Threshold current density for diffusion-controlled stability of electrolytic surface nanobubbles.

Understanding the stability mechanism of surface micro/nanobubbles adhered to gas-evolving electrodes is essential for improving the efficiency of water electrolysis, which is known to be hindered by the bubble coverage on electrodes. Using molecular simulations, the diffusion-controlled evolution of single electrolytic nanobubbles on wettability-patterned nanoelectrodes is investigated. These nanoelectrodes feature hydrophobic islands as preferential nucleation sites and allow the growth of nanobubbles in the pinning mode. In these simulations, a threshold current density distinguishing stable nanobubbles from unstable nanobubbles is found. When the current density remains below the threshold value, nucleated nanobubbles grow to their equilibrium states, maintaining their nanoscopic size. However, for the current density above the threshold value, nanobubbles undergo unlimited growth and can eventually detach due to buoyancy. Increasing the pinning length of nanobubbles increases the degree of nanobubble instability. By connecting the current density with the local gas oversaturation, an extension of the stability theory for surface nanobubbles [Lohse and Zhang, Phys. Rev. E 91, 031003(R) (2015)] accurately predicts the nanobubble behavior found in molecular simulations, including equilibrium contact angles and the threshold current density. For larger systems that are not accessible to molecular simulations, continuum numerical simulations with the finite difference method combined with the immersed boundary method are performed, again demonstrating good agreement between numerics and theories.

Spatial population genetics with fluid flow.

The growth and evolution of microbial populations is often subjected to advection by fluid flows in spatially extended environments, with immediate consequences for questions of spatial population genetics in marine ecology, planktonic diversity and origin of life scenarios. Here, we review recent progress made in understanding this rich problem in the simplified setting of two competing genetic microbial strains subjected to fluid flows. As a pedagogical example we focus on antagonsim, i.e., two killer microorganism strains, each secreting toxins that impede the growth of their competitors (competitive exclusion), in the presence of stationary fluid flows. By solving two coupled reaction-diffusion equations that include advection by simple steady cellular flows composed of characteristic flow motifs in two dimensions (2D), we show how local flow shear and compressibility effects can interact with selective advantage to have a dramatic influence on genetic competition and fixation in spatially distributed populations. We analyze several 1D and 2D flow geometries including sources, sinks, vortices and saddles, and show how simple analytical models of the dynamics of the genetic interface can be used to shed light on the nucleation, coexistence and flow-driven instabilities of genetic drops. By exploiting an analogy with phase separation with nonconserved order parameters, we uncover how thesegeneticdrops harness fluid flows for novel evolutionary strategies, even in the presence of number fluctuations, as confirmed by agent-based simulations as well.

Supergravitational turbulent thermal convection.

High-Rayleigh number convective turbulence is ubiquitous in many natural phenomena and in industries, such as atmospheric circulations, oceanic flows, flows in the fluid core of planets, and energy generations. In this work, we present a novel approach to boost the Rayleigh number in thermal convection by exploiting centrifugal acceleration and rapidly rotating a cylindrical annulus to reach an effective gravity of 60 times Earth's gravity. We show that in the regime where the Coriolis effect is strong, the scaling exponent of Nusselt number versus Rayleigh number exceeds one-third once the Rayleigh number is large enough. The convective rolls revolve in prograde direction, signifying the emergence of zonal flow. The present findings open a new avenue on the exploration of high-Rayleigh number turbulent thermal convection and will improve the understanding of the flow dynamics and heat transfer processes in geophysical and astrophysical flows and other strongly rotating systems.

Growth hormone receptor promotes breast cancer progression via the BRAF/MEK/ERK signaling pathway.

