bluuebunny/crossref_metadata_2025 huggingface dataset:
CTSE Overexpression Is an Adverse Prognostic Factor for Survival among Rectal Cancer Patients Receiving CCRT
Authors: Chou Chia-Lin , Chen Tzu-Ju , Tian Yu-Feng , Chan Ti-Chun , Yeh Cheng-Fa , Li Wan-Shan , Tsai Hsin-Hwa , Li Chien-Feng , Lai Hong-Yue
Published: July 2021

The introduction of preoperative concurrent chemoradiotherapy (CCRT) increases the rate of anal preservation and allows tumor downstaging for clinical stage T3/T4 or node-positive rectal cancer patients. However, there is no precise predictive tool to verify the presence of residual tumor apart from surgical resection. The gastrointestinal (GI) tract not only digests nutrients but also coordinates immune responses. As the outermost layer of the GI tract, mucus plays a key role in mediating the interaction between the digestive and immune systems, and aberrant mucus mesh formation may cause chemoresistance by impeding drug delivery. However, the correlations among digestion-related genes, mucin synthesis, and chemoresistance remain poorly understood. In the present study, we evaluated genes related to digestion (GO: 0007586) and identified cathepsin E (CTSE), which is involved in immune regulation, as the most significantly upregulated gene associated with CCRT resistance in rectal cancer in a public transcriptome dataset (GSE35452). We recovered 172 records of rectal cancer patients receiving CCRT followed by surgical resection from our biobank and evaluated the expression level of CTSE using immunohistochemistry. The results revealed that tumors with CTSE overexpression were significantly correlated with pre-CCRT and post-CCRT positive nodal status (both p < 0.001), advanced pre-CCRT and post-CCRT tumor status (p < 0.001 and p = 0.002), perineural invasion (p = 0.023), vascular invasion (p < 0.001), and a lesser degree of tumor regression (p = 0.003). At the univariate level, CTSE overexpression was an adverse prognostic factor for all three endpoints: disease-specific survival (DSS), metastasis-free survival (MeFS) (both p < 0.0001), and local recurrence-free survival (LRFS) (p = 0.0001). At the multivariate level, CTSE overexpression remained an independent prognostic factor for poor DSS, MeFS (both p = 0.005), and LRFS (p = 0.019). Through bioinformatics analysis, we speculated that CTSE overexpression may confer CCRT resistance by forming a defensive mucous barrier. Taken together, these results suggest that CTSE overexpression is related to CCRT resistance and inferior survival in rectal cancer patients, highlighting the potential predictive and prognostic value of CTSE expression.
Damage Mechanism of PTFE/Al Reactive Charge Liner Structural Parameters on a Steel Target
Authors: Zhang Xuepeng , Wang Zhijun , Yin Jianping , Yi Jianya , Wang Haifu
Published: July 2021

The incorporation of reactive material damage element technology in ammunition warheads is a research hotspot in the development of conventional ammunition. The research results are of great significance and military application value to promote the development of high-efficiency damage ammunition technology. In this paper, we aimed to understand the behavior of the reactive jet and its damage effect on a steel target by undertaking theoretical analysis, numerical simulation, and experimental research. We studied the influence of structural and material parameters on the shape of the reactive jet based on autodyn-2d finite element simulation software, and the formation behavior of the reactive jet was verified using a pulsed X-ray experiment. By studying the combined damage caused by the steel target penetrating and exploding the reactive jet, the influence of the structural and performance parameters, and the explosion height of the reactive jet liner on the damage effect to the steel target was studied. A static explosion experiment was carried out, and the optimal structural and performance parameters for the reactive material and explosion height of the reactive jet liner were obtained.
Identification of Volatile and Semi-Volatile Compounds in Polymeric Coatings Used in Metal Cans by GC-MS and SPME
Authors: Vázquez-Loureiro Patricia , Lestido-Cardama Antía , Sendón Raquel , López-Hernández Julia , Paseiro-Losada Perfecto , Rodríguez-Bernaldo de Quirós Ana
Published: July 2021

Polymeric coatings are used as a protective layer to preserve food or beverage quality and protect it from corrosion and avoid a metallic taste. These types of materials can contain some chemicals that are susceptible to migrate to food and constitute a risk for consumers’ health. This study is focused on the identification of volatile and semi-volatile low molecular weight compounds present in polymeric coatings used for metal food and beverage cans. A method based on solid–liquid extraction followed by gas chromatography–mass spectrometry (GC-MS) was optimized for the semi-volatile compounds. Different solvents were tried with the aim of extracting compounds with different polarities. Furthermore, a method based on solid-phase microextraction (SPME) in headspace (HS) mode and gas chromatography coupled with mass spectrometry (HSSPME-GC-MS) was developed for the identification of potential volatile migrants in polymeric coatings. Some parameters such as extraction time, equilibrium temperature, or the type of fiber were optimized. Different compounds, including aldehydes such as octanal or nonanal, alcohols such as α-terpineol or 2-butoxyethanol, ethers, alkenes, or phthalic compounds, among others, were identified and confirmed with analytical standards both via SPME analysis as well after solvent extraction.
Consideration of Lamination Structural Analysis in a Multi-Layered Composite and Failure Analysis on Wing Design Application
Authors: Basri Ernnie Illyani , Sultan Mohamed Thariq Hameed , Basri Adi Azriff , Mustapha Faizal , Ahmad Kamarul Arifin
Published: July 2021

