bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on Grinding Behavior Characteristics under Low-Speed Grinding Condition
Authors: Ma Shaojian , Yang Xiaojing , Li Hengjun , Xu Wenzhe , Deng Xingjian , Yang Jinlin
Published: June 2023

In order to explore the crushing mechanism of minerals, this paper attempts to eliminate the throwing effect of media and study the grinding characteristics of minerals only under the action of abrasion force. In this paper, the method of removing the throwing state of media is to adjust the mill to a lower rotational speed, so that the grinding media are all in a cascading state. Three single-component pure minerals, quartz, pyrrhotite, and pyrite, commonly found in complex ores, were selected as research objects to study the grinding behavior characteristics of the three minerals only under the force of abrasion. The effects of mineral species, feed-particle sizes, grinding time, and other factors on the particle-size distribution and product-generation rate of grinding products are studied. The results show that from the particle-size distribution of grinding products, the yield of coarse particles is the highest, while the yield and t10 value of other fine particles are very low. The feed-particle size and the hardness of the mineral sample affect the grinding behavior. The product particle size is mainly 0.71 times the feed-particle size, and the other fine particle sizes generated are less than 0.5 times the feed-particle size.
Geochemical Stratigraphy of the Prima Porta Travertine Deposit (Roma, Italy)
Authors: Brilli Mauro , Giustini Francesca
Published: June 2023

A stratigraphy of a buried travertine deposit was developed using stable isotope geochemistry, trace elements, and radiometric dating. The travertine was identified in a well at Prima Porta (north of Rome, Italy), located at the western boundary of the Tiber Valley, a morpho-tectonic depression of extensional origin. It deposited close to a spring that discharged groundwaters from the nearby volcanic aquifer and was associated with the rise of a deep-seated CO2-rich fluid. The deposition occurred between 53.5 ± 10 ka to 24.2 ± 4.7 ka; its activation was probably coeval with the wettest climatic conditions occurring during Marine Isotope Stage 3, and the end coincided with the cold and arid phase of the last glacial maximum. The chronostratigraphy showed a strong variation in the accumulation rate along the depositional sequence, greater in the lower half and much slower in the upper part, with a sharp decrease in the accumulation rate occurring between 47 and 43 ka. Isotope and chemical stratigraphy described a temporal evolution of events that are correlated to the global climatic variability; palaeoclimatic changes, in fact, influenced the hydrological regime and indirectly the tectonic activity by modulating the emission of deep CO2, the chemistry of the groundwater, and ultimately the precipitation of the travertine.
Fluvial Morphology as a Driver of Lead and Zinc Geochemical Dispersion at a Catchment Scale
Authors: Onnis Patrizia , Byrne Patrick , Hudson-Edwards Karen A. , Stott Tim , Hunt Chris O.
Published: June 2023

Metal-mining exploitation has caused ecosystem degradation worldwide. Legacy wastes are often concentrated around former mines where monitoring and research works are mostly focused. Geochemical and physical weathering can affect metal-enriched sediment locations and their capacity to release metals at a catchment scale. This study investigated how fluvial geomorphology and soil geochemistry drive zinc and lead dispersion along the Nant Cwmnewyddion (Wales, UK). Sediments from different locations were sampled for geochemical and mineralogical investigations (portable X-ray fluorescence, scanning electron microscope, X-ray diffraction, and electron microprobe analysis). The suspended sediment fluxes in the streamwater were estimated at different streamflows to quantify the metal dispersion. Topographical and slope analysis allowed us to link sediment erosion with the exposure of primary sulphide minerals in the headwater. Zinc and lead entered the streamwater as aqueous phases or as suspended sediments. Secondary sources were localised in depositional stream areas due to topographical obstruction and a decrease in stream gradient. Sediment zinc and lead concentrations were lower in depositional areas and associated with Fe-oxide or phyllosilicates. Streamwater zinc and lead fluxes highlighted their mobility under high-flow conditions. This multi-disciplinary approach stressed the impact of the headwater mining work on the downstream catchment and provided a low-cost strategy to target sediment sampling via geomorphological observations.
Novel Effect of p-Coumaric Acid on Hepatic Lipolysis: Inhibition of Hepatic Lipid-Droplets
Authors: Yuan Zhiyi , Lu Xi , Lei Fan , Sun Hong , Jiang Jingfei , Xing Dongming , Du Lijun
Published: June 2023

p-coumaric acid (p-CA), a common plant phenolic acid with multiple bioactivities, has a lipid-lowering effect. As a dietary polyphenol, its low toxicity, with the advantages of prophylactic and long-term administration, makes it a potential drug for prophylaxis and the treatment of nonalcoholic fatty liver disease (NAFLD). However, the mechanism by which it regulates lipid metabolism is still unclear. In this study, we studied the effect of p-CA on the down-regulation of accumulated lipids in vivo and in vitro. p-CA increased a number of lipase expressions, including hormone-sensitive lipase (HSL), monoacylglycerol lipase (MGL) and hepatic triglyceride lipase (HTGL), as well as the expression of genes related to fatty acid oxidation, including long-chain fatty acyl-CoA synthetase 1 (ACSL1), carnitine palmitoyltransferase-1 (CPT1), by activating peroxisome proliferator-activated receptor α, and γ (PPARα and γ). Furthermore, p-CA promoted adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and enhanced the expression of the mammalian suppressor of Sec4 (MSS4), a critical protein that can inhibit lipid droplet growth. Thus, p-CA can decrease lipid accumulation and inhibit lipid droplet fusion, which are correlated with the enhancement of liver lipases and genes related to fatty acid oxidation as an activator of PPARs. Therefore, p-CA is capable of regulating lipid metabolism and is a potential therapeutic drug or health care product for hyperlipidemia and fatty liver.
Effects of Synthetic Ligustrazine-Based Chalcone Derivatives on Trypanosoma brucei brucei and Leishmania spp. Promastigotes
Authors: Alkhaldi Abdulsalam A. M.
Published: June 2023

