bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Pre-Oxidation on the Reducibility of Chromite Using Hydrogen: A Preliminary Study
Authors: Davies Jamey , Tangstad Merete , Ringdalen Eli , Beukes Johan Paul , Bessarabov Dmitri , du Preez Stephanus Petrus
Published: July 2022

The majority of ferrochrome (FeCr) is produced through the carbothermic reduction of chromite ore. In recent years, FeCr producers have been pressured to curve carbon emissions, necessitating the exploration of alternative smelting methods. The use of hydrogen as a chromite reductant only yields water as a by-product, preventing the formation of carbon monoxide (CO)-rich off-gas. It is however understood that only the Fe-oxide constituency of chromite can be metalized by hydrogen, whereas the chromium (Cr)-oxide constituency requires significantly higher temperatures to be metalized. Considering the alternation of chromite’s spinel structure when oxidized before traditional smelting procedures, the effects on its reducibility using hydrogen were investigated. Firstly, the effect of hydrogen availability was considered and shown to have a significant effect on Fe metallization. Subsequently, spinel alternation induced by pre-oxidation promoted the hydrogen-based reducibly of the Fe-oxide constituency, and up to 88.4% of the Fe-oxide constituency was metallized. The Cr-oxide constituency showed little to no reduction. The increase in Fe-oxide reducibility was ascribed to the formation of an exsolved Fe2O3-enriched sesquioxide phase, which was more susceptible to reduction when compared to Fe-oxides present in the chromite spinel. The extent of Fe metallization of the pre-oxidized chromite was comparable to that of unoxidized chromite under significantly milder reduction conditions.
Petrogenesis and Tectonic Implications of the Ore-Associated Intrusions in Bayanbaolege Ag Polymetallic Deposit, Inner Mongolia, NE China
Authors: Wang Xi , Yang Qun , Sun Zhen-Ming , Ren Yun-Sheng
Published: July 2022

The large Bayanbaolege Ag polymetallic ore deposit is located in the Tuquan-Linxi Fe (Sn)-Cu-Pb-Zn-Ag-Nb (Ta) polymetallic metallogenic belt, which is an important part of the Great Xing’an Range metallogenic province, northeast China. The sulfide–quartz vein-type orebodies in the deposit are mainly hosted in the Cretaceous granodiorite porphyry and Late Permian Linxi formation. The U-Pb dating of the zircon from the post-ore diorite porphyrite yields an age of 124.8 ± 1.1 Ma, which constrains the mineralization time at the Early Cretaceous. The Sr-Nd isotope values (87Sr/86Sr)i = 0.708576~0.710536; εNd (t) = −0.51~+0.69; the Hf isotope values 176Hf/177Hf = 0.2827278~0.2830095, the εHf (t) = +3.1~+11.2, TDM2 = 615~1341 Ma of the metallogenic granodiorite porphyry. The Hf isotope values 176Hf/177Hf = 0.2828596~0.2829451, and the εHf (t) = +5.7~+8.8 of the diorite porphyrite, TDM2 = 827~1108 Ma, indicating that the ore-forming materials were the possible involvement of heterogeneous juvenile sources including moderately depleted mantle and newly underplated lower crust. The major and trace elements (including REEs) implied that these intrusions are the I-type granite and linked intimately to the westward subduction of the Paleo-Pacific Ocean plate. From these whole-rock major and trace elements and zircon U-Pb ages, as well as Sr-Nd-Hf isotope data, we conclude that the ore-associated I-type granites in the Bayanbaolege deposit formed in an extensional tectonic setting of the Early Cretaceous, and are compactly related to the retreat of the Paleo-Pacific Ocean subducted plate linked intimately to the westward subduction of the Paleo-Pacific Ocean plate rather than the closure of the Mongol–Okhotsk Ocean. Furthermore, by integrating geological background work and previous research work, implying the mineralization age of the Bayanbaolege deposit should have been formed in the 125–130 Ma.
Identification of Diagenetic Facies Logging of Tight Oil Reservoirs Based on Deep Learning—A Case Study in the Permian Lucaogou Formation of the Jimsar Sag, Junggar Basin
Authors: Qi Ming , Han Changcheng , Ma Cunfei , Liu Geng , He Xudong , Li Guan , Yang Yi , Sun Ruyuan , Cheng Xuhui
Published: July 2022

As a typical tight oil reservoir in a lake basin, the Permian Lucaogou Formation of the Jimsar Sag in the Junggar Basin has great potential for exploration and development. However, at present, there are few studies on the identification of the diagenetic facies of tight oil reservoir logging in the study area, and the control effect of diagenesis on tight oil reservoirs is not clear. The present work investigates the diagenesis and diagenetic facies logging of the study area, making full use of core data, thin sections, and logs, among other data, in order to understand the reservoir characteristics of the Permian Lucaogou Formation in the Jimsar Sag. The results show that the Lucaogou Formation has undergone diagenetic activity such as compaction, carbonate cementation, quartz cementation, and clay mineral infilling and dissolution. The diagenetic facies are classified according to mineral and diagenetic type, namely, tightly compacted facies, carbonate-cemented facies, clay mineral-filling facies, quartz-cemented facies, and dissolution facies. The GR, RT, AC, DEN, and CNL logging curves were selected, among others, and the convolutional neural network was introduced to construct a diagenetic facies logging recognition model. The diagenetic facies of a single well was divided and identified, and the predicted diagenetic facies types were compared with thin sections and SEM images of the corresponding depths. Prediction results had a high coincidence rate, which indicates that the model is of a certain significance to accurately identify the diagenetic facies of tight oil reservoirs. Assessing the physical properties of the studied reservoirs, dissolution facies are the dominant diagenetic facies in the study area and are also the preferred sequence for exploration—to find dominant reservoirs in the following stage.
Qualitative Analysis and Componential Differences of Chemical Constituents in Lysimachiae Herba from Different Habitats (Sichuan Basin) by UFLC-Triple TOF-MS/MS
Authors: Zhou Yongyi , Chen Haijie , Xue Jia , Yuan Jiahuan , Cai Zhichen , Wu Nan , Zou Lisi , Yin Shengxin , Yang Wei , Liu Xunhong , Chen Jianming , Liu Fushuangshuang
Published: July 2022

