bluuebunny/crossref_metadata_2025 huggingface dataset:
Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI)
Authors: Sohn Alexandria L. , Ping Lingyan , Glass Jonathan D. , Seyfried Nicholas T. , Hector Emily C. , Muddiman David C.
Published: November 2022

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS can be challenging. Comprehensive investigation of this disease is imperative to discovering unique features to expedite the diagnostic process and improve diagnostic accuracy. Here, we present untargeted metabolomics by mass spectrometry imaging (MSI) for comparing sporadic ALS (sALS) and C9orf72 positive (C9Pos) post-mortem frontal cortex human brain tissues against a control cohort. The spatial distribution and relative abundance of metabolites were measured by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI for association to biological pathways. Proteomic studies on the same patients were completed via LC-MS/MS in a previous study, and results were integrated with imaging metabolomics results to enhance the breadth of molecular coverage. Utilizing METASPACE annotation platform and MSiPeakfinder, nearly 300 metabolites were identified across the sixteen samples, where 25 were identified as dysregulated between disease cohorts. The dysregulated metabolites were further examined for their relevance to alanine, aspartate, and glutamate metabolism, glutathione metabolism, and arginine and proline metabolism. The dysregulated pathways discussed are consistent with reports from other ALS studies. To our knowledge, this work is the first of its kind, reporting on the investigation of ALS post-mortem human brain tissue analyzed by multiomic MSI.
AlScN Film Based Piezoelectric Micromechanical Ultrasonic Transducer for an Extended Long-Range Detection
Authors: Yang Haolin , Ji Meilin , Xiu Xueying , Lv Haochen , Gu Alex , Zhang Songsong
Published: November 2022

Piezoelectric micromachined ultrasonic transducers (PMUTs) have been widely applied in distance sensing. However, the sensing distance of currently reported miniaturized ultrasonic sensors (e.g., PMUTs or CMUT) is still limited up to a certain range (e.g., ≤5 m) compared to conventional bulk ultrasonic devices. This paper reports a PMUT array design using scandium-doped aluminum nitride (AlScN) as its piezoelectric layer for an extended long-range detection purpose. To minimize air attenuation, our device is resonating at 66 kHz for a high receive sensitivity of 5.7 mV/Pa. The proposed PMUT array can generate a sound pressure level (SPL) as high as 120 dB at a distance of 10 cm without beam forming. This PMUT design is catered for a pin-to-pin replacement of the current commercial bulk ultrasonic ranging sensor and works directly with the conventional range finding system (e.g., TI PGA460). In comparison with the common bulk transducer, the size of our device is 80% smaller. With the identical ranging detection setup, the proposed PMUT array improves the system SNR by more than 5 dB even at a distance as far as 6.8 m. The result of extended sensing distance validates our miniaturized PMUT array as the optimized candidate for most ultrasonic ranging applications. With the progressive development of piezoelectric MEMS, we believe that the PMUT technology could be a game changer in future long-range sensing applications.
A Simple Method for the Measurement of Young’s Moduli of Bilayer Thin Films Based on the Electrostatic Drive Approach
Authors: Liu Haiyun , Zhang Zhen , Gao Hongmin , Zhang Lili , Wang Lei
Published: November 2022

This paper presents a simple method for the in situ determination of Young’s moduli of surface-micromachined bilayer thin films. The test structure consists of a cantilever, a bottom drive electrode located near the anchor, and a bottom contact electrode placed below the free end of the cantilever. The cantilever is driven by applying a voltage sweep between the cantilever and the drive electrode, and bends due to the electrostatic force. A novel theoretical model is derived to relate Young’s modulus with the applied voltage and structure dimensions. The theoretical model is validated by finite element simulation. Test structures for Au/polysilicon thin films are fabricated by the PolyMUMPsand tested with the current–voltage measurement system. The measured Young modulus of polysilicon ranges from 152.344 GPa to 154.752 GPa, and the measured Young modulus of Au ranges from 71.794 GPa to 74.880 GPa. Compared with existing extraction methods, the proposed method is featured with simple operation, good repeatability, relatively high precision, and low requirements for equipment. It can be used alongside the application of a process control monitor (PCM) in surface-micromachining process lines.
Investigation of Needle Motion Profile Effect on Diesel Spray in Near-Nozzle Field
Authors: Gao Ya , Huang Weidi , Pratama Raditya Hendra , Gong Huifeng , Wang Jin
Published: November 2022

A variety of needle-motion profiles are used in diesel injectors. However, it is unclear what the underlying mechanism is to determine the needle-motion profiles and how they affect the spray dynamics. It has been of significant interest to examine how the spray dynamics will change if only altering the needle valve opening speed or closing speed while all other parameters are kept the same. The different needle-motion profiles were obtained using a piezo nozzle (Nozzle #P) and a solenoid nozzle (Nozzle #S), which have identical nozzle geometry. By utilizing the X-ray imaging technique, it was observed that the average needle valve speed of Nozzle #P was 51% higher at the opening stage but 17% lower at the closing stage than Nozzle #S. When the needle valve lift is low (approximately 200 μm), the needle valve opening speed has a crucial effect on spray dynamics. The faster needle valve opening of Nozzle #P results in a 42% larger spray spreading angle and 34% lower spray velocity at the downstream field. The spray dynamics may be controllable by properly designing the needle-motion profiles in the scenarios of the low needle lifts. However, when the needle valve is sufficiently open (approximately over 200 μm), almost identical spray characteristics were observed regardless of the needle-motion profiles.
A High Quality-Factor Optical Modulator with Hybrid Graphene-Dielectric Metasurface Based on the Quasi-Bound States in the Continuum
Authors: Li Chaolong , Cheng Hongbo , Luo Xin , Cheng Ziqiang , Zhai Xiang
Published: November 2022