Current medication therapy for leishmaniasis and trypanosomiasis remains a major challenge due to its limited efficacy, significant adverse effects, and inaccessibility. Consequently, locating affordable and effective medications is a pressing concern. Because of their easy-to-understand structure and high functionalization potential, chalcones are promising candidates for use as bioactive agents. Thirteen synthetic ligustrazine-containing chalcones were evaluated for their ability to inhibit the growth of leishmaniasis and trypanosomiasis in etiologic agents. The tetramethylpyrazine (TMP) analogue ligustrazine was chosen as the central moiety for the synthesis of these chalcone compounds. The most effective compound (EC50 = 2.59 µM) was the chalcone derivative 2c, which featured a pyrazin-2-yl amino on the ketone ring and a methyl substitution. Multiple actions were observed for certain derivatives, including 1c, 2a–c, 4b, and 5b, against all strains tested. Eflornithine served as a positive control, and three ligustrazine-based chalcone derivatives, including 1c, 2c, and 4b, had a higher relative potency. Compounds 1c and 2c are particularly efficacious; even more potent than the positive control, they are therefore promising candidates for the treatment of trypanosomiasis and leishmaniasis.
New Insight into the Substrate Selectivity of Bovine Milk γ-glutamyl Transferase via Structural and Molecular Dynamics Predictions
Authors: Cao Lichuang , Hunt Cameron J. , Meyer Anne S. , Lametsch René
Published: June 2023

Bovine milk γ-glutamyltransferase (BoGGT) can produce γ-glutamyl peptides using L-glutamine as a donor substrate, and the transpeptidase activity is highly dependent on both γ-glutamyl donors and acceptors. To explore the molecular mechanism behind the donor and acceptor substrate preferences for BoGGT, molecular docking and molecular dynamic simulations were performed with L-glutamine and L-γ-glutamyl-p-nitroanilide (γ-GpNA) as donors. Ser450 is a crucial residue for the interactions between BoGGT and donors. BoGGT forms more hydrogen bonds with L-glutamine than γ-GpNA, promoting the binding affinity between BoGGT and L-glutamine. Gly379, Ile399, and Asn400 are crucial residues for the interactions between the BoGGT intermediate and acceptors. The BoGGT intermediate forms more hydrogen bonds with Val-Gly than L-methionine and L-leucine, which can promote the transfer of the γ-glutamyl group from the intermediate to Val-Gly. This study reveals the critical residues responsible for the interactions of donors and acceptors with the BoGGT and provides a new understanding of the substrate selectivity and catalytic mechanism of GGT.
Computational Investigation of Interactions between Carbon Nitride Dots and Doxorubicin
Authors: Bartoli Mattia , Marras Elena , Tagliaferro Alberto
Published: June 2023

The study of carbon dots is one of the frontiers of materials science due to their great structural and chemical complexity. These issues have slowed down the production of solid models that are able to describe the chemical and physical features of carbon dots. Recently, several studies have started to resolve this challenge by producing the first structural-based interpretation of several kinds of carbon dots, such as graphene and polymeric ones. Furthermore, carbon nitride dot models established their structures as being formed by heptazine and oxidized graphene layers. These advancements allowed us to study their interaction with key bioactive molecules, producing the first computational studies on this matter. In this work, we modelled the structures of carbon nitride dots and their interaction with an anticancer molecule (Doxorubicin) using semi-empirical methods, evaluating both geometrical and energetic parameters.
Design, Synthesis, and Evaluation of the COX-2 Inhibitory Activities of New 1,3-Dihydro-2H-indolin-2-one Derivatives
Authors: Pan Taohua , He Maofei , Deng Lulu , Li Jiang , Fan Yanhua , Hao Xiaojiang , Mu Shuzhen
Published: June 2023

Thirty-three 1,3-dihydro-2H-indolin-2-one derivatives bearing α, β-unsaturated ketones were designed and synthesized via the Knoevenagel condensation reaction. The cytotoxicity, in vitro anti-inflammatory ability, and in vitro COX-2 inhibitory activity of all the compounds were evaluated. Compounds 4a, 4e, 4i-4j, and 9d exhibited weak cytotoxicity and different degrees of inhibition against NO production in LPS-stimulated RAW 264.7 cells. The IC50 values of compounds 4a, 4i, and 4j were 17.81 ± 1.86 μM, 20.41 ± 1.61 μM, and 16.31 ± 0.35 μM, respectively. Compounds 4e and 9d showed better anti-inflammatory activity with IC50 values of 13.51 ± 0.48 μM and 10.03 ± 0.27 μM, respectively, which were lower than those of the positive control ammonium pyrrolidinedithiocarbamate (PDTC). Compounds 4e, 9h, and 9i showed good COX-2 inhibitory activities with IC50 values of 2.35 ± 0.04 µM, 2.422 ± 0.10 µM and 3.34 ± 0.05 µM, respectively. Moreover, the possible mechanism by which COX-2 recognized 4e, 9h, and 9i was predicted by molecular docking. The results of this research suggested that compounds 4e, 9h, and 9i might be new anti-inflammatory lead compounds for further optimization and evaluation.
G-Quadruplexes Formation by the C9orf72 Nucleotide Repeat Expansion d(GGGGCC)n and Conformation Regulation by Fangchinoline
Authors: Zhang Yun , Huang Junliu , Yu Kainan , Cui Xiaojie
Published: June 2023

