Hepatic senescence, the good and the bad

Gradual alterations of cell's physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent cells. Once becoming senescent, the cell stops dividing permanently but remains metabolically active. Cellular senescence does not have a single marker but is characterized mainly by a combination of multiple markers, such as, morphological changes, expression of cell cycle inhibitors, senescence associated β-galactosidase activity, and changes in nuclear membrane. When cells in an organ become senescent, the entire organism can be affected. This may occur through the senescence-associated secretory phenotype (SASP). SASP may exert beneficial or harmful effects on the microenvironment of tissues. Research on senescence has become a very exciting field in cell biology since the link between age-related diseases, including cancer, and senescence has been established. The loss of regenerative and homeostatic capacity of the liver over the age is somehow connected to cellular senescence. The major contributors of senescence properties in the liver are hepatocytes and cholangiocytes. Senescent cells in the liver have been implicated in the etiology of chronic liver diseases including cirrhosis and hepatocellular carcinoma and in the interference of liver regeneration. This review summarizes recently reported findings in the understanding of the molecular mechanisms of senescence and its relationship with liver diseases

Autophagy, Metabolism, and Alcohol-Related Liver Disease: Novel Modulators and Functions

Alcohol-related liver disease (ALD) is caused by over-consumption of alcohol. ALD can develop a spectrum of pathological changes in the liver, including steatosis, inflammation, cirrhosis, and complications. Autophagy is critical to maintain liver homeostasis, but dysfunction of autophagy has been observed in ALD. Generally, autophagy is considered to protect the liver from alcohol-induced injury and steatosis. In this review, we will summarize novel modulators of autophagy in hepatic metabolism and ALD, including autophagy-mediating non-coding RNAs (ncRNAs), and crosstalk of autophagy machinery and nuclear factors. We will also discuss novel functions of autophagy in hepatocytes and non-parenchymal hepatic cells during the pathogenesis of ALD and other liver diseases

The HMGB1-RAGE axis modulates the growth of autophagy-deficient hepatic tumors

Autophagy is an intracellular lysosomal degradative pathway important for tumor surveillance. Autophagy deficiency can lead to tumorigenesis. Autophagy is also known to be important for the aggressive growth of tumors, yet the mechanism that sustains the growth of autophagy-deficient tumors is not unclear. We previously reported that progression of hepatic tumors developed in autophagy-deficient livers required high mobility group box 1 (HMGB1), which was released from autophagy-deficient hepatocytes. In this study we examined the pathological features of the hepatic tumors and the mechanism of HMGB1-mediated tumorigenesis. We found that in liver-specific autophagy-deficient (Atg7ΔHep) mice the tumors cells were still deficient in autophagy and could also release HMGB1. Histological analysis using cell-specific markers suggested that fibroblast and ductular cells were present only outside the tumor whereas macrophages were present both inside and outside the tumor. Genetic deletion of Hmgb1 or one of its receptors, receptor for advanced glycated end product (Rage), retarded liver tumor development. HMGB1 and RAGE enhanced the proliferation capability of the autophagy-deficient hepatocytes and tumors. However, RAGE expression was only found on ductual cells and Kupffer's cells but not on hepatoctyes, suggesting that HMGB1 might promote hepatic tumor growth through a paracrine mode, which altered the tumor microenvironment. Finally, RNAseq analysis of the tumors indicated that HMGB1 induced a much broad changes in tumors. In particular, genes related to mitochondrial structures or functions were enriched among those differentially expressed in tumors in the presence or absence of HMGB1, revealing a potentially important role of mitochondria in sustaining the growth of autophagy-deficient liver tumors via HMGB1 stimulation

Geochemical Characteristics of Chlorite in Xiangshan Uranium Ore Field, South China and Its Exploration Implication

