bluuebunny/crossref_metadata_2025 huggingface dataset:
An Upper Bound Solution for the Compression of an Orthotropic Cylinder
Authors: Lang Lihui , Alexandrov Sergei , Wang Yun-Che
Published: September 2021

The upper bound theorem is used in conjunction with Hill’s quadratic yield criterion for determining the force required to upset a solid cylinder. The kinematically admissible velocity field accounts for the singular behavior of the real velocity field in the vicinity of the friction surface if the maximum friction law is adopted. The regime of sticking is also taken into consideration. The effect of this regime on the upper bound limit load is revealed. In particular, the kinematically admissible velocity field that includes the regime of sticking may result in a lower upper bound than that with no sticking. The boundary value problem is classified by a great number of geometric and material parameters. Therefore, a systematic parametric analysis of the effect of these parameters on the compression force is practically impossible. An advantage of the solution found is that it provides a quick estimate of this force for any given set of parameters.
Mechanical and Abrasive Wear Performance of Titanium Di-Oxide Filled Woven Glass Fibre Reinforced Polymer Composites by Using Taguchi and EDAS Approach
Authors: Chairman Chelliah Anand , Ravichandran Manickam , Mohanavel Vinayagam , Sathish Thanikodi , Rashedi Ahmad , Alarifi Ibrahim M. , Badruddin Irfan Anjum , Anqi Ali E. , Afzal Asif
Published: September 2021

Two-body abrasive wear behavior of glass fabric reinforced (GC) epoxy and titanium dioxide (TiO2) filled composites have been conducted out by using a tribo test machine. GC and TiO2 filled GC composites were produced by the hand layup technique. The mechanical performances of the fabricated composites were calculated as per ASTM standards. Three different weight percentages were mixed with the polymer to develop the mechanical and abrasive wear features of the composites. Evaluation Based on Distance from Average Solution (EDAS), a multi-criteria decision technique is applied to find the best filler content. Based on the output, 2wt% TiO2 filler gave the best result. Abrasive wear tests were used to compare GC and TiO2 filled GC composites. The abrasion wear mechanisms of the unfilled and TiO2 filled composites have also been studied by scanning electron microscopy. The outcome of the paper suggests the correct proportion of filler required for the resin in order to improve the wear resistance of the filled composites. Taguchi combined with Multi-Criteria Decision Method (MCDM) is used to identify the better performance of the TiO2 filled epoxy composites.
Effect of Cerium on the Microstructure and Inclusion Evolution of C-Mn Cryogenic Vessel Steels
Authors: Wu Liping , Zhi Jianguo , Zhang Jiangshan , Zhao Bo , Liu Qing
Published: September 2021

The effects of Cerium (Ce) were studied on the casting slab quality, microstructure, and inclusion evolution of cryogenic vessel steel. An optical metallographic microscope, scanning electron microscope, energy dispersive spectrometer, and Thermo-calc thermodynamic software were used for characterization and analysis. The results indicated that the central segregation was significantly improved after adding Ce and reached the lowest level when the content of Ce was 0.0009 wt.%. Meanwhile, the presence of Ce reduces the size of ferrite and improves pearlite morphology. Ce also enables the modification of Al2O3 and MnS + Ti4C2S2 inclusions into ellipsoid CeAlO3 and spherical Ce2O2S + Ti4C2S2 composite inclusions, respectively, which are easier to remove. The formed Ce2O2S inclusions are fine and can work as heterogeneous nucleation points to refine the microstructure of steel.
Vanadia–Zirconia and Vanadia–Hafnia Catalysts for Utilization of Volatile Organic Compound Emissions
Authors: Ojala Satu , Laitinen Tiina , Leneuf de Neufville Sian , Honkanen Mari , Vippola Minnamari , Huuhtanen Mika , Keiski Riitta L.
Published: September 2021

Utilization is a sustainable and interesting alternative for the destructive treatment of volatile organic compounds due to avoided CO2 emission. This work concentrates on the development of active and sulfur-tolerant catalysts for the utilization of contaminated methanol. Impregnated and sol–gel prepared vanadia–zirconia and vanadia–hafnia catalysts were thoroughly characterized by N2 sorption, analytical (S)TEM, elemental analysis, XRD and Raman spectroscopy, and their performances were evaluated in formaldehyde production from methanol and methanethiol mixture. The results showed higher activity of the sol–gel prepared catalysts due to formation of mono- and polymeric vanadia species. Unfortunately, the most active vanadia sites were deactivated more easily than the metal-mixed oxide HfV2O7 and ZrV2O7 phases, as well as crystalline V2O5 observed in the impregnated catalysts. Metal-mixed oxide phases were formed in impregnated catalysts through formation of defects in HfO2 and ZrO2 structure during calcination at 600 °C, which was evidenced by Raman spectroscopy. The sol–gel prepared vanadia–zirconia and vanadia–hafnia catalysts were able to produce formaldehyde from contaminated methanol with high selectivity at temperature around 400 °C, while impregnated catalysts required 50–100 °C higher temperatures.
Experimental Investigation of Wind Pressure Characteristics for Cladding of Dome Roofs
Authors: Cheon Dong-Jin , Kim Yong-Chul , Lee Jong-Ho , Yoon Sung-Won
Published: September 2021