The G-quadruplex (GQ)-forming hexanucleotide repeat expansion (HRE) in the C9orf72 (C9) gene has been found to be the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (collectively, C9ALS/FTD), implying the great significance of modulating C9-HRE GQ structures in C9ALS/FTD therapeutic treatment strategies. In this study, we investigated the GQ structures formed by varied lengths of C9-HRE DNA sequences d(GGGGCC)4 (C9-24mer) and d(GGGGCC)8 (C9-48mer), and found that the C9-24mer forms anti-parallel GQ (AP-GQ) in the presence of potassium ions, while the long C9-48mer bearing eight guanine tracts forms unstacked tandem GQ consisting of two C9-24mer unimolecular AP-GQs. Moreover, the natural small molecule Fangchinoline was screened out in order to be able to stabilize and alter the C9-HRE DNA to parallel GQ topology. Further study of the interaction of Fangchinoline with the C9-HRE RNA GQ unit r(GGGGCC)4 (C9-RNA) revealed that it can also recognize and improve the thermal stability of C9-HRE RNA GQ. Finally, use of AutoDock simulation results indicated that Fangchinoline binds to the groove regions of the parallel C9-HRE GQs. These findings pave the way for further studies of GQ structures formed by pathologically related long C9-HRE sequences, and also provide a natural small-molecule ligand that modulates the structure and stability of C9-HRE GQ, both in DNA and RNA levels. Altogether, this work may contribute to therapeutic approaches of C9ALS/FTD which take the upstream C9-HRE DNA region, as well as the toxic C9-HRE RNA, as targets.
Small Molecule Inhibitors as Therapeutic Agents Targeting Oncogenic Fusion Proteins: Current Status and Clinical
Authors: Kong Yichao , Jiang Caihong , Wei Guifeng , Sun Kai , Wang Ruijie , Qiu Ting
Published: June 2023

Oncogenic fusion proteins, arising from chromosomal rearrangements, have emerged as prominent drivers of tumorigenesis and crucial therapeutic targets in cancer research. In recent years, the potential of small molecular inhibitors in selectively targeting fusion proteins has exhibited significant prospects, offering a novel approach to combat malignancies harboring these aberrant molecular entities. This review provides a comprehensive overview of the current state of small molecular inhibitors as therapeutic agents for oncogenic fusion proteins. We discuss the rationale for targeting fusion proteins, elucidate the mechanism of action of inhibitors, assess the challenges associated with their utilization, and provide a summary of the clinical progress achieved thus far. The objective is to provide the medicinal community with current and pertinent information and to expedite the drug discovery programs in this area.
Synthesis and Characterization of a New Series of Bis(allylic-α-aminophosphonates) under Mild Reaction Conditions
Authors: Souii Ichrak , Sanhoury Med Abderrahmane , Vicario Javier , Jiménez-Aberásturi Xabier , Efrit Mohamed L. , M’rabet Hedi , de los Santos Jesús M.
Published: June 2023

Several bis(α-aminophosphonates) have been conveniently prepared in good yields using a straightforward multicomponent Kabachnik–Fields reaction between ethane 1,2-diamine or propane 1,3-diamine, diethylphosphite and aldehydes under catalyst-free conditions. The nucleophilic substitution reaction of bis(α-aminophosphonates) prepared and ethyl (2-bromomethyl)acrylate under mild reaction conditions afforded an original synthetic approach to a new series of bis(allylic-α-aminophosphonates).
Non-Invasive Mapping of Cerebral Autoregulation Using Near-Infrared Spectroscopy: A Study Protocol
Authors: Sainbhi Amanjyot Singh , Vakitbilir Nuray , Gomez Alwyn , Stein Kevin Y. , Froese Logan , Zeiler Frederick A.
Published: June 2023

The ability of cerebral vessels to maintain a fairly constant cerebral blood flow is referred to as cerebral autoregulation (CA). Using near-infrared spectroscopy (NIRS) paired with arterial blood pressure (ABP) monitoring, continuous CA can be assessed non-invasively. Recent advances in NIRS technology can help improve the understanding of continuously assessed CA in humans with high spatial and temporal resolutions. We describe a study protocol for creating a new wearable and portable imaging system that derives CA maps of the entire brain with high sampling rates at each point. The first objective is to evaluate the CA mapping system’s performance during various perturbations using a block-trial design in 50 healthy volunteers. The second objective is to explore the impact of age and sex on regional disparities in CA using static recording and perturbation testing in 200 healthy volunteers. Using entirely non-invasive NIRS and ABP systems, we hope to prove the feasibility of deriving CA maps of the entire brain with high spatial and temporal resolutions. The development of this imaging system could potentially revolutionize the way we monitor brain physiology in humans since it would allow for an entirely non-invasive continuous assessment of regional differences in CA and improve our understanding of the impact of the aging process on cerebral vessel function.
The Effect of Iron Oxide Nanoparticles on the Menaquinone-7 Isomer Composition and Synthesis of the Biologically Significant All-Trans Isomer
Authors: Lal Neha , Seifan Mostafa , Ebrahiminezhad Alireza , Berenjian Aydin
Published: June 2023

