bluuebunny/crossref_metadata_2025 huggingface dataset:
Aggregation of ODC(I) and POL Defects in Bismuth Doped Silica Fiber
Authors: Li Xiaofei , Wang Binbin , Song Tingting , Zhang Min , Zeng Tixian , Chen Jiang , Zhang Feiquan
Published: February 2023

First-principles calculations were used to simulate the aggregation of the peroxy chain defect POL and the oxygen vacancy defect ODC(I). Defect aggregation’s electronic structure and optical properties were investigated. The two defects were most likely to accumulate on a 6-membered ring in ortho-position. When the two defects are aggregated, it is discovered that 0.75 ev absorption peaks appear in the near-infrared band, which may be brought on by the addition of oxygen vacancy defect ODC(I). We can draw the conclusion that the absorption peak of the aggregation defect of ODC(I) defect and POL is more prominent in the near infrared region and visible light area than ODC(I) defect and POL defect.
High Reflectivity and Thermal Conductivity Ag–Cu Multi-Material Structures Fabricated via Laser Powder Bed Fusion: Formation Mechanisms, Interfacial Characteristics, and Molten Pool Behavior
Authors: Chen Qiaoyu , Jing Yongbin , Yin Jie , Li Zheng , Xiong Wei , Gong Ping , Zhang Lu , Li Simeng , Pan Ruiqi , Zhao Xiya , Hao Liang
Published: February 2023

Ag and Cu have different advantages and are widely used in key fields due to their typical highly electrical and thermal conductive (HETC) properties. Laser powder bed fusion (LPBF), an innovative technology for manufacturing metallic multi-material components with high accuracy, has expanded the application of Ag–Cu in emerging high-tech fields. In this study, the multi-material sandwich structures of Ag7.5Cu/Cu10Sn/Ag7.5Cu were printed using LPBF, and the formation mechanism, interface characteristics, and molten pool behavior of the Ag7.5Cu/Cu10Sn (A/C) and Cu10Sn/Ag7.5Cu (C/A) interfaces were studied to reveal the influence of different building strategies. At the A/C interface, pre-printed Ag7.5Cu promoted Marangoni turbulence at a relatively low energy density (EA/C = 125 J/mm3). Due to the recoil pressure, the molten pool at the A/C interface transformed from a stable keyhole mode to an unstable keyhole mode. These phenomena promoted the extensive migration of elements, forming a wider diffusion zone and reduced thermal cracking. At the C/A interface, the molten pool was rationed from the conduction mode with more pores to the transition mode with fewer defects due to the high energy density (EC/A = 187.5 J/mm3). This work offers a theoretical reference for the fabrication of HETC multi-material structures via LPBF under similar conditions.
Experimental Investigation of Discharge Phenomena in Electrochemical Discharge Machining Process
Authors: Tang Weidong , Zhu Yuhao , Kang Xiaoming , Mao Cong
Published: February 2023

Electrochemical discharge machining (ECDM) is a promising non−traditional processing technology used to machine non−conductive materials, such as glass and ceramic, based on the evoked electrochemical discharge phenomena around the tool electrode. The discharge in ECDM is a key factor that affects the removal of material. Moreover, the discharge current is an important indicator reflecting the discharge state. However, the discharge characteristics remain an open topic for debate and require further investigation. There is still confusion regarding the distinction of the discharge current from the electrochemical reaction current in ECDM. In this study, high−speed imaging technology was applied to the investigation of the discharge characteristics. By comparing the captured discharge images with the corresponding discharge current, the discharge can be classified into three types. The observations of the discharge effect on the gas film indicate that a force was exerted on the gas film during the discharge process and the shape of the gas film was changed by the force. In addition, the energies released by different types of discharge were calculated according to the voltage and current waveforms. The discharge frequency was found to increase with the increase in applied voltage and the frequency of the second type of discharge was approximately equal to that of the third type when the applied voltage was higher than 40 V.
Procalcitonin and Adrenomedullin in Infectious Diseases
Authors: Kiriyama Yoshimitsu , Nochi Hiromi
Published: February 2023

Calcitonin (CT) and adrenomedullin (ADM) are members of the CT family. Procalcitonin (PCT) is a prohormone of CT. Elevations in serum PCT and ADM levels are associated with severe sepsis and coronavirus disease 2019 (COVID-19). PCT enhances sepsis mortality and it binds to the CGRP receptor, which is a heterodimer of CT receptor-like receptor and receptor activity-modifying protein 1. The N-terminal truncated form of PCT, PCT3-116, is produced by the cleavage of PCT by dipeptidyl peptidase 4 (DPP-4) and is the main form of PCT in serum during sepsis, inducing microvascular permeability. Mid-regional pro-adrenomedullin (MR-proADM) is used instead of ADM as a biological indicator because ADM is rapidly degraded, and MR-proADM is released at the same rate as ADM. ADM reduces endothelial permeability and promotes endothelial stability. Endothelial dysfunction is responsible for multiple organ failure in sepsis and COVID-19 patients. Therefore, ADM may be an important molecule for improving the severity associated with sepsis and COVID-19. This review focuses on the current knowledge of PCT and ADM in sepsis and COVID-19.
Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review
Authors: Ser Hooi-Leng , Au Yong Siu-Jung , Shafiee Mohamad Nasir , Mokhtar Norfilza Mohd , Ali Raja Affendi Raja
Published: February 2023

Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.
Silicification of Wood: An Overview
Authors: Mustoe George E.
Published: February 2023

For many decades, wood silicification has been viewed as a relatively simple process of permineralization that occurs when silica dissolved in groundwater precipitates to fill vacant spaces within the porous tissue. The presence of specific silica minerals is commonly ascribed to diagenetic changes. The possibility of rapid silicification is inferred from evidence from modern hot springs. Extensive examination of silicified wood from worldwide localities spanning long geologic time suggests that these generalizations are not dependable. Instead, wood silicification may occur via multiple pathways, permineralization being relatively rare. Mineralization commonly involves silica precipitation in successive episodes, where changes in the geochemical environment cause various polymorphs to coexist in a single specimen. Diagenetic changes may later change the mineral composition, but for many specimens diagenesis is not the dominant process that controls mineral distribution. Rates of silicification are primarily related to dissolved silica levels and permeability of sediment that encloses buried wood. Rapid silica deposition takes place on wood in modern hot springs, but these occurrences have dissimilar physical and chemical conditions compared to those that exist in most geologic environments. The times required for silicification are variable, and cannot be described by any generalization.
Orthorhombic-Cubic Phase Transition in Rb2CoSi5O12 Leucite Analogue
Authors: Bell Anthony Martin Thomas
Published: February 2023

An Rb2CoSi5O12 leucite analogue has been synthesized. An ambient temperature X-ray powder diffraction study shows that this analogue has the Pbca orthorhombic structure of Cs2CdSi5O12. A high temperature X-ray powder diffraction study on this analogue shows a Pbca orthorhombic to Pa3¯ cubic phase transition at 457 K. The Rb2CoSi5O12 unit cell volume initially decreases with increasing temperature on passing through this phase transition.
Activity Measurement of 44Sc and Calibration of Activity Measurement Instruments on Production Sites and Clinics
Authors: Juget Frederic , Durán Teresa , Nedjadi Youcef , Talip Zeynep , Grundler Pascal V. , Favaretto Chiara , Casolaro Pierluigi , Dellepiane Gaia , Braccini Saverio , Bailat Claude , van der Meulen Nicholas P.
Published: February 2023

44Sc is a promising radionuclide for positron emission tomography (PET) in nuclear medicine. As a part of the implementation of a production site for 44Sc, precise knowledge of the activity of the product is necessary. At the Paul Scherrer Institute (PSI) and the University of Bern (UniBE), 44Sc is produced by enriched 44CaO-target irradiation with a cyclotron. The two sites use different techniques for activity measurement, namely a dose calibrator at the PSI and a gamma-ray spectrometry system at UniBE and PSI. In this work, the 44Sc was produced at the PSI, and samples of the product were prepared in dedicated containers for onsite measurements at PSI, UniBE, and the Institute of Radiation Physics (IRA) in Lausanne for precise activity measurement using primary techniques and for the calibration of the reference ionization chambers. An accuracy of 1% was obtained for the activity measurement, allowing for a precise calibration of the dose calibrator and gamma-ray spectrometry of the two production sites. Each production site now has the capability of measuring 44Sc activity with an accuracy of 2%.
An Analytical Protocol for the Differentiation and the Potentiometric Determination of Fluorine-Containing Fractions in Bovine Milk
Authors: Spano Nadia , Bortolu Sara , Addis Margherita , Langasco Ilaria , Mara Andrea , Pilo Maria I. , Sanna Gavino , Urgeghe Pietro P.
Published: February 2023

Free fluoride ions are effective in combating caries in children, and their supplementation in milk has been widely used worldwide for this purpose. Furthermore, it is known that ionic fluoride added to milk is distributed among its components, but little is known about their quantitative relationships. This is likely due to the absence of an analytical protocol aimed at differentiating and quantifying the most important forms of fluorine present in milk. For the first time, a comprehensive protocol made up of six potentiometric methods devoted to quantifying the most important fractions of fluorine in milk (i.e., the free inorganic fluoride, the inorganic bonded fluorine, the caseins-bonded fluorine, the whey-bonded fluorine, the lipid-bonded fluorine, and the total fluorine) has been developed and tested on real samples. Four of the six methods of the procedure are original, and all have been validated in terms of limit of detection and quantification, precision, and trueness. The data obtained show that 9% of all fluorine was in ionic form, while 66.3% of total fluorine was bound to proteins and lipids, therefore unavailable for human absorption. Beyond applications in dental research, this protocol could be extended also to other foods, or used in environmental monitoring.
Beneficial Proapoptotic Effect of Heterobasidion Annosum Extract in Colorectal Cancer Xenograft Mouse Model
Authors: Sadowska Anna , Sawicka Diana , Godlewska Katarzyna , Guzińska-Ustymowicz Katarzyna , Zapora Ewa , Sokołowska Emilia , Car Halina
Published: February 2023