Cladding for dome roofs is often made of membrane materials that are light and easy to install. Due to these characteristics, wind damage to dome roof cladding is very common. In particular, open or retractable dome roofs are prone to wind damage because of inadequacies in wind load calculations. In this study, the wind pressure characteristics of a dome with a central opening were investigated. Wind tunnel tests were performed, and the pressure distribution was investigated by analyzing external and internal pressure coefficients. Based on the experimental results, the peak net pressure coefficients for the cladding design of a dome roof with a central opening were proposed. For the external peak pressure coefficients, the values of leeward regions were similar despite height–span ratios and turbulence intensity values. For the internal peak pressure coefficients, negative pressure was dominant, and the coefficients were not significantly affected by changes in height–span ratio. This tendency locally increased the negative peak net pressure, in which the load acts in the upward direction, and relatively significantly increased the positive peak net pressure, in which the load acts in the downward direction.
SBA-15 with Crystalline Walls Produced via Thermal Treatment with the Alkali and Alkali Earth Metal Ions
Authors: Park Sung Soo , Chu Sang-Wook , Shi Liyi , Yuan Shuai , Ha Chang-Sik
Published: September 2021

Crystalline walled SBA-15 with large pore size were prepared using alkali and alkali earth metal ions (Na+, Li+, K+ and Ca2+). For this work, the ratios of alkali metal ions (Si/metal ion) ranged from 2.1 to 80, while the temperatures tested ranged from 500 to 700 °C. The SBA-15 prepared with Si/Na+ ratios ranging from 2.1 to 40 at 700 °C exhibited both cristobalite and quartz SiO2 structures in pore walls. When the Na+ amount increased (i.e., Si/Na increased from 80 to 40), the pore size was increased remarkably but the surface area and pore volume of the metal ion-based SBA-15 were decreased. When the SBA-15 prepared with Li+, K+ and Ca2+ ions (Si/metal ion = 40) was thermally treated at 700 °C, the crystalline SiO2 of quartz structure with large pore diameter (i.e., 802.5 Å) was observed for Ca+2 ion-based SBA-15, while no crystalline SiO2 structures were observed in pore walls for both the K+ and Li+ ions treated SBA-15. The crystalline SiO2 structures may be formed by the rearrangement of silica matrix when alkali or alkali earth metal ions are inserted into silica matrix at elevated temperature.
Comparison of Cellulose Dissolution Behavior by Alkaline and Sulfuric Acid Solvents and Their Films’ Physical Properties
Authors: Han Jungsoo , Seo Yungbum
Published: September 2021

Three alkaline mixtures (NaOH/thiourea, NaOH/urea/thiourea, NaOH/urea/ZnO) and sulfuric acid were used at low temperatures as cellulose solvents, and their cellulose solubility and films’ physical properties for bleached chemical wood pulps and cotton linter were compared. Their degree of polymerization (DP) was controlled to 600–800 before dissolution. Among the alkaline solvents, NaOH/urea/ZnO gave the film the highest tensile strength and stretch. When compared to sulfuric acid, NaOH/urea/ZnO gave lower strength properties but higher crystallinity indices in the films. While alkaline solvents could not dissolve the high DP cellulose (DP ~ 2000), sulfuric acid could dissolve the high DP cellulose at below zero Celsius temperature, and the strength properties of the films were not much different from that of the low DP one. It appeared that the low-temperature sulfuric acid treatment did away with the cellulose’s DP controlling stage; it decreased cellulose DP very quickly for the high-DP cellulose at the initial stage, and as soon as the cellulose DP reached a DP low enough for dissolution, it began to dissolve the cellulose to result in stable cellulose solution.
Material Behavior and Fatigue Assessment of Old Steel Bridges of the Spanish Conventional Rail Network
Authors: Presno Vélez Álvaro , Bernardo Sánchez Antonio , Bruna Octavio Ariñez , Abella Diego Madera , de Prado Laura Álvarez , Fernández Marta Menéndez
Published: September 2021

This work presented salient features of the steel behavior of seven metallic bridges close to, or over, 100 years old, among the Spanish conventional rail network as well as the results of a fatigue life expectancy study. A preliminary study of the properties of the constituent materials obtained from the bridges samples was carried out followed by dynamic fatigue tests under service representative loads. Due to the steelmaking techniques in the late 19th and early 20th centuries, disperse fatigue behavior results were obtained. However, the wide safety margins with which these bridges were designed, as well as the mechanical properties of the steel (relatively good mechanical resistance but with low ductility), seem to guarantee a long fatigue life. This estimate decreases sharply with increasing loads.
Acceleration and Parallelization of a Linear Equation Solver for Crack Growth Simulation Based on the Phase Field Model
Authors: Ishii Gaku , Yamamoto Yusaku , Takaishi Takeshi
Published: September 2021

We aim to accelerate the linear equation solver for crack growth simulation based on the phase field model. As a first step, we analyze the properties of the coefficient matrices and prove that they are symmetric positive definite. This justifies the use of the conjugate gradient method with the efficient incomplete Cholesky preconditioner. We then parallelize this preconditioner using so-called block multi-color ordering and evaluate its performance on multicore processors. The experimental results show that our solver scales well and achieves an acceleration of several times over the original solver based on the diagonally scaled CG method.
Synthesis of Marine Natural Products and Molecules Inspired by Marine Substances II
Authors: Manzo Emiliano
Published: September 2021

The sea occupies more than 70% of the Earth’s surface and includes more than 300,000 organisms with huge biodiversity [...]
Bioactive Agent-Loaded Electrospun Nanofiber Membranes for Accelerating Healing Process: A Review
Authors: Mousavi Seyyed-Mojtaba , Nejad Zohre Mousavi , Hashemi Seyyed Alireza , Salari Marjan , Gholami Ahmad , Ramakrishna Seeram , Chiang Wei-Hung , Lai Chin Wei
Published: September 2021

