bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Simulation Study on the Influence of the Abrasive Flow Process on the Cutting of Iron-Carbon Alloys (α-Fe)
Authors: Li Junye , Zhao Zhenguo , Li Junwei , Xiao Fujun , Qiu Rongxian , Xie Hongcai , Meng Wenqing
Published: March 2023

The plastic deformation behavior and microstructural changes in workpieces during ultra-precision machining have piqued the interest of many researchers. In this study, a molecular dynamics simulation of nano-cutting iron-carbon alloy (α-Fe) is established to investigate the effects of the fluid medium and cutting angle on workpiece temperature, friction coefficient, workpiece surface morphology, and dislocation evolution by constructing a molecular model of C12H26 as a fluid medium in the liquid phase using an innovative combined atomic approach. It is demonstrated that the presence of the fluid phase reduces the machining temperature and the friction coefficient. The cutting angle has a significant impact on the formation of the workpiece’s surface profile and the manner in which the workpiece’s atoms are displaced. When the cutting angle is 0°, 5°, or 10°, the workpiece’s surface morphology flows to both sides in a 45° direction, and the height of atomic accumulation on the workpiece surface gradually decreases while the area of displacement changes increases. The depth of cut increases as the cutting angle increases, causing greater material damage, and the presence of a fluid medium reduces this behavior. A dislocation reaction network is formed by the presence of more single and double-branched structures within the workpiece during the cutting process. The presence of a fluid medium during large-angle cutting reduces the number of dislocations and the total dislocation length. The total length of dislocations inside the workpiece is shorter for small angles of cutting, but the effect of the fluid medium is not very pronounced. Therefore, small cutting angles and the presence of fluid media reduce the formation of defective structures within the workpiece and ensure the machining quality.
Robust, Superhydrophobic Aluminum Fins with Excellent Mechanical Durability and Self-Cleaning Ability
Authors: Su Wenbo , Lu Xiangyou , Shu Yunxiang , Liu Xianshuang , Gao Wen , Yao Jianjie , Niu Zhuang , Xie Yuanlai
Published: March 2023

The self-cleaning ability of superhydrophobic metal surfaces has attracted extensive attention. The preparation of superhydrophobic material using the coating method is a common processing method. In this experiment, aluminum fins were processed by laser etching and perfluorinated two-step coating. The aluminum surface was modified using a femtosecond laser and 1H,1H,2H,2H- perfluorooctane triethoxysilane (PFOTES). A superhydrophobic aluminum surface with excellent mechanical stability and self-cleaning properties was obtained with the superhydrophobic contact angle (WCA) of 152.8° and the rolling angle (SA) of 0.6°. The results show that the superhydrophobic surface has an excellent cleaning effect compared with an ordinary surface in unit time. Then, a wear resistance test of the superhydrophobic surface was carried out by using the physical wear method. The results show that physical wear had a low influence on the hydrophobic property of the specimen surface. Finally, the Vickers hardness analysis found that the superhydrophobic surface hardness was significantly better than the ordinary surface hardness compared with the superhydrophobic surface hardness. Based on the excellent self-cleaning properties, wear resistance, and robustness of superhydrophobic materials, the laser-etched and perfluorinated superhydrophobic aluminum fins designed and manufactured in this study have broad application prospects in improving the heat transfer efficiency of finned heat exchangers.
Bioactive C21 Steroidal Glycosides from Euphorbia kansui Promoted HepG2 Cell Apoptosis via the Degradation of ATP1A1 and Inhibited Macrophage Polarization under Co-Cultivation
Authors: Feng Xiaoyi , Li Jianchun , Li Hongmei , Chen Xuanqin , Liu Dan , Li Rongtao
Published: March 2023