A finite element (FE) model is developed to study the structural performance on a composite wing of a UAV with a tubercle design at the leading edge of the wing. The experimental study of the designation of the composite at the wing skin is carried out to prove the simulation validity through material characteristics. In this paper, the numerical modeling for simulation is highlighted to correlate the process parameter setting of simulation replicating the actual experimental tests. The percentage difference was calculated to be 11.1% by tensile and 10.47% by flexural. The numerical work applied the study of FE analysis and developed a standardized numerical approach for structural optimization, known as FE-ACP simulation. The significant findings of deformation are obtained according to Schrenk’s aerodynamic loading, while the prediction of failure mode of Tsai–Wu under interaction among stresses and strains was acquired at the seventh and eighth layer of both spars.
Nanomaterials for the Diagnosis and Treatment of Head and Neck Cancers: A Review
Authors: Ruiz-Pulido Gustavo , Medina Dora I. , Barani Mahmood , Rahdar Abbas , Sargazi Ghasem , Baino Francesco , Pandey Sadanand
Published: July 2021

Head and neck cancer (HNC) is a category of cancers that typically arise from the nose-, mouth-, and throat-lining squamous cells. The later stage of HNC diagnosis significantly affects the patient’s survival rate. This makes it mandatory to diagnose this cancer with a suitable biomarker and imaging techniques at the earlier stages of growth. There are limitations to traditional technologies for early detection of HNC. Furthermore, the use of nanocarriers for delivering chemo-, radio-, and phototherapeutic drugs represents a promising approach for improving the outcome of HNC treatments. Several studies with nanostructures focus on the development of a targeted and sustained release of anticancer molecules with reduced side effects. Besides, nanovehicles could allow co-delivering of anticancer drugs for synergistic activity to counteract chemo- or radioresistance. Additionally, a new generation of smart nanomaterials with stimuli-responsive properties have been developed to distinguish between unique tumor conditions and healthy tissue. In this light, the present article reviews the mechanisms used by different nanostructures (metallic and metal oxide nanoparticles, polymeric nanoparticles, quantum dots, liposomes, nanomicelles, etc.) to improve cancer diagnosis and treatment, provides an up-to-date picture of the state of the art in this field, and highlights the major challenges for future improvements.
Improvement of Osseointegration by Ultraviolet and/or Simvastatin Treatment on Titanium Implants with or without Bone Graft Materials
Authors: Jun Ji , Oh Kyung , Park Kyu-Hyung , Jung Narae , Li Jiayi , Moon Hong
Published: July 2021

We evaluated and compared ultraviolet (UV) treatment and simvastatin (SIM) immersion effects on the osseointegration of sandblasted, large-grit, acid-etched (SLA) titanium dental implants at two different time points in rabbit tibias, with or without xenogenic bone graft materials. The surface alteration on simvastatin treatment titanium discs was analyzed using an infrared spectrometer. Implants were categorized into four groups according to the surface treatment type. Twelve rabbits received two implants per tibia. A tibial defect model was created using a trephine bur, with implants in contact with the bone surface and bovine bone graft materials for gap filling. The rabbits were sacrificed after 2 or 4 weeks. UV treatment or SIM immersion increased the bone-to-implant contact (BIC) on nongrafted sides, and both increased the BIC and bone area (BA) on grafted sides. The application of both treatments did not result in higher BIC or BA than a single treatment. At two different time points, BIC in the nongrafted sides did not differ significantly among the UV and/or SIM treated groups, whereas BA differed significantly. UV or SIM treatment of SLA titanium implants accelerates osseointegration in tibias with or without xenogenic bone graft materials. The combination of both treatments did not show synergy.
Research on Properties of Borocarbide in High Boron Multi-Component Alloy with Different Mo Concentrations
Authors: Ren Xiangyi , Han Lihong , Fu Hanguang , Wang Jianjun
Published: July 2021

In this work, the microstructure, alloying element distribution, and borocarbide mechanical properties of high-boron multi-component alloy with Fe-2.0 wt.%B-0.4 wt.%C-6.0 wt.%Cr-x wt.%Mo-1.0%Al-1.0 wt.%Si-1.0 wt.%V-0.5 wt.%Mn (x = 0.0, 2.0, 4.0, 6.0, 8.0) are investigated. The theoretical calculation results and experiments indicate that the microstructure of high-boron multi-component alloy consists of ferrite, pearlite as a matrix and borocarbide as a hard phase. As a creative consideration, through the use of first-principles calculations, the comprehensive properties of borocarbide with different molybdenum concentrations have been predicted. The calculations of energy, state density, electron density and elastic constant of Fe2B crystal cell reveal that substitution of the molybdenum atom in the Fe2B crystal cell can remarkably improve its thermodynamic stability, bond strength, and covalent trend. For verifying the accuracy of this theoretical calculation, nano-indentation testing is carried out, the results of which indicate that the actual properties of borocarbide present favorable consistency with the theoretical calculations.
The Potential of Stereolithography for 3D Printing of Synthetic Trabecular Bone Structures
Authors: Grzeszczak Ana , Lewin Susanne , Eriksson Olle , Kreuger Johan , Persson Cecilia
Published: July 2021

