Neuropathic pain, a type of chronic pain as a result of direct central or peripheral nerve damage, is associated with significant quality of life and functional impairment. Its underlying mechanisms ...remain unclear. We investigated whether ROR2, a member of the receptor tyrosine kinase-like orphan receptor (ROR) family, participates in modulation of neuropathic pain.
Thermal hyperalgesia and mechanical allodynia were measured using radiant heat and von Frey filament testing. Immunofluorescence staining was used to detect expression of ROR2 in neuronal nuclei. Fos expression was determined by immunocytochemistry. Phosphorylation status was detected by western blot and immunoprecipitation. Small interfering RNA was used to knock down ROR2 expression.
ROR2 was upregulated and activated in spinal neurones after chronic constriction injury (CCI) in mice 1.3 (0.1) to 2.1 (0.1)-fold of sham, P<0.01 from Day 1–21. CCI induced significant demethylation of the CpG island in the ROR2 gene promoter 0.37 (0.06) vs 0.12 (0.03)% CpG methylation, P<0.001. Knockdown of ROR2 in the spinal cord prevented and reversed CCI-induced pain behaviours and spinal neuronal sensitisation Fos expression: 130 (12) vs 81 (8) cells, P<0.05; 120 (11) vs 70 (7) cells, P<0.05. In contrast, activation of spinal ROR2 by intrathecal injection of Wnt5a induced pain behaviours and spinal neuronal sensitisation Fos expression: 11 (1) vs 100 (12) cells, P<0.001 in wild-type mice. Furthermore, ROR2-mediated pain modulation required phosphorylation of N-methyl-D-aspartate receptor 2B subunit (GluN2B) at Ser 1303 and Tyr1472 by pathways involving protein kinase C (PKC) and Src family kinases. Intrathecal injection of GluN2B, PKC, or Src family kinase-specific inhibitors significantly attenuated Wnt5a-induced pain behaviours.
ROR2 in the spinal cord regulates neuropathic pain via phosphorylation of GluN2B, suggesting a potential target for prevention and relief of neuropathic pain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Plants typically release large quantities of volatiles in response to herbivory by insects. This benefits the plants by, for instance, attracting the natural enemies of the herbivores. We show that ...the brown planthopper (BPH) has cleverly turned this around by exploiting herbivore-induced plant volatiles (HIPVs) that provide safe havens for its offspring. BPH females preferentially oviposit on rice plants already infested by the rice striped stem borer (SSB), which are avoided by the egg parasitoid
, the most important natural enemy of BPH. Using synthetic versions of volatiles identified from plants infested by BPH and/or SSB, we demonstrate the role of HIPVs in these interactions. Moreover, greenhouse and field cage experiments confirm the adaptiveness of the BPH oviposition strategy, resulting in 80% lower parasitism rates of its eggs. Besides revealing a novel exploitation of HIPVs, these findings may lead to novel control strategies against an exceedingly important rice pest.
Streamflow recession, shaped by hydrological processes, runoff dynamics, and catchment storage, is heavily influenced by landscape structure and rainstorm characteristics. However, our understanding ...of how recession relates to landscape structure and rainstorm characteristics remains inconsistent, with limited research examining their combined impact. This study examines this interplay in shaping recession responses upon 291 sets of recession parameters obtained through the decorrelation process. The data originate from 19 subtropical mountainous rivers and cover events with a wide spectrum of rainfall amounts. Key findings indicate that the recession coefficient (a) increases while the exponent (b) decreases with the L/G ratio (the median of ratios between flow-path length and gradient), suggesting that longer and gentler hillslopes facilitate flow accumulation and aquifer connectivity, ultimately reducing nonlinearity. Additionally, in large catchments, the exponent (b) increases with increasing rainfall due to greater landscape heterogeneity. Conversely, in small catchments, it declines with rainfall, indicating that these catchments have less landscape heterogeneity and thus reduced runoff heterogeneity. Our findings underscore the necessity for further validation of how L/G and drainage area regulate recession responses to varying rainfall levels across diverse regions.
A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines ...from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Gravitational‐wave high‐energy Electromagnetic Counterpart All‐sky Monitor (GECAM) is a space‐borne instrument dedicated to monitoring high‐energy transients, including Terrestrial Gamma‐ray Flashes ...(TGFs) and Terrestrial Electron Beams (TEBs). We implemented a TGF/TEB search algorithm for GECAM, with which 147 bright TGFs, 2 typical TEBs and 2 special TEB‐like events are identified during an effective observation time of ∼9 months. We show that, with gamma‐ray and charged particle detectors, GECAM can effectively identify and distinguish TGFs and TEBs, and measure their temporal and spectral properties in detail. A very high TGF‐lightning association rate of ∼80% is obtained between GECAM and GLD360 in east Asia region.
Plain Language Summary
Terrestrial gamma‐ray flashes (TGFs) and Terrestrial Electron Beams (TEBs) represent the most energetic radioactive phenomena in the atmosphere of the Earth. They reflect a natural particle accelerator that can boost electrons up to at least several tens of mega electron volts and produce gamma‐ray radiation. With novel detection technologies, Gravitational‐wave high‐energy Electromagnetic Counterpart All‐sky Monitor (GECAM) is a new powerful instrument to observe TGFs and TEBs, as well as study their properties. For example, it is difficult for most space‐borne high‐energy instruments to distinguish between TGFs and TEBs. However, we show here that, with the joint observation of gamma‐ray and charged particle detectors, GECAM can effectively identify TGFs and TEBs. GECAM can also reveal their fine features in the light curves and spectra.
