bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclophosphamide Induces Lipid and Metabolite Perturbation in Amniotic Fluid during Rat Embryonic Development
Authors: Xu Jianya , Fang Huafeng , Chong Ying , Lin Lili , Xie Tong , Ji Jianjian , Shen Cunsi , Shi Chen , Shan Jinjun
Published: November 2022

Cyclophosphamide (CP) has been proven to be an embryo-fetal toxic. However, the mechanism responsible for the toxicity of the teratogenic agent has not been fully explored. This study aimed to examine the teratogenicity of CP when administered in the sensitive period of pregnant rats. The effect of CP on the lipid and metabolic profiles of amniotic fluid was evaluated using a UHPLC-Q-Exactive Orbitrap MS-based method. Metabolome analysis was performed using the MS-DIAL software with LipidBlast and NIST. Initially, we identified 636 and 154 lipid compounds in the positive and negative ion modes and 118 metabolites for differential analysis. Mainly 4 types of oxidized lipids in the amniotic fluid were found to accumulate most significantly after CP treatment, including very-long-chain unsaturated fatty acids (VLCUFAs), polyunsaturated fatty acid (PUFA)-containing triglycerides (TGs), oxidized phosphatidylcholine (PC), and sphingomyelin (SM). Tryptophan and some long-chain saturated fatty acids were lowered pronouncedly after CP treatment. These findings suggest that CP may exert teratogenic toxicity on pregnant rats through maternal and fetal oxidative stress. The UHPLC-Q-Exactive Orbitrap MS-based lipidomics approach is worthy of wider application for evaluating the potential toxicity of other agents (toxicants) during embryonic development.
Investigating the Potential Anti-SARS-CoV-2 and Anti-MERS-CoV Activities of Yellow Necklacepod among Three Selected Medicinal Plants: Extraction, Isolation, Identification, In Vitro, Modes of Action, and Molecular Docking Studies
Authors: Abd-Alla Howaida I. , Kutkat Omnia , Sweelam Heba-tollah M. , Eldehna Wagdy M. , Mostafa Marwa A. , Ibrahim Magda T. , Moatasim Yassmin , GabAllah Mohamed , Al-Karmalawy Ahmed A.
Published: November 2022

The anti-MERS-CoV activities of three medicinal plants (Azadirachta indica, Artemisia judaica, and Sophora tomentosa) were evaluated. The highest viral inhibition percentage (96%) was recorded for S. tomentosa. Moreover, the mode of action for both S. tomentosa and A. judaica showed 99.5% and 92% inhibition, respectively, with virucidal as the main mode of action. Furthermore, the anti-MERS-CoV and anti-SARS-CoV-2 activities of S. tomentosa were measured. Notably, the anti-SARS-CoV-2 activity of S. tomentosa was very high (100%) and anti-MERS-CoV inhibition was slightly lower (96%). Therefore, the phytochemical investigation of the very promising S. tomentosa L. led to the isolation and structural identification of nine compounds (1–9). Then, both the CC50 and IC50 values for the isolated compounds against SARS-CoV-2 were measured. Compound 4 (genistein 4’-methyl ether) achieved superior anti-SARS-CoV-2 activity with an IC50 value of 2.13 µm. Interestingly, the mode of action of S. tomentosa against SARS-CoV-2 showed that both virucidal and adsorption mechanisms were very effective. Additionally, the IC50 values of S. tomentosa against SARS-CoV-2 and MERS-CoV were found to be 1.01 and 3.11 µg/mL, respectively. In addition, all the isolated compounds were subjected to two separate molecular docking studies against the spike (S) and main protease (Mpr°) receptors of SARS-CoV-2.
An Optimised Monophasic Faecal Extraction Method for LC-MS Analysis and Its Application in Gastrointestinal Disease
Authors: Kelly Patricia E. , Ng H Jene , Farrell Gillian , McKirdy Shona , Russell Richard K. , Hansen Richard , Rattray Zahra , Gerasimidis Konstantinos , Rattray Nicholas J. W.
Published: November 2022

Liquid chromatography coupled with mass spectrometry (LC-MS) metabolomic approaches are widely used to investigate underlying pathogenesis of gastrointestinal disease and mechanism of action of treatments. However, there is an unmet requirement to assess faecal metabolite extraction methods for large-scale metabolomics studies. Current methods often rely on biphasic extractions using harmful halogenated solvents, making automation and large-scale studies challenging. The present study reports an optimised monophasic faecal extraction protocol that is suitable for untargeted and targeted LC-MS analyses. The impact of several experimental parameters, including sample weight, extraction solvent, cellular disruption method, and sample-to-solvent ratio, were investigated. It is suggested that a 50 mg freeze-dried faecal sample should be used in a methanol extraction (1:20) using bead beating as the means of cell disruption. This is revealed by a significant increase in number of metabolites detected, improved signal intensity, and wide metabolic coverage given by each of the above extraction parameters. Finally, we addressed the applicability of the method on faecal samples from patients with Crohn’s disease (CD) and coeliac disease (CoD), two distinct chronic gastrointestinal diseases involving metabolic perturbations. Untargeted and targeted metabolomic analysis demonstrated the ability of the developed method to detect and stratify metabolites extracted from patient groups and healthy controls (HC), highlighting characteristic changes in the faecal metabolome according to disease. The method developed is, therefore, suitable for the analysis of patients with gastrointestinal disease and can be used to detect and distinguish differences in the metabolomes of CD, CoD, and HC.
Flexible Actuator Based on Conductive PAM Hydrogel Electrodes with Enhanced Water Retention Capacity and Conductivity
Authors: Hong Yang , Lin Zening , Yang Yun , Jiang Tao , Shang Jianzhong , Luo Zirong
Published: November 2022

