bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiral separation of terbutaline by supercritical fluid chromatography with peak purity determination by UPLC–MS and modeling for chiral recognition mechanism
Authors: Ali Imran , Alam Syed Dilshad , Raja Rupak , Jain Arvind K , Mustaqeem Mohd , Locatelli Marcello , Aboul‐Enein Hassan Y , Yusuf Kareem
Published: February 2024

BACKGROUND

Terbutaline is the drug of choice for asthma patients but it exists in racemic mixture. (R)‐(−)‐terbutaline is 200 times more active than (S)‐(+)‐terbutaline yet it is not advisable to prescribe racemic mixture due to certain adverse effects of (S)‐(+)‐terbutaline. Therefore, a fast, effective and reproducible separation method is necessary.

RESULTS

Chiral separation was achieved on Chiralpak‐IE and Chiralpak‐IG columns (250 × 4.6 mm, 5 μm) using carbon dioxide‐methanol (CO2‐MeOH, 60:40) with a 0.2% triethylamine mobile phase. The flow was 1.0 mL min−1 with detection at 223 nm using a photodiode array (PDA) detector. The values of retention, separation and resolution factors were in the ranges 1.88–2.38, 1.14–1.26 and 0.91–1.17, respectively; with best separation with Chiralpak‐IE. The tailing factors and number of theoretical plates were in the range of 1.0–1.23 and 487–3699. The purity of the separated peaks was determined by ultra‐performance liquid chromatography–mass spectrometry (UPLC–MS); indicating 100% purity of the peaks. The chiral recognition was determined by modeling with binding affinities −5.0 and −6.0 for S‐ and R‐enantiomers, respectively; indicating S‐enantiomer elution first followed by R‐enantiomers. The major forces responsible for the chiral resolution were hydrogen bonding and π‐π interactions.

CONCLUSION

Owing to the great demand for optically active pure drugs and high economic pressure on analytical techniques, the chiral separation of terbutaline was achieved via inexpensive supercritical fluid chromatography. The reported method may be used to prepare optically active pure terbutaline drugs (R‐enantiomers) at a pilot scale. © 2024 Society of Chemical Industry (SCI).
Plasma lipidomics analysis reveals altered profile of triglycerides and phospholipids in children with Medium‐Chain Acyl‐CoA dehydrogenase deficiency
Authors: Guerra Inês M. S. , Ferreira Helena B. , Maurício Tatiana , Pinho Marisa , Diogo Luísa , Moreira Sónia , Goracci Laura , Bonciarelli Stefano , Melo Tânia , Domingues Pedro , Domingues M. Rosário , Moreira Ana S. P.
Published: February 2024

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid β‐oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l‐carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography–mass spectrometry was employed for the analysis of esterified fatty acids, while high‐resolution C18‐liquid chromatography‐mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non‐decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in‐depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long‐term impacts.
Triple band frequency selective surface design for 5G mm‐wave communication with artificial neural networks
Authors: Şahin Ufuk , Serinken Elif Seher , Vural Revna Acar , Tokan Nurhan Türker
Published: February 2024

High‐performance frequency selective surfaces (FSSs) have gained attention for their spatial filtering characteristics in 5G communication systems. In this work, we propose an efficient and accurate design methodology for the FSS. Three different artificial neural network methods (ANN) are employed, and their performances are compared for analysis and synthesis purposes. Results show that GRNN has the highest performance for both training and test phase of ANN based FSS analysis and synthesis. A novel, compact, low‐profile triple band FSS unit cell is introduced, and the working mechanism is described. By applying ANN based design procedure, the unit cell dimensions to resonate at the 5G mm‐wave frequency band is extracted. A unit cell with the extracted physical dimensions is simulated with a full‐wave analysis tool. The simulation results show that the FSS has the filtering feature at the predetermined mm‐wave frequencies of the 5G communication. The prototype of the FSS is fabricated, as well. The simulations are verified experimentally with measurement results. The results show that proposed ANN based analysis and synthesis method can be an effective tool for the design of FSS band‐pass filter for 5G applications.
Hybrid technique of conformal mapping and Chebyshev collocation method for solving time–space fractional order wave equation
Authors: El‐Sayed Adel Abd Elaziz , Boulaaras Salah
Published: February 2024

This work presents a numerical approach for solving the time–space fractional‐order wave equation. The time‐fractional derivative is described in the conformal sense, whereas the space‐fractional derivative is given in the Caputo sense. The investigated technique is based on the third‐kind of shifted Chebyshev polynomials. The main problem is converted into a system of ordinary differential equations using conformal mapping, Caputo derivatives, and the properties of the third‐kind shifted Chebyshev polynomials. Then, the Chebyshev collocation method and the non‐standard finite difference method will be used to convert this system into a system of algebraic equations. Finally, this system can be solved numerically via Newton's iteration method. In the end, physics numerical examples and comparison results are provided to confirm the accuracy, applicability, and efficiency of the suggested approach.
Willingness and understanding of the safety and effectiveness of COVID‐19 vaccines in young children: a cross‐sectional study among parents in Malaysia
Authors: Ibrahim Norkasihan , Afandi Muhammad Firdaus , Abu Bakar Karmila , Eng Caroline , Balan Shamala , Abd Wahab Mohd Shahezwan , Jamal Janattul‐Ain
Published: February 2024

Background

The safety and efficacy of COVID‐19 vaccinations are crucial factors that parents consider when deciding whether to vaccinate their children.

