bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of Cognitive Function and Interleukin 1 Beta Serum Concentrations Following Cardiac Pacemaker Implantation in Patients with Symptomatic Bradycardia
Authors: Martis Alexandru , Gusetu Gabriel , Cismaru Gabriel , Zdrenghea Dumitru , Leucuta Daniel-Corneliu , Pop Dana
Published: August 2021

Background and aim: Bradyarrhythmias cause a low cerebral blood flow with secondary neuronal ischemia and cognitive dysfunction. This study aims to assess the effect of cardiac pacemaker implantation (PI) on the cognitive function and inflammatory markers (TNF alpha, IL1β). Material and method: We conducted a prospective observational study on a number of 31 patients with symptomatic bradyarrhythmias. We performed the cognitive function assessment by two tests (Mini-Mental State Examination and Trail Making Test A), cardiac output assessment (echocardiographic), and determination of IL 1β and TNF alpha serum concentrations before pacemaker implantation and after an average period of 42 days from pacemaker implantation.Results: After pacemaker implantation we observed an increase in the cardiac index by 0.71 L/min/m2 (p < 0.001) and a better scoring in cognitive performance; the mean MMSE score increased by two points (p < 0.001), and Trail Making Test A had an improvement of 16 s (p < 0.001). Regarding the inflammatory markers, a significant decrease in IL-1β with 8.6 pg/mL (p = 0.049) after pacemaker implantation was observed. Additionally, we found statistically significant correlations between IL1β and TNF alpha (positive correlation, p = 0.005), between the MMSE and cardiac index (p < 0.001), between the Trail Making Test and cardiac index (p = 0.001), and between the MMSE and Trail Making Test (p = 0.003). Conclusions: Our findings suggest that cardiac pacemaker implantation was associated with improved cognitive function—possibly related to an increased cardiac output and with adecreased serum IL1β concentration in subjects with symptomatic bradycardia.
Formative and Summative Validation of Building Information Model-Based Cadastral Data
Authors: Asghari Ali , Kalantari Mohsen , Rajabifard Abbas
Published: August 2021

Among 3D models, Building Information Models (BIM) can potentially support the integrated management of buildings’ physical and legal aspects in cadastres. However, there is not a systematic approach to author the cadastral information into the BIM models. Moreover, the common approaches for data validation only check the final cadastral output, and they ignore the data generation steps as potential avenues for validation. Therefore, this study aims to develop the criteria and standards to check the spatial consistency and integrity of BIM-based cadastral data in the process of generating the data. The paper utilises a case study approach as its methodology to investigate the requirements of generating a BIM-based cadastral model and identify the issues within the process. The results include a formative assessment (i.e., multistep validation approach during the data generation) alongside a summative assessment (i.e., one-step validation approach at the end of data generation). This study found the summative assessment alone insufficient for 3D cadastral data validation. The paper concludes that a formative and summative assessment together can improve the validity of the data. The results will potentially bring more efficiency to modern land administration processes by avoiding the accumulation of errors in 3D cadastral data generation.
2-Diphenylphosphinomethyl-3-methylpyrazine
Authors: Boccuzzi Tiziana , Cicco Luciana , Quivelli Andrea Francesca , Vitale Paola , Perna Filippo Maria , Karaghiosoff Konstantin , Capriati Vito
Published: August 2021

The lateral metalation-electrophilic trapping reaction of alkyl-substituted pyrazines has always been challenging and poorly regioselective, with the corresponding derivatives often being isolated in moderate yield. In this contribution, we first report on the preparation of an unsymmetrically-substituted pyrazine, that is 2-diphenylphosphinomethyl-3-methylpyrazine, by subjecting to metalation with n-BuLi the commercially available 2,3-dimethylpyrazine, followed by interception of the putative lithiated benzyl-type intermediate with Ph2PCl. Such a functionalization has been successfully carried out in the absence of additional ligands, working either in THF at −78 °C or in a more environmentally friendly solvent like cyclopentyl methyl ether at 0 °C, with the desired phosphine derivative being isolated in 70–85% yield. The newly synthesized adduct has been fully characterized by means of multinuclear magnetic resonance spectroscopic techniques, and also by preparing a selenium derivative, which furnished single crystals that were suitable for X-ray analysis.
Multi-Objective Optimization and Performance Characterization of Asphalt Modified by Nanocomposite Flame-Retardant Based on Response Surface Methodology
Authors: Li Jiaqi , He Zhaoyi , Yu Le , He Lian , Shen Zuzhen
Published: August 2021