Conductive polyacrylamide (PAM) hydrogels with salts that act as electrolytes have been used as transparent electrodes with high elasticity in flexible electronic devices. Different types and contents of raw materials will affect their performance in all aspects. We tried to introduce highly hydratable salts into PAM hydrogels to improve their water retention capacity. Different salts can improve the water retention capacity of PAM hydrogels to a certain extent. In particular, PAM hydrogels containing higher concentrations of lithium chloride (LiCl) and calcium chloride (CaCl2) showed an extremely strong water retention capacity and could retain about 90% and more than 98% of the initial water in the experimental environment at a temperature of 25 °C and a relative humidity of 60% RH, respectively. In addition, we conducted electrical conductivity tests on these PAM hydrogels with different salts. The PAM hydrogels containing LiCl also show outstanding conductivity, and the highest conductivity value can reach up to about 8 S/m. However, the PAM hydrogels containing CaCl2, which also performed well in terms of their water retention capacity, were relatively common in terms of their electrical conductivity. On this basis, we attempted to introduce single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), and graphene (GO) electronic conductors to enhance the electrical conductivity of the PAM hydrogels containing LiCl. The conductivity of the PAM hydrogels containing LiCl was improved to a certain extent after the addition of these electronic conductors. The highest electrical conductivity was about 10 S/m after we added the SWCNTs. This experimental result indicates that these electronic conductors can indeed enhance the electrical conductivity of PAM hydrogels to a certain extent. After a maximum of 5000 repeated tensile tests, the conductive hydrogel samples could still maintain their original morphological characteristics and conductivity. This means that these conductive hydrogel samples have a certain degree of system reliability. We made the PAM conductive hydrogels with high water retention and good conductivity properties into thin electrodes and applied them to an electric response flexible actuator with dielectric elastomer as the functional material. This flexible actuator can achieve a maximum area strain of 18% under an external voltage of 10 kV. This new composite hydrogels with high water retention and excellent conductivity properties will enable more possibilities for the application of hydrogels.
Surface Modification of Polymethylmethacrylate (PMMA) by Ultraviolet (UV) Irradiation and IPA Rinsing
Authors: Bae Geundong , Park Taehyun , Song In-Hyouk
Published: November 2022

Polymethylmethacrylate (PMMA) is commonly applied to microfluidic devices due to its excellent biocompatibility, high optical transparency, and suitability for mass production. Recently, various surface treatment methods have been reported to improve the wettability of polymers, which is directly related to adhesion. In this research, the effect of a UV irradiation technique and an IPA rinsing technique as surface treatments for PMMA is investigated regarding the water contact angle of the PMMA surface. PMMA sheets that were 1.62 mm thick and commercially available were exposed to UV light with four different exposure times. Significant decreases in the water contact angle were observed after exposure to UV light, and the lowered contact angles due to the UV irradiation increased over time. According to the measurement, the water contact angle is a function of UV exposure dose as well as storage time after UV exposure. We examined the effect of a IPA rinsing process after UV irradiation and observed an increase in the water contact angle.
Active Tuning and Anisotropic Strong Coupling of Terahertz Polaritons in Van der Waals Heterostructures
Authors: Li Shaopeng , Xu Junhao , Xie Yajie
Published: November 2022

Electromagnetic field confinement is significant in enhancing light-matter interactions as well as in reducing footprints of photonic devices especially in Terahertz (THz). Polaritons offer a promising platform for the manipulation of light at the deep sub-wavelength scale. However, traditional THz polariton materials lack active tuning and anisotropic propagation simultaneously. In this paper, we design a graphene/α-MoO3 heterostructure and simulate polariton hybridization between isotropic graphene plasmon polaritons and anisotropic α-MoO3 phonon polaritons. The physical fundamentals for polariton hybridizations depend on the evanescent fields coupling originating from the constituent materials as well as the phase match condition, which can be severely affected by the α-MoO3 thickness and actively tuned by the gate voltages. Hybrid polaritons propagate with in-plane anisotropy that exhibit momentum dispersion characterized by elliptical, hyperboloidal and even flattened iso-frequency contours (IFCs) in the THz range. Our results provide a tunable and flexible anisotropic polariton platform for THz sensing, imaging, and modulation.
Grayscale Image Display Based on Nano-Polarizer Arrays
Authors: Pu Xinxin , Sun Xueping , Ge Shaobo , Cheng Jin , Zhou Shun , Liu Weiguo
Published: November 2022

Optical metasurfaces have shown unprecedented capabilities to control the two-dimensional distributions of phase, polarization, and intensity profiles of optical waves. Here, a TiO2 nanostructure functioning as a nano-polarizer was optimized considering that an anisotropic nanostructure is sensitive to the polarization states of incident light. We demonstrate two metasurfaces consisting of nano-polarizer arrays featured with different orientations, which can continuously manipulate the intensity distribution of the output light cell by cell according to Malus law and clearly display the detailed information of the target image. These metasurfaces have potential application in ultracompact displays, high-density optical information storage, and many other related polarization optics fields.
Real-Time Heart Rate Detection Method Based on 77 GHz FMCW Radar
Authors: Huang Xiaohong , Ju Zedong , Zhang Rundong
Published: November 2022