Fungal extracts possess potential anticancer activity against many malignant neoplastic diseases. In this research, we focused on the evaluation of Heterobasidion annosum (HA) extract in colorectal cancer in an in vivo model. The mice with implanted DLD-1 human cancer cells were given HA extract, the referential drug—5-fluorouracil (5FU), or were treated with its combination. Thereafter, tumor volume was measured and apoptotic proteins such as caspase-8, caspase-3, p53, Bcl-2, and survivin were analyzed in mice serum with an ELISA assay. The Ki-67 protein was assessed in tumor cells by immunohistochemical examination. The biggest volumes of tumors were confirmed in the DLD-1 group, while the lowest were observed in the population treated with 5FU and/or HA extract. The assessment of apoptosis showed increased concentrations of caspase 8 and p53 protein after the combined administration of 5FU and HA extract. The levels of survivin and Bcl-2 were decreased in all tested groups compared to the DLD-1 group. Moreover, we observed a positive reaction for Ki-67 protein in all tested groups. Our findings confirm the apoptotic effect of extract given alone or with 5FU. The obtained results are innovative and provide a basis for further research concerning the antitumor activity of the HA extract, especially in the range of its interaction with an anticancer chemotherapeutic agent.
Phytochemical Compounds, Acute Toxicity, Anti-Inflammatory and Antioxidant Activities of Thymus leptobotrys Murb Essential Oil
Authors: Oubihi Asmaa , Ballaoui Fatima Zahrae , Imtara Hamada , Jaber Hassna , Ettouil Abdessamad , Haida Sara , Ouhssine Mohammed , Noman Omar M. , Mothana Ramzi A. , Tarayrah Mahmoud , Guessous Zineb
Published: February 2023

The present study was conducted to evaluate the acute toxicity and anti-inflammatory effect in vivo, as well as the antioxidant activity, of the essential oil of Thymus leptobotrys Murb. The results indicate that the tested essential oil is non-toxic, with an estimated LD50 of 2500 mg kg−1 of mice body weight. The anti-inflammatory test revealed that, at a dose of 200 mg kg−1, the essential oil reduced rat paw edemas by 89.59% within 3 h of oral administration, this reduction in edema size was greater than that obtained with indomethacin (75.78%). The antioxidant activity (IC50) of Thymus leptobotrys Murb essential oil was 346.896 µg mL−1 and 861.136 mg Trolox equivalent/g essential oil in the 2.2-diphenyl1-picryl-hydrazyl radical scavenging capacity (DPPH) and Trolox equivalent antioxidant capacity (TEAC) assays, respectively. The toxicity test reveals an LD50 greater than 2500 mg kg−1 of body weight of mice which classifies it within category 5 of non-toxic substances that can be administered orally. These results suggest that the essential oil of Thymus leptobotrys Murb is not toxic, and it represents a valuable source of anti-inflammatory and antioxidant metabolites.
Identifying the Anti-MERS-CoV and Anti-HcoV-229E Potential Drugs from the Ginkgo biloba Leaves Extract and Its Eco-Friendly Synthesis of Silver Nanoparticles
Authors: Elshazly Ezzat H. , Nasr Alyaa , Elnosary Mohamed E. , Gouda Gamal A. , Mohamed Hassan , Song Yuanda
Published: February 2023

The present study aimed to estimate the antiviral activities of Ginkgo biloba (GB) leaves extract and eco-friendly free silver nanoparticles (Ag NPs) against the MERS-CoV (Middle East respiratory syndrome-coronavirus) and HCoV-229E (human coronavirus 229E), as well as isolation and identification of phytochemicals from GB. Different solvents and high-performance liquid chromatography (HPLC) were used to extract and identify flavonoids and phenolic compounds from GB leaves. The green, silver nanoparticle synthesis was synthesized from GB leaves aqueous extract and investigated for their possible effects as anti-coronaviruses MERS-CoV and HCoV-229E using MTT assay protocol. To verify the synthesis of Ag NPs, several techniques were employed, including X-ray diffraction (XRD), scan, transmission electron microscopy, FT-IR, and UV–visible spectroscopy. The highest contents of flavonoids and phenolic compounds were recorded for acetone, methanol, and ethanol as mixtures with water, in addition to pure water. HPLC flavonoids were detected as apegenin, luteolin, myricetin, and catechin, while HPLC phenolic compounds were pyrogallol, caffeic acid, gallic acid, and ellagic acid. In addition, our results revealed that Ag NPs were produced through the shift from yellow to dark brown. TEM examination of Ag NPs revealed spherical nanoparticles with mean sizes ranging from 5.46 to 19.40 nm and an average particle diameter of 11.81 nm. A UV–visible spectrophotometric investigation revealed an absorption peak at λ max of 441.56 nm. MTT protocol signified the use of GB leaves extract as an anti-coronavirus to be best from Ag NPs because GB extract had moderate anti-MERS-CoV with SI = 8.94, while had promising anti-HCov-229E, with an SI of 21.71. On the other hand, Ag NPs had a mild anti-MERS-CoV with SI = 4.23, and a moderate anti-HCoV-229E, with an SI of 7.51.
Electronic Structure Calculations on Endohedral Complexes of Fullerenes: Reminiscences and Prospects
Authors: Cioslowski Jerzy
Published: February 2023