Euphorbia kansui is clinically used for the treatment of esophageal cancer, lung cancer, cancerous melanoma, asthma, pleural disorders, ascites, and pertussis, among other conditions. In this study, 12 steroids were obtained and identified from E. kansui, and cynsaccatol L (5), which showed the best effects in terms of inhibiting the proliferation of HepG2 cells and the immune regulation of macrophages. Furthermore, 5 induced typical apoptotic characteristics in HepG2 cells, such as morphological changes and the caspase cascade, as well as inducing autophagy-dependent apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. The antitumor mechanism of 5 might be related to promoting the endocytosis and degradation of ATP1A1 protein and then down-regulating the downstream AKT and ERK signaling pathways. Furthermore, the antiproliferation effect of 5 in co-cultivation with macrophages was investigated, which showed that 5 promoted the apoptosis of HepG2 cells by modulating the release of inflammatory cytokines, such as TNF-α and IFN-γ; regulating the M2-subtype polarization of macrophages; promoting the phagocytosis of macrophages. In conclusion, 5 exerted anti-proliferative effects by promoting the degradation of ATP1A1 and inhibiting the ATP1A1-AKT/ERK signaling pathway in HepG2. Furthermore, it regulated macrophage function in co-cultivation, thereby further exerting adjuvant anti-HepG2 activity.
Exploring Edible Mushrooms for Diabetes: Unveiling Their Role in Prevention and Treatment
Authors: Shamim Mohammad Zaki , Mishra Awdhesh Kumar , Kausar Tahreem , Mahanta Saurov , Sarma Bhaskar , Kumar Vijay , Mishra Piyush Kumar , Panda Jibanjyoti , Baek Kwang-Hyun , Mohanta Yugal Kishore
Published: March 2023

Diabetes mellitus is a complex illness in which the body does not create enough insulin to control blood glucose levels. Worldwide, this disease is life-threatening and requires low-cost, side-effect-free medicine. Due to adverse effects, many synthetic hypoglycemic medications for diabetes fail. Mushrooms are known to contain natural bioactive components that may be anti-diabetic; thus, scientists are now targeting them. Mushroom extracts, which improve immune function and fight cancer, are becoming more popular. Mushroom-derived functional foods and dietary supplements can delay the onset of potentially fatal diseases and help treat pre-existing conditions, which leads to the successful prevention and treatment of type 2 diabetes, which is restricted to the breakdown of complex polysaccharides by pancreatic-amylase and the suppression of intestinal-glucosidase. Many mushroom species are particularly helpful in lowering blood glucose levels and alleviating diabetes symptoms. Hypoglycaemic effects have been observed in investigations on Agaricussu brufescens, Agaricus bisporus, Cordyceps sinensis, Inonotus obliqus, Coprinus comatus, Ganoderma lucidum, Phellinus linteus, Pleurotus spp., Poria cocos, and Sparassis crispa. For diabetics, edible mushrooms are high in protein, vitamins, and minerals and low in fat and cholesterol. The study found that bioactive metabolites isolated from mushrooms, such as polysaccharides, proteins, dietary fibers, and many pharmacologically active compounds, as well as solvent extracts of mushrooms with unknown metabolites, have anti-diabetic potential in vivo and in vitro, though few are in clinical trials.
Eco-Friendly Fluorine Functionalized Superhydrophobic/Superoleophilic Zeolitic Imidazolate Frameworks–Based Composite for Continuous Oil–Water Separation
Authors: Xiang Wenlong , Gong Siyu , Zhu Jiabin
Published: March 2023

