bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerating Molecular Docking using Machine Learning Methods
Authors: Bande Abdulsalam Y. , Baday Sefer 
Published: June 2024

AbstractVirtual screening (VS) is one of the well‐established approaches in drug discovery which speeds up the search for a bioactive molecule and, reduces costs and efforts associated with experiments. VS helps to narrow down the search space of chemical space and allows selecting fewer and more probable candidate compounds for experimental testing. Docking calculations are one of the commonly used and highly appreciated structure‐based drug discovery methods. Databases for chemical structures of small molecules have been growing rapidly. However, at the moment virtual screening of large libraries via docking is not very common. In this work, we aim to accelerate docking studies by predicting docking scores without explicitly performing docking calculations. We experimented with an attention based long short‐term memory (LSTM) neural network for an efficient prediction of docking scores as well as other machine learning models such as XGBoost. By using docking scores of a small number of ligands we trained our models and predicted docking scores of a few million molecules. Specifically, we tested our approaches on 11 datasets that were produced from in‐house drug discovery studies. On average, by training models using only 7000 molecules we predicted docking scores of approximately 3.8 million molecules with R2 (coefficient of determination) of 0.77 and Spearman rank correlation coefficient of 0.85. We designed the system with ease of use in mind. All the user needs to provide is a csv file containing SMILES and their respective docking scores, the system then outputs a model that the user can use for the prediction of docking score for a new molecule.
Kinematic analysis of kinases and their oncogenic mutations – Kinases and their mutation kinematic analysis
Authors: Chen Xiyu , Leyendecker Sigrid 
Published: June 2024

AbstractProtein kinases are crucial cellular enzymes that facilitate the transfer of phosphates from adenosine triphosphate (ATP) to their substrates, thereby regulating numerous cellular activities. Dysfunctional kinase activity often leads to oncogenic conditions. Chosen by using structural similarity to 5UG9, we selected 79 crystal structures from the PDB and based on the position of the phenylalanine side chain in the DFG motif, we classified these 79 crystal structures into 5 group clusters. Our approach applies our kinematic flexibility analysis (KFA) to explore the flexibility of kinases in various activity states and examine the impact of the activation loop on kinase structure. KFA enables the rapid decomposition of macromolecules into different flexibility regions, allowing comprehensive analysis of conformational structures. The results reveal that the activation loop of kinases acts as a “lock” that stabilizes the active conformation of kinases by rigidifying the adjacent α‐helices. Furthermore, we investigate specific kinase mutations, such as the L858R mutation commonly associated with non‐small cell lung cancer, which induces increased flexibility in active‐state kinases. In addition, through analyzing the hydrogen bond pattern, we examine the substructure of kinases in different states. Notably, active‐state kinases exhibit a higher occurrence of α‐helices compared to inactive‐state kinases. This study contributes to the understanding of biomolecular conformation at a level relevant to drug development.
Association Between the Postprandial Response to an Oral Glucose Tolerance Test and Anthropometric Changes After an 8‐Week Low‐Calorie Formula Diet – Results From the Lifestyle Intervention (LION) Study
Authors: Reik Anna , Schauberger Gunther , Wiechert Meike , Hauner Hans , Holzapfel Christina 
Published: June 2024