Aim

This study aimed to investigate parents' understanding of COVID‐19 vaccines and its association with the degree of willingness to vaccinate their young children.

Method

A cross‐sectional survey was conducted among the public with children younger than 12 years old. Information on parents' demography, understanding of COVID‐19 vaccines and their willingness to get their children vaccinated were collected. The association between the level of understanding and willingness was tested using the One‐way analysis of variance (ANOVA) test. Predictors of good understanding and high willingness were investigated using multiple linear regression. Ethics approval was granted by the Research Ethics Committee of Universiti Teknologi MARA (Reference no: REC [PH]/012/2022) and the study conforms with the Declaration of Helsinki. Informed consent was obtained from all participants. A web‐based survey link was distributed through social media platforms. The initial section of the survey included a project information sheet including the purpose of the study, length of questionnaire, identity of researchers and measures taken to ensure data confidentiality and anonymity of participants. Participants provided their consent electronically prior to being granted access to the questionnaire.

Results

Of the 386 respondents, 53.4% had a good understanding, and 74.6% had a high willingness. Only 42.5% agreed that the vaccines are effective in protecting children from getting COVID‐19, 79.5% and 73.3% misunderstood the severity and tendency to experience the side effects, respectively. A better understanding was associated with a higher willingness to vaccinate ([F(4381) = 54.417, p = 0.000). A higher understanding was significantly associated with higher educational status (postgraduate [β = 0.297, p = 0.028] and bachelor [β = 0.275, p = 0.034], work in a health‐related field [β = 0.300, p < 0.001]) and have received a COVID‐19 booster (β = 0.347, p < 0.001). A high willingness was prevalent among parents working in a health‐related field, had received a COVID‐19 booster and had medical condition. Low willingness was observed among parents aged above 30 years old and those who have used herbal medicines.

Conclusion

It is of utmost importance to comprehend parents’ understanding of this topic to minimise hesitancy toward COVID‐19 vaccination in children.
Status seizures as a secondary effect from the “squash drinking syndrome” in an infant
Authors: Rosell‐Camps Antonio , Bunce Lucinda F. , Barceló‐Martí Bernardí , Sharluyan‐Petrosyan Artur
Published: February 2024

The “hypotonic drink syndrome” is characterized by loss of appetite, normal activity levels and, in some cases, intestinal disturbances in children with an intake of more than 30% of the recommended daily calories in the form of non‐dairy drinks. Diarrhea and growth retardation are possible complications due to the amount of nonnutritive calorie intake (“empty calories”) contained in this type of hypotonic beverages.

We present the case of an 11‐month‐old boy who suffered a “Squash drinking syndrome” requiring admission to the pediatric intensive care unit because of a status seizure secondary to a severe hyponatremia (118 mmol/L) due to massive ingestion of hypotonic drinks, such as squash. The seizure did not subside until sodium levels reached 123 mmol/L with hypertonic saline (3%). Neurological, renal, digestive, endocrine and metabolic problems were all ruled out and normal sodium levels were maintained with dietary recommendations and a restriction of hypotonic fluid intake.

Conclusions

To prevent these situations it is important to be aware of this entity and to know how to identify the possible complications that may appear after excessive ingestion of hypotonic drinks, as in the case of our patient, ranging from lack of appetite, growth failure and diarrhea, to a status seizure.
Massive infected pancreatic necrosis in an 8‐year‐old: Endoscopic management
Authors: Abel William F. , Kesar Varun , Wasserman Reid D. , Kumar Manoj , Patel Vishal , Yeaton Paul , Kesar Vivek
Published: February 2024

Pancreatitis is a condition much more commonly found in adults, but when diagnosed in the pediatric population, is often due to medications, congenital pathology, and critical illness. This patient had previously undergone treatment with 6‐mercaptopurine and presented with pancreatitis that eventually worsened to a walled‐off necrotic collection with paracolic extensions reaching the pelvis. Given clinical worsening with development of shock, procedural options for source control were weighed with gastroenterology, pediatric surgery, and interventional radiology, before pancreatic necrosectomy was determined to be the treatment of choice, given the adjacency of the collection to the stomach. A total of three separate endoscopic pancreatic necrosectomy procedures were performed and the patient s clinical status improved greatly, with vast improvement later seen on outpatient imaging. This successful treatment course argues for the efficacy of pancreatic necrosectomy even in very large walled off collections, and most importantly, lead to a positive outcome in this young patient.
Phenolic composition and bioactivities of sea buckthorn (Hippophae rhamnoides L.) fruit and seeds: an unconventional source of natural antioxidants in North America
Authors: Danielski Renan , Shahidi Fereidoon
Published: February 2024

BACKGROUND

Sea buckthorn (Hippophae rhamnoides L.) was introduced into Canada in the early 2000s. This plant bears fruits with high commercial value in other countries due to its premium oil. Nevertheless, sea buckthorn berries are also a rich source of bioactives with nutraceutical potential, especially the variety grown in Newfoundland (Canada), which has not previously been characterized. As such, this study evaluated the composition of polyphenols in sea buckthorn pomace and seeds, as well as their prospective health‐promoting effects.

