Population phylogenomic analysis of mitochondrial DNA in wild boars and domestic pigs revealed multiple domestication events in East Asia

A fine-grained mitochondrial DNA phylogenomic analysis was conducted in domestic pigs and wild boars, revealing that pig domestication in East Asia occurred in the Mekong and the middle and downstream regions of the Yangtze river

Chronic Unpredictable Mild Stress Promotes Atherosclerosis via HMGB1/TLR4-Mediated Downregulation of PPARγ/LXRα/ABCA1 in ApoE-/- Mice

Background: Although our previous studies have confirmed that the activation of TLR4 is implicated in the development of atherosclerosis induced by chronic unpredicted mild stress (CUMS), the underling mechanism is largely unclear. Here, we hypothesized that CUMS accelerates atherosclerotic development through lowering PPARγ/LXRα-ABCA1 expression via HMGB1/TLR4 signaling.Methods: In present study, CUMS atherosclerotic animal models were established with AopE-/- mice, and CUMS Raw 264.7 macrophage models were mimicked by high corticosterone treatment, These models were treated with Ethyl pyruvate (EP, an inhibitor of HMGB1), TLR4 inhibitor TAK-242, and PPARγ agonist RSG (Rosiglitazone) to test our hypothesis, respectively.Results: Our results indicated that the protein levels of HMGB1, TLR4, and pro-inflammatory cytokines including IL-1β, TNF-α were elevated with the development of atherosclerosis in CUMS mice, while the expressions of PPARγ, LXRα, and ABCA1 declined. Notably, HMGB1 inhibition by EP reversed CUMS-induced atherosclerotic development, pro-inflammatory cytokines upregulation, and PPARγ/LXRα-ABCA1 downregulation. The same trend was observed in the stressed mice treatment with TAK-242. Further experimental evidences indicated that EP, TAK-242, and RSG treatment notably corrected foam cell formation, HMGB1 release, and down-regulation of LXRα and ABCA1 in CUMS Raw 264.7 macrophage model.Conclusion: These results indicate that CUMS exacerbates atherosclerosis is likely via HMGB1-mediated downregulation of PPARγ/LXRα-ABCA1 through TLR4. These data reveal a novel mechanism by which CUMS aggravates atherosclerosis and may offer a potential therapeutic target for this disease

The Hidden Nematic Fluctuations in the Triclinic (Ca0.85La0.15)10(Pt3As8)(Fe2As2)5 Superconductor Revealed by Ultrafast Optical Spectroscopy

We reported the quasiparticle relaxation dynamics of an optimally doped triclinic iron-based superconductor (Ca$_{0.85}$La$_{0.15}$)$_{10}$(Pt$_3$As$_8$)(Fe$_2$As$_2$)$_5$ with bulk $T_c$ = 30 K using polarized ultrafast optical pump-probe spectroscopy. Our results reveal anisotropic transient reflectivity induced by nematic fluctuations develops below $T_{nem}$ $\approx$ 120 K and persists in the superconducting states. Measurements under high pump fluence reveal three distinct, coherent phonon modes at frequencies of 1.6, 3.5, and 4.7 THz, corresponding to $A_{1g}(1)$, $E_g$, and $A_{1g}(2)$ modes, respectively. The high-frequency $A_{1g}(2)$ mode corresponds to the $c$-axis polarized vibrations of FeAs planes with a nominal electron-phonon coupling constant $\lambda _{A_{1g}(2)}$ $\approx$ 0.139 $\pm$ 0.02. Our findings suggest that the superconductivity and nematic state are compatible but competitive at low temperatures, and the $A_{1g}$ phonons play an important role in the formation of Cooper pairs in (Ca$_{0.85}$La$_{0.15}$)$_{10}$(Pt$_3$As$_8$)(Fe$_2$As$_2$)$_5$.Comment: 6 pages, 3 figures and Supplemental Material

Dynamic prostatic and laser-ablated lesion volume change after transperineal laser ablation in canine: preliminary observation and its clinical significance.