Lysimachiae Herba (LH), called Jinqiancao in Chinese, is an authentic medical herb in Sichuan Province often used in the prescription of traditional Chinese medicine (TCM). However, in recent years, there has been a lack of comprehensive research on its chemical components. In addition, the landform of Sichuan Province varies greatly from east to west and the terrain is complex and diverse, which has an important influence on the chemical constituents in LH. In this study, ultrafast liquid chromatography coupled with triple-quadrupole time-of-flight tandem mass spectrometry (UFLC-triple TOF-MS/MS) was used to analyze the samples of LH from eight different habitats in Sichuan Basin. The constituents were identified according to the precise molecular weight, the fragment ions of each chromatographic peak and the retention time of the compound obtained by high-resolution mass spectrometry, combined with software database searches, standard comparisons and the related literature. Differential chemical constituents were screened using partial least squares discriminant analysis (PLS-DA) and t-tests. The results showed that a total of 46 constituents were identified and inferred, including flavonoids, phenolic acids, amino acids, tannins, fatty acids and coumarins; the fragmentation pathways of the main constituents were preliminarily deduced. According to the variable importance in projection (VIP) and p-values, four common differential constituents were screened out, 2-O-galloylgalactaric acid, quercetin 3-O-xylosyl-rutinoside, nicotiflorin and kaempferol 3-rutinosyl 7-O-alpha-l-rhamnoside. This study provides basic information for the establishment of a comprehensive quality evaluation system for LH.
Characterization and Evaluation of Antimicrobial Potential of Trigonella incise (Linn) Mediated Biosynthesized Silver Nanoparticles
Authors: Fozia Fozia , Ahmad Nisar , Buoharee Zohra Aftab , Ahmad Ijaz , Aslam Madeeha , Wahab Abdul , Ullah Riaz , Ahmad Shakeel , Alotaibi Amal , Tariq Akash
Published: July 2022

The goal of the research was to explore a new green method used to synthesize silver nanoparticles (Ag NPs) from an aqueous extract of Trigonella incise, which serves as a reducing and stabilizing agent. The obtained results showed an 85% yield of nanoparticles by using 2:5 (v/v) of 5% plant extract with a 0.5 M solution of AgNO3. Different techniques were used to characterize the synthesized Ag NPs, including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and UV–visible spectroscopy. The UV–visible spectra of green synthesized silver nanoparticles showed maximum absorption at a wavelength of 440 nm. The FT-IR studies revealed the stretching oscillation frequency of synthesized silver nanoparticles in the absorption band near 860 cm−1. Similarly, the bending and stretching oscillation frequencies of the NH function group were assigned to the band in the 3226 cm−1 and 1647 cm−1 regions. The bending vibration of C-O at 1159 cm−1 confirmed the carbonyl functional group that was also assigned to the small intensity band in the range of 2361 cm−1. The X-ray diffraction analysis of Ag NPs revealed four distinct diffraction peaks at 2θ of 38°, 45°, 65° and 78°, corresponds to (111), (200), (220) and (311) of the face-centered cubic shape. The round shape morphology of Ag NPs with a mean diameter in the range 20–80 nm was analyzed via SEM images. Furthermore, the nanoparticles showed more significant antimicrobial activity against Salmonella typhi (S. typhi) and Staphylococcus aureus (S. aureus) with an inhibition zone of 21.5 mm and 20.5 mm at 6 μg/mL concentrations, respectively, once compared to the standard reference. At concentrations of 2 µg/mL and 4 µg/mL, all of the bacterial strains showed moderate activity, with inhibition zones ranging from 11 mm to 18.5 mm. Even at high concentrations of AgNPs, S. typhi showed maximum resistance. The best antifungal activity was observed by synthesized Ag NPs against Candida albicans (C. albicans) with 21 mm zone of inhibition, as compared to a standard drug which gives 22 mm of inhibition. Therefore, we conclude that the antibacterial and antifungal activities showed satisfactory results from the synthesized Ag NPs.
Perspectives of Positively Charged Nanocrystals of Tedizolid Phosphate as a Topical Ocular Application in Rabbits
Authors: Alshememry Abdullah , Alkholief Musaed , Abul Kalam Mohd , Raish Mohammad , Ali Raisuddin , Alhudaithi Sulaiman S. , Iqbal Muzaffar , Alshamsan Aws
Published: July 2022