ScopeInterindividual variations in postprandial metabolism and weight loss outcomes have been reported. The literature suggests links between postprandial metabolism and weight regulation. Therefore, the study aims to evaluate if postprandial glucose metabolism after a glucose load predicts anthropometric outcomes of a weight loss intervention.Methods and resultsAnthropometric data from adults with obesity (18–65 years, body mass index [BMI] 30.0–39.9 kg m−2) are collected pre‐ and post an 8‐week formula‐based weight loss intervention. An oral glucose tolerance test (OGTT) is performed at baseline, from which postprandial parameters are derived from glucose and insulin concentrations. Linear regression models explored associations between these parameters and anthropometric changes (∆) postintervention. A random forest model is applied to identify predictive parameters for anthropometric outcomes after intervention. Postprandial parameters after an OGTT of 158 participants (63.3% women, age 45 ± 12, BMI 34.9 ± 2.9 kg m−2) reveal nonsignificant associations with changes in anthropometric parameters after weight loss (p > 0.05). Baseline fat‐free mass (FFM) and sex are primary predictors for ∆ FFM [kg].ConclusionPostprandial glucose metabolism after a glucose load does not predict anthropometric outcomes after short‐term weight loss via a formula‐based low‐calorie diet in adults with obesity.
Models and sufficiency interpretation for estimating critical soil test values for the Fertilizer Recommendation Support Tool
Authors: Slaton N. A. , Pearce A. , Gatiboni L. , Osmond D. , Bolster C. , Miquez F. , Clark J. , Dhillon J. , Farmaha B. , Kaiser D. , Lyons S. , Margenot A. , Moore A. , Ruiz Diaz D. , Sotomayor D. , Spackman J. , Spargo J. , Yost M. 
Published: June 2024

AbstractSoil test correlation determines whether a soil test can be used to predict the need for fertilization based on the critical soil test value (CSTV). Our objectives were to compare the CSTV estimated from five combinations of correlation models and yield sufficiency interpretations and to select one method for soil test correlation performed with the Fertilizer Recommendation Support Tool (FRST). Four models were fit to three datasets with strong (Mehlich‐1 K), moderate (Mehlich‐3 K), or weak (Olsen P) correlations between soil test P or K and crop relative yield. We tested the arcsine‐log calibration curve (ALCC), exponential (EXP), linear plateau (LP), and quadratic plateau (QP) models. The CSTV was defined as 95% of the maximum predicted yield for the ALCC and EXP methods, the join point for LP, and both the join point and 95% of the maximum for the QP providing five CSTV predictions. The five CSTVs ranged from 46 to 66 mg kg−1 for the Mehlich‐1 K dataset, 115 to 165 mg kg−1 for the Mehlich‐3 K dataset, and 7 to 16 mg kg−1 for the Olsen P dataset. Ten pairwise comparisons showed the estimated CSTV was numerically and sometimes statistically influenced by the model and sufficiency level interpretation. Despite differences among CSTVs, the frequency of significant yield responses above and below the predicted CSTV was generally comparable among the methods, with false‐negative errors occurring at 0%–18% of sites for a given dataset. The QP model with a CSTV at 95% of the predicted maximum was selected as the modeling approach for FRST.
Effect of Trastuzumab and Lonidamine‐Loaded Lipid Nanoparticles (LNP) on HER2+ Breast Cancer
Authors: Ozlem Zurnaci Fatma , Ozdatli Kurtulus Sukran , Sengel Turk Ceyda Tuba , Hascicek Canan , Guzel Mustafa 
Published: June 2024

AbstractOur study involves inhibition of glycolysis and inhibition of the HER2 pathway, which is highly expressed in many types of cancer. Decreased survival, negative metastasis, and induced apoptosis are expected due to the combined inhibition of these two targets. Trastuzumab was used as the HER2 inhibitor and lonidamine was used as the HK2 inhibitor. Lonidamine (LND) was delivered to cells as hybrid nanoparticles to enhance the effect of lonidamine and make it target specific. Separate cytotoxicity studies were conducted for LND, LND‐NP and Tmab. While application of lonidamine alone gave an IC50 value of 124.6 μM, application in NP reduced the IC50 value to 44.18 μM. In addition, the combination of Tmab and LND‐NP showed synergistic effects compared to treatments alone in other analyses. On the aspect of apoptosis, this combination showed a 14‐fold increased apoptosis compared to the control group. This combination therapy can prevent drug resistance. In addition, the hybrid nanoparticle structure used will prevent the formation of toxicity as it will ensure that LND is administered to the body with less repetition. Our study aims to minimize the negative effects of the chemotherapy process by improving it with various variations in future studies.
Post‐Synthetic Modification of Mixed‐Metal UiO‐66 Framework for Rapid Neutralization of Chemical Warfare Agent Simulants
Authors: Kumar Yogesh , Banerjee Shaibal 
Published: June 2024