Superhydrophobic metal−organic framework (MOF)-based sponges have received increasing attention in terms of treating oil−water mixtures. However, highly fluorinated substances, commonly used as modifiers to improve the hydrophobicity of MOFs, have aroused much environmental concern. Developing a green hydrophobic modification is crucial in order to prepare superhydrophobic MOF-sponge composites. Herein, we report the preparation of a porous composite sponge via a polydopamine (PDA)-assisted growth of zeolitic imidazolate frameworks (ZIF-90) and eco-friendly hydrophobic short-chain fluorinated substances (trifluoroethylamine) on a melamine formaldehyde (MF) sponge. The composite sponge (F-ZIF-90@PDA-MF) exhibited superhydrophobicity (water contact angle, 153°) and superoleophilicity (oil contact angle, 0°), which is likely due to the combination of the low surface energy brought on by the grafted CF3 groups, as well as the rough surface structures that were derived from the in situ growth of ZIF-90 nanoparticles. F-ZIF-90@PDA-MF showed an excellent adsorption capacity of 39.4–130.4 g g−1 for the different organic compounds. The adsorbed organic compounds were easily recovered by physical squeezing. Continuous and selective separation for the different oil−water mixtures was realized by employing the composite sponge as an absorbent or a filter. The separation efficiency and flux reached above 99.5% and went up to 7.1 ×105 L m−2 h−1, respectively. The results illustrate that the superhydrophobic and superoleophilic F-ZIF-90@PDA-MF sponge has potential in the field of water−oil separation, especially for the purposes of large-scale oil recovery in a water environment.
Heat-Treated Lysozyme Hydrochloride: A Study on Its Structural Modifications and Anti-SARS-CoV-2 Activity
Authors: Delbue Serena , Pariani Elena , Parapini Silvia , Galli Cristina , Basilico Nicoletta , D’Alessandro Sarah , Pellegrino Sara , Pini Elena , Ciceri Samuele , Ferraboschi Patrizia , Grisenti Paride
Published: March 2023

Lysozyme (E.C. 3.2.1.17), an about 14 kDa protein and pI 11, widely spread in nature, is present in humans mainly in milk, saliva, and intestinal mucus as a part of innate defense mechanisms. It is endowed with antimicrobial activity due to its action as an N-acetylmuramidase, cleaving the 1-4β glycosidic linkage in the peptidoglycan layer of Gram-positive bacteria. This antimicrobial activity is exerted only against a limited number of Gram-negative bacteria. Different action mechanisms are proposed to explain its activity against Gram-negative bacteria, viruses, and fungi. The antiviral activity prompted the study of a possible application of lysozyme in the treatment of SARS-CoV-2 infections. Among the different sources of lysozyme, the chicken egg albumen was chosen, being the richest source of this protein (c-type lysozyme, 129 amino acids). Interestingly, the activity of lysozyme hydrochloride against SARS-CoV-2 was related to the heating (to about 100 °C) of this molecule. A chemical–physical characterization was required to investigate the possible modifications of native lysozyme hydrochloride by heat treatment. The FTIR analysis of the two preparations of lysozyme hydrochloride showed appreciable differences in the secondary structure of the two protein chains. HPLC and NMR analyses, as well as the enzymatic activity determination, did not show significant modifications.
The Extraction and High Antiproliferative Effect of Anthocyanin from Gardenblue Blueberry
Authors: Zhao Fengyi , Wang Jialuan , Wang Weifan , Lyu Lianfei , Wu Wenlong , Li Weilin
Published: March 2023

Blueberries are rich in flavonoids, anthocyanins, phenolic acids, and other bioactive substances. Anthocyanins are important functional components in blueberries. We collected 65 varieties of blueberries to investigate their nutritional and functional values. Among them, Gardenblue had the highest anthocyanin content, with 2.59 mg/g in fresh fruit. After ultrasound-assisted solvent extraction and macroporous resin absorption, the content was increased to 459.81 mg/g in the dried powder. Biological experiments showed that Gardenblue anthocyanins (L1) had antiproliferative effect on cervical cancer cells (Hela, 51.98 μg/mL), liver cancer cells (HepG2, 23.57 μg/mL), breast cancer cells (MCF-7, 113.39 μg/mL), and lung cancer cells (A549, 76.10 μg/mL), and no apparent toxic effects were indicated by methyl thiazolyl tetrazolium (MTT) assay, especially against HepG2 cells both in vitro and in vivo. After combining it with DDP (cisplatin) and DOX (doxorubicin), the antiproliferative effects were enhanced, especially when combined with DOX against HepG2 cells; the IC50 value was 0.02 μg/mL. This was further evidence that L1 could inhibit cell proliferation by inducing apoptosis. The detailed mechanism might be L1 interacting with DNA in an intercalation mode that changes or destroys DNA, causing apoptosis and inhibiting cell proliferation. The findings of this study suggest that L1 extract can be used as a functional agent against hepatoma carcinoma cells.
Effect of Electrode Spacing on the Performance of a Membrane-Less Microbial Fuel Cell with Magnetite as an Additive
Authors: Madondo Nhlanganiso Ivan , Rathilal Sudesh , Bakare Babatunde Femi , Tetteh Emmanuel Kweinor
Published: March 2023