The history of electronic structure calculations on the endohedral complexes of fullerenes is reviewed. First, the long road to the isolation of new allotropes of carbon that commenced with the seminal organic syntheses involving simple inorganic substrates is discussed. Next, the focus is switched to author’s involvement with fullerene research that has led to the in silico discovery of endohedral complexes. The predictions of these pioneering theoretical studies are juxtaposed against the data afforded by subsequent experimental developments. The successes and failures of the old and modern quantum-chemical calculations on endohedral complexes are summarized and their remaining deficiencies requiring further attention are identified.
Impact on Some Soil Physical and Chemical Properties Caused by Metal and Metallic Oxide Engineered Nanoparticles: A Review
Authors: Suazo-Hernández Jonathan , Arancibia-Miranda Nicolás , Mlih Rawan , Cáceres-Jensen Lizethly , Bolan Nanthi , Mora María de la Luz
Published: February 2023

In recent years, the release of metal and metallic oxide engineered nanoparticles (ENPs) into the environment has generated an increase in their accumulation in agricultural soils, which is a serious risk to the ecosystem and soil health. Here, we show the impact of ENPs on the physical and chemical properties of soils. A literature search was performed in the Scopus database using the keywords ENPs, plus soil physical properties or soil chemical properties, and elements availability. In general, we found that the presence of metal and metallic oxide ENPs in soils can increase hydraulic conductivity and soil porosity and reduce the distance between soil particles, as well as causing a variation in pH, cation exchange capacity (CEC), electrical conductivity (EC), redox potential (Eh), and soil organic matter (SOM) content. Furthermore, ENPs or the metal cations released from them in soils can interact with nutrients like phosphorus (P) forming complexes or precipitates, decreasing their bioavailability in the soil solution. The results depend on the soil properties and the doses, exposure duration, concentrations, and type of ENPs. Therefore, we suggest that particular attention should be paid to every kind of metal and metallic oxide ENPs deposited into the soil.
Efficient Iodine Removal by Porous Biochar-Confined Nano-Cu2O/Cu0: Rapid and Selective Adsorption of Iodide and Iodate Ions
Authors: Li Jiaqi , Wang Mengzhou , Zhao Xu , Li Zitong , Niu Yihui , Wang Sufeng , Sun Qina
Published: February 2023

Iodine is a nuclide of crucial concern in radioactive waste management. Nanomaterials selectively adsorb iodine from water; however, the efficient application of nanomaterials in engineering still needs to be developed for radioactive wastewater deiodination. Artemia egg shells possess large surface groups and connecting pores, providing a new biomaterial to remove contaminants. Based on the Artemia egg shell-derived biochar (AES biochar) and in situ precipitation and reduction of cuprous, we synthesized a novel nanocomposite, namely porous biochar-confined nano-Cu2O/Cu0 (C-Cu). The characterization of C-Cu confirmed that the nano-Cu2O/Cu0 was dispersed in the pores of AES biochar, serving in the efficient and selective adsorption of iodide and iodate ions from water. The iodide ion removal by C-Cu when equilibrated for 40 min exhibited high removal efficiency over the wide pH range of 4 to 10. Remarkable selectivity towards both iodide and iodate ions of C-Cu was permitted against competing anions (Cl−/NO3−/SO42−) at high concentrations. The applicability of C-Cu was demonstrated by a packed column test with treated effluents of 1279 BV. The rapid and selective removal of iodide and iodate ions from water is attributed to nanoparticles confined on the AES biochar and pore-facilitated mass transfer. Combining the advantages of the porous biochar and nano-Cu2O/Cu0, the use of C-Cu offers a promising method of iodine removal from water in engineering applications.
A Review on the Progress, Challenges, and Performances of Tin-Based Perovskite Solar Cells
Authors: Lye Yuen-Ean , Chan Kah-Yoong , Ng Zi-Neng
Published: February 2023

In this twenty-first century, energy shortages have become a global issue as energy demand is growing at an astounding rate while the energy supply from fossil fuels is depleting. Thus, the urge to develop sustainable renewable energy to replace fossil fuels is significant to prevent energy shortages. Solar energy is the most promising, accessible, renewable, clean, and sustainable substitute for fossil fuels. Third-generation (3G) emerging solar cell technologies have been popular in the research field as there are many possibilities to be explored. Among the 3G solar cell technologies, perovskite solar cells (PSCs) are the most rapidly developing technology, making them suitable for generating electricity efficiently with low production costs. However, the toxicity of Pb in organic–inorganic metal halide PSCs has inherent shortcomings, which will lead to environmental contamination and public health problems. Therefore, developing a lead-free perovskite solar cell is necessary to ensure human health and a pollution-free environment. This review paper summarized numerous types of Sn-based perovskites with important achievements in experimental-based studies to date.
Phosphate Capture Enhancement Using Designed Iron Oxide-Based Nanostructures
Authors: Ramirez Paula Duenas , Lee Chaedong , Fedderwitz Rebecca , Clavijo Antonia R. , Barbosa Débora P. P. , Julliot Maxime , Vaz-Ramos Joana , Begin Dominique , Le Calvé Stéphane , Zaloszyc Ariane , Choquet Philippe , Soler Maria A. G. , Mertz Damien , Kofinas Peter , Piao Yuanzhe , Begin-Colin Sylvie
Published: February 2023