Growth hormone receptor (GHR), a member of the class I cytokine receptor family, plays key roles in cancer progression. Recently, GHR has been reported to be associated with breast cancer development, but the molecular mechanism of GHR in this malignancy is not fully understood. To investigate this issue, we stably inhibited GHR in breast cancer cell lines, which were observed to reduce cell proliferation, tumor growth and induction of apoptosis, and arrest the cell-cycle arrest at the G1-S phase transition. In addition, GHR silencing suppressed the protein levels of B-Raf proto-oncogene, serine/threonine kinase (BRAF), Mitogen-activated protein kinase kinase (MEK) and Extracellular regulated protein kinases (ERK). These findings suggest that GHR may mediate breast cell progression and apoptosis through control of the cell cycle via the BRAF/MEK/ERK signaling pathway.

A novel cis antisense RNA AsfD promotes Salmonella enterica serovar Typhi motility and biofilm formation.

Bacterial non-coding RNAs (ncRNAs) can participate in multiple biological processes, including motility, biofilm formation, and virulence. Using high-throughput sequencing and transcriptome analysis of Salmonella enterica serovar Typhi (S. Typhi), we identified a novel antisense RNA located at the opposite strand of the flhDC operon. In this study, a northern blot and qRT-PCR were used to confirm the expression of this newfound antisense RNA in S. Typhi. Moreover, 5' RACE and 3' RT-PCR were performed to reveal the molecular characteristics of the antisense RNA, which was 2079 nt - 2179 nt in length, covered the entire flhDC operon sequence, and termed AsfD. The level of AsfD expression was higher during the stationary phase of S. Typhi and activated by the regulators, OmpR and Fis. When AsfD was overexpressed, the level of flagellar gene flhDC transcription increased; moreover, the level of fliA and fljB expression, as well as the motility and biofilm formation of S. Typhi were also enhanced. The results of this study suggest that AsfD is likely to enhance the motility and biofilm formation of S. Typhi by up-regulating flhDC expression.

Astrocyte-derived fatty acid-binding protein 7 protects blood-brain barrier integrity through a caveolin-1/MMP signaling pathway following traumatic brain injury.

The astrocyte-endothelial cell interaction is crucial for normal brain homeostasis and blood-brain barrier (BBB) disruption in pathological conditions. However, the mechanism by which astrocytes control BBB integrity, especially after traumatic brain injury (TBI), remains unclear. Here, we present evidence that astrocyte-derived fatty acid-binding protein 7 (FABP7), a differentiation- and migration-associated molecule, may function as a modulator of BBB permeability in a rat weight-drop model of TBI. Immunohistochemical analysis revealed that TBI induced increased expression of FABP7 in astrocytes, accompanied by caveolin-1 (Cav-1) upregulation in endothelial cells. Administration of recombinant FABP7 significantly ameliorated TBI-induced neurological deficits, brain edema, and BBB permeability, concomitant with upregulation of endothelial Cav-1 and tight junction protein expression, while FABP7 knockdown resulted in the opposite effects. Furthermore, pretreatment with daidzein, a specific inhibitor of Cav-1, reversed the inhibitory effects of recombinant FABP7 on matrix metalloproteinase (MMP)-2/9 expression and abolished its BBB protection after TBI. Altogether, these findings suggest that astrocyte-derived FABP7 upregulation may represent an endogenous protective response to BBB disruption partly mediated through a Cav-1/MMP signaling pathway following TBI.

Pharmacological inhibition of USP7 promotes antitumor immunity and contributes to colon cancer therapy.