AbstractMetal‐organic frameworks (MOFs) are a promising class of materials for catalysis, offering unique opportunities for designing efficient and selective catalysts. In this study, we have focused on the synthesis and catalytic activity of a novel mixed metal MOF, Ce/Zr−UiO‐66@LiOtBu, designed for the rapid hydrolysis of chemical warfare agents simulants: dimethyl 4‐nitrophenyl phosphate (DMNP) and 2‐chloroethyl ethyl sulfide (CEES). This MOF was thoroughly characterized using powder X‐ray diffraction (PXRD), BET surface area, and inductively coupled plasma optical emission spectrometry (ICP‐OES). The catalytic performance of Ce/Zr−UiO‐66@LiOtBu was monitored in the hydrolysis of DMNP and CEES by using 31P NMR and GC‐MS respectively. Remarkably, the MOF demonstrated rapid and efficient catalytic activity, breaking the P−O bond in DMNP with 2 min and the hydrolysis of CEES was observed in less than 45 min The results suggest the potential application of Ce/Zr−UiO‐66@LiOtBu as a robust catalyst in the detoxification of chemical warfare agent simulants. Our findings highlight the novelty of Ce/Zr−UiO‐66@LiOtBu as a catalytically active MOF, showcasing the successful integration of cerium ions and lithium tert‐butoxide to enhance basicity.
Antibacterial Effect, ADMET Properties, and Molecular Docking of Morpholine Derivatives with Varying Alkyl Chain Length Against Methicillin Resistant Staphylococcus aureus (MRSA) Isolates
Authors: Ahumada‐Santos Yesmi Patricia , Sánchez‐Lugo Yesenia , Romero‐Ávila Margarita , Maldonado‐Domínguez Mauricio , López‐Angulo Gabriela , Báez‐Flores María Elena , Díaz‐Camacho Sylvia Paz , Nieto‐López María Mercedes , Valenzuela‐Ramirez Gladymar Guadalupe , Pérez Blas Flores , Parra‐Unda Jesús Ricardo 
Published: June 2024

AbstractIn this work, we synthesized a series of nine tetraalkylammonium salts derived from N‐methyl morpholine and assessed their antibacterial efficacy against Methicillin‐Resistant Staphylococcus aureus (MRSA). The investigated morpholinium cations differ by the length of one linear alkyl chain, which ranges from 1 to 18 carbon atoms. We found that compounds with alkyl chains in the n‐C12H25‐(n‐dodecyl) to C16H33‐(n‐hexadecyl) display the highest bactericidal effects, exhibiting Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of 3.9 μg/mL – surpassing the effectiveness of the commercial drug Linezolid. Conversely, compounds with shorter chains (<5 carbon atoms) are inactive against MRSA, establishing a clear structure‐activity relationship. Assays on A. salina reveal that short‐alkyl‐chain morpholinium derivatives, inactive against MRSA), are moderately toxic, while the strongest bactericides of our set demonstrate high or extreme toxicity to A. salina. Our findings underscore the potential of morpholine derivatives as a means to control Methicillin‐Resistant Staphylococcus aureus and pinpoint the need to develop safe applications for these compounds given their potential toxicity.
Effects of Br Substitution on Inorganic Rudorffite AgBiI4 for Stable, Pb‐Free Solar Cells
Authors: Jeon Byeong‐Cheol , Kim Jinhyun , Moon Taeho 
Published: June 2024

