bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Qualified Public Safety Education Venues Using the Dempster–Shafer Theory-Based PROMETHEE Method under Linguistic Environments
Authors: Zhang Yiqian , Dai Yutong , Liu Bo
Published: February 2023

How to improve safety awareness is an important topic, and it is of great significance for the public to reduce losses in the face of disasters and crises. A public safety education venue is an important carrier to realize safety education, as it has the characteristics of professionalism, comprehensiveness, experience, interest, participation, and so on, arousing the enthusiasm of the public for learning. As a meaningful supplement to “formal safety education”, venue education has many advantages. However, there are problems in the current venue construction such as imperfect infrastructure, weak professionalism, poor service level, chaotic organizational structure, and low safety, which affect the effect of safety education. To evaluate safety education venues effectively, this study proposes an evidential PROMETHEE method under linguistic environments. The innovation of this study lies in the integration of various linguistic expressions into the Dempster–Shafer theory (DST) framework, realizing the free expression and choice of evaluation information. The results and contributions of this study are summarized as follows. First, a two-tier evaluation index system of public safety education venues including 18 sub-standards is constructed. Secondly, it sets up four levels of quality evaluation for public safety education venues. Third, the belief function is used to represent all kinds of linguistic information, so as to maximize the effect of linguistic information fusion. Fourthly, an evidential PROMETHEE model is proposed to rank the venues. Fifthly, a case study is presented to demonstrate the usage of the proposed method in detail, and the evaluation results are fully analyzed and discussed. The implications of this study are as follows. First of all, to enhance public safety education, people need to face the significance of experiential education venues. Second, experiential education venues can increase learners’ enthusiasm for learning. Thirdly, the evaluation index system provided in this paper can be used to guide the construction of appropriate education venues in cities. Fourthly, the method of linguistic information transformation based on DST is also applicable to other decision-making and evaluation problems. Finally, the evidential PROMETHEE method can not only evaluate the quality of education venues, but also be used to rank a group of alternative venues.
A Fouling Comparison Study of Algal, Bacterial and Humic Organic Matters in Seawater Desalination Pretreatment Using Ceramic UF Membranes
Authors: Al Namazi Mohammed , Li Sheng , Ghaffour Noreddine , Leiknes TorOve , Amy Gary
Published: February 2023

This study investigates three types of organic matter, namely algal organic matter (AOM), bacterial organic matter (BOM), and humic organic matter (HOM). These organics are different in properties and chemical composition. AOM, BOM and HOM were compared in terms of organic content, fouling behavior, and removal efficiency in ceramic UF filtration. UF experiments were conducted at a constant flux mode using 5 kDa and 50 kDa ceramic membranes. Results showed that 5 kDa membrane removed more transparent exopolymer particles (TEP)/organics than 50 kDa membranes, but less fouling formation for all the three types of organic matters tested. Membranes exhibited the lowest trans-membrane pressure (TMP) during the filtration of HOM, most probably due to the high porosity of the HOM cake layer, contributed by big HOM aggregates under Ca bridging effect. AOM shows the highest MFI-UF (modified fouling index-ultrafiltration) and TMP (transmembrane pressure) values among the three organics and during all filtration cycles for both membranes. The AOM fouling layer is well known for having high fouling potential due to its compressibility and compactness which increase the TMP and eventually the MFI values. AOM and BOM organics exhibited a similar fouling behavior and mechanism. Furthermore, the divalent cations such as calcium showed a significant impact on membrane fouling. That is probably because calcium ions made the membranes and organic matter less negatively charged and easier to deposit on membranes, thus, enhancing the membrane fouling significantly.
Research Progress of Titanium Sponge Production: A Review
Authors: Feng Qisheng , Lv Mingrui , Mao Lu , Duan Baohua , Yang Yuchen , Chen Guangyao , Lu Xionggang , Li Chonghe
Published: February 2023

Titanium has excellent all-round performance, but the high cost of its production limits its widespread use. Currently, the Kroll process used to commercially produce titanium sponge is inefficient, energy-intensive, and highly polluting to the environment. Over the past few decades, many new processes have been developed to replace the Kroll process in order to reduce the cost of producing titanium and make it a common metal with as many applications as iron. These new processes can be divided into two categories: thermal reduction and electrolysis. Based on their classification, this paper reviews the current development status of various processes and analyzes the advantages and disadvantages of each process. Finally, the development direction and challenges of titanium production process are put forward.
Serum Androgen Metabolites Correlate with Clinical Variables in African and European American Men with Localized, Therapy Naïve Prostate Cancer
Authors: Ramakrishnan Swathi , Kittles Rick A. , Huss Wendy J. , Wang Jianmin , Attwood Kristopher , Woloszynska Anna
Published: February 2023

