bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of Tactile Sensors Using Stiction Effect Temporary Handling
Authors: Zhong Peng , Sun Ke , Zheng Chaoyue , Yang Heng , Li Xinxin
Published: November 2021

A novel method for transfer of tactile sensors using stiction effect temporary handling (SETH) is presented to simplify the microelectromechanical-system (MEMS)/CMOS integration process, improve the process reliability and electrical performance, and reduce material constriction. The structure of the tactile sensor and the reroute substrate were first manufactured separately. Following the release process, the stiction-contact structures, which are designed to protect the low-stress silicon nitride diaphragm of the tactile sensor and prevent the low-stress silicon nitride diaphragm from moving during the subsequent bonding process, are temporarily bonded to the substrate owing to the stiction effect. After the released tactile sensor is bonded to the reroute substrate by Au–Si eutectic flip-chip bonding, a pulling force perpendicular to the bonded die is applied to break away the temporary supported beam of the tactile sensor, and the tactile sensor is then successfully transferred to the reroute substrate. The size of the transferred tactile sensor is as small as 180 μm × 180 μm × 1.2 μm, and the force area of the tactile sensor is only 120 μm × 120 μm × 1.2 μm. The maximum misalignment of the flip-chip bonding process is approximately 1.5 μm. The tactile sensors are tested from 0 to 17.1 kPa when the power supply is 5 V, resulting in a sensitivity of 0.22 mV/V/kPa, 0.26 mV/V/kPa, 0.27 mV/V/kPa and 0.27 mV/V/kPa, separately. The stress caused by the Au–Si eutectic flip-chip bonding ranges from −5.83 to +5.54 kPa. The temporary bonding strength caused by stiction is calculated to be larger than 7.06 kPa and less than 22.31 kPa. The shear strength of the bonded test structure is approximately 30.74 MPa and the yield of the transferred tactile sensors is as high as 90%.
Dual Laser Beam Asynchronous Dicing of 4H-SiC Wafer
Authors: Zhang Zhe , Wen Zhidong , Shi Haiyan , Song Qi , Xu Ziye , Li Man , Hou Yu , Zhang Zichen
Published: November 2021

SiC wafers, due to their hardness and brittleness, suffer from a low feed rate and a high failure rate during the dicing process. In this study, a novel dual laser beam asynchronous dicing method (DBAD) is proposed to improve the cutting quality of SiC wafers, where a pulsed laser is firstly used to introduce several layers of micro-cracks inside the wafer, along the designed dicing line, then a continuous wave (CW) laser is used to generate thermal stress around cracks, and, finally, the wafer is separated. A finite-element (FE) model was applied to analyze the behavior of CW laser heating and the evolution of the thermal stress field. Through experiments, SiC samples, with a thickness of 200 μm, were cut and analyzed, and the effect of the changing of continuous laser power on the DBAD system was also studied. According to the simulation and experiment results, the effectiveness of the DBAD method is certified. There is no more edge breakage because of the absence of the mechanical breaking process compared with traditional stealth dicing. The novel method can be adapted to the cutting of hard-brittle materials. Specifically for materials thinner than 200 μm, the breaking process in the traditional SiC dicing process can be omitted. It is indicated that the dual laser beam asynchronous dicing method has a great engineering potential for future SiC wafer dicing applications.
How to Control the Microfluidic Flow and Separate the Magnetic and Non-Magnetic Particles in the Runner of a Disc
Authors: Lin Yao-Tsung , Huang Chien-Sheng , Tseng Shi-Chang
Published: November 2021

Biochips play an important role in both medical and food industry safety testing. Moreover, magnetic activated cell sorting is a well-established technology for biochip development. However, biochips need to be manufactured by precision instruments, resulting in the high cost of biochips. Therefore, this study used magnetic-activation and mechanics theories to create a novel disc that could manipulate the microfluidic flow, mixing, reaction, and separation on the runner of the disc. The goal of the research was to apply in the field of biomedical detection systems to reduce the cost of biochips and simplify the operation process. The simulation and experimental investigation showed that the pattern of the reaction chamber was stomach-shaped and the reservoir chamber was rectangular-shaped on the disc. The microfluid could be controlled to flow to the reaction chamber from the buffer and sample chamber when the disc spun at 175~200 rpm within three minutes. This was defined as the first setting mode. The microfluid could then be controlled to flow to the reservoir chamber from the reaction chamber when the disc spun at 225 rpm within five to ten minutes. This was defined as the second setting mode. This verified that the pattern design of the disc was optimized for control of the microfluid flow, mixing, reaction, and separation in the runner of the disc by different setting modes.
Tissue Engineering Meets Nanotechnology: Molecular Mechanism Modulations in Cornea Regeneration
Authors: Mijanović Olja , Pylaev Timofey , Nikitkina Angelina , Artyukhova Margarita , Branković Ana , Peshkova Maria , Bikmulina Polina , Turk Boris , Bolevich Sergey , Avetisov Sergei , Timashev Peter
Published: November 2021

