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Analyzing the genetic diversity and selection characteristics of sheep (Ovis aries) holds significant value in understanding their environmental adaptability, enhancing breeding efficiency, and achieving effective conservation and rational utilization of genetic resources. In this study, we utilized Illumina Ovine SNP 50 K BeadChip data from four indigenous sheep breeds from the southern margin of the Taklamakan Desert (Duolang sheep: n = 36, Hetian sheep: n = 74, Kunlun sheep: n = 27, Qira black sheep: n = 178) and three foreign meat sheep breeds (Poll Dorset sheep: n = 105, Suffolk sheep: n = 153, Texel sheep: n = 150) to investigate the population structure, genetic diversity, and genomic signals of positive selection within the indigenous sheep. According to the Principal component analysis (PCA), the Neighbor-Joining tree (NJ tree), and Admixture, we revealed distinct clustering patterns of these seven sheep breeds based on their geographical distribution. Then used Cross Population Extended Haplotype Homozygosity (XP-EHH), Fixation Index (FST), and Integrated Haplotype Score (iHS), we identified a collective set of 32 overlapping genes under positive selection across four indigenous sheep breeds. These genes are associated with wool follicle development and wool traits, desert environmental adaptability, disease resistance, reproduction, and high-altitude adaptability. This study reveals the population structure and genomic selection characteristics in the extreme desert environments of native sheep breeds from the southern edge of the Taklimakan Desert, providing new insights into the conservation and sustainable use of indigenous sheep genetic resources in extreme environments. Additionally, these findings offer valuable genetic resources for sheep and other mammals to adapt to global climate change. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts. [ABSTRACT FROM AUTHOR]

Azoxy compounds have aroused extensive attention due to their unique biological activities, but the chemical synthesis of these compounds often suffers from limitations due to their requirement for stoichiometric oxidants, high costs, and restricted substrate range. Herein, a series of azoxy compounds were constructed via facile coupling reactions by using cost‐effective N‐methoxyformamide and nitroso compounds over Cu‐based catalysts, affording high product yields with excellent tolerance of functional groups. Significantly, the mesoporous silica nanosphere‐encapsulated ultrasmall Cu (Cu@MSN) catalyst was developed via a one‐pot synthetic method and first used for the synthesis of azoxy compounds. As compared with copper salt catalysts, the Cu@MSN catalyst exhibited remarkably enhanced catalytic activity and superior recycling stability. Such a Cu@MSN catalyst overcame the inherent drawbacks of low activity, fast deactivation, and difficult recycling of traditional metal salt catalysts in organic reactions. This work provides a green and efficient method for the construction of azoxy compounds and also creates new prospects for the application of nanoporous materials confined metal catalysts in organic synthesis. [ABSTRACT FROM AUTHOR]

The influences of ammonia (NH3) and greenhouse gas (GHG) emissions from livestock on environment recently become a major concern of the worldwide. The objective of the study was to evaluate the effects of Yucca schidigera extract (YSE) on ammonia emission in manure and the release of green-house gases including methane (CH4), nitrous oxide (N2O) and carbon dioxide (CO2) in artificial rumen of cows. Addition of YSE significantly decreased ammonia nitrogen (NH3-N) concentration (P < 0.01) and increased the percentage of total nitrogen (N) (P < 0.005) in manure incubation. The populations of total aerobic bacteria were significantly decreased by the addition of YSE with 1% and 2% (P < 0.05), while the populations of Lactobacilli were significantly increased in dose-dependent manner (P <0.001) in manure. In 1-12 h and 13-24h of ruminal fermentation in vitro, the yields of CH4, CO2 and N2O were dose-dependently reduced by the addition of YSE (P < 0.05). Results showed that YSE inhibit ammonia emission in manure and the release of green-house gases in artificial rumen of cows. [ABSTRACT FROM AUTHOR]

A rhodium-catalyzed synthesis of indoloquinazolinone from a readily available hypervalent iodonium reagent and N-carboxamide indole was developed. The protocol features broad functional group tolerance, mild conditions, and excellent yields. The target products were obtained simply by filtration, without tedious column chromatography. Notably, the noble metal catalyst system can be recycled effectively at least ten times. The strategy may be amenable to industrial production. [ABSTRACT FROM AUTHOR]

