PGE2 -EP3 axis promotes brown adipose tissue formation through stabilization of WTAP RNA methyltransferase.

Brown adipose tissue (BAT) functions as a thermogenic organ and is negatively associated with cardiometabolic diseases. N6 -methyladenosine (m6 A) modulation regulates the fate of stem cells. Here, we show that the prostaglandin E2 (PGE2 )-E-prostanoid receptor 3 (EP3) axis was activated during mouse interscapular BAT development. Disruption of EP3 impaired the browning process during adipocyte differentiation from pre-adipocytes. Brown adipocyte-specific depletion of EP3 compromised interscapular BAT formation and aggravated high-fat diet-induced obesity and insulin resistance in vivo. Mechanistically, activation of EP3 stabilized the Zfp410 mRNA via WTAP-mediated m6 A modification, while knockdown of Zfp410 abolished the EP3-induced enhancement of brown adipogenesis. EP3 prevented ubiquitin-mediated degradation of WTAP by eliminating PKA-mediated ERK1/2 inhibition during brown adipocyte differentiation. Ablation of WTAP in brown adipocytes abrogated the protective effect of EP3 overexpression in high-fat diet-fed mice. Inhibition of EP3 also retarded human embryonic stem cell differentiation into mature brown adipocytes by reducing the WTAP levels. Thus, a conserved PGE2 -EP3 axis promotes BAT development by stabilizing WTAP/Zfp410 signaling in a PKA/ERK1/2-dependent manner.

PGD 2 /DP1 axis promotes liver regeneration by secreting Wnt2 in KCs in mice.

BACKGROUND AND AIMS: The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin D 2 , a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of prostaglandin D 2 in the injury-induced liver regeneration remains unclear. APPROACH AND RESULTS: Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic prostaglandin D 2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67 + hepatocyte proliferation, and G2/M phase hepatocytes. In addition, DP1 deficiency, specifically in resident KCs, and not in endothelial cells or HSCs, retarded liver regeneration in mice after PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/ß-catenin signaling. Adeno-associated virus vector serotype 8-mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice after PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice. CONCLUSIONS: DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2 and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.

Effects of pressure on hydrogen diffusion behaviors in MgO.

Hydrogen, as the smallest atom and a key component of water, can penetrate into materials in various forms (e.g., atoms, molecules), which has significant effects on their properties; hence, the diffusion behavior of hydrogen has aroused widespread attention. One of the major compositions in the Earth's interior is MgO. Thus, the diffusion behavior of hydrogen in MgO under high pressure is vital for understanding the water cycle in the Earth's interior. However, the hydrogen diffusion behavior in MgO under high pressure is still poorly understood. Herein, the hydrogen diffusion behaviors in MgO with increasing pressure are systematically investigated in the framework of first-principles methods. Our results show that separated H atoms tend to converge to form H2 molecules, and H2 molecules tend to gather together. The energy barriers of both H and H2 diffusion in MgO increase with pressure. Notably, our results illustrate that hydrogen prefers to diffuse in solid MgO in its molecular state even under high pressure. Furthermore, the attempt frequency of hydrogen in MgO increases with temperature, while it decreases with pressure. This study will deepen our understanding of hydrogen diffusion behavior in MgO under high pressure and provide guidance for studies on particle diffusion in solid materials under extreme conditions.

Carbon phosphide nanoribbons with spatial inversion symmetry: robust generators of pure spin current with a photogalvanic effect.

Our recent work has demonstrated that the spin-dependent photogalvanic effect (PGE) is an ideal way to induce pure spin current in certain centrosymmetric systems (X. Tao, P. Jiang, H. Hao, X. Zheng, L. Zhang and Z. Zeng, Phys. Rev. B, 2020, 102, 081402), and thus the search for appropriate materials or structures is the key to realize it. Here, we theoretically propose a spin optoelectric device with α-phase carbon phosphide nanoribbons (α-CPNRs) to generate pure spin current by PGE using density functional theory simulation. By designing an α-CPNR based device with a centrosymmetric structure, due to the structural inversion symmetry and real space spin polarization antisymmetry of the system, the PGE induced pure spin current without any accompanying charge current can be always obtained, independent of polarization type and polarization angle of the photons. Furthermore, the magnitude of pure spin current can be greatly increased (nearly by an order of magnitude) by applying antiparallel electrical fields in the two leads to tune the spin density and band structure. Furthermore, by applying parallel electrical fields, a fully spin-polarized photocurrent can be produced in this system, suggesting a fantastic scheme to achieve half-metallic transport, another important goal in spintronics. These investigations suggest that the optoelectric devices constructed by α-CPNRs will have great potential in spintronics.

