Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like ...receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.
Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin ...magnetism with electric fields-a longstanding technological goal in spintronics and multiferroics
-can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic states in an orbital Chern insulator
, a magnetic system in which non-trivial band topology favours long-range order of orbital angular momentum but the spins are thought to remain disordered
. We use van der Waals heterostructures consisting of a graphene monolayer rotationally faulted with respect to a Bernal-stacked bilayer to realize narrow and topologically non-trivial valley-projected moiré minibands
. At fillings of one and three electrons per moiré unit cell within these bands, we observe quantized anomalous Hall effects
with transverse resistance approximately equal to h/2e
(where h is Planck's constant and e is the charge on the electron), which is indicative of spontaneous polarization of the system into a single-valley-projected band with a Chern number equal to two. At a filling of three electrons per moiré unit cell, we find that the sign of the quantum anomalous Hall effect can be reversed via field-effect control of the chemical potential; moreover, this transition is hysteretic, which we use to demonstrate non-volatile electric-field-induced reversal of the magnetic state. A theoretical analysis
indicates that the effect arises from the topological edge states, which drive a change in sign of the magnetization and thus a reversal in the favoured magnetic state. Voltage control of magnetic states can be used to electrically pattern non-volatile magnetic-domain structures hosting chiral edge states, with applications ranging from reconfigurable microwave circuit elements to ultralow-power magnetic memories.
Although flow diverters have been reported with favorable clinical and angiographic outcomes in various literatures, randomized trials determining their true effectiveness and safety are still in ...lack. The Parent Artery Reconstruction for Large or Giant Cerebral Aneurysms Using the Tubridge Flow Diverter (PARAT) trial was designed to evaluate the safety and efficacy of the Tubridge flow diverter in the treatment of large or giant aneurysms in comparison with Enterprise stent-assisted coiling.
This prospective, multicenter, randomized trial was conducted at 12 hospitals throughout China. Enrolled adults with unruptured large/giant intracranial aneurysms were randomly assigned (1:1) to receive either Enterprise stent-assisted coiling or Tubridge flow diverter implantation. The primary end point was complete occlusion at 6-month follow-up, while secondary end points included technical success, mortality, target vessel-related stroke, aneurysm bleeding, in-stent stenosis, parent artery occlusion, and the frequency of all adverse events.
Among 185 enrolled subjects, 41 withdrew before procedure initiation. Overall, 82 subjects underwent Tubridge implantation, and 62 subjects were primarily treated with stent-assisted coiling. The results of 6-month follow-up imaging included complete occlusion rates of 75.34% versus 24.53% for the Tubridge and stent-assisted coiling groups, respectively, with a calculated common odds ratio of 9.4 (95% confidence interval, 4.14-21.38;
< .001). There was a higher, nonsignificant frequency of complications for Tubridge subjects. Multivariate analysis showed a decreased stroke rate at the primary investigational site, with a marginal
value (
= .051).
This trial showed an obviously higher rate of large and giant aneurysm obliteration with the Tubridge FD over Enterprise stent-assisted coiling. However, this higher obliteration rate came at the cost of a nonsignificantly higher rate of complications. Investigational site comparisons suggested that a learning curve for flow-diverter implantation should be recognized and factored into trial designs.
The maximum potential of a dual-loop organic Rankine cycle (ORC) applied to a light-duty diesel engine is analyzed over the engine's operational range by developing a mathematical model based on ...physical processes and boundary conditions specified according to measured data from an engine test. We further evaluate the effects of three working parameters—expander isentropic efficiency, evaporation pressure of the high-temperature loop, and condensation temperature of the low-temperature loop—on the performance of the dual-loop ORC system. The results show that using the proposed dual-loop ORC system improves the net power output of a diesel automotive engine by 19–22% in the peak thermal-efficiency region under allowable working conditions of the engine, and by 53–72% in the high-speed and low-load regions. Over the engine's entire operational range, the effective thermal efficiency increases by a maximum of 8%. Moreover, the expander isentropic efficiency and the condensation temperature of the low-temperature loop are two critical parameters that affect combined system performance.
•The potential of a dual loop ORC is estimated over the engine's operating region.•Effect of expander isentropic efficiency is analyzed at engine speed of 1800 r/min.•Evaporation pressure and condensation temperature are also evaluated.