This paper proposes a real-time heart rate detection method based on 77 GHz FMCW radar. Firstly, the method establishes a new motion model according to respiratory and heartbeat rules, and extracts the motion signals of the chest and the abdomen; then, the random body motion (RBM) signal is eliminated by a combination of polynomial fitting and recursive least squares (RLS) adaptive filtering; lastly, multi-detection-point adaptive harmonics cancellation (AHC) is used to eliminate respiratory harmonics. In addition, the method introduces a spectrum analysis algorithm based on linear predictive coding (LPC). The experimental results show that the method can effectively eliminate the RBM signal and respiratory harmonics, and that the average real-time heart rate detection error rate is 2.925%.
Engineering of Optical and Electrical Properties of Electrodeposited Highly Doped Al:ZnO and In:ZnO for Cost-Effective Photovoltaic Device Technology
Authors: Papadimitriou Dimitra N.
Published: November 2022

Resistivity and transparency of zinc-oxide layers (ZnO) for chalcopyrite photovoltaic technology applications were engineered by activation of the Burstein–Moss (BM) effect at high concentrations of aluminium (Al) and indium (In) dopant. The Al:ZnO and In:ZnO layers were processed by cost-effective, large-area, fast-rate electrochemical deposition techniques from aqueous solution of zinc nitrate (Zn(NO3)2) and dopant trichlorides, at negative electrochemical potential of EC = (−0.8)–(−1.2) V, moderate temperature of 80 °C, and solute dopant concentrations of AlCl3 and InCl3 up to 20 and 15 mM, respectively. Both Al:ZnO and In:ZnO layers were deposited on Mo/glass substrates with ZnO and ZnO/ZnSe buffers (Al:ZnO/ZnO/Mo/glass, In:ZnO/ZnO/ZnSe/Mo/glass), respectively. Based on the band-gap energy broadening of Al:ZnO and In:ZnO originated by the BM effect, maximum carrier concentrations of the order 1020 and 1021 cm−3, respectively, were determined by optical characterization techniques. The (electrical) resistivity values of Al:ZnO calculated from optical measurements were commensurate with the results of electrical measurements (10−4 Ohm·cm). In both cases (Al:ZnO and In:ZnO), calibration of carrier density in dependence of solute dopant concentration (AlCl3 and InCl3) was accomplished. The p–n junctions of Au/In:ZnO/ZnO/ZnSe/CIGS/Mo on glass substrate exhibited current–voltage (I–V) characteristics competing with those of crystalline silicon (c-Si) solar cells.
A Study on the Resolution and Depth of Focus of ArF Immersion Photolithography
Authors: Song Jungchul , Kim Chae-Hwan , Lee Ga-Won
Published: November 2022

In this study, the resolution and depth of focus (DOF) of the ArF immersion scanner are measured experimentally according to numerical aperture (NA). Based on the experiment, the theoretical trade-off relationship between the resolution and depth of focus can be confirmed and k1 and k2 are extracted to be about 0.288 and 0.745, respectively. Another observation for a problem in small critical dimension realization is the increase in line width roughness (LWR) according to mask open area ratio. To mitigate the trade-off problem and critical dimension variation, the photoresist thickness effect on depth of focus is analyzed. Generally, the photoresist thickness is chosen considering depth of focus, which is decided by NA. In practice, the depth of focus is found to be influenced by the photoresist thickness, which can be caused by the intensity change of the reflected ArF light. This means that photoresist thickness can be optimized under a fixed NA in ArF immersion photolithography technology according to the critical dimension and pattern density of the target layer.
Guts Bacterial Communities of Porcellio dilatatus: Symbionts Predominance, Functional Significance and Putative Biotechnological Potential
Authors: Coelho Catarina , Tiago Igor , Veríssimo António
Published: November 2022

Terrestrial isopods are effective herbivorous scavengers with an important ecological role in organic matter cycling. Their guts are considered to be a natural enrichment environment for lignocellulosic biomass (LCB)-degrading bacteria. The main goal of this work was to assess the structural diversity of Porcellio dilatatus gut bacterial communities using NGS technologies, and to predict their functional potential using PICRUSt2 software. Pseudomonadota, Actinomycetota, Bacillota, Cyanobacteria, Mycoplasmatota, Bacteroidota, Candidatus Patescibacteria and Chloroflexota were the most abundant phyla found in P. dilatatus gut bacterial communities. At a family level, we identified the presence of eleven common bacterial families. Functionally, the P. dilatatus gut bacterial communities exhibited enrichment in KEGG pathways related to the functional module of metabolism. With the predicted functional profile of P. dilatatus metagenomes, it was possible to envision putative symbiotic relationships between P. dilatatus gut bacterial communities and their hosts. It was also possible to foresee the presence of a well-adapted bacterial community responsible for nutrient uptake for the host and for maintaining host homeostasis. Genes encoding LCB-degrading enzymes were also predicted in all samples. Therefore, the P. dilatatus digestive tract may be considered a potential source of LCB-degrading enzymes that is not to be neglected.
Inhibition of Listeria monocytogenes and Escherichia coli O157:H7 Growth by Ohelo Berry (Vaccinium calycinum) Fractions: Anthocyanins, Non-Anthocyanin Phenolics, and Organic Acids
Authors: Liu Xiaohan , Wu Biyu , Nakamoto Stuart T. , Imamura Joanne L. , Li Yong
Published: November 2022