Dihydrotestosterone (DHT) and testosterone (T), which mediate androgen receptor nuclear translocation and target gene transcription, are crucial androgens and essential molecular triggers required for the proliferation and survival of prostate cancer cells. Therefore, androgen metabolism is commonly targeted in the treatment of prostate cancer. Using a high-pressure liquid chromatographic assay with tandem mass spectral detection, we determined the serum levels of metabolites produced during DHT/T biosynthesis in African American (AA) and European American (EA) men with localized, therapy naïve prostate cancer. Serum progesterone and related metabolites were significantly lower in AA men than in EA men, and these differences were associated with rapid disease progression. Multivariate analysis revealed significant differences between a subset of intermediate androgen metabolites between AA and EA men and between men with <=3 + 4 and >=4 + 3 Gleason score disease. AA men have a significantly higher frequency of single nucleotide polymorphisms in CYP11B1 and CYP11B2, enzymes that regulate corticosterone-aldosterone conversion. Finally, higher levels of T and pregnenolone were associated with a lower risk of progression-free survival only in AA men. This work provides new insight into androgen metabolism and racial disparities in prostate cancer by presenting evidence of dysregulated androgen biosynthesis in therapy naïve disease that correlates with clinical variables.
An Introduction to Nanopore Sequencing: Past, Present, and Future Considerations
Authors: MacKenzie Morgan , Argyropoulos Christos
Published: February 2023

There has been significant progress made in the field of nanopore biosensor development and sequencing applications, which address previous limitations that restricted widespread nanopore use. These innovations, paired with the large-scale commercialization of biological nanopore sequencing by Oxford Nanopore Technologies, are making the platforms a mainstay in contemporary research laboratories. Equipped with the ability to provide long- and short read sequencing information, with quick turn-around times and simple sample preparation, nanopore sequencers are rapidly improving our understanding of unsolved genetic, transcriptomic, and epigenetic problems. However, there remain some key obstacles that have yet to be improved. In this review, we provide a general introduction to nanopore sequencing principles, discussing biological and solid-state nanopore developments, obstacles to single-base detection, and library preparation considerations. We present examples of important clinical applications to give perspective on the potential future of nanopore sequencing in the field of molecular diagnostics.
A Novel Multi-Modal Teleoperation of a Humanoid Assistive Robot with Real-Time Motion Mimic
Authors: Cerón Julio C. , Sunny Md Samiul Haque , Brahmi Brahim , Mendez Luis M. , Fareh Raouf , Ahmed Helal Uddin , Rahman Mohammad H.
Published: February 2023

This research shows the development of a teleoperation system with an assistive robot (NAO) through a Kinect V2 sensor, a set of Meta Quest virtual reality glasses, and Nintendo Switch controllers (Joycons), with the use of the Robot Operating System (ROS) framework to implement the communication between devices. In this paper, two interchangeable operating models are proposed. An exclusive controller is used to control the robot’s movement to perform assignments that require long-distance travel. Another teleoperation protocol uses the skeleton joints information readings by the Kinect sensor, the orientation of the Meta Quest, and the button press and thumbstick movements of the Joycons to control the arm joints and head of the assistive robot, and its movement in a limited area. They give image feedback to the operator in the VR glasses in a first-person perspective and retrieve the user’s voice to be spoken by the assistive robot. Results are promising and can be used for educational and therapeutic purposes.
Oleaginous Yeast Extracts and Their Possible Effects on Human Health
Authors: Vysoka Marie , Szotkowski Martin , Slaninova Eva , Dzuricka Lucia , Strecanska Paulina , Blazkova Jana , Marova Ivana
Published: February 2023

Four non-conventional oleaginous and pigmented yeast strains of Metschnikowia pulcherrima, Cystofilobasidium infirmominiatum, Phaffia rhodozyma, and Rhodotorula kratochvilovae were used in this study. Complex yeast extracts were prepared and tested for biological activity, safety, and effect on human health. In this paper, we measured the antioxidant activity and antimicrobial effect of yeast biomass as a whole and their extracts to compare the influence of carotenoids and other bioactive substances in the studied biomass. All yeast extracts exhibited a significant dose-dependent antimicrobial effect against both G+ and G- bacteria and had a strong antioxidant effect. No cytotoxicity in the mouse melanoma B16F1 cell line was found in concentrations up to 20% of rehydrated biomass in cell medium. All of the extracts were cytotoxic at a concentration of 5 mg of extract/g of dry biomass. All the pigmented yeast extracts showed some positive results for apoptosis of murine melanoma cell lines and are therefore strong candidates positively effect human health. Red yeast cell biomass is a prospective material with many attractive biological functions and can be used in the food industry, as a pharmaceutical material, or in the feed industry.
Synthesis, Photophysical Characterization and Evaluation of Biological Properties of C7, a Novel Symmetric Tetra-Imidazolium-Bis-Heterocycle
Authors: Kunstek Hannah , Wang Melaine , Hussein Hiba , Dhouib Ines , Khemakhem Bassem , Risler Arnaud , Philippot Stephanie , Frochot Celine , Arnoux Philippe , Fournier Bertrand , Varbanov Mihayl , Dumarçay-Charbonnier Florence
Published: February 2023

A novel symmetric tetra-imidazolium-bis-heterocycle, called C7, was designed and synthesized in a quick two-step pathway, with the objective to synthesize biologically active supramolecular assembly. The synthesized compound was then analyzed for its photophysical properties, for a potential application in theragnostic (fluorescence) or phototherapy (photodynamic therapy, with the production of reactive oxygen species, such as singlet oxygen 1O2). C7 was thus screened for its biological activity, in particular against important human pathogens of viral origin (respiratory viruses such as adenovirus type 2 and human coronavirus 229E) and of fungal and bacterial origin. The compound showed limited antiviral activity, combined with very good antiproliferative activity against breast cancer, and head and neck squamous cell carcinoma models. Interestingly, the selected compound showed excellent antibacterial activity against a large array of Gram-positive and Gram-negative clinically isolated pathogenic bacteria, with a possible inhibitory mechanism on the bacterial cell wall synthesis studied with electron microscopy and molecular docking tools. Collectively, the newly synthesized compound C7 could be considered as a potential lead for the development of new antibacterial treatment, endowed with basic photophysical properties, opening the door towards the future development of phototherapy approaches.
Design, Synthesis, Biological Evaluation, and Molecular Dynamics Simulation of Influenza Polymerase PB2 Inhibitors
Authors: Li Xinhong , Xu Yijie , Li Wei , Che Jinjing , Zhao Xu , Cao Ruyuan , Li Xingzhou , Li Song
Published: February 2023

