Innovation Experiences from Africa-Led Drug Discovery at the Holistic Drug Discovery and Development (H3D) Centre

As the so-called “next frontier” in global economic terms, Africa’s disease burden continues to choke and cripple economic growth across the continent. The highest burden is attributable to malaria and tuberculosis (TB), which also remain among the deadliest infectious diseases affecting mankind the world over (Malaria, 627,000 deaths; TB, 1.5 million deaths, in 2020). In achieving self-determination with respect to the health needs of all who live on the continent, Africa must align with global north efforts and be a source of health innovation. This will in part require the creation of an ecosystem of innovative pharmaceutical R&D and expanding it across the continent by scaling up through sustained performance and excellence. To this end, the Holistic Drug Discovery and Development (H3D) Centre at University of Cape Town in South Africa has risen to this challenge. Here, we highlight the innovation experiences gained at H3D, covering the advances made in our quest to contribute to a global pipeline of therapeutic interventions against malaria and TB. We discuss selected chemical series starting from their identification, structure–activity relationships, mode of action, safety, proof-of-concept studies, and lessons learned.     

脑白质病变MRI视觉分级方法的比较

目的:比较7种常用的脑白质病变(WMLs)MRI视觉分级方法,评价各分级之间的相关性和一致性,并计算两两间相互转化的参数.方法:随机选取50例MRI T2-FLAIR显示有不同程度WMLs患者,由两名医师分别用7种分级方法对其WMLs进行评分. 视觉分级间的相关性评价采用Spearman 等级相关分析,不同评估者之间的一致性分析采用Kappa检验,通过回归分析计算各分级间相互转化的参数.结果:不同视觉分级在WMLs评分上均有较强的相关性(相关系数rs: 0.579～0.917, P＜0.05). 除Schelten(modilified)分级和Ylikoski分级外,其它分级在不同观察者间的一致性好(κ＞0.585). 除Aharon-Peretz J分级和De Groot JC分级外,通过回归分析得出了其它5个分级间相互转化的参数,其确定系数R2的范围为0.5856～0.8892.结论:7种不同白质病变的MRI视觉分级间有较好的相关性,而不同评估者间Aharon-Peretz J分级的一致性最好.     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Approaches to Preceramic Polymer Fiber Fabrication and On-Demand Applications

The demand for lightweight, high-modulus, and temperature-resistant materials for aerospace and other high-temperature applications has contributed to the development of ceramic fibers that exhibit most of the favorable properties of monolithic ceramics. This review demonstrates preceramic-based polymer fiber spinning and fiber classifications. We discuss different types of fiber spinning and the advantages of each. Tuning the preceramic polymer chemical properties, molar mass, functional chemistry influences, and incorporation with fillers are thoroughly investigated. Further, we present the applications of preceramic-based polymer fibers in different fields including aerospace, biomedical, and sensor applications. This concise review summarizes recent developments in preceramic fiber chemistry and essential applications.     

Bending and Crack Evolution Behaviors of Cemented Soil Reinforced with Surface Modified PVA Fiber

To improve the flexural properties of cemented soils reinforced with fibers and avoid their brittle failure when subjected to complex loading conditions, a simple and cost-effective technique was explored to facilitate their application in retaining walls. In this study, how different fiber surface modifications, i.e., alkali treatment, acid treatment and silane coupling agent treatment, as well as different fiber contents, i.e., 0%, 0.25%, 0.5% and 1%, affect the bending properties of cemented soils was investigated by conducting three-point bending tests on notched beams. The digital image correlation (DIC) technology was used to examine the crack propagation process and the strain field distribution of cracks in specimens in the flexural tests. The results show that all fiber surface modifications increased peak strength and fracture energy, for example, the fracture energy of specimens AN1, AH1 and AK1 was increased by 180.4%, 121.5% and 155.4%, respectively, compared to PVA1. In addition, the crack tip strain, crack propagation rate and the initial crack width of the modified specimens were lower than those before modification. Lastly, scanning electron microscope (SEM) and mercury intrusion porosimetry tests were adopted to reveal the mechanism of bending performance in cemented soils reinforced by fiber surface modifications.     

Novel Electromagnetic Characterization Methods for New Materials and Structures in Aerospace Platforms

The tendency over the last decades in the aerospace industry is to substitute classic metallic materials with new composite materials such as carbon fiber composites (CFC), fiber glass, etc., as well as adding electronic devices to ensure the safety and proper platform operation. Due to this, to protect the aircraft against the Electromagnetic Environmental Effects (E3), it is mandatory to develop accurate electromagnetic (EM) characterization measurement systems to analyze the behavior of new materials and electronic components. In this article, several measurement methods are described to assess the EM behavior of the samples under test: microstrip transmission line for a surface current analysis, free space to obtain intrinsic features of the materials and shielding effectiveness (SE) approaches to figure out how well they isolate from EM fields. The results presented in this work show how the different facilities from the National Institute of Aerospace Technology (INTA) are suitable for such purposes, being capable of measuring a wide variety of materials, depending on the type of test to be carried out.     