Despite the advances that have been achieved in developing wound dressings to date, wound healing still remains a challenge in the healthcare system. None of the wound dressings currently used clinically can mimic all the properties of normal and healthy skin. Electrospinning has gained remarkable attention in wound healing applications because of its excellent ability to form nanostructures similar to natural extracellular matrix (ECM). Electrospun dressing accelerates the wound healing process by transferring drugs or active agents to the wound site sooner. This review provides a concise overview of the recent developments in bioactive electrospun dressings, which are effective in treating acute and chronic wounds and can successfully heal the wound. We also discuss bioactive agents used to incorporate electrospun wound dressings to improve their therapeutic potential in wound healing. In addition, here we present commercial dressings loaded with bioactive agents with a comparison between their features and capabilities. Furthermore, we discuss challenges and promises and offer suggestions for future research on bioactive agent-loaded nanofiber membranes to guide future researchers in designing more effective dressing for wound healing and skin regeneration.
Laser Micro Polishing of Tool Steel 1.2379 (AISI D2): Influence of Intensity Distribution, Laser Beam Size, and Fluence on Surface Roughness and Area Rate
Authors: Temmler André , Cortina Magdalena , Ross Ingo , Küpper Moritz E. , Rittinghaus Silja-Katharina
Published: September 2021

Within the scope of this study, basic research was carried out on laser micro polishing of the tool steel 1.2379 (AISI D2) using a square, top-hat shaped intensity distribution. The influence of three different quadratic laser beam sizes (100 µm, 200 µm, 400 µm side length) and fluences up to 12 J/cm2 on the resulting surface topography and roughness were investigated. Surface topography was analyzed by microscopy, white light interferometry, spectral roughness analysis, and 1D fast Fourier transformation. Scanning electron microscopy and electrical discharge analyses indicate that chromium carbides are the source of undesired surface features such as craters and dimples, which were generated inherently to the remelting process. Particularly for high laser fluences, a noticeable stripe structure was observed, which is typically a characteristic of a continuous remelting process. Although the micro-roughness was significantly reduced, often, the macro-roughness was increased. The results show that smaller laser polishing fluences are required for larger laser beam dimensions. Additionally, the same or even a lower surface roughness and less undesired surface features were created for larger laser beam dimensions. This shows a potential path for industrial applications of laser micro polishing, where area rates of up to several m2/min might be achievable with commercially available laser beam sources.
The Influence of Varying Aluminium and Manganese Content on the Corrosion Resistance and Mechanical Properties of High Strength Steels
Authors: Hajšman Jan , Kučerová Ludmila , Burdová Karolína
Published: September 2021

The aim of this paper is to evaluate the influence of small variations in chemical composition on the corrosion resistance and mechanical properties of low-manganese and medium manganese high strength steels. Six different steels with manganese content varying from 1.5 to 4.0 wt.% and aluminium from 0.008 to 6.5 wt.% were subjected to the analysis. The other subjects for evaluation included the effect of aluminium as a replacement for silicon, niobium microalloying and the effect of heat treatment. The effect of non-metallic inclusions on localized corrosion initiation and propagation was also documented. Using potentiodynamic testing, exposure testing, tensile and impact testing, it was found that the improvement in corrosion resistance associated with increasing aluminium content is accompanied by a significant deterioration of the mechanical properties. Niobium microalloying and heat treatment was found to have no quantifiable impact on the anti-corrosion properties. The effect of aluminium content proved to be superior to the effect of nonmetallic inclusions in terms of determining the overall corrosion resistance of the experimental steels.
Utilizing Iron as Reinforcement to Enhance Ambient Mechanical Response and Impression Creep Response of Magnesium
Authors: Jayalakshmi Subramanian , Sankaranarayanan Seetharaman , Arvind Singh Ramachandra , Shabadi Rajashekhara , Gupta Manoj
Published: September 2021

To realize light-weight materials with high strength and ductility, an effective route is to incorporate strong and stiff metallic elements in light-weight matrices. Based on this approach, in this work, magnesium–iron (Mg-Fe) composites were designed and characterized for their microstructure and mechanical properties. The Mg-Fe binary system has extremely low solubility of Fe in the Mg-rich region. Pure magnesium was incorporated with 5, 10, and 15 wt.% Fe particles to form Mg-Fe metal–metal composites by the disintegrated melt deposition technique, followed by hot extrusion. Results showed that the iron content influences (i) the distribution of Fe particles in the Mg matrix, (ii) grain refinement, and (iii) change in crystallographic orientation. Mechanical testing showed that amongst the composites, Mg-5Fe had the highest hardness, strength, and ductility due to (a) the uniform distribution of Fe particles in the Mg matrix, (b) grain refinement, (c) texture randomization, (d) Fe particles acting as effective reinforcement, and (e) absence of deleterious interfacial reactions. Under impression creep, the Mg-5Fe composite had a creep rate similar to those of commercial creep-resistant AE42 alloys and Mg ceramic composites at 473 K. Factors influencing the performance of Mg-5Fe and other Mg metal–metal composites having molybdenum, niobium, and titanium (elements with low solubility in Mg) are presented and discussed.
Lipid Metabolite Biomarkers in Cardiovascular Disease: Discovery and Biomechanism Translation from Human Studies
Authors: McGranaghan Peter , Kirwan Jennifer A. , Garcia-Rivera Mariel A. , Pieske Burkert , Edelmann Frank , Blaschke Florian , Appunni Sandeep , Saxena Anshul , Rubens Muni , Veledar Emir , Trippel Tobias Daniel
Published: September 2021