The PB2 subunit of the influenza RNA-dependent RNA polymerase (RdRp) has been identified as a promising target for the treatment of influenza. To expand the chemical space of the known influenza polymerase PB2 inhibitor–pimodivir (formerly VX-787) and improve its pharmacokinetic profile, two pimodivir analogs containing 2,3-dihydro-imidazopyridine fragment (comp. I and comp. II) were designed, synthesized, and evaluated for anti-influenza virus activity. In the cytopathic effect (CPE) inhibition assay, comp. I and comp. II showed IC50 values of 0.07 and 0.09 μM for A/Puerto Rico/8/34 (H1N1) and 0.04 and 0.07 μM for A/Hong Kong/8/68 (H3N2), respectively. Protein-binding affinity assay results showed a concentration-dependent association and dissociation pattern, with KD values of 1.398 and 1.670 μM, respectively. In vitro metabolic stability assays showed that comp. I and comp. II exhibited good stability to liver microsomes and considerably less sensitivity to aldehyde oxidase compared to pimodivir. The binding modes of comp. I and comp. II were similar to those of VX-787; however, comp. I and comp. II had lower structural adaptability to PB2 than VX-787. Our results provide helpful information regarding the structure–activity relationship for the design of novel PB2 inhibitors and a reference for the development of drugs containing 2,3-dihydro-imidazopyridine fragments.
R97 at “Handlebar” Binding Mode in Active Pocket Plays an Important Role in Fe(II)/α-Ketoglutaric Acid-Dependent Dioxygenase cis-P3H-Mediated Selective Synthesis of (2S,3R)-3-Hydroxypipecolic Acid
Authors: Guan Jiaojiao , Lu Yilei , Dai Zixuan , Zhao Songyin , Xu Yan , Nie Yao
Published: February 2023

Pipecolic acid (Pip) and its derivative hydroxypipecolic acids, such as (2S,3R)-3-hydroxypipecolic acid (cis-3-L-HyPip), are components of many natural and synthetic bioactive molecules. Fe(II)/α-ketoglutaric acid (Fe(II)/2-OG)-dependent dioxygenases can catalyze the hydroxylation of pipecolic acid. However, the available enzymes with desired activity and selectivity are limited. Herein, we compare the possible candidates in the Fe(II)/2-OG-dependent dioxygenase family, and cis-P3H is selected for potentially catalyzing selective hydroxylation of L-Pip. cis-P3H was further engineered to increase its catalytic efficiency toward L-Pip. By analyzing the structural confirmation and residue composition in substrate-binding pocket, a “handlebar” mode of molecular interactions is proposed. Using molecular docking, virtual mutation analysis, and dynamic simulations, R97, E112, L57, and G282 were identified as the key residues for subsequent site-directed saturation mutagenesis of cis-P3H. Consequently, the variant R97M showed an increased catalytic efficiency toward L-Pip. In this study, the kcat/Km value of the positive mutant R97M was about 1.83-fold that of the wild type. The mutation R97M would break the salt bridge between R97 and L-Pip and weaken the positive-positive interaction between R97 and R95. Therefore, the force on the amino and carboxyl groups of L-Pip was lightly balanced, allowing the molecule to be stabilized in the active pocket. These results provide a potential way of improving cis-P3H catalytic activity through rational protein engineering.
Stoichiometric Alkane and Aldehyde Hydroxylation Reactions Mediated by In Situ Generated Iron(III)-Iodosylbenzene Adduct
Authors: Török Patrik , Lakk-Bogáth Dóra , Kaizer József
Published: February 2023

Previously synthesized and spectroscopically characterized mononuclear nonheme, low-spin iron(III)-iodosylbenzene complex bearing a bidentate pyridyl-benzimidazole ligands has been investigated in alkane and aldehyde oxidation reactions. The in situ generated Fe(III) iodosylbenzene intermediate is a reactive oxidant capable of activating the benzylic C-H bond of alkane. Its electrophilic character was confirmed by using substituted benzaldehydes and a modified ligand framework containing electron-donating (Me) substituents. Furthermore, the results of kinetic isotope experiments (KIE) using deuterated substrate indicate that the C-H activation can be interpreted through a tunneling-like HAT mechanism. Based on the results of the kinetic measurements and the relatively high KIE values, we can conclude that the activation of the C-H bond mediated by iron(III)–iodosylbenzene adducts is the rate-determining step.
Effects of Hydroxytyrosol in Endothelial Functioning: A Comprehensive Review
Authors: Vijakumaran Ubashini , Shanmugam Janushaa , Heng Jun Wei , Azman Siti Sarah , Yazid Muhammad Dain , Haizum Abdullah Nur Atiqah , Sulaiman Nadiah
Published: February 2023

