First-in-Human Trial of EphA2-Redirected CAR T-Cells in Patients With Recurrent Glioblastoma: A Preliminary Report of Three Cases at the Starting Dose

Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 0342399

Hydrogen Sulfide Protects against Chemical Hypoxia-Induced Cytotoxicity and Inflammation in HaCaT Cells through Inhibition of ROS/NF-κB/COX-2 Pathway

Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H2S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl2), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H2S) for 30 min before exposure to CoCl2 for 24 h significantly attenuated CoCl2-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl2-induced COX-2 overexpression and PGE2 secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H2S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl2-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl2. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H2S against CoCl2-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H2S protects HaCaT cells against CoCl2-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway

Study on a Kind of Simulation Training System of Photoelectric Theodolite

A kind of system of target simulation training of photoelectric theodolite is presented. On the basis of the experiment duties, almost 40 operation courses are set according to five modules, which are equipment operation, parameter testing, maintaining, troubleshooting and task flow. Modeling strategy of several kinds of aircraft track is studied and set. The modeling and controlling of the key parts of photoelectric theodolite are achieved with the software of UG and Unity3D. Then the fault waveform of the equipment failure is completed by the soft LabVIEW. With the software Eduis, the multimedia of the operation courses are done. Then scientific and reasonable assessment model is studied and set to evaluate the operation of the trainees. Finally, with the examples of the trainees exams and troops using, it shows the system of target simulation training of photoelectric theodolite meets the requirements

Study on a Kind of Simulation Training System of Photoelectric Theodolite

A kind of system of target simulation training of photoelectric theodolite is presented. On the basis of the experiment duties, almost 40 operation courses are set according to five modules, which are equipment operation, parameter testing, maintaining, troubleshooting and task flow. Modeling strategy of several kinds of aircraft track is studied and set. The modeling and controlling of the key parts of photoelectric theodolite are achieved with the software of UG and Unity3D. Then the fault waveform of the equipment failure is completed by the soft LabVIEW. With the software Eduis, the multimedia of the operation courses are done. Then scientific and reasonable assessment model is studied and set to evaluate the operation of the trainees. Finally, with the examples of the trainees exams and troops using, it shows the system of target simulation training of photoelectric theodolite meets the requirements

Can Rural Road Construction Promote the Sustainable Development of Regional Agriculture in China?

The sustainable development of agriculture is significant in protecting natural resources, protecting the ecological environment, ensuring food security, and eliminating poverty. Rural road construction promotes the flow of labor and capital between urban and rural areas, and plays a vital role in agricultural production and rural revitalization. This study aims to analyze the effect of rural road construction on the sustainable development of regional agriculture in China. We select five-dimensional indexes of population, society, economy, resources, and environment and use the entropy method to calculate the agricultural sustainable development index of each province in China. Then, we construct the spatial econometric model to explore the influence based on the panel data of 31 provinces in China from 2002 to 2018. The benchmark results show that rural road construction significantly promotes the sustainable development of agriculture; however, it has a negative impact on environmental sustainability, and the influence is lagging. The results are also heterogeneous among regions. Rural road construction has significantly promoted the sustainable development of agriculture in eastern and central areas, but has no significant impact on western regions. The reason is that the siphoning effect caused by the construction of rural roads has led to a loss of talents and capital in the western region, which harms the sustainable development of the population and resource system. This effect offsets the positive effect of the other three systems. This research has substantial policy implications for promoting rural revitalization and agricultural development

The relationship between endorsing reporting guidelines or trial registration and the impact factor or total citations in surgical journals