In order to improve the safety of the tunnel asphalt pavement in the event of a fire, and reduce the deterioration of the low temperature crack resistance of the asphalt by the flame retardant. The research uses aluminum hydroxide (ATH) as a smoke suppressant, diethyl aluminum hypophosphite (ADP) as a flame retardant, and halloysite nanotubes (HNTs) as a synergist to modified styrene-butadiene-styrene block copolymer (SBS) modified asphalt (MA). First, the content of ATH, ADP, and HNTs was used as the response variable. The physical properties (Penetration, Softening point, Ductility) and static flame retardant properties (Limiting oxygen index meter, Ignition point) of the asphalt modified by nanocomposite flame-retardant (HNTs-CFRMA) were the response variables. The response surface methodology was used to design the test, and regression models were established to analyze the influence of flame retardants on the performance of asphalt. Then, comprehensively considering the effects of physical properties and flame retardant properties, the normalized desirability function was used to perform a multi-objective optimization design on the components of the nanocomposite flame retardant modifier to obtain the best flame retardant formula. Finally, the rheological properties of MA, conventional flame-retardant modified asphalt (CFRMA), and HNTs-CFRMA were tested based on Dynamic shear rheometer, Multiple stress creep test, Force ductility tester, and Bending beam rheometer. The performance of flame-retardant and smoke suppression were tested by the Cone calorimeter tests. The result shows that ATH, ADP, and HNTs can enhance the high temperature performance of asphalt, reduce the penetration. The addition of HNTs can increase significantly the softening point and reduce the deteriorating effect of flame retardants on the low temperature performance of asphalt; the addition of ATH and HNTs can improve significantly the flame retardancy of asphalt. Based on the desirability function of power exponent, the formulation of the nanocomposite flame retardant with better physical properties and flame retardant properties is ATH:ADP:HNTs = 3:5:1, and the total content is 9 wt%. Nanocomposite flame retardants can improve obviously the high temperature rheological properties of asphalt. The rutting factor and the cracking factor of HNTs-CFRMA improve markedly, and the irrecoverable creep compliance is reduced, compared with MA and CFRMA. Nanocomposite flame retardant can make up for the deterioration of conventional flame retardants on asphalt’s low temperature performance. At the same time, it has better flame-retardant performance and smoke suppression performance.
MAPbI3 Microrods-Based Photo Resistor Switches: Fabrication and Electrical Characterization
Authors: Raza Ehsan , Aziz Fakhra , Mishra Arti , Al-Thani Noora Jabor , Ahmad Zubair
Published: August 2021

The current work proposed the application of methylammonium lead iodide (MAPbI3) perovskite microrods toward photo resistor switches. A metal-semiconductor-metal (MSM) configuration with a structure of silver-MAPbI3(rods)-silver (Ag/MAPbI3/Ag) based photo-resistor was fabricated. The MAPbI3 microrods were prepared by adopting a facile low-temperature solution process, and then an independent MAPbI3 microrod was employed to the two-terminal device. The morphological and elemental compositional studies of the fabricated MAPbI3 microrods were performed using FESEM and EDS, respectively. The voltage-dependent electrical behavior and electronic conduction mechanisms of the fabricated photo-resistors were studied using current–voltage (I–V) characteristics. Different conduction mechanisms were observed at different voltage ranges in dark and under illumination. In dark conditions, the conduction behavior was dominated by typical trap-controlled charge transport mechanisms within the investigated voltage range. However, under illumination, the carrier transport is dominated by the current photogenerated mechanism. This study could extend the promising application of perovskite microrods in photo-induced resistor switches and beyond.
Classification of Explainable Artificial Intelligence Methods through Their Output Formats
Authors: Vilone Giulia , Longo Luca
Published: August 2021

Machine and deep learning have proven their utility to generate data-driven models with high accuracy and precision. However, their non-linear, complex structures are often difficult to interpret. Consequently, many scholars have developed a plethora of methods to explain their functioning and the logic of their inferences. This systematic review aimed to organise these methods into a hierarchical classification system that builds upon and extends existing taxonomies by adding a significant dimension—the output formats. The reviewed scientific papers were retrieved by conducting an initial search on Google Scholar with the keywords “explainable artificial intelligence”; “explainable machine learning”; and “interpretable machine learning”. A subsequent iterative search was carried out by checking the bibliography of these articles. The addition of the dimension of the explanation format makes the proposed classification system a practical tool for scholars, supporting them to select the most suitable type of explanation format for the problem at hand. Given the wide variety of challenges faced by researchers, the existing XAI methods provide several solutions to meet the requirements that differ considerably between the users, problems and application fields of artificial intelligence (AI). The task of identifying the most appropriate explanation can be daunting, thus the need for a classification system that helps with the selection of methods. This work concludes by critically identifying the limitations of the formats of explanations and by providing recommendations and possible future research directions on how to build a more generally applicable XAI method. Future work should be flexible enough to meet the many requirements posed by the widespread use of AI in several fields, and the new regulations.
Approximating Solutions of Non-Linear Troesch’s Problem via an Efficient Quasi-Linearization Bessel Approach
Authors: Izadi Mohammad , Yüzbaşi Şuayip , Noeiaghdam Samad
Published: August 2021