Lipids represent a valuable target for metabolomic studies since altered lipid metabolism is known to drive the pathological changes in cardiovascular disease (CVD). Metabolomic technologies give us the ability to measure thousands of metabolites providing us with a metabolic fingerprint of individual patients. Metabolomic studies in humans have supported previous findings into the pathomechanisms of CVD, namely atherosclerosis, apoptosis, inflammation, oxidative stress, and insulin resistance. The most widely studied classes of lipid metabolite biomarkers in CVD are phospholipids, sphingolipids/ceramides, glycolipids, cholesterol esters, fatty acids, and acylcarnitines. Technological advancements have enabled novel strategies to discover individual biomarkers or panels that may aid in the diagnosis and prognosis of CVD, with sphingolipids/ceramides as the most promising class of biomarkers thus far. In this review, application of metabolomic profiling for biomarker discovery to aid in the diagnosis and prognosis of CVD as well as metabolic abnormalities in CVD will be discussed with particular emphasis on lipid metabolites.
Editorial for the Special Issue on Microfluidic Brain-on-a-Chip
Authors: Luttge Regina
Published: September 2021

A little longer than a decade of Organ-on-Chip (OoC) developments has passed [...]
Do New-Generation Recycled Phosphorus Fertilizers Increase the Content of Potentially Toxic Elements in Soil and Plants?
Authors: Jastrzębska Magdalena , Kostrzewska Marta K. , Saeid Agnieszka , Jastrzębski Wiesław P.
Published: September 2021

Phosphorus (P)-rich secondary raw materials can provide a valuable base for modern mineral fertilizers, provided that the new formulations do not load the soil–plant system with potentially toxic elements. Fertilizers from sewage sludge ash (SSA) and/or animal bones, activated by phosphorus-solubilizing bacteria (Bacillus megaterium or Acidithiobacillus ferrooxidans), were tested in field experiments in north-eastern Poland. The reference provided treatments with superphosphate and treatment without phosphorus fertilization. In one experiment, all P-fertilizers were applied at a P dose of 21 kg·ha−1, and in the other three experiments, three P doses were adopted: 17.6, 26.4, and 35.2 kg·ha−1. The effect of recycled fertilizers on the content of arsenic (As), chromium (Cr), nickel (Ni), copper (Cu), and zinc (Zn) in the soil, in wheat grain and straw (test plant), weeds, and post-harvest residues was investigated. The application of recycled fertilizers in P amounts up to 35.2 kg·ha−1 did not change the As, Cr, Ni, Cu, or Zn contents in the soil and plant biomass. The contents of these elements in soil were below the permissible levels for arable land in Poland. Their concentrations in wheat grain and straw did not exceed the permissible or suggested limits for plant material to be used for food and feed, while in the weed and post-harvest residue biomass, they usually fell within the biological plant variability ranges.
Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS
Authors: Gómez Benito Blanco , López-Cortés Rubén , Casas-Nebra Francisco Javier , Vázquez-Estévez Sergio , Pérez-Fentes Daniel , Chantada-Vázquez María del Pilar , Bravo Susana B. , Núñez Cristina
Published: September 2021

Because cystoscopy is expensive and invasive, a new method of detecting non-invasive muscular bladder cancer (NMIBC) is needed. This study aims to identify potential serum protein markers for NMIBC to improve diagnosis and to find treatment approaches that avoid disease progression to a life-threatening phenotype (muscle-invasive bladder cancer, MIBC). Here, silver nanoparticles (AgNPs, 9.73 ± 1.70 nm) as a scavenging device together with sequential window acquisition of all theoretical mass spectra (SWATH-MS) were used to quantitatively analyze the blood serum protein alterations in two NMIBC subtypes, T1 and Ta, and they were compared to normal samples (HC). NMIBC’s analysis of serum samples identified three major groups of proteins, the relative content of which is different from the HC content: proteins implicated in the complement and coagulation cascade pathways and apolipoproteins. In conclusion, many biomarker proteins were identified that merit further examination to validate their useful significance and utility within the clinical management of NMIBC patients.
Effects of Nitrate Supplementation on Exercise Performance in Humans: A Narrative Review
Authors: Macuh Matjaž , Knap Bojan
Published: September 2021

Nitrates have become increasingly popular for their potential role as an ergogenic aid. The purpose of this article was to review the current scientific evidence of nitrate supplementation on human performance. The current recommendation of nitrate supplementation is discussed, as well as possible health complications associated with nitrate intake for athletes, and dietary strategies of covering nitrate needs through sufficient intake of nitrate-rich foods alone are presented. Pubmed, Scopus, and Web of Science were searched for articles on the effects of nitrate supplementation in humans. Nitrates are an effective ergogenic aid when taken acutely or chronically in the range of ~5–16.8 mmol (~300–1041 mg) 2–3 h before exercise and primarily in the case of exercise duration of ~10–17 min in less trained individuals (VO2max < 65 mL/kg/min). Nitrate needs are most likely meet by ingesting approximately 250–500 g of leafy and root vegetables per day; however, dietary supplements might represent a more convenient and accurate way of covering an athlete’s nitrate needs. Athletes should refrain from mouthwash usage when nitrate supplementation benefits are desired. Future research should focus on the potential beneficial effects of nitrate supplementation on brain function, possible negative impacts of chronic nitrate supplementation through different nitrate sources, and the effectiveness of nitrate supplementation on strength and high-intensity intermittent exercise.
Cardioprotective Effects of Nutraceuticals: Focus on Omega-3 Polyunsaturated Fatty Acids
Authors: Sypniewska Grazyna , Kruszewski Stefan
Published: September 2021

