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Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial–mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.

In winter, a branch of the China Coastal Current can turn in the Taiwan Strait to join the poleward-flowing Taiwan Coastal Current. The associated cross-strait flows have been inferred from hydrographic and satellite data, from observed abundances off northwestern Taiwan of cold-water copepod species Calanus sinicus and, in late March of 2012, also from debris found along the northwestern shore of Taiwan of a ship that broke two weeks earlier off the coast of China. The dynamics related to such cross flows have not been previously explained and are the focus of this study using analytical and numerical models. It is shown that the strait’s currents can be classified into three regimes depending on the strength of the winter monsoon: equatorward (poleward) for northeasterly winds stronger (weaker) than an upper (lower) bound and cross-strait flows for relaxing northeasterly winds between the two bounds. These regimes are related to the formation of the stationary Rossby wave over the Changyun Ridge off midwestern Taiwan. In the weak (strong) northeasterly wind regime, a weak (no) wave is produced. In the relaxing wind regime, cross-strait currents are triggered by an imbalance between the pressure gradient and wind and are amplified by the finite-amplitude meander downstream of the ridge where a strong cyclone develops.

The soil carbon (C) saturation concept suggests an upper limit to the storage of soil organic carbon (SOC). It is set by the mechanisms that protect soil organic matter from mineralization. Biochar has the capacity to protect new C, including rhizodeposits and microbial necromass. However, the decadal-scale mechanisms by which biochar influences the molecular diversity, spatial heterogeneity, and temporal changes in SOC persistence, remain unresolved. Here we show that the soil C storage ceiling of a Ferralsol under subtropical pasture was raised by a second application of Eucalyptus saligna biochar 8.2 years after the first application—the first application raised the soil C storage ceiling by 9.3 Mg new C ha −1 and the second application raised this by another 2.3 Mg new C ha −1 . Linking direct visual evidence from one-, two-, and three-dimensional analyses with SOC quantification, we found high spatial heterogeneity of C functional groups that resulted in the retention of rhizodeposits and microbial necromass in microaggregates (53–250 µm) and the mineral fraction (<53 µm). Microbial C-use efficiency was concomitantly increased by lowering specific enzyme activities, contributing to the decreased mineralization of native SOC by 18%. We suggest that the SOC ceiling can be lifted using biochar in (sub)tropical grasslands globally. A decadal-scale field trial revealed 1.01 Mg of rhizodeposit and necromass C was stored in soil microaggregate and mineral fractions per Mg biochar-C applied. Microspectroscopic analyses visualize mechanisms for this elevated soil C storage ceiling.

Tide gauge and satellite data reveal an interannual oscillation of the ocean’s thermoclines east of the Philippines and Taiwan, forced by a corresponding oscillation in the wind stress curl. This so-called Philippines–Taiwan Oscillation (PTO) is shown to control the interannual variability of the circulation of the subtropical and tropical western North Pacific. The PTO shares some characteristics of known Pacific indices, for example, Niño-3.4. However, unlike PTO, these other indices explain only portions of the western North Pacific circulation. The reason is because of the nonlinear nature of the forcing in which mesoscale (ocean) eddies play a crucial role. In years of positive PTO, the thermocline east of the Philippines rises while east of Taiwan it deepens. This results in a northward shift of the North Equatorial Current (NEC), increased vertical shear of the Subtropical Countercurrent (STCC)/NEC system, increased eddy activity dominated by warm eddies in the STCC, increased Kuroshio transport off the northeastern coast of Taiwan into the East China Sea, increased westward inflow through Luzon Strait into the South China Sea, and cyclonic circulation and low sea surface height anomalies in the South China Sea. The reverse applies in years of negative PTO.

Twenty‐nine years of tide‐gauge data are analyzed in conjunction with wind and satellite‐derived sea‐surface height and ocean velocity data to study the interannual and seasonal variations of the Kuroshio transport off the northeastern coast of Taiwan. The data reveals an interannual variation of ±0.1 m (transport‐variation of approximately ±3.5 Sv; 1 Sv = 106 m3 s−1), and a much weaker (5–10 times weaker) seasonal fluctuation that is minimum in May and maximum in November. The interannual fluctuations are not directly wind‐driven by linear dynamics; rather, the Kuroshio strengthens in years of abundant eddies of the Subtropical Counter Current, which is related to the current's instability state driven by the slow fluctuations of the large‐scale wind stress curl in the western Pacific. The seasonal transport fluctuation is also eddy‐forced, but has weaker amplitude because the seasonal time scale is of the same order as the eddy‐propagation time scale, and transport‐producing eddy signals tend to overlap east of Taiwan. Key Points Interannual Kuroshio variations Eddy‐driven dynamics Far‐reaching impacts on western Pacific

