bluuebunny/crossref_metadata_2025 huggingface dataset:
Does ACE2 mediate the detrimental effect of exposures related to COVID‐19 risk: A Mendelian randomization investigation
Authors: Au Yeung Shiu Lun , Wong Tommy Hon Ting , He Baoting , Luo Shan , Kwok Kin On
Published: October 2022

Objectives

Adiposity, smoking, and lower socioeconomic position (SEP) increase COVID‐19 risk while the association of vitamin D, blood pressure, and glycemic traits in COVID‐19 risk were less clear. Whether angiotensin‐converting enzyme 2 (ACE2), the key receptor for SARS‐CoV‐2, mediates these associations has not been investigated. We conducted a Mendelian randomization study to assess the role of these exposures in COVID‐19 and mediation by ACE2.

Methods

We extracted genetic variants strongly related to various exposures (vitamin D, blood pressure, glycemic traits, smoking, adiposity, and educational attainment [SEP proxy]), and ACE2 cis‐variants from genome‐wide association studies (GWAS, n ranged from 28 204 to 3 037 499) and applied them to GWAS summary statistics of ACE2 (n = 28 204) and COVID‐19 (severe, hospitalized, and susceptibility, n ≤ 2 942 817). We used inverse variance weighted as the main analyses, with MR‐Egger and weighted median as sensitivity analyses. Mediation analyses were performed based on product of coefficient method.

Results

Higher adiposity, lifetime smoking index, and lower educational attainment were consistently associated with higher risk of COVID‐19 phenotypes while there was no strong evidence for an association of other exposures in COVID‐19 risk. ACE2 partially mediates the detrimental effects of body mass index (ranged from 4.3% to 8.2%), waist‐to‐hip ratio (ranged from 11.2% to 16.8%), and lower educational attainment (ranged from 4.0% to 7.5%) in COVID‐19 phenotypes while ACE2 did not mediate the detrimental effect of smoking.

Conclusions

We provided genetic evidence that reducing ACE2 could partly lower COVID‐19 risk amongst people who were overweight/obese or of lower SEP.
Cytoprotective, antimutagenic/antirecombinogenic and antibacterial properties of Lallemantia iberica extracts
Authors: Yilmaz Kardas Begumhan , Diken Mehmet Emin , Bayhan Hamza , Acar Mikail , Dogan Serap
Published: October 2022

BACKGROUND

Plants have important chemical compounds to protect organisms from many mutagens but they may also have dangerous toxic substances that must be tested before use. Lallemantia iberica has been used by local people for treatment of some diseases but it was never tested for its cell protective and antimutagenic/antirecombinogenic properties. In this study, it was aimed to determine the cytoprotective, antimutagenic/antirecombinogenic, antibacterial, antioxidant and phenolic profile of L. iberica by MTS assay, micronucleus test/somatic mutation recombination test (SMART), disc diffusion method, ABTS/DPPH tests and liquid chromatography (LC), respectively.

RESULTS

MTS assay results showed that both of the extracts supported the normal growth of healthy human lymphocytes and there was no significant difference between extracts. Although there was no significant increase in micronucleus concentration (‰) of the cultures treated with ethanol or methanol extracts, methanol extract caused slightly lower micronucleus concentration (12.64 ± 3.65‰) than the ethanol extract (24.46 ± 4.50‰). SMART results showed that ethanol and methanol extracts prevented harmful mitotic recombination. Lallemantia iberica also showed antibacterial activity against all of the strains tested, and the largest inhibition zones were observed with Pseudomonas aeruginosa (17.9 mm) and Enterobacter aerogenes (13.8 mm). Methanol extracts showed better antioxidant activities (ABTS IC50: 104.07 μg mL−1, DPPH IC50: 58.8 μg mL−1) than ethanol extracts (ABTS IC50: 344.03 μg mL−1, DPPH IC50: 233.7 μg mL−1). According to the LC results, the most abundant phenolic compounds were rutin hydrate (1796.4 ± 62.9 mg kg−1) and p‐coumaric acid (228.1 ± 7.60 mg kg−1).

CONCLUSION

Lallemantia iberica extracts had cell‐protective, antimutagenic/antirecombinogenic, antibacterial and strong antioxidant characteristics in relation to their rich phenolic content. © 2022 Society of Chemical Industry.
Metabolites identification and pharmacokinetic profile of hirsuteine, a bioactive component in Uncaria in rats by ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Qi Wen , Zhou Chunwei , Bai Xue , Kano Yoshihiro , Chen Yan , Yuan Dan
Published: October 2022

Hirsuteine is one of the major bioactive tetracyclic indole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks, possessing a wide range of pharmacological activities including neuroprotective, anticonvulsant, antihypertensive, sedative and hypnotic, and so forth. The present study was undertaken to assess the metabolism and plasma pharmacokinetics of hirsuteine in rats. After oral administration of hirsuteine at the dose of 30 mg/kg, 13, 21, and 8 metabolites were detected in rat plasma, urine, and bile by ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry, respectively. Furthermore, plasma concentrations of hirsuteine and its four metabolites, 4‐hirsuteine N‐oxide, 3,4‐dehydrohirsuteine, 11‐hydroxyhirsuteine, and 11‐hydroxyhirsuteine‐11‐O‐glucuronide were simultaneously quantified in rat plasma, using carbamazepine as the internal standard. The linear calibration curve of hirsuteine was in the concentration range of 0.005–5.0 μg/ml. The lower limit of quantitation in the rat plasma was 5 ng/ml for hirsuteine. This study is the first to comprehensively investigate the metabolism process of hirsuteine and the pharmacokinetic profiles of hirsuteine and its major metabolite, and will provide a scientific basis to further elucidate the pharmacodynamic material basis and therapeutic mechanism of Uncaria prescriptions.
Inoculation with phosphate‐solubilizing bacteria alters microbial community and activates soil phosphorus supply to promote maize growth
Authors: Li Ning , Sheng Keyin , Zheng Qiyuan , Hu Dongnan , Zhang Ling , Wang Jiawei , Zhang Wenyuan
Published: October 2022