Phosphates in high concentrations are harmful pollutants for the environment, and new and cheap solutions are currently needed for phosphate removal from polluted liquid media. Iron oxide nanoparticles show a promising capacity for removing phosphates from polluted media and can be easily separated from polluted media under an external magnetic field. However, they have to display a high surface area allowing high removal pollutant capacity while preserving their magnetic properties. In that context, the reproducible synthesis of magnetic iron oxide raspberry-shaped nanostructures (RSNs) by a modified polyol solvothermal method has been optimized, and the conditions to dope the latter with cobalt, zinc, and aluminum to improve the phosphate adsorption have been determined. These RSNs consist of oriented aggregates of iron oxide nanocrystals, providing a very high saturation magnetization and a superparamagnetic behavior that favor colloidal stability. Finally, the adsorption of phosphates as a function of pH, time, and phosphate concentration has been studied. The undoped and especially aluminum-doped RSNs were demonstrated to be very effective phosphate adsorbents, and they can be extracted from the media by applying a magnet.
Sulforaphane Treatment in Children with Autism: A Prospective Randomized Double-Blind Study
Authors: Magner Martin , Thorová Kateřina , Župová Veronika , Houška Milan , Švandová Ivana , Novotná Pavla , Tříska Jan , Vrchotová Naděžda , Soural Ivo , Jílek Ladislav
Published: February 2023

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with repetitive behaviour which affects interaction and communication. Sulforaphane (SFN), an isothiocyanate abundant in the seeds and sprouts of cruciferous vegetables, has been shown to be effective in alleviating autistic behaviour. We performed a prospective double-blind placebo-controlled study to examine the possible effect of SFN in a paediatric cohort aged three to seven years based on measurements of the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Social Responsiveness Scale-2 (SRS-2), and the Aberrant Behaviour Checklist (ABC). The study consisted of three visits over the duration of 36 weeks (baseline, 18 weeks, and 36 weeks). Twenty-eight of the 40 randomized children completed the study. The mean total raw scores on ABC and SRS-2 improved in both groups, but none of the changes reached statistical significance (ABC: 0 weeks p = 0.2742, 18 weeks p = 0.4352, and 36 weeks 0.576; SRS-2: 0 weeks p = 0.5235, 18 weeks p = 0.9176, and 36 weeks 0.7435). Changes in the assessment of the ADOS-2 subscale scores also did not differ between the two study cohorts (ADOS-2: 0 weeks p = 0.8782, 18 weeks p = 0.4788, and 36 weeks 0.9414). We found no significant clinical improvement in the behavioural outcome measures evaluated in children with ASD aged 3–7 years that were treated with sulforaphane.
Associations between Timing and Duration of Eating and Glucose Metabolism: A Nationally Representative Study in the U.S.
Authors: Ali Marriam , Reutrakul Sirimon , Petersen Gregory , Knutson Kristen L.
Published: February 2023

Diabetes is highly prevalent and is associated with dietary behaviors. Time-restricted eating, which consolidates caloric intake to a shortened eating duration, has demonstrated improvement in metabolic health. Timing of eating could also impact metabolism. Our objective was to examine whether the timing of eating was associated with metabolic health independently of eating duration. Data (n = 7619) are from four cycles (2005–2012) of the National Health and Nutrition Examination Survey (NHANES), a nationally representative U.S. survey that included surveys, physical examinations, and dietary recalls. The primary exposures are eating duration and eating start time estimated from two non-consecutive dietary recalls. Primary outcomes were fasting glucose and estimated insulin resistance using the homeostatic model assessment method (HOMA-IR). The mean (95% CI) eating duration was 12.0 h (11.9–12.0) and the mean (95% CI) start time was 8:21 (8:15–8:26). Earlier eating start time was significantly associated with lower fasting glucose and estimated insulin resistance but eating interval duration was not. Every hour later that eating commenced was associated with approximately 0.6% higher glucose level and 3% higher HOMA-IR (both p < 0.001). In this cross-sectional study, earlier eating start time was associated with more favorable metabolic measures, indicating that meal timing is another important characteristic of dietary patterns that may influence metabolism.
Mechanistic Understanding of D-Glucaric Acid to Support Liver Detoxification Essential to Muscle Health Using a Computational Systems Biology Approach
Authors: Ayyadurai V. A. Shiva , Deonikar Prabhakar , Fields Christine
Published: February 2023

Liver and muscle health are intimately connected. Nutritional strategies that support liver detoxification are beneficial to muscle recovery. Computational–in silico–molecular systems’ biology analysis of supplementation of calcium and potassium glucarate salts and their metabolite D-glucaric acid (GA) reveals their positive effect on mitigation of liver detoxification via four specific molecular pathways: (1) ROS production, (2) deconjugation, (3) apoptosis of hepatocytes, and (4) β-glucuronidase synthesis. GA improves liver detoxification by downregulating hepatocyte apoptosis, reducing glucuronide deconjugates levels, reducing ROS production, and inhibiting β-Glucuronidase enzyme that reduces re-absorption of toxins in hepatocytes. Results from this in silico study provide an integrative molecular mechanistic systems explanation for the mitigation of liver toxicity by GA.
Estimation of Salt Intake in Normotensive and Hypertensive Children: The Role of Body Weight
Authors: Kos Martina , Nađ Tihana , Stanojević Lorena , Lukić Matea , Stupin Ana , Drenjančević Ines , Pušeljić Silvija , Davidović Cvetko Erna , Mihaljević Zrinka , Dumančić Dijana , Jukić Ivana
Published: February 2023