Synthetic bone models are used to train surgeons as well as to test new medical devices. However, currently available models do not accurately mimic the complex structure of trabecular bone, which can provide erroneous results. This study aimed to investigate the suitability of stereolithography (SLA) to produce synthetic trabecular bone. Samples were printed based on synchrotron micro-computed tomography (micro-CT) images of human bone, with scaling factors from 1 to 4.3. Structure replicability was assessed with micro-CT, and mechanical properties were evaluated by compression and screw pull-out tests. The overall geometry was well-replicated at scale 1.8, with a volume difference to the original model of <10%. However, scaling factors below 1.8 gave major print artefacts, and a low accuracy in trabecular thickness distribution. A comparison of the model–print overlap showed printing inaccuracies of ~20% for the 1.8 scale, visible as a loss of smaller details. SLA-printed parts exhibited a higher pull-out strength compared to existing synthetic models (Sawbones ™), and a lower strength compared to cadaveric specimens and fused deposition modelling (FDM)-printed parts in poly (lactic acid). In conclusion, for the same 3D model, SLA enabled higher resolution and printing of smaller scales compared to results reported by FDM.
Synthesis, Optical Characterizations and Solar Energy Applications of New Schiff Base Materials
Authors: Gomha Sobhi M. , Ahmed Hoda A. , Shaban Mohamed , Abolibda Tariq Z. , Khushaim Muna S. , Alharbi Khalid A.
Published: July 2021

A new set of laterally OCH3-substituted photoactive liquid crystalline analogues, 4-hexyloxy phenyl- imino-4ʹ-(3-methoxyphenyl)-4ʹ’-alkoxybenzoates, were synthesized and investigated for their mesomorphic behavior. The prepared set constitutes five analogues that differ from each other by the terminally attached compact polar group. Characterization of the synthesized derivatives is conducted using differential scanning calorimetry (DSC), polarized optical microscopy (POM), and UV-spectroscopy. Molecular structures were elucidated by elemental analyses, FT-IR and NMR spectroscopy. DSC and POM investigations indicated that all the prepared derivatives are monomorphic possessing the nematic (N) phase, except for the unsubstituted derivative that is nonmesomorphic. On the other side, the photophysical study and the optical spectra measurements confirm the photoactivity of the present compounds under UV/visible irradiation. The measured optical spectra showed impressive enhancement in the optical absorption and reduction in the optical bandgap from 3.63 to 3.0 eV depending on the terminal group. From the study of the DC electric properties, the lowest resistance, 106.5 GΩ at scan rate 0.1 V/s, was observed for the I6d film with Cl terminal, which decreased to 49.5 GΩ by increasing the scan rate to 0.5 V/s. Moreover, the electrical conductance is decreased from 9.39 pS to 1.35 pS at scan rate 0.1 V/s by changing the terminal group from Cl to F. The enhanced optical absorption and the reduced energy gap make the optimized samples suitable material for solar energy applications.
Evaluation of the Impact of Different Natural Zeolite Treatments on the Capacity of Eliminating/Reducing Odors and Toxic Compounds
Authors: Fuss Vanda Liliana Babalau , Bruj Gabriel , Dordai Lucian , Roman Marius , Cadar Oana , Becze Anca
Published: July 2021

Unlike odorants that mask odors, natural zeolite acts as a molecular sieve that captures and eliminates odors. Different treatment methods can be applied to influence the properties of the natural zeolites. To enhance the odor adsorption capacities of the natural zeolite two types of treatment methods were applied: chemical (acid, basic) and thermal. The initial natural zeolites and the activated one were characterized using X-ray diffraction (XRD) and scanning electron microscope (SEM-EDX). Two experiments were performed to establish the odor adsorption capacity of the activated natural zeolites. The best zeolite for the adsorption of humidity, ammonia and hydrogen sulfide was the 1–3 mm zeolite activated through thermal treatment. For the adsorption of PAHs, the best zeolite was the one activated through basic treatment, with an adsorption capacity of 89.6 ng/g.
The Mechanical Properties of Early Aged Shotcrete under Internal Sulfate Attack
Authors: Jin Xiaoguang , He Jie , Hou Chao , Luo Wei , He Wenjun
Published: July 2021

Shotcrete is the primary material for tunnel support due to its early rapid hardening characteristics. During tunnel construction in a sulfate environment, the hardening law of concrete will be affected. In this study, samples were prepared at six different curing times and immersed in four different concentrations of sulfate solutions. A uniaxial test was conducted and analyzed to investigate the effect of sulfate attack on the mechanical properties of early aged shotcrete materials. Results indicated that waterlogged shotcrete does not have apparent cracks on the outside. The stress–strain curve or ultimate compressive strength of the samples showed that the effect of sulfate on shotcrete should be differentiated into chemical and physical sulfate attacks, according to the concentration of sulfate ions. The two parameters in the equation of the hardening behaviors of sulfate attack samples, ultimate compressive strength, and time constant, are related to sulfate concentration. The crack damage stress threshold of samples demonstrates that high-concentration sulfate corrosion leads to an impact on the durability of shotcrete.
Fast and Precise Non-Contact Measurement of Cylindrical Surfaces with Air Gauges
Authors: Jermak Czeslaw Janusz , Jakubowicz Michal , Wieczorowski Michal , Rucki Miroslaw
Published: July 2021

In this paper, the results of an investigation on the application of air gauges in the measurement of out-of-roundness parameters are presented. The principle of the measuring system is explained, in particular the novel design of the floating gauge head. An algorithm for fully automated measurement and data processing is described. The results from a series of initial measurements provided the data for further simulations, which revealed possible sources of errors. The simulations helped to evaluate the influence of some of the parameters on the final measurement results. After various accuracy tests, the method accuracy (MA) parameter was calculated in relation to the dedicated reference form tester. The result MA = 9.29% was judged to be highly satisfactory considering the short measurement time and non-contact method.
Reuse of the Materials Recycled from Renewable Resources in the Civil Engineering: Status, Achievements and Government’s Initiatives in Taiwan
Authors: Tsai Chi-Hung , Shen Yun-Hwei , Tsai Wen-Tien
Published: July 2021