Phosphorus (P) is one of the essential macronutrients for plants, but agricultural soil generally lacks available P. This study aims to ascertain the impact of phosphate‐solubilizing bacterial inoculation on the development of maize, soil characteristics, P fractions, and the microbial population in the soil. In this experiment, we explored the P solubilizing ability of P‐solubilizing bacteria through liquid culture. In a maize pot experiment, soil P fractions and maize growth were examined, and a metagenomic sequence was constructed to analyze the soil microbial community and gene abundances and to link their relationship. In the shaking flask culture experiment, it was found that the Burkholderia (XQP35) and Raoultella (SQP80) have a strong capability for calcium phosphate and calcium phytate. Compared with the blank control, the XQP35 and SQP80 treatments could improve maize biomass and the soil nutrient status. Moreover, SQP80 treatments increased the soil acid phosphatase activity. SQP80 inoculation dramatically decreased the variety of the soil microbial community and the abundance of Acidobacteria. We found that the different treatments had no significant effect on the number of genes but that the SQP80 treatments significantly increased the P‐cycling pathway gene family phoA and phoD compared with the CK treatment. Our results demonstrated that inoculation with XQP35 and SQP80 could dissolve varieties of insoluble P and, together with functional pathways of P‐cycling, promote the transformation of P fractions and ultimately increase soil available P content to promote the development of maize.
Preservation of soil organic carbon in coastal wetlands promoted by glomalin–iron–organic carbon ternary system
Authors: Zhao Bo , Jia Yunlong , Wu Shengjie , Wei Lili , Li Jian , Hong Hualong , Yan Chongling , Williams Mark A. , Wang Qiang
Published: October 2022

Iron‐bound soil organic carbon (Fe‐bound SOC) and microbial residues are vital for SOC preservation, a process crucial for drawdown of anthropogenic carbon. However, the relative importance of Fe‐bound SOC in coastal wetlands, and its interaction with microbial residues remain poorly understood. Here, we used glomalin as a proxy for microbial residues, with the goal of determining microbial residues binding to Fe and Fe‐bound SOC across a 1000 km coastline of China including seven typical mangrove wetlands. As hypothesized, it was found that the glomalin fraction was strongly associated with and likely bound to Fe‐bound SOC complexes, which accounted for 21.4% ± 1.6% of mangrove SOC. Mean level of Fe‐bound glomalin was 1.2 ± 0.1 mg cm−3, accounting for 40.6% ± 1.5% of total glomalin and 35.4% ± 3.2% of Fe‐bound SOC in the top 10 cm mangrove soil layer at regional scale. Due to the growing realization that Fe may be a crucial factor of glomalin cycling, we performed multiple chemical characterization techniques to identify the association between Fe and glomalin. Our results suggested that association to Fe was a main stabilization mechanism of glomalin in soils, and glomalin served as organic ligands in the formation of Fe‐bound SOC. We also found that the bulk glomalin extracts were a glomalin–Fe–OC ternary complex, which constituted an important proportion of mangrove SOC. These findings highlight the important effect of glomalin bound to Fe as a major mechanism of SOC persistence in coastal wetlands.
Far‐Field Polarization Engineering from Nonlinear Nanoresonators
Authors: Weissflog Maximilian A. , Cai Marcus , Parry Matthew , Rahmani Mohsen , Xu Lei , Arslan Dennis , Fedotova Anna , Marino Giuseppe , Lysevych Mykhaylo , Tan Hark Hoe , Jagadish Chennupati , Miroshnichenko Andrey , Leo Giuseppe , Sukhorukov Andrey A. , Setzpfandt Frank , Pertsch Thomas , Staude Isabelle , Neshev Dragomir N.
Published: October 2022

Nanoresonators fabricated from low‐loss dielectrics with second‐order nonlinearity have emerged as a widespread platform for nonlinear frequency conversion at the nanoscale. However, a persisting challenge in this research is the generated complex far‐field polarization state of the upconverted light, which is a limiting factor in many applications. It will be highly desirable to generate uniform far‐field polarization states across all propagation directions, to control the polarization truly along the optical axis and to simultaneously be able to tune the polarization along the entire circumference of the Poincaré sphere by solely modifying the excitation polarization. Here, a nonlinear nanoresonator combining all these properties is theoretically proposed and experimentally demonstrated. At first, an analytical model connecting the induced multipolar content of a nanoresonator with a desired far‐field polarization is derived. Based on this, a nonlinear dielectric nanoresonator is designed to enable sum‐frequency generation (SFG) with highly pure and tuneable far‐field polarization states. In the experiment, the nanoresonators fabricated from the III‐V semiconductor gallium arsenide in (110)‐orientation are excited in an SFG scheme with individually controllable excitation beams. The generation of highly uniform and tuneable far‐field polarization states is demonstrated by combining back‐focal plane measurements with Stokes polarimetry.
Evaluation and characterization of facial skin aging using optical coherence tomography
Authors: Vingan Nicole R. , Parsa Shyon , Barillas Jennifer , Culver Abby , Kenkel Jeffrey M.
Published: October 2022

Objectives

The skin aging exposome encompasses internal and external factors that contribute to clinical signs of facial aging. Aging skin can be characterized by distinctive features such as wrinkles, lentigines, elastosis, and roughness. Optical coherence tomography (OCT) is capable of noninvasively measuring skin characteristics. This study aimed to assess bilateral features using OCT to explore temporal skin changes among decades and potential changes in facial skin aging based on laterality.