Two collocation-based methods utilizing the novel Bessel polynomials (with positive coefficients) are developed for solving the non-linear Troesch’s problem. In the first approach, by expressing the unknown solution and its second derivative in terms of the Bessel matrix form along with some collocation points, the governing equation transforms into a non-linear algebraic matrix equation. In the second approach, the technique of quasi-linearization is first employed to linearize the model problem and, then, the first collocation method is applied to the sequence of linearized equations iteratively. In the latter approach, we require to solve a linear algebraic matrix equation in each iteration. Moreover, the error analysis of the Bessel series solution is established. In the end, numerical simulations and computational results are provided to illustrate the utility and applicability of the presented collocation approaches. Numerical comparisons with some existing available methods are performed to validate our results.
Multiple Criteria Decision Analysis of Sustainable Urban Public Transport Systems
Authors: Romero-Ania Alberto , Rivero Gutiérrez Lourdes , De Vicente Oliva María Auxiliadora
Published: August 2021

Urban public transport systems must be economically efficient and additionally environmentally sustainable. Available decision support systems, including multiple criteria decision models, allow identifying which urban public transport vehicles are acceptable and those that should no longer be used in efficient and environmentally friendly cities. Previous research has ranked urban public transport vehicles by applying analytic hierarchy process multi-criteria decision-making models, from economic and non-polluting perspectives. However, until now, the types of vehicles acceptable for fleet renewal have not been identified. This study proposes a consistent combination of the ELECTRE TRI multiple criteria decision sorting method and the DELPHI procedure, the objective of which is to identify which urban public transport vehicles are acceptable, taking into consideration a suggested sustainable threshold, which includes economic and environmental strict requirements. The proposed model is based on 2020 Madrid urban public road transport data, published by Madrid City Council, which were compiled by the authors, and assessed by a panel of 20 experts to identify criteria and factors included in the model. Findings help local administrations to identify which urban public transport vehicles should be progressively replaced by those classified as economically efficient and additionally environmentally sustainable.
Existence of Nontrivial Solutions for Sixth-Order Differential Equations
Authors: Bonanno Gabriele , Candito Pasquale , O’Regan Donal
Published: August 2021

We show the existence of at least one nontrivial solution for a nonlinear sixth-order ordinary differential equation is investigated. Our approach is based on critical point theory.
Herb–Drug Interactions: Worlds Intersect with the Patient at the Center
Authors: Babos Mary , Heinan Michelle , Redmond Linda , Moiz Fareeha , Souza-Peres Joao , Samuels Valerie , Masimukku Tarun , Hamilton David , Khalid Myra , Herscu Paul
Published: August 2021

This review examines three bodies of literature related to herb–drug interactions: case reports, clinical studies, evaluations found in six drug interaction checking resources. The aim of the study is to examine the congruity of resources and to assess the degree to which case reports signal for further study. A qualitative review of case reports seeks to determine needs and perspectives of case report authors. Methods: Systematic search of Medline identified clinical studies and case reports of interacting herb–drug combinations. Interacting herb–drug pairs were searched in six drug interaction resources. Case reports were analyzed qualitatively for completeness and to identify underlying themes. Results: Ninety-nine case-report documents detailed 107 cases. Sixty-five clinical studies evaluated 93 mechanisms of interaction relevant to herbs reported in case studies, involving 30 different herbal products; 52.7% of these investigations offered evidence supporting reported reactions. Cohen’s kappa found no agreement between any interaction checker and case report corpus. Case reports often lacked full information. Need for further information, attitudes about herbs and herb use, and strategies to reduce risk from interaction were three primary themes in the case report corpus. Conclusions: Reliable herb–drug information is needed, including open and respectful discussion with patients.
Model Based Simulation and Genetic Algorithm Based Optimisation of Spiral Wound Membrane RO Process for Improved Dimethylphenol Rejection from Wastewater
Authors: Al-Obaidi Mudhar A. , Ruiz-García Alejandro , Hassan Ghanim , Li Jian-Ping , Kara-Zaïtri Chakib , Nuez Ignacio , Mujtaba Iqbal M.
Published: August 2021

