bluuebunny/crossref_metadata_2025 huggingface dataset:
Reservoir Quality Prediction of Gas-Bearing Carbonate Sediments in the Qadirpur Field: Insights from Advanced Machine Learning Approaches of SOM and Cluster Analysis
Authors: Rashid Muhammad , Luo Miao , Ashraf Umar , Hussain Wakeel , Ali Nafees , Rahman Nosheen , Hussain Sartaj , Aleksandrovich Martyushev Dmitriy , Vo Thanh Hung , Anees Aqsa
Published: December 2022

The detailed reservoir characterization was examined for the Central Indus Basin (CIB), Pakistan, across Qadirpur Field Eocene rock units. Various petrophysical parameters were analyzed with the integration of various cross-plots, complex water saturation, shale volume, effective porosity, total porosity, hydrocarbon saturation, neutron porosity and sonic concepts, gas effects, and lithology. In total, 8–14% of high effective porosity and 45–62% of hydrocarbon saturation are superbly found in the reservoirs of the Eocene. The Sui Upper Limestone is one of the poorest reservoirs among all these reservoirs. However, this reservoir has few intervals of rich hydrocarbons with highly effective porosity values. The shale volume ranges from 30 to 43%. The reservoir is filled with effective and total porosities along with secondary porosities. Fracture–vuggy, chalky, and intracrystalline reservoirs are the main contributors of porosity. The reservoirs produce hydrocarbon without water and gas-emitting carbonates with an irreducible water saturation rate of 38–55%. In order to evaluate lithotypes, including axial changes in reservoir characterization, self-organizing maps, isoparametersetric maps of the petrophysical parameters, and litho-saturation cross-plots were constructed. Estimating the petrophysical parameters of gas wells and understanding reservoir prospects were both feasible with the methods employed in this study, and could be applied in the Central Indus Basin and anywhere else with comparable basins.
In Situ Argon Isotope Analyses of Chondrule-Forming Materials in the Allende Meteorite: A Preliminary Study for 40Ar/39Ar Dating Based on Cosmogenic 39Ar
Authors: Takeshima Yuko , Hyodo Hironobu , Tsujimori Tatsuki , Gouzu Chitaro , Itaya Tetsumaru
Published: December 2022

The argon isotopic compositions of chondrule-forming minerals of the Allende (CV3) meteorite were examined to evaluate the possibility of in situ 40Ar/39Ar dating of planetary surface rocks based on cosmogenic 39Ar without neutron irradiation in a reactor. The investigated Allende meteorite sample (ME-247H: 50 mm × 45 mm × 5 mm; 28.85 g) contains at least three textural types of chondrules: barred olivine chondrule (BOC), porphyritic olivine chondrule (POC), and unclassified chondrule (UC). Most chondrules contain olivine, low-Ca pyroxene, clinopyroxene, and plagioclase as primary phases, with minor amounts of nepheline and sodalite formed during aqueous alteration of the CV3 parent body of the early solar system. In situ argon isotope analyses on selected chondrule-forming minerals in petrographic sections of two BOCs, two POCs, and one UC using a Nd:YAG pulse laser confirmed a significant amount of cosmogenic 39Ar that formed by a 39K (n, p) 39Ar reaction in an extraterrestrial environment. Laser step-heating analyses of five bulk chondrules irradiated in a reactor revealed a plateau age (3.32 ± 0.06 Ga) from one of the five chondrules. The age spectra of all chondrules show the younger age in the low-temperature fractions, resulting in the integrated ages from 2.7 to 3.2 Ga. These results suggest that the Allende meteorite experienced argon isotopic homogenization at 3.3 Ga and the argon loss in part after the 3.3 Ga. Apparent ages of chondrule-forming minerals that were calculated using the J values of nephelines in one BOC and two POCs do not show any consistent relationship among the three types of chondrules (BOC, POC, and UC). This might be attributed to the fact that the isotopic heterogeneity among minerals took place during the heterogeneous argon loss stage after the 3.3 Ga event.
Organic Geochemistry and Hydrocarbon Generation Characteristics of Shale of the Fourth Member of Yingcheng Formation in the South Shuangcheng Fault Depression, Songliao Basin
Authors: Shi Lidong , Sun Lidong , Yang Liang , Xu Jinshuang , Du Changpeng , Chen Fangwen
Published: December 2022

In order to evaluate the potential for oil and gas resources in the deep fault depression of the Northern Songliao Basin, shale from the fourth member of the Yingcheng Formation (K1yc4) in the South Shuangcheng Fault Depression was selected as an example. The organic geochemical characteristics such as abundance, type and maturity from experiments on low-maturity source rock samples, the hydrocarbon generation conversion rate, hydrocarbon generation amount and hydrocarbon generation period of the shale from K1yc4 were evaluated via the chemical kinetics method. The hydrocarbon generation threshold of shale from K1yc4 in the South Shuangcheng Fault Depression was analyzed by examining the organic matter (OM) in shale core samples from K1yc4. Based on the thermal simulations to an approximate buried depth of 750 m, the maximum oil-generation stage corresponds to an approximate buried depth of 1380 m. The amounts of generated oil and gas from the shale in K1yc4 are approximately 2.417 × 108 t and 0.546 × 1011 m3, respectively. The shale in K1yc4 generated crude oil mainly during the sedimentary period of the Qingshankou Formation, Yaojia Formation and Nenjiang Formation, and mainly generated natural gas during the sedimentary period of the Nenjiang Formation. In the South Shuangcheng Fault Depression, the high parts of the local structure are the favorable areas for oil and gas exploration of K1yc4 in the sag zone, which could be used for the combined production of shale oil, tight sandstone oil and conventional oil.
Interpreting Surface Large-Loop Time-Domain Electromagnetic Data for Deep Mineral Exploration Using 3D Forward Modeling and Inversion
Authors: Cheng Ming , Yang Dikun , Luo Qiang
Published: December 2022