In this paper, we combine the dielectric metasurface with monolayer graphene to realize a high quality(Q)-factor quasi-BIC-based optical modulator, and the corresponding modulation performances are investigated by using the finite-difference time-domain (FDTD) method, which can be well fitting by the Fano formula based on the temporal couple-mode theory. The results demonstrate that bound states in the continuum (BIC) will turn into the quasi-BIC with high Q-factor by breaking the symmetry of every unit of the metasurface. Meanwhile, the amplitude and bandwidth of transmission based on the quasi-BIC mode can be efficiently adjusted by changing the Fermi energy (EF) of monolayer graphene, and the maximum difference in transmission up to 0.92 is achieved. Moreover, we also discuss the influence of the asymmetry degree to further investigate the modulation effect of graphene on the quasi-BIC mode.
Picoliter Droplet Generation and Dense Bead-in-Droplet Encapsulation via Microfluidic Devices Fabricated via 3D Printed Molds
Authors: Anyaduba Tochukwu , Otoo Jonas , Schlappi Travis
Published: November 2022

Picoliter-scale droplets have many applications in chemistry and biology, such as biomolecule synthesis, drug discovery, nucleic acid quantification, and single cell analysis. However, due to the complicated processes used to fabricate microfluidic channels, most picoliter (pL) droplet generation methods are limited to research in laboratories with cleanroom facilities and complex instrumentation. The purpose of this work is to investigate a method that uses 3D printing to fabricate microfluidic devices that can generate droplets with sizes <100 pL and encapsulate single dense beads mechanistically. Our device generated monodisperse droplets as small as ~48 pL and we demonstrated the usefulness of this droplet generation technique in biomolecule analysis by detecting Lactobacillus acidophillus 16s rRNA via digital loop-mediated isothermal amplification (dLAMP). We also designed a mixer that can be integrated into a syringe to overcome dense bead sedimentation and found that the bead-in-droplet (BiD) emulsions created from our device had <2% of the droplets populated with more than 1 bead. This study will enable researchers to create devices that generate pL-scale droplets and encapsulate dense beads with inexpensive and simple instrumentation (3D printer and syringe pump). The rapid prototyping and integration ability of this module with other components or processes can accelerate the development of point-of-care microfluidic devices that use droplet-bead emulsions to analyze biological or chemical samples with high throughput and precision.
Development of Heterojunction c-Si/a-Si1−xCx:H PIN Light-Emitting Diodes
Authors: Meneses-Meneses Maricela , Moreno-Moreno Mario , Morales-Sánchez Alfredo , Ponce-Pedraza Arturo , Flores-Méndez Javier , Mendoza-Cervantes Julio , Palacios-Huerta Liliana
Published: November 2022

In this work, we explored the feasibility of the fabrication of PIN light-emitting diodes (LEDs) consisting of heterojunctions of amorphous silicon-carbide (a-Si1−xCx:H) thin films and crystalline silicon wafers (c-Si). The objective is the future development of electro-photonic systems in the same c-Si wafer, containing transistors, sensors, LEDs and waveguides. Two different heterojunction LEDs were fabricated consisting of PIN and PIN+N structures, where a-Si1−xCx:H thin films were used as P-type and I-type layers, while an N-type c-Si substrate was used as an active part of the device. The amorphous layers were deposited by the plasma-enhanced chemical vapor deposition (PECVD) technique at a substrate temperature of 200 °C. The PIN device presented electroluminescence (EL) only in the forward bias, while the PIN+N device presented in both the forward and reverse biases. The EL in reverse bias was possible due to the addition of an N+-type a-Si:H layer between the c-Si substrate and the I-type a-Si1−xCx:H active layer. Likewise, the EL intensity of the PIN+N structure was higher than that of the PIN device in forward bias, indicating that the addition of the N-type a-Si:H layer makes electrons flow more efficiently to the I layer. In addition, both devices presented red EL in the full area, which is observed with the naked eye.
Acoustic Emission Parameter Characterization of Damage Process of the Limestone with Different Rockburst Tendencies
Authors: Zhang He , Chen Qinglin , Wang Xiaojun , Zhao Kui , Zeng Qiang
Published: November 2022

The laboratory discrimination tests of the rockburst tendency and AE tests under the uniaxial compression were conducted on the limestone. Three criterions were used to judge the rockburst tendency of the limestone with a buried depth of 600–1000 m under the same borehole. The rock damages were quantified by the AE events, ring count and energy. The fractal characteristics of these parameters were compared and analyzed. The characterization accuracy of these parameters on the damage process of the limestone with different rockburst tendencies was discussed. The AE parameters of the limestone with different rockburst tendencies increase sharply when the stress is near its peak. With the increase in the rockburst tendency, the variation of the AE event rate and ring count of the limestone is more and more consistent with the AE energy. Based on the characterization of the AE events and ring count, the damage process is characterized by a gradual evolution, while based on the energy characterization, it is characterized by a stepped evolution. The damage represented by the AE energy reveals the intensity and instantaneity of the rockburst failure. According to the verification of the CV value, the fractal dimension D of the AE energy fluctuates more gently with the increase in the rockburst tendency. It reflects the energy storage characteristics of the rock with a rockburst tendency in the loading process, which is consistent with the failure mechanism of the rockburst. Therefore, AE energy is more accurate to characterize and predict the failure of the limestone with a rockburst tendency.
Solid Carriers of Potentially Toxic Elements and Their Fate in Stream Sediments in the Area Affected by Iron Ore Mining and Processing
Authors: Kos Saša , Zupančič Nina , Gosar Mateja , Miler Miloš
Published: November 2022