A microbial fuel cell (MFC) is a bioelectrochemical system that can be employed for the generation of electrical energy under microbial activity during wastewater treatment practices. The optimization of electrode spacing is perhaps key to enhancing the performance of an MFC. In this study, electrode spacing was evaluated to determine its effect on the performance of MFCs. The experimental work was conducted utilizing batch digesters with electrode spacings of 2.0 cm, 4.0 cm, 6.0 cm, and 8.0 cm. The results demonstrate that the performance of the MFC improved when the electrode spacing increased from 2.0 to 6.0 cm. However, the efficiency decreased after 6.0 cm. The digester with an electrode spacing of 6.0 cm enhanced the efficiency of the MFC, which led to smaller internal resistance and greater biogas production of 662.4 mL/g VSfed. The electrochemical efficiency analysis demonstrated higher coulombic efficiency (68.7%) and electrical conductivity (177.9 µS/cm) for the 6.0 cm, which was evident from the enrichment of electrochemically active microorganisms. With regards to toxic contaminant removal, the same digester also performed well, revealing removals of over 83% for chemical oxygen demand (COD), total solids (TS), total suspended solids (TSS), and volatile solids (VS). Therefore, these results indicate that electrode spacing is a factor affecting the performance of an MFC, with an electrode spacing of 6.0 cm revealing the greatest potential to maximize biogas generation and the degradability of wastewater biochemical matter.
Interlaboratory Evaluation of a User-Friendly Benchtop Mass Spectrometer for Multiple-Attribute Monitoring Studies of a Monoclonal Antibody
Authors: Butré Claire I. , D’Atri Valentina , Diemer Hélène , Colas Olivier , Wagner Elsa , Beck Alain , Cianferani Sarah , Guillarme Davy , Delobel Arnaud
Published: March 2023

In the quest to market increasingly safer and more potent biotherapeutic proteins, the concept of the multi-attribute method (MAM) has emerged from biopharmaceutical companies to boost the quality-by-design process development. MAM strategies rely on state-of-the-art analytical workflows based on liquid chromatography coupled to mass spectrometry (LC–MS) to identify and quantify a selected series of critical quality attributes (CQA) in a single assay. Here, we aimed at evaluating the repeatability and robustness of a benchtop LC–MS platform along with bioinformatics data treatment pipelines for peptide mapping-based MAM studies using standardized LC–MS methods, with the objective to benchmark MAM methods across laboratories, taking nivolumab as a case study. Our results evidence strong interlaboratory consistency across LC–MS platforms for all CQAs (i.e., deamidation, oxidation, lysine clipping and glycosylation). In addition, our work uniquely highlights the crucial role of bioinformatics postprocessing in MAM studies, especially for low-abundant species quantification. Altogether, we believe that MAM has fostered the development of routine, robust, easy-to-use LC–MS platforms for high-throughput determination of major CQAs in a regulated environment.
Antifungal Action of Herbal Plants’ Glycolic Extracts against Candida Species
Authors: Meccatti Vanessa Marques , Santos Lana Ferreira , de Carvalho Lara Steffany , Souza Clara Bulhões , Carvalho Cláudio Antonio Talge , Marcucci Maria Cristina , Abu Hasna Amjad , de Oliveira Luciane Dias
Published: March 2023

