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.     

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.     

Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

Surface Reconstruction Engineering with Synergistic Effect of Mixed-Salt Passivation Treatment toward Efficient and Stable Perovskite Solar Cells

Surface passivation treatment is a widely used strategy to resolve trap-mediated nonradiative recombination toward high-efficiency metal-halide perovskite photovoltaics. However, a lack of passivation with mixture treatment has been investigated, as well as an in-depth understanding of its passivation mechanism. Here, a systematic study on a mixed-salt passivation strategy of formamidinium bromide (FABr) coupled with different F-substituted alkyl lengths of ammonium iodide is demonstrated. It is obtained better device performance with decreasing chain length of the F-substituted alkyl ammonium iodide in the presence of FABr. Moreover, they unraveled a synergistic passivation mechanism of the mixed-salt treatment through surface reconstruction engineering, where FABr dominates the reformation of the perovskite surface via reacting with the excess PbI₂. Meanwhile, ammonium iodide passivates the perovskite grain boundaries both on the surface and top perovskite bulk through penetration. This synergistic passivation engineer results in a high-quality perovskite surface with fewer defects and suppressed ion migration, leading to a champion efficiency of 23.5% with mixed-salt treatment. In addition, the introduction of the moisture resisted F-substituted groups presents a more hydrophobic perovskite surface, thus enabling the decorated devices with excellent long-term stability under a high humid atmosphere as well as operational conditions.     

Novel measurement system for respiratory aerosols and droplets in indoor environments

The SARS-CoV-2 pandemic has created a great demand for a better understanding of the spread of viruses in indoor environments. A novel measurement system consisting of one portable aerosol-emitting mannequin (emitter) and a number of portable aerosol-absorbing mannequins (recipients) was developed that can measure the spread of aerosols and droplets that potentially contain infectious viruses. The emission of the virus from a human is simulated by using tracer particles solved in water. The recipients inhale the aerosols and droplets and quantify the level of solved tracer particles in their artificial lungs simultaneously over time. The mobile system can be arranged in a large variety of spreading scenarios in indoor environments and allows for quantification of the infection probability due to airborne virus spreading. This study shows the accuracy of the new measurement system and its ability to compare aerosol reduction measures such as regular ventilation or the use of a room air purifier.