Reverse Osmosis (RO) has already proved its worth as an efficient treatment method in chemical and environmental engineering applications. Various successful RO attempts for the rejection of organic and highly toxic pollutants from wastewater can be found in the literature over the last decade. Dimethylphenol is classified as a high-toxic organic compound found ubiquitously in wastewater. It poses a real threat to humans and the environment even at low concentration. In this paper, a model based framework was developed for the simulation and optimisation of RO process for the removal of dimethylphenol from wastewater. We incorporated our earlier developed and validated process model into the Species Conserving Genetic Algorithm (SCGA) based optimisation framework to optimise the design and operational parameters of the process. To provide a deeper insight of the process to the readers, the influences of membrane design parameters on dimethylphenol rejection, water recovery rate and the level of specific energy consumption of the process for two different sets of operating conditions are presented first which were achieved via simulation. The membrane parameters taken into consideration include membrane length, width and feed channel height. Finally, a multi-objective function is presented to optimise the membrane design parameters, dimethylphenol rejection and required energy consumption. Simulation results affirmed insignificant and significant impacts of membrane length and width on dimethylphenol rejection and specific energy consumption, respectively. However, these performance indicators are negatively influenced due to increasing the feed channel height. On the other hand, optimisation results generated an optimum removal of dimethylphenol at reduced specific energy consumption for a wide sets of inlet conditions. More importantly, the dimethylphenol rejection increased by around 2.51% to 98.72% compared to ordinary RO module measurements with a saving of around 20.6% of specific energy consumption.
Molecular Dynamics Study of Bulk Properties of Polycrystalline NiTi
Authors: Lee Jeongwoo , Shin Yung C.
Published: August 2021

Molecular dynamics (MD) simulations were carried out to study the bulk polycrystalline properties of NiTi. Thermally driven phase transitions of NiTi between martensite and austenitewere simulated using single crystalline simulation domains. With external stress boundary conditions, MD simulation successfully predicted experimentally observed phase transformation temperatures of bulk polycrystalline. Elastic characteristics of NiTi martensite were simulated using polycrystalline simulation domains that consist of realistic disorientations and grain boundary structures. The existence of grain disorientation and grain boundary lowered the potential energy of the simulation domain, which led to more realistic elastic modulus prediction. Analysis of simulation domains that predicted realistic bulk polycrystalline properties showed that the major difference between single crystalline and polycrystalline structures is atomic stress distribution.
Hot Deformation Behaviors of as Cast 321 Austenitic Stainless Steel
Authors: Zhao Deli , Ren Liguo , Wang Yong , Wang Wei , Zhu Zhe , Fu Wantang
Published: August 2021

AISI 321 stainless steel has excellent resistance to intergranular corrosion and is generally used in nuclear power reactor vessels and other components. The as-cast and wrought structures are quite different in hot workability, so physical simulation, electron back-scatter diffraction, and hot processing maps were used to study the mechanical behavior and microstructure evolution of as-cast nuclear grade 321 stainless steel in the temperature range of 900–1200 °C and strain rate range of 0.01–10 s−1. The results showed that the flow curve presented work-hardening characteristics. The activation energy was calculated as 478 kJ/mol. The fraction of dynamic recrystallization (DRX) increased with increasing deformation temperature and decreasing strain rate. DRX grain size decreased with increasing Z value. Combining the hot working map and DRX state map, the suggested hot working window was 1000–1200 °C and 0.01–0.1 s−1. The main form of instability was necklace DRX. The nucleation mechanism of DRX was the migration of subgrains. The δ phase reduced the activation energy and promoted DRX nucleation of the tested steel.
Coordinated Diel Gene Expression of Cyanobacteria and Their Microbiome
Authors: Wang Kai , Mou Xiaozhen
Published: August 2021

Diel rhythms have been well recognized in cyanobacterial metabolisms. However, whether this programmed activity of cyanobacteria could elicit coordinated diel gene expressions in microorganisms (microbiome) that co-occur with cyanobacteria and how such responses in turn impact cyanobacterial metabolism are unknown. To address these questions, a microcosm experiment was set up using Lake Erie water to compare the metatranscriptomic variations of Microcystis cells alone, the microbiome alone, and these two together (whole water) over two day-night cycles. A total of 1205 Microcystis genes and 4779 microbiome genes exhibited significant diel expression patterns in the whole-water microcosm. However, when Microcystis and the microbiome were separated, only 515 Microcystis genes showed diel expression patterns. A significant structural change was not observed for the microbiome communities between the whole-water and microbiome microcosms. Correlation analyses further showed that diel expressions of carbon, nitrogen, phosphorous, and micronutrient (iron and vitamin B12) metabolizing genes were significantly coordinated between Microcystis and the microbiome in the whole-water microcosm. Our results suggest that diel fluxes of organic carbon and vitamin B12 (cobalamin) in Microcystis could cause the diel expression of microbiome genes. Meanwhile, the microbiome communities may support the growth of Microcystis by supplying them with recycled nutrients, but compete with Microcystis for iron.
Carbon Mineralization with North American PGM Mine Tailings—Characterization and Reactivity Analysis
Authors: Woodall Caleb M. , Lu Xueya , Dipple Gregory , Wilcox Jennifer
Published: August 2021