The downsizing of solder balls results in larger interfacial intermetallic compound (IMC) grains and less Cu substrate consumption in lead-free soldering on Cu substrates. This size effect on the ...interfacial reaction is experimentally demonstrated and theoretically analyzed using Sn-3.0Ag-0.5Cu and Sn-3.5Ag solder balls. The interfacial reaction between the Sn-xAg-yCu solders and Cu substrates is a dynamic response to a combination of effects of interfacial IMC growth, Cu substrate consumption and composition variation in the interface zone. A concentration gradient controlled (CGC) kinetics model is proposed to explain the combined effects. The concentration gradient of Cu at the interface, which is a function of solder volume, initial Cu concentration and reaction time, is the root cause of the size effect. We found that a larger Cu concentration gradient results in smaller Cu(6)Sn(5) grains and more consumption of Cu substrate. According to our model, the growth kinetics of interfacial Cu(6)Sn(5) obeys a t(1/3) law when the molten solder has approached the solution saturation, and will be slower otherwise due to the interfering dissolution mechanism. The size effect introduced in this model is supported by a good agreement between theoretical and experimental results. Finally, the scope of application of this model is discussed.
The preBötzinger Complex (preBötC), a compact medullary region essential for generating normal breathing rhythm and pattern, is the kernel of the breathing central pattern generator (CPG). Excitatory ...preBötC neurons in rats project to major breathing‐related brainstem regions. Here, we provide a brainstem connectivity map in mice for both excitatory and inhibitory preBötC neurons. Using a genetic strategy to label preBötC neurons, we confirmed extensive projections of preBötC excitatory neurons within the brainstem breathing CPG including the contralateral preBötC, Bötzinger Complex (BötC), ventral respiratory group, nucleus of the solitary tract, parahypoglossal nucleus, parafacial region (RTN/pFRG or alternatively, pFL/pFV), parabrachial and Kölliker‐Füse nuclei, as well as major projections to the midbrain periaqueductal gray. Interestingly, preBötC inhibitory projections paralleled the excitatory projections. Moreover, we examined overlapping projections in the pons in detail and found that they targeted the same neurons. We further explored the direct anatomical link between the preBötC and suprapontine brain regions that may govern emotion and other complex behaviors that can affect or be affected by breathing. Forebrain efferent projections were sparse and restricted to specific nuclei within the thalamus and hypothalamus, with processes rarely observed in cortex, basal ganglia, or other limbic regions, e.g., amygdala or hippocampus. We conclude that the preBötC sends direct, presumably inspiratory‐modulated, excitatory and inhibitory projections in parallel to distinct targets throughout the brain that generate and modulate breathing pattern and/or coordinate breathing with other behaviors, physiology, cognition, or emotional state.
The preBötzinger Complex (preBötC) in the brainstem generates inspiratory rhythm, but how it is wired within the core central pattern generator neural circuit to produce and modulate breathing movements remains to be determined. We examined the connectivity of two populations of preBötC neurons, one excitatory expressing the peptide somatostatin and one inhibitory expressing the glycine transporter GlyT2, to other brainstem regions that modulate breathing and identified projections to suprapontine regions that may regulate voluntary and emotional control of breathing. PreBötC inhibitory projections parallel excitatory projections and, at least in the pons, may target the same neurons. Our brain‐wide connectivity mapping shows that the preBötC sends direct, presumably inspiratory‐modulated, excitatory, and inhibitory projections in parallel to distinct targets throughout the brain.
Topological Weyl semimetals (TWSs) represent a novel state of topological quantum matter which not only possesses Weyl fermions (massless chiral particles that can be viewed as magnetic monopoles in ...momentum space) in the bulk and unique Fermi arcs generated by topological surface states, but also exhibits appealing physical properties such as extremely large magnetoresistance and ultra-high carrier mobility. Here, by performing angle-resolved photoemission spectroscopy (ARPES) on NbP and TaP, we directly observed their band structures with characteristic Fermi arcs of TWSs. Furthermore, by systematically investigating NbP, TaP and TaAs from the same transition metal monopnictide family, we discovered their Fermiology evolution with spin-orbit coupling (SOC) strength. Our experimental findings not only reveal the mechanism to realize and fine-tune the electronic structures of TWSs, but also provide a rich material base for exploring many exotic physical phenomena (for example, chiral magnetic effects, negative magnetoresistance, and the quantum anomalous Hall effect) and novel future applications.