Surface transient electromagnetic (TEM) data with large transmitter loops for deep mineral exploration are often complicated by the non-trivial coupling between extended sources and arbitrarily oriented geological targets. This case study reports a TEM field data set acquired across terranes with strong lateral inhomogeneity, which is responsible for the high inconsistency in TEM data patterns along the survey line, as well as for the negative TEM transients (sign reversal) at some near-central loop stations. 3D forward modeling and inversion, as maturing tools in recent years, offer unique opportunities to extract as much geological information from such data as possible. 3D forward simulations of representative synthetic models found that the phenomenon of sign reversal at some TEM stations is associated with compact conductors enclosed by the transmitter loop and receivers that are in the loop, but off the conductor–a situation that is common in large-loop TEM and can only be explained by 3D models. However, 3D inversion of the field data with a uniform subspace as the initial and reference model fails to converge, another point of evidence that 3D inversions of large-loop TEM data are more likely to be subject to stability issues. Our solution is to warm-start the inversion with the representative model in the forward simulation experiments as the initial model, so the ill-posed 3D inversion can escape from local minima. Finally, the vertical contact structure in our 3D-inversion model is verified by a resistivity cross section of the CSAMT method. Our case study demonstrates the demand and capability of 3D electromagnetic modeling and inversion for high-resolution deep mineral exploration. It also provides an easy-to-follow template for carrying out 3D interpretation for complex geology in practice.
Removal Mechanism of Mineral Impurities in Molybdenum Concentrate Treatment Process
Authors: Liu Qihang , Liu Ruilin , Yang Shuangping , Feng Weiguo , Wang Miao
Published: December 2022

The removal of impurities in molybdenum concentrate has become a new challenge for enterprises due to the cancellation of pickling. Whether impurity minerals can be converted into soluble ions during roasting is important for the impurity removal by current water washing. In this work, the interaction between various impurity elements in the treatment process of molybdenum concentrate was studied by process simulation experiments combined with X-ray fluorescence (XRF) and X-ray diffraction (XRD), inductively coupled plasma-optical emission spectrometer (ICP-OES), ion chromatography (IC), scanning electron microscope-energy dispersive spectrometry (SEM-EDS), the use of FactSage7.0 modeling and the mineral liberation analyzer (MLA). The results show that most of the impurity elements such as K, Si and Al exist in the form of alkaline minerals with large molecular weight. In the roasting process of molybdenum concentrate, K-containing minerals, such as muscovite and orthoclase, can be transformed into K+, Al3+ and other soluble ions, and then can be removed by water washing. Humidification increased the conversion degree of orthoclase to soluble ions, which was conducive to the removal of impurities by the washing process. The results of MLA microscopic analysis confirmed that impurities such as FeS2, CaSO4, SiO2, and especially FeS2, would form a high density mixture with MoO3 during the high temperature roasting process, and thus reduced the leaching rate of Mo. Therefore, the humidification and control of the molybdenum concentrate is an effective measure to remove impurities.
The Earliest Generation of Diamond: The First Find of a Diamond Inclusion in Kimberlitic Olivine
Authors: Pokhilenko Lyudmila , Pokhilenko Nikolay , Malkovets Vladimir , Alifirova Taisia
Published: December 2022

Today, it is known that the majority of diamonds are crystallized mostly from a metasomatic agent close in the main characteristics to carbonatite melts acting upon mantle rocks, and therefore, diamonds are located in the interstitial space of these rocks. So far, diamond has never been found included in other kimberlitic or xenolithic minerals. We have found a diamond inclusion inside the kimberlitic olivine grain, which is the first find of its kind. The diamond crystal is to have been captured by the growing olivine at quite high temperatures (more than 1400 °C) early in the history of the cratonic lithospheric mantle formation. The event had taken place long before the depleted peridotite cooled down to the temperature of the Middle Archean cratonic geotherm corresponding to the diamond stability field at depths where carbonatite melts can react with depleted peridotite, making it a diamond-bearing rock. On the one hand, this find provides evidence that diamonds can crystallize from the high-temperature silicate melt with some carbonate component. On the other hand, the diamond was found coexisting with a sulfide inclusion in the same olivine, i.e., crystallization from a sulfide melt may be another way of diamond formation.
Alteration of Feldspathoids Changes pH of Late-Magmatic Fluids: A Case Study from the Lovozero Peralkaline Massif, Russia
Authors: Mikhailova Julia A. , Pakhomovsky Yakov A. , Lyalina Lyudmila M. , Selivanova Ekaterina A.
Published: December 2022