Menaquinone-7 (MK-7) is the most therapeutically valuable K vitamin owing to its excellent bioavailability. MK-7 occurs as geometric isomers, and only all-trans MK-7 is bioactive. The fermentation-based synthesis of MK-7 entails various challenges, primarily the low fermentation yield and numerous downstream processing steps. This raises the cost of production and translates to an expensive final product that is not widely accessible. Iron oxide nanoparticles (IONPs) can potentially overcome these obstacles due to their ability to enhance fermentation productivity and enable process intensification. Nevertheless, utilisation of IONPs in this regard is only beneficial if the biologically active isomer is achieved in the greatest proportion, the investigation of which constituted the objective of this study. IONPs (Fe3O4) with an average size of 11 nm were synthesised and characterised using different analytical techniques, and their effect on isomer production and bacterial growth was assessed. The optimum IONP concentration (300 μg/mL) improved the process output and resulted in a 1.6-fold increase in the all-trans isomer yield compared to the control. This investigation was the first to evaluate the role of IONPs in the synthesis of MK-7 isomers, and its outcomes will assist the development of an efficient fermentation system that favours the production of bioactive MK-7.
Constitutive Modeling of Mechanical Behaviors of Carbon-Based CNTs and GSs, and Their Sensing Applications as Nanomechanical Resonators: A Review
Authors: Natsuki Toshiaki , Natsuki Jun
Published: June 2023

Carbon-based nanomaterials, including carbon nanotubes (CNTs) and graphene sheets (GSs), have garnered considerable research attention owing to their unique mechanical, physical, and chemical properties compared with traditional materials. Nanosensors are sensing devices with sensing elements made of nanomaterials or nanostructures. CNT- and GS-based nanomaterials have been proved to be very sensitive nanosensing elements, being used to detect tiny mass and force. In this study, we review the developments in the analytical modeling of mechanical behavior of CNTs and GSs, and their potential applications as next-generation nanosensing elements. Subsequently, we discuss the contributions of various simulation studies on theoretical models, calculation methods, and mechanical performance analyses. In particular, this review intends to provide a theoretical framework for a comprehensive understanding of the mechanical properties and potential applications of CNTs/GSs nanomaterials as demonstrated by modeling and simulation methods. According to analytical modeling, nonlocal continuum mechanics pose small-scale structural effects in nanomaterials. Thus, we overviewed a few representative studies on the mechanical behavior of nanomaterials to inspire the future development of nanomaterial-based sensors or devices. In summary, nanomaterials, such as CNTs and GSs, can be effectively utilized for ultrahigh-sensitivity measurements at a nanolevel resolution compared to traditional materials.
Gut Symptoms during FODMAP Restriction and Symptom Response to Food Challenges during FODMAP Reintroduction: A Real-World Evaluation in 21,462 Participants Using a Mobile Application
Authors: Dimidi Eirini , Belogianni Katerina , Whelan Kevin , Lomer Miranda C. E.
Published: June 2023

Background: There is limited evidence regarding the use of low FODMAP diet apps. This study aimed to evaluate the effectiveness of an app intended to reduce symptoms in FODMAP restriction and symptoms and tolerance of high FODMAP food challenges during FODMAP reintroduction and personalisation. Methods: Data were collected from 21,462 users of a low FODMAP diet app. Self-reported gut symptoms during FODMAP restriction, reintroduction, and personalisation and dietary triggers were identified from symptom response data for FODMAP food challenges. Results: Compared with baseline, at the end of FODMAP restriction, participants (n = 20,553) reported significantly less overall symptoms (11,689 (57%) versus 9105 (44%)), abdominal pain (8196 (40%) versus 6822 (33%)), bloating (11,265 (55%) versus 9146 (44%)), flatulence (10,318 (50%) 8272 (40%)), and diarrhoea (6284 (31%) versus 4961 (24%)) and significantly more constipation (5448 (27%) versus 5923 (29%)) (p < 0.001 for all). During FODMAP reintroduction, participants (n = 2053) completed 8760 food challenges; the five most frequent challenges and n/N (%) of dietary triggers identified were wheat bread 474/1146 (41%), onion 359/918 (39%), garlic 245/699 (35%), milk 274/687 (40%), and wheat pasta 222/548 (41%). The most frequently reported symptoms during food challenges were overall symptoms, abdominal pain, bloating, and flatulence. Conclusions: In a real-world setting, a low FODMAP diet app can help users improve gut symptoms and detect dietary triggers for long-term self-management.
Assessment of Nutritional Status by Bioelectrical Impedance in Adult Patients with Celiac Disease: A Prospective Single-Center Study
Authors: Maniero Daria , Lorenzon Greta , Marsilio Ilaria , D’Odorico Anna , Savarino Edoardo Vincenzo , Zingone Fabiana
Published: June 2023

The gluten-free diet [GFD] has been linked to an increased risk of weight gain and the development of metabolic disorders. Most of the studies have focused on the effect of GFD on the Body Mass Index [BMI]. We aimed to evaluate the nutritional status using specific nutritional parameters in patients with celiac disease [CeD] at diagnosis and on a GFD compared to healthy controls. We recruited subjects at our outpatient clinic at the University of Padua. We collected demographic and clinical data and values obtained with bioelectrical impedance analysis. A total of 24 CeD patients and 28 healthy controls were enrolled. CeD patients at diagnosis had a lower body cell mass index [BCMI, p = 0.006], fat-free mass index [FFMI, p = 0.02], appendicular skeletal muscle index [ASMI, p = 0.02], and phase angle [PA] [p < 0.001] compared to controls. Their percentage of extracellular water [ECW] was also higher [p < 0.001]. Considering CeD patients after GFD, nutritional status significantly improved after 6 months of GFD. We did not observe differences in BMI among groups [p = ns]. CeD patients at diagnosis were found to have a poorer nutritional status than healthy controls, with a positive effect of the GFD on their nutritional status, underlining the inefficacy of evaluating this aspect through only BMI evaluation.
Increasing Our Understanding of How Dietary Components Can Affect Cellular Mechanisms That Regulate Aging and Slow the Onset of Frailty and Chronic Diseases
Authors: Capurso Cristiano
Published: June 2023