Methods

A total of 97 subjects between 20 and 89 years old with Fitzpatrick skin types I to IV were enrolled. VivoSight, a Multi‐Beam OCT system intended to gather topographical and histological images of skin, was used to scan the area inferolateral to the lateral canthus, bilaterally. Investigators compared characteristics of skin roughness, attenuation coefficient and blood flow across age groups and based on laterality to determine any differences.

Results

Only data from successful OCT scans were used. Seventy subjects, 10 from each specified decade, had successful bilateral scans and were thus included in the analysis. Chronological aging was characterized by significantly decreased dermal attenuation coefficient with increased age. Skin roughness measurements showed trends of increased roughness with age; however, no statistically significant changes were seen between groups. Qualitative differences amongst scans taken on right and left sides of the face showed no significance regarding roughness, density or blood flow at depths ranging from 0.05 to 0.5 mm.

Conclusions

OCT is an effective method for evaluating changes in aging skin. Our results illustrate a decline in skin density with chronological age. Additionally, it was illustrated that structural change in the epidermis and dermis does occur, however on a microscopic scale, there are no significant differences based on laterality. OCT holds promise as a noninvasive technique for characterization of aging skin. Its utility and application in the clinical management and treatment of aged skin requires further research; however, the technology has potential to personalize therapies based on objective findings.
Synthesis of Well‐Defined Block Copolymers of Hyperbranched Polyamide and Polystyrene and Their Micelle‐to‐Vesicle Transformation in Organic Solvents
Authors: Ohta Yoshihiro , Huang Chih‐Feng , Lee Yi‐Huan , Dai Chi‐An , Yokozawa Tsutomu
Published: October 2022

Well‐defined block copolymers consisting of hyperbranched polyamide (HBPA) and polystyrene (PSt) are synthesized, and their self‐assembled structures in solutions are investigated. Atom transfer radical polymerization (ATRP) of styrene initiated from an HBPA macroinitiator, prepared by the chain‐growth condensation polymerization of an AB2 monomer, followed by introduction of an ATRP initiator unit at the focal point, gives the desired block copolymers, PSt‐b‐HBPAs, with well‐defined molecular weight and narrow molecular weight distribution. The block copolymer (PSt/HBPA = 84/16) undergoes self‐assembly in toluene to form spherical micelles (≈10–20 nm), but upon addition of methanol to the toluene solution (toluene/methanol = 0.97/0.03), the morphology changes to vesicles. Further addition of methanol (toluene/methanol = 0.90/0.10) leads to an increase in vesicle size (200–300 nm) and the morphology further transforms from vesicles to large aggregates (>100 nm) at toluene/methanol = 0.80/0.20. In the case of PSt‐b‐HBPA with shorter PSt segments (PSt/HBPA = 76/24 and 60/40), spherical micelles are formed in toluene, but the micelle morphology remains unchanged when 10 wt% methanol is added, though large aggregates (>100 nm) are still formed in toluene/methanol = 0.80/0.20. Interestingly, the morphological transformations of linear/hyperbranched block copolymers are different from those of their double linear block copolymer counterparts.
Doublecortin‐like kinase 1 is a therapeutic target in squamous cell carcinoma
Authors: Standing David , Arnold Levi , Dandawate Prasad , Ottemann Brendan , Snyder Vusala , Ponnurangam Sivapriya , Sayed Afreen , Subramaniam Dharmalingam , Srinivasan Pugazhendhi , Choudhury Sonali , New Jacob , Kwatra Deep , Ramamoorthy Prabhu , Roy Badal C. , Shadoin Melissa , Al‐Rajabi Raed , O'Neil Maura , Gunewardena Sumedha , Ashcraft John , Umar Shahid , Weir Scott J. , Tawfik Ossama , Padhye Subhash B. , Biersack Bernhard , Anant Shrikant , Thomas Sufi Mary
Published: October 2022

Doublecortin like kinase 1 (DCLK1) plays a crucial role in several cancers including colon and pancreatic adenocarcinomas. However, its role in squamous cell carcinoma (SCC) remains unknown. To this end, we examined DCLK1 expression in head and neck SCC (HNSCC) and anal SCC (ASCC). We found that DCLK1 is elevated in patient SCC tissue, which correlated with cancer progression and poorer overall survival. Furthermore, DCLK1 expression is significantly elevated in human papilloma virus negative HNSCC, which are typically aggressive with poor responses to therapy. To understand the role of DCLK1 in tumorigenesis, we used specific shRNA to suppress DCLK1 expression. This significantly reduced tumor growth, spheroid formation, and migration of HNSCC cancer cells. To further the translational relevance of our studies, we sought to identify a selective DCLK1 inhibitor. Current attempts to target DCLK1 using pharmacologic approaches have relied on nonspecific suppression of DCLK1 kinase activity. Here, we demonstrate that DiFiD (3,5‐bis [2,4‐difluorobenzylidene]−4‐piperidone) binds to DCLK1 with high selectivity. Moreover, DiFiD mediated suppression of DCLK1 led to G2/M arrest and apoptosis and significantly suppressed tumor growth of HNSCC xenografts and ASCC patient derived xenografts, supporting that DCLK1 is critical for SCC growth.
Challenges in modeling the Agility multileaf collimator in treatment planning systems and current needs for improvement
Authors: Hernandez V. , Angerud A. , Bogaert E. , Hussein M. , Lemire M. , García‐Miguel J. , Saez J.
Published: October 2022

Background

The Agility multileaf collimator (MLC) mounted in Elekta linear accelerators features some unique design characteristics, such as large leaf thickness, eccentric curvature at the leaf tip, and defocused leaf sides (‘tilting'). These characteristics offer several advantages but modeling them in treatment planning systems (TPSs) is challenging.