The 360-370-Ma-old Lovozero peralkaline massif (NW Russia) is a layered nepheline syenitic–foidolitic pluton. In the rocks of the massif, late-stage (auto)metasomatic alterations of rock-forming minerals are quite intense. We studied the products of the alteration of nepheline and sodalite via microtextural, microprobe, and spectroscopic methods. We found that these minerals are extensively replaced by the association between natrolite + nordstrandite ± böhmite ± paranatrolite in accordance with the following reactions: 3Nph + 4H2O → Ntr + Nsd + NaOH; 6Nph + 9H2O → Ntr + Pntr + 2Nsd + 2NaOH; Sdl + 4H2O → Ntr + Nsd + NaOH + NaCl, where Nph is nepheline, Ntr is natrolite, Nsd is nordstrandite, Pntr is paranatrolite, and Sdl is sodalite. As a result, about one-third of the sodium from nepheline (and sodalite) is set free and passes into the fluid. This leads to an increase in the Na/Cl ratio and, hence, the pH of the fluid. An increase in pH stabilizes hyperagpaitic minerals (e.g., ussingite, villiaumite, thermonatrite, and trona), which can crystallize in close proximity to pseudomorphized nepheline and sodalite. Thus, the alteration of feldspathoids increases the pH of late-magmatic fluids, which in turn can lead to the crystallization of hyperagpaitic minerals.
Synthetic Analogs of Marine Alkaloid Aplysinopsin Suppress Anti-Apoptotic Protein BCL2 in Prostate Cancer
Authors: El-Sawy Eslam R. , El-Shahid Zeinab A. , Soliman Ahmed A. F. , Nassrallah Amr , Abdelwahab Ahmed B. , Kirsch Gilbert , Abdelmegeed Heba
Published: December 2022

Aplysinopsins are a class of indole alkaloids that possess various pharmacological activities. Although their action has been studied in regard to many diseases, their effect on prostate cancer has not yet been examined. Therefore, we synthesized a new series of aplysinopsin analogs and investigated their cytotoxic activity against prostate cancer. Five analogs showed high antitumor activity via suppressing the expression of the anti-apoptotic gene Bcl2, simulationously increasing the expression of the pro-apoptotic genes p53, Bax and Caspase 3. The inhibition of BCL2 led to the activation of BAX, which in turn activated Caspase 3, leading to apoptosis. This dual mechanism of action via apoptosis and cell cycle arrest induction is responsible for aplysinopsin analogs antitumor activity. Hence, our newly synthesized analogs are highly promising candidates for further preclinical studies against prostate cancer.
Amaranth Seeds and Sprouts as Functional Ingredients for the Development of Dietary Fiber, Betalains, and Polyphenol-Enriched Minced Tilapia Meat Gels
Authors: Pérez-Ramírez Iza F. , Sotelo-González Ana M. , López-Echevarría Gerardo , Martínez-Maldonado Miguel A.
Published: December 2022

There is an increasing interest in the development of meat processed products enriched with antioxidant dietary fiber to augment the consumption of these health beneficial compounds. This study aimed to evaluate the nutritional, nutraceutical, and antioxidant potential, as well as the physicochemical properties of minced tilapia fillets (meat) gels with added amaranth seed or sprout flours (0%, 2%, 4%, 8%, and 10% w/w). Dietary fiber content was significantly increased with the addition of amaranth seed (1.25–1.75-fold) and sprout flours (1.99–3.21-fold). Tilapia gels with added 10% amaranth seed flour showed a high content of extractable dihydroxybenzoic acid and cinnamic acid, whereas the addition of 10% amaranth sprout flour provided a high and wide variety of bioactive compounds, mainly amaranthine and bound ferulic acid. The addition of amaranth seed and sprout flours increased hardness (1.01–1.73-fold) without affecting springiness, decreased luminosity (1.05–1.15-fold), and increased redness and yellowness. Therefore, amaranth seed and sprout flours could be used as functional ingredients for the development of fish products rich in bioactive compounds.
Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors
Authors: Alkahtani Hamad M. , Zen Amer Alhaj , Obaidullah Ahmad J. , Alanazi Mohammed M. , Almehizia Abdulrahman A. , Ansari Siddique Akber , Aleanizy Fadilah Sfouq , Alqahtani Fulwah Yahya , Aldossari Rana M. , Algamdi Raghad Abdullah , Al-Rasheed Lamees S. , Abdel-Hamided Sami G. , Abdel-Aziz Alaa A.-M. , El-Azab Adel S.
Published: December 2022

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski’s rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.
Resolvin D5 (RvD5) Reduces Renal Damage Caused by LPS Endotoxemia in Female Mice
Authors: Cardoso Renato D. R. , Chambo Sandmary D. , Zaninelli Tiago H. , Bianchini Beatriz H. S. , Silva Matheus Deroco Veloso da , Bertozzi Mariana M. , Saraiva-Santos Telma , Franciosi Anelise , Martelossi-Cebinelli Geovana , Garcia-Miguel Pamela E. , Borghi Sergio M. , Casagrande Rubia , Verri Waldiceu A.
Published: December 2022