RESULTS

Polyphenolic identification by high‐performance liquid chromatography–ultraviolet–mass spectrometry–time of flight revealed the presence of 24 compounds in the seeds and 16 compounds in the pomace, including phenolic acids, flavonoids, and tannins, with ellagic acid derivative IV (pomace, 52.13 μg g−1) and (+)‐catechin (seeds, 690.8 μg g−1) being the most dominant. Sea buckthorn extracts displayed in vitro antidiabetic and anti‐obesity potential by inhibiting α‐glucosidase (71.52–99.31%) and pancreatic lipase (15.80–35.61%) enzymes, respectively. The extracts also protected low‐density‐lipoprotein cholesterol (50.97–89.67%) and supercoiled DNA (35.11–79.84%) from oxidative damage.

CONCLUSION

Sea buckthorn berries grown in Canada showed promising health benefits induced by their rich and diverse polyphenolic profile and need to be considered for further commercial expansion as a bioactive‐loaded superfruit. © 2024 Society of Chemical Industry.
Comparison of filter membranes in the analysis of 183 veterinary and other drugs by liquid chromatography‐tandem mass spectrometry
Authors: Michlig Nicolás , Lehotay Steven J. , Lightfield Alan R.
Published: February 2024

Although filtration is one of the most common steps in sample preparation for chemical analysis, filter membrane materials can leach contaminants and/or retain some analytes in the filtered solutions. In multiclass, multiresidue analysis of veterinary drugs, it is challenging to find one type of filter membrane that does not retain at least some of the analytes before injection in ultrahigh‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐MS/MS). In this study, different filter membranes were tested for use in UHPLC‐MS/MS analysis of 183 diverse drugs in bovine muscle, kidney, and liver tissues. Membranes evaluated consisted of polytetrafluoroethylene (PTFE), polyvinylidene difluoride (PVDF), polyethersulfone, nylon, and regenerated cellulose. Drug classes represented among the analytes included β‐agonists, β‐lactams, anthelmintics, macrolides, tetracyclines, sulfonamides, tranquilizers, (fluoro)quinolones, anti‐inflammatories, nitroimidazoles, coccidiostats, phenicols, and others. Although the presence of a matrix helped reduce the binding of analytes on surface active sites, all of the filter types partially retained at least some of the drugs in the final extracts. In testing by flow‐injection analysis, all of the membrane filters were also observed to leach interfering components. Ultimately, filtration was avoided altogether in the final sample preparation approach known as the quick, easy, cheap, effective, rugged, safe, efficient, and robust (QuEChERSER) mega‐method, and ultracentrifugation was chosen as an alternative.
Comparison of the applicability of electromembrane extraction and liquid‐phase microextraction for extraction of non‐polar basic drugs from different biological samples: Using clozapine as the model analyte
Authors: Xiong Jianhua , Tian Linxin , Shen Xiantao , Huang Chuixiu
Published: February 2024

Understanding and comparing the applicability of electromembrane extraction (EME) and liquid‐phase microextraction (LPME) is crucial for selecting an appropriate microextraction approach. In this work, EME and LPME based on supported liquid membranes were compared using biological samples, including whole blood, urine, saliva, and liver tissue. After optimization, efficient EME and LPME of clozapine from four biological samples were achieved. EME provided higher recovery and faster mass transfer for blood and liver tissue than LPME. These advantages were attributed to the electric field disrupting clozapine binding to interfering substances. For urine and saliva, EME demonstrated similar recoveries while achieving faster mass transfer rates. Finally, efficient EME and LPME were validated and evaluated combined with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The coefficient of determination of all methods was greater than 0.999, and all methods showed acceptable reproducibility (≤14%), accuracy (90%–110%), and matrix effect (85%–112%). For liver and blood with high viscosity and complex matrices, EME‐LC‐MS/MS provided better sensitivity than LPME‐LC‐MS/MS. The above results indicated that both EME and LPME could be used to isolate non‐polar basic drugs from different biological samples, although EME demonstrated higher recovery rates for liver tissue and blood.
Preparation and Hemocompatibility of Novel Antioxidant‐Modified Polyethersulfone Membranes as Red Blood Cell Thrombosis Inhibitors
Authors: Fu Xiao , Lei Ting , Song Shitao , Xia Luling , Xiao Yuan , Xiao Gong
Published: February 2024

The contact between the dialysis membrane and blood can induce oxidative stress and thrombosis, causing oxidative organ damage and impaired toxin clearance. To date, the selection of anticoagulants has focused on mechanisms inhibiting white, but not red (erythrocytes) thrombus formation. In the present study, polyethersulfone (PES) membranes are modified with the antioxidant drug tiopronin; the physicochemical properties and dialysis performance of the Tio‐PES membranes are evaluated. The effects on erythrocyte thrombosis are evaluated in terms of erythrocyte morphology, prothrombotic properties (adhesion, aggregation, viscosity, sedimentation, and hemolysis), and fibrinogen (FIB)‐erythrocyte interactions. The regular anticoagulant and antiplatelet properties are also assessed. Superoxide dismutase, malondialdehyde, plasma protein, and complement C3a are further determined. Finally, the biosafety of the Tio‐PES membranes is evaluated both in vitro and in vivo. The Tio‐PES membranes exhibit excellent physicochemical properties and improved dialysis performance. It is found that the Tio‐PES membranes stabilize erythrocyte morphology, reduce erythrocyte prothrombotic properties, decrease FIB adsorption, and prevent red thrombus formation. In addition, the Tio‐PES membranes exhibit excellent antioxidant properties and show biosafety in primary toxicity studies. Thus, Tio‐PES membranes hold promise as novel, safe, and effective dialysis materials for potential clinical application.
One‐Step Solvent‐Free Synthesis of Dimer Diamine‐Based Autocatalytic Polyol for the Preparation of Polyurethane Foams
Authors: Nasuhoglu Büşra , Çakmakçi Emrah , Kahraman Memet Vezir
Published: February 2024