Downregulation of Programmed Death-1 Pathway Promoting CD8 + T Cell Cytotoxicity in Primary Biliary Cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune disease. CD8 + T cell (CTLs) cytotoxicity played a crucial rule in of PBC with unclear detailed pathogenesis. AIMS: The role of the programmed death-1 (PD-1) pathway in CD8 + T cell cytotoxicity in patients with PBC was determined. METHODS: We recruited 69 patients with PBC and 57 healthy controls (HCs). PD-1 pathway in peripheral CD8 + T cells and related cytokines were detected, and gene expression levels were detected. Immunofluorescence staining of PD-1/PD-L1 was performed on liver tissue. PD-1 ± CTLs were cocultured with human intrahepatic biliary epithelial cells (HiBECs) to measure CTL cytotoxicity, proliferation and cytokine levels and HiBEC apoptosis. The upstream signaling pathway of PD-1 was detected. RESULTS: PBC patients exhibited Tbet gene upregulation and PD-1 downregulation in CTLs, with PD-1 expression reduced in CTLs and PD-L1 reduced in the liver portal region relative to HCs. Higher plasma IL-10, interferon-γ and transforming growth factor-ß concentrations were observed in the PBC group than the HC group. In CTL and HiBEC coculture experiment, compared with PD-1- CTLs, PD-1 + CTLs exhibited weaker cytotoxicity, less proliferation and lower cytokine production. When the system was blocked by anti-PD-1 antibodies, these effects were antagonized. CONCLUSIONS: PD-1 expression in CD8 + T cells decreased, and PD-1 pathway-related cytokines changed in patients with PBC. PD-1/PD-L1 pathway silencing increased CD8 + T cell proliferation, related cytokine production and CTL cytotoxic effects on HiBECs in coculture experiment. The PD-1/PD-L1 pathway might represent an important pathway in the immunological mechanism underlying PBC.

Multimodal photoacoustic/ultrasonic imaging system: a promising imaging method for the evaluation of disease activity in rheumatoid arthritis.

OBJECTIVES: We aimed to assess the clinical value of multimodal photoacoustic/ultrasound (PA/US) articular imaging scores, a novel imaging method which can reflect the micro-vessels and oxygenation level of inflamed joints of rheumatoid arthritis (RA). METHODS: Seven small joints were examined by the PA/US imaging system. A 0-3 scoring system was used to semi-quantify the PA and power-Doppler (PD) signals, and the sums of PA and PD scores (PA-sum and PD-sum scores) of the seven joints were calculated. The relative oxygen saturation (SO2) values of the inflamed joints were measured and classified into 3 PA+SO2 patterns. The correlations between the PA/US imaging scores and the disease activity scores were assessed. RESULTS: Thirty-one patients of RA and a total of 217 joints were examined using the PA/US system. The PA-sum had high positive correlations with the standard clinical scores of RA (DAS28 [ESR] ρ = 0.754, DAS28 [CRP] ρ = 0.796, SDAI ρ = 0.836, CDAI ρ = 0.837, p < 0.001), which were superior to the PD-sum (DAS28 [ESR] ρ = 0.651, DAS28 [CRP] ρ = 0.676, SDAI ρ = 0.716, CDAI ρ = 0.709, p < 0.001). For the patients with high PA-sum scores, significant differences between hypoxia and hyperoxia were identified in pain visual analog score (p = 0.020) and patient's global assessment (p = 0.026). The PA+SO2 patterns presented moderate and high correlation with PGA (ρ = 0.477, p = 0.0077) and VAS pain score (ρ = 0.717, p < 0.001). CONCLUSION: The PA scores have significant correlations with standard clinical scores for RA, and the PA+SO2 patterns are also related with clinical scores that reflect pain severity. PA may have clinical potential in evaluating RA. KEY POINTS: • Multimodal photoacoustic/ultrasound imaging is a novel method to assess micro-vessels and oxygenation of local lesions. • Significant correlations between multimodal imaging parameters and clinical scores of RA patients were verified. • The multimodal PA/US system can provide objective imaging parameters, including PA scores of micro-vessels and relative SO2 value, as a supplementary to disease activity evaluation.

Graphene-based nano-devices: high spin Seebeck and pure spin photogalvanic effects.