In self-revolving gram-negative Escherichia coli infection, Resolvin D5 (RvD5) was found to enhance bacteria phagocytosis and reduce the production of inflammatory mediators, contributing to the resolution of infection. LPS (lipopolysaccharide) is a gram-negative bacterial structure product which activates the immune system and, at high doses, leads to endotoxemia. To our knowledge, the effect of RvD5 against LPS endotoxemia has not been investigated to date. Female Swiss mice received an i.p. treatment with RvD5 (0.1, 1 or 10 ng/animal). After 1 h, they were stimulated with LPS (10 mg/kg, i.v.), and samples were collected after additional 6 h. The resulting data demonstrated that RvD5 protected the kidneys (urea and creatinine serum levels) from tissue injury. These effects were related to an improvement in histopathological parameters and a reduction of enzymatic markers of leukocyte infiltration, pro-inflammatory cytokine (IL-1β, TNF-α, and IL-6) production, and oxidative stress. Antioxidant markers were also increased by RvD5, but IL-10 (an anti-inflammatory cytokine) levels were unaltered. We also observed that RvD5 reduced the infiltration of CD45+ hematopoietic cells into the kidneys, reduced the activation of NFκB and promoted the Nrf2 pathway by reducing Keap-1 levels. Our data indicate that RvD5 may be a therapeutic possibility to reduce kidney lesions in LPS endotoxemia.
The Use of Flavylium Salts as Dynamic Inhibitor Moieties for Human Cb5R
Authors: Martínez-Costa Oscar H. , Rodrigues-Miranda Laura , Clemente Sofia M. , Parola António Jorge , Basilio Nuno , Samhan-Arias Alejandro K.
Published: December 2022

Cytochrome b5 reductase (Cb5R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by Cb5R has been observed. A search for specific inhibitors of Cb5R to understand the role of this protein in these new functions has been initiated. Previous studies have shown the ability of different flavonoids to inhibit Cb5R. Anthocyanins are a subgroup of flavonoids responsible for most red and blue colors found in flowers and fruits. Although usually represented by the flavylium cation form, these species are only stable at rather acidic pH values (pH ≤ 1). At higher pH values, the flavylium cation is involved in a dynamic reaction network comprising different neutral species with the potential ability to inhibit the activities of Cb5R. This study aims to provide insights into the molecular mechanism of interaction between flavonoids and Cb5R using flavylium salts as dynamic inhibitors. The outcome of this study might lead to the design of improved specific enzyme inhibitors in the future.
Fluorescence Lifetimes of NIR-Emitting Molecules with Excited-State Intramolecular Proton Transfer
Authors: Li Yonghao , Dahal Dipendra , Pang Yi
Published: December 2022

Molecular probes based on the excited-state intramolecular proton-transfer (ESIPT) mechanism have emerged to be attractive candidates for various applications. Although the steady-state fluorescence mechanisms of these ESIPT-based probes have been reported extensively, less information is available about the fluorescence lifetime characteristics of newly developed NIR-emitting dyes. In this study, four NIR-emitting ESIPT dyes with different cyanine terminal groups were investigated to evaluate their fluorescence lifetime characteristics in a polar aprotic solvent such as CH2Cl2. By using the time-correlated single-photon counting (TCSPC) method, these ESIPT-based dyes revealed a two-component exponential decay (τ1 and τ2) in about 2–4 nanoseconds (ns). These two components could be related to the excited keto tautomers. With the aid of model compounds (5 and 6) and low-temperature fluorescence spectroscopy (at −189 ℃), this study identified the intramolecular charge transfer (ICT) as one of the major factors that influenced the τ values. The results of this study also revealed that both fluorescence lifetimes and fractional contributions of each component were significantly affected by the probe structures.
Initial Maximum Overlap Method Embedded with Extremely Localized Molecular Orbitals for Core-Ionized States of Large Systems
Authors: Macetti Giovanni , Genoni Alessandro
Published: December 2022

Despite great advances in X-ray absorption spectroscopy for the investigation of small molecule electronic structure, the application to biosystems of experimental techniques developed within this research field remains a challenge. To partially circumvent the problem, users resort to theoretical methods to interpret or predict the X-ray absorption spectra of large molecules. To accomplish this task, only low-cost computational strategies can be exploited. For this reason, some of them are single Slater determinant wavefunction approaches coupled with multiscale embedding techniques designed to treat large systems of biological interest. Therefore, in this work, we propose to apply the recently developed IMOM/ELMO embedding method to the determination of core-ionized states. The IMOM/ELMO technique resulted from the combination of the single Slater determinant Δself-consistent-field-initial maximum overlap approach (ΔSCF-IMOM) with the QM/ELMO (quantum mechanics/extremely localized molecular orbital) embedding strategy, a method where only the chemically relevant region of the examined system is treated at fully quantum chemical level, while the rest is described through transferred and frozen extremely localized molecular orbitals (ELMOs). The IMOM/ELMO technique was initially validated by computing core-ionization energies for small molecules, and it was afterwards exploited to study larger biosystems. The obtained results are in line with those reported in previous studies that applied alternative ΔSCF approaches. This makes us envisage a possible future application of the proposed method to the interpretation of X-ray absorption spectra of large molecules.
Synthesis and Crystal Structure of Adamantylated 4,5,6,7-Tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors); X-ray/DFT/QTAIM/Hirshfeld Surfaces/Molecular Docking Study
Authors: Latosińska Jolanta Natalia , Latosińska Magdalena , Orzeszko Andrzej , Maurin Jan Krzysztof
Published: December 2022