Herein, this work reports the facile synthesis of a dimer diamine‐based autocatalytic polyol (ACP) and its use in polyurethane foam preparation. The ACP, namely TETRAOL is synthesized in one step, without using solvent, and with 100% atom economy. Additionally, a phosphorous‐modified polyol is synthesized by using 9,10‐dihydro‐9‐oxa‐10‐phosphaphenanthrene‐10‐oxide (DOPO) and castor oil. In this study, all of the polyol components of the foams are of vegetable oil origin, and amine or tin‐based auxiliary catalysts are not used. The structures of the synthesized autocatalytic polyol as well as other bio‐polyols are characterized by Fourier‐transform infrared (FTIR) and Nuclear magnetic resonance (NMR) spectroscopies. The densities, rise and gel time values, and thermal and mechanical properties of the foams are determined and compared to foams prepared by using a petroleum‐based commercial ACP. The bio‐based TETRAOL‐containing foams display comparable densities and improve thermal properties but longer rise and gel time values concerning the foam prepared by using the commercial ACP.
Looking a gift horse in the mouth: Suspicion of large gift expenditures undermines gift appreciation
Authors: Mutluoglu Aybike , Ashworth Laurence , Robitaille Nicole
Published: February 2024

Prior work shows that gift recipients are surprisingly insensitive to the amount of money givers spend, even though more expensive gifts represent a greater investment by givers and impart greater value to recipients. We suggest that recipients' apparent indifference may be explained by competing reactions to gift expenditure. Specifically, we propose that recipients are not unresponsive to gift expenditure, per se, but that money's association with instrumentality means that conspicuous monetary expenditures can cause recipients to contemplate givers' instrumental motives (i.e., become suspicious). Four studies show that large gift expenditures can cause recipients to become suspicious of givers' motives and that suspicion undermines recipients' otherwise positive reactions. We further show that expenditures that are less strongly associated with instrumentality (time and effort) and gifts that have a weaker association with money and instrumentality (experiential gifts) are less prone to suspicion and are appreciated more.
Probabilistic seasonal forecasts of North Atlantic atmospheric circulation using complex systems modelling and comparison with dynamical models
Authors: Sun Yiming , Simpson Ian , Wei Hua‐Liang , Hanna Edward
Published: February 2024

Dynamical seasonal forecast models are improving with time but tend to underestimate the amplitude of atmospheric circulation variability and to have lower skill in predicting summer variability than in winter. Here, we construct Nonlinear AutoRegressive Moving Average models with eXogenous inputs (NARMAX) to develop the analysis of drivers of North Atlantic atmospheric circulation and jet‐stream variability, focusing on the East Atlantic (EA) and Scandinavian (SCA) patterns as well as the North Atlantic Oscillation (NAO) index. New time series of these indices are developed from empirical orthogonal function (EOF) analysis. Geopotential height data from the ERA5 reanalysis are used to generate the EOFs. Sets of predictors with known associations with these drivers are developed and used to formulate a sliding‐window NARMAX model. This model demonstrates a high degree of predictive accuracy, as indicated by its average correlation coefficients over the testing period (2006–2021): 0.78 for NAO, 0.83 for EA and 0.68 for SCA. In comparison, the SEAS5 and GloSea5 dynamical forecast models exhibit lower correlations with observed circulation changes: for NAO, the correlation coefficients are 0.51 for SEAS5 and 0.34 for GloSea5, for EA they are 0.15 and 0.09, respectively, and for SCA, they are 0.28 and 0.24, respectively. Comparison of NARMAX predictions with forecasts and hindcasts from the SEAS5 and GloSea5 models highlights areas where NARMAX can be used to help improve seasonal forecast skill and inform the development of dynamical models, especially in the case of summer.
Slope stability analysis with a hypoplastic constitutive model: Investigating a stochastic anisotropy model and a hydro‐mechanical coupled simulation
Authors: Xue Yang , Miao Fasheng , Wang Shun , Tang Yang , Wu Yiping , Dias Daniel
Published: February 2024