Nowadays, tissue engineering is one of the most promising approaches for the regeneration of various tissues and organs, including the cornea. However, the inability of biomaterial scaffolds to successfully integrate into the environment of surrounding tissues is one of the main challenges that sufficiently limits the restoration of damaged corneal tissues. Thus, the modulation of molecular and cellular mechanisms is important and necessary for successful graft integration and long-term survival. The dynamics of molecular interactions affecting the site of injury will determine the corneal transplantation efficacy and the post-surgery clinical outcome. The interactions between biomaterial surfaces, cells and their microenvironment can regulate cell behavior and alter their physiology and signaling pathways. Nanotechnology is an advantageous tool for the current understanding, coordination, and directed regulation of molecular cell–transplant interactions on behalf of the healing of corneal wounds. Therefore, the use of various nanotechnological strategies will provide new solutions to the problem of corneal allograft rejection, by modulating and regulating host–graft interaction dynamics towards proper integration and long-term functionality of the transplant.
The Interaction between DNA and Three Intercalating Anthracyclines Using Electrochemical DNA Nanobiosensor Based on Metal Nanoparticles Modified Screen-Printed Electrode
Authors: Karadurmus Leyla , Dogan-Topal Burcu , Kurbanoglu Sevinc , Shah Afzal , Ozkan Sibel A.
Published: November 2021

The screen-printed electrodes have gained increasing importance due to their advantages, such as robustness, portability, and easy handling. The manuscript presents the investigation of the interaction between double-strand deoxyribonucleic acid (dsDNA) and three anthracyclines: epirubicin (EPI), idarubicin (IDA), and doxorubicin (DOX) by differential pulse voltammetry on metal nanoparticles modified by screen-printed electrodes. In order to investigate the interaction, the voltammetric signals of dsDNA electroactive bases were used as an indicator. The effect of various metal nanomaterials on the signals of guanine and adenine was evaluated. Moreover, dsDNA/PtNPs/AgNPs/SPE (platinum nanoparticles/silver nanoparticles/screen-printed electrodes) was designed for anthracyclines–dsDNA interaction studies since the layer-by-layer modification strategy of metal nanoparticles increases the surface area. Using the signal of multi-layer calf thymus (ct)-dsDNA, the within-day reproducibility results (RSD%) for guanine and adenine peak currents were found as 0.58% and 0.73%, respectively, and the between-day reproducibility results (RSD%) for guanine and adenine peak currents were found as 1.04% and 1.26%, respectively. The effect of binding time and concentration of three anthracyclines on voltammetric signals of dsDNA bases were also evaluated. The response was examined in the range of 0.3–1.3 ppm EPI, 0.1–1.0 ppm IDA and DOX concentration on dsDNA/PtNPs/AgNPs/SPE. Electrochemical studies proposed that the interaction mechanism between three anthracyclines and dsDNA was an intercalation mode.
Analysis, Modeling, and Simulation of Thin-Film Cells-Based Photovoltaic Generator Combined with Multilayer Thermoelectric Generator
Authors: Dakwar Yasir Musa , Lineykin Simon , Sitbon Moshe
Published: November 2021

A new model for a multi-stage thermoelectric generator (TEG) is developed. An electrical and thermal model is built and simulated for different configurations of photovoltaic (PV) stand-alone hybrid systems, combining different stages of a TEG. The approach is evaluated with and without cooling by coupling a cold plate to a multi-stage hybrid PVTEG system. The model can be adjusted by sizing and specifying the influence of stage number on the overall produced power. Amorphous silicon thin-film (a-Si) is less affected by rising temperature compared to other technology. Hence, it was chosen for evaluating the lower limit gain in a hybrid system under various ambient temperatures and irradiances. The dynamics of the PVTEG system are presented under different coolant water flow rates. Finally, comparative electrical efficiency in reference to PV stand-alone was found to be 99.2% for PVTEG without cooling, 113.5% for PVTEG, and 117.3% for multi-stage PVTEG, accordingly installing multi-stage PVTEG at Israel in a typical year with an average PV yield of 1750 kWh/kW/year generates an extra 24 kWh/year per module hence avoiding fossil energy and equivalent CO2 emissions.
FPGA Implementation of Threshold-Type Binary Memristor and Its Application in Logic Circuit Design
Authors: Yang Liu , Wang Yuqi , Wu Zhiru , Wang Xiaoyuan
Published: November 2021

In this paper, a memristor model based on FPGA (field programmable gate array) is proposed, by using which the circuit of AND gate and OR gate composed of memristors is built. Combined with the original NOT gate in FPGA, the NAND gate, NOR gate, XOR gate and the XNOR gate are further realized, and then the adder design is completed. Compared with the traditional gate circuit, this model has distinct advantages in size and non-volatility. At the same time, the establishment of this model will add new research methods and tools for memristor simulation research.
Fused Deposition Modeling of Microfluidic Chips in Transparent Polystyrene
Authors: Mader Markus , Rein Christof , Konrat Eveline , Meermeyer Sophia Lena , Lee-Thedieck Cornelia , Kotz-Helmer Frederik , Rapp Bastian E.
Published: November 2021

Polystyrene (PS) is one of the most commonly used thermoplastic materials worldwide and plays a ubiquitous role in today’s biomedical and life science industry and research. The main advantage of PS lies in its facile processability, its excellent optical and mechanical properties, as well as its biocompatibility. However, PS is only rarely used in microfluidic prototyping, since the structuring of PS is mainly performed using industrial-scale replication processes. So far, microfluidic chips in PS have not been accessible to rapid prototyping via 3D printing. In this work, we present, for the first time, 3D printing of transparent PS using fused deposition modeling (FDM). We present FDM printing of transparent PS microfluidic channels with dimensions as small as 300 µm and a high transparency in the region of interest. Furthermore, we demonstrate the fabrication of functional chips such as Tesla-mixer and mixer cascades. Cell culture experiments showed a high cell viability during seven days of culturing, as well as enabling cell adhesion and proliferation. With the aid of this new PS prototyping method, the development of future biomedical microfluidic chips will be significantly accelerated, as it enables using PS from the early academic prototyping all the way to industrial-scale mass replication.
Biomimetic Composite Coatings for Activation of Titanium Implant Surfaces: Methodological Approach and In Vivo Enhanced Osseointegration
Authors: Oltean-Dan Daniel , Dogaru Gabriela-Bombonica , Jianu Elena-Mihaela , Riga Sorin , Tomoaia-Cotisel Maria , Mocanu Aurora , Barbu-Tudoran Lucian , Tomoaia Gheorghe
Published: November 2021