The potential environmental impact of historical mining and ore processing on stream sediments and water was studied in a small siderite iron ore deposit with diverse sulfide mineral paragenesis. The main aim was to characterize solid carriers of potentially toxic elements (PTEs) in stream sediments and mine waste, to understand their fate in fluvial systems. General mineralogy (X-ray powder diffraction) and individual solid PTE carriers (scanning electron microscopy/energy dispersive spectroscopy) were correlated with the geochemical composition of stream sediments, mine waste, and stream waters (inductively coupled plasma mass spectrometry). Primary solid PTE carriers were pyrite, chalcopyrite, sphalerite, Hg-bearing sphalerite, galena, and siderite. Slightly alkaline and oxidizing conditions in stream water promoted the transformation of primary phases into secondary PTE carriers. Fe(Mn)-oxide/oxyhydroxides were major sinks for Pb, Zn, and As. Compared to background levels, Co (14.6 ± 2.1 mg/kg), Cu (30 ± 2.9 mg/kg), Ni (32.1 ± 2.9 mg/kg), Pb (64.5 ± 16.4 mg/kg), Zn (175.3 ± 22.5 mg/kg), As (81.1 ± 63.7 mg/kg), and Hg (2 ± 0.8 mg/kg) were elevated in mining area. Mine waste contained similar PTE carriers as stream sediments, but much higher PTE contents. Prevailingly low PTE concentrations in streams, with the exception of As (1.97 ± 2.4 µg/L) and Zn (4.5 ± 5.7 µg/L), indicate the stability of PTE carriers. Environmental effects were not significant, and additional monitoring is recommended.
Fractal Dimension Analysis of Pores in Coal Reservoir and Their Impact on Petrophysical Properties: A Case Study in the Province of Guizhou, SW China
Authors: Fu Wei , Hu Wangshui , Yi Tongsheng , Kane Oumar Ibrahima , Zhang Manting , Huang Xin
Published: November 2022

Coal is a complex, porous medium with pore structures of various sizes. Therefore, it is difficult to accurately describe the characteristics of pore structure by using the traditional geometry method. The results from the present investigation suggest that the porous media system of the coal reservoir has obvious fractal characteristics at different scales. To study the complexity of the pores in the coal reservoir, 27 coal samples from Guizhou, SW China were studied. The fractal dimensions of coal pores were calculated, and the fractal dimension of a pore in a coal reservoir can be classified into two types: percolation and diffusion. The comprehensive fractal dimension can be obtained using the weighted summation method and the pore volume fraction of different fractal segments as the weight. The percolation fractal dimensions (Dp) of coal samples are between 2.88 and 3.12, the diffusion fractal dimensions (Dd) are between 3.57 and 3.84, and the comprehensive fractal dimensions (Dt) are between 3.05 and 3.63. The Dd values of all coal samples are all larger than the Dp values, which indicates that the random distribution and complexity of diffusion pores in coal are stronger than those of the percolation pores. The percolation fractal dimension decreases as the maturity degree increases, whereas the diffusion and comprehensive fractal dimensions increase. The diffusion pore volume fraction and total pore volume are all highly correlated with the comprehensive and diffusion fractal dimensions, respectively. The correlation between the comprehensive fractal dimension, diffusion pore volume fraction, and coal reservoir porosity is negative exponential, whereas the correlation between the total pore volume and coal reservoir porosity is positive linear. In comparison with the percolation and diffusion fractal dimensions, the comprehensive fractal dimension is better suited for characterizing the permeability of coal reservoirs. The fractal analysis of this paper is beneficial for understanding the relationship between the fractal characteristics of coal pores and properties.
Evaluation of Different Dispersants on the Dispersion/Sedimentation Behavior of Halloysite, Kaolinite, and Quartz Suspensions in the Enrichment of Halloysite Ore by Mechanical Dispersion
Authors: Durgut Emrah , Cinar Mustafa , Terzi Mert , Kursun Unver Ilgin , Yildirim Yildiz , Ozdemir Orhan
Published: November 2022