Growing concerns about the circular economy and sustainable waste management for civil applications of non-hazardous mineral industrial waste have increased in recent years. Therefore, this study presents a trend analysis of industrial waste generation and treatment during the years of 2010–2020, and focused on promotion policies and regulatory measures for mandatory renewable resources from industrial sources in Taiwan, including reclaimed asphalt pavement (RAP) material, water-quenched blast furnace slag, and ilmenite chlorination furnace slag. According to the official database of the online reported statistics during the period of 2010–2020, approximately three million metric tons per year of renewable resources were totally reused in civil engineering or related cement products, reflecting a balanced supply chain in the domestic market. Among these, water-quenched blast furnace slag accounted for about 90% (about 2.7 million metric tons) in Taiwan. Currently, the legislative framework of sustainable waste management in Taiwan is based on the Waste Management Act and the Resource Recycling Act, but there are some problems with them. In order to effectively reduce environmental loadings and conserve natural resources to mitigate climate change, some recommendations are addressed from different points of view.
Poly(2-oxazoline)-Based Amphiphilic Gradient Copolymers as Nanocarriers for Losartan: Insights into Drug–Polymer Interactions
Authors: Chroni Angeliki , Mavromoustakos Thomas , Pispas Stergios
Published: July 2021

The current study is focused on the development of highly stable drug nanocarriers by encapsulating losartan potassium (LSR) into an amphiphilic biocompatible poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (PMeOxz72-grad-PPhOxz28) gradient copolymer (GC). Based on dynamic light scattering (DLS), the PMeOxz72-grad-PPhOxz28 (where the subscripts denote %wt composition of the components) GC formed micelles and aggregates of 13 nm and 96 nm in aqueous milieu. The presence of hydrophobic LSR molecules altered the structural characteristics of the GC, modulating the organization of the polymeric components and revealing the formation of hyper micellar nanostructures in addition to micelles. The 2D-NOESY experiments evidenced intermolecular interactions between the phenyl ring of LSR with the phenyl group of PPhOxz and eminent correlations between the butyl chain of LSR with the phenyl group of PPhOxz and methylene group of PMeOxz, respectively. Additionally, NMR studies as a function of temperature demonstrated that the presence of hydrophilic PMeOxz segments in the gradient core of PMeOxz72-grad-PPhOxz28 nanoassemblies induced an increased fluidity of the core matrix, especially upon heating, thus causing water penetration, resulting in increased proton mobility. Lastly, the ultrasound release profile of LSR signified that a great amount of the encapsulated LSR is tightly bound to the PMeOxz72-grad-PPhOxz28 nanoassemblies.
Physicochemical, Nutritional and In Vitro Antidiabetic Characterisation of Blue Whiting (Micromesistiuspoutassou) Protein Hydrolysates
Authors: Harnedy-Rothwell Pádraigín A , Khatib Neda , Sharkey Shaun , Lafferty Ryan A , Gite Snehal , Whooley Jason , O’Harte Finbarr PM , FitzGerald Richard J
Published: July 2021

Protein hydrolysates from low-value underutilised fish species are potential sources of high-quality dietary protein and health enhancing peptides. Six blue whiting soluble protein hydrolysates (BW-SPH-A_F), generated at industrial scale using different hydrolysis conditions, were assessed in terms of their protein equivalent content, amino acid profile and score and physicochemical properties in addition to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) and stimulate the secretion of insulin from BRIN-BD11 cells. Furthermore, the effect of simulated gastrointestinal digestion (SGID) on the stability of the BW-SPHs and their associated in vitro antidiabetic activity was investigated. The BW-SPHs contained between 70–74% (w/w) protein and all essential and non-essential amino acids. All BW-SPHs mediated DPP-IV inhibitory (IC50: 2.12–2.90 mg protein/mL) and insulin secretory activity (2.5 mg/mL; 4.7 to 6.4-fold increase compared to the basal control (5.6 mM glucose alone)). All BW-SPHs were further hydrolysed during SGID. While the in vitro DPP-IV inhibitory and insulin secretory activity mediated by some BW-SPHs was reduced following SGID, the activity remained high. In general, the insulin secretory activity of the BW-SPHs were 4.5–5.4-fold higher than the basal control following SGID. The BW-SPHs generated herein provide potential for anti-diabetic related functional ingredients, whilst also enhancing environmental and commercial sustainability.
Effect of Ultrasonic Excitation on Discharge Performance of a Button Zinc–Air Battery
Authors: Luo Zhao , Tang Qiang , Hu Junhui
Published: July 2021

In this paper, a method to increase the output power of a button zinc–air battery by applying acoustofluidics induced by ultrasonic excitation to the battery is proposed and demonstrated. In the structural design of the device, a flat piezoelectric ring was bonded onto the top of the outer surface of the cathode shell to excite an ultrasonic field in the battery. The maximum output power of the zinc–air battery increased by 46.8% when the vibration velocity and working frequency were 52.8 mm/s (the corresponding vibration amplitude was 277 nm) and 161.2 kHz and the rating capacity increased by about 20% with the assistance of the acoustofluidic field induced by ultrasonic excitation. Further analyses indicated that the discharge performance improvement can be attributed to the acoustic microstreaming vortices and the decrease of the viscosity coefficient in the electrolyte solution, which were both caused by ultrasonic excitation of the piezoelectric ring.
Leaching Behaviors of Calcium and Aluminum from an Ionic Type Rare Earth Ore Using MgSO4 as Leaching Agent
Authors: He Qiang , Qiu Jiang , Rao Minglu , Xiao Yanfei
Published: July 2021

