlated with the protein expression level of a previously identified target gene, programmed cell death 4 (PDCD4). In HepG2 cells, inhibition of miR-21 expression repressed cell migration and invasion by upregulating both mRNA and protein levels of PDCD4 and downregulating key downstream signaling pathway molecules, including phosphoc-Jun, matrix metalloproteinases (MMP)-2 and MMP-9. Moreover, activation protein 1 (AP-1) could directly activate miR-21 transcription. Taken together, these results provide evidence that miR-21 promotes migration and invasion in HCC through the miR-21-PDCD4-AP-1 feedback loop, suggesting that targeting the miR-21-PDCD4-AP-1 loop may represent a promising strategy in the management of HCC.

It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A hydrolase (LTAH) mediates opposing proinflammatory and anti-inflammatory activities, through the generation of leukotriene B (LTB) and degradation of proneutrophilic matrikine Pro-Gly-Pro (PGP), respectively. We show that abrogation of LTB signaling ameliorated inflammation and airway hyperresponsiveness (AHR) in a murine asthma model, yet global loss of LTAH exacerbated AHR, despite the absence of LTB This exacerbated AHR was attributable to a neutrophil-independent capacity of PGP to promote pathological airway epithelial remodeling. Thus, we demonstrate a disconnect between airway inflammation and AHR and the ability of a matrikine to promote an epithelial remodeling phenotype that negatively affects lung function. Subsequently, we show that substantial quantities of PGP are detectable in the sputum of moderate-severe asthmatics in two distinct cohorts of patients. These studies have implications for our understanding of remodeling phenotypes in asthma and may rationalize the failure of LTAH inhibitors in the clinic.