Background A journal’s impact factor (IF) and total citations are often used as indicators of its publication quality. Furthermore, journals that require authors to abide by reporting guidelines or conduct trial registration generally have a higher quality of reporting. In this study, we sought to explore the potential associations between the enforcement of reporting guidelines or trial registration and a surgical journal’s IF or total citations in order to find new approaches and ideas to improve journal publication quality. Methods We examined surgical journals from the 2018 Journal Citation Report’s Expanded Scientific Citation Index to quantify the use of reporting guidelines or study registration. We reviewed the “instructions for authors” from each journal and used multivariable linear regression analysis to determine which guidelines were associated with the journal IF and total citations. The dependent variable was the logarithm base 10 of the IF in 2018 or the logarithm base 10 of total citations in 2018 (the results were presented as geometric means, specifically the ratio of the “endorsed group” results to “not endorsed group” results). The independent variable was one of the requirements (endorsed and not endorsed). Models adjust for the publication region, language, start year, publisher and journal size (only used to adjust total citations). Results We included 188 surgical journals in our study. The results of multivariable linear regression analysis showed that journal IF was associated (P < 0.01) with the following requirements: randomized controlled trial (RCT) registration (geometric means ratio (GR) = 1.422, 95% CI [1.197–1.694]), Consolidated Standards of Reporting Trials (CONSORT) statement (1.318, [1.104–1.578]), Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) statement (1.390, [1.148–1.683]), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement (1.556, [1.262–1.919]), Standards for Reporting Diagnostic Accuracy (STARD) statement (1.585, [1.216–2.070]), and Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement (2.113, [1.422–3.133]). We found associations between the endorsement of RCT registration (GR = 1.652, 95% CI [1.268–2.153]), CONSORT (1.570, [1.199–2.061]), PRISMA (1.698, [1.271–2.270]), STROBE (2.023, [1.476–2.773]), STARD (2.173, [1.452–3.243]), and MOOSE statements (2.249, [1.219–4.150]) and the number of total citations. Conclusion The presence of reporting guidelines and trial registration was associated with higher IF or more total citations in surgical journals. If more surgical journals incorporate these policies into their submission requirements, this may improve publication quality, thus increasing their IF and total citations

Fermentation characteristics in stirred-tank reactor of exopolysaccharides with hypolipidemic activity produced by Pleurotus geesteranus 5#

In this study, the hypolipidemic effect of exopolysaccharides (EPS) from Pleurotus geesteranus 5# fermenting liquor by the optimal culture conditions in a 5-L stirred-tank reactor was investigated. The hypolipidemic effect of the polysaccharide, investigated in streptozotocin induced diabetic mice, decreased plasma glucose, total cholesterol and triacylglycerol concentrations by 17.1 %, 18.8 % and 12.0 %, respectively. The results of the present investigation strongly demonstrate the potential of this polysaccharide to prevent hyperglycemia in the experimental animals. Under optimal culture conditions, the maximum concentrations of mycelial and EPS were 22.63 g/L after 7 d cultivation and 11.09 g/L after 10 d, respectively. Furthermore, the morphological parameters (i.e. mean diameter, circularity, roughness and compactness) of the pellets and the broth viscosity were characterized. It was proved that compactness of the pellet morphology (R2=0.963, p<0.01) was significantly and positively determined with mycelial biomass. Moreover, mean diameter (R2=93.3, p<0.01) and broth viscosity (R2=0.950, p<0.01) were significantly and positively determined with EPS content

Triaxial Experimental Study of Zinc Contaminated Red Clay under Different Temperature Conditions

Temperature is one of the important factors affecting the mechanical properties of geotechnical soils, and its role in engineering construction in China cannot be underestimated. In order to study the effects of temperature and zinc contamination concentration on the mechanical properties of Guilin local red clay, a temperature-controlled triaxial shear test was conducted on Guilin red clay under three variables of temperature, zinc contamination concentration and surrounding pressure. The test findings revealed that there are significant differences in the effects of temperature, zinc contamination concentration and surrounding pressure on the mechanical properties of Guilin red clay. The stress&ndash;strain curves of the red clay at various temperatures, contamination concentrations and envelope pressures are of the strain-hardening type, and the deformation modulus showed a tendency to increase rapidly with increasing strain, then decrease rapidly, and finally, decrease slowly. With the increase of temperature, the cohesion of Zn-contaminated red clay increases, while the angle of internal friction increases and then decreases, both of which increase the shear strength of red clay. As the concentration of Zn contamination grows, the shear strength of the red clay increases, while the internal friction angle increases and then decreases, and the shear strength of the soil increases and then decreases. The shear strength of the Zn-contaminated red clay improved as the surrounding pressure increased