Cardiovascular diseases are the leading cause of mortality worldwide [...]
Nanopore-Based Surveillance of Zoonotic Bacterial Pathogens in Farm-Dwelling Peridomestic Rodents
Authors: Jahan Nusrat A. , Lindsey Laramie L. , Kipp Evan J. , Reinschmidt Adam , Heins Bradley J. , Runck Amy M. , Larsen Peter A.
Published: September 2021

The effective control of rodent populations on farms is crucial for food safety, as rodents are reservoirs and vectors for several zoonotic pathogens. Clear links have been identified between rodents and farm-level outbreaks of pathogens throughout Europe and Asia; however, comparatively little research has been devoted to studying the rodent–agricultural interface in the USA. Here, we address this knowledge gap by metabarcoding bacterial communities of rodent pests collected from Minnesota and Wisconsin food animal farms. We leveraged the Oxford Nanopore MinION sequencer to provide a rapid real-time survey of putative zoonotic foodborne pathogens, among others. Rodents were live trapped (n = 90) from three dairy and mixed animal farms. DNA extraction was performed on 63 rodent colons along with 2 shrew colons included as outgroups in the study. Full-length 16S amplicon sequencing was performed. Our farm-level rodent-metabarcoding data indicate the presence of multiple foodborne pathogens, including Salmonella spp., Campylobacter spp., Staphylococcus aureus, and Clostridium spp., along with many mastitis pathogens circulating within five rodent species (Microtus pennsylvanicus, Mus musculus, Peromyscus leucopus, Peromyscus maniculatus, and Rattus norvegicus) and a shrew (Blarina brevicauda). Interestingly, we observed a higher abundance of enteric pathogens (e.g., Salmonella) in shrew feces compared to the rodents analyzed in our study. Knowledge gained from our research efforts will directly inform and improve farm-level biosecurity efforts and public health interventions to reduce future outbreaks of foodborne and zoonotic disease.
Development and Characterisation of Antibody-Based Optical Imaging Probes for Inflammatory Bowel Disease
Authors: Linssen Matthijs David , Hooghiemstra Wouter Tjerk Rudolph , Jorritsma-Smit Annelies , Allersma Derk Pieter , Dijkstra Gerard , Nagengast Wouter Bastiaan
Published: September 2021

Monoclonal antibodies are an important addition to the medicinal treatment paradigm for IBD patients. While effective, these agents show a high degree of primary and secondary non-response, and methods to predict response are highly desired. Information on drug distribution at the target level is often lacking. Fluorescent endoscopic imaging using labelled antibody drugs may provide insight regarding drug distribution, target engagement and drug response, but these assessments require stable and functional fluorescently-conjugated probes. Infliximab, vedolizumab, adalimumab and ustekinumab were conjugated to IRDye 800CW, IRDye 680LT and ZW800-1. The resulting 12 tracer candidates were analysed and characterised on SE-HPLC, SDS-PAGE, iso-electric focussing (IEF) and ELISA in order to evaluate their feasibility as candidate clinical tracers for cGMP development. Major differences in the conjugation results could be seen for each conjugated drug. For Infliximab, 2 conjugates (800CW and 680LT) showed formation of aggregates, while conjugates of all drugs with ZW800-1 showed reduced fluorescent brightness, reduced purification yield and formation of fragments. All 6 of these candidates were considered unfeasible. From the remaining 6, ustekinumab-680LT showed reduced binding to IL23, and was therefore considered unfeasible. Out of 12 potential tracer candidates, 5 were considered feasible for further development: vedolizumab-800CW, vedolizumab-680LT, adalimumab-800CW, adalimumab-680LT and ustekinumab-800CW. Infliximab-680LT and ustekinumab-680LT failed to meet the standards for this panel, but may be rendered feasible if tracer production methods were further optimized.
Enhancement of Skin Delivery of Drugs Using Proposome Depends on Drug Lipophilicity
Authors: Kathuria Himanshu , Handral Harish K. , Cha Saera , Nguyen Diep T. P. , Cai Junyu , Cao Tong , Wu Chunyong , Kang Lifeng
Published: September 2021

The study aims to investigate the propylene glycol-based liposomes named ‘proposomes’ in enhancing skin permeation of drugs with different physicochemical properties. Ibuprofen, tofacitinib citrate, rhodamine B, and lidocaine were loaded into proposomes. These drug formulations were analyzed for particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro skin permeation. The confocal laser scanning microscopy was performed on skin treated with calcein and rhodamine B laden proposomes. The transdermal delivery relative to physicochemical properties of drugs such as logP, melting point, molecular weight, solubility, etc., were analyzed. We tested the safety of the proposomes using reconstructed human skin tissue equivalents, which were fabricated in-house. We also used human cadaver skin samples as a control. The proposomes had an average diameter of 128 to 148 nm. The drug’s entrapment efficiencies were in the range of 42.9–52.7%, translating into the significant enhancement of drug permeation through the skin. The enhancement ratio was 1.4 to 4.0, and linearly correlated to logP, molecular weight, and melting point. Confocal imaging also showed higher skin permeation of calcein and rhodamine B in proposome than in solution. The proposome was found safe for skin application. The enhancement of skin delivery of drugs through proposomes was dependent on the lipophilicity of the drug. The entrapment efficiency was positively correlated with logP of the drug, which led to high drug absorption.
An Insulin-like Growth Factor-1 Conjugated Bombyx mori Silk Fibroin Film for Diabetic Wound Healing: Fabrication, Physicochemical Property Characterization, and Dosage Optimization In Vitro and In Vivo
Authors: Lin Meng-Jin , Lu Mei-Chun , Chan Yun-Chen , Huang Yu-Fen , Chang Hwan-You
Published: September 2021