BACKGROUND: Effectiveness of clinical therapy such as chemotherapy for solid tumors is limited by acquired drug resistance and side effects. Available antitumor immunity methods showed promising prospect of cancer therapy. However, more drug targets for boosting antitumor immunity still need to be explored and selective and effective compounds are yet to be developed. PURPOSE: To study the effect and possible mechanism of compound P5091, a selective USP7 inhibitor, on CT26 xenografts growth in mice. MATERIALS AND METHODS: CT26 xenografts model was employed to examine the anti-tumor effect of P5091. RT-PCR and ELISA analysis were used to detect the level of IFN-γ, TNF-α and IL-10 in tumor tissue and serum, respectively. IFN-γ expression in CD4+ and CD8+ T cells was analyzed by intracellular stain. The level of FOXP3 in Treg cells was confirmed by intracellular stain and western blotting. RESULTS: Compound P5091, a selective USP7 inhibitor, was found to inhibit CT26 xenografts growth in mice, which is comparable to the effect of Anti-PD-1 antibody. RT-PCR analysis showed that P5091 treatment decreased IL-10 mRNA level in tumor tissue while elevated mRNA level of IFN-γ and TNF-α. Moreover, ELISA analysis manifested decreased of IL-10 and elevation of IFN-γ and TNF-α in serum from tumor bearing mice. Intracellular stain showed increased IFN-g expression both in CD4+ and CD8+ T cells after P5091 treatment. Furthermore, P5091 treatment caused FOXP3 loss in Treg cells decreased the proportion of Treg cells in tumor bearing mice. CONCLUSION: Our study here showed that P5091 may be a candidate for cancer immunotherapy.

Coffee and tea consumption and the risk for subarachnoid hemorrhage: A meta-analysis.

OBJECTIVES: Reports on the association between coffee or tea consumption and subarachnoid hemorrhage (SAH) risk are inconsistent. The aim of this study was to determine if an association exists between consumption of coffee or tea and the risk for SAH. METHODS: A random-effects model was used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity among studies was assessed using the statistics Cochran's Q and I2. Seven studies on coffee consumption and five on tea consumption were included in the meta-analysis. RESULTS: The pooled RRs of SAH for the highest versus the lowest categories of coffee and tea consumption were 1.31 (95% CI, 0.84-2.05) and 0.83 (95% CI, 0.65-1.08), respectively. There was evidence of heterogeneity among studies of coffee consumption (Pheterogeneity = 0.002, I2 = 71.7%) but not among studies of tea consumption (Pheterogeneity = 0.34, I2 = 11.3%). Omitting one study that substantially contributed to the heterogeneity among studies of coffee consumption yielded a pooled RR of 1.51 (95% CI, 1.10-2.06). Dose-response analysis showed that the summary RRs of SAH for an increase of one cup of coffee and tea consumption per day were 1.00 (95% CI, 0.96-1.04) and 0.97 (95% CI, 0.85-1.11), respectively. There was no evidence of publication bias. CONCLUSION: Our meta-analysis of current evidence does not support an association between the consumption of coffee or tea and SAH risk. Further studies with prospective designs that control for important confounders and provide sufficient data for dose-response analysis are warranted.

Rough-wall turbulent Taylor-Couette flow: The effect of the rib height.

In this study, we combine experiments and direct numerical simulations to investigate the effects of the height of transverse ribs at the walls on both global and local flow properties in turbulent Taylor-Couette flow. We create rib roughness by attaching up to 6 axial obstacles to the surfaces of the cylinders over an extensive range of rib heights, up to blockages of 25% of the gap width. In the asymptotic ultimate regime, where the transport is independent of viscosity, we emperically find that the prefactor of the [Formula: see text] scaling (corresponding to the drag coefficient [Formula: see text] being constant) scales with the number of ribs [Formula: see text] and by the rib height [Formula: see text]. The physical mechanism behind this is that the dominant contribution to the torque originates from the pressure forces acting on the rib which scale with the rib height. The measured scaling relation of [Formula: see text] is slightly smaller than the expected [Formula: see text] scaling, presumably because the ribs cannot be regarded as completely isolated but interact. In the counter-rotating regime with smooth walls, the momentum transport is increased by turbulent Taylor vortices. We find that also in the presence of transverse ribs these vortices persist. In the counter-rotating regime, even for large roughness heights, the momentum transport is enhanced by these vortices.

Tumor necrosis factor-α, interleukin-8 and eosinophil cationic protein as serum markers of glucocorticoid efficacy in the treatment of bronchial asthma.