In this study, the dispersion properties of pure halloysite, kaolinite, and quartz minerals in halloysite ore were determined in the absence and presence of dispersants (sodium silicate, STPP, SHMP). First of all, the samples were characterized by chemical, mineralogical, BET, FTIR, and TEM analyses. Afterward, the physico-chemical properties of these minerals were investigated by zeta potential measurements and dispersion/sedimentation experiments in the absence and presence of the dispersants. The zeta potential measurements showed that the surface charges of all minerals changed from negative to positive as the PH changed from basic to acidic. The presence of dispersants at natural pHs indicated that the mineral surface charges tended to become more negative as the concentration increased in the zeta potential measurements. SHMP showed the most effect on the zeta potential. In the dispersion/sedimentation experiments, settling was slowed down with the use of dispersants. Finally, the dispersion properties of halloysite ore in the presence of dispersants were explored using mechanical dispersion and pulp viscosity experiments based on the amount of material passing to <38 μm size and the chemical changes in the materials. As a result of the mechanical dispersion tests carried out in the presence of dispersants (sodium silicate, STPP, SHMP), 71.3% of the material with 30.8% Al2O3 and 50.5% SiO2 content passed to <38 μm size without using dispersant, and 73.2% of <38 μm sized material with 35.5% Al2O3 and 46.1% SiO2 content was gained in the use of 7.5 kg/ton SHMP, which was determined as the optimum within the scope of the study. In conclusion, dispersant use enhanced the mechanical dispersion effect for plastic clay mineral separation from hard minerals in an aqueous medium.
Petrogenesis and Metallogenesis of Granitoids in the Yangla Cu-W Polymetallic Deposit, Southwest China: Evidence from Zircon Trace Elements and Hf Isotope
Authors: Wang Xinfu , Li Bo , Tang Guo , Lei Zhen , Chang He
Published: November 2022

Magmatic zircon tends to present characteristic trends in trace element compositions in response to magma petrogenesis and metallogenesis, such that zircon may provide a window into melt evolution not accessible by whole rock chemistry. The Yangla large Cu deposit is located in the central part of the Jinshajiang Suture Zone, southwest China, constrained between the Jinshajiang and Yangla Faults. In this study, the trace elements and hafnium isotopic compositions of zircons from quartz diorite were studied. Previous published relevant data of Yangla granitoid plutons (i.e., dioritic enclave, granodiorite, and quartz monzonite porphyry) also have been systematically cited and discussed. The result shows that the crystallization temperature and two-stage Hf mode ages (tCDM; the age of the source rocks for the magmas) gradually increased while the oxygen fugacity (fO2) and εHf(t) values gradually decreased, corresponding to the diorite enclave (~232 Ma), through granodiorite (~208 Ma) and quartz monzonite porphyry (~202 Ma), and to quartz diorite (~195 Ma). It is suggested that four plutons were from the same three-component mixing of upper crust + lower crust + mantle magmas, while the upper crustal metasediments ratios were gradually increased from the early to late stage. The increasing upper crust inputs resulted in higher melting temperatures and compositions of the initial magma. All melts experienced distinct fractional crystallization of apatite, titanite, and amphibole, and the later granite melts experienced higher assimilation and fractional crystallization degrees than the early ones in the evolution processes four stages of intrusive rocks. These Yangla granitoids are the products of large-scale acid magmatic emplacement activities in the Triassic-early Jurassic and have a good metallogenic potential of the Cu-W polymetallic deposit.
Numerical Study on the Vibratory Compaction Mechanism of the Sand-Gabion Backfills in Underground Coal Mines
Authors: Zhang Zhiyi , Wang Wei , Zhao Bo
Published: November 2022

Coal mine backfilling can effectively prevent large-scale movement of rock formations, not only improving the overall production capacity of the mine but also protecting the surface from destruction and maintaining the original ecological environment. Backfilling extent and backfills compactness are two factors determining the supporting effect on the overburdens in underground coal mines. To make full use of the aeolian sand as the backfill materials in underground coal mines in the desertification areas, Northwest China. Then, vibratory compaction was proposed to enlarge the compactness of these sand-gabion backfills by considering the limited working space. After that, the movement law of the sand particles during vibratory compaction, the influencing law of the vibratory parameters, and the gabion constraint on the ultimate compactness of the sand-gabion backfills were studied using the discrete element software PFC3D from the microscopic point of view. It was found that the aeolian sand particles are more likely to inter-squeeze under vibration than under static load. Furthermore, there are a series of optimal vibratory compaction parameters to the inner aeolian sand for each external gabion constraint strength. The optimal vibration parameters were frequency 50 HZ, excitation force 0.3 MPa, amplitude 40 KPa, and vibration time 4 s. Conclusions of this study can provide references for enlarging the compactness of the sand-gabion backfills in the underground goaf in the desertification area of Northwest China.
Mineral Changes to the Tufa Columns of Ikka Fjord, SW Greenland
Authors: Stockmann Gabrielle J. , Seaman Paul , Balic-Zunic Tonci , Peternell Mark , Sturkell Erik , Liljebladh Bengt , Gyllencreutz Richard
Published: November 2022

The submarine tufa columns of Ikka Fjord in Southwest Greenland have been studied during multiple field campaigns since 1995. The fjord contains close to thousand columns previously shown to consist of the metastable carbonate mineral ikaite (CaCO3·6H2O), which requires near-freezing conditions to remain stable over longer periods of time. During a field campaign to Ikka Fjord in the summer of 2019, seawater temperatures of 6–9 °C and visual physical changes to the columns were observed. These are the highest recorded seawater temperatures measured in Ikka Fjord in over three decades of research. In response, three selected columns at three different locations were sampled at their bases, middle, and top sections for mineralogical analysis. These samples were supplemented by a four further column samples and an extensive hydrographical campaign during fieldwork in the summer 2021. Here, we report the results of the mineralogical analyses performed by X-ray diffraction and µ-Raman Spectroscopy on these column samples. The results show that the columns analysed now consist of the less hydrated carbonate minerals, monohydrocalcite (CaCO3·H2O), aragonite, and calcite (CaCO3). One of the columns has completely altered into monohydrocalcite, whereas the other columns have crusts of ikaite and cores of monohydrocalcite ± aragonite and calcite. This change is interpreted as a dehydration reaction and mineral alteration from ikaite to monohydrocalcite continuing to aragonite ± calcite in response to being bathed in warming seawater. Hydrographic profilers and static dataloggers recorded seawater temperatures of 4–8 °C in the column-containing fjord areas during June–August 2021. The upper parts of the columns are particularly exposed to temperatures > 6 °C, considered to be the long-term stability threshold of ikaite in Ikka Fjord. The mineral dehydration reactions are irreversible. It is therefore predicted in a warming Arctic, ikaite will only appear as new growth on the columns for a short period, and that with time, the columns of Ikka Fjord will change mineralogy into mainly monohydrocalcite.
M-Carboxylic Acid Induced Formation of New Coordination Polymers for Efficient Photocatalytic Degradation of Ciprofloxacin
Authors: Li Jian , Wang Xiaojia , Niu Yunyin
Published: November 2022

