Biosafey evaluation and anti-oxidative effects of ceria nanoparticles in vitro

Ceria nanoparticles are well known as high-performance catalysts due to the presence of mixed valence states of Ce3+ and Ce4+, and the presence of oxygen vacancies. Ceria nanoparticles are also potent free-radical scavengers due to its SOD mimics, catalase mimics and oxidase mimics. It is speculated that nanoceria would promote cell survival under conditions of oxidative stress due to its selective antioxidant properties. The antioxidant properties can be affected by the physicochemical properties of the materials and the target cells species. Therefore, in the present study, we evaluate the biosafety and protective effect of two different sizes of ceria nanoparticles in human umbilical vein endothelial cells (HUVECS) and human bronchial epithelial cells (HBE), as they are the primary routes of human exposure to nanoparticles through inhalation and injection. Based on the results of cell viability assay and cell membrane integrity assay, we found that ceria nanoparticles of both sizes are biocompatible to both HUVECS and HBE cells, though ceria nanoparticles have a slightly interference in the intracellular redox balance. In addition, ceria nanoparticles showed protective effect on the cell viability of both cells under oxidative stress. Detailed studies on the intracellular molecular mechanisms for the anti-oxidative effects will be studies to understand the nanoparticles-cell interactions. These results obtained in vitro may provide insights for real biomedical applications and risk assessment of ceria nanoparticle

Multiple asymmetric couplings induced unconventional corner mode in topolectrical circuits

We investigate the emergence of unconventional corner mode in a two-dimensional topolectrical circuits induced by asymmetric couplings. The non-Hermitian skin effect of two kinked one-dimensional lattices with multiple asymmetric couplings are explored. Then we extend to the two-dimensional model, derive conditions for the non-Hermitian hybrid skin effect and show how the corner modes are formed by non-reciprocal pumping based on one-dimensional topological modes. We provide explicit electrical circuit setups for realizing our observations via realistic LTspice simulation. Moreover, we show the time varying behaviors of voltage distributions to confirm our results. Our study may help to extend the knowledge on building the topological corner modes in the non-Hermitian presence

Retracted: Safranal induces autophagy by AMPK activation and protects neurons against amyloid beta in Alzheimer’s disease

This article has been retracted by the authors

Interference of steroidogenesis by gold nanorod core/silver shell nanostructures: Implications for reproductive toxicity of silver nanomaterials

Silver nanomaterials are widely used in personal care products. Recent studies have indicated that these nanomaterials may penetrate the blood-placental barrier and gain access to the ovaries. It is largely unknown how silver nanomaterials influence ovarian physiology and functions such as hormone production. This study examines the in vitro toxicology of silver nanomaterials, focusing especially on cytotoxicity and steroidogenesis while exploring their underlying mechanisms. In this study, primary rat granulosa cells were exposed to gold nanorod core/silver shell nanostructures (Au@Ag NRs), which were compared to cells exposed to gold nanorods only. The Au@Ag NRs generated more reactive oxygen species (ROS), reduced mitochondrial membrane potential, and decreased production of adenosine triphosphate. Au@Ag NRs promoted steroidogenesis, including progesterone and estradiol, in a time and dose-dependent manner. Chemical reactivity and transformation of Au@Ag NRs were then studied by electron spin resonance spectroscopy (ESR) and X-ray absorption near edge structure, which identified the generation of free radicals and intracellular silver species. These results suggested that both particle-specific activity and intracellular silver ion release of Au@Ag Please click Additional Files below to see the full abstract

Deep learning for the design of non-Hermitian topolectrical circuits

Non-Hermitian topological phases can produce some remarkable properties, compared with their Hermitian counterpart, such as the breakdown of conventional bulk-boundary correspondence and the non-Hermitian topological edge mode. Here, we introduce several algorithms with multi-layer perceptron (MLP), and convolutional neural network (CNN) in the field of deep learning, to predict the winding of eigenvalues non-Hermitian Hamiltonians. Subsequently, we use the smallest module of the periodic circuit as one unit to construct high-dimensional circuit data features. Further, we use the Dense Convolutional Network (DenseNet), a type of convolutional neural network that utilizes dense connections between layers to design a non-Hermitian topolectrical Chern circuit, as the DenseNet algorithm is more suitable for processing high-dimensional data. Our results demonstrate the effectiveness of the deep learning network in capturing the global topological characteristics of a non-Hermitian system based on training data