This study aimed to develop a silk fibroin (SF)-film for the treatment of chronic diabetic wounds. Silk fibroin was purified through a newly developed heating degumming (HD) process and casted on a hydrophobic surface to form SF-films. The process allowed the fabricated film to achieve a 42% increase in transparency and a 32% higher proliferation rate for BALB/3T3 fibroblasts compared to that obtained by conventional alkaline degumming treatment. Fourier transform infrared analysis demonstrated that secondary structure was retained in both HD- and alkaline degumming-derived SF preparations, although the crystallinity of beta-sheet in SF-film after the HD processing was slightly increased. This study also investigated whether conjugating insulin-like growth factor-1 (IGF-1) would promote diabetic wound healing and what the optimal dosage is. Using BALB/3T3 cells grown in hyperglycemic medium as a model, it was demonstrated that the optimal IGF-1 dosage to promote the cell growth was approximately 0.65 pmol. Further analysis of wound healing in a diabetic mouse model indicated that SF-film loaded with 3.25 pmol of IGF-1 showed significantly superior wound closure, a 13% increase at the 13th day after treatment relative to treatment with 65 pmol of free IGF-1. Improvement in diabetic wound healing was exerted synergistically by SF-film and IGF-1, as reflected by parameters including levels of re-epithelialization, epithelial tissue area, and angiogenesis. Finally, IGF-1 increased the epithelial tissue area and micro-vessel formation in a dose-dependent manner in a low dosage range (3.25 pmol) when loaded to SF-films. Together, these results strongly suggest that SF-film produced using HD and loaded with a low dosage of IGF-1 is a promising dressing for diabetic wound therapy.
Development and Evaluation of Tannic Acid-Coated Nanosuspension for Enhancing Oral Bioavailability of Curcumin
Authors: Lee Hyeonmin , Bang Jun-Bae , Na Young-Guk , Lee Jae-Young , Cho Cheong-Weon , Baek Jong-Suep , Lee Hong-Ki
Published: September 2021

Curcumin (CUR) has been used in the treatment of various diseases such as cough, fever, skin disease, and infection because of various biological benefits such as anti-inflammatory, antiviral, antibacterial, and antitumor activity. However, CUR is a BCS class 4 group and has a limitation of low bioavailability due to low solubility and permeability. Therefore, the purpose of this study is to prepare a nanosuspension (NSP) loaded with CUR (CUR-NSP) using a statistical design approach to improve the oral bioavailability of CUR, and then to develop CUR-NSP coated with tannic acid to increase the mucoadhesion in the GI tract. Firstly, the optimized CUR-NSP, composed of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone/vinyl acetate (PVP/VA), was modified with tannic acid (TA). The particle size and polydispersity index of the formulation measured by laser scattering analyzer were 127.7 ± 1.3 nm and 0.227 ± 0.010, respectively. In addition, the precipitation in distilled water (DW) was 1.52 ± 0.58%. Using a differential scanning calorimeter and X-ray diffraction analysis, the stable amorphous form of CUR was confirmed in the formulation, and it was confirmed that CUR-NSP formulation was coated with TA through a Fourier transform-infrared spectroscopy. In the mucoadhesion assay using the turbidity, it was confirmed that TA-CUR-NSP had higher affinity for mucus than CUR-NSP under all pH conditions. This means that the absorption of CUR can be improved by increasing the retention time in the GI tract of the formulation. In addition, the drug release profile showed more than 80% release, and in the cellular uptake study, the absorption of the formulation (TA-CUR-NSP) containing TA acting as an inhibitor of P-gp was increased by 1.6-fold. In the evaluation of antioxidant activity, the SOD activity of TA-CUR-NSP was remarkably high due to TA, which improves cellular uptake and has antioxidant activity. In the pharmacokinetic evaluation, the maximum drug plasma concentration of the TA-coated NSP formulation was 7.2-fold higher than that of the pure drug. In all experiments, it was confirmed that the TA-CUR-NSP is a promising approach to overcome the low oral bioavailability of CUR.
90Y/177Lu-DOTATOC: From Preclinical Studies to Application in Humans
Authors: Uccelli Licia , Boschi Alessandra , Cittanti Corrado , Martini Petra , Panareo Stefano , Tonini Eugenia , Nieri Alberto , Urso Luca , Caracciolo Matteo , Lodi Luca , Carnevale Aldo , Giganti Melchiore , Bartolomei Mirco
Published: September 2021

The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177. In this review, covering twenty five years of literature, we describe the characteristics and performances of the two most used therapeutic radiopharmaceuticals for the NETs radio-treatment: [90Y]Y-DOTATOC and [177Lu]Lu-DOTATOC taking this opportunity to retrace the most significant results that have determined their success, promoting them from preclinical studies to application in humans.
Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release
Authors: Yang Yang , Yang Fuwei , Shan Xiaotian , Xu Jiamin , Fang Wenjie , Zhou Juan , Qiu Lipeng , Chen Jinghua
Published: September 2021