Candida spp. cause fungal infection that affects patients’ oral health. This study aimed to evaluate the isolated and synergistic antifungal effect of Rosa centifolia L., Curcuma longa L., Rosmarinus officinalis L., and Punica granatum L. glycolic extracts against Candida albicans, Candida dubliniensis, Candida tropicalis, and Candida krusei planktonic and biofilm forms. The plant extracts were chemically characterized and the main compounds were quantified by high-performance liquid chromatography (HPLC-DAD) analysis. The minimum inhibitory and minimum fungicidal concentrations of the extracts were determined, and antibiofilm activity was evaluated by MTT assay. Data were analyzed by one-way ANOVA and Tukey’s tests, and by Kruskal–Wallis and Dunn’s tests, considering a significance level of 5%. The main compounds identified in each of the extracts were: p-coumaric acid (2153.22 μg/100 mL) in the rosemary extract, gallotannins (4318.31 μg/100 mL) in the pomegranate extract, quercetin derivatives (3316.50 μg/100 mL) in the extract of white roses, and curcumin (135.09 μg/100 mL) in the turmeric extract. The combination of R. centifolia and C. longa glycolic extracts was effective against C. albicans, C. dubliniensis, and C. tropicalis biofilms over different periods (p < 0.05). The combination of R. officinalis and P. granatum glycolic extracts was effective against C. albicans and C. krusei biofilms after 30 min, and against C. tropicalis after 24 h, with all combinations showing an average reduction of 50% in cell viability (p < 0.05). In conclusion, the combined plant extracts have antifungal and antibiofilm action against Candida spp. in different concentrations and times of action.
Trap-and-Track for Characterizing Surfactants at Interfaces
Authors: Kim Jeonghyeon , Martin Olivier J. F.
Published: March 2023

Understanding the behavior of surfactants at interfaces is crucial for many applications in materials science and chemistry. Optical tweezers combined with trajectory analysis can become a powerful tool for investigating surfactant characteristics. In this study, we perform trap-and-track analysis to compare the behavior of cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC) at water–glass interfaces. We use optical tweezers to trap a gold nanoparticle and statistically analyze the particle’s movement in response to various surfactant concentrations, evidencing the rearrangement of surfactants adsorbed on glass surfaces. Our results show that counterions have a significant effect on surfactant behavior at the interface. The greater binding affinity of bromide ions to CTA+ micelle surfaces reduces the repulsion among surfactant head groups and enhances the mobility of micelles adsorbed on the interface. Our study provides valuable insights into the behavior of surfactants at interfaces and highlights the potential of optical tweezers for surfactant research. The development of this trap-and-track approach can have important implications for various applications, including drug delivery and nanomaterials.
Thermodynamics Evaluation of Selective Hydride Reduction for α,β-Unsaturated Carbonyl Compounds
Authors: Chen Bao-Long , Jing Sha , Zhu Xiao-Qing
Published: March 2023

The selective reduction of α,β-unsaturated carbonyl compounds is one of the core reactions and also a difficult task for organic synthesis. We have been attempting to study the thermodynamic data of these compounds to create a theoretical basis for organic synthesis and computational chemistry. By electrochemical measurement method and titration calorimetry, in acetonitrile at 298 K, the hydride affinity of two types of unsaturated bonds in α,β-unsaturated carbonyl compounds, their single-electron reduction potential, and the single-electron reduction potential of the corresponding radical intermediate are determined. Their hydrogen atom affinity, along with the hydrogen atom affinity and proton affinity of the corresponding radical anion, is also derived separately based on thermodynamic cycles. The above data are used to establish the corresponding “Molecule ID Card” (Molecule identity card) and analyze the reduction mechanism of unsaturated carbonyl compounds. Primarily, the mixture of any carbonyl hydride ions and Ac-tempo+ will stimulate hydride transfer process and create corresponding α,β-unsaturated carbonyl compounds and Ac-tempoH from a thermodynamic point of view.
Inorganic Nanomaterials Used in Anti-Cancer Therapies:Further Developments
Authors: Długosz Olga , Matyjasik Wiktoria , Hodacka Gabriela , Szostak Krzysztof , Matysik Julia , Krawczyk Patrycja , Piasek Anna , Pulit-Prociak Jolanta , Banach Marcin
Published: March 2023

