Design, purification and assessment of GRP78 binding peptide-linked Subunit A of Subtilase cytotoxic for targeting cancer cells

The sequence of primers for GBP-SubA and optimization of E. coli strain and vector of GBP-SubA expression. (DOC 710 kb

Experimental Research on Fuel Oil Corrosion Resistance of Asphalt Mixtures

Asphalt mixtures were immersed in the fuel oil to study the oil corrosion resistance. The mechanical performance of asphalt mixtures in the oil was evaluated by the observation, mass loss measurement, Marshall stability test and splitting strength test. Effects of immersion time, binder types, and anti-oil corrosion additive content were analyzed. It is found that there is the evident stripping after immersing the mixture in the oil. The stability test and strength significantly decrease. Using the anti-oil corrosion additive can effectively improve the mechanical performance of asphalt mixtures in the oil. It still can satisfy the criteria after immersing for 7 days. Finally, the optimum anti-oil corrosion additive content of 0.4% is recommended

Acetylation modification regulates GRP78 secretion in colon cancer cells

High glucose-regulated protein 78 (GRP78) expression contributes to the acquisition of a wide range of phenotypic cancer hallmarks, and the pleiotropic oncogenic functions of GRP78 may result from its diverse subcellular distribution. Interestingly, GRP78 has been reported to be secreted from solid tumour cells, participating in cell-cell communication in the tumour microenvironment. However, the mechanism underlying this secretion remains elusive. Here, we report that GRP78 is secreted from colon cancer cells via exosomes. Histone deacetylase (HDAC) inhibitors blocked GRP78 release by inducing its aggregation in the ER. Mechanistically, HDAC inhibitor treatment suppressed HDAC6 activity and led to increased GRP78 acetylation; acetylated GRP78 then bound to VPS34, a class III phosphoinositide-3 kinase, consequently preventing the sorting of GRP78 into multivesicular bodies (MVBs). Of note, we found that mimicking GRP78 acetylation by substituting the lysine at residue 633, one of the deacetylated sites of HDAC6, with a glutamine resulted in decreased GRP78 secretion and impaired tumour cell growth in vitro. Our study thus reveals a hitherto-unknown mechanism of GRP78 secretion and may also provide implications for the therapeutic use of HDAC inhibitors

Protective Efficacy of Vitamins C and E on p,p′-DDT-Induced Cytotoxicity via the ROS-Mediated Mitochondrial Pathway and NF-κB/FasL Pathway

Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p′-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p′-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p′-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p′-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p′-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway

Design of Partially Etched GaP-OI Microresonators for Two-Color Kerr Soliton Generation at NIR and MIR

We present and theoretically investigate a dispersion engineered GaP-OI microresonator containing a partially-etched gap of 250 nm x 410 nm in a 600 nm x 2990 nm waveguide. This gap enables a 3.25 {\mu}m wide anomalous dispersion spectral span covering both the near-infrared and the mid-infrared spectra. This anomalous dispersion is manifested by two mechanisms, being the hybridization of the fundamental TE modes around 1550 nm and the geometric dispersion of the higher order TE mode around the 3100 nm wavelengths, respectively. Two Kerr soliton combs can be numerically generated with 101 GHz and 97 GHz teeth spacings at these spectral windows. The proposed structure demonstrates the design flexibility thanks to the partially etched gap and paves the way towards potential coherent multicolor frequency comb generation in the emerging GaP-OI platform

A novel defined risk signature of cuproptosis-related long non-coding RNA for predicting prognosis, immune infiltration, and immunotherapy response in lung adenocarcinoma