A reliable constitutive model is essential for accurately predicting slope deformation in numerical analysis, which includes assessing slope stability as an integral component. However, calculating slope stability in numerical models can be challenging due to complex boundary conditions and advanced constitutive models, especially when probabilistic and hydro‐mechanical coupled simulations are required. In this paper, we use a vector‐sum method‐based framework for slope stability analysis that incorporates a critical state hypoplastic constitutive model. The rationality and accuracy of the stability results are initially verified through critical slip surface analysis and a factor of safety evaluation. Subsequently, we investigate the probability‐based slope stability and failure characteristics by incorporating the spatial variability of strength parameters into the hypoplastic model. Finally, the Baishuihe landslide in the Three Gorges Reservoir Region is examined as a case study, where hydro‐mechanical coupled simulations are conducted under actual water level and rainfall conditions. The time‐varying stability and deformation characteristics of the landslide are analyzed and compared with the results obtained from the Mohr‐Coulomb model. The analysis results demonstrate the practicality and efficiency of using a hypoplastic model for probabilistic and time‐varying slope stability calculations. Furthermore, it highlights the superior ability of the hypoplastic model to accurately describe reservoir landslide deformation processes.
The effects of a galectin‐3 inhibitor on bladder pain syndrome in mice with cyclophosphamide‐induced cystitis
Authors: Xiao Helong , Wang Ting , Gao Bo , Liu Junjiang , Li Shoubin , Ma Jianguo
Published: February 2024

Aims

To explore the effect of blocking galectin‐3 in the bladder pain syndrome associated with interstitial cystitis.

Methods

A galectin‐3 inhibitor was used to treat mice with cyclophosphamide‐induced cystitis. The expression of galectin‐3 in bladder tissues and urine was examined by immunohistochemistry and enzyme‐linked immunosorbent assay (ELISA), respectively. Suprapubic‐pelvic pain, bladder voiding, bladder pain‐like nociceptive behavior, and referred hyperalgesia were assessed. The weights of the bladders were also measured, and inflammatory cell infiltration and inflammatory cytokine levels were examined by histopathological evaluation. The inflammatory cytokines interleukin 1β (IL‐1β), nerve growth factor (NGF), IL‐6, and tumor necrosis factor α (TNF‐α) were measured by ELISA.

Results

Increases in galectin‐3 levels, inflammation, bladder weight, and bladder pain‐related symptoms were observed in bladders with cyclophosphamide‐induced cystitis. Administration of the galectin‐3 inhibitor significantly mitigated bladder pain‐related symptoms and inflammatory response. In response to the 500 μM dose of the galectin‐3 inhibitor, nociceptive behaviors, nociceptive score, and bladder‐to‐body weight ratios were reduced by 65.1%, 65.3%, and 40.3%, respectively, while 500 μM Gal‐3 inhibitor increased pelvic pain threshold by 86.7%. Moreover, galectin‐3 inhibitor treatment inhibited the inflammation. Compared to untreated CYP‐induced mice, there were significant changes in the levels of IL‐1β (41.72 ± 2.05 vs. 18.91 ± 2.26 pg/mg tissues), NGF (9.64 ± 0.38 vs. 1.88 ± 0.05 pg/mg tissues), IL‐6 (42.67 + 1.51 vs. 21.26 + 2.78 pg/mg tissues, and TNF‐α (22.02 ± 1.08 vs. 10.70 ± 0.80 pg/mg tissues) in response to the highest dose of the Gal‐3 inhibitor subgroup (500 μM), and 500 μM Gal‐3 inhibitor reduced mast cell infiltration ratios by 71.8%.

Conclusions

The galectin‐3 inhibitor relieved pelvic pain, urinary symptoms, and bladder inflammation in mice with cyclophosphamide‐induced cystitis. Thus, galectin‐3 inhibitors may be novel agents in interstitial cystitis treatment.
Face‐centred finite volume methods for Stokes flows with variable viscosity
Authors: Sevilla Ruben , Duretz Thibault
Published: February 2024

Six face‐centred finite volume formulations are derived and compared for the simulation of Stokes flows with spatially varying viscosity. The main difference between the methods derived is the mixed variable used in the mixed formulation and the use of a weak or strong form in each element using integration by parts. A brief discussion about the properties of the different methods is provided, including comments on the computational cost and the symmetry of the resulting global system of equations. Finally, numerical examples in two and three dimensions are used to compare the accuracy of all the formulations presented. The examples include a problem where the methods are employed to simulate a steep variation of the viscosity, showing the ability to perform these simulations without using a mesh conforming to a material interface. The performance of different element types and different choices of the stabilisation is also discussed.
An implicit Updated Lagrangian Fragile Points Method with a support domain refinement scheme for solving large deformation problems
Authors: Dai Xueyan , Ke Zetao , Li Mingjing , Dong Leiting , Atluri Satya N.
Published: February 2024

Engineering structures may undergo large deformations, but simulating is still challenging for existing numerical methods, for example, the element‐based methods struggle from the mesh distortion and the strong form particle‐based methods exhibit tensile instability. This article aims on presenting a novel numerical method for large deformation simulations, which is named the implicit Updated Lagrangian Fragile Points Method (ULFPM). The point‐based nature of the proposed method ensures immunity to mesh distortion, and its stability is guaranteed by its foundation on weak form formulations. For verifications, the proposed implicit ULFPM has been applied to several large deformation problems. For all the examples, the proposed method is able to provide reliable results with a good agreement with the reference results. Moreover, the implicit ULFPM performs better than the Finite Element Method to some extent for extremely large deformation problems. It is also discussed that the accuracy of the implicit ULFPM is improved significantly by using the support domain refinement scheme. The examples indicate that the proposed method can serve as a reliable tool for predicting the large deformations of structures in engineering practices.
An adaptive mesh refinement method based on a characteristic‐compression embedded shock wave indicator for high‐speed flows
Authors: Feng Yiwei , Lv Lili , Liu Tiegang , Xu Liang , Yuan Weixiong
Published: February 2024