Innovative nanomaterials are required for the coatings of titanium (Ti) implants to ensure the activation of Ti surfaces for improved osseointegration, enhanced bone fracture healing and bone regeneration. This paper presents a systematic investigation of biomimetic composite (BC) coatings on Ti implant surfaces in a rat model of a diaphyseal femoral fracture. Methodological approaches of surface modification of the Ti implants via the usual joining methods (e.g., grit blasting and acid etching) and advanced physicochemical coating via a self-assembled dip-coating method were used. The biomimetic procedure used multi-substituted hydroxyapatite (ms-HAP) HAP-1.5 wt% Mg-0.2 wt% Zn-0.2 wt% Si nanoparticles (NPs), which were functionalized using collagen type 1 molecules (COL), resulting in ms-HAP/COL (core/shell) NPs that were embedded into a polylactic acid (PLA) matrix and finally covered with COL layers, obtaining the ms-HAP/COL@PLA/COL composite. To assess the osseointegration issue, first, the thickness, surface morphology and roughness of the BC coating on the Ti implants were determined using AFM and SEM. The BC-coated Ti implants and uncoated Ti implants were then used in Wistar albino rats with a diaphyseal femoral fracture, both in the absence and the presence of high-frequency pulsed electromagnetic shortwave (HF-PESW) stimulation. This study was performed using a bone marker serum concentration and histological and computer tomography (micro-CT) analysis at 2 and 8 weeks after surgical implantation. The implant osseointegration was evaluated through the bone–implant contact (BIC). The bone–implant interface was investigated using FE-SEM images and EDX spectra of the retrieved surgical implants at 8 weeks in the four animal groups. The obtained results showed significantly higher bone–implants contact and bone volume per tissue volume, as well as a greater amount of newly formed bone, in the BC-coated Ti implants than in the uncoated Ti implants. Direct bone–implant contact was also confirmed via histological examination. The results of this study confirmed that these biomimetic composite coatings on Ti implants were essential for a significant enhancement of osseointegration of BC-coated Ti implants and bone regeneration. This research provides a novel strategy for the treatment of bone fractures with possible orthopedic applications.
Microchip Immunoassays for Monitoring Renal Function: Rapid, Low-Cost, and Highly Sensitive Quantification of Urinary Biomarkers of Diabetic Nephropathy
Authors: Kasama Toshihiro , Sun Miaomiao , Kaji Noritada , Akiyama Shin’ichi , Yuzawa Yukio , Tokeshi Manabu , Matsuo Seiichi , Baba Yoshinobu
Published: November 2021

This study developed low-cost and highly sensitive immunoassay devices possessing the ability to rapidly analyze urine samples. Further, they can quantitatively detect three biomarkers indicating renal injury: monocyte chemotactic protein 1 (MCP-1), angiotensinogen (AGT), and liver-type fatty acid binding protein (L-FABP). The devices were used to successfully estimate the concentrations of the three biomarkers in urine samples within 2 min; the results were consistent with those obtained via conventional enzyme-linked immunosorbent assay (ELISA), which requires several hours. In addition, the estimated detection limits for the three biomarkers were comparable to those of commercially available ELISA kits. Thus, the proposed and fabricated devices facilitate high-precision and frequent monitoring of renal function.
Comprehensive Design Method of a High-Frequency-Response Fast Tool Servo System Based on a Full-Frequency Error Control Algorithm
Authors: Li Zelong , Guan Chaoliang , Dai Yifan , Xue Shuai , Yin Lianmin
Published: November 2021

With the development of optoelectronic information technology, high-performance optical systems require an increasingly higher surface accuracy of optical mirrors. The fast tool servo (FTS) based on the piezoelectric actuator is widely used in the compensation machining of high-precision optical mirrors. However, with the low natural frequency of mechanical structures, hysteresis of the piezoelectric actuators, and phase delay of the control systems, conventional FTS systems face problems such as a low working frequency and a large tracking error. This study presents a method for the design of a high-performance FTS system. First, a flexure hinge servo turret with a high natural frequency was designed through multi-objective optimization and finite element simulations. Subsequently, a composite control algorithm was proposed, targeting the problems of hysteresis and phase delay. The modified Prandtl–Ishlinskii inverse hysteresis model was used to overcome the hysteresis effect and a zero-phase error tracker was designed to reduce the phase error. The experimental results reveal that the tracking error of the designed FTS system was <10% in the full frequency range (0–1000 Hz).
Onychites from Polish Jura and Their Functional Morphology
Authors: Sztajner Przemysław
Published: November 2021

Onychites aff. barbatus is excessively rare in the Polish Jura. This paper describes a recent find from the basal middle Oxfordian. The specimen is preserved in a manner typical for other finds of this kind in platy limestones, i.e., as compressed and flattened imprints with remnants of carbonized organic matter. Excellent preservation of the surfaces enables a precise reconstruction of the original structure. Accordingly, I hypothesize on the attachment to soft parts and the function of the belemnite onychites. The high diversity of known onychites, especially from Europe (NW Tethys), indicates that they served a variety of purposes.
Concentration Levels and Features of the Distribution of Trace Elements in the Sapropel Deposits of Small Lakes (South of Western Siberia)
Authors: Strakhovenko Vera , Ovdina Ekaterina , Malov Georgy , Yermolaeva Nadezhda , Zarubina Eugeniya
Published: November 2021