NQO1 targeting prodrug triggers innate sensing to overcome checkpoint blockade resistance

Lack of proper innate sensing inside tumor microenvironment (TME) limits T cell-targeted immunotherapy. NAD(P)H:quinone oxidoreductase 1 (NQO1) is highly enriched in multiple tumor types and has emerged as a promising target for direct tumor-killing. Here, we demonstrate that NQO1-targeting prodrug β-lapachone triggers tumor-selective innate sensing leading to T cell-dependent tumor control. β-Lapachone is catalyzed and bioactivated by NQO1 to generate ROS in NQO1high tumor cells triggering oxidative stress and release of the damage signals for innate sensing. β-Lapachone-induced high mobility group box 1 (HMGB1) release activates the host TLR4/MyD88/type I interferon pathway and Batf3 dendritic cell-dependent cross-priming to bridge innate and adaptive immune responses against the tumor. Furthermore, targeting NQO1 is very potent to trigger innate sensing for T cell re-activation to overcome checkpoint blockade resistance in well-established tumors. Our study reveals that targeting NQO1 potently triggers innate sensing within TME that synergizes with immunotherapy to overcome adaptive resistance

IL28B is associated with outcomes of chronic HBV infection

Purpose The role of IL28B gene variants and expression in hepatitis B virus (HBV) infections are not well understood. Here, we evaluated whether IL28B gene expression and rs12979860 variations are associated with HBV outcomes. Materials and Methods IL28B genetic variations (rs12979860) were genotyped by pyrosequencing of DNA samples from 137 individuals with chronic HBV infection [50 inactive carriers (IC), 34 chronic hepatitis B (CHB), 27 cirrhosis, 26 hepatocellular carcinoma (HCC)], and 19 healthy controls. IL28A/B mRNA expression in peripheral blood mononuclear cells was determined by qRT-PCR, and serum IL28B protein was measured by ELISA. Results Patients with IL28B C/C genotype had greater IL28A/B mRNA expression and higher IL28B protein levels than C/T patients. Within the various disease stages, compared to IC and healthy controls, IL28B expression was reduced in the CHB, cirrhosis, and HCC cohorts (CHB vs. IC, p=0.02; cirrhosis vs. IC, p=0.01; HCC vs. IC, p=0.001; CHB vs. controls, p&#60;0.01; cirrhosis vs. controls, p&#60;0.01; HCC vs. controls, p&#60;0.01). When stratified with respect to serum HBV markers in the IC and CHB cohorts, IL28B mRNA and protein levels were higher in HBeAg-positive than negative individuals (p=0.01). Logistic regression analysis revealed that factors associated with high IL28B protein levels were C/C versus C/T genotype [p=0.016, odds ratio (OR)=0.25, 95% confidence interval (CI)=0.08-0.78], high alanine aminotransferase values (p&#60;0.001, OR=8.02, 95% CI=2.64-24.4), and the IC stage of HBV infection (p&#60;0.001). Conclusion Our data suggest that IL28B genetic variations may play an important role in long-term development of disease in chronic HBV infections.</p

Abound Hepatic Mitosis: Unusual Morphology in the Intrahepatic Cholelithiasis Patient

To explore the clinicopathological features of abound mitosis of the hepatocytes in intrahepatic cholelithiasis. The clinicopathological data of one case diagnosed as intrahepatic cholelithiasis was collected from Yantai Yuhuangding Hospital and the clinicopathological characters were discussed. A 68-year-old man suffered from the pain in the right upper quadrant and radiology showed multiple stones in the gallbladder and left liver. The images suggested intrahepatic cholelithiasis. The patient received gallbladder and partial hepatectomy. A large number of mitosis was observed and twelve nuclear fissions were found under high magnification, even in some area pathological nuclear fission could be observed in morphology. On the basis of detection in laboratory, the diagnosis of intrahepatic cholelithiasis was made. The patient did not receive any therapy after surgery. The patient was in a good condition after 18 months follow-up. Increased number of hepatic mitosis might be due to the stimulation from stones, hepatic biliary or secondary inflammatory. High index of proliferation should be prevented from the potential misdiagnosis of hepatic tumor

Toll-Like Receptor 9 Is Required for Opioid-Induced Microglia Apoptosis

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or μ-opioid receptor (μOR) deficient primary microglia, suggesting an involvement of MAPK and μOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and μOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of μOR is capable of preventing opioid-induced brain damage