The observed seasonal preferences of Loop Current eddy shedding, more in summer and winter and less in fall and spring, are shown for the first time to be due to a curious combination of forcing by the seasonal winds in the Caribbean Sea and the Gulf of Mexico. The conditions are favorable for the Loop to shed eddies in summer and winter when strong trade winds in the Caribbean produce large Yucatan transport and Loop's intrusion, and concurrently when weak easterlies in the Gulf offer little impediment to eddy shedding. The conditions are less favorable in fall and spring as the trade winds and Yucatan transport weaken, and the strengthening of the Gulf's easterlies impedes shedding. Key Points The observed seasonal preferences of Loop Current eddy shedding, more in summer The preference is forced, instead of the natural shedding It is due to the be due to a curious combination of forcing by the seasonal wind

SummaryDue to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate.IntroductionA significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention.MethodsPatients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year.ResultsMean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively.ConclusionsThe OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

The North Pacific Subtropical Countercurrent (STCC) has a weak eastward velocity near the surface, but the region is populated with eddies. Studies have shown that the STCC is baroclinically unstable with a peak growth rate of 0.015 day−1 in March, and the ~60-day growth time has been used to explain the peak eddy kinetic energy (EKE) in May observed from satellites. It is argued here that this growth time from previously published normal-mode instability analyses is too slow. Growth rates calculated from an initial-value problem without the normal-mode assumption are found to be 1.5 to 2 times faster and at shorter wavelengths, due to the existence of (i) nonmodal solutions and (ii) sea surface temperature front in the mixed layer in winter. At interannual time scales it is shown that because of rapid surface adjustments, the STCC geostrophic shear, hence also the instability growth, is approximately in phase with surface forcing, leading to EKE modulation that peaks approximately 10 months later. However, the EKE can only be partially explained by this mechanism of modulation by baroclinic instability. It is suggested that the unexplained variance may be caused additionally by modulation of the EKE by dissipation.

Air–sea coupling in the IntraAmerican seas (IAS; Caribbean Sea and Gulf of Mexico) is studied through analyses of observational data from satellite, reanalysis products, and in situ measurements. A strong coupling is found between the easterly trade wind −U and meridional SST gradient ∂T/∂y across a localized region of the southern-central Caribbean Sea from seasonal and interannual to decadal time scales. The ∂T/∂y anomaly is caused by a variation in the strength of coastal upwelling off the Venezuelan coast by the wind, which in turn strengthens (weakens) for stronger (weaker) ∂T/∂y. Wind speeds and seasonal fluctuations in IAS have increased in the past two decades with a transition near 1994 coinciding approximately with when the Atlantic multidecadal oscillation (AMO) turned from cold to warm phases. In particular, the seasonal swing from summer's strong to fall's weak trade wind has become larger. The ocean's upper-layer depth has also deepened, by as much as 50% on average in the eastern Gulf of Mexico. These conditions favor the shedding of eddies from the Loop Current, making it more likely to shed at a biannual frequency, as has been observed from altimetry data.

This study demonstrates the use of oxygen vacancy-induced planar defects to significantly enhance electrical polarization through a local flexoelectric effect. By introducing an appropriate level of aliovalent dopants, numerous local planar defects are induced in (Bi 0.5 , Na 0.5 )TiO 3 -based thin films. These defects, identified as oxygen-deficient structures through direct visualization of oxygen atoms and oxygen vacancies using integrated differential phase-contrast microscopy, result in the formation of head-to-head domain structures. Geometric phase analysis confirms that these structures exhibit a substantial local strain gradient of up to 10 9  m -1 , contributing significantly to the flexoelectric polarization. Consequently, a giant maximum polarization ( P m ) of 161 μC cm -2 under 750 kV cm -1 and a remanent polarization P r  = 115 μC cm -2 along with a coercive field of 250 kV cm -1 are achieved, allowing these (Bi 0.5 , Na 0.5 )TiO 3 -based thin films to be used in low-power electronic applications. Crucially, the P m and P r of the thin films can be sustained at 133 and 98 μC cm -2 , respectively, at 230 °C. Additionally, they exhibit exceptional high-temperature fatigue endurance, with P m and P r demonstrating a negligible reduction of less than 9% after 10 7 cycles under 750 kV cm -1 at 230 °C. These values surpass those previously reported for oxide perovskite thin films at elevated temperatures, demonstrating potential applications of our thin films in high-temperature environments. Our findings offer promising avenues for advancing the application fields of ferroelectric thin films. This study shows that oxygen-vacancy planar defects greatly enhance polarization in (Bi, Na)TiO 3 -based thin films via local flexoelectric effects, enabling strong performance and thermal stability for low-power electronic applications.