Four new 2–3D materials were designed and synthesized by hydrothermal methods, namely, {[(L1·Cu·2H2O) (4,4-bipy)0.5] (β-Mo8O26)0.5·H2O} (1), {[(L1·Cu)2·(4,4-bipy)] (Mo5O16)} (2), {Co(L1)2}n (3), and {[(L1)2][β-Mo8O26]0.5·5H2O} (4). [L1=5-(4-aminopyridine) isophthalic acid]. The degradation of ciprofloxacin (CIP) in water by compounds 1–4 was studied under visible light. The experimental results show that compounds 1–4 have obvious photocatalytic degradation effect on CIP. In addition, for compound 1, the effects of temperature, pH, and adsorbent dosage on photocatalytic performance were also investigated. The stability of compound 1 was observed by a cycle experiment, indicating that there was no significant change after three cycles of CIP degradation.
Structural Homology-Based Drug Repurposing Approach for Targeting NSP12 SARS-CoV-2
Authors: Aljuaid Abdulelah , Salam Abdus , Almehmadi Mazen , Baammi Soukayna , Alshabrmi Fahad M. , Allahyani Mamdouh , Al-Zaydi Khadijah M. , Izmirly Abdullah M. , Almaghrabi Sarah , Baothman Bandar K. , Shahab Muhammad
Published: November 2022

The severe acute respiratory syndrome coronavirus 2, also known as SARS-CoV-2, is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 has a highly conserved non-structural protein 12 (NSP-12) involved in RNA-dependent RNA polymerase (RdRp) activity. For the identification of potential inhibitors for NSP-12, computational approaches such as the identification of homologous proteins that have been previously targeted by FDA-approved antivirals can be employed. Herein, homologous proteins of NSP-12 were retrieved from Protein DataBank (PDB) and the evolutionary conserved sequence and structure similarity of the active site of the RdRp domain of NSP-12 was characterized. The identified homologous structures of NSP-12 belonged to four viral families: Coronaviridae, Flaviviridae, Picornaviridae, and Caliciviridae, and shared evolutionary conserved relationships. The multiple sequences and structural alignment of homologous structures showed highly conserved amino acid residues that were located at the active site of the RdRp domain of NSP-12. The conserved active site of the RdRp domain of NSP-12 was evaluated for binding affinity with the FDA-approved antivirals, i.e., Sofosbuvir and Dasabuvir in a molecular docking study. The molecular docking of Sofosbuvir and Dasabuvir with the active site that contains conserved motifs (motif A-G) of the RdRp domain of NSP-12 revealed significant binding affinity. Furthermore, MD simulation also inferred the potency of Sofosbuvir and Dasabuvir. In conclusion, targeting the active site of the RdRp domain of NSP-12 with Dasabuvir and Sofosbuvir might reduce viral replication and pathogenicity and could be further studied for the treatment of SARS-CoV-2.
Mass Spectrometry-Based Identification of Bioactive Bee Pollen Proteins: Evaluation of Allergy Risk after Bee Pollen Supplementation
Authors: Matuszewska Eliza , Plewa Szymon , Pietkiewicz Dagmara , Kossakowski Kacper , Matysiak Joanna , Rosiński Grzegorz , Matysiak Jan
Published: November 2022

Bee pollen, because of its high content of nutrients, is a very valuable medicinal and nutritional product. However, since its composition is not completely studied, the consumption of this product may cause adverse effects, including allergic reactions. Therefore, this study aimed to discover and characterize the bioactive proteins of bee pollen collected in Poland, focusing mainly on the allergens. For this purpose, the purified and concentrated pollen aqueous solutions were analyzed using the nanoLC-MALDI-TOF/TOF MS analytical platform. As a result of the experiments, 197 unique proteins derived from green plants (Viridiplantae) and 10 unique proteins derived from bees (Apis spp.) were identified. Among them, potential plant allergens were discovered. Moreover, proteins belonging to the group of hypothetical proteins, whose expression had not been confirmed experimentally before, were detected. Because of the content of bioactive compounds—both beneficial and harmful—there is a critical need to develop guidelines for standardizing bee pollen, especially intended for consumption or therapeutic purposes. This is of particular importance because awareness of the allergen content of bee pollen and other bee products can prevent health- or life-threatening incidents following the ingestion of these increasingly popular “superfoods”.
Effects of Hydroxypropyl-Beta-Cyclodextrin on Cultured Brain Endothelial Cells
Authors: Veszelka Szilvia , Mészáros Mária , Porkoláb Gergő , Rusznyák Ágnes , Réti-Nagy Katalin Szászné , Deli Mária A. , Vecsernyés Miklós , Bácskay Ildikó , Váradi Judit , Fenyvesi Ferenc
Published: November 2022