Purpose

The goals of this study were to investigate the challenges faced when modeling the Agility in two commercial TPSs (Monaco and RayStation) and to explore how the implemented MLC models could be improved in the future.

Methods

Four linear accelerators equipped with the Agility, located at different centers, were used for the study. Three centers use the RayStation TPS and the other one uses Monaco. For comparison purposes, data from four Varian linear accelerators with the Millennium 120 MLC were also included. Average doses measured with asynchronous sweeping gap tests were used to characterize and compare the characteristics of the Millennium and the Agility MLCs and to assess the MLC model in the TPSs. The FOURL test included in the ExpressQA package, provided by Elekta, was also used to evaluate the tongue‐and‐groove with radiochromic films. Finally, raytracing was used to investigate the impact of the MLC geometry and to understand the results obtained for each MLC.

Results

The geometry of the Agility produces dosimetric effects associated with the rounded leaf end up to a distance 20 mm away from the leaf tip end measured at the isocenter plane. This affects the tongue‐and‐groove shadowing, which progressively increases along the distance to the tip end. The RayStation and Monaco TPSs did not account for this effect, which made trade‐offs in the MLC parameters necessary and greatly varied the final MLC parameters used by different centers. Raytracing showed that these challenging leaf tip effects were directly related to the MLC geometry and that the characteristics mainly responsible for the large leaf tip effects of the Agility were its tilting design and its small source‐to‐collimator distance.

Conclusions

The MLC models implemented in RayStation and Monaco could not accurately reproduce the leaf tip effects for the Agility. Therefore, trade‐offs are needed and the optimal MLC parameters are dependent on the specific characteristics of treatment plans. Refining the MLC models for the Agility to better approximate the measured leaf tip and tongue‐and‐groove effects would extend the validity of the MLC model, reduce the variability in the MLC parameters used by the community, and facilitate the standardization of the MLC configuration process.
Integrating serum pharmacochemistry and network pharmacology to identify chemical markers for quality control of Apocyni Veneti Folium
Authors: Shi Xi , Long Fang , Wu Cheng‐Ying , Zhou Jing , Shen Hong , Zhou Shan‐Shan , Xu Jin‐Di , Zhang Wei , Li Song‐Lin
Published: October 2022

Introduction

Apocyni Veneti Folium (AVF) is a commonly used traditional Chinese medicinal herb for the treatment of hypertension. Chemical markers are crucial for the quality control of herbal medicines; however, the therapeutic components of AVF remain to be well elucidated.

Objectives

This study was intended to integrate serum pharmacochemistry and network pharmacology to identify chemical markers of AVF and establish an efficacy‐related quality control method of AVF.

Material and methods

Ultra‐performance liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS/MS) was applied to identify the absorbed AVF constituents in rat serum. Network pharmacology was further used to identify anti‐hypertension‐related chemical markers. Subsequently, a quantitative method was established using UPLC with diode array detection (DAD) and applied for quality evaluation of commercial AVF samples.

Results

Thirteen prototype constituents were unequivocally or tentatively characterized in serum samples, among which quercetin, kaempferol, hyperoside, isoquercitrin, chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid were identified as dominant chemicals related to anti‐hypertensive efficacy. The quantitative data showed that the total contents of seven marker components even showed 2‐fold variation among 14 batches of commercial AVF samples with RSD values ranging from 12.15% to 75.61%. Hierarchical cluster analysis and heatmap analysis showed that 14 batches of commercial AVF samples could be divided into three main groups.

Conclusion

The chemical markers obtained from this study could be applicable for efficacy‐related quality control of AVF.
Heliox simulations for initial management of congenital laryngotracheal stenosis
Authors: Del Puppo Marine , Meister Lionel , Médale Marc , Allary Chloé , Nicollas Richard , Moreddu Eric
Published: October 2022

Objectives

Congenital laryngotracheal stenosis is rare, potentially severe, and difficult to manage. Heliox is a medical gas effective in obstructive airway pathologies, given its physical properties. This study aims to model the interest of Heliox in reducing the respiratory work in congenital laryngotracheal stenosis, using numerical fluid flow simulations, before considering its clinical use.

Design

This is a retrospective study, performing Computational Fluid Dynamics numerical simulations of the resistances to airflow and three types of Heliox, on 3D reconstructions from CT scans of children presenting with laryngotracheal stenosis.

Patients

Infants and children who were managed in the Pediatric ENT department of a tertiary‐care center and underwent CT scanning for laryngotracheal stenosis between 2008 and 2018 were included.

Results

Fourteen models of congenital laryngotracheal stenosis were performed in children aged from 16 days to 5 years, and one model of the normal trachea in a 5‐year‐old child. Tightest stenosis obtained the highest airway resistances, ranging from 40 to 10 kPa/L/s (up to 800 times higher than in the normal case). Heliox enabled a decrease in pressure drops and airway resistances in all stenosis cases, correlated to increasing Helium concentration.