Listeria monocytogenes and Escherichia coli O157:H7 are common causes of foodborne illness worldwide. Ohelo berry (Vaccinium calycinum) juice was found to possess inhibitory activity against L. monocytogenes. This study aimed to determine which constituents of ohelo berry have the most potent antimicrobial effects. The crude extract of ohelo berry was separated into sugar plus organic acids (F1), non-anthocyanin phenolics (F2), and anthocyanins (F3). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the fractions were determined against L. monocytogenes and E. coli O157:H7. The results demonstrated that F3 contained the highest concentrations of total phenolics and anthocyanins. All fractions caused a significant growth reduction in two bacteria compared to controls. F1 at native pH had the same MIC (1.39/0.36 Bx/acid) and MBC (5.55/1.06 Bx/acid) against the two bacteria, while neutralized F1 did not inhibit the growth of either pathogen. The MIC of F3 against L. monocytogenes was 13.69 mg/L cyanidin-3-glucoside equivalent, which was not affected by neutralization. Besides, L. monocytogenes was more sensitive than E. coli O157:H7 to all fractions. These findings suggest that both phenolics and organic acids contribute to the antimicrobial properties of ohelo berry, which have the potential to be used as natural food preservatives.
Impact of Fe2+ and Shear Stress on the Development and Mesoscopic Structure of Biofilms—A Bacillus subtilis Case Study
Authors: Gierl Luisa , Horn Harald , Wagner Michael
Published: November 2022

Bivalent cations are known to affect the structural and mechanical properties of biofilms. In order to reveal the impact of Fe2+ ions within the cultivation medium on biofilm development, structure and stability, Bacillus subtilis biofilms were cultivated in mini-fluidic flow cells. Two different Fe2+ inflow concentrations (0.25 and 2.5 mg/L, respectively) and wall shear stress levels (0.05 and 0.27 Pa, respectively) were tested. Mesoscopic biofilm structure was determined daily in situ and non-invasively by means of optical coherence tomography. A set of ten structural parameters was used to quantify biofilm structure, its development and change. The study focused on characterizing biofilm structure and development at the mesoscale (mm-range). Therefore, biofilm replicates (n = 10) were cultivated and analyzed. Three hypotheses were defined in order to estimate the effect of Fe2+ inflow concentration and/or wall shear stress on biofilm development and structure, respectively. It was not the intention to investigate and describe the underlying mechanisms of iron incorporation as this would require a different set of tools applied at microscopic levels as well as the use of, i.e., omic approaches. Fe2+ addition influenced biofilm development (e.g., biofilm accumulation) and structure markedly. Experiments revealed the accumulation of FeO(OH) within the biofilm matrix and a positive correlation of Fe2+ inflow concentration and biofilm accumulation. In more detail, independent of the wall shear stress applied during cultivation, biofilms grew approximately four times thicker at 2.5 mg Fe2+/L (44.8 µmol/L; high inflow concentration) compared to the low Fe2+ inflow concentration of 0.25 mg Fe2+/L (4.48 µmol/L). This finding was statistically verified (Scheirer–Ray–Hare test, ANOVA) and hints at a higher stability of Bacillus subtilis biofilms (e.g., elevated cohesive and adhesive strength) when grown at elevated Fe2+ inflow concentrations.
Comparison of the Peel-Associated Epiphytic Bacteria of Anthocyanin-Rich “Sun Black” and Wild-Type Tomatoes under Organic and Conventional Farming
Authors: Gorrasi Susanna , Pasqualetti Marcella , Muñoz-Palazon Barbara , Novello Giorgia , Mazzucato Andrea , Campiglia Enio , Fenice Massimiliano
Published: November 2022

Tomatoes are among the most consumed vegetables worldwide and represent a source of health-beneficial substances. Our study represents the first investigating the peel-associated epiphytic bacteria of red and purple (anthocyanin-rich) tomatoes subjected to organic and conventional farming systems. Proteobacteria was the dominant phylum (relative abundances 79–91%) in all experimental conditions. Enterobacteriaceae represented a large fraction (39.3–47.5%) of the communities, with Buttiauxella and Atlantibacter as the most represented genera. The core microbiota was composed of 59 operational taxonomic units (OTUs), including the majority of the most abundant ones. The occurrence of the most abundant OTUs differed among the experimental conditions. OTU 1 (Buttiauxella), OTU 2 (Enterobacteriales), and OTU 6 (Bacillales) were higher in red and purple tomatoes grown under organic farming. OTU 5 (Acinetobacter) had the highest abundance in red tomatoes subjected to organic farming. OTU 3 (Atlantibacter) was among the major OTUs in red tomatoes under both farming conditions. OTU 7 (Clavibacter) and OTU 8 (Enterobacteriaceae) had abundances ≥1% only in red tomatoes grown under conventional farming. PCA and clustering analysis highlighted a high similarity between the bacterial communities of red and purple tomatoes grown under organic farming. Furthermore, the bacterial communities of purple tomatoes grown under organic farming showed the lowest diversity and evenness. This work paves the way to understand the role of nutritional superior tomato genotypes, combined with organic farming, to modulate the presence of beneficial/harmful bacteria and supply healthier foods within a sustainable agriculture.
A Cyanophage MarR-Type Transcription Factor Regulates Host RNase E Expression during Infection
Authors: Lambrecht S. Joke , Stappert Nils , Sommer Frederik , Schroda Michael , Steglich Claudia
Published: November 2022