The application of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the treatment of the rare cholesterol and lipid storage disorder Niemann–Pick disease type C opened new perspectives in the development of an efficient therapy. Even if the systemic administration of HPBCD was found to be effective, its low permeability across the blood–brain barrier (BBB) limited the positive neurological effects. Nevertheless, the cellular interactions of HPBCD with brain capillary endothelial cells have not been investigated in detail. In this study, the cytotoxicity, permeability, and cellular internalization of HPBCD on primary rat and immortalized human (hCMEC/D3) brain capillary endothelial cells were investigated. HPBCD shows no cytotoxicity on endothelial cells up to 100 µM, measured by impedance kinetics. Using a fluorescent derivative of HPBCD (FITC-HPBCD) the permeability measurements reveal that on an in vitro triple co-culture BBB model, FITC-HPBCD has low permeability, 0.50 × 10−6 cm/s, while on hCMEC/D3 cell layers, the permeability is higher, 1.86 × 10−5 cm/s. FITC-HPBCD enters brain capillary endothelial cells, is detected in cytoplasmic vesicles and rarely localized in lysosomes. The cellular internalization of HPBCD at the BBB can help to develop new strategies for improved HPBCD effects after systemic administration.
Melatonin: A Neurotrophic Factor?
Authors: Miranda-Riestra Armida , Estrada-Reyes Rosa , Torres-Sanchez Erandis D. , Carreño-García Silvia , Ortiz Genaro Gabriel , Benítez-King Gloria
Published: November 2022

Melatonin, N-acetyl-5-hydroxytryptamine, is a hormone that synchronizes the internal environment with the photoperiod. It is synthesized in the pineal gland and greatly depends on the endogenous circadian clock located in the suprachiasmatic nucleus and the retina’s exposure to different light intensities. Among its most studied functions are the regulation of the waking-sleep rhythm and body temperature. Furthermore, melatonin has pleiotropic actions, which affect, for instance, the modulation of the immune and the cardiovascular systems, as well as the neuroprotection achieved by scavenging free radicals. Recent research has supported that melatonin contributes to neuronal survival, proliferation, and differentiation, such as dendritogenesis and axogenesis, and its processes are similar to those caused by Nerve Growth Factor, Brain-Derived Neurotrophic Factor, Neurotrophin-3, and Neurotrophin-4/5. Furthermore, this indolamine has apoptotic and anti-inflammatory actions in specific brain regions akin to those exerted by neurotrophic factors. This review presents evidence suggesting melatonin’s role as a neurotrophic factor, describes the signaling pathways involved in these processes, and, lastly, highlights the therapeutic implications involved.
Uncovering the Mechanisms of Active Components from Toad Venom against Hepatocellular Carcinoma Using Untargeted Metabolomics
Authors: Liang Pan , Ma Yining , Yang Luyin , Mao Linshen , Sun Qin , Sun Changzhen , Liu Zengjin , Mazhar Maryam , Yang Sijin , Ren Wei
Published: November 2022

Toad venom, a dried product of secretion from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has had the therapeutic effects of hepatocellular carcinoma confirmed. Bufalin and cinobufagin were considered as the two most representative antitumor active components in toad venom. However, the underlying mechanisms of this antitumor effect have not been fully implemented, especially the changes in endogenous small molecules after treatment. Therefore, this study was designed to explore the intrinsic mechanism on hepatocellular carcinoma after the cotreatment of bufalin and cinobufagin based on untargeted tumor metabolomics. Ultraperformance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the absorbed components of toad venom in rat plasma. In vitro experiments were determined to evaluate the therapeutic effects of bufalin and cinobufagin and screen the optimal ratio between them. An in vivo HepG2 tumor-bearing nude mice model was established, and a series of pharmacodynamic indicators were determined, including the body weight of mice, tumor volume, tumor weight, and histopathological examination of tumor. Further, the entire metabolic alterations in tumor after treating with bufalin and cinobufagin were also profiled by UHPLC-MS/MS. Twenty-seven active components from toad venom were absorbed in rat plasma. We found that the cotreatment of bufalin and cinobufagin exerted significant antitumor effects both in vitro and in vivo, which were reflected in inhibiting proliferation and inducing apoptosis of HepG2 cells and thereby causing cell necrosis. After cotherapy of bufalin and cinobufagin for twenty days, compared with the normal group, fifty-six endogenous metabolites were obviously changed on HepG2 tumor-bearing nude mice. Meanwhile, the abundance of α-linolenic acid and phenethylamine after the bufalin and cinobufagin intervention was significantly upregulated, which involved phenylalanine metabolism and α-linolenic acid metabolism. Furthermore, we noticed that amino acid metabolites were also altered in HepG2 tumor after drug intervention, such as norvaline and Leu-Ala. Taken together, the cotreatment of bufalin and cinobufagin has significant antitumor effects on HepG2 tumor-bearing nude mice. Our work demonstrated that the in-depth mechanism of antitumor activity was mainly through the regulation of phenylalanine metabolism and α-Linolenic acid metabolism.
Superconducting Properties of YBa2Cu3O7−δ with a Multiferroic Addition Synthesized by a Capping Agent-Aided Thermal Treatment Method
Authors: Dzul-Kifli Nur Athirah Che , Kechik Mohd Mustafa Awang , Baqiah Hussein , Shaari Abdul Halim , Lim Kean Pah , Chen Soo Kien , Sukor Safia Izzati Abd , Shabdin Muhammad Kashfi , Karim Muhammad Khalis Abdul , Shariff Khairul Khaizi Mohd , Miryala Muralidhar
Published: November 2022