Conclusions

Heliox appears to reduce pressure drops and airway resistances in 3D models of laryngotracheal stenosis. It may represent a supportive treatment for laryngotracheal stenosis, while waiting for specialized care, thanks to the reduction of respiratory work.
Implementation of the urban parameterization scheme in the Delhi model with an improved urban morphology
Authors: Theethai Jacob Anurose , Jayakumar A. , Gupta Kshama , Mohandas Saji , Hendry Margaret A. , Smith Daniel K. E. , Francis Timmy , Bhati Shweta , Parde Avinash N. , Mohan Manju , Mitra A. K. , Kumar Gupta Prasun , Chauhan Prakash , Jenamani Rajendra Kumar , Ghude Sachin
Published: October 2022

The current study highlights the importance of a detailed representation of urban processes in numerical weather prediction models and emphasizes the need for accurate urban morphology data for improving the near‐surface weather prediction over Delhi, a tropical Indian city. The Met Office Reading Urban Surface Exchange Scheme (MORUSES), a two‐tile urban energy‐budget parameterization scheme, is introduced in a high‐resolution (330‐m) model of Delhi. A new empirical relationship is established for the MORUSES scheme from the local urban morphology of Delhi. The performance is evaluated using both the newly developed empirical relationships (MORUSES‐IND) and the existing empirical relationships for the MORUSES scheme (MORUSES‐LON) against the default one‐tile configuration (BEST‐1t) for clear and foggy events and validations are performed against ground observations. MORUSES‐IND exhibits a significant improvement in the diurnal evolution of the wind speed in terms of amplitude and phase, compared with the other two configurations. Screen temperature () simulations using MORUSES‐IND reduce the warm bias, especially during the evening and night hours. The root‐mean‐square error of is reduced up to 29% using MORUSES‐IND for both synoptic conditions. The diurnal cycle of surface‐energy fluxes is reproduced well using MORUSES‐IND. The net longwave fluxes are underestimated in the model and biases are more significant during foggy events, partly due to the misrepresentation of fog. An urban cool island (UCI) effect is observed in the early morning hours during clear‐sky conditions, but it is not evident on foggy days. Compared with BEST‐1t, MORUSES‐IND represents the impact of urbanization more realistically, which is reflected in the reduction of the urban heat island and UCI in both synoptic conditions. Future works would improve the coupling between the urban surface energy budget and anthropogenic aerosols by introducing MORUSES‐IND in a chemistry aerosol framework model.
Studying the Interaction Behavior of Protein Coronated Gold Nanorods with Polystyrene Nanoplastics
Authors: Chakraborty Debolina , Rawat Ravindra Singh , Kumar Sanjit , Chandrasekaran Natarajan , Mukherjee Amitava
Published: October 2022

The formation of protein corona and their modulatory effects on the physicochemical and biological activity of the nanomaterial is well established. The active protein corona on the nanoparticles can further mediate interactions with trace amounts of exogenous entities present in the systemic circulation. In the present study, we utilize an in vitro simulation system wherein, protein corona is strategically engineered by varying the serum concentration on a model nanoparticle i. e. cationic‐gold nanorods (GNRs). Quantitative analysis indicated that the 4 nm cationic GNRs can accumulate as high as ∼1 mg/mL protein corona upon incubation with serum. The size distribution pattern of the bound corona and their subsequent impact on the physicochemical properties of GNRs were determined. To understand how these coronated nanorods would interact with a potent pollutant, the second layer of interaction was further introduced by interacting the coronated‐GNRs with 1 ppm nanoplastic. The impact of differently functionalized polystyrene beads (plain, aminated, and carboxylated) on the core size, hydrodynamic diameter, surface charge, and optical properties of the coronated GNRs is highlighted. A complex interplay of several interactive forces and amino acid‐mediated binding of the GNRs to the styrene and benzene rings of the nanoplastic leads to the formation of a coronated‐GNR‐PS complex (>400 nm). Further, upon subjecting the hybrid‐conjugate system to acidic pH conditions (pH‐5.6 and 4.3), a considerable increase in protein leaching was observed. The novel approach of the present study aims to look into the layered interactive patterns for nanomaterials that are utilized for in vivo applications.
Acetohydroxyacid Synthase (AHAS) Inhibitor‐Based Commercial Sulfonylurea Herbicides as Glutathione Reductase Inhibitors: in Vitro and in Silico Studies
Authors: Sel Sedat , Tunç Turgay , Ortaakarsu Ahmet Buğra , Mamaş Serhat , Karacan Nurcan , Karacan Mehmet Sayım
Published: October 2022

In this study, in vitro inhibitory effect of AHAS inhibiting‐based commercial sulfonylurea herbicides on human GR and S. cerevisiae GR was determined by electrochemical method. Our findings, the first report in literature, show that the four commercial herbicides were found to be the inhibitors in the range of 4.90–9.75 μM for ScGR, and in the range of 8.54–18.84 μM for hGR. Global reactivity descriptors (energy gaps, electronegativity, hardness and electrophilicity index) of the herbicides were calculated by DFT/B3LYP/6‐31G(d,p) method in gas phase. The electrochemical behavior of the herbicides was studied by cyclic voltammetry. Single‐electron half‐wave reduction potentials and global reactivity descriptors were correlated with the IC50 values of the herbicides. Molecular docking analysis using Schrödinger Suite was applied to examine the interaction between the herbicides and human GR (PDB ID:1XAN and 2GH5), S. cerevisiae GR (PDB ID:2HQM), P. falciparum GR (PDB ID:1ONF), C. albicans AHAS (PDB ID:6DEL) and ScAHAS (PDB ID: 5FEM. Based on the docking results, it can be predicted that (a) herbicides have similar binding potential to two different binding sites of hGRs, (b) herbicides may have antimalarial potential against P. falciparum (c) herbicides may have antifungal potential against C. albicans.
2,4‐Bis(2‐(E)‐arylidenehydrazinyl)quinazolines: Expeditious Synthesis, Characterization, Antiproliferative Effects against Breast Cancer Cell Line and Molecular Docking Studies
Authors: Kumar Ravinder , Kumar Vipan , Kamal Raj , Kumar Ajay , Kaur Satwinderjeet , Bansal Arubhi , Chetti Prabhakar
Published: October 2022