The current average life expectancy at birth is well over 80 years [...]
The Association between Serum Vitamin D Levels and Urinary Tract Infection Risk in Children: A Systematic Review and Meta-Analysis
Authors: Gan Yan , You Siyi , Ying Junjie , Mu Dezhi
Published: June 2023

The association between serum vitamin D levels and urinary tract infection (UTI) in children is unclear. We undertook a systematic review and meta-analysis to evaluate the relationships between different vitamin D levels and the likelihood of UTI in children. Online databases, including Web of Science, PubMed, Embase, and Cochrane Library, were searched up to 6 February 2023 for studies based on the inclusion criteria. Weighted mean difference (WMD) and Odds Ratios (ORs), along with their 95% confidence intervals (CI), were calculated, and the random-effects model was used for analysis. Twelve case–control studies and one cross-sectional study (839 children with UTI and 929 controls) were included. We found that children with UTI had lower levels of serum vitamin D than healthy controls (WMD: −7.730, 95% CI: −11.57, −3.89; p < 0.001). Low vitamin D levels were significantly associated with UTI in children (OR: 2.80; 95% CI: 1.55, 5.05; p = 0.001). The likelihood of children having a UTI significantly increased when their serum vitamin D level was less than 20 ng/mL (OR: 5.49, 95% CI: 1.12, 27.04; p = 0.036). Therefore, vitamin D level, especially when less than 20 ng/mL, is a risk factor in UTI.
Muscle Traits, Sarcopenia, and Sarcopenic Obesity: A Vitamin D Mendelian Randomization Study
Authors: Sutherland Joshua P. , Zhou Ang , Hyppönen Elina
Published: June 2023

(1) Background: Observational studies associate vitamin D deficiency with muscle disorders, while some clinical trial data support a minor association between the vitamin and skeletal muscle performance in healthy subjects. Vitamin D receptor knockout mice studies confirm the relationship between vitamin D and skeletal muscle; however, causal inference in humans is challenging due to the ethical implications of including vitamin D-deficient participants in randomized trials. This study uses genetic methods to safely explore causal underpinnings for the relationship between 25(OH)D concentrations and skeletal muscle-related traits, including grip strength and combined arm skeletal muscle mass, and extends this analysis to suspected pathophysiology in the form of probable sarcopenia and sarcopenic obesity. (2) Methods: We conducted Mendelian randomization (MR) analyses in up to 307,281 participants from the UK Biobank of whom 25,414 had probable sarcopenia and 16,520 had sarcopenic obesity. In total, 35 variants were used to instrument 25(OH)D and MR analyses conducted using multiple approaches. (3) Results: Genetic analyses provided support for a relationship between genetically predicted higher 25(OH)D and skeletal muscle traits, with linear MR analyses for grip strength showing 0.11 kg (95% CI 0.04, 0.19) greater contractile force per 10 unit higher 25(OH)D, while there was a modest association with skeletal muscle mass (0.01 kg (95% CI 0.003, 0.02) greater muscle mass). For probable sarcopenia risk, there was suggestive evidence for lower odds by higher 25(OH)D (OR 0.96 (95% CI 0.92, 1.00)); however, this did not reflect an association with sarcopenic obesity (OR 0.97 (95% CI 0.93, 1.02)), but was seen in probable sarcopenia cases who were not obese (OR 0.92 (95% CI 0.86, 0.98)). Results were similar across multiple MR approaches. (4) Conclusions: Our study supports a causal relationship between 25(OH)D and skeletal muscle health. While evidence for benefit did not extend to lower risk of sarcopenic obesity, effective vitamin D-deficiency prevention strategies may help reduce age-related muscle weakness.
Development of Type A Quadrupole Magnet for Siam Photon Source II
Authors: Prawanta Supachai , Leetha Thongchai , Singthong Pariwat , Numanoy Pajeeraphorn , Kwankasem Apichai , Sooksrimuang Visitchai , Preecha Chaiyut , Klinkiew Supat , Sunwong Prapaiwan
Published: June 2023

A prototype of a type A quadrupole magnet has been designed and manufactured for the 3 GeV storage ring of Siam Photon Source II, the second synchrotron light source in Thailand. The required quadrupole gradient is 51 T/m with the magnet effective length being 162 mm. Magnet modeling and magnetic field calculation were performed using Radia and Opera-3D. The bore radius of the magnet is 16 mm. The magnet will be operated at the excitation of 5544 A-turns. A mechanical analysis of the magnet structure was performed in SOLIDWORKS and ANSYS, where the maximum deformation of 0.003 mm was found at the magnet poles, and the first-mode natural frequency was higher than 100 Hz. The magnet yoke is made of AISI 1006 low-carbon steel with a fabrication tolerance of ±0.020 mm. Magnet coils are water-cooled and made of high-purity copper. The temperature rise of the coils was below 3.0 °C at the maximum excitation of 6664 A-turns, which is 20% above the operating point. Magnetic field measurement was carried out using the Hall probe technique. The measured magnetic field and coil temperature of the prototype show good agreement with the calculations.
Study on the Intervention Mechanism of Cryptotanshinone on Human A2780 Ovarian Cancer Cell Line Using GC-MS-Based Cellular Metabolomics
Authors: Wang Tong , Yin Shusheng , Gu Juan , Li Jingjing , Zhang Mengmeng , Shan Jinjun , Wu Xiao , Li Yongming
Published: June 2023

