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Additional file 1: Figure S1. Characterization of hADMSCs. Figure S2. TGF-β1 activates hepatic stellate cells leading to ECM deposition and EMT progression. Figure S3. Inhibition of activated HSCs proliferation and activation by hADMSCs. Figure S4. Liver cirrhosis was successfully induced in C57BL/6J mice with CCl4 i.p. injections twice a week for 8 weeks. Figure S5. Ex vivo organ distribution of PKH26-hADMSCs-Exo in CCl4-induced liver fibrosis mouse model. Figure S6. Liver stiffness of mouse with different treatments was measured by shear wave elastrography (SWE) at predetermined time. Figure S7. Representative histopathology analysis of liver sections after 0, 2 and 4 weeks of hADMSCs-Exo treatment. Figure S8. GO and KEGG pathway analyses between LFG vs hADMSCs-Exo or REG. Figure S9. Western blot assay for AKT, mTOR and phosphorylated and total PI3K p85 and PI3K p110 in vivo (A) and in vitro (B). Figure S10. The gene coding for the key metabolite expression analysis in transcriptome. Figure S11. Western blot assay for pro-fibrogenic and PI3K/AKT/mTOR signaling protein expression in aHSCs following supplementation with hADMSCs-Exo and 10 mM choline or 10 mM phosphorylcholine simultaneously in vitro. Table S1. Primer sequences used in reverse transcription quantitative PCR (RT-qPCR). Table S2. Antibodies utilized in Western blot, immunohistochemistry or Immunofluorescence staining. Table S3. The top 25 significant KEGG pathway between hADMSCs-Exo group (n=3) and regression group (REG, n=3). Table S4. Significant metabolites between hADMSCs-Exo treatment group (n=6) and regression group (n=6) in the liver tissue samples. Table S5. Significant metabolites between hADMSCs-Exo treatment group (n=6) and liver fibrosis group (n=6) in the liver tissue samples.

Objective: To explore the molecular mechanism of umbilical cord blood mesenchymal stem cells (UCBMSCs) in the treatment of advanced osteoarthritis pain. Methods: Normal healthy rats were selected to establish advanced osteoarthritis (OA) model, and the rats were randomly divided into control group, intravenous group, intracavitary group and intrathecal group. The intravenous group received intravenous injection of UCBMSCs, intracavitary group received intra-articular injection of UCBMSCs, and intrathecal group received subarachnoid injection of UCBMSCs. The pain behavior and serum pro-inflammatory factor levels were evaluated before and after treatment. microRNA-29a-3p and FOS mRNA in spinal dorsal horn was detected using qPCR, the phosphorylation of c-fos protein and NR1, NR2B, ERK and PKCg was detected using Western blot, and the level of LncRNA H19 was detected using qPCR. Results: LncRNA H19 was enriched in the exosomes of UCBMSCs. microRNA-29a-3p was the target gene of LncRNA H19, while FOS was the downstream target of microRNA-29a-3p. Pain and inflammation of rats in the intrathecal group improved best, and the phosphorylation levels of c-fos and NR1, NR2B, ERK and PKCg in the spinal dorsal horn of the intrathecal group decreased. LncRNA H19 regulated the central sensitization of astrocytes through microRNA-29a-3p/FOS axis. Conclusion: Intrathecal injection of umbilical cord blood mesenchymal stem cells can improve the pain and central sensitization of advanced osteoarthritis through LncRNA H19/microRNA-29a-3p/FOS axis.

Uranium-series dating of carbonatitic ejecta clasts constrains the crystallization and differentiation timescales of the Laacher See volcano, which erupted 6·3 km3 of magma (dense rock equivalent) during one of the largest Late Quaternary eruptions in Central Europe. Carbonatites form a distinct population among plutonic ejecta that are present in the middle and late erupted Laacher See tephra. Characteristic trace element patterns of the carbonatites, including negative Eu anomalies, and mantle-like oxygen isotopic compositions preserved in zircon indicate that the Laacher See carbonatites are cogenetic with their phonolite host. Carbonatite U-Th zircon isochron ages range from 32·6 ± 4·1 ka (2σ; MSWD = 1·7; n = 24) to near-eruption age (12·9 ka). Uranium-series carbonatite ages qualitatively agree with alkali feldspar compositions that lack prominent magmatic zonation, but show evidence for perthitic unmixing during subsolidus residence at elevated temperatures (720°C). Model differentiation ages and crystallization ages for the carbonatites overlap within a few thousand years as resolved by U-Th dating and indicate rapid crystallization following carbonatite segregation from its parental phonolite. Model differentiation and zircon isochron ages peak at ∼17 ka, suggesting a major phase of differentiation of the Laacher See magma system at this time, although the onset of phonolite differentiation dates back to at least ∼10-20 kyr prior to eruption. Phenocrysts in the middle and late erupted phonolite magma crystallized shortly before eruption, and the lack of older crystals implies crystal removal through settling or resorption. Crystal ages from both crystal-rich and liquid-dominated parts of a magma system are thus complementary, and reveal different aspects of magma differentiation and residence timescales

Despite the theoretical advantages of laparoscopic hepatectomy, it is still not considered the standard treatment for hepatocellular carcinoma patients because of criticism concerning oncologic stability. This study aimed at examining the short- and long-term follow-up results of laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma and at investigating clinical outcomes, oncologic safety, and any potential advantages of laparoscopic hepatectomy for hepatocellular carcinoma. A series of 53 patients who underwent laparoscopic hepatectomy (Lap group) for hepatocellular carcinoma were matched with 53 patients who underwent open hepatectomy during the same time period (Open group). The short- and long-term outcomes were compared between the two groups of patients. The patients who underwent the laparoscopic procedure showed a significantly faster recovery and less blood loss compared with patients who underwent open surgery. No differences were found in 5-year overall and disease-free survival rates. Our results suggested that the laparoscopic approach was as safe as the open alternative. Laparoscopic hepatectomy has been shown to be a favorable surgical option with better short-term outcomes and similar long-term oncological control compared with open hepatectomy.

Magmatism in SE China was dormant during 204–180 Ma, but was reactivated in 180–170 Ma (early J2), and then became more and more intensive towards the end of early Cretaceous. The small-scale early J2 magmatism is the incipience to long-term and large-scale magmatism in this region. A near east-west (EW) trend volcanic belt was distributed across south Hunan, south Jiangxi and southwest Fujian was formed during early J2 time. Along this belt from the inland toward the coast, the lithology of basalts changes from alkali into tholeiite, and the amount of erupted volcanic rocks and the proportions of rhyolites coexisting with the basalts increase. On the basis of geochemical characteristics of these basalts, we infer that the melting degree of source rocks and the extent of fractional crystallization and crustal contamination all increased whereas the depth of mantle source decreased from the inland to the coast, which led to the variations of geological characteristics of the volcanic belt. In early J2, the western spreading Pacific plate began to subduct underneath SE China continental block, reactivating near EW trend deep fault that was originally formed during the Indosinian event. The stress of the western spreading Pacific plate and the extent of asthenosphere upwelling increased from the inland to the coast, which is consistent with the generation and evolution of early J2 basalts.

The Fuchuan ophiolite suite in Shexian County, Anhui Province, was formed in the Middle-Late Proterozoic. It is characterized by varying Nd [∈Nd (T) =0.7−3.8], Sr [∈Sr(T) = 30.7−53.9] and O(δ18O=3.2−11.0%.) and low ratios of Nd/La (