A series of new congeners, 1-[2-(1-adamantyl)ethyl]-1H-benzimidazole (AB) and 1-[2-(1-adamantyl)ethyl]-4,5,6,7-tetrahalogeno-1H-benzimidazole (Hal=Cl, Br, I; tClAB, tBrAB, tIAB), have been synthesized and studied. These novel multi-target ligands combine a benzimidazole ring known to show antitumor activity and an adamantyl moiety showing anti-influenza activity. Their crystal structures were determined by X-ray, while intermolecular interactions were studied using topological Bader’s Quantum Theory of Atoms in Molecules, Hirshfeld Surfaces, CLP and PIXEL approaches. The newly synthesized compounds crystallize within two different space groups, P-1 (AB and tIAB) and P21/c (tClAB and tBrAB). A number of intramolecular hydrogen bonds, C−H⋯Hal (Hal=Cl, Br, I), were found in all halogen-containing congeners studied, but the intermolecular C−H⋯N hydrogen bond was detected only in AB and tIAB, while C−Hal⋯π only in tClAB and tBrAB. The interplay between C−H⋯N and C−H⋯Hal hydrogen bonds and a shift from the strong (C−H⋯Cl) to the very weak (C−H⋯I) attractive interactions upon Hal exchange, supplemented with Hal⋯Hal overlapping, determines the differences in the symmetry of crystalline packing and is crucial from the biological point of view. The hypothesis about the potential dual inhibitor role of the newly synthesized congeners was verified using molecular docking and the congeners were found to be pharmaceutically attractive as Human Casein Kinase 2, CK2, inhibitors, Membrane Matrix 2 Protein, M2, blockers and Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, inhibitors. The addition of adamantyl moiety seems to broaden and modify the therapeutic indices of the 4,5,6,7-tetrahalogeno-1H-benzimidazoles.
Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors
Authors: Jadhav Prerana B. , Jadhav Shailaja B. , Zehravi Mehrukh , Mubarak Mohammad S. , Islam Fahadul , Jeandet Philippe , Khan Sharuk L. , Hossain Nazmul , Rashid Salma , Ming Long Chiau , Sarker Md. Moklesur Rahman , Azlina Mohd Fahami Nur
Published: December 2022

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a–5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber’s guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.
Two Biosensors for the Determination of VEGF-R2 in Plasma by Array SPRi
Authors: Oldak Lukasz , Zelazowska-Rutkowska Beata , Lesniewska Anna , Mrozek Piotr , Skoczylas Marcin , Lukaszewski Zenon , Gorodkiewicz Ewa
Published: December 2022

Vascular endothelial growth factor receptor 2 (VEGF-R2) is a marker of angiogenesis and metastasis of cancer. Two biosensors for the determination of VEGF-R2 in plasma have been developed. One of them is based on a pure gold chip, and the other on a silver/gold bimetallic chip; both have the receptor, monoclonal rabbit antibody specific for human VEGF-R2, attached to the chip via a cysteamine linker. The biosensor with the gold chip exhibits linearity of the analytical signal between 0.03 and 2 ng/mL, a precision of 1.4% and recovery between 99% and 102%. The biosensor with the bimetallic chip exhibits linearity between 0.03 and 1 ng/mL, a precision of 2.2% and recovery between 99% and 103%. Both biosensors tolerate a 1:100 excess of VEGF, VEGF-R1 and VEGF-R3. Both biosensors were validated by parallel determination of VEGF-R2 in 27 different plasma samples using the ELISA immunosensor assay, with very good agreement of the results. Thermodynamic parameters of the interaction of VEGF-R2 with the antibody were determined by QCM (Quartz Crystal Microbalance) and SPRi (Surface Plasmon Resonance imaging) measurements.
Molecular Mechanisms of Aggregation of Canine SOD1 E40K Amyloidogenic Mutant Protein
Authors: Wakayama Kento , Kimura Shintaro , Kobatake Yui , Kamishina Hiroaki , Nishii Naohito , Takashima Satoshi , Honda Ryo , Kamatari Yuji O.
Published: December 2022

Canine degenerative myelopathy (DM) is a human amyotrophic lateral sclerosis (ALS)-like neurodegenerative disease. It is a unique, naturally occurring animal model of human ALS. Canine DM is associated with the aggregation of canine superoxide dismutase 1 (cSOD1), which is similar to human ALS. Almost 100% of cases in dogs are familial, and the E40K mutation in cSOD1 is a major causative mutation of DM. Therefore, it is important to understand the molecular mechanisms underlying cSOD1(E40K) aggregation. To address this, we first analyzed the structural model of wild type cSOD1. Interactions were evident between amino acid E40 and K91. Therefore, the mutation at residue E40 causes loss of the interaction and may destabilize the native structure of cSOD1. Differential scanning fluorimetry revealed that the E40K mutant was less stable than the wild type. Moreover, stability could be recovered by the E40K and K91E double mutation. Acceleration of amyloid fibril formation in vitro and aggregate formation in cells of cSOD1(E40K) was also suppressed by the introduction of this double mutation in thioflavin T fluorescence assay results and in transfectant cells, respectively. These results clearly show the importance of the interaction between amino acid residues E40 and K91 in cSOD1 for the stability of the native structure and aggregation.
Identification of Polyphenol Derivatives as Novel SARS-CoV-2 and DENV Non-Nucleoside RdRp Inhibitors
Authors: Gao Shenghua , Song Letian , Xu Hongtao , Fikatas Antonios , Oeyen Merel , De Jonghe Steven , Zhao Fabao , Jing Lanlan , Jochmans Dirk , Vangeel Laura , Cheng Yusen , Kang Dongwei , Neyts Johan , Herdewijn Piet , Schols Dominique , Zhan Peng , Liu Xinyong
Published: December 2022