The marine picocyanobacterium Prochlorococcus contributes significantly to global primary production, and its abundance and diversity is shaped in part by viral infection. Here, we identified a cyanophage-encoded MarR-type transcription factor that induces the gene expression of host Prochlorococcus MED4 endoribonuclease (RNase) E during phage infection. The increase in rne transcript levels relies on the phage (p)MarR-mediated activation of an alternative promoter that gives rise to a truncated yet enzymatically fully functional RNase E isoform. In this study, we demonstrate that pMarR binds to an atypical activator site downstream of the transcriptional start site and that binding is enhanced in the presence of Ca2+ ions. Furthermore, we show that dimeric pMarR interacts with the α subunit of RNA polymerase, and we identified amino acid residues S66, R67, and G106, which are important for Ca2+ binding, DNA binding, and dimerization of pMarR, respectively.
Bacterial Communities in Various Parts of Air-Conditioning Units in 17 Japanese Houses
Authors: Watanabe Kensuke , Yanagi U , Shiraishi Yoshiki , Harada Kazuhiro , Ogino Fumitoshi , Asano Koichiro
Published: November 2022

HVAC systems have a significant impact on the indoor environment, and microbial contamination in HVAC systems has a significant effect on the indoor air quality. In this study, to gain a better understanding of the microbial contamination inside ACs, we used NGS to analyze the 16S rRNA gene of bacteria adhering to AC filters, cooling coils, fans, and air outlet surfaces. The five phyla in terms of the highest relative abundance were Proteobacteria, Firmicutes, Actinobacteria, Cyanobacteria, and Bacteroidetes. The surface of an AC filter provides a history of indoor airborne bacterial contamination, and of the 10 bacterial genera we detected with the highest abundance (in the following order: Pseudomonas > Staphylococcus > Paracoccus > Corynebacterium > Acinetobacter > Streptococcus > Methylobacterium > Enhydrobacter > Sphingomonas > Actinotignum) on the filter surface, the top 6 genera were Gram-negative bacteria. Furthermore, the seventh-most abundant genus adhering to the filter surface (Methylobacterium) was the second-most abundant genus on the cooling coil and fan, and the ninth-most abundant genus on the air filter (Sphingomonas) was the third-most abundant genus on the cooling coil. Various factors impact the bacterial flora inside AC units, including the location of the house, AC unit usage, and occupant activity.
Subsurface Insights of the Maricunga Gold Belt through Local Earthquake Tomography
Authors: Bugueño Felipe , Calle-Gardella Daniela , Comte Diana , Reyes-Wagner Valentina , Ojeda Marcia , Rietbrock Andreas , Roecker Steven
Published: November 2022

With the advancement of the use of geophysical methods in mining exploration, the possibility of restudying known mineral deposits that could have greater potential than that previously estimated is opening up, as is the case in the Maricunga Belt (MB), which is a metallogenic belt located east of Copiapó, Chile, with a length of 200 km and oriented in the NNE-SSW direction. This belt hosts significant gold deposits classified as porphyry gold (-copper), epithermal gold (-silver) of a high sulphidation type, and transitional gold, in some districts. In this work we studied the characteristics of the MB through local earthquake tomography (LET), which revealed a clear spatial correlation between low Vp/Vs anomalies and the gold deposits, demonstrating that lithologic interpretation using Vp and Vs values of the seismic tomography makes sense for the most common rocks associated with the genesis of porphyry-type deposits. Furthermore, high Vp/Vs anomalies were correlated to the main regional faults around the study zone, which seem to have a robust structural control regarding the location of the deposits.
Advances in Hydraulic Fracture Propagation Research in Shale Reservoirs
Authors: Gong Xun , Ma Xinhua , Liu Yuyang , Li Guanfang
Published: November 2022

The characterization of artificial fracture propagation law in the fracturing process of shale reservoirs is the basis for evaluating the fracture conductivity and a key indicator of the reservoir stimulated effect. In order to improve the fracture stimulated volume of shale reservoirs, this paper systematically discusses the current status of research on artificial fracture propagation law from the research methods and main control factors and provides an outlook on its future development direction. The analysis finds that the study of fracture propagation law by using indoor physical simulation experiments has the advantages of simple operation and intuitive image, and the introduction of auxiliary technologies such as acoustic emission monitoring and CT scanning into indoor physical model experiments can correct the experimental results so as to better reveal the propagation mechanism of artificial fractures. At present, the numerical simulation methods commonly used to study the propagation law of artificial fractures include the finite element method, extended finite element method, discrete element method, boundary element method and phase field method, etc. The models established based on these numerical simulation methods have their own advantages and applicability, so the numerical algorithms can be integrated and the numerical methods selected to model and solve the different characteristics of the propagation law of artificial fractures in different regions at different times can greatly improve the accuracy of the model solution and better characterize the propagation law of artificial fractures. The propagation law of artificial fracture in the fracturing process is mainly influenced by geological factors and engineering factors, so when conducting research, geological factors should be taken as the basis, and through detailed study of geological factors, the selection of the fracturing process can be guided and engineering influencing factors can be optimized.
The Ability of Acid-Based Natural Deep Eutectic Solvents to Co-Extract Elements from the Roots of Glycyrrhiza glabra L. and Associated Health Risks
Authors: Shikov Alexander N. , Shikova Veronika A. , Whaley Anastasiia O. , Burakova Marina A. , Flisyuk Elena V. , Whaley Andrei K. , Terninko Inna I. , Generalova Yulia E. , Gravel Irina V. , Pozharitskaya Olga N.
Published: November 2022