The aim of this study was the successful utilization of the positively charged nanocrystals (NCs) of Tedizolid Phosphate (TZP) (0.1% w/v) for topical ocular applications. TZP belongs to the 1, 3-oxazolidine-2-one class of antibiotics and has therapeutic potential for the treatment of many drug-resistant bacterial infections, including eye infections caused by MRSA, penicillin-resistant Streptococcus pneumonia and vancomycin-resistant Enterococcus faecium. However, its therapeutic usage is restricted due to its poor aqueous solubility and limited ocular availability. It is a prodrug and gets converted to Tedizolid (TDZ) by phosphatases in vivo. The sterilized NC1 was subjected to antimicrobial testing on Gram-positive bacteria. Ocular irritation and pharmacokinetics were performed in rabbits. Around a 1.29 to 1.53-fold increase in antibacterial activity was noted for NC1 against the B. subtilis, S. pneumonia, S. aureus and MRSA (SA-6538) as compared to the TZP-pure. The NC1-AqS was “practically non-irritating” to rabbit eyes. There was around a 1.67- and 1.43 fold increase in t1/2 (h) and Cmax (ngmL−1) while there were 1.96-, 1.91-, 2.69- and 1.41-times increases in AUC0–24h,AUC0–∞,AUMC0–∞ and MRT0–∞, respectively, which were found by NC1 as compared to TZP-AqS in the ocular pharmacokinetic study. The clearance of TDZ was faster (11.43 mLh−1) from TZP-AqS as compared to NC1 (5.88 mLh−1). Relatively, an extended half-life (t1/2; 4.45 h) of TDZ and the prolonged ocular retention (MRT0–∞; 7.13 h) of NC1 was found, while a shorter half-life (t1/2; 2.66 h) of TDZ and MRT0–∞(t1/2; 5.05 h)was noted for TZP-AqS, respectively. Cationic TZP-NC1 could offer increased transcorneal permeation, which could mimic the improved ocular bioavailability of the drug in vivo. Conclusively, NC1 of TZP was identified as a promising substitute for the ocular delivery of TZP, with better performance as compared to its conventional AqS.
Synthesis and Biological Activity Screening of Newly Synthesized Trimethoxyphenyl-Based Analogues as Potential Anticancer Agents
Authors: Al-Warhi Tarfah , Abualnaja Matokah , Abu Ali Ola A. , Althobaiti Fayez , Alharthi Fahad , Elsaid Fahmy G. , Shati Ali A. , Fayad Eman , Elghareeb Doaa , Abu Almaaty Ali H. , Zaki Islam
Published: July 2022

A group of novel trimethoxyphenyl (TMP)-based analogues were synthesized by varying the azalactone ring of 2-(3,4-dimethoxyphenyl)-4-(3,4,5-trimethoxybenzylidene)oxazolone 1 and characterized using NMR spectral data as well as elemental microanalyses. All synthesized compounds were screened for their cytotoxic activity utilizing the hepatocellular carcinoma (HepG2) cell line. Compounds 9, 10 and 11 exhibited good cytotoxic potency with IC50 values ranging from 1.38 to 3.21 μM compared to podophyllotoxin (podo) as a reference compound. In addition, compounds 9, 10 and 11 exhibited potent inhibition of β-tubulin polymerization. DNA flow cytometry analysis of compound 9 shows cell cycle disturbance at the G2/M phase and a significant increase in Annexin-V-positive cells compared with the untreated control. Compound 9 was further studied regarding its apoptotic potential in HepG2 cells; it decreased the level of MMP and Bcl-2 as well as boosted the level of p53 and Bax compared with the control HepG2 cells.
New Benzil and Isoflavone Derivatives with Cytotoxic and NO Production Inhibitory Activities from Placolobium vietnamense
Authors: Do Lien T. M. , Huynh Tuyet T. N. , Sichaem Jirapast
Published: July 2022

The phytochemical investigation of Placolobium vietnamense stems led to the isolation of a new isoflavone derivative (1) and three new benzil derivatives (2–4), together with four known pyranoisoflavones (5–8). The structures of all isolated compounds were determined on the basis of extensive spectroscopic analyses, including NMR and HRMS spectral data, as well as comparison of their spectroscopic data with those reported in the literature. The cytotoxicity of all isolated compounds was assessed against the human liver hepatocellular carcinoma (Hep G2) cell line, and compound 1 displayed the most significant cytotoxicity with an IC50 value of 8.0 μM. Furthermore, all isolated compounds were also tested for their inhibitory activity against NO production in RAW 264.7 macrophages. Of these, compound 1 exhibited the strongest inhibitory efficacy against the LPS-induced NO production with the IC50 value of 13.7 μM.
Optimisation of Glycerol and Itaconic Anhydride Polycondensation
Authors: Kolankowski Krzysztof , Miętus Magdalena , Ruśkowski Paweł , Gadomska-Gajadhur Agnieszka
Published: July 2022