Numerical simulation of high‐speed flows often needs a fine grid for capturing detailed structures of shock or contact wave, which makes high‐order discontinuous Galerkin methods (DGMs) extremely costly. In this work, a characteristic‐compression based adaptive mesh refinement (AMR, h‐adaptive) method is proposed for efficiently improving resolution of the high‐speed flows. In order to allocate computational resources to needed regions, a characteristic‐compression embedded shock wave indicator is developed on incompatible grids and employed as the criterion for AMR. This indicator applies the admissible jumps of eigenvalues to measure the local compression of homogeneous characteristic curves, and theoretically can capture regions of characteristic‐compression which contain structures of shock, contact waves and vortices. Numerical results show that the proposed h‐adaptive DGM is robust, efficient and high‐resolution, it can capture dissipative shock, contact waves of different strengths and vortices with low noise on a rather coarse grid, and can significantly improve resolution of these structures through mild increase of computational resources as compared with the residual‐based h‐adaptive method.
Study of the matrix–particle interactions of polymer nanocomposites in the low‐frequency regime
Authors: Kontou Evagelia
Published: February 2024

In this study, the dynamic moduli, in a wide frequency scale, of two series of polymer nanocomposites were qualitatively discussed. The dynamic mechanical analysis experimental results of polylactic acid (PLA)/silica nanocomposites, as well as PLA/graphene oxide‐carbon nanotubes hybrid nanocomposites, were employed. The study has been focused on the low‐frequency regime, estimating the terminal incline of the storage and loss modulus. In addition, the relative position of the two dynamic moduli was examined and results about the nanofiller's dispersion quality, as well as their interaction with the matrix were extracted. The consequence of nanofiller kind, loading, and distribution quality on the mechanical enhancement was thoroughly studied. In addition, the storage modulus master curves could be simulated by a model from the literature, considering the topological constraints of an entangled polymer reinforced by nanoparticles. It was shown that by adopting the linear contribution of the free and adsorbed chains to the relaxation function, the details of the master curves could be captured in the entire frequency range, quite effectively. The estimated model parameter values confirmed the analysis of the matrix–particle interactions.

Highlights

The SiO2 size effect on the terminal zone slope of the dynamic moduli.

Successful description of the dynamic moduli by the tube reptation concept.

Analysis of the physical meaning of the model parameter values.

Relation between SiO2 dispersion quality and molecular motion restriction.

Matrix‐particle interactions is the governing mechanism of enhancement.
Mechanical behavior of carbon/glass polypropylene hybrid composites
Authors: Ost Charles Antonio , Camargo Monique Camille R. , Rego Artur S. C. , de Bortoli Bruna Farias , Ornaghi Heitor Luiz , Piazza Diego , Zattera Ademir José
Published: February 2024

This research investigates the influence of graphene and some additives on the mechanical behavior of polypropylene (PP). Anhydride maleic coupling agent (MAPP), graphene nanoplatelets (GNPs), and glass fiber (GF) were incorporated into the polymer matrix. The incorporation of MAPP and/or GNP significantly improved the affinity between the PP matrix and fibers while altering the surface morphology. More than 60% of the fibers showed a dimension lower than 0.5 mm. The tensile strength increased from 27.45 to 41 MPa for the neat PP compared to one of the composites. The strength modulus varied from 0.5 to 0.9 GPa. Mechanical tests showed that the addition of MAPP improved the tensile toughness (from 27.45 to 41 N mm mm−2) by 49%, while the GF increased tensile strength, albeit reducing elongation at break. The dynamic mechanical thermal analysis uncovered distinct behavioral variations among fiber‐reinforced samples, particularly in modulus peak differences. In rheological assessment, the presence of GF notably increased viscosity within certain shear rate ranges (at 100 [1/s], the viscosity goes from 200 to 300 Pa s to neat PP for some composites). This research highlights how chosen additives can influence a PP homopolymer's properties, offering useful insights for practical material processing and design.

Highlights

MAPP and GNP can increase PP and glass fiber interfacial bonding.

Glass fiber raises tensile strength and decreases elongation.

Sample with just GNP has a rougher surface, implying better energy dissipation.

Glass fiber raises viscosity in the observed shear rate ranges.

DMA demonstrates that MAPP and GNP have an influence on energy dissipation.
Where are the data to assess the safety of paternal drug exposure? A systematic review of secondary databases: A contribution from IMI concePTION
Authors: Gaitonde Sneha , Moride Yola , Suarez Elizabeth , Lopez‐Leon Sandra
Published: February 2024

Background

Most studies assessing the safety of parental drug exposures during pregnancy and around the time of conception describe the effects of maternal exposure. Recent publications have raised awareness of the need for additional research regarding the safety of paternal drug exposures on pregnancy outcomes.

Objectives

To identify and describe studies that use secondary databases in paternal drug safety studies and to describe the secondary databases that were used.

Methods

A systematic review of studies assessing paternal medication exposure and pregnancy and infant outcomes using secondary databases was performed. In addition, the secondary databases used for these studies was described. Literature search was conducted using Embase, Web of Science, and PubMed, over the period January 1, 2012 to April 30, 2023. For each eligible study, paternal drug exposure, outcome, and data source characteristics were extracted in a data extraction form.