The roots of licorice (Glycyrrhiza glabra L.) have been widely used in traditional and officinal medicines for the treatment of different diseases. Natural deep eutectic solvents (NADES) have become popular for the extraction of active principles from medicinal plants. However, the ability of NADES to co-extract trace elements during the isolation of target active compounds is rarely investigated. The aim of this study was to analyze the content of trace elements in acid-based NADES extracts from the roots of G. glabra and the health risks associated with them. In this study, we have tested for the first time the ability of several acid-based NADES to co-extract glycyrrhizic acid (GA) and trace elements from the roots of G. glabra. GA has been identified as the dominant phytochemical in G. glabra NADES extracts (0.145–0.495 mg/g). Due to the close pKa of lactic acid and GA, the yield of GA in lactic acid-based NADES was higher in comparison with other tested NADES. The yield of GA in NADES3-NADES5 was statistically significant and surpassed the yield of GA in water. The recovery of all elements (except Li) by all tested NADES was low (less than 6%). According to an ANOVA test, the hydrogen bond donor type plays a decisive role in the extraction of elements. A strong positive correlation between the recovery of GA and MPI was noted. The metal pollution index, hazard quotient, hazard index, and chronic daily intake were calculated and suggest that all tested NADES extracts of G. glabra roots were nontoxic and possess no health risk for both ingestion and topical application.
VH-4-A Bioactive Peptide from Soybean and Exercise Training Constrict Hypertension in Rats through Activating Cell Survival and AMPKα1, Sirt1, PGC1α, and FoX3α
Authors: Baskaran Rathinasamy , Balasubramanian Balamuralikrishnan , Ho Jou-Hsuan , Wang Ming-Fu , Abomughaid Mosleh Mohammad , Yang Hong-Siang , Lin Wan-Teng
Published: November 2022

Hypertension is a chronic disease related to age, which affects tens of millions of people around the world. It is an important risk factor that causes myocardial infarction, heart failure, stroke, and kidney damage. Bioactive peptide VHVV (VH-4) from soybean has shown several biological activities. Physical exercise is a cornerstone of non-pharmacologic treatment for hypertension and has established itself as an effective and complementary strategy for managing hypertension. The present study evaluates the efficacy of VH-4 supplement and swimming exercise training in preventing hypertension in spontaneously hypertensive rats (SHR). SHR animals were treated with VH-4 (25 mg/kg by intraperitoneal administration) and swimming exercise (1 h daily) for eight weeks, and the hemodynamic parameters, histology, and cell survival pathway protein expression were examined. In SHR rats, increased heart weight, blood pressure, and histological aberrations were observed. Cell survival protein p-PI3K and p-AKT and antiapoptosis proteins Bcl2 and Bcl-XL expression decreased in SHR animals. SIRT1 and FOXO3 were decreased in hypertensive rats. Both bioactive peptide VH-4 treatment and swimming exercise training in hypertensive rats increased the cell survival proteins p-PI3K and p-AKT and AMPKα1, Sirt1, PGC1α, and FoX3α proteins. Soy peptide VH-4, along with exercise, acts synergistically and prevents hypertension by activating cell survival and AMPKα1, Sirt1, PGC1α, and FoX3α proteins.
Conditions for Shake-Gel Formation: The Relationship between the Size of Poly(Ethylene Oxide) and the Distance between Silica Particles
Authors: Huang Yi , Sato Shunsuke , Kobayashi Motoyoshi
Published: November 2022

Colloidal silica suspensions are widely used in many fields, including environmental restoration, oil drilling, and food and medical industries. To control the rheological property of suspensions, poly(ethylene oxide) (PEO) polymers are often used. Under specific conditions, the silica-PEO suspension can create a phenomenon called a shake-gel. Previous works discussed the conditions necessary to form a shake-gel and suggested that the bridging effect of the polymer is one of the important mechanisms for shake-gel formation. However, we noted that the influence of PEO size compared to the separation distance between silica particles regarding shake-gel formation has not been systematically investigated, while the PEO size should be larger than the particle–particle separation distance for polymer bridging in order to form gels. Thus, we conducted a series of experiments to examine the effects of the radius of gyration of the PEO and the distance between the silica particles by controlling the PEO molecular weight and the silica concentration. Our results elucidated that the radius of gyration of the PEO should be 2.5 times larger than the distance between the silica surfaces in order to promote the formation of a shake-gel. This result supports the hypothesis that the bridging effect is the main cause of shake-gel formation, which can help us to understand the conditions necessary for shake-gel preparation.
Natural Reno-Protective Agents against Cyclosporine A-Induced Nephrotoxicity: An Overview
Authors: Ibrahim Sabrin R. M. , Abdallah Hossam M. , El-Halawany Ali M. , Mohamed Gamal A. , Alhaddad Aisha A. , Samman Waad A. , Alqarni Ali A. , Rizq Akaber T. , Ghazawi Kholoud F. , El-Dine Riham Salah
Published: November 2022