Cryptotanshinone (CT), an active component of the traditional Chinese medicine Salvia miltiorrhiza Bunge, exhibits a wide range of biological and pharmacological activities. Although the anticancer activity of CT is well known, the knowledge of its effect on the regulation of cancer cell metabolism is relatively new. The present study investigated the anticancer mechanism of CT in ovarian cancer with a focus on cancer metabolism. CCK8 assays, apoptosis assays, and cell cycle assays were conducted to reveal the growth-suppressive effect of CT on ovarian cancer A2780 cells. To explore the potential underlying mechanisms of CT, the changes in endogenous metabolites in A2780 cells before and after CT intervention were investigated using the gas chromatography–mass spectrometry (GC-MS) approach. A total of 28 important potential biomarkers underwent significant changes, mainly involving aminoacyl-tRNA biosynthesis, energy metabolism, and other pathways. Changes in the ATP and amino acid contents were verified with in vitro and in vivo experiments. Our results indicate that CT may exert an anti-ovarian cancer effect by inhibiting ATP production, promoting the protein catabolic process, and inhibiting protein synthesis, which may lead to cell cycle arrest and apoptosis.
Targeting Spike Glycoprotein S1 Mediated by NLRP3 Inflammasome Machinery and the Cytokine Releases in A549 Lung Epithelial Cells by Nanocurcumin
Authors: Chittasupho Chuda , Srisawad Kamonwan , Arjsri Punnida , Phongpradist Rungsinee , Tingya Wipawan , Ampasavate Chadarat , Dejkriengkraikul Pornngarm
Published: June 2023

Chronic inflammation and tissue damage can result from uncontrolled inflammation during SARS-CoV-2 or COVID-19 infections, leading to post-acute COVID conditions or long COVID. Curcumin, found in turmeric, has potent anti-inflammatory properties but limited effectiveness. This study developed nanocurcumin, a curcumin nanoparticle, to enhance its physical and chemical stability and investigate its in vitro anti-inflammatory properties upon CoV2-SP induction in lung epithelial cells. Nanocurcumin was prepared by encapsulating curcumin extract in phospholipids. The particle size, polydispersity index, and zeta potential of nanocurcumin were measured using dynamic light scattering. The encapsulated curcumin content was determined using HPLC analysis. The encapsulation efficiency of curcumin was 90.74 ± 5.35% as determined by HPLC. Regarding the in vitro release of curcumin, nanocurcumin displayed a higher release content than non-nanoparticle curcumin. Nanocurcumin was further investigated for its anti-inflammatory properties using A549 lung epithelial cell line. As determined by ELISA, nanocurcumin showed inhibitory effects on inflammatory cytokine releases in CoV2-SP-stimulated conditions, as evidenced by a significant decrease in IL-6, IL-1β and IL-18 cytokine secretions compared with the spike-stimulated control group (p < 0.05). Additionally, as determined by RT-PCR, nanocurcumin significantly inhibited the CoV2-SP-stimulated expression of inflammatory genes (IL-6, IL-1β, IL-18, and NLRP3) compared with the spike-stimulated control group (p < 0.05). Regarding the inhibition of NLRP3 inflammasome machinery proteins by Western blot, nanocurcumin decreased the expressions of inflammasome machinery proteins including NLRP3, ASC, pro-caspase-1, and the active form of caspase-1 in CoV2-SP-stimulated A549 cells compared with the spike-stimulated control group (p < 0.05). Overall, the nanoparticle formulation of curcumin improved its solubility and bioavailability, demonstrating anti-inflammatory effects in a CoV2-SP-induced scenario by inhibiting inflammatory mediators and the NLRP3 inflammasome machinery. Nanocurcumin shows promise as an anti-inflammatory product for preventing COVID-19-related airway inflammation.
Isolation and Cultivation of Porcine Endothelial Cells, Pericytes and Astrocytes to Develop an In Vitro Blood–Brain Barrier Model for Drug Permeation Testing
Authors: Ledwig Verena , Reichl Stephan
Published: June 2023

The blood–brain barrier (BBB) is the bottleneck in the development of new drugs to reach the brain. Due to the BBB, toxic substances cannot enter the brain, but promising drug candidates also pass the BBB poorly. Suitable in vitro BBB models are therefore of particular importance during the preclinical development process, as they can not only reduce animal testing but also enable new drugs to be developed more quickly. The aim of this study was to isolate cerebral endothelial cells, pericytes, and astrocytes from the porcine brain to produce a primary model of the BBB. Additionally, as primary cells are well suited by their properties but the isolation is complex and better reproducibility with immortalized cells must be ensured, there is a high demand for immortalized cells with suitable properties for use as a BBB model. Thus, isolated primary cells can also serve as the basis for a suitable immortalization technique to generate new cell lines. In this work, cerebral endothelial cells, pericytes, and astrocytes were successfully isolated and expanded using a mechanical/enzymatic method. Furthermore, in a triple coculture model, the cells showed a significant increase in barrier integrity compared with endothelial cell monoculture, as determined by transendothelial electrical resistance measurement and permeation studies using sodium fluorescein. The results demonstrate the opportunity to obtain all three cell types significantly involved in BBB formation from one species, thus providing a suitable tool for testing the permeation properties of new drug candidates. In addition, the protocols are a promising starting point to generate new cell lines of BBB-forming cells as a novel approach for BBB in vitro models.
Evidence of a New Crystalline Phase of Prednisolone Obtained from the Study of the Hydration–Dehydration Mechanisms of the Sesquihydrate
Authors: Lemercier Aurélien , Couvrat Nicolas , Cartigny Yohann , Sanselme Morgane , Corvis Yohann , Espeau Philippe , Coquerel Gérard
Published: June 2023