The Coronavirus Disease 2019 (COVID-19) and dengue fever (DF) pandemics both remain to be significant public health concerns in the foreseeable future. Anti-SARS-CoV-2 drugs and vaccines are both indispensable to eliminate the epidemic situation. Here, two piperazine-based polyphenol derivatives DF-47 and DF-51 were identified as potential inhibitors directly blocking the active site of SARS-CoV-2 and DENV RdRp. Data through RdRp inhibition screening of an in-house library and in vitro antiviral study selected DF-47 and DF-51 as effective inhibitors of SARS-CoV-2/DENV polymerase. Moreover, in silico simulation revealed stable binding modes between the DF-47/DF-51 and SARS-CoV-2/DENV RdRp, respectively, including chelating with Mg2+ near polymerase active site. This work discovered the inhibitory effect of two polyphenols on distinct viral RdRp, which are expected to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with new scaffold.
Reaction Mechanism for the Removal of NOx by Wet Scrubbing Using Urea Solution: Determination of Main and Side Reaction Paths
Authors: Gan Lina , Liu Yang , Ye Peng , Niu Hejingying , Li Kezhi
Published: December 2022

Secondary problems, such as the occurrence of side reactions and the accumulation of by-products, are a major challenge in the application of wet denitrification technology through urea solution. We revealed the formation mechanism of urea nitrate and clarified the main and side reaction paths and key intermediates of denitrification. Urea nitrate would be separated from urea absorption solution only when the concentration product of [urea], [H+] and [NO3−] was greater than 0.87~1.22 mol3/L3. The effects of the urea concentration (5–20%) and reaction temperature (30–70 °C) on the denitrification efficiency could be ignored. Improving the oxidation degree of the flue gas promoted the removal of nitrogen oxides. The alkaline condition was beneficial to the dissolution process, while the acidic condition was beneficial to the reaction process. As a whole, the alkaline condition was the preferred process parameter. The research results could guide the optimization of process conditions in theory, improve the operation efficiency of the denitrification reactor and avoid the occurrence of side reactions.
Quaternary Ammonium Groups Modified Magnetic Cyclodextrin Polymers for Highly Efficient Dye Removal and Sterilization in Water Purification
Authors: Liu Bingjie , Wang Shuoxuan , Wang He , Wang Yong , Xiao Yin , Cheng Yue
Published: December 2022

Water recovery is a significant proposition for human survival and sustainable development, and we never stop searching for more efficient, easy-operating, low-cost and environmentally friendly methods to decontaminate water bodies. Herein, we combined the advantages of β-cyclodextrin (β-CD), magnetite nanoparticles (MNs), and two kinds of quaternary ammonium salts to synthesize two porous quaternary ammonium groups capped magnetic β-CD polymers (QMCDP1 and QMCDP2) to remove organic pollutants and eradicate pathogenic microorganisms effectively through a single implementation. In this setting, β-CD polymer (CDP) was utilized as the porous substrate material, while MNs endowed the materials with excellent magnetism enhancing recyclability in practical application scenarios, and the grafting of quaternary ammonium groups was beneficial for the adsorption of anionic dyes and sterilization. Both QMCDPs outperformed uncapped MCDPs in their adsorption ability of anionic pollutants, using methyl blue (MB) and orange G (OG) as model dyes. Additionally, QMCDP2, which was modified with longer alkyl chains than QMCDP1, exhibits superior bactericidal efficacy with a 99.47% removal rate for Staphylococcus aureus. Accordingly, this study provides some insights into designing a well-performed and easily recyclable adsorbent for simultaneous sterilization and adsorption of organic contaminants in wastewater.
Application of Synthesized Vanadium–Titanium Oxide Nanocomposite to Eliminate Rhodamine-B Dye from Aqueous Medium
Authors: Elamin Mohamed R. , Abdulkhair Babiker Y. , Elamin Nuha Y. , Ibnaouf Khalid H. , Idriss Hajo , Bakheit Rafia , Modwi Abueliz
Published: December 2022

In this study, a V@TiO2 nanocomposite is examined for its ability to eliminate carcinogenic Rhodamine (Rh-B) dye from an aqueous medium. A simple ultrasonic method was used to produce the nanosorbent. In addition, V@TiO2 was characterized using various techniques, including XRD, HRTEM, XPS, and FTIR. Batch mode studies were used to study the removal of Rh-B dye. In the presence of pH 9, the V@TiO2 nanocomposite was able to remove Rh-B dye to its maximum extent. A correlation regression of 0.95 indicated that the Langmuir model was a better fit for dye adsorption. Moreover, the maximum adsorption capacity of the V@TiO2 nanocomposite was determined to be 158.8 mg/g. According to the thermodynamic parameters, dye adsorption followed a pseudo-first-order model. Based on the results of the study, a V@TiO2 nanocomposite can be reused for dye removal using ethanol.
Upcycling Rocha do Oeste Pear Pomace as a Sustainable Food Ingredient: Composition, Rheological Behavior and Microstructure Alone and Combined with Yeast Protein Extract
Authors: Fernandes Ana , Simões Sara , Ferreira Isabel M. P. L. V. O. , Alegria Maria João , Mateus Nuno , Raymundo Anabela , de Freitas Victor
Published: December 2022