Considering the immense significance of molecular hybridization in development of efficacious antiproliferative agents, the present research work demonstrates the expeditious synthesis of twelve electronically different and novel 2,4‐bis(2‐(E)‐arylidenehydrazinyl)quinazolines 4 a–4 l. Their exact molecular structures have been established by careful analysis of spectroscopic (IR, 1H & 13C‐NMR) and HRMS data. Observed results from the MTT assay indicated that all synthesized derivatives 4 a–4 l displayed substantial growth arrest for breast (MCF‐7) cancer cell line. Specifically, 2,4‐bis(2‐(E)‐4‐methoxy benzylidenehydrazinyl)quinazoline (4 a) and 2,4‐bis(2‐(E)‐4‐bromobenzylidenehydrazinyl) quinazoline (4 b) displayed lowest GI50=139.34±7.44 μM and 145.34±2.11 μM respectively, against breast (MCF‐7) cancer cell line. Additionally, molecular docking studies have been performed to investigate the type of favourable interactions of quinazoline bis‐hydrazones with active sites of protein (PDB ID : 4ASD). Computational studies show that derivative 4 a displayed high binding affinity into the ATP binding sites of 4ASD, which support in vitro results obtained in the present study.
Recent advances of metal–organic frameworks‐based proton exchange membranes in fuel cell applications
Authors: Li Xiao‐Min , Gao Junkuo
Published: October 2022

In recent years, proton exchange membrane (PEM) fuel cell (FC; PEMFC) has been widely studied and gradually applied to vehicle power supply, portable supply, communication base station backup, emergency power supply, and so on. Especially in new energy vehicles, PEMFC has absolute advantages and a broad market. PEM, which is the core component of PEMFC, has a close correlation between its property and the performance of FC. Therefore, developing excellent PEMs is the focus of researchers. Metal–organic frameworks (MOFs) composed of metal ions/clusters and organic ligands have attracted extensive attention in the field of proton conduction. The hybrid membranes formed by MOFs and polymers show excellent performances and design concepts, which have great prospects in commercial application. This paper summarizes the research progress of MOFs‐based hybrid membranes as PEMs applied in hydrogen–oxygen FCs and direct methanol FCs, in which the different polymers used as substrates are also summed up.
Small molecule superposition: A comprehensive overview on pose scoring of the latest methods
Authors: Hönig Sophia M. N. , Lemmen Christian , Rarey Matthias
Published: October 2022

The superposition of small molecules is a standard technique in molecular modeling and for some more advanced in silico applications of drug discovery a critical prerequisite. The aims of superposing molecules are manifold. An assessment of the 3D similarity, an understanding of the SAR in a compound series, or ultimately an estimate of the likelihood of a compound to be active and selective against a target protein of interest. Considering so many objectives it is not surprising that new superpositioning methods are continuously developed and the overlay problem cannot be considered solved. We present 51 superposition methods with a focus on those published in the 21st century. For 36 methods that are currently available, we briefly describe and compare the respective pose generation and scoring processes. While the modeling community got a wealth of methods at hand, the scientific necessity of rigorous and comparable benchmarking becomes apparent.

This article is categorized under:

Data Science > Chemoinformatics

Software > Molecular Modeling
Synthesis and Crystal‐Structure Analysis of the K2NiF4‐Type Hydride Oxides LiLnEuH2−xO2 (Ln=La, Ce, Pr, Nd, Sm) and LiEu2H3O by Neutron and X‐Ray Diffraction
Authors: Hoslauer Jean‐Louis , Zapp Nicolas , Fischer Henry E. , Rudolph Daniel , Kohlmann Holger , Schleid Thomas
Published: October 2022

The hydride oxides LiLnEuH2−xO2 (Ln=La, Ce, Pr, Nd and Sm) were synthesized by reaction of the lanthanide sesquioxides with europium monoxide, europium dihydride and lithium hydride under inert conditions at 750 °C as black powders. They crystallize in the tetragonal K2NiF4‐type structure (space group: I4/mmm) with a mixed Ln3+/Eu2+ occupation. The crystal structures of the europium representatives LiLaEuH2−xO2 and LiLaEuD2−xO2 were analyzed by powder neutron diffraction data at short wavelengths (λ=70 pm). Hydrogen (deuterium) and oxygen atoms occupy distinct crystallographic sites with considerable vacancy concentrations on the hydrogen positions (a=363.80(8) pm, c=1323.3(3) pm, c/a=3.637 for LiLaEuH1.26(4)O2 and a=363.43(5) pm, c=1321.6(2) pm, c/a=3.636 for LiLaEuD1.41(2)O2). Moving from the mixed Ln/Eu occupation in LiLnEuH2O2 to Ln=Eu2+, we obtained the mixed‐anionic phase LiEu2H3O, which crystallizes in the same structure type with a=370.04(2) pm, c=1317.32(8) pm and c/a=3.560.
Study of the Roberge-Weiss phase caused by external uniform classical electric field using lattice QCD approach
Authors: Yang Ji-Chong , Chang Xiao-Ting , Chen Jian-Xing
Published: October 2022

