Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.     

Resource management in UAV-assisted MEC: state-of-the-art and open challenges

Wireless Networks - Unmanned aerial vehicles (UAV) have been widely used in various fields because of their high mobility and portability. At the same time, due to the rapid development of...     

A new smart smudge attack using CNN

International Journal of Information Security - This paper deals with a well-known problem in the area of the smudge attacks: when a user draws a pattern to unlock the pattern lock on a smartphone...     

Transgenerational Effects of Di(2-Ethylhexyl) Phthalate on Anogenital Distance,Sperm Functions and DNA Methylation in Rat Offspring

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in the manufacture of polyvinylchloride plastics and has been associated with concerns regarding male reproductive toxicity. In this study, we hypothesized that maternal exposure to DEHP induces transgenerational inheritance of adult-onset adverse reproductive outcomes through the male germline in the F1, F2, and F3 generations of male offspring. Pregnant rats were treated with 5 or 500 mg of DEHP/kg/day through gavage from gestation day 0 to birth. The offspring body weight, anogenital distance (AGD), anogenital index (AGI), sperm count, motility, and DNA fragmentation index (DFI) were measured for all generations. Methyl-CpG binding domain sequencing was performed to analyze sperm DNA methylation status in the F3. DEHP exposure at 500 mg/kg affected AGD, AGI, sperm count, mean DFI, and %DFI in the F1; AGD, sperm count, and mean DFI in the F2; and AGD, AGI, mean DFI, and %DFI in the F3. DEHP exposure at 5 mg/kg affected AGD, AGI, sperm count, and %DFI in the F1; sperm count in the F2; and AGD and AGI in F3. Compared with the control group, 15 and 45 differentially hypermethylated genes were identified in the groups administered 5 mg/kg and 500 mg/kg DEHP, respectively. Moreover, 130 and 6 differentially hypomethylated genes were observed in the groups administered 5 mg/kg and 500 mg/kg DEHP. Overall, these results demonstrated that prenatal exposure to DEHP caused transgenerational epigenetic effects, which may explain the observed phenotypic changes in the male reproductive system.     

Noncentrosymmetric Tetrel Pnictides RuSi4P4 and IrSi3P3: Nonlinear Optical Materials with Outstanding Laser Damage Threshold

Noncentrosymmetric (NCS) tetrel pnictides have recently generated interest as nonlinear optical (NLO) materials due to their second harmonic generation (SHG) activity and large laser damage threshold (LDT). Herein nonmetal-rich silicon phosphides RuSi₄P₄ and IrSi₃P₃ are synthesized and characterized. Their crystal structures are reinvestigated using single crystal X-ray diffraction and ²⁹Si and ³¹P magic angle spinning NMR. In agreement with previous report RuSi₄P₄ crystallizes in NCS space group P1, while IrSi₃P₃ is found to crystallize in NCS space group Cm, in contrast with the previously reported space group C2. A combination of DFT calculations and diffuse reflectance measurements reveals RuSi₄P₄ and IrSi₃P₃ to be wide bandgap (E_g) semiconductors, E_g = 1.9 and 1.8 eV, respectively. RuSi₄P₄ and IrSi₃P₃ outperform the current state-of-the-art infrared SHG material, AgGaS₂, both in SHG activity and laser inducer damage threshold. Due to the combination of high thermal stabilities (up to 1373 K), wide bandgaps (≈2 eV), NCS crystal structures, strong SHG responses, and large LDT values, RuSi₄P₄ and IrSi₃P₃ are promising candidates for longer wavelength NLO materials.     

Syndecan-1 (CD138), Carcinomas and EMT

Cell surface proteoglycans are known to be important regulators of many aspects of cell behavior. The principal family of transmembrane proteoglycans is the syndecans, of which there are four in mammals. Syndecan-1 is mostly restricted to epithelia, and bears heparan sulfate chains that are capable of interacting with a large array of polypeptides, including extracellular matrix components and potent mediators of proliferation, adhesion and migration. For this reason, it has been studied extensively with respect to carcinomas and tumor progression. Frequently, but not always, syndecan-1 levels decrease as tumor grade, stage and invasiveness and dedifferentiation increase. This parallels experiments that show depletion of syndecan-1 can be accompanied by loss of cadherin-mediated adhesion. However, in some tumors, levels of syndecan-1 increase, but the characterization of its distribution is relevant. There can be loss of membrane staining, but acquisition of cytoplasmic and/or nuclear staining that is abnormal. Moreover, the appearance of syndecan-1 in the tumor stroma, either associated with its cellular component or the collagenous matrix, is nearly always a sign of poor prognosis. Given its relevance to myeloma progression, syndecan-1-directed antibody—toxin conjugates are being tested in clinical and preclinical trials, and may have future relevance to some carcinomas.     

Dysprosium doped copper oxide (Cu1-xDyxO) nanoparticles enabled bifunctional electrode for overall water splitting

The production of hydrogen, a favourable alternative to an unsustainable fossil fuel remains as a significant hurdle with the pertaining challenge in the design of proficient, highly productive and sustainable electrocatalyst for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Herein, the dysprosium (Dy) doped copper oxide (Cu_1-xDy_xO) nanoparticles were synthesized via solution combustion technique and utilized as a non-noble metal based bi-functional electrocatalyst for overall water splitting. Due to the improved surface to volume ratio and conductivity, the optimized Cu_1-xDy_xO (x = 0.01, 0.02) electrocatalysts exhibited impressive HER and OER performance respectively in 1 M KOH delivering a current density of 10 mAcm^?2 at a potential of ?0.18 V vs RHE for HER and 1.53 V vs RHE for OER. Moreover, the Dy doped CuO electrocatalyst used as a bi-functional catalyst for overall water splitting achieved a potential of 1.56 V at a current density 10 mAcm^?2 and relatively high current density of 66 mAcm^?2 at a peak potential of 2 V. A long term stability of 24 h was achieved for a cell voltage of 2.2 V at a constant current density of 30 mAcm^?2 with only 10% of the initial current loss. This showcases the accumulative opportunity of dysprosium as a dopant in CuO nanoparticles for fabricating a highly effective and low-cost bi-functional electrocatalyst for overall water splitting.