Global efforts to combat climate change call for methods to capture and store CO2. Meanwhile, the global transition away from fossil energy will result in increased production of tailings (i.e., wastes) from the mining of nickel and platinum group metals (PGMs). Through carbon mineralization, CO2 can be permanently stored in calcium- and magnesium-bearing mine tailings. The Stillwater mine in Nye, Montana produces copper, nickel, and PGMs, along with 1 Mt of tailings each year. Stillwater tailings samples have been characterized, revealing that they contain a variety of mineral phases, most notably Ca-bearing plagioclase feldspar. Increases in inorganic carbon in the tailings and ion concentration in the tailings storage facilities suggest carbonation has taken place at ambient conditions over time within the tailings storage facilities. Two experiments were performed to simulate carbon mineralization at ambient temperature and pressure with elevated CO2 concentration (10% with N2), revealing that less than 1% of the silicate-bound calcium within the tailings is labile, or easily released from silicate structures at low-cost ambient conditions. The Stillwater tailings could be useful for developing strategies of waste management as production of nickel and PGM minerals increases during the global transition away from fossil energy, but further work is needed to develop a process that can realize their full carbon storage potential.
A Simple Method for Evaluating the Bioactive Phenolic Compounds’ Presence in Brazilian Craft Beers
Authors: Silva Marcelo Coelho , dos Anjos Jeancarlo Pereira , Guarieiro Lilian Lefol Nani , Machado Bruna A. Souza
Published: August 2021

There are a significant number of analytical methodologies employing different techniques to determine phenolic compounds in beverages. However, these methods employ long sample preparation processes and great time consumption. The aim of this paper was the development of a simple method for evaluating the phenolic compounds’ presence in Brazilian craft beers without a previous extraction step. Catechin, caffeic acid, epicatechin, p-coumaric acid, hydrated rutin, trans-ferulic acid, quercetin, kaempferol, and formononetin were analyzed in fifteen different craft beers. The method showed good linearity (R2 ≥ 0.9966). The limit of detection ranged from 0.08 to 0.83 mg L−1, and limits of quantification were between 0.27 and 2.78 mg L−1. The method showed a satisfactory precision (RSD ≤ 16.2%). A good accuracy was obtained by the proposed method for all phenolic compounds in craft beer (68.6% ˂ accuracy ˂ 112%). Catechin showed higher concentrations (up to 124.8 mg L−1) in the samples, followed by epicatechin (up to 51.1 mg L−1) and caffeic acid (up to 8.13 mg L−1). Rutin and formononetin were observed in all analyzed samples (0.52 mg L−1 to 2.40 mg L−1), and kaempferol was less present in the samples. The presence of plant origin products was determinant for the occurrence of the highest concentrations of phenolic compounds in Brazilian craft beers.
Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin
Authors: Abdelrahman Sherin , Alghrably Mawadda , Campagna Marcello , Hauser Charlotte Armgard Emma , Jaremko Mariusz , Lachowicz Joanna Izabela
Published: August 2021

Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells, as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is enhanced in the presence of copper ions.
Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα
Authors: Reddi Kiran , Li Hanxuan , Li Wei , Tetali Sarada
Published: August 2021

Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders.
New Insights on the Interaction of Phenanthroline Based Ligands and Metal Complexes and Polyoxometalates with Duplex DNA and G-Quadruplexes
Authors: Sánchez-González Ángel , Bandeira Nuno A. G. , Ortiz de Luzuriaga Iker , Martins Frederico F. , Elleuchi Sawssen , Jarraya Khaled , Lanuza Jose , Lopez Xabier , Calhorda Maria José , Gil Adrià
Published: August 2021

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.
Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, Fusobacterium nucleatum
Authors: Toole Jamie , Bolt Hannah L. , Marley John J. , Patrick Sheila , Cobb Steven L. , Lundy Fionnuala T.
Published: August 2021

Peptoids (oligo N-substituted glycines) are peptide analogues, which can be designed to mimic host antimicrobial peptides, with the advantage that they are resistant to proteolytic degradation. Few studies on the antimicrobial efficacy of peptoids have focused on Gram negative anaerobic microbes associated with clinical infections, which are commonly recalcitrant to antibiotic treatment. We therefore studied the cytotoxicity and antibiofilm activity of a family of peptoids against the Gram negative obligate anaerobe Fusobacterium nucleatum, which is associated with infections in the oral cavity. Two peptoids, peptoid 4 (NaeNpheNphe)4 and peptoid 9 (NahNspeNspe)3 were shown to be efficacious against F. nucleatum biofilms at a concentration of 1 μM. At this concentration, peptoids 4 and 9 were not cytotoxic to human erythrocytes or primary human gingival fibroblast cells. Peptoids 4 and 9 therefore have merit as future therapeutics for the treatment of oral infections.
Dissections of Larval, Pupal and Adult Butterfly Brains for Immunostaining and Molecular Analysis
Authors: Toh Yi Peng , Dion Emilie , Monteiro Antónia
Published: August 2021