In this article, we provide an overview of the progress of scientists working to improve the quality of life of cancer patients. Among the known methods, cancer treatment methods focusing on the synergistic action of nanoparticles and nanocomposites have been proposed and described. The application of composite systems will allow precise delivery of therapeutic agents to cancer cells without systemic toxicity. The nanosystems described could be used as a high-efficiency photothermal therapy system by exploiting the properties of the individual nanoparticle components, including their magnetic, photothermal, complex, and bioactive properties. By combining the advantages of the individual components, it is possible to obtain a product that would be effective in cancer treatment. The use of nanomaterials to produce both drug carriers and those active substances with a direct anti-cancer effect has been extensively discussed. In this section, attention is paid to metallic nanoparticles, metal oxides, magnetic nanoparticles, and others. The use of complex compounds in biomedicine is also described. A group of compounds showing significant potential in anti-cancer therapies are natural compounds, which have also been discussed.
Multi-Parametric Birefringence Control in Ultrashort-Pulse Laser-Inscribed Nanolattices in Fluorite
Authors: Kudryashov Sergey , Rupasov Alexey , Smayev Mikhail , Danilov Pavel , Kuzmin Evgeny , Mushkarina Irina , Gorevoy Alexey , Bogatskaya Anna , Zolot’ko Alexander
Published: March 2023

An ultrashort-pulse laser inscription of embedded birefringent microelements was performed inside bulk fluorite in pre-filamentation (geometrical focusing) and filamentation regimes as a function of laser wavelength, pulsewidth and energy. The resulting elements composed of anisotropic nanolattices were characterized by retardance (Ret) and thickness (T) quantities, using polarimetric and 3D-scanning confocal photoluminescence microscopy, respectively. Both parameters exhibit a monotonous increase versus pulse energy, going over a maximum at 1-ps pulsewidth at 515 nm, but decrease versus laser pulsewidth at 1030 nm. The resulting refractive-index difference (RID) Δn = Ret/T ~ 1 × 10−3 remains almost constant versus pulse energy and slightly decreases at a higher pulsewidth, generally being higher at 515 nm. The birefringent microelements were visualized using scanning electron microscopy and chemically characterized using energy-dispersion X-ray spectroscopy, indicating the increase of calcium and the contrary decrease of fluorine inside them due to the non-ablative inscription character. Dynamic far-field optical diffraction of the inscribing ultrashort laser pulses also demonstrated the accumulative inscription character, depending on the pulse energy and the laser exposure. Our findings revealed the underlying optical and material inscription processes and demonstrated the robust longitudinal homogeneity of the inscribed birefringent microstructures and the facile scalability of their thickness-dependent retardance.
Exploring the Potential of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 as Promising Psychobiotics Using SHIME
Authors: De Oliveira Fellipe Lopes , Salgaço Mateus Kawata , de Oliveira Marina Toscano , Mesa Victoria , Sartoratto Adilson , Peregrino Antonio Medeiros , Ramos Williams Santos , Sivieri Katia
Published: March 2023