The processes of the migration and concentration of trace elements during sedimentation in small continental lakes in various landscape zones of the south of Western Siberia have been studied. We provide a quantitative assessment of the concentration levels and changes in the regional geochemical background of Cd, Hg, Sb, Zn, and Pb in sapropel deposits over the past 200 years. It was shown that complex natural processes determined by a combination of azonal factors play a fundamental role in the formation of the geochemical and mineral compositions of the bottom sediments of small lakes in various landscape zones in the south of Western Siberia. These consist of: the formation of sedimentary material in the lake catchment depending on the relief, geology, soil, and vegetation cover, as well as anthropogenic influences; the formation of authigenic organic and mineral matter as a result of biological, biochemical, and physicochemical processes; and the deposition of a complex mixture of allochthonous and autochthonous matter at the bottom of a lake, which flows under conditions of prolonged ice formation (anaerobic conditions).
Keggin-Al13 Polycations: Influence of Synthesis and Intercalation Parameters on the Structural Properties of Al-Pillared Clays
Authors: Parodia Anderson , Prasniski Janaina A. , Bertella Francine , Pergher Sibele B. C.
Published: November 2021

Pillared clays are interesting materials with applications in catalysis and adsorption processes. To obtain these materials, several preparation procedures are necessary and must be optimized to tune the final properties of the resulting pillared clay. Therefore, this article reports the influence of synthesis parameters (temperature and concentration) of Keggin-Al13 polycations and different intercalation times (0.5 up to 72 h) on the structural properties of Al-pillared clays. The natural clays are from Brazil, and they are composed mainly of montmorillonite. By XRD, N2 sorption, XRF and 27Al NMR results of the Al-PILCs, we verified that the pillaring solution could be prepared at room temperature with an aging time of 24 h. For the cation exchange process, a period of at least 2 h is necessary to ensure the formation of pillared materials. The concentration of the Keggin-Al13 polycations was evaluated by using diluted pillaring solutions followed by applying re-pillaring procedures. After submitting the pillared clay to another pillaring process, the number of pillars in the interlamellar space increased; however, the micropore volume decreased concomitantly. Thus, by optimizing the synthesis conditions of the Keggin-Al13 polycations, Al-PILCs could be obtained with good values of basal spacing and specific surface area.
Relative Contributions of Mg Hydration and Molecular Structural Restraints to the Barrier of Dolomite Crystallization: A Comparison of Aqueous and Non-Aqueous Crystallization in (BaMg)CO3 and (CaMg)CO3 Systems
Authors: Zhou Shi , Wang Yuebo , Teng Henry
Published: November 2021

Carbonate mineralization is reasonably well-understood in the Ca–CO2–H2O system but continuously poses difficulties to grasp when Mg is present. One of the outstanding questions is the lack of success in dolomite MgCa(CO3)2 crystallization at atmospheric conditions. The conventional view holds that hydration retards the reactivity of Mg2+ and is supported by solvation shell chemistry. This theory however is at odds with the easy formation of norsethite MgBa(CO3)2, a structural analogue of dolomite, leading to the premise that crystal or molecular structural constrains may also be at play. The present study represents our attempts to evaluate the separate contributions of the two barriers. Crystallization in the Mg–Ba–CO2 system was examined in a non-aqueous environment and in H2O to isolate the effect of hydration by determining the minimal relative abundance of Mg required for norsethite formation. The results, showing an increase from 1:5 to 6:4 in the solution Mg/Ba ratio, represented a ~88% reduction in Mg2+ reactivity, presumably due to the hydration effect. Further analyses in the context of transition state theory indicated that the decreased Mg2+ reactivity in aqueous solutions was equivalent to an approximately 5 kJ/mol energy penalty for the formation of the activated complex. Assuming the inability of dolomite to crystallizes in aqueous solutions originates from the ~40 kJ/mol higher (relative to norsethite) Gibbs energy of formation for the activated complex, a hydration effect was estimated to account for ~12% of the energy barrier. The analyses present here may be simplistic but nevertheless consistent with the available thermodynamic data that show the activated complex of dolomite crystallization reaction is entropically favored in comparison with that of norsethite formation but is significantly less stable due to the weak chemical bonding state.
Effects of Pyrite Texture on Flotation Performance of Copper Sulfide Ores
Authors: Can İlkay B. , Özçelik Seda , Ekmekçi Zafir
Published: November 2021