Chlorite is one of the most important hydrothermal minerals in many hydrothermal uranium deposits worldwide and is commonly closely associated with the uranium mineralization. Trace elements in chlorite have been extensively applied to fingerprinting the hydrothermal fluid evolution and indicating the concealed ore bodies in porphyry Cu (-Au) deposits and skarn-related Pb-Zn deposits. However, this approach was rarely attempted on hydrothermal uranium deposits to date. Xiangshan uranium ore field, located in the southeast part of Gan-Hang Metallogenic (or Volcanic) Belt (GHMB), is the largest volcanic-related ore field in the whole country. In this study, the focus was placed on the petrographic characteristics and trace elements in hydrothermal chlorite from two typical deposits (Zoujiashan and Yunji) at Xiangshan. Four types of chlorites were identified, i.e., Chl1-Y and Chl2 from Yunji deposit, and Chl1-Z and Chl3 from Zoujiashan deposit. The pre-ore Chl1-Y and Chl1-Z are formed through replacing the original magmatic biotite. Chl2 and Chl3 occur as veinlets or disseminated, and are closely associated with early-ore U mineralization and main-ore U mineralization, respectively. All the four types of chlorites are typically trioctahedral chlorite. Vein-type/disseminated Chl2 and Chl3 in ore veins were precipitated directly from the hydrothermal fluids through dissolution-migration-precipitation mechanism, whereas the replacement-type chlorite was formed by the dissolution–crystallization mechanism. Empirical geothermometry indicates that the chlorite from Yunji and Zoujiashan were crystallized at 179~277 °C, indicating a mesothermal-epithermal precipitation environment. EPMA and LA-ICP-MS results show that the replacement-type chlorite has relatively consistent compositions at Yunji and Zoujiashan. Both Chl2 and Chl3 are enriched in U, Th but depleted in Mn and Ti. Compared with the Chl2 related to early-ore U mineralization, Chl3 that formed at main-ore stage has higher concentrations of Fe, U, Th, REEs, Mn and Ti, as well as higer Fe/(Fe + Mg) ratios. Such compositional differences between Chl2 and Chl3 are mainly attributed to the formation temperatures and fluid compositions/natures. Combined with petrology and chemical compositions of different types of chlorite, we propose that the presence of vein-type/disseminated chlorite with high U and Fe/(Fe + Mg) ratio but relatively low Mn, Ti and Pb contents can be regarded as an effective vector toward the most economic (high U grade) mineralized zone, whereas the occurrence of Chl2 is likely to indicate the subeconomic U mineralization and less potential exploration for uranium at depth

Fabrication of Microglass Nozzle for Microdroplet Jetting

An ejection aperture nozzle is the essential part for all microdrop generation techniques. The diameter size, the flow channel geometry, and fluid impedance are the key factors affecting the ejection capacity. A novel low-cost fabrication method of microglass nozzle involving four steps is developed in this work. In the first heating step, the glass pipette is melted and pulled. Then, the second heating step is to determine the tip cone angle and modify the flow channel geometry. The desired included angle is usually of 30~45 degrees. Fine grind can determine the exact diameter of the hole. Postheating step is the final process and it can reduce the sharpness of the edges of the hole. Micronozzles with hole diameters varying from 30 to 100 µm are fabricated by the homemade inexpensive and easy-to-operate setup. Hydrophobic treating method of microglass nozzle to ensure stable and accurate injection is also introduced in this work. According to the jetting results of aqueous solution, UV curing adhesive, and solder, the fabricated microglass nozzle can satisfy the need of microdroplet jetting of multimaterials

An Implementation of Interactive Jobs Submission for Grid Computing Portals

The Globus Toolkit has been widely used as middleware in Grid computing environments. Java CoG, Web Service and Portlet help to build Grid computing portals easily and productively. Many Grid Portals can provide a customizable interface allowing scientists and researchers to perform Grid operations such as remote submission of their own programs, staging input and ouput files, and querying resources and queues information. However, the Globus Toolkit does not support interactive jobs submission, nor is there an interactive extension for Grid computing portals. In this paper, a Grid Security Infrastructure (GSI) enabled Java SSH client is introduced and implemented as a novel way to submit interactive jobs to the computing resources in ScGrid, which is a scientific computing environment provided by the Supercomputing Center, Computer Network Information Center, Chinese Academy of Sciences (SCCAS). Keywords: Grid Computing, Grid Portals, Interactive Jobs, GSISSH