CA (cyclosporine A) is a powerful immunosuppressing agent that is commonly utilized for treating various autoimmune illnesses and in transplantation surgery. However, its usage has been significantly restricted because of its unwanted effects, including nephrotoxicity. The pathophysiology of CA-induced kidney injury involves inflammation, apoptosis, tubular injury, oxidative stress, and vascular injury. Despite the fact that exact mechanism accountable for CA’s effects is inadequately understood, ROS (reactive oxygen species) involvement has been widely proposed. At present, there are no efficient methods or drugs for treating CA-caused kidney damage. It is noteworthy that diverse natural products have been investigated both in vivo and in-vitro for their possible preventive potential in CA-produced nephrotoxicity. Various extracts and natural metabolites have been found to possess a remarkable potential for restoring CA-produced renal damage and oxidative stress alterations via their anti-apoptosis, anti-inflammatory, and antioxidative potentials. The present article reviews the reported studies that assess the protective capacity of natural products, as well as dietary regimens, in relation to CA-induced nephrotoxicity. Thus, the present study presents novel ideas for designing and developing more efficient prophylactic or remedial strategies versus CA passive influences.
Dihydrotanshinone I Inhibits the Proliferation and Growth of Oxaliplatin-Resistant Human HCT116 Colorectal Cancer Cells
Authors: Wang Mengge , Xiang Yusen , Wang Ruyu , Zhang Lijun , Zhang Hong , Chen Hongzhuan , Luan Xin , Chen Lili
Published: November 2022

Oxaliplatin (OXA) is a first-line chemotherapeutic drug for the treatment of colorectal cancer (CRC), but acquired drug resistance becomes the main cause of treatment failure. Increasing evidence has shown that some natural components may serve as chemoresistant sensitizers. In this study, we discovered Dihydrotanshinone I (DHTS) through virtual screening using a ligand-based method, and explored its inhibitory effects and the mechanism on OXA-resistant CRC in vitro and in vivo. The results showed that DHTS could effectively inhibit the proliferation of HCT116 and HCT116/OXA resistant cells. DHTS-induced cell apoptosis blocked cell cycle in S and G2/M phases, and enhanced DNA damage of HCT116/OXA cells in a concentration-dependent manner. DHTS also exhibited the obvious inhibition of tumor growth in the HCT116/OXA xenograft model. Mechanistically, DHTS could downregulate the expression of Src homology 2 structural domain protein tyrosine phosphatase (SHP2) and Wnt/β-catenin, as well as conventional drug resistance and apoptosis-related proteins such as multidrug resistance associated proteins (MRP1), P-glycoprotein (P-gp), Bcl-2, and Bcl-xL. Thus, DHTS markedly induces cell apoptosis and inhibits tumor growth in OXA-resistant HCT116 CRC mice models, which can be used as a novel lead compound against OXA-resistant CRC.
Exosomes as Novel Delivery Systems for Application in Traditional Chinese Medicine
Authors: Chen Qi , Wu Di , Wang Yi , Chen Zhong
Published: November 2022

Exosomes, as gifts of nature derived from various cell types with a size range from ~40 to 160 nm in diameter, have gained attention recently. They are composed of a lipid membrane bilayer structure containing different constituents, such as surface ligands and receptors, from the parental cells. Originating from a variety of sources, exosomes have the ability to participate in a diverse range of biological processes, including the regulation of cellular communication. On account of their ideal native structure and characteristics, exosomes are taken into account as drug delivery systems (DDSs). They can provide profound effects on conveying therapeutic agents with great advantages, including specific targeting, high biocompatibility, and non-toxicity. Further, they can also be considered to ameliorate natural compounds, the main constituents of traditional Chinese medicine (TCM), which are usually ignored due to the complexity of their structures, poor stability, and unclear mechanisms of action. This review summarizes the classification of exosomes as well as the research progress on exosome-based DDSs for the treatment of different diseases in TCM. Furthermore, this review discusses the advantages and challenges faced by exosomes to contribute to their further investigation and application.
Identification of Dihydrolipoamide Dehydrogenase as Potential Target of Vemurafenib-Resistant Melanoma Cells
Authors: Tabolacci Claudio , Giordano Deborah , Rossi Stefania , Cordella Martina , D’Arcangelo Daniela , Moschella Federica , D’Atri Stefania , Biffoni Mauro , Facchiano Angelo , Facchiano Francesco
Published: November 2022

Background: Despite recent improvements in therapy, the five-year survival rate for patients with advanced melanoma is poor, mainly due to the development of drug resistance. The aim of the present study was to investigate the mechanisms underlying this phenomenon, applying proteomics and structural approaches to models of melanoma cells. Methods: Sublines from two human (A375 and SK-MEL-28) cells with acquired vemurafenib resistance were established, and their proteomic profiles when exposed to denaturation were identified through LC-MS/MS analysis. The pathways derived from bioinformatics analyses were validated by in silico and functional studies. Results: The proteomic profiles of resistant melanoma cells were compared to parental counterparts by taking into account protein folding/unfolding behaviors. Several proteins were found to be involved, with dihydrolipoamide dehydrogenase (DLD) being the only one similarly affected by denaturation in all resistant cell sublines compared to parental ones. DLD expression was observed to be increased in resistant cells by Western blot analysis. Protein modeling analyses of DLD’s catalytic site coupled to in vitro assays with CPI-613, a specific DLD inhibitor, highlighted the role of DLD enzymatic functions in the molecular mechanisms of BRAFi resistance. Conclusions: Our proteomic and structural investigations on resistant sublines indicate that DLD may represent a novel and potent target for overcoming vemurafenib resistance in melanoma cells.
The C30-Modulation of Betulinic Acid Using 1,2,4-Triazole: A Promising Strategy for Increasing Its Antimelanoma Cytotoxic Potential
Authors: Nistor Gabriela , Mioc Marius , Mioc Alexandra , Balan-Porcarasu Mihaela , Racoviceanu Roxana , Prodea Alexandra , Milan Andreea , Ghiulai Roxana , Semenescu Alexandra , Dehelean Cristina , Șoica Codruța
Published: November 2022