AIM: The purpose of this study is to observe the volume change of prostate and laser-ablated lesions in the canine and to explore the mechanism and clinical significance through histopathology. MATERIALS AND METHODS: Transperineal laser ablation (TPLA) was performed under the guidance of transrectal ultrasound (TRUS) in eight canines. Two canines were sacrificed 1 day and 1 week after TPLA, respectively. The remaining six canines were sacrificed after finishing transrectal contrast-enhanced ultrasound (TR-CEUS) at three phases. RESULTS: The prostatic volumes immediately following TPLA and 1 week later were larger than before TPLA (20.1 ± 3.9 vs 17.1 ± 3.8 ml; 21.7 ± 3.6 vs 17.1 ± 3.8 ml, p \u3c 0.05), but 1 month later, returned to the preoperative level (17.4 ± 3.2 ml). At three time points, the mean volumes of laser-ablated lesions at 3 W/600 J were 0.6 ± 0.2, 1.1 ± 0.4, and 1.7 ± 0.5 ml, respectively, while those of laser-ablated lesions at 3 W/1200 J were 1.2 ± 0.2, 1.6 ± 0.3, and 2.2 ± 0.5 ml, respectively. The mean volumes of laser-ablated lesions increased significantly over time after TPLA (p \u3c 0.050). CONCLUSION: The prostate volume transient enlarges after TPLA, which prompts for clinical application that it should prolong appropriately the duration of urinary catheterization to avoid acute urinary retention. Many inflammatory cells were observed in the laser-ablated lesions and adjacent normal prostate parenchyma through histopathology. It is speculated that the inflammatory response is involved in the progression of tissue damage

EBV-Encoded LMP1 Upregulates Igκ 3′Enhancer Activity and Igκ Expression in Nasopharyngeal Cancer Cells by Activating the Ets-1 through ERKs Signaling

Accumulating evidence indicates that epithelial cancer cells, including nasopharyngeal carcinoma (NPC) cells, express immunoglobulins (Igs). We previously found that the expression of the kappa light chain protein in NPC cells can be upregulated by the EBV-encoded latent membrane protein 1 (LMP1). In the present study, we used NPC cell lines as models and found that LMP1-augmented kappa production corresponds with elevations in ERKs phosphorylation. PD98059 attenuates LMP1-induced ERKs phosphorylation resulting in decreased expression of the kappa light chain. ERK-specific small interfering RNA blunts LMP1-induced kappa light chain gene expression. Luciferase reporter assays demonstrate that immunoglobulin κ 3′ enhancer (3′Eκ) is active in Igκ-expressing NPC cells and LMP1 upregulates the activity of 3′Eκ in NPC cells. Moreover, mutation analysis of the PU binding site in 3′Eκ and inhibition of the MEK/ERKs pathway by PD98059 indicate that the PU site is functional and LMP1-enhanced 3′Eκ activity is partly regulated by this site. PD98059 treatment also leads to a concentration-dependent inhibition of LMP1-induced Ets-1 expression and phosphorylation, which corresponds with a dose-dependent attenuation of LMP1-induced ERK phosphorylation and kappa light chain expression. Suppression of endogenous Ets-1 by small interfering RNA is accompanied by a decrease of Ig kappa light chain expression. Gel shift assays using nuclear extracts of NPC cells indicate that the transcription factor Ets-1 is recruited by LMP1 to the PU motif within 3′Eκ in vitro. ChIP assays further demonstrate Ets-1 binding to the PU motif of 3′Eκ in cells. These results suggest that LMP1 upregulates 3′Eκ activity and kappa gene expression by activating the Ets-1 transcription factor through the ERKs signaling pathway. Our studies provide evidence for a novel regulatory mechanism of kappa expression, by which virus-encoded proteins activate the kappa 3′ enhancer through activating transcription factors in non-B epithelial cancer cells

Hepcidin Is Involved in Iron Regulation in the Ischemic Brain

Oxidative stress plays an important role in neuronal injuries caused by cerebral ischemia. It is well established that free iron increases significantly during ischemia and is responsible for oxidative damage in the brain. However, the mechanism of this ischemia-induced increase in iron is not completely understood. In this report, the middle cerebral artery occlusion (MCAO) rat model was performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion was studied. The expression of L-ferritin was significantly increased in the cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H-ferritin was reduced in the striatum and increased in the cerebral cortex and hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1) significantly decreased, while the expression of transferrin receptor 1 (TfR1) was increased. In order to elucidate the mechanisms of FPN1 regulation, we studied the expression of the key regulator of FPN1, hepcidin. We observed that the hepcidin level was significantly elevated in the ischemic side of the brain. Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1 invoked by ischemia-reperfusion. The results indicate that hepcidin is an important contributor to iron overload in cerebral ischemia. Furthermore, our results demonstrated that the levels of hypoxia-inducible factor-1α (HIF-1α) were significantly higher in the cerebral cortex, hippocampus and striatum on the ischemic side; therefore, the HIF-1α-mediated TfR1 expression may be another contributor to the iron overload in the ischemia-reperfusion brain