Butterflies possess impressive cognitive abilities, and investigations into the neural mechanisms underlying these abilities are increasingly being conducted. Exploring butterfly neurobiology may require the isolation of larval, pupal, and/or adult brains for further molecular and histological experiments. This procedure has been largely described in the fruit fly, but a detailed description of butterfly brain dissections is still lacking. Here, we provide a detailed written and video protocol for the removal of Bicyclus anynana adult, pupal, and larval brains. This species is gradually becoming a popular model because it uses a large set of sensory modalities, displays plastic and hormonally controlled courtship behaviour, and learns visual mate preference and olfactory preferences that can be passed on to its offspring. The extracted brain can be used for downstream analyses, such as immunostaining, DNA or RNA extraction, and the procedure can be easily adapted to other lepidopteran species and life stages.
Review of ZnO Binary and Ternary Composite Anodes for Lithium-Ion Batteries
Authors: Bui Vu Khac Hoang , Pham Tuyet Nhung , Hur Jaehyun , Lee Young-Chul
Published: August 2021

To enhance the performance of lithium-ion batteries, zinc oxide (ZnO) has generated interest as an anode candidate owing to its high theoretical capacity. However, because of its limitations such as its slow chemical reaction kinetics, intense capacity fading on potential cycling, and low rate capability, composite anodes of ZnO and other materials are manufactured. In this study, we introduce binary and ternary composites of ZnO with other metal oxides (MOs) and carbon-based materials. Most ZnO-based composite anodes exhibit a higher specific capacity, rate performance, and cycling stability than a single ZnO anode. The synergistic effects between ZnO and the other MOs or carbon-based materials can explain the superior electrochemical characteristics of these ZnO-based composites. This review also discusses some of their current limitations.
Membrane-Interacting DNA Nanotubes Induce Cancer Cell Death
Authors: Kocabey Samet , Ekim Kocabey Aslihan , Schneiter Roger , Rüegg Curzio
Published: August 2021

DNA nanotechnology offers to build nanoscale structures with defined chemistries to precisely position biomolecules or drugs for selective cell targeting and drug delivery. Owing to the negatively charged nature of DNA, for delivery purposes, DNA is frequently conjugated with hydrophobic moieties, positively charged polymers/peptides and cell surface receptor-recognizing molecules or antibodies. Here, we designed and assembled cholesterol-modified DNA nanotubes to interact with cancer cells and conjugated them with cytochrome c to induce cancer cell apoptosis. By flow cytometry and confocal microscopy, we observed that DNA nanotubes efficiently bound to the plasma membrane as a function of the number of conjugated cholesterol moieties. The complex was taken up by the cells and localized to the endosomal compartment. Cholesterol-modified DNA nanotubes, but not unmodified ones, increased membrane permeability, caspase activation and cell death. Irreversible inhibition of caspase activity with a caspase inhibitor, however, only partially prevented cell death. Cytochrome c-conjugated DNA nanotubes were also efficiently taken up but did not increase the rate of cell death. These results demonstrate that cholesterol-modified DNA nanotubes induce cancer cell death associated with increased cell membrane permeability and are only partially dependent on caspase activity, consistent with a combined form of apoptotic and necrotic cell death. DNA nanotubes may be further developed as primary cytotoxic agents, or drug delivery vehicles, through cholesterol-mediated cellular membrane interactions and uptake.
An Interface Heterostructure of NiO and CeO2 for Using Electrolytes of Low-Temperature Solid Oxide Fuel Cells
Authors: Li Junjiao , Xie Jun , Li Dongchen , Yu Lei , Xu Chaowei , Yan Senlin , Lu Yuzheng
Published: August 2021

Interface engineering can be used to tune the properties of heterostructure materials at an atomic level, yielding exceptional final physical properties. In this work, we synthesized a heterostructure of a p-type semiconductor (NiO) and an n-type semiconductor (CeO2) for solid oxide fuel cell electrolytes. The CeO2-NiO heterostructure exhibited high ionic conductivity of 0.2 S cm−1 at 530 °C, which was further improved to 0.29 S cm−1 by the introduction of Na+ ions. When it was applied in the fuel cell, an excellent power density of 571 mW cm−1 was obtained, indicating that the CeO2-NiO heterostructure can provide favorable electrolyte functionality. The prepared CeO2-NiO heterostructures possessed both proton and oxygen ionic conductivities, with oxygen ionic conductivity dominating the fuel cell reaction. Further investigations in terms of electrical conductivity and electrode polarization, a proton and oxygen ionic co-conducting mechanism, and a mechanism for blocking electron transport showed that the reconstruction of the energy band at the interfaces was responsible for the enhanced ionic conductivity and cell power output. This work presents a new methodology and scientific understanding of semiconductor-based heterostructures for advanced ceramic fuel cells.
Biogenic Selenium Nanoparticles: Potential Solution to Oxidative Stress Mediated Inflammation in Rheumatoid Arthritis and Associated Complications
Authors: Rehman Ayesha , John Peter , Bhatti Attya
Published: August 2021

