E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.     

The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.     

Remediation of oil spill polluted water from Niger Delta Nigeria by sorption onto ammonium sulfate modified Dialium guineense seed husk

The abstraction of crude oil molecules from aqueous solution (produced water) and from real petroleum polluted water (collected from River State, Nigeria) by Dialium guineense Seed Husk (DGSH) and its ammonium sulfate functionalized form (AS-DGSH) was studied using a batch technique. The sorbents were characterized using Fourier transform infrared (FTIR), BET surface area analysis and the Scanning electron microscopy (SEM). Crude oil characterization revealed a light crude oil based on the API gravity of 35.6⁰. The Langmuir and Freundlich models gave good fits for crude oil sorption on DGSH and AS-DGSH respectively. The sorbents were found to remove over 50% of crude oil from the real polluted water at the natural pH of 6.1 and showed increase in removal with increase in sorbent dose. The potential of DGSH and its ammonium sulfate modified derivative as effective low cost sorbents for oil spill treatment was established.     

Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies

Gastric cancer’s bad incidence, prognosis, cellular and molecular heterogeneity amongst others make this disease a major health issue worldwide. Understanding this affliction is a priority for proper patients’ management and for the development of efficient therapeutical strategies. This review gives an overview of major scientific advances, made during the past 5-years, to improve the comprehension of gastric adenocarcinoma. A focus was made on the different actors of gastric carcinogenesis, including, Helicobacter pylori cancer stem cells, tumour microenvironment and microbiota. New and recent potential biomarkers were assessed as well as emerging therapeutical strategies involving cancer stem cells targeting as well as immunotherapy. Finally, recent experimental models to study this highly complex disease were discussed, highlighting the importance of gastric cancer understanding in the hard-fought struggle against cancer relapse, metastasis and bad prognosis.     

Precise Extraction of Charge Carrier Mobility for Organic Transistors

Unreliable mobility values, and particularly greatly overestimated values and severely distorted temperature dependences, have recently hampered the development of the organic transistor field. Given that organic field‐effect transistors (OFETs) have been routinely used to evaluate mobility, precise parameter extraction using the electrical properties of OFETs is thus of primary importance. This review examines the origins of the various mobilities that must be determined for OFET applications, the relevant extraction methods, and the data selection limitations, which help in avoiding conceptual errors during mobility extraction. For increased precision, the review also discusses device fabrication considerations, calibration of both the specific gate‐dielectric capacitance and the threshold voltage, the contact effects, and the bias and temperature dependences, which must actually be handled with great care but have mostly been overlooked to date. This review serves as a systematic overview of the OFET mobility extraction process to ensure high precision and will also aid in improving future research.     

Characterization of the structure and properties of processed alumina-graphene and alumina-zirconia composites

The onset of hybrid alumina-based composites, which combines two or more nano-particles within the alumina matrix has already shown promising improvements in the matrix material. However, variations in mechanical properties including the optimum compositions that give improved properties faced with the development of alumina-based composites require further studies to understand the underlying mechanisms and synergistic effects of the nano-particle additions on the alumina matrix. In the current study, the structure and properties of Al?O?-graphene (0.5 wt%) and Al?O?–ZrO? (4 wt% and 10 wt%) composites fabricated via hot-pressing was studied as a baseline for multiple combinations. Even though the addition of 10 wt%ZrO? resulted in a 23% reduction in the grain size of the alumina matrix, the 4 wt%ZrO? addition resulted in a 14% increase in grain size as compared to the parent alumina matrix. X-ray diffraction analysis revealed that there was approximately 85% monoclinic (m-ZrO₂) vs. 15% tetragonal (t-ZrO₂) crystal structures in the A4ZrO? sample whilst the A₁₀ZrO? had approximately 93% m-ZrO₂ vs. 7% t-ZrO₂. The high-volume fraction of the monoclinic crystal structures in the A₁₀ZrO? accounts for the induced microcracks in the sample since the transition from the ductile-tetragonal to brittle-monoclinic is associated with the exertion of compressive stresses on the alumina matrix by the associated elastic volume expansion of m-ZrO₂. Also, the addition of 0.5 wt%graphene resulted in about 37% reduction in the grain size of the alumina matrix, and approximately 10% increase in hardness as a result of the distribution of graphene along the grain boundaries of the parent alumina matrix, which restricts grain coalescence and growth during processing. Furthermore, an increase up to 115% and 164% were observed in the fracture toughness (K_IC) with the inclusion of 0.5 wt%graphene and 10 wt%ZrO? respectively, which was primarily ascribed to the fine-grained microstructures and toughening mechanisms of the intergranular graphene and ZrO? particles.     

Rheological and textural properties of lafun,a stiff dough,from improved cassava varieties

We studied the textural and rheological (viscoelastic) properties of fresh lafun dough, a fermented cassava product, and their changes during storage at 45 °C for 5 and 24 h, in order to determine after-cooking storability. Lafun flours were produced from three types of cassava varieties: seven improved white-fleshed varieties, seven improved provitamin A carotenoids (pVAC) varieties and two local white-fleshed varieties; and processed into lafun doughs. Pasting properties of the flours were assessed. Flours from local varieties had pasting profiles with highest viscosities, while pVAC flours had the lowest. The three types of cassava varieties varied significantly in most of their pasting properties. Four promising improved varieties were identified, based on high peak viscosity (55.8–61.5 P) and stiffer texture than local varieties during storage. Undesirable varieties were also found, which softened during storage instead of hardening. Optimum texture of lafun dough was obtained after 5 h of storage.     

Supporting primary students' learning of fraction conceptual knowledge through digital games

With the advent of mobile technologies, well-designed fraction apps can be used to help children gain fraction knowledge, a challenging topic for both teachers and students. The present pilot study adopted a quasi-experimental design to investigate whether children can learn fraction concepts equally well if half of the lesson time (20 min) is replaced with game-based learning. Keeping the total lesson time (40 min) identical, the control group (N = 33) received traditional instruction, and the experimental group (N = 32) was presented with a blended learning approach spending half of the class time (20 min) playing tablet-based fraction games, where each of the learners had their own tablet. The results suggested that in the posttest, the experimental group achieved similar learning gains to the control group and appear to have achieved better performance in the transfer test than the control group. This paper also discusses the efficiency of game-based learning, the mechanism of how fraction games might enhance learning, and the potential of integrating game-based learning in educational settings.     

Influence of design and operating conditions on the performance of tandem photoelectrochemical reactors

Solar-driven photoelectrochemical water splitting technology is a promising avenue for a sustainable hydrogen production. In this work, a comprehensive 2-dimensional model is developed and numerically simulated with hematite (α-Fe₂O₃) as the principal photoelectrode. The model evaluates light absorption, charge transport and electrochemical reactions to elucidate the effects of light transmitting materials, electrolyte height and electrolyte velocity on hydrogen and oxygen gas production. Results indicated that major losses in photocurrents are attributed to the transparent conducting oxide while losses due to the electrolyte increase with its height. Gas concentrations increase with increasing photocurrent densities and also in the direction of the flow. Gas bubbles however decrease with increasing electrolyte velocity. From these results, light reception in the reactor is uneven and poses a bigger challenge due to the bias in gas bubble distribution. Prospects of upscaling tandem schemes hence not only lie in the semiconductor material combinations but rather in the proper integration of system components and operating conditions.