During the leaching process of ionic rare earth ore (ICREO), ion-exchangeable phase calcium (IEP-Ca) and ion-exchangeable phase aluminum (IEP-Al) are leached along with rare earth, which causes many problems in the enrichment process, such as increasing the precipitant agent consumption and rare earth loss, etc. The agitation leaching kinetics and the column leaching mass transfer process of IEP-Ca and IEP-Al were studied to understand the leaching behavior of impurity in ICREO, which provides guides for the adjustment of the leaching process and to limit the co-leaching of impurities. IEP-Ca and IEP-Al were leached by ion exchange, with the leaching agent cations and the leaching kinetics described by an internal diffusion-controlled shrinking core model with an apparent activation energy of 8.97 kJ/mol and 10.48 kJ/mol, respectively. In addition, a significant reduction in the leaching efficiency of aluminum was caused by the hydrolysis reaction reinforced by the increase in MgSO4 concentration and temperature. The leaching kinetic data of IEP-Ca and IEP-Al was verified by the column leaching mass transfer process. There was a synchronous increase in the peak concentration of the outflow curve and leaching efficiency of calcium with the concentration of MgSO4 since IEP-Ca was easily leached. Therefore, as the leaching efficiency of calcium was already very high in the 0.20 mol/L MgSO4 leaching process, the leaching rate of calcium was limited by the leaching temperature and injection rate of MgSO4. For aluminum, the hydrolysis of Al3+ was promoted by increasing the MgSO4 concentration and the leaching temperature, thereby effectively reducing the content of aluminum in the leachate.
Immunoproteasome and Non-Covalent Inhibition: Exploration by Advanced Molecular Dynamics and Docking Methods
Authors: Culletta Giulia , Zappalà Maria , Ettari Roberta , Almerico Anna Maria , Tutone Marco
Published: July 2021

The selective inhibition of immunoproteasome is a valuable strategy to treat autoimmune, inflammatory diseases, and hematologic malignancies. Recently, a new series of amide derivatives as non-covalent inhibitors of the β1i subunit with Ki values in the low/submicromolar ranges have been identified. Here, we investigated the binding mechanism of the most potent and selective inhibitor, N-benzyl-2-(2-oxopyridin-1(2H)-yl)propanamide (1), to elucidate the steps from the ligand entrance into the binding pocket to the ligand-induced conformational changes. We carried out a total of 400 ns of MD-binding analyses, followed by 200 ns of plain MD. The trajectories clustering allowed identifying three representative poses evidencing new key interactions with Phe31 and Lys33 together in a flipped orientation of a representative pose. Further, Binding Pose MetaDynamics (BPMD) studies were performed to evaluate the binding stability, comparing 1 with four other inhibitors of the β1i subunit: N-benzyl-2-(2-oxopyridin-1(2H)-yl)acetamide (2), N-cyclohexyl-3-(2-oxopyridin-1(2H)-yl)propenamide (3), N-butyl-3-(2-oxopyridin-1(2H)-yl)propanamide (4), and (S)-2-(2-oxopyridin-1(2H)-yl)-N,4-diphenylbutanamide (5). The obtained results in terms of free binding energy were consistent with the experimental values of inhibition, confirming 1 as a lead compound of this series. The adopted methods provided a full dynamic description of the binding events, and the information obtained could be exploited for the rational design of new and more active inhibitors.
Cyanine-5-Driven Behaviours of Hyperbranched Polymers Designed for Therapeutic Delivery Are Cell-Type Specific and Correlated with Polar Lipid Distribution in Membranes
Authors: Simpson Joshua D. , Currin-Ross Denni L. , Ediriweera Gayathri R. , Schirra Horst Joachim , Fletcher Nicholas L. , Bell Craig A. , Arno Maria C. , Thurecht Kristofer J.
Published: July 2021

The ability to predict the behaviour of polymeric nanomedicines can often be obfuscated by subtle modifications to the corona structure, such as incorporation of fluorophores or other entities. However, these interactions provide an intriguing insight into how selection of molecular components in multifunctional nanomedicines contributes to the overall biological fate of such materials. Here, we detail the internalisation behaviours of polymeric nanomedicines across a suite of cell types and extrapolate data for distinguishing the underlying mechanics of cyanine-5-driven interactions as they pertain to uptake and endosomal escape. By correlating the variance of rate kinetics with endosomal escape efficiency and endogenous lipid polarity, we identify that observed cell-type dependencies correspond with an underlying susceptibility to dye-mediated effects and nanomedicine accumulation within polar vesicles. Further, our results infer that the ability to translocate endosomal membranes may be improved in certain cell types, suggesting a potential role for diagnostic moieties in trafficking of drug-loaded nanocarriers.
Ferromagnetic Resonance and Antiresonance in Composite Medium with Flakes of Finemet-Like Alloy
Authors: Perov Dmitry V. , Rinkevich Anatoly B.
Published: July 2021

Propagation of microwaves is studied in a composite material containing flakes of Fe-Si-Nb-Cu-B alloy placed into an epoxyamine matrix. The theory is worked out, which permits to calculate the coefficients of the dynamic magnetic permeability tensor and the effective magnetic permeability of the transversely magnetized composite. The measurements of magnetic field dependences of the transmission and reflection coefficients were carried out at frequencies from 12 to 38 GHz. Comparison between calculated and measured coefficients were conducted, which show that the calculation reproduces all main features of the resonance variations caused by ferromagnetic resonance and antiresonance. The dissipation of microwave power was calculated and measured. It is shown that the penetration depth of the electromagnetic field increases under antiresonance condition and decreases under resonance.
Infant Feeding and Ethnic Differences in Body Mass Index during Childhood: A Prospective Study
Authors: Sirkka Outi , Vrijkotte Tanja , Houtum Lieke van , Abrahamse-Berkeveld Marieke , Halberstadt Jutka , Olthof Margreet R. , Seidell Jacob C.
Published: July 2021