Pyrite particles, having framboidal/altered texture, are known to significantly affect pulp chemistry and adversely affect flotation performance. Therefore, the main objectives of this study were to demonstrate influence of pyrite mineralogy on the flotation of copper (sulphidic) ores and develop alternative conditions to improve the performance. Two copper ore samples (Ore A and Ore B) having different textural/modal mineralogy and flotation characteristics were taken from different zones of the same ore deposit. Ore B contained framboidal pyrite and altered pyrite/marcasite, which is considered the main reason for the low flotation performance in both copper and pyrite flotation sections of the process plant. Flotation tests were conducted under different conditions using the two ore samples and a 50:50 blend. The results showed that Ore A could be concentrated under the base conditions, as applied in the existing flotation plant. On the other hand, Ore B did not respond to the base conditions and a copper recovery of only 5% could be obtained. Besides, blending Ore B with Ore A negatively affected the flotation behavior of Ore A. An alternative flotation chemistry was applied on Ore B using Na2S for surface cleaning and Na-Metabisulfite (MBS) for pyrite depression in the copper flotation stage. The surface cleaning reduced the rate of oxidation of the framboidal pyrite in Ore B. As a result, the copper recovery could be increased to 52% Cu for Ore B, and 65% for the mixed ore sample.
Effective Removal of Barrier Layer on the Surface of Low-Nickel Matte in an FeCl3-HCl-H2O Solution
Authors: Zhu Chuncheng , Lei Yu , Hu Xinbo , Xu Qian , Zou Xingli , Cheng Hongwei , Lu Xionggang
Published: November 2021

Using ferric chloride as an oxidant, here, we investigated the leaching effect of low-nickel matte in a flow field produced by mechanical agitation. The factors affecting a leaching reaction, such as stirring speed, leaching time, low-nickel matte particle size, and inert abrasive quartz sand, were studied. X-ray diffraction (XRD), X-ray fluorescence spectroscopy (XRF), a laser particle size analyzer, optical microscopy (OM), a scanning electron microscopy (SEM) with an energy dispersive X-ray detector (EDS), and a Raman spectrometer were used to characterize the materials before and after the leaching reaction. The contents of the main metal ions such as Ni, Cu, and Co in the leaching solution were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Using the control variable method, the optimal experimental conditions were as follows: 2 mol/L FeCl3—0.5 mol/L HCl-H2O system with low-nickel matte and quartz sand (mass ratio is 1:5) and leaching at 90 °C for 8 h. The results showed that the blocking effect of the solid product sulfur layer was effectively removed and continuous leaching was realized. The leaching efficiencies of Ni, Cu, and Co were 98.9%, 99.3%, and 98.1%, respectively.
Mollusc-Derived Brominated Indoles for the Selective Inhibition of Cyclooxygenase: A Computational Expedition
Authors: Rahman Md. Mominur , Junaid Md. , Hosen S. M. Zahid , Mostafa Mohammad , Liu Lei , Benkendorff Kirsten
Published: November 2021

Inflammation plays an important role in different chronic diseases. Brominated indoles derived from the Australian marine mollusk Dicathais orbita (D. orbita) are of interest for their anti-inflammatory properties. This study evaluates the binding mechanism and potentiality of several brominated indoles (tyrindoxyl sulfate, tyrindoleninone, 6-bromoisatin, and 6,6′-dibromoindirubin) against inflammatory mediators cyclooxygenases-1/2 (COX-1/2) using molecular docking, followed by molecular dynamics simulation, along with physicochemical, drug-likeness, pharmacokinetic (pk), and toxicokinetic (tk) properties. Molecular docking identified that these indole compounds are anchored, with the main amino acid residues, positioned in the binding pocket of the COX-1/2, required for selective inhibition. Moreover, the molecular dynamics simulation based on root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), and root mean square fluctuation (RMSF) analyses showed that these natural brominated molecules transit rapidly to a progressive constant configuration during binding with COX-1/2 and seem to accomplish a consistent dynamic behavior by maintaining conformational stability and compactness. The results were comparable to the Food and Drug Administration (FDA)-approved selective COX inhibitor, aspirin. Furthermore, the free energy of binding for the compounds assessed by molecular mechanics–Poisson–Boltzmann surface area (MM–PBSA) confirmed the binding capacity of indoles towards COX-1/2, with suitable binding energy values except for the polar precursor tyrindoxyl sulfate (with COX-1). The physicochemical and drug-likeness analysis showed zero violations of Lipinski’s rule, and the compounds are predicted to have excellent pharmacokinetic profiles. These indoles are projected to be non-mutagenic and free from hepatotoxicity, with no inhibition of human ether-a-go–go gene (hERG) I inhibitors, and the oral acute toxicity LD50 in rats is predicted to be similar or lower than aspirin. Overall, this work has identified a plausible mechanism for selective COX inhibition by natural marine indoles as potential therapeutic candidates for the mitigation of inflammation.
Synthesis of Boronated Amidines by Addition of Amines to Nitrilium Derivative of Cobalt Bis(Dicarbollide)
Authors: Bogdanova Ekaterina V. , Stogniy Marina Yu. , Suponitsky Kyrill Yu. , Sivaev Igor B. , Bregadze Vladimir I.
Published: November 2021

A series of novel cobalt bis(dicarbollide) based amidines were synthesized by the nucleophilic addition of primary and secondary amines to highly activated B-N+≡C–R triple bond of the propionitrilium derivative [8-EtC≡N-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)]. The reactions with primary amines result in the formation of mixtures of E and Z isomers of amidines, whereas the reactions with secondary amines lead selectively to the E-isomers. The crystal molecular structures of E-[8-EtC(NMe2)=HN-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)], E-[8-EtC(NEt2)=HN-3,3′-Co(1,2- C2B9H10)(1′,2′-C2B9H11)] and E-[8-EtC(NC5H10)=HN-3,3′-Co(1,2-C2B9H10)(1′,2′-C2B9H11)] were determined by single crystal X-ray diffraction.
Thymodepressin—Unforeseen Immunosuppressor
Authors: Deigin Vladislav , Vinogradova Yulia , Vinogradov Dmitry , Krasilshchikova Marina , Ivanov Vadim
Published: November 2021