Abstract

The effect of an external electric field on the quark matter is an important question due to the presence of strong electric fields in heavy ion collisions. In the lattice QCD approach, the case of a real electric field suffers from the ‘sign problem’, and a classical electric field is often used similar as the case of chemical potential. Interestingly, in axial gauge a uniform classical electric field actually can correspond to an inhomogeneous imaginary chemical potential that varies with coordinate. On the other hand, with imaginary chemical potential, Roberge-Weiss (R-W) phase transition occurs. In this work, the case of a uniform classical electric field is studied by using lattice QCD approach, with the emphasis on the properties of the R-W phase. Novel phenomena show up at high temperatures. It is found that, the chiral condensation oscillates with z at high temperatures, and so is the absolute value of the Polyakov loop. It is verified that the charge density also oscillates with z at high temperatures. The Polyakov loop can be described by an ansatz Ap + Σq=u,dCq exp (LτQqiazeEz), where Ap is a complex number and Cd> 0, Cu ≥ 0 are real numbers that are fitted for different temperatures and electric field strengths. As a consequence, the behavior of the phase of Polyakov loop is different depending on whether the Polyakov loop encloses the origin, which implies a possible phase transition.
Paranilpotency in uncountable groups
Authors: Trombetti Marco
Published: October 2022

The aim of this paper is to provide a contribution to the theory of uncountable groups and to that of paranilpotent groups. Extending the structural results in Franciosi and de Giovanni (Ricerche Mat 40:321–333, 1991) and de Giovanni et al. (Comm Algebra 49:3020–3033, 2021), we prove that locally soluble minimal non-paranilpotent groups, i.e. non-paranilpotent groups whose proper subgroups are paranilpotent, are soluble. It is also shown that the class of paranilpotent groups is countably recognizable and, as an application of these results, that a soluble uncountable group whose proper uncountable subgroups are paranilpotent is itself paranilpotent.
Changes in bioavailability of zinc during malting process and wort production
Authors: Nobis Arndt , Berg Benjamin , Gastl Martina , Becker Thomas
Published: October 2022

Trace metals, particularly zinc, influence the growth and metabolism of yeast. In the literature the recommended concentration of zinc in pitching wort is > 0.15 mg/L; lower concentrations cause fermentation problems and reduce in consequence final beer quality. The aim of this study was the exploration of changes in bioavailability (available zinc), which was never considered before, and in the mass balance of total zinc during malting process and wort production. Therefore, the work comprised two parts: (1) investigating the effect of malt modification on zinc content and bioavailability of, respectively, produced malt depending on malt modification by varying the steeping degree (38–48%) in the malting process and (2) examining the effect of zinc losses and changes in bioavailability in the by-products (spent grain and hot break) by performing brewing trials up to pitching wort. Zinc was measured by atomic absorption spectroscopy. We applied a specific extraction scheme to evaluate first the bioavailability of zinc in brewing-related samples. In the malting process, total zinc losses increased with greater modification level of the malt samples, although bioavailability increased simultaneously. Spent grain was the primary zinc loss by-product (98%) in the brewing process. The distribution of the binding forms of zinc in hot break and spent grain was significantly altered with an increase in the less water-soluble binding forms of zinc.
Quinone binding site in a type VI sulfide:quinone oxidoreductase
Authors: Miklovics Nikolett , Duzs Ágnes , Balogh Fanni , Paragi Gábor , Rákhely Gábor , Tóth András
Published: October 2022

Monotopic membrane-bound flavoproteins, sulfide:quinone oxidoreductases (SQRs), have a variety of physiological functions, including sulfide detoxification. SQR enzymes are classified into six groups. SQRs use the flavin adenine dinucleotide (FAD) cofactor to transfer electrons from sulfide to quinone. A type VI SQR of the photosynthetic purple sulfur bacterium, Thiocapsa roseopersicina (TrSqrF), has been previously characterized, and the mechanism of sulfide oxidation has been proposed. This paper reports the characterization of quinone binding site (QBS) of TrSqrF composed of conserved aromatic and apolar amino acids. Val331, Ile333, and Phe366 were identified near the benzoquinone ring of enzyme-bound decylubiquinone (dUQ) using the TrSqrF homology model. In silico analysis revealed that Val331 and Ile333 alternately connected with the quinone head group via hydrogen bonds, and Phe366 and Trp369 bound the quinones via hydrophobic interactions. TrSqrF variants containing alanine (V331A, I333A, F366A) and aromatic amino acid (V331F, I333F, F366Y), as well as a C-terminal α-helix deletion (CTD) mutant were generated. These amino acids are critical for quinone binding and, thus, catalysis. Spectroscopic analyses proved that all mutants contained FAD. I333F replacement resulted in the lack of the charge transfer complex. In summary, the interactions described above maintain the quinone molecule’s head in an optimal position for direct electron transfer from FAD. Surprisingly, the CTD mutant retained a relatively high level of specific activity while remaining membrane-anchored. This is a unique study because it focuses on the QBS and the oxidative stage of a type VI sulfide-dependent quinone reduction.