This work explores the potential of Rocha do Oeste pear pomace to be used as a sustainable and healthy food ingredient. Moreover, the enrichment with yeast protein extract (YPE) may be useful to design innovative food products. The main goals of this study were to assess pear pomace concerning: (i) chemical composition and antioxidant capacity; (ii) rheology, texture, and microstructure characterization (alone or enriched with YPE), before and after heating. The results showed that pear pomace was a rich source of dietary fibers (74.5% DW), with phenolic compounds (3.9 mg chlorogenic acid equivalents/g dry weight), also presenting antiradical activity (3.90 μmol Trolox equivalents/g DW). Pear pomace showed a shear thinning behavior and a typical soft-gel behavior, which was not affected by YPE enrichment, thus suggesting that YPE did not affect pear pomace technological properties. Thermal treatment also did not alter pear pomace rheological properties. YPE addition induced a decrease in the apparent viscosity and a destabilizing effect, compared to the samples that were subjected to thermal processing. These results highlight the importance of pear pomace and the use of YPE for protein enrichment, opening new opportunities for their exploitation.
Synthesis, Biological Evaluation, DNA Binding, and Molecular Docking of Hybrid 4,6-Dihydrazone Pyrimidine Derivatives as Antitumor Agents
Authors: Lan Hairong , Song Junying , Yuan Juan , Xing Aiping , Zeng Dai , Hao Yating , Zhang Zhenqiang , Feng Shuying
Published: December 2022

In the present paper, on the basis of molecular hybridization, a series of 4,6-dihydrazone pyrimidine derivatives containing the pyridine moiety were synthesized, structurally characterized, and evaluated in vitro for their antitumor activity. According to the results, all the tested compounds demonstrated broad-spectrum antitumor activity against selected tumor cell lines (MCF-7, BGC-823, A549, and BEL-7402) and no obvious toxicity toward normal cells HL-7702. In particular, compounds 10a and 10f were found to be the most promising antitumor agents among the tested compounds against BGC-823 cells (IC50 = 9.00 μM and 7.89 μM) and BEL-7402 cells (IC50 = 6.70 μM and 7.66 μM), respectively. Compounds 10a and 10f exhibited higher potency against BGC-823 and BEL-7402 than the positive control 5-FU (IC50 = 15.18 μM and 15.81 μM). Further mechanism investigations demonstrated that compounds 10a and 10f could significantly increase the level of cellular ROS and induce early apoptosis of BGC-823 cells in a dose-dependent manner. Moreover, the DNA binding results from UV/Vis, CD spectroscopy, and molecular docking studies indicated that 10a and 10f bind with DNA via groove binding and partial intercalation. These results demonstrated that 10a and 10f may serve as novel lead compounds for the discovery of more dihydrazone pyrimidine derivatives with improved antitumor potency and selectivity.
Carbon Nanotube Supported Molybdenum Carbide as Robust Electrocatalyst for Efficient Hydrogen Evolution Reaction
Authors: Huang Yunjie , Bao Yaqi , Huang Tieqi , Hu Chengzhi , Qiu Haiou , Liu Hongtao
Published: December 2022

Molybdenum carbide is considered to be one of the most competitive catalysts for hydrogen evolution reaction (HER) regarding its high catalytic activity and superior corrosion resistance. But the low electrical conductivity and poor interfacial contact with the current collector greatly inhibit its practical application capability. Herein, carbon nanotube (CNT) supported molybdenum carbide was assembled via electrostatic adsorption combined with complex bonding. The N-doped molybdenum carbide nanocrystals were uniformly anchored on the surfaces of amino CNTs, which depressed the agglomeration of nanoparticles while strengthening the migration of electrons. The optimized catalyst (250-800-2h) showed exceptional electrocatalytic performance towards HER under both acidic and alkaline conditions. Especially in 0.5 M H2SO4 solution, the 250-800-2h catalyst exhibited a low overpotential of 136 mV at a current density of 10 mA/cm2 (η10) with the Tafel slope of 49.9 mV dec−1, and the overpotential only increased 8 mV after 20,000 cycles of stability test. The active corrosive experiment revealed that more exposure to high-activity γ-Mo2N promoted the specific mass activity of Mo, thus, maintaining the catalytic durability of the catalyst.
Recent Advances in Surface Modifications of Elemental Two-Dimensional Materials: Structures, Properties, and Applications
Authors: Chen Junbo , Wang Chenhui , Li Hao , Xu Xin , Yang Jiangang , Huo Zhe , Wang Lixia , Zhang Weifeng , Xiao Xudong , Ma Yaping
Published: December 2022

The advent of graphene opens up the research into two-dimensional (2D) materials, which are considered revolutionary materials. Due to its unique geometric structure, graphene exhibits a series of exotic physical and chemical properties. In addition, single-element-based 2D materials (Xenes) have garnered tremendous interest. At present, 16 kinds of Xenes (silicene, borophene, germanene, phosphorene, tellurene, etc.) have been explored, mainly distributed in the third, fourth, fifth, and sixth main groups. The current methods to prepare monolayers or few-layer 2D materials include epitaxy growth, mechanical exfoliation, and liquid phase exfoliation. Although two Xenes (aluminene and indiene) have not been synthesized due to the limitations of synthetic methods and the stability of Xenes, other Xenes have been successfully created via elaborate artificial design and synthesis. Focusing on elemental 2D materials, this review mainly summarizes the recently reported work about tuning the electronic, optical, mechanical, and chemical properties of Xenes via surface modifications, achieved using controllable approaches (doping, adsorption, strain, intercalation, phase transition, etc.) to broaden their applications in various fields, including spintronics, electronics, optoelectronics, superconducting, photovoltaics, sensors, catalysis, and biomedicines. These advances in the surface modification of Xenes have laid a theoretical and experimental foundation for the development of 2D materials and their practical applications in diverse fields.
Traditional Machine and Deep Learning for Predicting Toxicity Endpoints
Authors: Norinder Ulf
Published: December 2022