The paper summarizes the available information concerning the biological properties and biomedical applications of Thymodepressin. This synthetic peptide drug displays pronounced immunoinhibitory activity across a wide range of conditions in vitro and in vivo. The history of its unforeseen discovery is briefly reviewed, and the current as well as potential expansion areas of medicinal practice are outlined. Additional experimental evidence is obtained, demonstrating several potential advantages of Thymodepressin over another actively used immunosuppressor drug, cyclosporin A.
Effect of Resveratrol Treatment on Human Pancreatic Cancer Cells through Alterations of Bcl-2 Family Members
Authors: Ratajczak Katarzyna , Glatzel-Plucińska Natalia , Ratajczak-Wielgomas Katarzyna , Nowińska Katarzyna , Borska Sylwia
Published: November 2021

Pancreatic cancers are among of the most lethal types of neoplasms, and are mostly detected at an advanced stage. Conventional treatment methods such as chemotherapy or radiotherapy often do not bring the desired therapeutic effects. For this reason, natural compounds are increasingly being used as adjuvants in cancer therapy. Polyphenolic compounds, including resveratrol, are of particular interest. The aim of this study is to analyze the antiproliferative and pro-apoptotic mechanisms of resveratrol on human pancreatic cells. The study was carried out on three human pancreatic cancer cell lines: EPP85-181P, EPP85-181RNOV (mitoxantrone-resistant cells) and AsPC-1, as well as the normal pancreatic cell line H6c7. The cytotoxicity of resveratrol in the tested cell lines was assessed by the colorimetric method (MTT) and the flow cytometry method. Three selected concentrations of the compound (25, 50 and 100 µM) were tested in the experiments during a 48-h incubation. TUNEL and Comet assays, flow cytometry, immunocytochemistry, confocal microscopy, real-time PCR and Western Blot analyses were used to evaluate the pleiotropic effect of resveratrol. The results indicate that resveratrol is likely to be anticarcinogenic by inhibiting human pancreatic cancer cell proliferation. In addition, it affects the levels of Bcl-2 pro- and anti-apoptotic proteins. However, it should be emphasized that the activity of resveratrol was specific for each of the tested cell lines, and the most statistically significant changes were observed in the mitoxantrone-resistant cells.
Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
Authors: Dymova Maya Alexandrovna , Utkin Yaroslav Alexandrovich , Dmitrieva Maria Denisovna , Kuligina Elena Vladimirovna , Richter Vladimir Alexandrovich
Published: November 2021

Background: Tumor-targeting bacteriophages can be used as a versatile new platform for the delivery of diagnostic imaging agents and therapeutic cargo. This became possible due to the development of viral capsid modification method. Earlier in our laboratory and using phage display technology, phages to malignant breast cancer cells MDA-MB 231 were obtained. The goal of this study was the optimization of phage modification and the assessment of the effect of the latter on the efficiency of phage particle penetration into MDA-MB 231 cells. Methods: In this work, we used several methods, such as chemical phage modification using FAM-NHS ester, spectrophotometry, phage amplification, sequencing, phage titration, flow cytometry, and confocal microscopy. Results: We performed chemical phage modification using different concentrations of FAM-NHS dye (0.5 mM, 1 mM, 2 mM, 4 mM, 8 mM). It was shown that with an increase of the modification degree, the phage titer decreases. The maximum modification coefficient of the phage envelope with the FAM–NHS dye was observed with 4 mM modifying agent and had approximately 804,2 FAM molecules per phage. Through the immunofluorescence staining and flow cytometry methods, it was shown that the modified bacteriophage retains the ability to internalize into MDA-MB-231 cells. The estimation of the number of phages that could have penetrated into one tumor cell was conducted. Conclusions: Optimizing the conditions for phage modification can be an effective strategy for producing tumor-targeting diagnostic and therapeutic agents, i.e., theranostic drugs.
Dibenzofuran Derivatives Inspired from Cercosporamide as Dual Inhibitors of Pim and CLK1 Kinases
Authors: Dao Viet Hung , Ourliac-Garnier Isabelle , Logé Cédric , McCarthy Florence O. , Bach Stéphane , da Silva Teresinha Gonçalves , Denevault-Sabourin Caroline , Thiéfaine Jérôme , Baratte Blandine , Robert Thomas , Gouilleux Fabrice , Brachet-Botineau Marie , Bazin Marc-Antoine , Marchand Pascal
Published: November 2021

Pim kinases (proviral integration site for Moloney murine leukemia virus kinases) are overexpressed in various types of hematological malignancies and solid carcinomas, and promote cell proliferation and survival. Thus, Pim kinases are validated as targets for antitumor therapy. In this context, our combined efforts in natural product-inspired library generation and screening furnished very promising dibenzo[b,d]furan derivatives derived from cercosporamide. Among them, lead compound 44 was highlighted as a potent Pim-1/2 kinases inhibitor with an additional nanomolar IC50 value against CLK1 (cdc2-like kinases 1) and displayed a low micromolar anticancer potency towards the MV4-11 (AML) cell line, expressing high endogenous levels of Pim-1/2 kinases. The design, synthesis, structure–activity relationship, and docking studies are reported herein and supported by enzyme, cellular assays, and Galleria mellonella larvae testing for acute toxicity.
Synergistic Effect of Biphasic Calcium Phosphate and Platelet-Rich Fibrin Attenuate Markers for Inflammation and Osteoclast Differentiation by Suppressing NF-κB/MAPK Signaling Pathway in Chronic Periodontitis
Authors: Kumar Anil , Mahendra Jaideep , Mahendra Little , Abdulkarim Hesham H. , Sayed Mohammed , Mugri Maryam H. , Ahmad Zeeshan Heera , Bhati Ashok Kumar , Faqehi Hadeel Hussain , Algregri Waleed Omar , Varadarajan Saranya , Balaji Thodur Madapusi , Baeshen Hosam Ali , Patil Shankargouda
Published: November 2021