Normally, hepatic progenitor cells (HPCs) are activated and differentiate into hepatocytes or bile ductular cells to repair liver damage during liver injury. However, it remains controversial whether the abnormal differentiation of HPCs occurs under abnormal conditions. Lipopolysaccharide (LPS), a component of the microenvironment, promotes liver fibrosis. In the present study, HPCs promoted liver fibrosis in rats following carbon tetrachloride (CCl4) treatment. Meanwhile, the LPS level in the portal vein was elevated and played a primary role in the fate of HPCs.In vitro, LPS inhibited the hepatobiliary differentiation of HPCs. Concurrently, HPCs co-cultured with LPS for 2 weeks showed a tendency to differentiate into myofibroblasts (MFs). Thus, we conclude that LPS promotes the aberrant differentiation of HPCs into MFs as a third type of descendant. This study provides insight into a novel differentiation fate of HPCs in their microenvironment, and could thus lead to the development of HPCs for treatment methods in liver fibrosis. [ABSTRACT FROM PUBLISHER]

Hyperimmunoglobulinemia is frequently observed in patients with chronic liver diseases. However, the exact mechanism underlying the high level of antibody formation is not fully understood. In our study, we provide evidence for the functional role of the liver and the stimulation of plasma cell proliferation in hyperimmunoglobulinemia. We collected sera from patients with chronic liver diseases, and the level of serum immunoglobulins in patients was examined; this was also investigated in animal models of liver cirrhosis and hepatocellular carcinoma. An end-to-side microsurgical portacaval shunt was used to mimic liver dysfunction in rats. We used portal vein serum and inferior vena cava serum to immunize healthy rats and mice in order to confirm the function of the healthy liver in disposing of antigens and endotoxins from the gut. For the analysis of the state of plasma cell activation, plasma cells from mice were stained with PE-conjugated anti-CD138 and FITC-conjugated anti-BrdU for flow cytometry analysis. Hyperimmunoglobulinemia was observed both in patients with chronic liver diseases and in related animal models, and high plasma LPS levels were also observed. There was a significant increase in the activation and proliferation of plasma cell in mice immunized with antigens or LPS-positive serum compared with controls that were immunized with antigens and LPS-negative serum. We confirmed that the healthy liver plays an important role in disposing of antigens and endotoxins derived from the gut. Hyperimmunoglobulinemia in chronic liver diseases mainly arises due to the collateral circulation secondary to portal hypertension, gut antigens and endotoxins that bypass the liver and reach the antibody-producing cells. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs), the major stem cells for cell therapy, have been used in the clinic for approximately 10 years. From animal models to clinical trials, MSCs have afforded promise in the treatment of numerous diseases, mainly tissue injury and immune disorders. In this review, we summarize the recent opinions on methods, timing and cell sources for MSC administration in clinical applications, and provide an overview of mechanisms that are significant in MSC-mediated therapies. Although MSCs for cell therapy have been shown to be safe and effective, there are still challenges that need to be tackled before their wide application in the clinic. [ABSTRACT FROM AUTHOR]

Background: Babao Dan (BBD), a traditional Chinese medicine, has been used as a complementary and alternative medicine to treat multifarious liver diseases. In this study, we aimed to observe its protective effect on ethanol-induced liver injury and explore potential mechanisms. Methods: Mice pretreated with BBD (0.125, 0.25 and 0.5 g/kg BW) were administrated by ethanol gavage (5 g/kg BW). Liver injury biomarkers and hepatic redox parameters were evaluated by histopathology as well as serum and hepatic content analysis. AML-12 cell was also utilized to determine the efficacy of BBD against ethanol-induced hepatotoxicity. Results: Drunkenness experiment showed that the latency was significantly increased and the drunken sleep time was decreased in mice pretreated with BBD. We then found that BBD could reduce hepatic lipid peroxidation and steatosis induced by ethanol exposure. BBD could also suppress ethanol-induced depletion of hepatic antioxidant enzyme. Besides that, BBD treatment lessened the induction of hepatic cytochrome P450 2E1, a major contributor to ethanol-mediated oxidative stress, and up-regulated the expression of nuclear factor erythroid 2-related factor 2 and its two transcriptional targets hemeoxygenase-1 and glutamate-cysteine ligase catalytic subunit. Furthermore, autophagy induced by BBD contributed to hepatoprotection activity. Conclusions: Our results suggest that BBD can markedly dispel acute ethanol-induced hepatotoxicity through multiple pathways including attenuation of ethanol-mediated oxidative stress, enhancement of the oxidative defense systems and activation of autophagy. [ABSTRACT FROM AUTHOR]