Molecular structure property modeling is an increasingly important tool for predicting compounds with desired properties due to the expensive and resource-intensive nature and the problem of toxicity-related attrition in late phases during drug discovery and development. Lately, the interest for applying deep learning techniques has increased considerably. This investigation compares the traditional physico-chemical descriptor and machine learning-based approaches through autoencoder generated descriptors to two different descriptor-free, Simplified Molecular Input Line Entry System (SMILES) based, deep learning architectures of Bidirectional Encoder Representations from Transformers (BERT) type using the Mondrian aggregated conformal prediction method as overarching framework. The results show for the binary CATMoS non-toxic and very-toxic datasets that for the former, almost equally balanced, dataset all methods perform equally well while for the latter dataset, with an 11-fold difference between the two classes, the MolBERT model based on a large pre-trained network performs somewhat better compared to the rest with high efficiency for both classes (0.93–0.94) as well as high values for sensitivity, specificity and balanced accuracy (0.86–0.87). The descriptor-free, SMILES-based, deep learning BERT architectures seem capable of producing well-balanced predictive models with defined applicability domains. This work also demonstrates that the class imbalance problem is gracefully handled through the use of Mondrian conformal prediction without the use of over- and/or under-sampling, weighting of classes or cost-sensitive methods.
Efficient Antibacterial/Antifungal Activities: Synthesis, Molecular Docking, Molecular Dynamics, Pharmacokinetic, and Binding Free Energy of Galactopyranoside Derivatives
Authors: Ahmmed Faez , Islam Anis Ul , Mukhrish Yousef E. , Bakri Youness El , Ahmad Sajjad , Ozeki Yasuhiro , Kawsar Sarkar M. A.
Published: December 2022

The chemistry and biochemistry of carbohydrate esters are essential parts of biochemical and medicinal research. A group of methyl β-d-galactopyranoside (β-MGP, 1) derivatives was acylated with 3-bromobenzoyl chloride and 4-bromobenzoyl chloride in anhydrous N,N-dimethylformamide/triethylamine to obtain 6-O-substitution products, which were subsequently converted into 2,3,4-tri-O-acyl derivatives with different aliphatic and aromatic substituents. Spectroscopic and elemental data exploration of these derivatives confirmed their chemical structures. In vitro biological experiments against five bacteria and two fungi and the prediction of activity spectra for substances (PASS) revealed ascending antifungal and antibacterial activities compared with their antiviral activities. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were performed for two derivatives, 3 and 9, based on their antibacterial activities. Most of these derivatives showed >780% inhibition of fungal mycelial growth. Density functional theory (DFT) was used to calculate the chemical descriptors and thermodynamic properties, whereas molecular docking was performed against antibacterial drug targets, including PDB: 4QDI, 5A5E, 7D27, 1ZJI, 3K8E, and 2MRW, and antifungal drug targets, such as PDB: 1EA1 and 1AI9, to identify potential drug candidates for microbial pathogens. A 100 ns molecular dynamics simulation study revealed stable conformation and binding patterns in a stimulating environment by their uniform RMSD, RMSF, SASA, H-bond, and RoG profiles. In silico pharmacokinetic and quantitative structure–activity relationship (QSAR) calculations (pIC50 values 3.67~8.15) suggested that all the designed β-MGP derivatives exhibited promising results due to their improved kinetic properties with low aquatic and non-aquatic toxicities. These biological, structure–activity relationship (SAR) [lauroyl-(CH3(CH2)10CO-) group was found to have potential], and in silico computational studies revealed that the newly synthesized MGP derivatives are potential antibacterial/antifungal candidates and can serve as therapeutic targets for human and plant pathogens.
N,N′-Diaryldihydrophenazines as a Sustainable and Cost-Effective Alternative to Precious Metal Complexes in the Photoredox-Catalyzed Alkylation of Aryl Alkyl Ketones
Authors: Dulov Dmitry A. , Bogdanov Alexey V. , Dorofeev Sergey G. , Magdesieva Tatiana V.
Published: December 2022

An inexpensive and highly efficient metal-free alternative to commonly used Ru- and Ir-based catalysts was proposed. It was shown that the new 2,7-di-tert-butyl-5,10-bis(4-trifluoromethylphenyl)-5,10-dihydrophenazine outcompeted the iridium phenylpyridyl complex in photoredox activity in the alkylation of silyl enol ethers yielding aryl alkyl ketones. The reaction occurred under visible light irradiation at room temperature and was also applicable to drug derivatives (ibuprofen and naproxen). In-depth photophysical, electrochemical, and quantum chemical studies showed that the aforementioned N,N-diaryldihydrophenazine exhibited enhanced properties that were essential for the photoredox catalysis (a long-lived triplet excited state, strong reducing ability, high stability of the radical cations formed in single-electron-transfer event, and chemical inertness of the catalyst with respect to reactants). Importantly, the substituted N,N′-diaryldihydrophenazines could be obtained directly from diaryl amines; a facile, easily handled and scaled-up one-pot synthetic procedure was elaborated.