BACKGROUND: Bronchial asthma (BA) is a common chronic respiratory disease that has exhibited a rising global incidence in recent years. Glucocorticoids are used for the treatment of BA. Emerging evidence has demonstrated the roles of tumor necrosis factor (TNF-α), interleukin-8 (IL-8) and eosinophil cationic protein (ECP) in BA. The present study investigated whether TNF-α, IL-8 and ECP were associated with the clinical stages and severity of BA and the efficacy of glucocorticoids in the treatment of BA. METHODS: A total of 199 patients with BA and 174 healthy individuals were included in this study. Patients with BA underwent glucocorticoid treatment, and the TNF-α, IL-8 and ECP levels and lung functions of the subjects were measured. The correlations of the TNF-α, IL-8 and ECP levels with BA severity, clinical staging and lung functions were assessed. We investigated whether the TNF-α, IL-8 and ECP levels aided in evaluating the efficacy of using glucocorticoids for the treatment of BA. RESULTS: TNF-α, IL-8 and ECP exhibited high levels in patients with BA, and glucocorticoid treatment notably decreased these levels. The TNF-α, IL-8 and ECP levels were positively correlated with the clinical stages and severity of BA and negatively correlated with lung function. TNF-α, IL-8 and ECP can be used as serum markers to predict the efficacy of glucocorticoids in the treatment of BA. CONCLUSION: The key findings of this study collectively support a role for TNF-α, IL-8 and ECP in BA development, and TNF-α, IL-8 and ECP can be used as serum markers of glucocorticoid efficacy in BA.

Flutter to tumble transition of buoyant spheres triggered by rotational inertia changes.

Heavy particles sink straight in water, while buoyant bubbles and spheres may zigzag or spiral as they rise. The precise conditions that trigger such path-instabilities are still not completely understood. For a buoyant rising sphere, two parameters are believed to govern the development of unsteady dynamics: the particle's density relative to the fluid, and its Galileo number. Consequently, with these parameters specified, the opportunities for variation in particle dynamics appear limited. In contrast to this picture, here we demonstrate that vigorous path-oscillations can be triggered by modulating a spherical particle's moment of inertia (MoI). For a buoyant sphere rising in a turbulent flow, MoI reduction triggers a tumble-flutter transition, while in quiescent liquid, it induces a modification of the sphere wake resulting in large-amplitude path-oscillations. The present finding opens the door for control of particle path- and wake-instabilities, with potential for enhanced mixing and heat transfer in particle-laden and dispersed multiphase environments.

Prenatal maternal stress induces visceral hypersensitivity of adult rat offspring through activation of cystathionine-ß-synthase signaling in primary sensory neurons.

Irritable bowel syndrome is a disorder of unknown etiology characterized by widespread, chronic abdominal pain associated with altered bowel movements. Increasing amounts of evidence indicate that stressors presented during gestational periods could have long-term effects on the offspring's tissue structure and function, which may predispose to gastrointestinal diseases. The aim of the present study is to determine whether prenatal maternal stressis a adverse factor affecting gastrointestinal sensitivity and to investigate possible mechanisms underlying prenatal maternal stress-induced visceral hypersensitivity in adult offspring. Prenatal maternal stress was induced in pregnant Sprague-Dawley rats by exposure to heterotypic intermitent stress from gestational day 7 to delivery. Prenatal maternal stress significantly increased visceromotor response to colorectal distention in adult offspring from the age of 6 weeks to 10 weeks. Prenatal maternal stress also enhanced neuronal excitability including depolarization of resting membrane potentials, reduction in rheobase, and an increase in the number of action potentials evoked by 2× and 3× rheobase current stimultion of colon-specific dorsal root ganglion neurons. Prenatal maternal stress remarkably enhanced expression of cystathionine-ß-synthase and Nav1.7 in T13-L2 thoracolumbar dorsal root ganglions both at protein and mRNA levels. Intraperitoneal injection of aminooxyacetic acid, an inhibitor of cystathionine-ß-synthase, attenuated prenatal maternal stress-induced visceral hypersensitivity in a dose-dependent manner. A consecutive seven-day administration of aminooxyacetic acid reversed the hyperexcitability of colon-specific dorsal root ganglion neurons and markedly reduced Nav1.7 expression. These results indicate that the presence of multiple psychophysical stressors during pregnancy is associated with visceral hypersensitivity in offspring, which is likely mediated by an upregualtion of cystathionine-ß-synthase and Nav1.7 expression. Prenatal maternal stress might be a significant contributor to irritable bowel syndrome, and cystathionine-ß-synthase might be a potential target for treatment for chronic visceral hypersensitivity in patients with irritable bowel syndrome.