Objective: The connection between increased dietary salt intake and arterial hypertension has been recognized for a long time, even in children. This study aimed to investigate salt consumption in normotensive and hypertensive children and evaluate their dietary habits. Materials and Methods: A total of fifty participants were included in this cross-sectional study: twenty-five normotensive children and 25 children of both sexes with essential arterial hypertension from 12–17 years old. Subjects’ body mass index, waist-to-hip ratio, body composition and arterial blood pressure were measured, and their daily salt intake was calculated from 24-h urine samples. Using the food frequency questionnaire (FFQ), the data on the average daily total energy and food intakes were collected and analyzed using a suitable program. Results: Estimated daily salt intake was significantly higher in hypertensive compared to normotensive children, and this is positively associated with blood pressure and body mass index (BMI). Hypertensive children had significantly higher BMIs, which also positively correlated with blood pressure. Consistently, resting metabolic rate (kcal) is higher in hypertensive children compared to normotensive, and this is also associated with blood pressure. Reported energy intake is also enlarged in hypertensive compared to normotensive children and for both groups, levels are significantly higher than the recommended values. Conclusions: Our study results confirm the relationship between daily salt consumption, blood pressure and body weight. Sodium consumption related to blood pressure and body weight among children. Cardiovascular disease prevention should start in early childhood by reducing salt intake and preventing overweight/obesity since these are two of the most important modifiable risk factors for hypertension.
Chemical Characterization, Antioxidant Capacity and Anti-Oxidative Stress Potential of South American Fabaceae Desmodium tortuosum
Authors: Rodríguez José-Luis , Berrios Paola , Clavo Zoyla-Mirella , Marin-Bravo Manuel , Inostroza-Ruiz Luis , Ramos-Gonzalez Mariella , Quispe-Solano Miguel , Fernández-Alfonso Maria S. , Palomino Olga , Goya Luis
Published: February 2023

It has been proposed that oxidative stress is a pathogenic mechanism to induce cytotoxicity and to cause cardiovascular and neuronal diseases. At present, natural compounds such as plant extracts have been used to reduce the cytotoxic effects produced by agents that induce oxidative stress. Our study aimed to evaluate the antioxidant and cytoprotective capacity of Desmodium tortuosum (D. tortuosum) extract in the co- and pre-treatment in EA.hy926 and SH-SY5Y cell lines subjected to oxidative stress induced by tert-butylhydroperoxide (t-BOOH). Cell viability, reactive oxygen species (ROS), nitric oxide (NO), caspase 3/7 activity, reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and molecular expression of oxidative stress biomarkers (SOD2, NRF2 and NFκB1) and cell death (APAF1, BAX, Caspase3) were all evaluated. It was observed that the D. tortuosum extract, in a dose-dependent manner, was able to reduce the oxidative and cytotoxicity effects induced by t-BOOH, even normalized to a dose of 200 µg/mL, which would be due to the high content of phenolic compounds mainly phenolic acids, flavonoids, carotenoids and other antioxidant compounds. Finally, these results are indicators that the extract of D. tortuosum could be a natural alternative against the cytotoxic exposure to stressful and cytotoxic chemical agents.
Nursing Staff’s Observations of BPSD Amongst Older Adults with Dementia Living in a Nursing Home: A Qualitative Study
Authors: Grootscholten Emerentia , Poslawsky Irina , Bakker Ton
Published: February 2023

The majority of older adults with dementia living in a nursing home exhibit behavioral and psychological symptoms of dementia (BPSD). This behavior is difficult for residents to cope with. Early recognition of BPSD is important in order to implement personalized integrated treatment, and nursing staff are in the unique position to consistently observe residents’ behavior. The aim of this study was to explore nursing staff’s experiences observing BPSD of nursing home residents with dementia. A generic qualitative design was chosen. Twelve semi-structured interviews were conducted with nursing staff members until data saturation. Data were analyzed using inductive thematic analysis. Four themes were identified: “group harmony” observations from a group perspective, focused on the disturbance of group harmony; an “intuitive approach”, which involves observing unconsciously and without a set method; “reactive intervention”, which refers to immediate removal of observed triggers without exploring the causes of behaviors; and “sharing information”, which is delayed sharing of observed behavior with other disciplines. The current way in which nursing staff observe BPSD and share observations within the multidisciplinary team explain several existing barriers to achieving high treatment fidelity for BPSD with personalized integrated treatment. Therefore, nursing staff must be educated to structure their daily observations methodologically and interprofessional collaboration improved to share their information in a timely manner.
Editorial on the Research Topic of the Special Issue “Current Status of Acinetobacter Infections”
Authors: Nocera Francesca Paola , De Martino Luisa
Published: February 2023