Pharmacologists have been emphasizing and applying plant and herbal-based treatments in vascular diseases for decades now. Olives, for example, are a traditional symbol of the Mediterranean diet. Hydroxytyrosol is an olive-derived compound known for its antioxidant and cardioprotective effects. Acknowledging the merit of antioxidants in maintaining endothelial function warrants the application of hydroxytyrosol in endothelial dysfunction salvage and recovery. Endothelial dysfunction (ED) is an impairment of endothelial cells that adversely affects vascular homeostasis. Disturbance in endothelial functioning is a known precursor for atherosclerosis and, subsequently, coronary and peripheral artery disease. However, the effects of hydroxytyrosol on endothelial functioning were not extensively studied, limiting its value either as a nutraceutical supplement or in clinical trials. The action of hydroxytyrosol in endothelial functioning at a cellular and molecular level is gathered and summarized in this review. The favorable effects of hydroxytyrosol in the improvement of endothelial functioning from in vitro and in vivo studies were scrutinized. We conclude that hydroxytyrosol is capable to counteract oxidative stress, inflammation, vascular aging, and arterial stiffness; thus, it is beneficial to preserve endothelial function both in vitro and in vivo. Although not specifically for endothelial dysfunction, hydroxytyrosol safety and efficacy had been demonstrated via in vivo and clinical trials for cardiovascular-related studies.
Preparation and Evaluation of Thermosensitive Liposomes Encapsulating I-125-Labeled Doxorubicin Derivatives for Auger Electron Therapy
Authors: Elghobary Mohamed Elsaid Nasr , Munekane Masayuki , Mishiro Kenji , Fuchigami Takeshi , Ogawa Kazuma
Published: February 2023

Auger electrons (AEs) are very low-energy electrons emitted by radionuclides such as I-125 (125I). This energy is deposited across a small distance (<0.5 μm), resulting in high linear energy transfer that is potent for causing lethal damage to cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for cancer treatment. In this study, thermosensitive liposomes (TSLs) encapsulating 125I-labeled doxorubicin (DOX) derivatives were developed for Auger electron therapy, targeting the DNA of cancer cells. A radioiodinated DOX derivative [125I]5 highly accumulated in the nuclei of cancer cells and showed potent cytotoxicity against Colon 26 cancer cells by AEs. Subsequently, [125I]5 was loaded into the TSLs with high encapsulation efficiency. Potent release of [125I]5 from TSLs was achieved with heating, whereas a decreased release was observed without heating. Furthermore, TSLs encapsulating [125I]5 showed a high uptake in the nuclei at 42 °C for 1 h. We supposed that [125I]5 was released by heating at 42 °C and accumulated in the nuclei in the cells. These results suggest that the combination of TSLs encapsulating [125I]5 and hyperthermia is an effective cancer therapy.
Berberine Ameliorates Metabolic-Associated Fatty Liver Disease Mediated Metabolism Disorder and Redox Homeostasis by Upregulating Clock Genes: Clock and Bmal1 Expressions
Authors: Ye Cunsi , Zhang Yajing , Lin Shaomin , Chen Yi , Wang Zimiao , Feng Haoyinghua , Fang Guangqing , Quan Shijian
Published: February 2023

Metabolic-associated fatty liver disease (MAFLD) is one of the most common chronic liver diseases, which in turn triggers mild inflammation, metabolic dysfunction, fibrosis, and even cancer. Accumulating evidence has suggested that Berberine (BBR) could significantly improve MAFLD progression. Clock and Bmal1 as heterodimer proteins highly participated in the development of MAFLD, but whether BBR targets Clock and Bmal1 in MAFLD remains poorly understood. The result suggested that the protein levels of Clock and Bmal1 were decreased in MAFLD mice, which was negatively correlated with elevated reactive oxygen species (ROS) accumulation, the H2O2 level, liver inflammation, metabolic dysfunction, and insulin resistance. The mRNA and protein levels of Clock and Bmal1 were also decreased in glucosamine-induced HepG2 cells, which were are negatively related to glucose uptake, the ROS level, and the H2O2 level. More importantly, Bmal1 siRNA could mimic the effect of glucosamine in HepG2 cells. Interestingly, Berberine (BBR) could rescue metabolism disorder and redox homeostasis through enhancing Clock and Bmal1 expression in vivo and in vitro. Therefore, BBR might be an effective natural compound for alleviating redox homeostasis, metabolism disorder, and liver pathological changes in MAFLD by activating Clock and Bmal1 expression.
Portable Nanocomposite System for Wound Healing in Space
Authors: Zagni Chiara , Scamporrino Andrea Antonino , Riccobene Paolo Maria , Floresta Giuseppe , Patamia Vincenzo , Rescifina Antonio , Carroccio Sabrina Carola
Published: February 2023