Results

After reviewing the literature, 17 studies met inclusion criteria. The medications assessed for paternal safety were anti‐rheumatic drugs (n = 10), anti‐depressants (n = 3), anticonvulsants (n = 2), and anti‐diabetes medications (n = 2). Pregnancy safety outcomes included congenital malformations, birth weight, and developmental disorders. The studies used five different databases across Europe and North America. The included studies used databases from Denmark (n = 12), Norway (n = 2), Sweden (n = 1), Canada (n = 1), and the United States (n = 1). The European studies utilized national patient registers that linked fathers to births and prescription histories. The North American databases used included insurance claims and electronic health records.

Conclusions

Our review shows that few studies have been completed on paternal medication exposures and pregnancy outcomes, despite the availability of secondary databases that contain data necessary to link fathers to infants. More research on the potential adverse impacts of paternal medication exposures is needed.
Quantum chemical explanation and APT atomic charge index of substituent orienting effect proposed by DFT calculation and MO Theory
Authors: Shi Hongchang
Published: February 2024

In organic chemistry textbooks, the electron resonance states are used to explain the orienting effect of benzene substituent. However, these resonance states do not exist in the C6H5‐S + E+ electrophilic addition, so the resonance state discussions actually are meaningless. The density functional theory (DFT) calculation shows that the C6H5‐S + E+ addition follows the transition state theory and needs to overcome a barrier. Benzene molecule C6H6 has two degenerate highest occupied molecular orbitals (HOMOs), but after becoming substituted benzenes, the two HOMOs split to HOMO and HOMO‐1 with different orbital energies and electron distributions. It makes the addition barrier on two or three benzene ring carbons is low, and the addition rate is fast, but the barrier of other carbons is high, and the rate is slow. Therefore, substituent splits the two degenerate HOMOs of benzene molecule, which is the origin of substituent orienting effect. For the substituted benzenes with halogen group ‐X and electron‐releasing group, their HOMO images alone can determine that the two types of substituents are the ortho‐ and para‐orienting groups, but for the substituted benzenes with electron‐withdrawing group, their HOMO alone cannot determine whether the substituent is a meta‐orienting group. The study found that atomic polar tensor (APT) charges are a good judgment index of substituent orienting effect because based on its physic‐chemical model, the charges represent the number of active electrons on the benzene ring carbons. The DFT calculation gives the APT charges of 19 mono‐substituted and 12 di‐substituted benzenes and some aromatic molecules. The APT charges can all correctly determine their orienting effects, showing that APT atomic charge from quantum theoretical calculation is a good substituent orienting index.
NIR Responsive Drug Cocktail Using J‐Aggregates of Indocyanine Green Loaded Polydopamine Nanoparticles for Chemo‐Phototherapy of Cancer
Authors: Vincy Antony , Gaikwad Yohan , Vankayala Raviraj
Published: February 2024

Co‐loading of drugs/dyes onto nanoparticles is a widely adapted strategy to achieve synergistic/combinatorial effects. However, one of the co‐loaded drugs may show dominant loading which reduces the loading efficiency of the other depending on the properties of the drug/dye loaded. Cisplatin (CDDP), a potent chemotherapeutic drug has very limited usage because of its poor aqueous solubility and systemic toxicity. A novel J‐aggregate is formulated using indocyanine green (ICG) and CDDP called the ICG J‐aggregate (IJA) which coordinates CDDP with ICG and enhances its water solubility resulting in higher loading. Further, polydopamine nanoparticles (PDA NPs) are used, which has shown excellent loading efficiency of IJA to form P‐IJA nano formulation. The results for the first time provide evidence of 2–4 folds increase in CDDP's loading in IJA formulation in comparison to loading of free CDDP under the same conditions. The overall P‐IJA formulation is capable of multi‐modal cancer therapy, i.e., chemotherapy, photothermal therapy, photodynamic therapy, and ferroptosis‐like selective cancer killing. The formulated P‐IJA is also found to be biocompatible, hemocompatible, and stable. The finding of the study suggests that P‐IJA can be effectively activated under NIR laser/pH as stimuli for deep‐tissue synergistic therapy.
Identification of small‐molecule binding sites of a ubiquitin‐conjugating enzyme‐UBE2T through fragment‐based screening
Authors: Loh Yong Yao , Anantharajan Jothi , Huang Qiwei , Xu Weijun , Fulwood Justina , Ng Hui Qi , Ng Elizabeth Yihui , Gea Chong Yu , Choong Meng Ling , Tan Qian Wen , Koh Xiaoying , Lim Wan Hsin , Nacro Kassoum , Cherian Joseph , Baburajendran Nithya , Ke Zhiyuan , Kang CongBao
Published: February 2024