Glycerol polyesters have recently become objects of interest in tissue engineering. Barely known so far is poly(glycerol itaconate) (PGItc), a biocompatible, biodegradable polyester. Due to the presence of a C=C electron-acceptor moiety, it is possible to post-modify the product by Michael additions to change the properties of PGItc. Thus, using PGItc as one of the elements of cellular scaffold crosslinked in situ for bone tissue regeneration seems to be a very attractive yet unexplored solution. This work aims to optimize the synthesis of PGItc to obtain derivatives with a double bond in the side chain with the highest conversion rates. The experiments were performed with itaconic anhydride and glycerol using mathematical planning of experiments according to the Box-Behnken plan without solvent and catalyst. The input variables of the process were the ratio of the OH/COOH, temperature, and reaction time. The optimised output variables were: the degree of esterification (EDtitr), the degree of esterification calculated from the analysis of 1H NMR spectra (EDNMR), and the degree of itaconic anhydride conversion—calculation based on 13C NMR spectra (%X13CNMR). In each of statistical models, the significance of the changed synthesis parameters was determined. Optimal conditions are when OH/COOH ratio is equal to 1.5, temperature is 140 °C and time of reaction is 5 h. The higher OH/COOH ratio, temperature and longer the experiment time, the higher the value of the degree of esterification and the degree of anhydride conversion.
Gene Expression and Protein Abundance of Nuclear Receptors in Human Intestine and Liver: A New Application for Mass Spectrometry-Based Targeted Proteomics
Authors: Wenzel Christoph , Gödtke Lisa , Reichstein Anne , Keiser Markus , Busch Diana , Drozdzik Marek , Oswald Stefan
Published: July 2022

Background: Unwanted drug-drug interactions (DDIs), as caused by the upregulation of clinically relevant drug metabolizing enzymes and transporter proteins in intestine and liver, have the potential to threaten the therapeutic efficacy and safety of drugs. The molecular mechanism of this undesired but frequently occurring scenario of polypharmacy is based on the activation of nuclear receptors such as the pregnane X receptor (PXR) or the constitutive androstane receptor (CAR) by perpetrator agents such as rifampin, phenytoin or St. John’s wort. However, the expression pattern of nuclear receptors in human intestine and liver remains uncertain, which makes it difficult to predict the extent of potential DDIs. Thus, it was the aim of this study to characterize the gene expression and protein abundance of clinically relevant nuclear receptors, i.e., the aryl hydrocarbon receptor (AhR), CAR, farnesoid X receptor (FXR), glucocorticoid receptor (GR), hepatocyte nuclear factor 4 alpha (HNF4α), PXR and small heterodimer partner (SHP), in the aforementioned organs. Methods: Gene expression analysis was performed by quantitative real-time PCR of jejunal, ileal, colonic and liver samples from eight human subjects. In parallel, a targeted proteomic method was developed and validated in order to determine the respective protein amounts of nuclear receptors in human intestinal and liver samples. The LC-MS/MS method was validated according to the current bioanalytical guidelines and met the criteria regarding linearity (0.1–50 nmol/L), within-day and between-day accuracy and precision, as well as the stability criteria. Results: The developed method was successfully validated and applied to determine the abundance of nuclear receptors in human intestinal and liver samples. Gene expression and protein abundance data demonstrated marked differences in human intestine and liver. On the protein level, only AhR and HNF4α could be detected in gut and liver, which corresponds to their highest gene expression. In transfected cell lines, PXR and CAR could be quantified. Conclusions: The substantially different expression pattern of nuclear receptors in human intestinal and liver tissue may explain the different extent of unwanted DDIs in the dependence on the administration route of drugs.
Maleimide-Functionalized Liposomes: Prolonged Retention and Enhanced Efficacy of Doxorubicin in Breast Cancer with Low Systemic Toxicity
Authors: Tang Chuane , Yin Dan , Liu Tianya , Gou Rui , Fu Jiao , Tang Qi , Wang Yao , Zou Liang , Li Hanmei
Published: July 2022

Cell surface thiols can be targeted by thiol-reactive groups of various materials such as peptides, nanoparticles, and polymers. Here, we used the maleimide group, which can rapidly and covalently conjugate with thiol groups, to prepare surface-modified liposomes (M-Lip) that prolong retention of doxorubicin (Dox) at tumor sites, enhancing its efficacy. Surface modification with the maleimide moiety had no effect on the drug loading efficiency or drug release properties. Compared to unmodified Lip/Dox, M-Lip/Dox was retained longer at the tumor site, it was taken up by 4T1 cells to a significantly greater extent, and exhibited stronger inhibitory effect against 4T1 cells. The in vivo imaging results showed that the retention time of M-Lip at the tumor was significantly longer than that of Lip. In addition, M-Lip/Dox also showed significantly higher anticancer efficacy and lower cardiotoxicity than Lip/Dox in mice bearing 4T1 tumor xenografts. Thus, the modification strategy with maleimide may be useful for achieving higher efficient liposome for tumor therapy.
Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents
Authors: Frasinyuk Mykhaylo , Chhabria Dimple , Kartsev Victor , Dilip Haritha , Sirakanyan Samvel N. , Kirubakaran Sivapriya , Petrou Anthi , Geronikaki Athina , Spinelli Domenico
Published: July 2022

Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose–response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.
Discrimination and Prediction of Lonicerae japonicae Flos and Lonicerae Flos and Their Related Prescriptions by Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy Combined with Multivariate Statistical Analysis
Authors: Tang Yang-Qiannan , Li Li , Lin Tian-Feng , Lin Li-Mei , Li Ya-Mei , Xia Bo-Hou
Published: July 2022