A bulk YBa2Cu3O7−δ (Y-123) superconductor synthesized by a thermal treatment method was added with different weight percentages (x = 0.0, 0.2, 1.0, 1.5, and 2.0 wt.%) of BiFeO3 (BFO) nanoparticle. X-ray diffraction (XRD), alternating current susceptibility (ACS), and field emission scanning electron microscopy (FESEM) were used to determine the properties of the samples. From the XRD results, all samples showed an orthorhombic crystal structure with a Pmmm space group. The sample x = 1.0 wt.% gave the highest value of Y-123. The high amounts of BFO degraded the crystallite size of the sample, showing that the addition did not promote the grain growth of Y-123. From ACS results, the Tc-onset value was shown to be enhanced by the addition of the BFO nanoparticle, where x = 1.5 wt.% gave the highest Tc value (91.91 K). The sample with 1.5 wt.% showed a high value of Tp (89.15 K). The FESEM analysis showed that the average grain size of the samples decreased as BFO was introduced. However, the small grain size was expected to fill in the boundary, which would help in enhancing the grain connectivity. Overall, the addition of the BFO nanoparticles in Y-123 helped to improve the superconducting properties, mainly for x = 1.5 wt.%.
Facile Preparation of a Bispherical Silver–Carbon Photocatalyst and Its Enhanced Degradation Efficiency of Methylene Blue, Rhodamine B, and Methyl Orange under UV Light
Authors: Islam Md. , Akter Jeasmin , Lee Insup , Shrestha Santu , Pandey Anil , Gyawali Narayan , Hossain Md. , Hanif Md. , Jang Se , Hahn Jae
Published: November 2022

The combination of organic and inorganic materials is attracting attention as a photocatalyst that promotes the decomposition of organic dyes. A facile thermal procedure has been proposed to produce spherical silver nanoparticles (AgNPs), carbon nanospheres (CNSs), and a bispherical AgNP–CNS nanocomposite. The AgNPs and CNSs were each synthesized from silver acetate and glucose via single- and two-step annealing processes under sealed conditions, respectively. The AgNP–CNS nanocomposite was synthesized by the thermolysis of a mixture of silver acetate and a mesophase, where the mesophase was formed by annealing glucose in a sealed vessel at 190 °C. The physicochemical features of the as-prepared nanoparticles and composite were evaluated using several analytical techniques, revealing (i) increased light absorption, (ii) a reduced bandgap, (iii) the presence of chemical interfacial heterojunctions, (iv) an increased specific surface area, and (v) favorable band-edge positions of the AgNP–CNS nanocomposite compared with those of the individual AgNP and CNS components. These characteristics led to the excellent photocatalytic efficacy of the AgNP–CNS nanocomposite for the decomposition of three pollutant dyes under ultraviolet (UV) radiation. In the AgNP–CNS nanocomposite, the light absorption and UV utilization capacity increased at more active sites. In addition, effective electron–hole separation at the heterojunction between the AgNPs and CNSs was possible under favorable band-edge conditions, resulting in the creation of reactive oxygen species. The decomposition rates of methylene blue were 95.2, 80.2, and 73.2% after 60 min in the presence of the AgNP–CNS nanocomposite, AgNPs, and CNSs, respectively. We also evaluated the photocatalytic degradation efficiency at various pH values and loadings (catalysts and dyes) with the AgNP–CNS nanocomposite. The AgNP–CNS nanocomposite was structurally rigid, resulting in 93.2% degradation of MB after five cycles of photocatalytic degradation.
Advances in Biopolymeric Nanopesticides: A New Eco-Friendly/Eco-Protective Perspective in Precision Agriculture
Authors: Kumar Ravinder , Kumar Naresh , Rajput Vishnu D. , Mandzhieva Saglara , Minkina Tatiana , Saharan Baljeet Singh , Kumar Dharmender , Sadh Pardeep Kumar , Duhan Joginder Singh
Published: November 2022

Pesticides are essential to contemporary agriculture and are required to safeguard plants from hazardous pests, diseases, and weeds. In addition to harming the environment, overusing these pesticides causes pests to become resistant over time. Alternative methods and agrochemicals are therefore required to combat resistance. A potential solution to pesticide resistance and other issues may be found in nanotechnology. Due to their small size, high surface-area-to-volume ratio, and ability to offer novel crop protection techniques, nanoformulations, primarily biopolymer-based ones, can address specific agricultural concerns. Several biopolymers can be employed to load pesticides, including starch, cellulose, chitosan, pectin, agar, and alginate. Other biopolymeric nanomaterials can load pesticides for targeted delivery, including gums, carrageenan, galactomannans, and tamarind seed polysaccharide (TSP). Aside from presenting other benefits, such as reduced toxicity, increased stability/shelf life, and improved pesticide solubility, biopolymeric systems are also cost-effective; readily available; biocompatible; biodegradable; and biosafe (i.e., releasing associated active compounds gradually, without endangering the environment) and have a low carbon footprint. Additionally, biopolymeric nanoformulations support plant growth while improving soil aeration and microbial activity, which may favor the environment. The present review provides a thorough analysis of the toxicity and release behavior of biopolymeric nanopesticides for targeted delivery in precision crop protection.
Influences of Glimepiride Self-Nanoemulsifying Drug Delivery System Loaded Liquisolid Tablets on the Hypoglycemic Activity and Pancreatic Histopathological Changes in Streptozotocin-Induced Hyperglycemic Rats
Authors: Ahmed Tarek A. , Alotaibi Hanadi A. , Almehmady Alshaimaa M. , Safo Martin K. , El-Say Khalid M.
Published: November 2022