It is well known that skin wound healing could be severely impaired in space. In particular, the skin is the tissue at risk of injury, especially during human-crewed space missions. Here, we propose a hybrid system based on the biocompatible poly 2-hydroxyethyl methacrylate (pHEMA) to actively support a nanocontainer filled with the drug. Specifically, during the cryo-polymerization of HEMA, halloysite nanotubes (HNTs) embedded with thymol (Thy) were added as a component. Thy is a natural pharmaceutical ingredient used to confer wound healing properties to the material, whereas HNTs were used to entrap the Thy into the lumen to ensure a sustained release of the drug. The as-obtained material was characterized by chemical–physical methods, and tests were performed to assess its ability for a prolonged drug release. The results showed that the adopted synthetic procedure allows the formation of a super absorbent system with good swelling ability that can contain up to 5.5 mg of Thy in about 90 mg of dried sponge. Releasing tests demonstrated the excellent material’s ability to perform a slow controlled delivery of 62% of charged Thy within a week. As humans venture deeper into space, with more extended missions, limited medical capabilities, and a higher risk of skin wounds, the proposed device would be a versatile miniaturized device for skin repair in space.
Mesoporous Cobalt Oxide (CoOx) Nanowires with Different Aspect Ratios for High Performance Hybrid Supercapacitors
Authors: Ji Haomin , Ma Yifei , Cai Zhuo , Yun Micun , Han Jiemin , Tong Zhaomin , Wang Mei , Suhr Jonghwan , Xiao Liantuan , Jia Suotang , Chen Xuyuan
Published: February 2023

Cobalt oxide (CoOx) nanowires have been broadly explored as advanced pseudocapacitive materials owing to their impressive theoretical gravimetric capacity. However, the traditional method of compositing with conductive nanoparticles to improve their poor conductivity will unpredictably lead to a decrease in actual capacity. The amelioration of the aspect ratio of the CoOx nanowires may affect the pathway of electron conduction and ion diffusion, thereby improving the electrochemical performances. Here, CoOx nanowires with various aspect ratios were synthesized by controlling hydrothermal temperature, and the CoOx electrodes achieve a high gravimetric specific capacity (1424.8 C g−1) and rate performance (38% retention at 100 A g−1 compared to 1 A g−1). Hybrid supercapacitors (HSCs) based on activated carbon anode reach an exceptional specific energy of 61.8 Wh kg−1 and excellent cyclic performance (92.72% retention, 5000 cycles at 5 A g−1). The CoOx nanowires exhibit great promise as a favorable cathode material in the field of high-performance supercapacitors (SCs).
Effect of Supplementation with Black Chokeberry (Aronia melanocarpa) Extract on Inflammatory Status and Selected Markers of Iron Metabolism in Young Football Players: A Randomized Double-Blind Trial
Authors: Stankiewicz Błażej , Cieślicka Mirosława , Mieszkowski Jan , Kochanowicz Andrzej , Niespodziński Bartłomiej , Szwarc Andrzej , Waldziński Tomasz , Reczkowicz Joanna , Piskorska Elżbieta , Petr Miroslav , Skarpańska-Stejnborn Anna , Antosiewicz Jędrzej
Published: February 2023

The use of herbal medicinal products and supplements in amateur and professional sports has increased in the last decades. This is because most of these products and supplements contain bioactive compounds with a variety of biological properties that exert a physiological effect on the human body. The aim of this study was to analyze the effect of dietary supplementation with lyophilized black chokeberry extract on the levels of pro-inflammatory cytokines, hepcidin, and selected markers of iron metabolism in a group of young football players. This double-blind study included 22 male football players (mean = 19.96 ± 0.56), divided into two groups: supplemented and placebo. Before and after a 90-day period of training combined with supplementation (6 g of lyophilized black chokeberry extract), participants performed maximal multistage 20-m shuttle run tests at the beginning and at the end of the supplementation period, with blood sampled for analysis at different times before and after exercise. The levels of IL-6, IL-10, ferritin, myoglobin, hepcidin, 8-OHdG, albumin, and TAC were analyzed. The analysis of variance revealed a significant effect of 90-day supplementation with the lyophilized extract on changes in the IL-6 and IL-10 levels, and TAC induced by maximal aerobic effort. In conclusion, supplementation with lyophilized black chokeberry extract improves the performance and antioxidant status of serum in humans and induces protective changes in inflammatory markers.
Allergic March in Children: The Significance of Precision Allergy Molecular Diagnosis (PAMD@) in Predicting Atopy Development and Planning Allergen-Specific Immunotherapy
Authors: Knyziak-Mędrzycka Izabela , Majsiak Emilia , Cukrowska Bożena
Published: February 2023

The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3–5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recent years saw the emergence of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient’s allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. This review presents possible predictions regarding the allergic march and the means of controlling it based on PAMD@ results.
Dietary Supplementation of Cedryl Acetate Ameliorates Adiposity and Improves Glucose Homeostasis in High-Fat Diet-Fed Mice
Authors: Guo Jingya , Li Mengjie , Zhao Yuhan , Kang Seong-Gook , Huang Kunlun , Tong Tao
Published: February 2023