AbstractDespite the rapid development of Pb‐based perovskites, the presence of toxic Pb and insufficient stability remain discouraging factors for the commercialization of perovskite solar cells. Therefore, research on Pb‐free absorbers exhibiting long‐term stability is required. Herein, AgBi(I1−xBrx)4 thin films having a hexagonal rudorffite structure were fabricated using a solution process in ambient atmosphere for cost‐effective and environmentally benign photovoltaics. Br substitution increases the grain size and results in a pinhole‐free morphology. Furthermore, photoluminescence analyses confirm that Br substitution reduces the trap‐state density. Consequently, device efficiency is enhanced through Br substitution. Importantly, Br substitution results in considerably improved device stability, with devices maintaining 80 % of their initial efficiency for 26 days in ambient atmosphere without encapsulation.
The Role of Catechol in Caffeic Acid Phenethyl Ester Derivatives for Neuroprotective Effects
Authors: Hao Yameng 
Published: June 2024

AbstractNeurodegenerative disorders are chronic, progressive neurological diseases characterized by damage to neuron cells. Oxidative stress and neuroinflammation play crucial roles in inducing these disorders. Caffeic acid phenethyl ester (CAPE) and its sulfone derivatives have demonstrated antioxidant and anti‐inflammatory effects, suggesting their potential as neuroprotective agents. In this study, 8 sulfone derivatives were designed and synthesized to explore the importance of catechol and structure–activity relationship of CAPE sulfone derivatives. Hydroxyl groups in catechol were replaced by ‐NO2, ‐NH2 or ‐H, and their free radical scavenging, antioxidant, and anti‐inflammatory abilities were evaluated. It was found that the antioxidant activitiy was dominated by the catechol moiety in CAPE derivatives, while the anti‐inflammtory activity was not. Furthermore, the stabilization of catechol after affording H⋅ to eliminate free radicals possibly occurred through hydrogen bond ranther than electron transfer via p‐π conjugation. After the analysis, all the target compounds lost antioxidant properties at cellular level, and among them, the target compound (E)‐2‐amino‐4‐(2‐(phenethylsulfonyl)vinyl) phenol with p‐NH2 and m‐OH showed the best free radical scavaging acivitity and retained anti‐inflammatory activity.
Molybdenum (VI) Complexes and their Dual Role as Antidiabetic and Anticancer Agents
Authors: Saravanan Tharani , Sheela Angappan 
Published: June 2024

AbstractTwo molybdenum complexes, MoHL1 and MoHL2, are prepared from the corresponding tetradentate salen type (ONNO) ligands, HL1 and HL2, obtained from 3, 5‐dichloro salicylaldehyde, and substituted o‐phenylenediamines. The complexes are characterized by 1H NMR, FTIR, HRMS, and UV‐visible spectral techniques. The DFT studies provide insight into their structural parameters. The band gap energy and molecular orbital energies influence the charge transfer interactions within the molecule. Further, the complexes are assessed for their antioxidant efficacy, α–amylase inhibitory potential, binding propensity with deoxyribonucleic acid, and cytotoxicity studies against breast cancer cell line, MCF7. The DPPH assay demonstrates high radical scavenging ability, as evidenced by the IC50 value of 133.85±1.18 μg/mL, higher than ascorbic acid. From the results of α–amylase inhibitory assay, MoHL1 shows good inhibitory action with the IC50 value of 32.72±2.49 μg/mL higher than that of the standard acarbose. The absorption titration method, to track the binding interactions of the metal complexes with DNA, shows a marked hyperchromic effect indicating preferential binding of the complexes to the grooves of DNA helical structure. MoHL2 exerts higher cytotoxicity against cancer cell lines than MoHL1. Thus, the complexes have the potential to be developed as antidiabetic and anticancer agents.
A Theoretical and Computational Study of Structure‐Property Relationship in Five Binary Liquid Alloys
Authors: Singh Arvind , Patel Raj Kumar , Mishra Raj Kumar , Lalneihpuii R. 
Published: June 2024