LJF and LF are commonly used in Chinese patent drugs. In the Chinese Pharmacopoeia, LJF and LF once belonged to the same source. However, since 2005, the two species have been listed separately. Therefore, they are often misused, and medicinal materials are indiscriminately put in their related prescriptions in China. In this work, firstly, we established a model for discriminating LJF and LF using ATR-FTIR combined with multivariate statistical analysis. The spectra data were further preprocessed and combined with spectral filter transformations and normalization methods. These pretreated data were used to establish pattern recognition models with PLS-DA, RF, and SVM. Results demonstrated that the RF model was the optimal model, and the overall classification accuracy for LJF and LF samples reached 98.86%. Then, the established model was applied in the discrimination of their related prescriptions. Interestingly, the results show good accuracy and applicability. The RF model for discriminating the related prescriptions containing LJF or LF had an accuracy of 100%. Our results suggest that this method is a rapid and effective tool for the successful discrimination of LJF and LF and their related prescriptions.
Correlation between Irradiation Treatment and Metabolite Changes in Bactrocera dorsalis (Diptera: Tephritidae) Larvae Using Solid-Phase Microextraction (SPME) Coupled with Gas Chromatography-Mass Spectrometry (GC-MS)
Authors: Shan Changyao , Li Baishu , Li Li , Li Beibei , Ren YongLin , Liu Tao
Published: July 2022

The metabolites produced by the larvae of Bactrocera dorsalis (Diptera: Tephritidae) exposed to different doses of irradiation were analyzed using solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS), and a metabonomic analysis method of irradiated insects based on GC-MS was established. The analysis revealed 67 peaks, of which 23 peaks were identified. The metabolites produced by larvae treated with different irradiation doses were compared by multivariate statistical analysis, and eight differential metabolites were selected. Irradiation seriously influenced the fatty acid metabolic pathway in larvae. Using the R platform combined with the method of multivariate statistical analysis, changes to metabolite production under four irradiation doses given to B. dorsalis larvae were described. Differential metabolites of B. dorsalis larvae carried chemical signatures that indicated irradiation dose, and this method is expected to provide a reference for the detection of irradiated insects.
Design Considerations for Immersive Virtual Reality Applications for Older Adults: A Scoping Review
Authors: Ijaz Kiran , Tran Tram Thi Minh , Kocaballi Ahmet Baki , Calvo Rafael A. , Berkovsky Shlomo , Ahmadpour Naseem
Published: July 2022

Immersive virtual reality (iVR) has gained considerable attention recently with increasing affordability and accessibility of the hardware. iVR applications for older adults present tremendous potential for diverse interventions and innovations. The iVR literature, however, provides a limited understanding of guiding design considerations and evaluations pertaining to user experience (UX). To address this gap, we present a state-of-the-art scoping review of literature on iVR applications developed for older adults over 65 years. We performed a search in ACM Digital Library, IEEE Xplore, Scopus, and PubMed (1 January 2010–15 December 2019) and found 36 out of 3874 papers met the inclusion criteria. We identified 10 distinct sets of design considerations that guided target users and physical configuration, hardware use, and software design. Most studies carried episodic UX where only 2 captured anticipated UX and 7 measured longitudinal experiences. We discuss the interplay between our findings and future directions to design effective, safe, and engaging iVR applications for older adults.
Stable Dried Catalase Particles Prepared by Electrospraying
Authors: Schlosser Corinna S. , Brocchini Steve , Williams Gareth R.
Published: July 2022

Therapeutic proteins and peptides are clinically important, offering potency while reducing the potential for off-target effects. Research interest in developing therapeutic polypeptides has grown significantly during the last four decades. However, despite the growing research effort, maintaining the stability of polypeptides throughout their life cycle remains a challenge. Electrohydrodynamic (EHD) techniques have been widely explored for encapsulation and delivery of many biopharmaceuticals. In this work, we explored monoaxial electrospraying for encapsulation of bovine liver catalase, investigating the effects of the different components of the electrospraying solution on the integrity and bioactivity of the enzyme. The catalase was successfully encapsulated within polymeric particles made of polyvinylpyrrolidone (PVP), dextran, and polysucrose. The polysorbate 20 content within the electrospraying solution (50 mM citrate buffer, pH 5.4) affected the catalase loading—increasing the polysorbate 20 concentration to 500 μg/mL resulted in full protein encapsulation but did not prevent loss in activity. The addition of ethanol (20% v/v) to a fully aqueous solution improves the electrospraying process by reducing surface tension, without loss of catalase activity. The polymer type was shown to have the greatest impact on preserving catalase activity within the electrosprayed particles. When PVP was the carrier there was no loss in activity compared with fresh aqueous solutions of catalase. The optimum particles were obtained from a 20% w/v PVP or 30% w/v PVP-trehalose (1:1 w/w) solution. The addition of trehalose confers stability advantages to the catalase particles. When trehalose-PVP particles were stored at 5 °C, enzymatic activity was maintained over 3 months, whereas for the PVP-only analogue a 50% reduction in activity was seen. This demonstrates that processing catalase by monoaxial electrospraying can, under optimised conditions, result in stable polymeric particles with no loss of activity.
Biomimetic Nanomaterials: Diversity, Technology, and Biomedical Applications
Authors: Gareev Kamil G. , Grouzdev Denis S. , Koziaeva Veronika V. , Sitkov Nikita O. , Gao Huile , Zimina Tatiana M. , Shevtsov Maxim
Published: July 2022