Background: Periodontitis is characterized by excessive osteoclastic activity, which is closely associated with inflammation. It is well established that MAPK/NF-kB axis is a key signaling pathway engaged in osteoclast differentiation. It is stated that that biphasic calcium phosphate (BCP) and platelet-rich fibrin (PRF) have significant antiostoeclastogenic effects in chronic periodontitis. Objective: We aimed to elucidate the synergetic effect of PRF/BCP involvement of the nuclear factor kappa–light–chain–enhancer of activated B cells (NF-kB) and the mitogen-activated protein kinase (MAPK) signaling pathway in osteoclast differentiation in chronic periodontitis. Methods: We induced osteoclast differentiation in vitro using peripheral blood mononuclear cells (PBMCs) derived from patients with chronic periodontitis. We assessed osteoclast generation by tartrate-resistant acid phosphatase (TRAP) activity, proinflammatory cytokines were investigated by ELISA and NF-κB, and IKB by immunoblot, respectively. MAPK proteins and osteoclast transcription factors were studied by Western blot analysis and osteoclast transcriptional genes were assessed by RT-PCR. Results: The results showed that the potent inhibitory effect of PRF/BCP on osteoclastogenesis was evidenced by decreased TRAP activity and the expression of transcription factors, NFATc1, c-Fos, and the osteoclast marker genes, TRAP, MMP-9, and cathepsin-K were found to be reduced. Further, the protective effect of PRF/BCP on inflammation-mediated osteoclastogenesis in chronic periodontitis was shown by decreased levels of proinflammatory cytokines, NF-kB, IKB, and MAPK proteins. Conclusions: PRF/BCP may promote a synergetic combination that could be used as a strong inhibitor of inflammation-induced osteoclastogenesis in chronic periodontitis.
Pyrrolizine/Indolizine-NSAID Hybrids: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies
Authors: Abourehab Mohammed A. S. , Alqahtani Alaa M. , Almalki Faisal A. , Zaher Dana M. , Abdalla Ashraf N. , Gouda Ahmed M. , Beshr Eman A. M.
Published: November 2021

In the current study, eight new hybrids of the NSAIDs, ibuprofen and ketoprofen with five pyrrolizine/indolizine derivatives were designed and synthesized. The chemical structures of these hybrids were confirmed by spectral and elemental analyses. The antiproliferative activities of these hybrids (5 μM) was investigated against MCF-7, A549, and HT-29 cancer cell lines using the cell viability assay, MTT assay. The results revealed 4–71% inhibition of the growth of the three cancer cell lines, where 8a,e,f were the most active. In addition, an investigation of the antiproliferative activity of 8a,e,f against MCF-7 cells revealed IC50 values of 7.61, 1.07, and 3.16 μM, respectively. Cell cycle analysis of MCF-7 cells treated with the three hybrids at 5 μM revealed a pro-apoptotic increase in cells at preG1 and cell cycle arrest at the G1 and S phases. In addition, the three hybrids induced early apoptotic events in MCF-7 cells. The results of the molecular docking of the three hybrids into COX-1/2 revealed higher binding free energies than their parent compounds 5a,c and the co-crystallized ligands, ibuprofen and SC-558. The results also indicated higher binding free energies toward COX-2 over COX-1. Moreover, analysis of the binding modes of 8a,e,f into COX-2 revealed partial superposition with the co-crystallized ligand, SC-558 with the formation of essential hydrogen bonds, electrostatic, or hydrophobic interactions with the key amino acid His90 and Arg513. The new hybrids also showed drug-likeness scores in the range of 1.06–2.03 compared to ibuprofen (0.65) and ketoprofen (0.57). These results above indicated that compounds 8a,e,f deserve additional investigation as potential anticancer candidates.
Deposition of Hybrid Photocatalytic Layers for Air Purification Using Commercial TiO2 Powders
Authors: Cosaert Ewoud , Wolfs Cédric , Lambert Stéphanie D. , Heynderickx Geraldine J. , Poelman Dirk
Published: November 2021

Photocatalytic nanomaterials, using only light as the source of excitation, have been developed for the breakdown of volatile organic compounds (VOCs) in air for a long time. It is a tough challenge to immobilize these powder photocatalysts and prevent their entrainment with the gas stream. Conventional methods for making stable films typically require expensive deposition equipment and only allow the deposition of very thin layers with limited photocatalytic performance. The present work presents an alternative approach, using the combination of commercially available photocatalytic nanopowders and a polymer or inorganic sol–gel-based matrix. Analysis of the photocatalytic degradation of ethanol was studied for these layers on metallic substrates, proving a difference in photocatalytic activity for different types of stable layers. The sol–gel-based TiO2 layers showed an improved photocatalytic activity of the nanomaterials compared with the polymer TiO2 layers. In addition, the used preparation methods require only a limited amount of photocatalyst, little equipment, and allow easy upscaling.
Synthesis and Evaluation of Antioxidant Properties of 2-Substituted Quinazolin-4(3H)-ones
Authors: Mravljak Janez , Slavec Lara , Hrast Martina , Sova Matej
Published: November 2021