The development of an oral anti-diabetic medication characterized by enhanced hypoglycemic activity is in high demand. The goal was to study the hypoglycemic activity and pancreatic histopathology after the black-seed-based self-nanoemulsifying drug delivery system (SNEDDS) loaded with glimepiride liquisolid tablets to diabetic rats. The solubility of glimepiride in various vehicles was investigated. An optimization SNEDDS formulation was developed using a mixture of the experimental design approach. Box–Behnken design (BBD) was used to develop glimepiride liquisolid tablets utilizing Avicel PH 101 and Neusilin as a carrier mixture and FujiSil as a coating material. The quality attributes of the prepared tablets were assessed. Following the administration of the optimized tablets to diabetic rats, the pharmacodynamics and histopathological changes were investigated and compared to a commercial drug product. Results revealed that the optimized SNEDDS formulation that contains 15.43% w/w black seed oil, 40% w/w Tween 80, and 44.57% w/w Polyethylene glycol 400 showed an average droplet size of 34.64 ± 2.01 nm and a drug load of 36.67 ± 3.13 mg/mL. The optimized tablet formulation contained 0.31% Avicel in the carrier mixture, a 14.99 excipient ratio, and 8% superdisintegrant. Pre- and post-compression properties were satisfactory, and the optimized glimepiride liquisolid tablet showed a two-fold increase in dissolution. The optimized tablet demonstrated superior pharmacodynamics. The pancreatic tissues of the group treated with the optimized tablet displayed normal histological structure. The obtained data offered a commercially viable alternative for manufacturing solid dosage forms containing water-insoluble drugs, but additional clinical research is required.
Exploration of Single and Co-Toxic Effects of Polypropylene Micro-Plastics and Cadmium on Rice (Oryza sativa L.)
Authors: Kaur Mandeep , Shen Chengcheng , Wang Lin , Xu Ming
Published: November 2022

The widespread application of micro-plastics (MP) and their release in the open environment has become a matter of worldwide concern. When interacting with contaminants such as heavy metals in the soil ecosystem, MPs can result in detrimental effects on the soil environment and plant growth and development. However, information based on the interaction between MPs and heavy metals and their effects on terrestrial plants is still limited. Keeping this in mind, the present study was conducted to explore the single and combined toxicity of polypropylene (PP) MPs (13 and 6.5 μm) and cadmium (Cd) on germination indices; root and stem growth; fresh and dry weight; and anti-oxidative enzyme activities of rice (Oryza sativa L.) seedlings. Our results indicated that a single application of PP MP and Cd on rice seedlings inhibited most of the germination indicators, while their co-occurrence (PP + Cd) showed a reduction in the overall toxicity to some extent. A single application of both the contaminants significantly inhibited root length, stem length, fresh weight and the activities of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) enzymes in rice seedling, while no significant effect on dry weight was observed. The combined toxicity of both PP and Cd revealed that 13 μm PP + Cd had an antagonistic effect on the growth of rice seedlings, while 6.5 μm PP + Cd showed a synergistic effect. The present study revealed that smaller PP MP particles (6.5 µm) prominently affected plant growth more as compared to larger particles (13 µm). Our work reported the combined effect of PP MP and Cd on the germination and growth of rice for the first time. This study can provide the basis for future research on the combined effects of different types and sizes of MPs and heavy metals on the terrestrial ecosystem.
Facilitated Photocatalytic Degradation of Rhodamine B over One-Step Synthesized Honeycomb-Like BiFeO3/g-C3N4 Catalyst
Authors: Cui Haoran , Wang Zhipeng , Cao Guoqiang , Wu Yiwan , Song Jian , Li Yu , Zhang Le , Mu Jiliang , Chou Xiujian
Published: November 2022

In the present work, a facile one-step methodology was used to synthesize honeycomb-like BiFeO3/g-C3N4 composites, where the well-dispersed BiFeO3 strongly interacted with the hg-C3N4. The 10BiFeO3/hg-C3N4 could completely degrade RhB under visible light illumination within 60 min. The degradation rate constant was remarkably improved and approximately three times and seven times that of pristine hg-C3N4 and BiFeO3, respectively. This is ascribed to the following factors: (1) the unique honeycomb-like morphology facilitates the diffusion of the reactants and effectively improves the utilization of light energy by multiple reflections of light; (2) the charged dye molecules can be tightly bound to the spontaneous polarized BiFeO3 surface to form the Stern layer; (3) the Z-scheme heterojunction and the ferroelectric synergistically promoted the efficient separation and migration of the photogenerated charges. This method can synchronously tune the micro-nano structure, surface property, and internal field construction for g-C3N4-based photocatalysts, exhibiting outstanding potential in environmental purification.