Cancer, in all its types and manifestations, remains one of the most frequent causes of death worldwide; an important number of anticancer drugs have been developed from plants, fungi and animals, starting with natural compounds that were later derivatized in order to achieve an optimized pharmacokinetic/pharmacological profile. Betulinic acid is a pentacyclic triterpenic compound that was identified as an anticancer agent whose main advantage consists in its selective activity, which ensures the almost total lack of cytotoxic side effects. Conjugates of betulinic acid with substituted triazoles, scaffolds with significant pharmacological properties, were synthesized and tested as anticancer agents in order to achieve new therapeutic alternatives. The current paper aims to obtain a C30-1,2,4-triazole derivative of betulinic acid simultaneously acetylated at C3 whose biological activity was tested against RPMI melanoma cells. The compound revealed significant cytotoxic effects at the tested concentrations (2, 10 and 50 μΜ) by significantly decreasing the cell viability to 88.3%, 54.7% and 24.5%, respectively, as compared to the control. The compound’s testing in normal HaCaT cells showed a lack of toxicity, which indicates its selective dose-dependent anticancer activity. The investigation of its underlying molecular mechanism revealed an apoptotic effect induced at the mitochondrial level, which was validated through high-resolution respirometry studies.
Silica Nanospheres Coated Silver Islands as an Effective Opto-Plasmonic SERS Active Platform for Rapid and Sensitive Detection of Prostate Cancer Biomarkers
Authors: Pandey Anamika , Sarkar Subhankar , Pandey Sumit Kumar , Srivastava Anchal
Published: November 2022

The in vitro diagnostics of cancer are not represented well yet, but the need for early-stage detection is undeniable. In recent decades, surface-enhanced Raman spectroscopy (SERS) has emerged as an efficient, adaptable, and unique technique for the detection of cancer molecules in their early stages. Herein, we demonstrate an opto-plasmonic hybrid structure for sensitive detection of the prostate cancer biomarker sarcosine using silica nanospheres coated silver nano-islands as a facile and efficient SERS active substrate. The SERS active platform has been developed via thin (5–15 nm) deposition of silver islands using a simple and cost-effective Radio Frequency (RF) sputtering technique followed by the synthesis and decoration of silica nanospheres (~500 nm) synthesized via Stober’s method. It is anticipated that the coupling of Whispering Gallery Modes and photonic nano-jets in SiO2 nanospheres induce Localized Surface Plasmon Resonance (LSPR) in Ag nano-islands, which is responsible for the SERS enhancement. The as-fabricated SERS active platform shows a linear response in the physiological range (10 nM to 100 μM) and an extremely low limit of detection (LOD) of 1.76 nM with a correlation coefficient of 0.98 and enhancement factor ~2 × 107. The findings suggest that our fabricated SERS platform could be potentially used for the rapid detection of bio-chemical traces with high sensitivity.
Iridium-Catalyzed and pH-Dependent Reductions of Nitroalkenes to Ketones
Authors: Wang Tingting , Liu Changmeng , Xu Dong , Xu Jiaxi , Yang Zhanhui
Published: November 2022

A highly chemoselective conversion of α,β-disubstituted nitroalkenes to ketones is developed. An acid-compatible iridium catalyst serves as the key to the conversion. At a 2500 S/C ratio, nitroalkenes were readily converted to ketones in up to 72% isolated yields. A new mechanistic mode involving the reduction of nitroalkene to nitrosoalkene and N-alkenyl hydroxylamine is proposed. This conversion is ready to amplify to a gram-scale synthesis. The pH value plays an indispensable role in controlling the chemoselectivity.
Potential Benefits of Black Chokeberry (Aronia melanocarpa) Fruits and Their Constituents in Improving Human Health
Authors: Ren Yulin , Frank Tyler , Meyer Gunnar , Lei Jizhou , Grebenc Jessica R. , Slaughter Ryan , Gao Yu G. , Kinghorn A. Douglas
Published: November 2022

Aronia berry (black chokeberry) is a shrub native to North America, of which the fresh fruits are used in the food industry to produce different types of dietary products. The fruits of Aronia melanocarpa (Aronia berries) have been found to show multiple bioactivities potentially beneficial to human health, including antidiabetic, anti-infective, antineoplastic, antiobesity, and antioxidant activities, as well as heart-, liver-, and neuroprotective effects. Thus far, phenolic compounds, such as anthocyanins, cyanidins, phenolic acids, proanthocyanidins, triterpenoids, and their analogues have been identified as the major active components of Aronia berries. These natural products possess potent antioxidant activity, which contributes to the majority of the other bioactivities observed for Aronia berries. The chemical components and the potential pharmaceutical or health-promoting effects of Aronia berries have been summarized previously. The present review article focuses on the molecular targets of extracts of Aronia berries and the examples of promising lead compounds isolated from these berries, including cyanidin-3-O-galactoside, chlorogenic acid, quercetin, and ursolic acid. In addition, presented herein are clinical trial investigations for Aronia berries and their major components, including cancer clinical trials for chlorogenic acid and COVID-19 trial studies for quercetin. Additionally, the possible development of Aronia berries and their secondary metabolites as potential therapeutic agents is discussed. It is hoped that this contribution will help stimulate future investigations on Aronia berries for the continual improvement of human health.