At present, the drug is still difficult to release completely and quickly only with single stimulation. In order to promote the rapid release of polymeric micelles at tumor site, pH/reduction sensitive polymers (PCT) containing disulfide bonds and orthoester groups were synthesized. The PCT polymers can self-assemble in water and entrap doxorubicin to form drug-loaded micelles (DOX/PCT). In an in vitro drug release experiment, the cumulative release of DOX/PCT micelles in the simulated tumor microenvironment (pH 5.0 with GSH) reached (89.7 ± 11.7)% at 72 h, while it was only (16.7 ± 6.1)% in the normal physiological environment (pH 7.4 without GSH). In addition, pH sensitive DOX loaded micellar system (DOX/PAT) was prepared as a control. Furthermore, compared with DOX/PAT micelles, DOX/PCT micelles showed the stronger cytotoxicity against tumor cells to achieve an effective antitumor effect. After being internalized by clathrin/caveolin-mediated endocytosis and macropinocytosis, DOX/PCT micelles were depolymerized in intercellular acidic and a reductive environment to release DOX rapidly to kill tumor cells. Additionally, DOX/PCT micelles had a better inhibitory effect on tumor growth than DOX/PAT micelles in in vivo antitumor activity studies. Therefore, pH/reduction dual sensitive PCT polymers have great potential to be used as repaid release nanocarriers for intercellular delivery of antitumor drugs.
Effects of Light Condition on Growth and Physiological Characteristics of the Endangered Species Sedirea japonica under RCP 6.0 Climate Change Scenarios
Authors: Lee Kyeong Cheol , An Jiae , Hwang Jung Eun , Kim Pyoung Beom , Park Hyeong Bin , Kim Seongjun , Park Hwan Joon , Lee Chang Woo , Lee Byoung-Doo , Kim Nam Young
Published: September 2021

This study was conducted to evaluate the physiological and growth responses of Sedirea japonica cultured in chambers under RCP 6.0 and different light conditions. S. japonica was grown in a soil–plant daylight system chamber under two treatments, a control (CO2 = 400 ppm) and a climate change treatment (CCT) (CO2 = 650 ppm, temperature = control + 3 °C), and three different shading treatments (60%, 90%, and no-shading). S. japonica showed the characteristics of typical Crassulacean acid metabolism (CAM) plants. As the shading rate increased, it increased chlorophyll content, leaf area, and leaf dry weight to efficiently absorb and use light. The CCT had a lower CO2 absorption rate, stomatal conductance, and growth rate and slightly higher water utilization efficiency than the control. This was because stomatal closure occurred in the CCT to reduce water loss due to a relatively higher temperature. As CO2 fixation decreased and consumption increased due to respiration, the overall growth was inhibited. The CCT without shading revealed a dynamic photoinhibition phenomenon showing a significant increase in ABS/RC, TRo/RC, ETo/RC, and DIo/RC and a decrease in PI ABS and DF ABS. In this group, leaf, root, and total dry weight, chlorophyll content, and carotenoid content were the worst growth indices.
Antibacterial, Antihemolytic, Cytotoxic, Anticancer, and Antileishmanial Effects of Ajuga bracteosa Transgenic Plants
Authors: Rubnawaz Samina , Okla Mohammad K. , Akhtar Nosheen , Khan Imdad Ullah , Bhatti Muhammad Zeeshan , Duong Hong-Quan , El-Tayeb Mohamed A. , Elbadawi Yahaya B. , Almaary Khalid S. , Moussa Ihab M. , Abbas Zahid Khurshid , Mirza Bushra
Published: September 2021

Herbal and traditional medicines can play a pivotal role in combating cancer and neglected tropical diseases. Ajuga bracteosa, family Lamiaceae, is an important medicinal plant. The genetic transformation of A. bracteosa with rol genes of Agrobacterium rhizogenes further enhances its metabolic content. This study aimed at undertaking the molecular, phytochemical, and in vitro biological analysis of A. bracteosa extracts. We transformed the A. bracteosa plant with rol genes and raised the regenerants from the hairy roots. Transgenic integration and expression of rolB were confirmed by conventional polymerase chain reaction (PCR) and qPCR analysis. The methanol: chloroform crude extracts of wild-type plants and transgenic regenerants were screened for in vitro antibacterial, antihemolytic, cytotoxic, anticancer, and leishmanial activity. Among all plants, transgenic line 3 (ABRL3) showed the highest expression of the rolB gene. Fourier transform infra-red (FTIR) analysis confirmed the enhanced number of functional groups of active compounds in all transgenic lines. Moreover, ABRL3 exhibited the highest antibacterial activity, minimum hemolytic activity (CC50 = 7293.05 ± 7 μg/mL) and maximum antileishmanial activity (IC50 of 56.16 ± 2 μg/mL). ABRL1 demonstrated the most prominent brine shrimp cytotoxicity (LD5039.6 ± 4 μg/mL). ABRL3 was most effective against various human cancer cell lines with an IC50 of 57.1 ± 2.2 μg/mL, 46.2 ± 1.1 μg/mL, 72.4 ± 1.3 μg/mL, 73.3 ± 2.1 μg/mL, 98.7 ± 1.6 μg/mL, and 97.1 ± 2.5 μg/mL against HepG2, LM3, A549, HT29, MCF-7, and MDA-MB-231, respectively. Overall, these transgenic extracts may offer a cheaper therapeutic source than the more expensive synthetic drugs.
Anticancer Potential of Natural Bark Products—A Review
Authors: Burlacu Ema , Tanase Corneliu
Published: September 2021