Rheumatoid arthritis (RA) is a common chronic inflammation-mediated disorder having systematic complications. RA triggers a self-directed inflammatory and immunological cascade that culminates in joint destruction. Though a range of treatment options are available, none of them are without adverse effects and this has led researchers to search for alternative solutions. Nanomedicine has emerged as a powerful therapeutic alternative, and selenium (Se) is an essential micronutrient trace element that has a crucial role in human health and disease. Selenium nanoparticles (SeNPs) derived from biological sources, such as plants, bacteria, fungi, and proteins, have exhibited remarkable candidate properties and toxicological profiles, and hence have shown potential to be used as antirheumatic agents. The potential of SeNPs can be attributed to the effect of functional groups bound to them, concentration, and most importantly to their nano range size. The antirheumatic effect of SeNPs is considerable due to its potential in amelioration of oxidative stress-mediated inflammation via downregulation of radical and nonradical species, markers of inflammation, and upregulation of inherent antioxidant defenses. The size and concentration impact of SeNPs has been shown in the subsequent antioxidant and anti-inflammatory properties. Moreover, the article emphasizes the role of these biogenic SeNPs as a notable option in the nanomedicine arena that needs to be further studied as a prospective remedial alternative to cure RA and medication-related adverse events.
Stand-Alone CuFeSe2 (Eskebornite) Nanosheets for Photothermal Cancer Therapy
Authors: Liu Mimi , Radu Daniela R. , Selopal Gurpreet Singh , Bachu Saiphaneendra , Lai Cheng-Yu
Published: August 2021

Two-dimensional CuFeSe2 nanosheets have been successfully obtained via solution-phase synthesis using a sacrificial template method. The high purity was confirmed by X-ray diffraction and the two-dimensional morphology was validated by transmission electron microscopy. The intense absorption in the 400–1400 nm region has been the basis for the CuFeSe2 nanosheets’ photothermal capabilities testing. The colloidal CuFeSe2 (CFS) nanosheets capped with S2− short ligands (CFS-S) exhibit excellent biocompatibility in cell culture studies and strong photothermal effects upon 808 nm laser irradiation. The nanosheets were further loaded with the cancer drug doxorubicin and exposed to laser irradiation, which accelerated the release of doxorubicin, achieving synergy in the therapeutic effect.
Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review
Authors: Edinoff Amber N. , Akuly Haseeb A. , Hanna Tony A. , Ochoa Carolina O. , Patti Shelby J. , Ghaffar Yahya A. , Kaye Alan D. , Viswanath Omar , Urits Ivan , Boyer Andrea G. , Cornett Elyse M. , Kaye Adam M.
Published: August 2021

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs.
Gallbladder Interleukins in Children with Calculous Cholecystitis
Authors: Deņisova Arina , Pilmane Māra , Eņģelis Arnis , Pētersons Aigars
Published: August 2021

Calculous cholecystitis connects to inflammation and various complications. It is a common disease in the paediatric population, yet it is still uncertain how inflammation factors are involved in its morphopathogenesis. Twenty calculous cholecystitis surgery tissue samples were obtained from 20 children. As a control, seven unaffected gallbladders were used. Tissues were immunohistochemically stained for IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, and IL-17A, and the slides were inspected by light microscopy. To evaluate statistical differences and correlations between interleukins, Mann–Whitney U and Spearman’s tests were used. Statistically significant difference between patient and control gallbladder epithelium was for IL-1α and IL-17A, but connective tissue—IL-1α, IL-4, IL-6, IL-7, IL-8, and IL-17A positive structures. A strong positive correlation in patients was detected between epithelial IL-1α and IL-1α in connective tissue, epithelial IL-6 and IL-7, IL-6 and IL-17A, IL-7 and IL-10, IL-7 and IL-17A, as well as between IL-6 and IL-7, IL-7 and IL-10 in connective tissue. The increase of IL-1α, IL-4, IL-6, IL-7, IL-8 and IL-17A positive structures suggests their role in the morphopathogenesis of calculous cholecystitis. The correlations between interleukins in epithelium and in connective tissues prove that the epithelial barrier function and inflammatory response in deeper layers are sustained through intercellular signalling pathways.
Construction of Hierarchical-Targeting pH-Sensitive Liposomes to Reverse Chemotherapeutic Resistance of Cancer Stem-like Cells
Authors: Ba Shuang , Qiao Mingxi , Jia Li , Zhang Jiulong , Zhao Xiuli , Hu Haiyang , Chen Dawei
Published: August 2021