We investigate the magnetic, thermoelectric transport, and photogalvanic effect (PGE) properties of two nano-devices based on sawtooth edged graphene nanoribbons (SGNRs). It is found that a robust spin-semiconducting property exists in SGNRs. When SGNRs are arranged in a configuration, a large spin Seebeck coefficient is obtained, indicating a high Seebeck effect under a temperature difference. In addition, we also propose a new spatial inversion symmetry nano-device, which is constructed by two head to head semi-infinite SGNRs in a configuration. The results show that spin-up and spin-down currents are generated by the PGE with opposite flowing directions and the same magnitude. As a result, only a finite pure spin current arises without an accompanying charge current. More importantly, the pure spin current is robustly induced by photons and is independent of the photon energy, polarization angle and the model of polarization (linear or elliptical polarization), which is attributed to the symmetry of the spatial inversion and anti-symmetry of the spin density inversion. The results presented here provide a useful insight into the real application of both spin caloritronics and photoelectric carbon-based nano-devices.

[Identification of mouse lines with HA-tagged prostaglandin receptors].

Prostaglandins are a class of poly-unsaturated fatty acids-derived bioactive lipids with important physiological function by binding to specific receptors. Prostaglandin receptors lack specific antibodies, which greatly impedes the research on our understanding of the signaling of prostaglandins. The aim of this study was to identify nine mouse lines with amino terminal (-NH2, -N) HA-tagged prostaglandin receptors by using the combination of artificial sperm and CRISPR-Cas9 technology. The guide RNA expression plasmid and labeled targeting vector plasmids were transferred into "artificial sperm cells". The "artificial sperm cells" containing labeled proteins were selected and injected into mouse oocytes, and implanted into pseudopregnant mice to obtain labeled mice. The genomic DNA of the prostaglandin receptor tagged mice was extracted, and the genotypes of mice were detected by PCR method. We also isolated mouse peritoneal macrophages to verify the protein expression of HA-labeled prostaglandin receptor by Western blot. Specific DNA bands were amplified in prostaglandin receptor labeled mice, and specific HA protein bands were detected in macrophage proteins, which was not detected in wild type mice. In summary, we successfully constructed 9 mouse lines with HA-tagged prostaglandin receptors, providing a powerful tool for further study of the pathophysiological functions of prostaglandin signaling both in vivo and in vitro.

Coherent charge-phonon correlations and exciton dynamics in orthorhombic CH3NH3PbI3 measured by ultrafast multi-THz spectroscopy.

We use time-resolved multi-terahertz spectroscopy for the range 4-40 meV to probe coherent and incoherent ultrafast charge carrier and exciton dynamics in the low temperature orthorhombic phase of the hybrid metal halide perovskite CH3NH3PbI3. Time- and energy-resolved terahertz reflectivity maps reveal strongly damped but coherent oscillations in the 2-4 THz reststrahlen band, indicating charge coupling to a distribution of low energy phonon modes centered at 0.9 THz (3.7 meV or 30 cm-1). First-principles calculations reveal that these modes are entirely of mixed organic/inorganic sublattice character, with the power spectrum of the coherent oscillations showing a high frequency cutoff just at the onset of organic cation-only vibrations. Two anomalous reflectivity signatures are observed which are not phonon related, which we assign to a free exciton at 12 meV appearing on a 0.5 ps time scale and a defect bound exciton at 29-32 meV appearing on slower 1 ps time scale. Our measurements reveal the coherent coupling of charges to low energy vibrations of mixed sublattice character and the presence of two distinct populations of free and bound excitons at low temperatures.

Carbon Nanotubes with Cobalt Corroles for Hydrogen and Oxygen Evolution in pH†0-14 Solutions.

Water splitting is promising to realize a hydrogen-based society. The practical use of molecular water-splitting catalysts relies on their integration onto electrode materials. We describe herein the immobilization of cobalt corroles on carbon nanotubes (CNTs) by four strategies and compare the performance of the resulting hybrids for H2 and O2 evolution. Co corroles can be covalently attached to CNTs with short conjugated linkers (the hybrid is denoted as H1) or with long alkane chains (H2), or can be grafted to CNTs via strong π-π interactions (H3) or via simple adsorption (H4). An activity trend H1≫H3>H2≈H4 is obtained for H2 and O2 evolution, showing the critical role of electron transfer ability on electrocatalysis. Notably, H1 is the first Janus catalyst for both H2 and O2 evolution reactions in pH 0-14 aqueous solutions. Therefore, this work is significant to show potential uses of electrode materials with well-designed molecular catalysts in electrocatalysis.