Quinazolinones represent an important scaffold in medicinal chemistry with diverse biological activities. Here, two series of 2-substituted quinazolin-4(3H)-ones were synthesized and evaluated for their antioxidant properties using three different methods, namely DPPH, ABTS and TEACCUPRAC, to obtain key information about the structure–antioxidant activity relationships of a diverse set of substituents at position 2 of the main quinazolinone scaffold. Regarding the antioxidant activity, ABTS and TEACCUPRAC assays were more sensitive and gave more reliable results than the DPPH assay. To obtain antioxidant activity of 2-phenylquinazolin-4(3H)-one, the presence of at least one hydroxyl group in addition to the methoxy substituent or the second hydroxyl on the phenyl ring in the ortho or para positions is required. An additional ethylene linker between quinazolinone ring and phenolic substituent, present in the second series (compounds 25a and 25b), leads to increased antioxidant activity. Furthermore, in addition to antioxidant activity, the derivatives with two hydroxyl groups in the ortho position on the phenyl ring exhibited metal-chelating properties. Our study represents a successful use of three different antioxidant activity evaluation methods to define 2-(2,3-dihydroxyphenyl)quinazolin-4(3H)-one 21e as a potent antioxidant with promising metal-chelating properties.
Naringin Exhibited Therapeutic Effects against DSS-Induced Mice Ulcerative Colitis in Intestinal Barrier–Dependent Manner
Authors: Cao Ruige , Wu Xing , Guo Hui , Pan Xin , Huang Rong , Wang Gangqiang , Liu Jikai
Published: November 2021

Naringin is a kind of multi-source food additive which has been explored broadly for its various biological activities and therapeutic potential. In the present study, the protective effect and mechanism of naringin on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice were investigated. The results showed that naringin significantly alleviated DSS-induced colitis symptoms, including disease activity index (DAI), colon length shortening, and colon pathological damage. The tissue and serum secretion of inflammatory cytokines, as well as the oxidative stress, were decreased accordingly upon naringin intervention. Naringin also decreased the proteins involved in inflammation and increased the expression of tight junction (TJ) proteins. Moreover, naringin increased the relative abundance of Firmicutes/Bacteroides and reduced the content of Proteobacteria to improve the intestinal flora disorder caused by DSS, which promotes the intestinal health of mice. It was concluded that naringin can significantly ameliorate the pathogenic symptoms of UC through inhibiting inflammatory response and regulating intestinal microbiota, which might be a promising natural therapeutic agent for the dietary treatment of UC and the improvement of intestinal symbiosis.
Concentration-Dependent Multi-Potentiality of L-Arginine: Antimicrobial Effect, Hydroxyapatite Stability, and MMPs Inhibition
Authors: Bijle Mohammed Nadeem , Pichika Mallikarjuna Rao , Mak Kit-Kay , Parolia Abhishek , Babar Muneer Gohar , Yiu Cynthia , Daood Umer
Published: November 2021

This study’s objective was to examine L-arginine (L-arg) supplementation’s effect on mono-species biofilm (Streptococcus mutans/Streptococcus sanguinis) growth and underlying enamel substrates. The experimental groups were 1%, 2%, and 4% arg, and 0.9% NaCl was used as the vehicle control. Sterilised enamel blocks were subjected to 7-day treatment with test solutions and S. mutans/S. sanguinis inoculum in BHI. Post-treatment, the treated biofilms stained for live/dead bacterial cells were analysed using confocal microscopy. The enamel specimens were analysed using X-ray diffraction crystallography (XRD), Raman spectroscopy (RS), and transmission electron microscopy (TEM). The molecular interactions between arg and MMP-2/MMP-9 were determined by computational molecular docking and MMP assays. With increasing arg concentrations, bacterial survival significantly decreased (p < 0.05). The XRD peak intensity with 1%/2% arg was significantly higher than with 4% arg and the control (p < 0.05). The bands associated with the mineral phase by RS were significantly accentuated in the 1%/2% arg specimens compared to in other groups (p < 0.05). The TEM analysis revealed that 4% arg exhibited an ill-defined shape of enamel crystals. Docking of arg molecules to MMPs appears feasible, with arg inhibiting MMP-2/MMP-9 (p < 0.05). L-arginine supplementation has an antimicrobial effect on mono-species biofilm. L-arginine treatment at lower (1%/2%) concentrations exhibits enamel hydroxyapatite stability, while the molecule has the potential to inhibit MMP-2/MMP-9.
Synthesis of New Modified with Rhodamine B Peptides for Antiviral Protection of Textile Materials
Authors: Todorov Petar , Georgieva Stela , Staneva Desislava , Peneva Petia , Grozdanov Petar , Nikolova Ivanka , Grabchev Ivo
Published: November 2021

Here we report on the synthesis and characterization of three new N-modified analogues of hemorphin-4 with rhodamine B. Modified with chloroacetyl, chloride cotton fabric has been dyed and color coordinates of the obtained textile materials were determined. Antiviral and virucidal activities of both the peptide-rhodamine B compounds and the dyed textile material were studied. Basic physicochemical properties (acid-base behavior, solvent influence, kinetics) related to the elucidation of structural activity of the new modified peptides based on their steric open/closed ring effect were studied. The obtained results lead to the conclusion that in protic solvent with change in pH of the environment, direct control over the dyeing of textiles can be achieved. Both the new hybrid peptide compounds and the modification of functionalized textile materials with these bioactive hemorphins showed virucidal activity against the human respiratory syncytial virus (HRSV-S2) and human adenovirus serotype 5 (HAdV-5) for different time intervals (30 and 60 min) and the most active compound was Rh-3.