Cancer stem-like cells (CSLCs) have been considered to be one of the main problems in tumor treatment owing to high tumorigenicity and chemotherapy resistance. In this study, we synthesized a novel mitochondria-target derivate, triphentlphosphonium-resveratrol (TPP-Res), and simultaneously encapsulated it with doxorubicin (Dox) in pH-sensitive liposomes (PSL (Dox/TPP-Res)), to reverse chemotherapeutic resistance of CSLCs. PSL (Dox/TPP-Res) was approximately 165 nm in size with high encapsulation efficiency for both Dox and TPP-Res. Cytotoxicity assay showed that the optimal synergistic effect was the drug ratio of 1:1 for TPP-Res and Dox. Cellular uptake and intracellular trafficking assay indicated that PSL (Dox/TPP-Res) could release drugs in acidic endosomes, followed by mitochondrial targeting of TPP-Res and nucleus transports for Dox. The mechanisms for reversing the resistance in CSLCs were mainly attributed to a synergistic effect for reduction of mitochondrial membrane potential, activation of caspase cascade reaction, reduction of ATP level and suppression of the Wnt/β-catenin pathway. Further, in vivo assay results demonstrated that the constructed liposomes could efficiently accumulate in the tumor region and possess excellent antineoplastic activity in an orthotopic xenograft tumor model with no evident systemic toxicity. The above experimental results determined that PSL (Dox/TPP-Res) provides a new method for the treatment of heterogenecity tumors.
Aberrant Neurogliovascular Unit Dynamics in Cerebral Small Vessel Disease: A Rheological Clue to Vascular Parkinsonism
Authors: Che Mohd Nassir Che Mohd Nasril , Damodaran Thenmoly , Yusof Siti R. , Norazit Anwar , Chilla Geetha , Huen Isaac , K. N. Bhanu Prakash , Mohamed Ibrahim Norlinah , Mustapha Muzaimi
Published: August 2021

The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood–brain barrier permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the glymphatic system that manages the flow of interstitial solutes, metabolic waste, and clearance through the venous circulation. As a physiologically integrated neurogliovascular unit (NGVU) serving a particularly vulnerable cerebral white matter (from hypoxia, metabolic insults, infection, and inflammation), a likely insidious process over a lifetime could inflict microenvironment damages that may lead to pathological conditions. Two such conditions, cerebral small vessel disease (CSVD) and vascular parkinsonism (VaP), with poorly understood pathomechanisms, are frequently linked to this brain-wide NGVU. VaP is widely regarded as an atypical parkinsonism, described by cardinal motor manifestations and the presence of cerebrovascular disease, particularly white matter hyperintensities (WMHs) in the basal ganglia and subcortical region. WMHs, in turn, are a recognised imaging spectrum of CSVD manifestations, and in relation to disrupted NGVU, also include enlarged perivascular spaces. Here, in this narrative review, we present and discuss on recent findings that argue for plausible clues between CSVD and VaP by focusing on aberrant multicellular dynamics of a unique integrated NGVU—a crossroad of the immune–vascular–nervous system—which may also extend fresher insights into the elusive interplay between cerebral microvasculature and neurodegeneration, and the potential therapeutic targets.
The Therapeutic Effect of Human Serum Albumin Dimer-Doxorubicin Complex against Human Pancreatic Tumors
Authors: Kinoshita Ryo , Ishima Yu , Chuang Victor T. G. , Watanabe Hiroshi , Shimizu Taro , Ando Hidenori , Okuhira Keiichiro , Otagiri Masaki , Ishida Tatsuhiro , Maruyama Toru
Published: August 2021

Human serum albumin (HSA) is a versatile drug carrier with active tumor targeting capacity for an antitumor drug delivery system. Nanoparticle albumin-bound (nab)-technology, such as nab-paclitaxel (Abraxane®), has attracted significant interest in drug delivery research. Recently, we demonstrated that HSA dimer (HSA-d) possesses a higher tumor distribution than HSA monomer (HSA-m). Therefore, HSA-d is more suitable as a drug carrier for antitumor therapy and can improve nab technology. This study investigated the efficacy of HSA-d-doxorubicin (HSA-d-DOX) as next-generation nab technology for tumor treatment. DOX conjugated to HSA-d via a tunable pH-sensitive linker for the controlled release of DOX. Lyophilization did not affect the particle size of HSA-d-DOX or the release of DOX. HSA-d-DOX showed significantly higher cytotoxicity than HSA-m-DOX in vitro. In the SUIzo Tumor-2 (SUIT2) human pancreatic tumor subcutaneous inoculation model, HSA-d-DOX could significantly inhibit tumor growth without causing serious side effects, as compared to the HSA binding DOX prodrug, which utilized endogenous HSA as a nano-drug delivery system (DDS) carrier. These results indicate that HSA-d could function as a natural solubilizer of insoluble drugs and an active targeting carrier in intractable tumors with low vascular permeability, such as pancreatic tumors. In conclusion, HSA-d can be an effective drug carrier for the antitumor drug delivery system against human pancreatic tumors.