AbstractA theoretical model is proposed in this work for the evaluation of composition‐dependent thermophysical properties such as the isothermal compressibility, velocity of sound and Debye temperature of liquid binary alloys. Using a square‐well (SW) model potential function under mean spherical model approximation, the composition‐dependent atomic‐level structural functions of Al1‐xCux, Ag1‐xCux, Au1‐xCux, Ag1‐xAlx, and Au1‐xAgx alloys have been determined and compared with available experimental data. An extensive computation was done to calculate the composition‐dependent isothermal compressibility through the structure factor in the long wavelength limit (k→0), and then we employed this data to investigate the velocity of sound in the considered melts. This yields the fundamental maximum frequency with which the constituent particles are vibrating in the melts and is used to determine the composition‐dependent Debye temperature, ΘD. The computed Debye temperature of considered melts using the Square‐well potential function is found to be in satisfactory agreement with the available DFT and MD simulation results.
Fly‐Ash Cenosphere as Non‐Porous Ag‐Nanoparticle Support for Epoxidation of Styrene
Authors: Tarasova N. , Khanov M. , Vorobiev D. , Abramyan A. , Uchaev D. , Sozykin S. , Bol'shakov O. 
Published: June 2024

AbstractThe global strategy to reduce waste production implies development of recycling technologies and conversion of various waste into value‐added products. Fly ash is an industrial waste produced in a large amount. It comprised an aluminosilicate cenosphere, which seems perspective as a support for heterogeneous catalysts. Here we report the preparation and application of heterogeneous silver nanocatalysts deposited on cenosphere in the epoxidation reaction, a relevant process for preparation of valuable organic precursors and target chemicals. Reductive wet deposition method yields Ag nano‐dispersed coating of improved quality represented by Ag particles of about 2.7 nm on the surface of the microspheres size of 50–250 microns for catalytic synthesis of styrene‐oxide. The 0.1 mmol/g Ag/cenosphere provided best catalytic results with threefold excess oftret‐butyl hydroperoxide in acetonitrile at 80 °C. Comparison of fly ash cenosphere with other supports suggests that low porosity of microspherical support allows for an easier access of reagents to active sites of the catalyst and significantly increases the yield of epoxide and selectivity of the reaction.
Cu‐Catalyzed Synthesis of Coumarin‐1,2,3‐Triazole Hybrids connected with Quinoline or Pyridine Framework**
Authors: Douka Matina D. , Sigala Ioanna M. , Nikolakaki Eleni , Prousis Kyriakos C. , Hadjipavlou‐Litina Dimitra J. , Litinas Konstantinos E. 
Published: June 2024

AbstractCoumarin‐1,2,3‐triazole hybrids connected to quinoline or pyridine framework have been synthesized in good to excellent yield by the 1,3‐dipolar azide alkyne cycloaddition reaction (CuACC) of 4‐azidocoumarin with propargyl quinoline or propargyl pyridine derivatives in the presence of CuSO4.5H2O or CuI as catalyst. Similar reaction of 4‐azidocoumarin or tetrazolo[1,5‐a]pyridine with 4‐propargyloxycoumarin and 4‐propargylaminocoumarin resulted in the synthesis of the corresponding coumarin‐1,2,3‐triazole hybrids. Some preliminary screening test for some biological activities of new compounds have been performed.
Evaluating the impact of metabolic and cognitive stress on ghrelin and nesfatin‐1 hormones in patients with diabetes and diabetic depression
Authors: Algul Sermin , Ozcelik Oguz 
Published: June 2024