Biomimetic nanomaterials (BNMs) are functional materials containing nanoscale components and having structural and technological similarities to natural (biogenic) prototypes. Despite the fact that biomimetic approaches in materials technology have been used since the second half of the 20th century, BNMs are still at the forefront of materials science. This review considered a general classification of such nanomaterials according to the characteristic features of natural analogues that are reproduced in the preparation of BNMs, including biomimetic structure, biomimetic synthesis, and the inclusion of biogenic components. BNMs containing magnetic, metal, or metal oxide organic and ceramic structural elements (including their various combinations) were considered separately. The BNMs under consideration were analyzed according to the declared areas of application, which included tooth and bone reconstruction, magnetic and infrared hyperthermia, chemo- and immunotherapy, the development of new drugs for targeted therapy, antibacterial and anti-inflammatory therapy, and bioimaging. In conclusion, the authors’ point of view is given about the prospects for the development of this scientific area associated with the use of native, genetically modified, or completely artificial phospholipid membranes, which allow combining the physicochemical and biological properties of biogenic prototypes with high biocompatibility, economic availability, and scalability of fully synthetic nanomaterials.
Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress
Authors: Mastropasqua Leonardo , Agnifili Luca , Ferrante Claudio , Sacchi Matteo , Figus Michele , Rossi Gemma Caterina Maria , Brescia Lorenza , Aloia Raffaella , Orlando Giustino
Published: July 2022

Background: The present study aimed to investigate the rationale and efficacy of using a citicoline, coenzyme Q10 (CAVAQ10) and vitamin B3 fixed combination in combating inflammation and oxidation in neuronal cells exposed to oxidative stress. Methods: HypoE22 cells and isolated hypothalamic specimens were selected as in vitro models to conduct the experiments. The efficacy of citicoline, CAVAQ10, and vitamin B3, with their fixed combination, were assayed after the exposure of hypothalamic cells to hydrogen peroxide (concentration range 1 nM–10 µM), in order to evaluate the biocompatibility of treatments. The activity of neuroprotective and pro-inflammatory factors, namely, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα), involved in the neuronal cell damage in neurodegenerative diseases, were assayed in isolated hypothalamus. Results: Neither citicoline, CAVAQ10, nor vitamin B3 significantly altered hypothalamic cell viability, thus suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. In the same condition, citicoline and CAVAQ10 were also effective in reducing the gene expression of monoaminoxidase-B, involved in dopamine degradation. However, only citicoline demonstrated an ability to reduce dopamine levels. Conversely, all compounds were effective in reducing the gene expression of IL-6, and TNFα, and in inducing the gene expression of BDNF, with the co-administration of citicoline/CAVAQ10/vitamin B3 being generally more effective than single ingredients. Conclusions: The present findings support the beneficial and synergistic effects of citicoline, CAVAQ10, and vitamin B3 in fixed combination in reducing inflammation and oxidation, and in stimulating neurotrophin production in neuronal cells.
Optimization of Omega-3 Index Levels in Athletes at the US Naval Academy: Personalized Omega-3 Fatty Acid Dosage and Molecular Genetic Approaches
Authors: Rittenhouse Melissa , Sambuughin Nyamkhishig , Deuster Patricia
Published: July 2022

The Dietary Guidelines for Americans recommend increasing the intake of omega-3 polyunsaturated fatty acids. The Omega-3 Index (O3I) is one marker used to assess omega-3 status. The O3I national average is 4.3%, which translates into a high risk for developing cardiovascular disease. Research has reported an association between variants in the two desaturase encoding genes, fatty acid desaturase 1 and fatty acid desaturase 2 (FADS1/2), and the concentration of O3I. The aim of this study was to assess whether a personalized dosage of omega-3 supplementation would lead to an O3I ≥ 8%. A secondary aim was to identify if changes in O3I levels would be associated with either of the two FADS1/2 variants. Methods: This interventional study had a pre- and post-intervention design to assess changes in O3I. Ninety participants completed demographic, biometrics, O3I, and genetic testing. Participants were provided a personalized dose of omega-3 supplements based on their baseline O3I. Results: The majority (63%) of participants were 20 year old white males with an average O3I at baseline of 4.6%; the post-supplementation average O3I was 5.6%. The most frequent genetic variants expressed in the full sample for FADS1/2 were GG (50%) and CA/AA (57%). Conclusions: O3I was significantly increased following omega-3 supplementation. However, it was not possible to conclude whether the two FADS1/2 variants led to differential increases in OI3 or if a personalized dosage of omega-3 supplementation led to an O3I ≥ 8%, due to our study limitations.
Communicating Health to Young Adults Using Social Media: How, Where, and When?
Authors: Dix Clare F. , Brennan Linda , McCaffrey Tracy A. , Reid Mike , Molenaar Annika , Barklamb Amy , Chin Shinyi , Truby Helen
Published: July 2022

Communication with young adults about healthy lifestyle behaviours needs to result in improvements in dietary choices to impact the prevalence of diet-related diseases. This paper presents the health beliefs, behaviours, and communication practices in young Australian adults (n = 2019) by their pre-defined psycho-behavioural characteristics: Lifestyle Mavens, Health-Conscious, Aspirational Healthy Eaters, Balanced-All Rounders, Contemplating Another Day, or Blissfully Unconcerned. The Lifestyle Mavens and Health-Conscious groups were more likely to actively seek out health information on social media (p < 0.05). Lifestyle Mavens were the most likely to engage with health and food content on social media, whereas the Blissfully Unconcerned were the least likely to engage (p < 0.05). Lifestyle Mavens are more likely to report creating food and health-related content for social media, whereas Aspirational Healthy Eaters are more likely to report searching for food and health-related content online, but are less likely to share or create content. Contemplating Another Day are more likely to report interactions with commercial content. This paper defines how psycho-behavioural segments communicate about health, where they look for information, how they may prefer to receive health messages, and when they are most receptive to messages. By applying existing robust market segmentation techniques, this paper provides nuanced information that challenges the assumption that online social media health information is preferred by all young adults.
Spore Powder of Paecilomyces hepiali Shapes Gut Microbiota to Relieve Exercise-Induced Fatigue in Mice
Authors: Guan Tianyue , Li Shuoshuo , Guan Qijie , Shi Jin-Song , Lu Zhen-Ming , Xu Zheng-Hong , Geng Yan
Published: July 2022