Transition to the Ultimate Regime in Two-Dimensional Rayleigh-Bénard Convection.

The possible transition to the so-called ultimate regime, wherein both the bulk and the boundary layers are turbulent, has been an outstanding issue in thermal convection, since the seminal work by Kraichnan [Phys. Fluids 5, 1374 (1962)PFLDAS0031-917110.1063/1.1706533]. Yet, when this transition takes place and how the local flow induces it is not fully understood. Here, by performing two-dimensional simulations of Rayleigh-Bénard turbulence covering six decades in Rayleigh number Ra up to 10^{14} for Prandtl number Pr=1, for the first time in numerical simulations we find the transition to the ultimate regime, namely, at Ra^{*}=10^{13}. We reveal how the emission of thermal plumes enhances the global heat transport, leading to a steeper increase of the Nusselt number than the classical Malkus scaling Nu∼Ra^{1/3} [Proc. R. Soc. A 225, 196 (1954)PRLAAZ1364-502110.1098/rspa.1954.0197]. Beyond the transition, the mean velocity profiles are logarithmic throughout, indicating turbulent boundary layers. In contrast, the temperature profiles are only locally logarithmic, namely, within the regions where plumes are emitted, and where the local Nusselt number has an effective scaling Nu∼Ra^{0.38}, corresponding to the effective scaling in the ultimate regime.

Diffusive interaction of multiple surface nanobubbles: shrinkage, growth, and coarsening.

Surface nanobubbles are nanoscopic spherical-cap shaped gaseous domains on immersed substrates which are stable, even for days. After the stability of a single surface nanobubble has been theoretically explained, i.e. contact line pinning and gas oversaturation are required to stabilize it against diffusive dissolution [Lohse and Zhang, Phys. Rev. E, 2015, 91, 031003(R)], here we focus on the collective diffusive interaction of multiple nanobubbles. For that purpose we develop a finite difference scheme for the diffusion equation with the appropriate boundary conditions and with the immersed boundary method used to represent the growing or shrinking bubbles. After validation of the scheme against the exact results of Epstein and Plesset for a bulk bubble [J. Chem. Phys., 1950, 18, 1505] and of Lohse and Zhang for a surface bubble, the framework of these simulations is used to describe the coarsening process of competitively growing nanobubbles. The coarsening process for such diffusively interacting nanobubbles slows down with advancing time and increasing bubble distance. The present results for surface nanobubbles are also applicable for immersed surface nanodroplets, for which better controlled experimental results of the coarsening process exist.

Controlling Heat Transport and Flow Structures in Thermal Turbulence Using Ratchet Surfaces.

In this combined experimental and numerical study on thermally driven turbulence in a rectangular cell, the global heat transport and the coherent flow structures are controlled with an asymmetric ratchetlike roughness on the top and bottom plates. We show that, by means of symmetry breaking due to the presence of the ratchet structures on the conducting plates, the orientation of the large scale circulation roll (LSCR) can be locked to a preferred direction even when the cell is perfectly leveled out. By introducing a small tilt to the system, we show that the LSCR orientation can be tuned and controlled. The two different orientations of LSCR give two quite different heat transport efficiencies, indicating that heat transport is sensitive to the LSCR direction over the asymmetric roughness structure. Through a quantitative analysis of the dynamics of thermal plume emissions and the orientation of the LSCR over the asymmetric structure, we provide a physical explanation for these findings. The current work has important implications for passive and active flow control in engineering, biofluid dynamics, and geophysical flows.

Antihypertensive drug use and breast cancer risk: a meta-analysis of observational studies.