Effects of Wollastonite Fiber and Styrene–Butadiene Latex Polymer on the Long-Term Durability of Cement-Based Repair Materials

Concrete structures are constructed in various geographical environments and climates, and frequently fail to fulfill their original functions over time due to issues such as aging and damage. Research on concrete structure repair materials is being conducted to solve these problems. This study evaluated the durability of a repair material composed of ultra-rapid hardening cement, styrene–butadiene (SB) latex polymer, and wollastonite mineral fiber. The performance targets were as follows: compressive strength of 20 MPa at 1 day of age and 45 MPa at 28 days of age, chloride ion charge passed of less than 1000 Coulombs, carbonation depth of 20 mm or less, and resistance to repeated freezing and thawing (relative dynamic modulus of elasticity) of 80% or more. The ultra-rapid hardening cement:silica sand ratio of 1:1.5 was the experimental variable, and the unit weight of each material in the mix proportion was determined to satisfy the flow requirement of 200 ± 5 mm. This flow ensured sufficient fluidity for spraying, which is the most widely used method for applying repair material. Wollastonite mineral fiber and SB latex polymer were added at 3% and 5% of the unit weight of the binder, respectively. The mechanical property of the repair material was evaluated through compressive strength, and durability was evaluated through chloride ion penetration, alkali resistance, resistance to carbonation, water absorption, and repeated freezing and thawing tests. The compressive strength satisfied both target values, regardless of the addition of SB latex polymer and wollastonite mineral fiber. The chloride ion penetration test, which was used as an indicator of durability, showed that mixtures without SB latex and wollastonite mineral fiber were not satisfied the target charge passed of 1000 Coulombs, while mixtures with latex and mineral fiber reached the target value. Notably, the co-addition of latex and wollastonite fiber showed the highest resistance to chloride ion penetration, alkali ion, carbonation, repeated freezing and thawing, and the least absorption. The results confirmed that the durability of the repair material based on ultra-rapid hardening cement was most effectively improved by the co-addition of SB latex polymer and wollastonite mineral fiber.     

浅谈搪玻璃产品材料特性和不足

分析归纳搪玻璃产品材料的五大特性和五大不足。并阐述发扬这些特性,能扩大产品应用范围;克服它的不足,能提高产品的使用性能。     

Study on the Actuating Performance of an Embedded Macro Fiber Composite Considering the Shear Lag Effect

Macro fiber composite (MFC), which are new ultrathin piezoelectric smart materials, are mostly applied in the fields of shell structure deformation and vibration control. Among others, the application of embedded MFCs in sandwich structures has received wide attention. Currently, its actuating force formula is primarily acquired based on the Bernoulli–Euler Model, which does not consider the shear lag effect and actuating force of MFC ends. To study the actuating performance of an MFC in a sandwich structure, according to its action characteristics, the MFC is divided into upper and lower actuating units without any interaction between to two under the condition of plane strain, and the shear lag effect is considered between the units and the top and bottom of the sandwich structure. The actuating force of the MFC ends is obtained by considering its influence on the bending deformation of the sandwich structure, which deduces the actuating force formula of the embedded MFC. In contrast to ANSYS piezoelectric simulation, the distribution of the MFC interior normal stress is similar to the result from ANSYS piezoelectric simulation, and there is a very small deviation between the MFC end and central normal stress and the result from ANSYS piezoelectric simulation. Taking the end deflection of the sandwich structure with an embedded MFC as an example, the actuating force simulation of the MFC considering the shear lag effect is compared with the ANSYS piezoelectric simulation and actuating force simulation based on the Bernoulli–Euler model. The result indicates that the actuating force simulation of the MFC considering the shear lag effect is closer to the ANSYS piezoelectric simulation, which proves the rationality and necessity of considering the shear lag effect and end actuating force of the MFC.     

Improved Shear Strength Prediction Model of Steel Fiber Reinforced Concrete Beams by Adopting Gene Expression Programming

In this study, an artificial intelligence tool called gene expression programming (GEP) has been successfully applied to develop an empirical model that can predict the shear strength of steel fiber reinforced concrete beams. The proposed genetic model incorporates all the influencing parameters such as the geometric properties of the beam, the concrete compressive strength, the shear span-to-depth ratio, and the mechanical and material properties of steel fiber. Existing empirical models ignore the tensile strength of steel fibers, which exercise a strong influence on the crack propagation of concrete matrix, thereby affecting the beam shear strength. To overcome this limitation, an improved and robust empirical model is proposed herein that incorporates the fiber tensile strength along with the other influencing factors. For this purpose, an extensive experimental database subjected to four-point loading is constructed comprising results of 488 tests drawn from the literature. The data are divided based on different shapes (hooked or straight fiber) and the tensile strength of steel fiber. The empirical model is developed using this experimental database and statistically compared with previously established empirical equations. This comparison indicates that the proposed model shows significant improvement in predicting the shear strength of steel fiber reinforced concrete beams, thus substantiating the important role of fiber tensile strength.