Paecilomyces hepiali, a fungal strain isolated from natural Ophiocordyceps sinensis, contains similar pharmacologically active components, has been used widely as a substitute of O. sinensis in functional food and medicine. However, the components and anti-fatigue effects of P.hepiali spores and their mechanisms of action are largely unknown. Here, we compared the chemical composition in P.hepiali spore (HPS) and mycelium (HPM) by liquid chromatography with tandem mass spectrometry analysis. We found 85 metabolites with significant differences, and HPS contains more L-Malic acid, Oxalacetic acid, Fructose-1,6-bisphosphate, and L-Arginine than HPM. Then we evaluated their anti-fatigue effects and regulatory effects on the gut microbiota in mice. The forced swimming time (SW) was only significantly increased in HPS groups: the high and low dose of the HPS group was 101% and 72% longer than the control group, respectively. Both HPS and HPM treatment decreased lactic acid, blood urea nitrogen, creatine kinase while increased lactate dehydrogenase (LDH) levels in the blood. Moreover, mice treated with HPS and HPM showed less skeletal muscle fiber spacing and breakage. The relative abundance of Alistips, Eubacterium, Bacterium, Parasutterella, and Olsenella in the gut microbiota of the HPS group was higher than that in the HPM group through 16S rRNA gene sequencing analysis. These changes may be related to the regulation of nucleotide, amino acid, and carbohydrate metabolism. Correlation analysis between the gut microbiota and fatigue-related indicators suggested that Alistips, Clostridium, Akkermansia, Olsenella, and Lactobacillus were positively correlated with the SW and LDH content. Our findings demonstrated that HPS has beneficial anti-fatigue effects by regulating gut microbiota.
Entanglement of Steller Sea Lions in Marine Debris and Fishing Gear on the Central Oregon Coast from 2005–2009
Authors: Raum-Suryan Kimberly L. , Suryan Robert M.
Published: July 2022

Entanglement in marine debris and fishing gear is an increasing problem for the world’s pinnipeds and a contributing factor in Steller sea lion (Eumetopias jubatus) injury and mortality. From 2005–2009, we surveyed (n = 389 days) two haul-outs on the central Oregon coast containing a combined median of 402 animals (range 33–1240, or ca. 1–19% of the Oregon coast population). We recorded 72 individuals entangled in marine debris (n = 70) or with ingested salmon hook-and-line fishing gear (n = 2). Of the identifiable neck entanglements, black rubber bands were the most common neck-entangling material (62%), followed by plastic packing bands (36%), nets (1.2%), yellow rubber bands (0.4%), and a flying disc (0.4%). The estimated prevalence of entanglement for individuals in Oregon was 0.34%. Juveniles were the most frequently entangled age class (60%), followed by adult females (28%), and subadult males (12%). Supply chain and industry-based solutions are needed to prevent entangling debris from entering the ocean, along with eliminating, modifying, or cutting entangling loops of synthetic material.
Palladium-Catalyzed Cross-Coupling Reactions of Borylated Alkenes for the Stereoselective Synthesis of Tetrasubstituted Double Bond
Authors: Tobrman Tomáš , Mrkobrada Sergej
Published: July 2022

The stereoselective formation of tetrasubstituted alkenes remains one of the key goals of modern organic synthesis. In addition to other methods, the stereoselective synthesis of tetrasubstituted alkenes can be achieved by means of cross-coupling reactions of electrophilic and nucleophilic alkene templates. The use of electrophilic templates for the stereoselective synthesis of tetrasubstituted alkenes has previously been described. Therefore, the present review summarizes the procedures available for the stereoselective preparation of tetrasubstituted alkenes using stable and isolable nucleophilic templates.
Nutraceutical Interventions for Post-Traumatic Stress Disorder in Animal Models: A Focus on the Hypothalamic–Pituitary–Adrenal Axis
Authors: Cai Mudan , Park Hee Ra , Yang Eun Jin
Published: July 2022

Post-traumatic stress disorder (PTSD) occurs after exposure to traumatic events and is characterized by overwhelming fear and anxiety. Disturbances in the hypothalamic–pituitary–adrenal (HPA) axis are involved in the pathogenesis of mood disorders, including anxiety, PTSD, and major depressive disorders. Studies have demonstrated the relationship between the HPA axis response and stress vulnerability, indicating that the HPA axis regulates the immune system, fear memory, and neurotransmission. The selective serotonin reuptake inhibitors (SSRIs), sertraline and paroxetine, are the only drugs that have been approved by the United States Food and Drug Administration for the treatment of PTSD. However, SSRIs require long treatment times and are associated with lower response and remission rates; therefore, additional pharmacological interventions are required. Complementary and alternative medicine therapies ameliorate HPA axis disturbances through regulation of gut dysbiosis, insomnia, chronic stress, and depression. We have described the cellular and molecular mechanisms through which the HPA axis is involved in PTSD pathogenesis and have evaluated the potential of herbal medicines for PTSD treatment. Herbal medicines could comprise a good therapeutic strategy for HPA axis regulation and can simultaneously improve PTSD-related symptoms. Finally, herbal medicines may lead to novel biologically driven approaches for the treatment and prevention of PTSD.
Transport Mechanisms at the Blood–Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs
Authors: Ronaldson Patrick T. , Davis Thomas P.
Published: July 2022