We conducted a meta-analysis of observational studies to examine the hypothesized association between breast cancer and antihypertensive drug (AHT) use. Fixed- or random- effect models were used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all AHTs and individual classes (i.e., angiotensin-converting enzyme inhibitors, [ACEi]; angiotensin-receptor blockers, [ARBs]; calcium channel blockers, [CCBs]; beta-blockers, [BBs], and diuretics). Twenty-one studies with 3,116,266 participants were included. Overall, AHT use was not significantly associated with breast cancer risk (RR = 1.02, 95% CI: 0.98-1.06), and no consistent association was found for specific AHT classes with pooled RRs of 1.02 (95% CI: 0.96-1.09) for BBs, 1.07 (95% CI: 0.99-1.16) for CCBs, 0.99 (95% CI: 0.93-1.05) for ACEi/ARBs, and 1.05 (95% CI: 0.99-1.12) for diuretics. When stratified by duration of use, there was a significantly reduced breast cancer risk for ACEi/ARB use ≥10 years (RR = 0.80, 95% CI: 0.67-0.95). Although there was no significant association between AHT use and breast cancer risk, there was a possible beneficial effect was found for long-term ACEi/ARB. Large, randomized controlled trials with long-term follow-up are needed to further test the effect of these medications on breast cancer risk.

Roughness-Facilitated Local 1/2 Scaling Does Not Imply the Onset of the Ultimate Regime of Thermal Convection.

In thermal convection, roughness is often used as a means to enhance heat transport, expressed in Nusselt number. Yet there is no consensus on whether the Nusselt vs Rayleigh number scaling exponent (Nu∼Ra^{ß}) increases or remains unchanged. Here we numerically investigate turbulent Rayleigh-Bénard convection over rough plates in two dimensions, up to Ra≈10^{12}. Varying the height and wavelength of the roughness elements with over 200 combinations, we reveal the existence of two universal regimes. In the first regime, the local effective scaling exponent can reach up to 1/2. However, this cannot be explained as the attainment of the so-called ultimate regime as suggested in previous studies, because a further increase in Ra leads to the second regime, in which the scaling saturates back to a value close to the smooth wall case. Counterintuitively, the transition from the first to the second regime corresponds to the competition between bulk and boundary layer flow: from the bulk-dominated regime back to the classical boundary-layer-controlled regime. Our study demonstrates that the local 1/2 scaling does not necessarily signal the onset of ultimate turbulence.

Universal nanodroplet branches from confining the Ouzo effect.

We report the self-organization of universal branching patterns of oil nanodroplets under the Ouzo effect [Vitale S, Katz J (2003) Langmuir 19:4105-4110]-a phenomenon in which spontaneous droplet formation occurs upon dilution of an organic solution of oil with water. The mixing of the organic and aqueous phases is confined under a quasi-2D geometry. In a manner analogous to the ramification of ground stream networks [Devauchelle O, Petroff AP, Seybold HF, Rothman DH (2012) Proc Natl Acad Sci USA 109: 20832-20836 and Cohen Y, et al. (2015) Proc Natl Acad Sci USA 112:14132-14137] but on a scale 10 orders of magnitude smaller, the angles between the droplet branches are seen to exhibit remarkable universality, with a value around 74° ± 2°, independent of the various control parameters of the process. Numerical simulations reveal that these nanodroplet branching patterns are governed by the interplay between the local concentration gradient, diffusion, and collective interactions. We further demonstrate the ability of the local concentration gradient to drive autonomous motion of colloidal particles in the highly confined space, and the possibility of using the nucleated nanodroplets for nanoextraction of a hydrophobic solute. The understanding obtained from this work provides a basis for quantitatively understanding the complex dynamical aspects associated with the Ouzo effect. We expect that this will facilitate improved control in nanodroplet formation for many applications, spanning from the preparation of pharmaceutical polymeric carriers, to the formulation of cosmetics and insecticides, to the fabrication of nanostructured materials, to the concentration and separation of trace analytes in liquid-liquid microextraction.