Key Points
During 9‐month observation, Gravitational‐wave high‐energy Electromagnetic Counterpart All‐sky Monitor (GECAM) has detected 147 bright Terrestrial Gamma‐ray Flashes (TGFs), 2 typical Terrestrial Electron Beams (TEBs), and 2 special TEB‐like events
With novel detector design, GECAM can effectively classify TGFs and TEBs, and reveal their fine temporal features
We obtained a very high TGF‐lightning association rate (∼80%) between GECAM and GLD360 in east Asia region
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We report a measurement of the positive muon lifetime to a precision of 1.0 ppm; it is the most precise particle lifetime ever measured. The experiment used a time-structured, low-energy muon beam ...and a segmented plastic scintillator array to record more than 2×10(12) decays. Two different stopping target configurations were employed in independent data-taking periods. The combined results give τ(μ(+)) (MuLan)=2 196 980.3(2.2) ps, more than 15 times as precise as any previous experiment. The muon lifetime gives the most precise value for the Fermi constant: G(F) (MuLan)=1.166 378 8(7)×10(-5) GeV(-2) (0.6 ppm). It is also used to extract the μ(-)p singlet capture rate, which determines the proton's weak induced pseudoscalar coupling g(P).
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
► A TiAl3 coating has been developed on Ti–6Al–4V by hot-dip aluminizing. ► The coating provides a high degree of protection for Ti–6Al–4V at 700°C. ► A layered structure of ...Al2O3/TiAl3/TiAl2/TiAl/alloy forms at 700°C. ► A layered structure of Al2O3/(TiAl3+TiAl2)/TiAl/Ti3Al/alloy forms at 800°C.
Hot-dip aluminizing and interdiffusion treatment were used to develop a TiAl3-rich coating on Ti–6Al–4V alloy. Interrupted oxidation at temperatures from 600 to 900°C and isothermal oxidation at 700 and 800°C of the coating were conducted. The coating markedly decreases the oxidation rate in comparison with the alloy at temperatures below 800°C during the interrupted oxidation. The oxidation kinetics follows parabolic relations at 700 and 800°C during the isothermal oxidation. A layered structure of Al2O3/TiAl3/TiAl2/TiAl/alloy from the outside to the inside forms after oxidation at 700°C without changing the main body of the coating.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A high precision calibration of the nonlinearity in the energy response of the Daya Bay Reactor Neutrino Experiment’s antineutrino detectors is presented in detail. The energy nonlinearity originates ...from the particle-dependent light yield of the scintillator and charge-dependent electronics response. The nonlinearity model is constrained by γ calibration points from deployed and naturally occurring radioactive sources, the β spectrum from 12B decays, and a direct measurement of the electronics nonlinearity with a new flash analog-to-digital converter readout system. Less than 0.5% uncertainty in the energy nonlinearity calibration is achieved for positrons of kinetic energies greater than 1 MeV.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Brain inflammation is a primary pathological driving force of many neurodegenerative disorders. In the destructive process, pro-inflammatory cytokines (IL-1β and TNF-α), are robustly released, ...affecting normal neural progenitor cell (NPC) differentiation, and resulting in a vast number of astrocytes and a diminished neural population. A counteractive mechanism is still unknown. In this study, we have identified a link between brain inflammation and the signal transducer and activator of transcription 3 (STAT3) pathway: IL-1β and TNF-α induce STAT3 activation in NPCs. Then to investigate STAT3's effects on NPC fate, we observed that an inhibition of STAT3 expression by siRNA inhibited astrocytic differentiation and increased neuronal differentiation of human NPCs in fetal bovine serum (FBS)-induced astrocyte differentiation condition. Furthermore, STAT3-targeting siRNA abrogated IL-1β and TNF-α-induced astrocyte differentiation and partially restored neuronal differentiation. Elimination of STAT3 expression also countered IL-1β and TNF-α-induced inhibition of proneural bHLH genes, mammalian achaete-schute homologue-1 (Mash1), Neurogenin1 (Ngn1), and Neurogenin2 (Ngn2). These data suggest that a suppression of STAT3 during brain inflammation would inhibit astrogliogenesis and promote neurogenesis. Thus, STAT3 could be a potential target of drug therapy for neurodegenerative disorders.
Atherosclerotic plaques develop in the inner intimal layer of arteries and can cause heart attacks and strokes
. As plaques lack innervation, the effects of neuronal control on atherosclerosis remain ...unclear. However, the immune system responds to plaques by forming leukocyte infiltrates in the outer connective tissue coat of arteries (the adventitia)
. Here, because the peripheral nervous system uses the adventitia as its principal conduit to reach distant targets
, we postulated that the peripheral nervous system may directly interact with diseased arteries. Unexpectedly, widespread neuroimmune cardiovascular interfaces (NICIs) arose in mouse and human atherosclerosis-diseased adventitia segments showed expanded axon networks, including growth cones at axon endings near immune cells and media smooth muscle cells. Mouse NICIs established a structural artery-brain circuit (ABC): abdominal adventitia nociceptive afferents
entered the central nervous system through spinal cord T
-T
dorsal root ganglia and were traced to higher brain regions, including the parabrachial and central amygdala neurons; and sympathetic efferent neurons projected from medullary and hypothalamic neurons to the adventitia through spinal intermediolateral neurons and both coeliac and sympathetic chain ganglia. Moreover, ABC peripheral nervous system components were activated: splenic sympathetic and coeliac vagus nerve activities increased in parallel to disease progression, whereas coeliac ganglionectomy led to the disintegration of adventitial NICIs, reduced disease progression and enhanced plaque stability. Thus, the peripheral nervous system uses NICIs to assemble a structural ABC, and therapeutic intervention in the ABC attenuates atherosclerosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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