This study investigated ethnic differences in childhood body mass index (BMI) in children from Dutch and Turkish descent and the role of infant feeding factors (breastfeeding duration, milk feeding frequency, as well as the timing, frequency and variety of complementary feeding (CF)). We used data from 244 children (116 Dutch and 128 Turkish) participating in a prospective study in the Netherlands. BMI was measured at 2, 3 and 5 years and standard deviation scores (sds) were derived using WHO references. Using linear mixed regression analyses, we examined ethnic differences in BMI-sds between 2 and 5 years, and the role of infant feeding in separate models including milk or CF factors, or both (full model). Relative to Dutch children, Turkish children had higher BMI-sds at age 3 (mean difference: 0.26; 95%CI: 0.04, 0.48) and 5 (0.63; 0.39, 0.88), but not at 2 years (0.08; −0.16, 0.31). Ethnic differences in BMI-sds were somewhat attenuated by CF factors at age 3 (0.16; −0.07, 0.40) and 5 years (0.50; 0.24, 0.77), whereas milk feeding had a minor impact. Of all factors, only CF variety was associated with BMI-sds in the full model. CF factors, particularly CF variety, explain a small fraction of the BMI-sds differences between Dutch and Turkish children. The role of CF variety on childhood BMI requires further investigation.
The Relevance of Obesity for Activities of Daily Living in Geriatric Rehabilitation Patients
Authors: Wojzischke Julia , Bauer Jürgen M. , Hein Andreas , Diekmann Rebecca
Published: July 2021

The obesity pandemic has reached old age but the effect of obesity on functional recovery in geriatric rehabilitation patients has not been investigated to date. In this prospective cohort study, patients admitted into geriatric rehabilitation were consecutively included between September 2015 and September 2016, aged ≥70 years. Individual activities of daily living were documented by the Barthel index (BI, 0–100 points). Obesity was assessed by the measurement of body mass index (BMI, kg/m²), waist circumference (WC, cm) and percentage of body fat mass (%FM) based on triceps’ skinfold thickness at admission (t1), discharge (t2) and six months after discharge (t3). A total of 122 patients were included in the analysis. Prevalence of obesity according to BMI, WC and %FM was 33.6%, 83.6% and 71.3% respectively. Patients with a high WC and patients with a high BMI had lower BI values at t1, t2, t3 and the improvement in BI (t1–t2, t2–t3) was lower than in those with low WC and low BMI, but without statistical significance. In multiple regression analysis, BMI, WC and %FM were not associated with BI at t3 and improvement of BI (t2–t3). Obesity was highly prevalent in geriatric rehabilitation patients, but it was not associated with BI during the 6-month follow-up.
Do Bioactive Food Compound with Avena sativa L., Linum usitatissimum L. and Glycine max L. Supplementation with Moringa oleifera Lam. Have a Role against Nutritional Disorders? An Overview of the In Vitro and In Vivo Evidence
Authors: Ferreira Rosângela dos Santos , Mendonça Lígia Aurélio Bezerra Maranhão , Santos Cristiane dos , Hiane Priscila Aiko , Matias Rosemary , Franco Octávio Luiz , de Oliveira Ademir Kleber Morbeck , do Nascimento Valter Aragão , Pott Arnildo , Carvalho Cristiano Marcelo Espinola , Guimarães Rita de Cássia Avellaneda
Published: July 2021

Functional clinical nutrition is an integrative science; it uses dietary strategies, functional foods and medicinal plants, as well as combinations thereof. Both functional foods and medicinal plants, whether associated or not, form nutraceuticals, which can bring benefits to health, in addition to being included in the prevention and treatment of diseases. Some functional food effects from Avena sativa L. (oats), Linum usitatissimum L. (brown flaxseed), Glycine max L. (soya) and Moringa oleifera have been proposed for nutritional disorders through in vitro and in vivo tests. A formulation called a bioactive food compound (BFC) showed efficiency in the association of oats, flaxseed and soy for dyslipidemia and obesity. In this review, we discuss the effects of BFC in other nutritional disorders, as well as the beneficial effects of M. oleifera in obesity, cardiovascular disease, diabetes mellitus type 2, metabolic syndrome, intestinal inflammatory diseases/colorectal carcinogenesis and malnutrition. In addition, we hypothesized that a BFC enriched with M. oleifera could present a synergistic effect and play a potential benefit in nutritional disorders. The traditional consumption of M. oleifera preparations can allow associations with other formulations, such as BFC. These nutraceutical formulations can be easily accepted and can be used in sweet preparations (fruit and/or vegetable juices, fruit and/or vegetable vitamins, porridges, yogurt, cream, mousses or fruit salads, cakes and cookies) or savory (vegetable purees, soups, broths and various sauces), cooked or not. These formulations can be low-cost and easy-to-use. The association of bioactive food substances in dietary formulations can facilitate adherence to consumption and, thus, contribute to the planning of future nutritional interventions for the prevention and adjuvant treatment of the clinical conditions presented in this study. This can be extended to the general population. However, an investigation through clinical studies is needed to prove applicability in humans.
Serum Trace Element Levels and Their Correlation with Picky Eating Behavior, Development, and Physical Activity in Early Childhood
Authors: Chao Hsun-Chin , Lu Jang-Jih , Yang Chang-Yo , Yeh Pai-Jui , Chu Shih-Ming
Published: July 2021