Cell biology, plant-based extracts, structural chemistry, and laboratory in vitro or in vivo experiments are the principal aspects or interfaces that can contribute to discovering new possibilities in cancer therapy and to developing improved chemotherapeutics. Forestry residues can be used for their wealthy resource in polyphenols and other phytoconstituents known for anticancer properties. This review is designed to bring together information on the in vitro or in vivo anticancer potential of woody vascular plants especially the bark extracts (BE) and biosynthesized metallic nanoparticles (BMN) using bark extracts. Type of extracts, main phytoconstituents found in extracts responsible for the anticancer activity, and targeted cancerous cell lines were followed. The literature data were collected via Clarivate Analytics, Science Direct, PubMed, and Google Academic (2011–2021). The search terms were: bark extracts, metallic nanoparticles, silver nanoparticles, gold nanoparticles, anticancer, cytotoxic activity, antiproliferative effect, and antimetastatic potential in vitro and in vivo. All of the search terms listed above were used in different combinations. The literature data highlight the efficaciousness of the BE and BMN as anticancer agents in in vitro experiments and showed the mechanism of action and their advantage of nontoxicity on normal cells. In vitro testing has shown promising results of the BE and BMN effect on different cancer cell lines. In vivo testing is lacking and more data is necessary for drug development on animal models.
A Concise Review of Dendrocalamus asper and Related Bamboos: Germplasm Conservation, Propagation and Molecular Biology
Authors: Mustafa Anis Adilah , Derise Mohammad Rahmat , Yong Wilson Thau Lym , Rodrigues Kenneth Francis
Published: September 2021

Bamboos represent an emerging forest resource of economic significance and provide an avenue for sustainable development of forest resources. The development of the commercial bamboo industry is founded upon efficient molecular and technical approaches for the selection and rapid multiplication of elite germplasm for its subsequent propagation via commercial agro-forestry business enterprises. This review will delve into the micropropagation of Dendrocalamus asper, one of the most widely cultivated commercial varieties of bamboo, and will encompass the selection of germplasm, establishment of explants in vitro and micropropagation techniques. The currently available information pertaining to molecular biology, DNA barcoding and breeding, has been included, and potential areas for future research in the area of genetic engineering and gene regulation have been highlighted. This information will be of relevance to both commercial breeders and molecular biologists who have an interest in establishing bamboo as a crop of the future.
Jawbones Scaffold Constructed by TGF-β1 and BMP-2 Loaded Chitosan Microsphere Combining with Alg/HA/ICol for Osteogenic-Induced Differentiation
Authors: Tan Yongxin , Zhang Liqun , Rajoka Muhammad Shahid Riaz , Mai Zhanhua , Bahadur Ali , Mehwish Hafiza Mahreen , Umair Muhammad , Zhao Liqing , Wu Yiguang , Song Xun
Published: September 2021

Bone scaffolds based on multi-components are the leading trend to address the multifaceted prerequisites to repair various bone defects. Chitosan is the most useable biopolymer, having excellent biological applications. Therefore, in the present study, the chitosan microsphere was prepared by the ion–gel method; transforming growth factor β (TGF-β1) and bone morphogenetic protein 2 (BMP-2) were loaded onto it and then combined with alginate/hyaluronic acid/collagen (Alg/HA/ICol) to construct a jawbones scaffold. The Alg/HA/ICol scaffolds were characterized by FTIR and SEM, and the water content, porosity, tensile properties, biocompatibility, and osteogenic-induced differentiation ability of the Alg/HA/ICol jawbones scaffolds were studied. The results indicate that a three-dimensional porous jawbone scaffold was successfully constructed having 100–250 μm of pore size and >90% of porosity without cytotoxicity against adipose-derived stem cells (ADSCs). Its ALP quantification, osteocalcin expression, and Von Kossamineralized nodule staining was higher than the control group. The jawbones scaffold constructed by TGF-β1 and BMP-2 loaded chitosan microsphere combining with Alg/HA/ICol has potential biomedical application in the future.
Effect of Luting Cement Film Thickness on the Pull-Out Bond Strength of Endodontic Post Systems
Authors: Aleisa Khalil , Habib Syed Rashid , Ansari Abdul Sadekh , Altayyar Ragad , Alharbi Shahad , Alanazi Sultan Ali S. , Alduaiji Khalid Tawfik
Published: September 2021

Optimal bond strength between the prefabricated post/dowel to the surrounding dentin is essential. The present study aimed to analyze and compare the effect of three different cement film thicknesses on the pull-out bond strength of three different prefabricated post systems. Extracted natural teeth (N = 90) with similar root dimensions were acquired. Teeth were mounted in resin blocks, endodontically treated, sectioned at cemento-enamel junction, divided into three groups (A: Parapost Fiber Lux plus; B: 3M ESPE Relyx fiber post; and C: Parapost XP), and stored. Uniform post spaces were prepared for the groups (A and C: Length = 8 mm, Width = 1.5 mm; B: Length = 8 mm, Width = 1.6 mm). Each group (N = 30) was further subdivided into three subgroups (n = 10) based on the size (4, 5, and 6) of the post and cemented with resin cement (MultiLink-N, Ivoclar Vivadent). After thermocycling, the specimens were subjected to a pull-out test using a universal testing machine, and tensile force was recorded (MPa). Digital microscopic evaluations were performed for modes of failure. ANOVA and Tukey-HSD tests were used for statistics. Significant differences were observed for each tested material (p = 0.000). The lowest and highest bond strength values were recorded for Group C (Titanium post) and Group A (000), respectively. Multiple comparisons showed significance (p < 0.05) among all the groups, except for space 1 and space 2 (p = 0.316) for Group A. Most of the failures occurred within the cement-dentin and post-cement interface (Adhesive failures, 73.5%). An increase in the luting cement film thickness results in the decrease in pull-out bond strength of prefabricated posts luted with resin cement, irrespective of the type/material/shape of the post. The serrated fiber posts showed the highest pull-out bond strength compared to the smooth surfaced fiber posts or serrated metal posts. Increased pull-out bond strengths were observed when appropriate post space was created with the same sized drill as the post size.