Background: Cuproptosis is a newly discovered non-apoptotic form of cell death that may be related to the development of tumors. Nonetheless, the potential role of cuproptosis-related lncRNAs in tumor immunity formation and patient-tailored treatment optimization of lung adenocarcinoma (LUAD) is still unclear.Methods: RNA sequencing and survival data of LUAD patients were downloaded from The Cancer Genome Atlas (TCGA) database for model training. The patients with LUAD in GSE29013, GSE30219, GSE31210, GSE37745, and GSE50081 were used for validation. The proofed cuproptosis-related genes were extracted from the previous studies. The Pearson correlation was applied to select cuproptosis-related lncRNAs. We chose differentially expressed cuproptosis-related lncRNAs in the tumor and normal tissues and allowed them to go to a Cox regression and a LASSO regression for a lncRNA signature that predicts the LUAD prognosis. Kaplan–Meier estimator, Cox model, ROC, tAUC, PCA, nomogram predictor, decision curve analysis, and real-time PCR were further deployed to confirm the model’s accuracy. We examined this model’s link to other regulated cell death forms. Applying TMB, immune-related signatures, and TIDE demonstrated the immunotherapeutic capabilities of signatures. We evaluated the relationship of our signature to anticancer drug sensitivity. GSEA, immune infiltration analysis, and function experiments further investigated the functional mechanisms of the signature and the role of immune cells in the prognostic power of the signature.Results: An eight-lncRNA signature (TSPOAP1-AS1, AC107464.3, AC006449.7, LINC00324, COLCA1, HAGLR, MIR4435-2HG, and NKILA) was built and demonstrated owning prognostic power by applied to the validation cohort. Each signature gene was confirmed differentially expressed in the real world by real-time PCR. The eight-lncRNA signature correlated with 2321/3681 (63.05%) apoptosis-related genes, 11/20 (55.00%) necroptosis-related genes, 34/50 (68.00%) pyroptosis-related genes, and 222/380 (58.42%) ferroptosis-related genes. Immunotherapy analysis suggested that our signature may have utility in predicting immunotherapy efficacy in patients with LUAD. Mast cells were identified as key players that support the predicting capacity of the eight-lncRNA signature through the immune infiltrating analysis.Conclusion: In this study, an eight-lncRNA signature linked to cuproptosis was identified, which may improve LUAD management strategies. This signature may possess the ability to predict the effect of LUAD immunotherapy. In addition, infiltrating mast cells may affect the signature’s prognostic power

Molecular characterization of methicillin-resistant and -susceptible Staphylococcus aureus recovered from hospital personnel

Introduction Methicillin resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital acquired infections. Over the past two decades MRSA has become ‘epidemic’ in many hospitals worldwide. However, little is known about the genetic background of S. aureus recovered from hospital personnel in China. Aim The aim of this study was to determine the genetic diversity of MRSA and methicillin susceptible S. aureus (MSSA) recovered from hospital personnel in Tianjin, North China. Methodology Three hundred and sixty-eight hand or nasal swabs were collected from 276 hospital personnel in four tertiary hospitals in Tianjin, North China between November 2017 and March 2019. In total, 535 gram-positive bacteria were isolated, of which 59 were identified as S. aureus. Staphylococcal cassette chromosome mec (SCCmec) typing, multi-locus sequence typing (MLST) and spa typing were performed to determine molecular characteristics of S. aureus. Results Thirty-one out of 276 (11%) hospital personnel were S. aureus carriers, whereas 11/276 (4%) carried MRSA. Fifty out of 59 (85%) of S. aureus isolates were resistant or intermediate resistant to erythromycin. The dominant genotypes of MRSA recovered from hospital personnel were ST398-t034-SCCmecIV/V, and ST630-t084/t2196, whereas major genotypes of MSSA included ST15-t078/t084/t346/t796/t8862/ t8945/t11653 and ST398-t189/t034/ t078/t084/t14014. Conclusion Although, the predominant genotypes of MRSA recovered from hospital personnel in this study were different from those main genotypes that have previously been reported to cause infections in Tianjin and in other geographic areas of China, the MRSA ST398-t034 genotype has previously been reported to be associated with livestock globally. The dominant MSSA genotypes recovered from hospital personnel were consistent with those previously reported MSSA genotypes recovered from the clinic. The diversity of S. aureus genotypes warrantee further surveillance and genomic studies to better understand the relatedness of these bacteria with those recovered from patients and community

Possible Luttinger liquid behavior of edge transport in monolayer transition metal dichalcogenide crystals.

In atomically-thin two-dimensional (2D) semiconductors, the nonuniformity in current flow due to its edge states may alter and even dictate the charge transport properties of the entire device. However, the influence of the edge states on electrical transport in 2D materials has not been sufficiently explored to date. Here, we systematically quantify the edge state contribution to electrical transport in monolayer MoS2/WSe2 field-effect transistors, revealing that the charge transport at low temperature is dominated by the edge conduction with the nonlinear behavior. The metallic edge states are revealed by scanning probe microscopy, scanning Kelvin probe force microscopy and first-principle calculations. Further analyses demonstrate that the edge-state dominated nonlinear transport shows a universal power-law scaling relationship with both temperature and bias voltage, which can be well explained by the 1D Luttinger liquid theory. These findings demonstrate the Luttinger liquid behavior in 2D materials and offer important insights into designing 2D electronics