Trace elements are vital components for healthy growth, development, and physical activity. The aim of this study was to investigate the relationship between trace element (iron, zinc, copper) deficiencies and picky eating behavior, development level, and physical activity level. This cross-sectional study involved 203 children aged 4–7 years; picky eating behavior, development level, and physical activity level were assessed through questionnaires. Zinc deficiency has the highest prevalence (37.4%); 67.5% of the children were assessed as picky eaters. Children with picky eating behaviors, poor development level, or poor physical activity level have significantly lower zinc levels, and higher prevalence of zinc deficiency. Pearson’s correlation coefficient indicated a positive correlation between serum zinc level and development scores (r = 0.221, p = 0.002) and physical activity scores (r = 0.469, p < 0.001). In multivariate analysis, zinc deficiency independently related to picky eating (OR = 2.124, p = 0.037, CI = 1.042–4.312), developmental level (OR = 0.893, p = 0.022, CI = 0.810–0.984), and physical activity level (OR = 0.785, p < 0.001, CI = 0.700–0.879). In conclusion, the prevalence of zinc deficiency in children aged 4–7 was high, especially in picky eaters. Zinc deficiency was significantly associated with low development and poor physical activity in early childhood.
The Effects of 12-Week Beta-Hydroxy-Beta-Methylbutyrate Supplementation in Patients with Liver Cirrhosis: Results from a Randomized Controlled Single-Blind Pilot Study
Authors: Lattanzi Barbara , Bruni Angelo , Di Cola Simone , Molfino Alessio , De Santis Adriano , Muscaritoli Maurizio , Merli Manuela
Published: July 2021

Background and Aim: Sarcopenia is considered an important risk factor for morbidity and mortality in liver cirrhosis. Beta-hydroxy-beta-methylbutyrate (HMB) has the potential to increase muscle mass and performance by stimulating protein synthesis and reducing muscle catabolism. The present study aimed at evaluating the effect of HMB supplementation on muscle mass and function in patients with liver cirrhosis. Changes in frailty during the study were also estimated, and the safety of HMB supplementation was verified. Methods: This is a randomized, single-blind, placebo-controlled pilot trial. Twenty-four patients (14 HMB and 10 placebo) affected by liver cirrhosis were enrolled in the study. Each patient received dedicated counseling, which included nutrition and physical activity recommendations for chronic liver disease patients. Patients were randomized to receive 3 g/day of HMB or placebo (sorbitol powder) for 12 consecutive weeks. A diet interview, anthropometry, electrical bioimpedance analysis (BIA), quadriceps ultrasound, physical performance battery, Liver Frailty Index (LFI), and cognitive tests were completed at enrolment (T0), at 12 weeks (T1), and 24 weeks after enrolment (T2). Results: At baseline, the two groups were similar in demography, severity of liver disease, muscle mass, muscle function, and cognitive tests. LFI at baseline was higher in patients in the HMB group vs. those in the placebo group (4.1 ± 0.4 vs. 3.4 ± 0.6, p < 0.01). After treatment, a statistically significant increase in muscle function was seen in the HMB group (chair stand test: 14.2 ± 5 s vs. 11.7 ± 2.6 s, p < 0.05; six-minute walk test: 361.8 ± 68 m vs. 409.4 ± 58 m, p < 0.05). Quadriceps muscle mass measured by ultrasound also increased (4.9 ± 1.8 vs. 5.4 ± 1.8 mm, p < 0.05) after HMB, while LFI decreased (4.1 ± 0.4 vs. 3.7 ± 0.4, p < 0.05). HMB was well tolerated by patients, and no adverse events were documented. Conclusions: Our study suggests the efficacy of 12-week beta-hydroxy-beta-methylbutyrate supplementation in promoting improvements in muscle performance in compensated cirrhotic patients. LFI was also ameliorated. Further studies with a greater number of patients are required to reinforce this hypothesis.
Pet Pyometra: Correlating Bacteria Pathogenicity to Endometrial Histological Changes
Authors: Lopes Cassiane Elisabete , De Carli Silvia , Riboldi Camila Imperico , De Lorenzo Cíntia , Panziera Welden , Driemeier David , Siqueira Franciele Maboni
Published: July 2021

Pyometra is a life-threatening infectious disease that frequently affects bitches and queens. Although histopathological patterns of pyometra have been extensively explored, the microbiological aspects, such as bacteria pathogenicity, have not been correlated to microscopy endometrial lesions so far. In this study, these two pathological aspects of pyometra were analysed and correlated. Uterus fragments and intrauterine content samples were collected from pets diagnosed with pyometra (30) and submitted to histopathology analysis and bacterial culture, respectively. The degree of endometrial histopathological lesions in pyometra cases were classified as mild, moderate and severe. Thirty different bacteria isolates were identified from intrauterine content culture. Escherichia coli (E. coli) was pure isolated in 57.7% and highly related to severe endometrial lesions. Immunohistochemistry assay revealed the adhesion and invasion of this bacteria agent to the injured endometrium. Virulence aspects of these E. coli strains were explored, demonstrating biofilm formation ability and a set of virulence genes in most isolates. These results support the adaptive genetic and phenotypic advantages of E. coli for uterus infection, and justify the high frequency of this agent involved in pyometra cases.
Investigation of the Genomic and Pathogenic Features of the Potentially Zoonotic Streptococcus parasuis
Authors: Wang Jianping , Yi Xueli , Liang Pujun , Tao Yuanmeihui , Wang Yan , Jin Dong , Luo Bin , Yang Jing , Zheng Han
Published: July 2021