The mass absorption efficiency (MAE) of elemental carbon (EC) in Beijing was quantified using a thermal-optical carbon analyzer. The MAE measured at 632 nm was 8.45±1.71 and 9.41±1.92 m2 g−1 during ...winter and summer respectively. The daily variation of MAE was found to coincide with the abundance of organic carbon (OC), especially the OC to EC ratio, perhaps due to the enhancement by coating with organic aerosol (especially secondary organic aerosol, SOA) or the artifacts resulting from the redistribution of liquid-like organic particles during the filter-based absorption measurements. Using a converting approach that accounts for the discrepancy caused by measurements methods of both light absorption and EC concentration, previously published MAE values were converted to the equivalent-MAE, which is the estimated value if using the same measurement methods as used in this study. The equivalent-MAE was found to be much lower in the regions heavily impacted by biomass burning (e.g., below 2.7 m2 g−1 for two Indian cities). Results from source samples (including diesel exhaust samples and biomass smoke samples) also demonstrated that emissions from biomass burning would decrease the MAE of EC. Moreover, optical properties of water-soluble organic carbon (WSOC) in Beijing were presented. Light absorption by WSOC exhibited strong wavelength (λ) dependence such that absorption varied approximately as λ−7, which was characteristic of the brown carbon spectra. The MAE of WSOC (measured at 365 nm) was 1.79±0.24 and 0.71±0.20 m2 g−1 during winter and summer respectively. The large discrepancy between the MAE of WSOC during winter and summer was attributed to the difference in the precursors of SOA such that anthropogenic volatile organic compounds (AVOCs) should be more important as the precursors of SOA in winter. The MAE of WSOC in Beijing was much higher than results from the southeastern United States which were obtained using the same method as used in this study, perhaps due to the stronger emissions of biomass burning in China.
Cu/55 vol%diamond (Ti) composites are prepared by hot forging of cold-pressed powder preforms, consisted of pure Cu powders and 50 nm-thick Ti-coated diamond particles, at 800 °C (800-Cu/55Dia) and ...1050 °C (1050-Cu/55Dia), respectively. It finds that the TiC coverage of diamond surface is 96% in 800-Cu/55Dia and 70% in 1050-Cu/55Dia. Nano-spherical TiC particles are homogeneously dispersed on diamond surface to form a rough surface for 800-Cu/55Dia. This leads to a strong interface bonding is formed in 800-Cu/55Dia, having a flexural strength of 418 MPa. Sever interfacial layer spallation, smooth and flat surface of interfacial layer make 1050-Cu/55Dia have a relatively low interface bonding. The high coverage of diamond by interfacial layer, formation of dispersed nano-spherical TiC particles, and strong interface bonding enables the thermal conductivity (TC) of 800-Cu/55Dia is as high as 550 W/mK (99% of the theoretical value), and a CTE of 7 × 10−6/K at 313 K. The fabricated copper/diamond composite has better mechanical and thermophysical properties than the most reported copper/diamond (the diamond particle size is < 100 μm) composites, demonstrating that powder hot-forging technique we developed is a cost-effective process and feasible to produce a copper/diamond composite with high mechanical and thermophysical performance for high-power thermal management applications.
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•Nano-thick Ti-coated diamond reinforced Cu composites aresuccessfully fabricated by hot forging of elemental powder mixture.•Nano-spherical TiC particles are distributed on the diamond surface, which provides effective mechanical interlocking.•Thehot-forged compositehas better mechanical and thermophysical properties than most of the reported copper/diamond composites that have similar diamond particle size.•The formed chemical bonding, good wettability and strong mechanical interlocking help achieve a excellent flexural properties, and thermal conductivity of 550 W/mK.
The increasing impact of both climatic change and human activities on global river systems necessitates an increasing need to identify and quantify the various drivers and their impacts on fluvial ...water and sediment discharge. Here we show that mean Yangtze River water discharge of the first decade after the closing of the Three Gorges Dam (TGD) (2003-2012) was 67 km(3)/yr (7%) lower than that of the previous 50 years (1950-2002), and 126 km(3)/yr less compared to the relatively wet period of pre-TGD decade (1993-2002). Most (60-70%) of the decline can be attributed to decreased precipitation, the remainder resulting from construction of reservoirs, improved water-soil conservation and increased water consumption. Mean sediment flux decreased by 71% between 1950-1968 and the post-TGD decade, about half of which occurred prior to the pre-TGD decade. Approximately 30% of the total decline and 65% of the decline since 2003 can be attributed to the TGD, 5% and 14% of these declines to precipitation change, and the remaining to other dams and soil conservation within the drainage basin. These findings highlight the degree to which changes in riverine water and sediment discharge can be related with multiple environmental and anthropogenic factors.
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