UBE2T is an attractive target for drug development due to its linkage with several types of cancers. However, the druggability of ubiquitin‐conjugating E2 (UBE2T) is low because of the lack of a deep and hydrophobic pocket capable of forming strong binding interactions with drug‐like small molecules. Here, we performed fragment screening using 19F‐nuclear magnetic resonance (NMR) and validated the hits with 1H‐15N‐heteronuclear single quantum coherence (HSQC) experiment and X‐ray crystallographic studies. The cocrystal structures obtained revealed the binding modes of the hit fragments and allowed for the characterization of the fragment‐binding sites. Further screening of structural analogues resulted in the identification of a compound series with inhibitory effect on UBE2T activity. Our current study has identified two new binding pockets in UBE2T, which will be useful for the development of small molecules to regulate the function of this protein. In addition, the compounds identified in this study can serve as chemical starting points for the development of UBE2T modulators.
The catalytic domain of free or ligand bound histone deacetylase 4 occurs in solution predominantly in closed conformation
Authors: Schweipert Markus , Nehls Thomas , Frühauf Anton , Debarnot Cecilé , Kumar Adarsh , Knapp Stefan , Lermyte Frederik , Meyer‐Almes Franz‐Josef
Published: February 2024

Human histone deacetylase 4 (HDAC4) is a key epigenetic regulator involved in a number of important cellular processes. This makes HDAC4 a promising target for the treatment of several cancers and neurodegenerative diseases, in particular Huntington's disease. HDAC4 is highly regulated by phosphorylation and oxidation, which determine its nuclear or cytosolic localization, and exerts its function through multiple interactions with other proteins, forming multiprotein complexes of varying composition. The catalytic domain of HDAC4 is known to interact with the SMRT/NCOR corepressor complex when the structural zinc‐binding domain (sZBD) is intact and forms a closed conformation. Crystal structures of the HDAC4 catalytic domain have been reported showing an open conformation of HDAC4 when bound to certain ligands. Here, we investigated the relevance of this HDAC4 conformation under physiological conditions in solution. We show that proper zinc chelation in the sZBD is essential for enzyme function. Loss of the structural zinc ion not only leads to a massive decrease in enzyme activity, but it also has serious consequences for the overall structural integrity and stability of the protein. However, the Zn2+ free HDAC4 structure in solution is incompatible with the open conformation. In solution, the open conformation of HDAC4 was also not observed in the presence of a variety of structurally divergent ligands. This suggests that the open conformation of HDAC4 cannot be induced in solution, and therefore cannot be exploited for the development of HDAC4‐specific inhibitors.
Impact of the Crystal Structure of Interlayer on the Properties of Zr‐Doped Hafnia‐Based Ferroelectric Capacitor
Authors: Park Inseon , Choi Yejoo , Shin Changhwan
Published: February 2024

In this work, the effect of interlayer on the ferroelectric properties of Hf0.5Zr0.5O2(HZO)‐based metal–ferroelectric–metal (MFM) capacitor is investigated. In detail, a 1 nm thick interlayer of amorphous Al2O3and fluorite‐structured ZrO2is inserted in the HZO ferroelectric film. Grazing incidence X‐ray diffraction (GIXRD) analysis reveals that the amorphous structure of Al2O3(vs. the fluorite‐structured ZrO2) effectively blocks the grain boundary growth of HZO layer. In contrast, X‐ray photoelectron spectroscopy (XPS) analysis demonstrates that ZrO2with a fluorite structure like HZO induces fewer oxygen vacancies at the ferroelectric–insulator interface, and thereby, it provides fewer defects in the HZO layer, achieving fatigue‐free endurance characteristics and a higher remanent polarization (2Pr) of 4.6 μC cm−2.
Phillygenin prevents osteoclast differentiation and bone loss by targeting RhoA
Authors: Zhang Jiahui , Jiang Tao , Zhang Yuxin , Yang Kai , Zhao Yichen , Zhou Qi , Yang Zhuo , Yang Renhao , Ning Ruonan , Liu Tao , Deng Lianfu , Xi Xiaobing , Xu Xing , Jiang Min
Published: February 2024

Forsythia suspensa tea is a popular traditional Chinese medicine decoction for its healthy and therapeutic benefits. However, its effects in bone metabolism were not clear. In recent study, we uncovered anti‐osteoclastogenesis property of Phillygenin (Phi), a compound abundant in Forsythia suspensa leaves, and aimed to investigate the effect and mechanism of Phi on bone metabolism in vivo and in vitro. Lipopolysaccharides‐induced murine calvaria osteolysis and ovariectomy‐induced bone loss animal models were used to identify the bone‐protective effect of Phi in vivo and micro‐CT, pQCT, and TRAP staining were applied. We used CCK8, TUNEL, BrdU, and TRAP staining to evaluate the efficacy of Phi on the proliferation and formation of OCs in primary mBMMs. RNA sequence, activity‐based protein profiling, molecular docking, G‐LISA, and WB were used to inspect the target and underlying mechanism of Phi's actions in mBMMs. We found Phi significantly inhibited bone resorption in vivo and inhibited mBMMs osteoclastogenesis in vitro. Ras homolog gene family member A (RhoA) was identified as the direct target of Phi. It counteracted the effects of RhoA activator and acted as a RhoA inhibitor. By targeting RhoA, Phi modulated Rho‐associated coiled‐coil containing protein kinase 1 (ROCK1) activity and regulated its downstream NF‐κB/NFATc1/c‐fos pathway. Furthermore, Phi depressed the disassembling of F‐actin ring through cofilin and myosin1a. Our findings provided Phi as a potential option for treating bone loss diseases by targeting RhoA and highlighted the importance of F. suspensa as a preventive approach in bone disorders.