The dehydration of prednisolone sesquihydrate is studied and characterized by different physico-chemical analysis methods. The meticulous study of this dehydration led to the highlighting of a new solid form (form 3), metastable, never identified before. In a second step, the rehydration of anhydrous forms 1 and 2 of prednisolone is studied, in particular by Dynamic Vapor Sorption. It is then demonstrated that neither of the two forms is sensitive to humidity. By means of solid-gas equilibria, the sesquihydrate can only be obtainable from the isomorphic anhydrous form. Finally, a classification of the sesquihydrate is made, taking into account, in particular, the activation energy determined during dehydration.
Designing Aerosol Therapies Based on the Integrated Evaluation of In Vitro, In Vivo, and In Silico Data
Authors: Bourlon Margaret , Feng Yu , Garcia-Contreras Lucila
Published: June 2023

Despite the advantages of the pulmonary route of administration and inhalable dosage forms, other routes of administration and dosage forms are often considered first to treat lung diseases. This occurs, in part, due to the perceived limitations of inhaled therapies resulting from the improper design and interpretation of their in vitro and in vivo evaluation. The present study outlines the elements that should be considered in the design, performance, and interpretation of the results of the preclinical evaluation of novel inhaled therapies. These elements are illustrated using an optimized model poly(lactic-co-glycolic) acid (PLGA) microparticle (MP) formulation to optimize the site of MPs deposition. The different expressions of MP size were determined, and their aerosol performance in devices used for animal (Microsprayer® and Insufflator®) and human studies (nebulizer and DPIs) was assessed using inertial impaction. Radiolabeled MPs were delivered to the lungs of rats by spray instillation to determine their site of deposition using single-photon emission computed tomography (SPECT) imaging. Recommendations to optimize the in vitro determinations are given, as well as suggestions to evaluate and interpret in vivo data in the context of the anatomy and physiology of the animal model and the corresponding in vitro data. Recommendations for the proper selection of in vitro parameters to inform in silico modeling are also given, as well as their integration with in vivo data.
Pomegranate Peel Extract Attenuates Isoprenaline-Induced Takotsubo-like Myocardial Injury in Rats
Authors: Marinković Sonja T. , Đukanović Đorđe , Duran Mladen , Bajic Zorislava , Sobot Tanja , Uletilović Snežana , Mandić-Kovacević Nebojša , Cvjetković Tanja , Maksimović Žana M. , Maličević Uglješa , Vesić Nikolina , Jovičić Sanja , Katana Maja , Šavikin Katarina , Djuric Dragan M. , Stojiljković Miloš P. , Škrbić Ranko
Published: June 2023

Takotsubo syndrome (TTS) is an acute heart failure syndrome characterised by catecholamine-induced oxidative tissue damage. Punica granatum, a fruit-bearing tree, is known to have high polyphenolic content and has been proven to be a potent antioxidant. This study aimed to investigate the effects of pomegranate peel extract (PoPEx) pre-treatment on isoprenaline-induced takotsubo-like myocardial injury in rats. Male Wistar rats were randomised into four groups. Animals in the PoPEx(P) and PoPEx + isoprenaline group (P + I) were pre-treated for 7 days with 100 mg/kg/day of PoPEx. On the sixth and the seventh day, TTS-like syndrome was induced in rats from the isoprenaline(I) and P + I groups by administering 85 mg/kg/day of isoprenaline. PoPEx pre-treatment led to the elevation of superoxide dismutase and catalase (p < 0.05), reduced glutathione (p < 0.001) levels, decreased the thiobarbituric acid reactive substances (p < 0.001), H2O2, O2− (p < 0.05), and NO2− (p < 0.001), in the P + I group, when compared to the I group. In addition, a significant reduction in the levels of cardiac damage markers, as well as a reduction in the extent of cardiac damage, was found. In conclusion, PoPEx pre-treatment significantly attenuated the isoprenaline-induced myocardial damage, primarily via the preservation of endogenous antioxidant capacity in the rat model of takotsubo-like cardiomyopathy.
Encapsulation of Thymol in Gelatin Methacryloyl (GelMa)-Based Nanoniosome Enables Enhanced Antibiofilm Activity and Wound Healing
Authors: Moghtaderi Maryam , Bazzazan Saba , Sorourian Ghazal , Sorourian Maral , Akhavanzanjani Yasaman , Noorbazargan Hassan , Ren Qun
Published: June 2023

Non-healing wounds impose huge cost on patients, healthcare, and society, which are further fortified by biofilm formation and antimicrobial resistance (AMR) problems. Here, Thymol, an herbal antimicrobial agent, is utilized to combat AMR. For efficient delivery of Thymol gelatin methacryloyl (GelMa), a hydrophilic polymeric hydrogel with excellent biocompatibility combined with niosome was used to encapsulate Thymol. After optimization of the niosomal Thymol (Nio–Thymol) in the company of GelMa (Nio–Thymol@GelMa) to achieve maximum entrapment efficiency, minimum size, and low polydispersity index, the Thymol release peaked at 60% and 42% from Nio–Thymol@GelMa in medium with pH values of 6.5 and 7.4 after 72 h, respectively. Furthermore, Nio–Thymol@GelMa demonstrated higher antibacterial and anti-biofilm activity than Nio–Thymol and free Thymol against both Gram-negative and Gram-positive bacteria. Interestingly, compared with other obtained formulations, Nio–Thymol@GelMa also led to greater enhancement of migration of human dermal fibroblasts in vitro, and higher upregulation of the expression of certain growth factors such as FGF-1, and matrix metalloproteinases such as MMP-2 and MMP-13. These results suggest that Nio–Thymol@GelMa can represent a potential drug preparation for Thymol to enhance the wound healing process and antibacterial efficacy.
Ecology Meets Physiology: Phenotypic Plasticity and the Ability of Animals to Adjust to Changing Environmental Conditions
Authors: Hildebrandt Jan-Peter
Published: June 2023