Cedryl acetate (CA), also called acetyl cedrene, is approved by the FDA as a flavoring or adjuvant to be added to foods. In this study, we aimed to investigate the preventive benefits of CA on obesity and obesity-related metabolic syndrome caused by a high-fat diet (HFD). Three groups of C57BL/6J mice (ten-week-old) were fed Chow, an HFD, or an HFD with CA supplementation (100 mg/kg) for 19 weeks. We observed that CA supplementation significantly reduced weight gain induced by an HFD, decreased the weight of the visceral fat pads, and prevented adipocyte hypertrophy in mice. Moreover, mice in the CA group showed significant improvements in hepatic lipid accumulation, glucose intolerance, insulin resistance, and gluconeogenesis compared with the mice in the HFD group. Since 16S rRNA analysis revealed that the gut microbiota in the CA and HFD groups were of similar compositions at the phylum and family levels, CA may have limited effects on gut microbiota in HFD-fed mice. The beneficial effects on the metabolic parameters of CA were reflected by CA’s regulation of metabolism-related gene expression in the liver (including Pepck, G6Pase, and Fbp1) and the epididymal white adipose tissues (including PPARγ, C/EBPα, FABP4, FAS, Cytc, PGC-1α, PRDM16, Cidea, and COX4) of the mice. In summary, a potent preventive effect of CA on HFD-induced obesity and related metabolic syndrome was highlighted by our results, and CA could be a promising dietary component for obesity intervention.
The Consumption of Animal and Plant Foods in Areas of High Prevalence of Stroke and Colorectal Cancer
Authors: Mayfield Kellie E. , Plasencia Julie , Ellithorpe Morgan , Anderson Raeda K. , Wright Nicole C.
Published: February 2023

Diets of red and processed meat have been reported as important risk factors for developing colorectal cancer. Given the racial and ethnic differences in the incidence of colorectal cancer, patterns of food consumption, and areas of residence, particularly in the South, more data is needed on the relationship between residing in a high stroke area, colorectal cancer incidence levels, and red meat and processed meat consumption. We created online surveys to ascertain meat, red meat, and healthy food consumption levels. We used OLS regression to evaluate the association between residence in Stroke Belt states and colorectal cancer incidence quartiles with food consumption. We further used path analysis using structural equation modeling to evaluate if age, sex, race/ethnicity, income, and comorbidity index mediated the association between residence in the eight-state Stroke Belt, colorectal cancer incidence groups, and meat consumption. Our sample included 923 participants, with 167 (18.1%) residing in the Stroke Belt and 13.9% being in the highest colorectal cancer incidence group. The findings show that residing in a Stroke Belt state is predictive of the consumption of overall meat 0.93 more days per week or red meat 0.55 more days per week compared to those not residing in a Stroke Belt state. These data can be used to develop future diet interventions in these high-risk areas to reduce rates of colorectal cancer and other negative health outcomes.
Recombinant Escherichia coli BL21 with LngA Variants from ETEC E9034A Promotes Adherence to HT-29 Cells
Authors: Espinosa-Mazariego Karina , Saldaña-Ahuactzi Zeus , Ochoa Sara , González-Pedrajo Bertha , Cevallos Miguel , Rodríguez-Martínez Ricardo , Romo-Castillo Mariana , Hernández-Castro Rigoberto , Cruz-Córdova Ariadnna , Xicohtencatl-Cortes Juan
Published: February 2023

The CS21 pilus produced by enterotoxigenic Escherichia coli (ETEC) is involved in adherence to HT-29 intestinal cells. The CS21 pilus assembles proteins encoded by 14 genes clustered into the lng operon. Aim. This study aimed to determine whether E. coli BL21 (ECBL) transformed with the lng operon lacking the lngA gene (pE9034AΔlngA) and complemented in trans with lngA variants of ETEC clinical strains, as well as point substitutions, exhibited modified adherence to HT-29 cells. Methods. A kanamycin cassette was used to replace the lngA gene in the lng operon of the E9034A strain, and the construct was transformed into the ECBL strain. The pJET1.2 vector carrying lngA genes with allelic variants was transformed into ECBLpE9034AΔlngA (ECBLΔlngA). The point substitutions were performed in the pJETlngAFMU073332 vector. Results. Bioinformatic alignment analysis of the LngA proteins showed hypervariable regions and clustered the clinical ETEC strains into three groups. Variations in amino acid residues affect the adherence percentages of recombinant ECBL strains with lngA variants and site-specific mutations with HT-29 cells. Conclusion. In this study, ECBL carrying the lng operon harboring lngA variants of six clinical ETEC strains, as well as point substitutions, exerted an effect on the adherence of ECBL to HT-29 cells, thereby confirming the importance of the CS21 pilus in adherence.
Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy
Authors: Ruaro Barbara , Gandin Ilaria , Pozzan Riccardo , Tavano Stefano , Bozzi Chiara , Hughes Michael , Kodric Metka , Cifaldi Rossella , Lerda Selene , Confalonieri Marco , Baratella Elisa , Confalonieri Paola , Salton Francesco
Published: February 2023

Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ~3 years. Nintedanib (NTD) has been shown to be useful in controlling interstitial lung disease (ILD) in IPF. Here we describe the experience of NTD use in IPF in a real-life setting. Objective. Our objective was to examine the safety profile and efficacy of nintedanib even in subjects treated with anticoagulants. Clinical data of patients with IPF treated with NTD at our center were retrospectively evaluated at baseline and at 6 and 12 months after the introduction of NTD. The following parameters were recorded: IPF clinical features, NTD tolerability, and pulmonary function tests (PFT) (i.e., Forced Vital Capacity (FVC) and carbon monoxide diffusing capacity (DLCO)). In total, 56 IPF patients (34% female and 66% male, mean onset age: 71 ± 11 years, mean age at baseline: 74 ± 9 years) treated with NTD were identified. At enrollment, HRCT showed an UIP pattern in 45 (80%) and a NSIP in 11 (20%) patients. For FVC and FEV1 we found no significant change between baseline and 6 months, but for DLCO we observed a decrease (p = 0.012). We identified a significant variation between baseline and 12 months for FEV1 (p = 0.039) and for DLCO (p = 0.018). No significant variation was observed for FVC. In the cohort, 18 (32%) individuals suspended NTD and 10 (18%) reduced the dosage. Among individuals that suspended the dosage, 14 (78%) had gastrointestinal (GI) collateral effects (i.e., diarrhea being the most common complaint (67%), followed by nausea/vomiting (17%) and weight loss (6%). Bleeding episodes have also not been reported in patients taking anticoagulant therapy. (61%). One patient died within the first 6 months and two subjects died within the first 12 months. In a real-life clinical scenario, NTD may stabilize the FVC values in IPF patients. However, GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in IPF patients. This study confirms the safety of NTD, even in patients treated with anticoagulant drugs.
Characterization of Potential Intoxications with Medicines in a Regional Setting
Authors: Nascimento Tânia , Santos Teresa , Rato Fátima , De Sousa-Coelho Ana Luísa
Published: February 2023