Recently, Streptococcus suis reference strains of serotype 20, 22, and 26 were reclassified as Streptococcus parasuis. The public health significance of S. parasuis is underestimated due to the lack of clinical isolates. In the present study, we first reported two sporadic S. parasuis infections in humans, after using full-length 16S rRNA and housekeeping genes’ phylogeny and ANI values of genome sequence comparisons to determine the species of their isolates BS26 and BS27. Compared to highly pathogenic S. suis strain P1/7, S. parasuis strains BS26 and BS27 possessed a delayed capacity to initiate lethal infection, which may attribute to the later production of higher level of pro-inflammatory cytokines. Differed to S. suis strain P1/7, S. parasuis strains did not induce significant inflammatory response in the brain of mice. Histopathological changes in liver and lungs were widely present in mice infected with S. parasuis strains. Our data indicated that the pathogenic mechanism of S. parasuis may be different from that of S. suis. Three lineages in the core-genome phylogenetic tree and ten types of cps gene cluster were found in 13 S. parasuis genomes, indicating high heterogeneity of this species. The similarity of CPS structure and antibiotic-resistant genes relative to S. suis indicated the evolutionary affinity between the two species. Our data suggested S. parasuis is a potential zoonotic pathogen and poses severe threat to health of susceptible people. Further study on the epidemiology and public health significance of S. parasuis is urgently necessary.
Development of Dual ARV-825 and Nintedanib-Loaded PEGylated Nano-Liposomes for Synergistic Efficacy in Vemurafnib-Resistant Melanoma
Authors: Fu Yige , Saraswat Aishwarya , Wei Zenghui , Agrawal Manas Yogendra , Dukhande Vikas V. , Reznik Sandra E. , Patel Ketan
Published: July 2021

A novel treatment strategy by co-targeting c-Myc and tumor stroma was explored in vemurafenib-resistant melanoma. BRD4 proteolysis targeting chimera (ARV-825) and nintedanib co-loaded PEGylated nanoliposomes (ARNIPL) were developed to incorporate a synergistic cytotoxic ratio. Both the molecules have extremely poor aqueous solubility. A modified hydration method with citric acid was used to improve the loading of both the molecules in liposomes. ARNIPL with mean particle size 111.1 ± 6.55 nm exhibited more than 90% encapsulation efficiency for both the drugs and was found to be physically stable for a month at 4 °C. Both the molecules and ARNIPL showed significantly higher cytotoxicity, apoptosis and down-regulation of target proteins BRD4 and c-Myc in vemurafenib-resistant cell line (A375R). Vasculogenic mimicry and clonogenic potential of A375R were significantly inhibited by ARNIPL. Tumor growth inhibition in 3D spheroids with reduction of TGF-β1 was observed with ARNIPL treatment. Therefore, ARNIPL could be a promising therapeutic approach for the treatment of vemurafenib-resistant melanoma.
Peptide Allergen Immunotherapy: A New Perspective in Olive-Pollen Allergy
Authors: Calzada David , Cremades-Jimeno Lucía , López-Ramos María , Cárdaba Blanca
Published: July 2021

Allergic diseases are highly prevalent disorders, mainly in industrialized countries where they constitute a high global health problem. Allergy is defined as an immune response “shifted toward a type 2 inflammation” induced by the interaction between the antigen (allergen) and IgE antibodies bound to mast cells and basophils that induce the release of inflammatory mediators that cause the clinical symptoms. Currently, allergen-specific immunotherapy (AIT) is the only treatment able to change the course of these diseases, modifying the type 2 inflammatory response by an allergenic tolerance, where the implication of T regulatory (Treg) cells is considered essential. The pollen of the olive tree is one of the most prevalent causes of respiratory allergic diseases in Mediterranean countries, inducing mainly nasal and conjunctival symptoms, although, in areas with a high antigenic load, olive-tree pollen may cause asthma exacerbation. Classically, olive-pollen allergy treatment has been based on specific immunotherapy using whole-olive pollen extracts. Despite extracts standardization, the effectiveness of this strategy varies widely, therefore there is a need for more effective AIT approaches. One of the most attractive is the use of synthetic peptides representing the B- or T-cell epitopes of the main allergens. This review summarizes experimental evidence of several T-cell epitopes derived from the Ole e 1 sequence to modulate the response to olive pollen in vitro, associated with several possible mechanisms that these peptides could be inducing, showing their usefulness as a safe preventive tool for these complex diseases.
Clinical Advances of siRNA-Based Nanotherapeutics for Cancer Treatment
Authors: Hattab Dima , Gazzali Amirah Mohd , Bakhtiar Athirah
Published: July 2021

Cancer is associated with single or multiple gene defects. Recently, much research has focused on incorporating genetic materials as one of the means to treat various types of carcinomas. RNA interference (RNAi) conveys an alternative genetic approach for cancer patients, especially when conventional medications fail. RNAi involves the inhibition of expression of specific messenger RNA that signals for uncontrollable cell growth and proliferation, most notably with carcinoma cells. This molecular technology is promising as genetic materials allow us to overcome issues associated with chemotherapeutic agents including organ damage associated with severe drug toxicities. Nonetheless, vast challenges impede successful gene therapy application, including low tumor localization, low stability and rapid clearance from the blood circulation. Owing to the limited treatment opportunities for the management of cancer, the development of effective siRNA carrier systems involving nanotherapeutics has been extensively explored. Over the past years, several siRNA nanotherapeutics have undergone a period of clinical investigation, with some demonstrating promising antitumor activities and safety profiles. Extensive observation of siRNA-nanoparticles is necessary to ensure commercial success. Therefore, this review mainly focuses on the progress of siRNAs-loaded nanoparticles that have undergone clinical trials for cancer treatment. The status of the siRNA nanotherapeutics is discussed, allowing comprehensive understanding of their gene-mediated therapeutics.