Ischemic stroke is a primary origin of morbidity and mortality in the United States and around the world. Indeed, several research projects have attempted to discover new drugs or repurpose existing therapeutics to advance stroke pharmacotherapy. Many of these preclinical stroke studies have reported positive results for neuroprotective agents; however, only one compound (3K3A-activated protein C (3K3A-APC)) has advanced to Phase III clinical trial evaluation. One reason for these many failures is the lack of consideration of transport mechanisms at the blood–brain barrier (BBB) and neurovascular unit (NVU). These endogenous transport processes function as a “gateway” that is a primary determinant of efficacious brain concentrations for centrally acting drugs. Despite the knowledge that some neuroprotective agents (i.e., statins and memantine) are substrates for these endogenous BBB transporters, preclinical stroke studies have largely ignored the role of transporters in CNS drug disposition. Here, we review the current knowledge on specific BBB transporters that either limit drug uptake into the brain (i.e., ATP-binding cassette (ABC) transporters) or can be targeted for optimized drug delivery (i.e., solute carrier (SLC) transporters). Additionally, we highlight the current knowledge on transporter expression in astrocytes, microglia, pericytes, and neurons with an emphasis on transport mechanisms in these cell types that can influence drug distribution within the brain.
Reducing the Kidney Uptake of High Contrast CXCR4 PET Imaging Agents via Linker Modifications
Authors: Kwon Daniel , Zhang Zhengxing , Zeisler Jutta , Kuo Hsiou-Ting , Lin Kuo-Shyan , Benard Francois
Published: July 2022

Purpose: The C-X-C chemokine receptor 4 (CXCR4) is highly expressed in many subtypes of cancers, notably in several kidney-based malignancies. We synthesized, labeled, and assessed a series of radiotracers based on a previous high contrast PET imaging radiopharmaceutical [68Ga]Ga-BL02, with modifications to its linker and metal chelator, in order to improve its tumor-to-kidney contrast ratio. Methods: Based on the design of BL02, a piperidine-based cationic linker (BL06) and several anionic linkers (tri-Aad (BL17); tri-D-Glu (BL20); tri-Asp (BL25); and tri-cysteic acid (BL31)) were substituted for the triglutamate linker. Additionally, the DOTA chelator was swapped for a DOTAGA chelator (BL30). Each radiotracer was labeled with 68Ga and evaluated in CXCR4-expressing Daudi xenograft mice with biodistribution and/or PET imaging studies. Results: Of all the evaluated radiotracers, [68Ga]Ga-BL31 showed the most promising biodistribution profile, with a lower kidney uptake compared to [68Ga]Ga-BL02, while retaining the high imaging contrast capabilities of [68Ga]Ga-BL02. [68Ga]Ga-BL31 also compared favorably to [68Ga]Ga-Pentixafor, with superior imaging contrast in all non-target organs. The other anionic linker-based radiotracers showed either equivocal or worse contrast ratios compared to [68Ga]Ga-BL02; however, [68Ga]Ga-BL25 also showed lower kidney uptake, as compared to that of [68Ga]Ga-BL02. Meanwhile, [68Ga]Ga-BL06 had high non-target organ uptake and relatively lower tumor uptake, while [68Ga]Ga-BL30 showed significantly increased kidney uptake and similar tumor uptake values. Conclusions: [68Ga]Ga-BL31 is an optimized CXCR4-targeting radiopharmaceutical with lower kidney retention that has clinical potential for PET imaging and radioligand therapy.
Opening the Blood Brain Barrier with an Electropermanent Magnet System
Authors: Jafari Sahar , Baum Ittai S. , Udalov Oleg G. , Lee Yichien , Rodriguez Olga , Fricke Stanley T. , Jafari Maryam , Amini Mostafa , Probst Roland , Tang Xinyao , Chen Cheng , Ariando David J. , Hevaganinge Anjana , Mair Lamar O. , Albanese Christopher , Weinberg Irving N.
Published: July 2022

Opening the blood brain barrier (BBB) under imaging guidance may be useful for the treatment of many brain disorders. Rapidly applied magnetic fields have the potential to generate electric fields in brain tissue that, if properly timed, may enable safe and effective BBB opening. By tuning magnetic pulses generated by a novel electropermanent magnet (EPM) array, we demonstrate the opening of tight junctions in a BBB model culture in vitro, and show that induced monophasic electrical pulses are more effective than biphasic ones. We confirmed, with in vivo contrast-enhanced MRI, that the BBB can be opened with monophasic pulses. As electropermanent magnets have demonstrated efficacy at tuning B0 fields for magnetic resonance imaging studies, our results suggest the possibility of implementing an EPM-based hybrid theragnostic device that could both image the brain and enhance drug transport across the BBB in a single sitting.