The Portuguese Poison Information Center (from Portuguese—CIAV) is a call center that offers medical assistance in case of possible intoxication with any kind of product, including medicines. This center´s main goal is to inform and guide the general public and health professionals. This work aimed to analyze and compare data corresponding to the telephone calls from the Algarve region (South of Portugal), received by CIAV during 2019 and 2020, regarding potential intoxications with medicines. To this end, data provided by CIAV on possible cases of medication intoxication in the Algarve region were collected, including the number of calls received, the place of origin of the call, the age group and sex of the intoxicated individual, the route of exposure to the drug, the circumstances of contact with the substance, the existence of symptoms, and the drug or drugs involved in the potential intoxication. The results showed that the number of cases slightly decreased in 2020 (n = 1261) compared with 2019 (n = 1340), with a high number of cases of intoxication in children between one and four years old in both years (21.2%; n = 152 in 2019; 16.4%; n = 115 in 2020). The drugs belonging to the locomotor system group (paracetamol and ibuprofen) were the main drugs involved, followed by the central nervous system pharmacotherapeutic group, namely benzodiazepines (diazepam and alprazolam). Paracetamol was the main drug responsible for the calls to CIAV (n = 71 in 2019; n = 63 in 2020), while for the remaining drugs there were fluctuations in their positions between both years. In some cases, this swinging may be explained by the possible changes in therapy due to potential interactions with drugs used for the treatment of symptoms of COVID-19 or perhaps related to misleading information released by the media about the use of some drugs, such as ibuprofen, during lockdown periods. Although there has been a decrease in calls to report possible drug intoxication in the Algarve region, the profile of calls was very similar. Paracetamol was the drug with the highest number of reported cases and the group of psychotropic drugs showed the largest increase between 2019 and 2020.
Coupling of NIR Spectroscopy and Chemometrics for the Quantification of Dexamethasone in Pharmaceutical Formulations
Authors: Biancolillo Alessandra , Scappaticci Claudia , Foschi Martina , Rossini Claudia , Marini Federico
Published: February 2023

Counterfeit or substandard drugs are pharmaceutical formulations in which the active pharmaceutical ingredients (APIs) have been replaced or ingredients do not comply with the drug leaflet. With the outbreak of the COVID-19 pandemic, fraud associated with the preparation of substandard or counterfeit drugs is expected to grow, undermining health systems already weakened by the state of emergency. Analytical chemistry plays a key role in tackling this problem, and in implementing strategies that permit the recognition of uncompliant drugs. In light of this, the present work represents a feasibility study for the development of a NIR-based tool for the quantification of dexamethasone in mixtures of excipients (starch and lactose). Two different regression strategies were tested. The first, based on the coupling of NIR spectra and Partial Least Squares (PLS) provided good results (root mean square error in prediction (RMSEP) of 720 mg/kg), but the most accurate was the second, a strategy exploiting sequential preprocessing through orthogonalization (SPORT), which led (on the external set of mixtures) to an R2pred of 0.9044, and an RMSEP of 450 mg/kg. Eventually, Variable Importance in Projection (VIP) was applied to interpret the obtained results and determine which spectral regions contribute most to the SPORT model.
3D-Printing of Capsule Devices as Compartmentalization Tools for Supported Reagents in the Search of Antiproliferative Isatins
Authors: Malatini Camilla , Carbajales Carlos , Luna Mariángel , Beltrán Osvaldo , Amorín Manuel , Masaguer Christian F. , Blanco José M. , Barbosa Silvia , Taboada Pablo , Coelho Alberto
Published: February 2023

The application of high throughput synthesis methodologies in the generation of active pharmaceutical ingredients (APIs) currently requires the use of automated and easily scalable systems, easy dispensing of supported reagents in solution phase organic synthesis (SPOS), and elimination of purification and extraction steps. The recyclability and recoverability of supported reagents and/or catalysts in a rapid and individualized manner is a challenge in the pharmaceutical industry. This objective can be achieved through a suitable compartmentalization of these pulverulent reagents in suitable devices for it. This work deals with the use of customized polypropylene permeable-capsule devices manufactured by 3D printing, using the fused deposition modeling (FDM) technique, adaptable to any type of flask or reactor. The capsules fabricated in this work were easily loaded “in one step” with polymeric reagents for use as scavengers of isocyanides in the work-up process of Ugi multicomponent reactions or as compartmentalized and reusable catalysts in copper-catalyzed cycloadditions (CuAAC) or Heck palladium catalyzed cross-coupling reactions (PCCCRs). The reaction products are different series of diversely substituted isatins, which were tested in cancerous cervical HeLa and murine 3T3 Balb fibroblast cells, obtaining potent antiproliferative activity. This work demonstrates the applicability of 3D printing in chemical processes to obtain anticancer APIs.
Intranasal Lipid Nanoparticles Containing Bioactive Compounds Obtained from Marine Sources to Manage Neurodegenerative Diseases
Authors: Torres Joana , Costa Inês , Peixoto Andreia F. , Silva Renata , Sousa Lobo José Manuel , Silva Ana Catarina
Published: February 2023