Emerging bacterial infections will continue to be an important issue for public health, mostly because of the constant changes on our earth [...]
Protection of H2S against Hypoxia/Reoxygenation Injury in Rat Hippocampal Neurons through Inhibiting Phosphorylation of ROCK2 at Thr436 and Ser575
Authors: Fang Fang , Sheng Ju , Guo Yan , Wen Jiyue , Chen Zhiwu
Published: February 2023

Background: H2S (hydrogen sulfide) protects cerebral vasodilatation and endothelial cells against oxygen-glucose deprivation/reoxygenation injury via the inhibition of the RhoA-ROCK pathway and ROCK2 expression. However, the inhibitory mechanism of H2S on ROCK2 expression is still unclear. The study aimed to investigate the target and mechanism of H2S in inhibition of ROCK2. Methods: His-ROCK2wild protein was constructed, expressed, and was used for phosphorylation assay in vitro. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) was used to determine the potential phosphorylation sites of ROCK2. Recombinant ROCK2wild-pEGFP-N1, ROCK2T436A-pEGFP-N1, and ROCK2S575F-pEGFP-N1 plasmids were constructed and transfected into rat hippocampal neurons (RHNs). ROCK2 expression, cell viability, the release of lactate dehydrogenase (LDH), nerve-specific enolase (NSE), and Ca2+ were detected to evaluate the neuroprotective mechanism of H2S. Results: Phosphorylation at Thr436 and Ser575 of ROCK2 was observed by mass spectrometry when Polo-like kinase 1 (PLK1) and protein kinase A (PKA) were added in vitro, and NaHS significantly inhibited phosphorylation at Thr436 and Ser575. Additionally, NaHS significantly inhibited the expression of ROCK2 and recombinant proteins GFP-ROCK2, GFP-ROCK2T436A, and GFP-ROCK2S575F in transfected RHNs. Compared with empty plasmid, GFP-ROCK2T436A, and GFP-ROCK2S575F groups, NaHS significantly inhibited the release of LDH, NSE, and Ca2+ and promoted ROCK2 activity in the GFP-ROCK2wild group. Thr436 and Ser575 may be dominant sites that mediate NaHS inhibition of ROCK2 protein activity in RHNs. Compared with the empty plasmid, GFP-ROCK2T436A, and the GFP-ROCK2S575F group, NaHS had more significant inhibitory effects on hypoxia/reoxygenation (H/R) injury-induced cell viability reduction and increased LDH and NSE release in the GFP-ROCK2wild group. Conclusion: Exogenous H2S protected the RHNs against H/R injury via Thr436 and Ser575 of ROCK2. These findings suggested that Thr436 and Ser575 may be the dominant sites that mediated the effect of NaHS on protecting RHNs against H/R injury.
Synergistic Combination of Irinotecan and Rapamycin Orally Delivered by Nanoemulsion for Enhancing Therapeutic Efficacy of Pancreatic Cancer
Authors: Liu Yu-Hsuan , Chen Ling-Chun , Cheng Wen-Ting , Wei Pu-Sheng , Hsieh Chien-Ming , Sheu Ming-Thau , Lin Shyr-Yi , Ho Hsiu-O , Lin Hong-Liang
Published: February 2023

In recent years, combining different types of therapy has emerged as an advanced strategy for cancer treatment. In these combination therapies, oral delivery of anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENPir/ra) and evaluated its synergistic combination effects on pancreatic cancer. LBSNENP loaded with irinotecan and rapamycin at a ratio of 1:1 (LBSNENPir10/ra10) had a better drug release profile and smaller particle size (<200 nm) than the drug powder. Moreover, LBSNENPir10/ra10 exhibited a strong synergistic effect (combination index [CI] < 1.0) in cell viability and combination effect studies. In the tumor inhibition study, the antitumor activity of LBSNENPir10/ra10/sily20 against MIA PaCa-2 (a human pancreatic cancer cell line) was significantly increased compared with the other groups. When administered with rapamycin and silymarin, the area under the curve and the maximum concentration of irinotecan significantly improved compared with the control. We successfully developed an irinotecan/rapamycin-loaded oral self-nanoemulsifying nanoemulsion system to achieve treatment efficacy for pancreatic cancer.
Bioactive Polymeric Nanoparticles of Moringa oleifera Induced Phyto-Photothermal Sensitization for the Enhanced Therapy of Retinoblastoma
Authors: Mudigunda Sushma Venkata , Pemmaraju Deepak B. , Sankaranarayanan Sri Amruthaa , Rengan Aravind Kumar
Published: February 2023