AbstractNesfatin‐1 and ghrelin, initially recognised as hormones involved in regulating energy, have emerged as crucial players with vital functions in various human body systems. In this study, we conducted a comparative assessment of nesfatin‐1 and ghrelin responses in individuals experiencing metabolic stress due to diabetes, those with depressive diabetes characterised by both metabolic and mental stress, and healthy controls. We collected blood samples from a total of 90 participants, consisting of 30 people with type II diabetes mellitus (DM), 30 people with type II DM and major depressive disorders, and 30 healthy individuals. Diabetes was diagnosed based on glycated haemoglobin (HbA1c) levels, while depression was assessed using DSM‐V criteria. Insulin resistance (HOMA‐IR) was calculated, and serum ghrelin and nesfatin‐1 levels were measured using ELISA kits. We observed statistically significant decreases in nesfatin‐1 and ghrelin levels in the diabetic group (p < 0.0001). However, in the depressive diabetic group, nesfatin‐1 levels increased significantly, while ghrelin levels decreased further. The nesfatin‐1 to ghrelin ratio decreased in the diabetic group but increased significantly in the depressive diabetic group (p < 0.0001). Nesfatin‐1 and ghrelin hormones exhibit parallel impacts in response to metabolic stress, but nesfatin‐1 demonstrates contrasting actions compared to ghrelin when mental stress is added to metabolic stress. The findings of this study suggest that nesfatin‐1 and ghrelin hormones may play active roles as protective, prognostic, and even etiological factors in various stress situations, particularly those involving mental stress, in addition to their known functions in regulating energy.
Leaf‐Inspired Hetero‐Structure WS2/WO3 In Situ Embedded on Pomelo Peel Derived Carbon for Supercapacitor and Capacitive Deionization
Authors: Zheng Yujing , Lian Yue , Zhao Jing , Hu Yong Feng , Zhang Huaihao 
Published: June 2024

AbstractComposite materials have occupied a reliable position in electrochemical energy storage and conversion due to their double electric layer and pseudocapacitance. In this work, a leaf‐like heterostructure composite, obtained by peeling – carbonizing – in situ sulfuration/oxidation approach for the first time, is investigated as electrode material for electrochemical capacitance behavior. The thin and highly active transition metal WS2 acts as an energetic “blade” to trap free ions, which are then transported across the material through a strong “tendon skeleton” WO3. The derived carbon PPC with a large aspect ratio holds up the overall leaf structure, also as a “warehouse” for ion storage, thus enhancing the conductivity and wettability of the material. The above three (WS2+WO3+PPC) synergistically provide outstanding double‐layer capacitance and pseudocapacitance. In particular, the vacancy defects, constructed at the heterogenous interface from WS2‐WO3 in situ growth, can still achieve superior ion absorption/desorption ability even under large current density and high concentration brackish solution.
Stabilizing High‐Valence Copper(I) Sites with Cu–Ni Interfaces Enhances Electroreduction of CO2 to C2+ Products
Authors: Du Yi‐Ran , Li Xiao‐Qiang , Yang Xian‐Xia , Duan Guo‐Yi , Chen Yong‐Mei , Xu Bao‐Hua 
Published: June 2024

AbstractIn this study, the copper‐nickel (Cu–Ni) bimetallic electrocatalysts for electrochemical CO2 reduction reaction(CO2RR) are fabricated by taking the finely designed poly(ionic liquids) (PIL) containing abundant Salen and imidazolium chelating sites as the surficial layer, wherein Cu–Ni, PIL–Cu and PIL–Ni interaction can be readily regulated by different synthetic scheme. As a proof of concept, Cu@Salen‐PIL@Ni(NO3)2 and Cu@Salen‐PIL(Ni) hybrids differ significantly in the types and distribution of Ni species and Cu species at the surface, thereby delivering distinct Cu–Ni cooperation fashion for the CO2RR. Remarkably, Cu@Salen‐PIL@Ni(NO3)2 provides a C2+ faradaic efficiency (FEC2+) of 80.9% with partial current density (jC2+) of 262.9 mA cm−2 at −0.80 V (versus reversible hydrogen electrode, RHE) in 1 m KOH in a flow cell, while Cu@Salen‐PIL(Ni) delivers the optimal FEC2+ of 63.8% at jC2+ of 146.7 mA cm−2 at −0.78 V. Mechanistic studies indicates that the presence of Cu–Ni interfaces in Cu@Salen‐PIL@Ni(NO3)2 accounts for the preserve of high‐valence Cu(I) species under CO2RR conditions. It results in a high activity of both CO2‐to‐CO conversion and C–C coupling while inhibition of the competitive HER.