Marine sources contain several bioactive compounds with high therapeutic potential, such as remarkable antioxidant activity that can reduce oxidative stress related to the pathogenesis of neurodegenerative diseases. Indeed, there has been a growing interest in these natural sources, especially those resulting from the processing of marine organisms (i.e., marine bio-waste), to obtain natural antioxidants as an alternative to synthetic antioxidants in a sustainable approach to promote circularity by recovering and creating value from these bio-wastes. However, despite their expected potential to prevent, delay, or treat neurodegenerative diseases, antioxidant compounds may have difficulty reaching the brain due to the need to cross the blood–brain barrier (BBB). In this regard, alternative delivery systems administered by different routes have been proposed, including intranasal administration of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which have shown promising results. Intranasal administration shows several advantages, including the fact that molecules do not need to cross the BBB to reach the central nervous system (CNS), as they can be transported directly from the nasal cavity to the brain (i.e., nose-to-brain transport). The benefits of using SLN and NLC for intranasal delivery of natural bioactive compounds for the treatment of neurodegenerative diseases have shown relevant outcomes through in vitro and in vivo studies. Noteworthy, for bioactive compounds obtained from marine bio-waste, few studies have been reported, showing the open potential of this research area. This review updates the state of the art of using SLN and NLC to transport bioactive compounds from different sources, in particular, those obtained from marine bio-waste, and their potential application in the treatment of neurodegenerative diseases.
Current Advances in Lipid Nanosystems Intended for Topical and Transdermal Drug Delivery Applications
Authors: Akombaetwa Nakamwi , Ilangala Ange B. , Thom Lorraine , Memvanga Patrick B. , Witika Bwalya Angel , Buya Aristote B.
Published: February 2023

Skin delivery is an exciting and challenging field. It is a promising approach for effective drug delivery due to its ease of administration, ease of handling, high flexibility, controlled release, prolonged therapeutic effect, adaptability, and many other advantages. The main associated challenge, however, is low skin permeability. The skin is a healthy barrier that serves as the body’s primary defence mechanism against foreign particles. New advances in skin delivery (both topical and transdermal) depend on overcoming the challenges associated with drug molecule permeation and skin irritation. These limitations can be overcome by employing new approaches such as lipid nanosystems. Due to their advantages (such as easy scaling, low cost, and remarkable stability) these systems have attracted interest from the scientific community. However, for a successful formulation, several factors including particle size, surface charge, components, etc. have to be understood and controlled. This review provided a brief overview of the structure of the skin as well as the different pathways of nanoparticle penetration. In addition, the main factors influencing the penetration of nanoparticles have been highlighted. Applications of lipid nanosystems for dermal and transdermal delivery, as well as regulatory aspects, were critically discussed.
Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario
Authors: Candido Marina Ferreira , Medeiros Mariana , Veronez Luciana Chain , Bastos David , Oliveira Karla Laissa , Pezuk Julia Alejandra , Valera Elvis Terci , Brassesco María Sol
Published: February 2023

Childhood cancer is considered rare, corresponding to ~3% of all malignant neoplasms in the human population. The World Health Organization (WHO) reports a universal occurrence of more than 15 cases per 100,000 inhabitants around the globe, and despite improvements in diagnosis, treatment and supportive care, one child dies of cancer every 3 min. Consequently, more efficient, selective and affordable therapeutics are still needed in order to improve outcomes and avoid long-term sequelae. Alterations in kinases’ functionality is a trademark of cancer and the concept of exploiting them as drug targets has burgeoned in academia and in the pharmaceutical industry of the 21st century. Consequently, an increasing plethora of inhibitors has emerged. In the present study, the expression patterns of a selected group of kinases (including tyrosine receptors, members of the PI3K/AKT/mTOR and MAPK pathways, coordinators of cell cycle progression, and chromosome segregation) and their correlation with clinical outcomes in pediatric solid tumors were accessed through the R2: Genomics Analysis and Visualization Platform and by a thorough search of published literature. To further illustrate the importance of kinase dysregulation in the pathophysiology of pediatric cancer, we analyzed the vulnerability of different cancer cell lines against their inhibition through the Cancer Dependency Map portal, and performed a search for kinase-targeted compounds with approval and clinical applicability through the CanSAR knowledgebase. Finally, we provide a detailed literature review of a considerable set of small molecules that mitigate kinase activity under experimental testing and clinical trials for the treatment of pediatric tumors, while discuss critical challenges that must be overcome before translation into clinical options, including the absence of compounds designed specifically for childhood tumors which often show differential mutational burdens, intrinsic and acquired resistance, lack of selectivity and adverse effects on a growing organism.