Treatment of retinoblastoma is limited due to its delayed detection and inaccesbility of drugs to reach the retina crossing the blood-retinal barrier. With the advancements in nanotechnology, photothermal therapy (PTT) employing plasmonic nanomaterials and/or NIR dyes have emerged as an affordable alternative owing to the spatial control that is offered by the modality leading to localized and enhanced therapeutic efficacy with minimal invasiveness. However, the modality is limited in its clinical application owing to the increased heat shock resistance of the tumor cells in response to the heat that is generated via PTT. Hence, in this study, we explore the role of novel biomolecular fraction of Moringa oleifera (DFM) encapsulated within a polymeric nanosystem, for its anti-heat shock protein (HSP) activity. The MO extract was co-encapsulated with NIR sensitizing dye, IR820 into a biodegradable polycaprolactone (PCL) nano-delivery system (PMIR NPs). The photothermal transduction efficacy of PMIR NPs was validated in vitro against retinoblastoma cell lines. The inherent fluorescence of DFM was utilized to evaluate the cellular internalization of the PMIR NPs using fluorescence microscopy and flow cytometry. The overall oxidative protein damage and downregulation of HSP70 expression upon treatment with PMIR NPs and NIR laser irradiation was evaluated using densiometric protein analysis and Western blotting. Overall, the PMIR NPs exhibited excellent anti-cancer activity when combined with PTT with downregulated HSP70 expression against retinoblastoma cells.
Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery
Authors: Shen Zhigao , Liu Cong , Wang Ziqian , Xie Fengfei , Liu Xingwu , Dong Lingkai , Pan Xuehua , Zeng Chen , Wang Peng George
Published: February 2023

Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy.
Development of L-Lysine-Loaded PLGA Microparticles as a Controlled Release System for Angiogenesis Enhancement
Authors: Gallo Nunzia , Quarta Stefano , Massaro Marika , Carluccio Maria Annunziata , Barca Amilcare , Cannoletta Donato , Siculella Luisa , Salvatore Luca , Sannino Alessandro
Published: February 2023

Vascularization is a highly conserved and considerably complex and precise process that is finely driven by endogenous regulatory processes at the tissue and systemic levels. However, it can reveal itself to be slow and inadequate for tissue repair and regeneration consequent to severe lesions/damages. Several biomaterial-based strategies were developed to support and enhance vasculogenesis by supplying pro-angiogenic agents. Several approaches were adopted to develop effective drug delivery systems for the controlled release of a huge variety of compounds. In this work, a microparticulate system was chosen to be loaded with the essential amino acid L-lysine, a molecule that has recently gained interest due to its involvement in pro-angiogenic, pro-regenerative, and anti-inflammatory mechanisms. Poly (lactic-co-glycolic acid), the most widely used FDA-approved biodegradable synthetic polymer for the development of drug delivery systems, was chosen due to its versatility and ability to promote neovascularization and wound healing. This study dealt with the development and the effectiveness evaluation of a PLGA-based microparticulate system for the controlled release of L-lysine. Therefore, in order to maximize L-lysine encapsulation efficiency and tune its release kinetics, the microparticle synthesis protocol was optimized by varying some processing parameters. All developed formulations were characterized from a morphological and physicochemical point of view. The optimized formulation was further characterized via the evaluation of its preliminary biological efficacy in vitro. The cellular and molecular studies revealed that the L-lysine-loaded PLGA microparticles were non-toxic, biocompatible, and supported cell proliferation and angiogenesis well by stimulating the expression of pro-angiogenic genes such as metalloproteinase-9, focal adhesion kinases, and different growth factors. Thus, this work showed the potential of delivering L-lysine encapsulated in PLGA microparticles as a cost-effective promoter system for angiogenesis enhancement and rapid healing.
A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer
Authors: Gonzalez Paulina , Debnath Sashi , Chen Yu-An , Hernandez Elizabeth , Jha Preeti , Dakanali Marianna , Hsieh Jer-Tsong , Sun Xiankai
Published: February 2023

After androgen deprivation therapy, a significant number of prostate cancer cases progress with a therapy-resistant neuroendocrine phenotype (NEPC). This represents a challenge for diagnosis and treatment. Based on our previously reported design of theranostic small-molecule prodrug conjugates (T-SMPDCs), herein we report a T-SMPDC tailored for targeted positron emission tomography (PET) imaging and chemotherapy of NEPC. The T-SMPDC is built upon a triazine core (TZ) to present three functionalities: (1) a chelating moiety (DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for PET imaging when labeled with 68Ga (t1/2 = 68 min) or other relevant radiometals; (2) an octreotide (Octr) that targets the somatostatin receptor 2 (SSTR2), which is overexpressed in the innervated tumor microenvironment (TME); and (3) fingolimod, FTY720—an antagonist of sphingosine kinase 1 that is an intracellular enzyme upregulated in NEPC. Polyethylene glycol (PEG) chains were incorporated via conventional conjugation methods or a click chemistry reaction forming a 1,4-disubstituted 1,2,3-triazole (Trz) linkage for the optimization of in vivo kinetics as necessary. The T-SMPDC, DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 (PEGn: PEG with n repeating ethyleneoxy units (n = 2, 3, or 4); Val: valine; Cit: citrulline; pABOC: p-amino-benzyloxycarbonyl), showed selective SSTR2 binding and mediated internalization of the molecule in SSTR2 high cells. Release of FTY720 was observed when the T-SMPDC was exposed to cathepsin B, and the released FTY720 exerted cytotoxicity in cells. In vivo PET imaging showed significantly higher accumulation (2.1 ± 0.3 %ID/g; p = 0.02) of [68Ga]Ga-DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 in SSTR2high prostate cancer xenografts than in the SSTR2low xenografts (1.5 ± 0.4 %ID/g) at 13 min post-injection (p.i.) with a rapid excretion through the kidneys. Taken together, these proof-of-concept results validate the design concept of the T-SMPDC, which may hold a great potential for targeted diagnosis and therapy of NEPC.