Key points

• V331, I333, F366, and W369 were shown to interact with decylubiquinone in T. roseopersicina SqrF

• These amino acids are involved in proper positioning of quinones next to FAD

• I333 is essential in formation of a charge transfer complex from FAD to quinone

Graphical abstract
Modularizing Earth system models for interactive simulation
Authors: Claus Martin , Gundlach Sven , Hasselbring Wilhelm , Jung Reiner , Rath Willi , Schnoor Henning
Published: October 2022

Interactive exploration of Earth system simulations may have great potential to improve the scientific modeling process. It will allow monitoring of the state of the simulation via dashboards presenting real-time diagnostics within a digital twin world. We present the state of the art for Earth system modeling in this context. Cross-domain data handling and fusion will make it possible to integrate model and observation data in the context of digital twins of the ocean. Domain-driven modularization of monolithic Earth system models allows one to recover interfaces for such a cross-domain fusion. Reverse engineering with static and dynamic analysis enables modularization of Earth system models. The modularization does not only help with restructuring existing Earth system models, it also makes it possible to integrate additional scientific domains into the interactive simulation environment.
LSPIV analysis of ship-induced wave wash
Authors: Fleit Gábor , Baranya Sándor
Published: October 2022

Ship-induced wave wash affects the hydromorphological and ecological state of rivers through various mechanisms. The direct proximity of the riverbank is usually the most exposed, as the hydrodynamic stresses are the highest in these shallow water areas. Contrary to the steady and almost still, natural flow conditions (i.e., no waves of anthropogenic source), shoaling and breaking of ship waves increase the hydrodynamic stresses by orders of magnitudes, having notable ecological consequences, and resulting in bank erosion as well. Due to the shallow water depths and temporary drying, conventional measurement techniques are no longer applicable in these areas. In this study, large-scale particle image velocimetry (LSPIV) is used to quantify the prevailing flow conditions. In the absence of ground truth data in the wave breaking region, a high-resolution computational fluid dynamics model—verified with field pressure and acoustic Doppler velocimetry data—is used for the cross-validation of the LSPIV results. The results underline the applicability of LSPIV for the hydrodynamic analysis of wave velocities in this special riverine swash zone, which is of key importance from the aspect of ecology and bank erosion as well.

Graphical abstract
Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?
Authors: Madas Balázs G. , Boei Jan , Fenske Nora , Hofmann Werner , Mezquita Laura
Published: October 2022

Exposure to radon progeny results in heterogeneous dose distributions in many different spatial scales. The aim of this review is to provide an overview on the state of the art in epidemiology, clinical observations, cell biology, dosimetry, and modelling related to radon exposure and its association with lung cancer, along with priorities for future research. Particular attention is paid on the effects of spatial variation in dose delivery within the organs, a factor not considered in radiation protection. It is concluded that a multidisciplinary approach is required to improve risk assessment and mechanistic understanding of carcinogenesis related to radon exposure. To achieve these goals, important steps would be to clarify whether radon can cause other diseases than lung cancer, and to investigate radon-related health risks in children or persons at young ages. Also, a better understanding of the combined effects of radon and smoking is needed, which can be achieved by integrating epidemiological, clinical, pathological, and molecular oncology data to obtain a radon-associated signature. While in vitro models derived from primary human bronchial epithelial cells can help to identify new and corroborate existing biomarkers, they also allow to study the effects of heterogeneous dose distributions including the effects of locally high doses. These novel approaches can provide valuable input and validation data for mathematical models for risk assessment. These models can be applied to quantitatively translate the knowledge obtained from radon exposure to other exposures resulting in heterogeneous dose distributions within an organ to support radiation protection in general.
Exact series solutions of composite beams with rotationally restrained boundary conditions: static analysis
Authors: Zhang Yuan , Zhang Lei , Zhang Sigong
Published: October 2022

The structural performance of composite beams is sensitive to load distribution as well as actual boundary conditions. Although the composite beam theory has been solidly established and exact solutions have been readily developed for various loading and boundary conditions, almost all of them are limited to classical boundary conditions (free, pinned and clamped) and there has been little discussion about the actual support conditions in real structures. The general representation of actual boundary conditions can be defined as rotationally restrained edges. In this research, an analytical model with exact series-type solutions was developed for composite beams with rotationally restrained edges. The model and displacement solutions were validated by other analytical methods and numerical results. The influence of rotational and end-slip restraints was investigated. It was found that the deflection and interface slip of composite beams are highly affected by both restraints introduced by the actual boundary conditions. The current model can be used as a benchmark for future design methods considering the realistic boundary conditions of composite beams.
Faster Graph Coloring in Polynomial Space
Authors: Gaspers Serge , Lee Edward J.
Published: October 2022

We present a polynomial-space algorithm that computes the number of independent sets of any input graph in time $$O(1.1389^n)$$

O
(
1
.

1389
n

)

for graphs with maximum degree 3 and in time $$O(1.2356^n)$$

O
(
1
.

2356
n

)

for general graphs, where n is the number of vertices in the input graph. Together with the inclusion-exclusion approach of Björklund, Husfeldt, and Koivisto [SIAM J. Comput. 2009], this leads to a faster polynomial-space algorithm for the graph coloring problem with running time $$O(2.2356^n)$$

O
(
2
.

2356
n

)

as well as an exponential-space $$O(1.2330^n)$$

O
(
1
.

2330
n

)

time algorithm for counting independent sets. Our main algorithm counts independent sets in graphs with maximum degree at most 3 and no vertex with three neighbors of degree 3. This polynomial-space algorithm is designed and analyzed using the recently introduced Separate, Measure and Conquer approach [Gaspers & Sorkin, ICALP 2015]. Using Wahlström’s compound measure approach, this improvement in running time for small degree graphs is then bootstrapped to larger degrees, giving the improvement for general graphs. Combining both approaches leads to some inflexibility in choosing vertices to branch on for the small-degree cases, which we counter by structural graph properties.