Background: The endotoxin level in the portal and peripheral veins of hepatocellular carcinoma (HCC) patients is higher and lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to inhibit tumor growth. However, in this study, we found that LPS-induced toll-like receptor 4 (TLR4) signaling was involved in tumor invasion and survival, and the molecular mechanism was investigated,Methods: Four HCC cell lines and a splenic vein metastasis of the nude mouse model were used to study the invasion ability of LPS-induced HCC cells and the epithelia-mesenchymal transition (EMT) in vitro and in vivo. A total of 106 clinical samples from HCC patients were used to evaluate TLR4 expression and analyze its association with clinicopathological characteristicsResults: The in vitro and in vivo experiments demonstrated that LPS could significantly enhance the invasive potential and induce EMT in HCC cells with TLR4 dependent. Further studies showed that LPS could directly activate nuclear factor kappa B (NF-κB) signaling through TLR4 in HCC cells. Interestingly, blocking NF-κB signaling significantly inhibited transcription factor Snail expression and thereby inhibited EMT occurrence. High expression of TLR4 in HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients.Conclusions: Our results indicate that TLR4 signaling is required for LPS-induced EMT, tumor cell invasion and metastasis, which provide molecular insights for LPS-related pathogenesis and a basis for developing new strategies against metastasis in HCC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC), which frequently metastasizes to the liver, is one of the three leading causes of cancer-related deaths worldwide. Growing evidence suggests that a subset of cells exists among cancer stem cells. This distinct subpopulation is thought to contribute to liver metastasis; however, it has not been fully explored in CRC yet.Methods: Flow cytometry analysis was performed to detect distinct subsets with CD133 and CXCR4 markers in human primary and metastatic CRC tissues. The 'stemness' and metastatic capacities of different subpopulations derived from the colon cancer cell line HCT116 were compared in vitro and in vivo. The roles of epithelial-mesenchymal transition (EMT) and stromal-cell derived factor-1 (SDF-1) in the metastatic process were also investigated. A survival curve was used to explore the correlation between the content of CD133(+)CXCR4(+) cancer cells and patient survival.Results: In human specimens, the content of CD133(+)CXCR4(+) cells was higher in liver metastases than in primary colorectal tumors. Clonogenic and tumorigenic cells were restricted to CD133(+) cells in the HCT116 cell line, with CXCR4 expression having no impact on the 'stemness' properties. We found that CD133(+)CXCR4(+)cancer cells had a high metastatic capacity in vitro and in vivo. Compared with CD133(+)CXCR4(-) cells, CD133(+)CXCR4(+)cancer cells experienced EMT, which contributed partly to their metastatic phenotype. We then determined that SDF-1/CXCL12 treatment could further induce EMT in CD133(+)CXCR4(+)cancer cells and enhance their invasive behavior, while this could not be observed in CD133(+)CXCR4- cancer cells. Blocking SDF-1/CXCR4 interaction with a CXCR4 antagonist, AMD3100 (1,10-[1,4-phenylenebis(methylene)]bis-1,4,8,11 -tetraazacyclotetradecane octahydrochloride), inhibited metastatic tumor growth in a mouse hepatic metastasis model. Finally, a high percentage of CD133(+)CXCR4(+)cells in human primary CRC was associated with a reduced two-year survival rate.Conclusions: Strategies targeting the SDF-1/CXCR4 interaction may have important clinical applications in the suppression of colon cancer metastasis. Further investigations on how high expression of CXCR4 and EMT occur in this identified cancer stem cell subset are warranted to provide insights into our understanding of tumor biology. [ABSTRACT FROM AUTHOR]