Hyperplasia and hypertrophy, or their counterparts hypoplasia and hypotrophy, are elements of the adjustment of organ size and function in animals according to their needs under altered environmental conditions. As such processes are costly in terms of energy and biomaterials, it is assumed that they are beneficial for the survival of the individual. The ability of animals to perform such adjustments and the limitations in the scope of the adjustments are considered to be adaptive genetic traits which enable individual animals to survive regularly occurring changes in the environmental conditions in their habitats as long as such changes stay within critical limits. The restructuring of mono-functional glands in ducklings, which serve the animals in getting rid of excess amounts of ingested salt from the body, is presented as an example of complex plastic changes in organ structure. Phenotypic adjustments in these salt glands encompass both reversible processes, when environmental conditions switch back to the original state (‘phenotypic elasticity’), and irreversible ones (‘phenotypic plasticity’ in the narrow sense). As more information on genomes or transcriptomes of non-model animal species becomes available, we will better understand the biological significance of such phenotypic adjustments in animals in their natural environments and the underlying molecular mechanisms.
Silicon Supply Improves Nodulation and Dinitrogen Fixation and Promotes Growth in Trifolium incarnatum Subjected to a Long-Term Sulfur Deprivation
Authors: Coquerel Raphaël , Arkoun Mustapha , Dupas Quentin , Leroy Fanny , Laîné Philippe , Etienne Philippe
Published: June 2023

In many crops species, sulfur (S) deprivation negatively affects growth, seed yield quality and plant health. Furthermore, silicon (Si) is known to alleviate many nutritional stresses but the effects of Si supply on plants subjected to S deficiency remain unclear and poorly documented. The objective of this study was to evaluate whether Si supply would alleviate the negative effects of S deprivation on root nodulation and atmospheric dinitrogen (N2) fixation capacity in Trifolium incarnatum subjected (or not) to long-term S deficiency. For this, plants were grown for 63 days in hydroponic conditions with (500 µM) or without S and supplied (1.7 mM) or not with Si. The effects of Si on growth, root nodulation and N2 fixation and nitrogenase abundance in nodules have been measured. The most important beneficial effect of Si was observed after 63 days. Indeed, at this harvest time, a Si supply increased growth, the nitrogenase abundance in nodules and N2 fixation in S-fed and S-deprived plants while a beneficial effect on the number and total biomass of nodules was only observed in S-deprived plants. This study shows clearly for the first time that a Si supply alleviates negative effects of S deprivation in Trifolium incarnatum.
Quality and Phytochemical Composition of Sweet Cherry Cultivars Can Be Influenced by Altitude
Authors: Nacouzi Diana , Masry Rim , El Kayal Walid
Published: June 2023

Sweet cherries (Prunus avium L.) are among the most important stone fruits in Lebanon. They are harvested between May and July; however, the introduction of new early varieties in low and medium altitudes (500–1000 m) and late varieties in higher altitudes (1800–2200 m) along with postharvest technologies can extend harvesting season. In this study, physicochemical characteristics along with total phenolic content, total anthocyanin content, and antioxidant activity of the most commercial cherry cultivars were evaluated at different altitudes to determine optimum harvesting time. Findings indicated that some varieties, such as “Teliani” and “Irani”, are more significantly impacted by altitude than the other varieties in terms of maturity indices. Duration of fruit development was prolonged with altitude, and in most instances, higher fresh weights and sizes were observed; however, fruit firmness decreased. While total phenolic content (expressed as gallic acid equivalent) did not significantly vary between varieties, the antioxidant activity (FRAP and DPPH assays) showed the lowest value in “Banni” and the total anthocyanin content showed the highest levels in “Irani” and ”Feraouni” and the lowest in “Mkahal” and “Banni”. Furthermore, total phenolic content and reduction of ferric complex (FRAP) were interestingly influenced by geographical locations, in contrast to total anthocyanin content and radical scavenging activity (DPPH) which were unaffected.
Phylogeography of 912 Cherry Accessions Insight into Independent Origins of Fruiting Cherries and Domestication Footprints of Cultivated Chinese Cherry (Prunus pseudocerasus Lindl.)
Authors: Chen Tao , Chen Qing , Zhang Jing , Wang Yan , Wang Hao , Zhang Yong , Luo Ya , Tang Haoru , Wang Xiaorong
Published: June 2023

The subgenus Cerasus (Rosaceae) contain numerous fruit trees and ornamentals with high economic values. The origin and genetic divergence among various types of fruiting cherries always remain a perplexing issue. We employed three plastom fragments and ITS sequence matrices derived from 912 cherry accessions to elucidate the phylogeographic structure and genetic relationship among fruiting cherries, as well as the origin and domestication of cultivated Chinese cherry. The integration of haplotype genealogies, Approximate Bayesian computation (ABC) approach and estimation of genetic differentiation within and between different groups and lineages has facilitated the resolution of several previously unresolved questions. Firstly, distant phylogenetic relationships between Cerasus and Microcerasus accessions, as indicated by both nuclear and chloroplast data, suggested independent origins and evolution for these two taxa. Moreover, two distinct geographic origin centers (Europe and China) have been confirmed, with significant phylogeographic signals and high genetic differentiation observed between cherries from these regions. This may be attributed to long-term geographic isolation caused by Himalaya-Hengduan Mountains. Our phylogeographic analyses and ABC analysis suggested that cherries inhabiting in China may have undergone multiple hybridization events during the glacial refugia of the eastern edge and southern Himalaya-Hengduan Mountains, followed by rapid radiation throughout their current habitats during interglacial period. The discrepancy between nuclear and chloroplast data may be attributed to hybridization events and incomplete lineage sorting. Furthermore, we speculated that the domesticated Chinese cherries were derived from wild accessions in Longmenshan Fault Zones approximately 2600 years ago. We have also traced the domestication processes and dispersal routes of cultivated Chinese cherries.