Psychobiotics are probiotics that have the characteristics of modulating central nervous system (CNS) functions or reconciled actions by the gut–brain axis (GBA) through neural, humoral and metabolic pathways to improve gastrointestinal activity as well as anxiolytic and even antidepressant abilities. The aim of this work was to evaluate the effect of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 on the gut microbiota of mildly anxious adults using SHIME®. The protocol included a one-week control period and two weeks of treatment with L. helveticus R0052 and B. longum R0175. Ammonia (NH4+), short chain fatty acids (SCFAs), gamma-aminobutyric acid (GABA), cytokines and microbiota composition were determined. Probiotic strains decreased significantly throughout the gastric phase. The highest survival rates were exhibited by L. helveticus R0052 (81.58%; 77.22%) after the gastric and intestinal phase when compared to B. longum (68.80%; 64.64%). At the genus level, a taxonomic assignment performed in the ascending colon in the SHIME® model showed that probiotics (7 and 14 days) significantly (p < 0.005) increased the abundance of Lactobacillus and Olsenella and significantly decreased Lachnospira and Escheria-Shigella. The probiotic treatment (7 and 14 days) decreased (p < 0.001) NH4+ production when compared to the control period. For SCFAs, we observed after probiotic treatment (14 days) an increase (p < 0.001) in acetic acid production and total SCFAs when compared to the control period. Probiotic treatment increased (p < 0.001) the secretion of anti-inflammatory (IL-6 and IL-10) and decreased (p < 0.001) pro-inflammatory cytokines (TNF-alpha) when compared to the control period. The gut–brain axis plays an important role in the gut microbiota, producing SCFAs and GABA, stimulating the production of anti-anxiety homeostasis. The signature of the microbiota in anxiety disorders provides a promising direction for the prevention of mental illness and opens a new perspective for using the psychobiotic as a main actor of therapeutic targets.
Polymorphisms in VDR, CYP27B1, CYP2R1, GC and CYP24A1 Genes as Biomarkers of Survival in Non-Small Cell Lung Cancer: A Systematic Review
Authors: Pineda-Lancheros Laura Elena , Gálvez-Navas José María , Rojo-Tolosa Susana , Membrive-Jiménez Cristina , Valverde-Merino María Isabel , Martínez-Martínez Fernando , Sánchez-Martín Almudena , Ramírez-Tortosa MCarmen , Pérez-Ramírez Cristina , Jiménez-Morales Alberto
Published: March 2023

The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in the genes involved in the metabolic pathway of vitamin D and overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). This systematic review was conducted in accordance with the PRISMA guidelines. It included all the literature published up to 1 November 2022 and was carried out in four databases (Medline [PubMed], Scopus, Web of Science, and Embase), using the PICO strategy, with relevant keywords related to the objective. The quality of the studies included was evaluated with an assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Six studies were included in this systematic review. Our findings showed that the BsmI (rs1544410), Cdx-2 (rs11568820), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236), rs4646536, rs6068816, rs7041, and rs10741657 SNPs in the genes that play a part in vitamin D synthesis (CYP2R1, CYP27B1), transport (GC), and metabolism (CYP24A1), as well as in the vitamin D receptor (VDR), are associated with OS and/or PFS in patients with NSCLC. The SNPs in VDR have been the most extensively analyzed. This systematic review summed up the available evidence concerning the association between 13 SNPs in the main genes involved in the vitamin D metabolic pathway and prognosis in NSCLC. It revealed that SNPs in the VDR, CYP27B1, CYP24A1, GC, and CYP2R1 genes could have an impact on survival in this disease. These findings suggest the identification of prognostic biomarkers in NSCLC patients. However, evidence remains sparse for each of the polymorphisms examined, so these findings should be treated with caution.
Maternal Vitamin B12 Status during Pregnancy and Early Infant Neurodevelopment: The ECLIPSES Study
Authors: Cruz-Rodríguez Josué , Díaz-López Andrés , Canals-Sans Josefa , Arija Victoria
Published: March 2023

In this prospective cohort study of 434 mother–infant pairs from the ECLIPSES study, we examine the association between maternal vitamin B12 status at the beginning and end of pregnancy and the neurodevelopmental outcomes of infants 40 days after birth in a pregnant population from a Mediterranean region of northern Spain. Maternal vitamin B12 concentrations were determined in the first and third trimesters, and sociodemographic, nutritional, and psychological data were collected. At 40 days postpartum, the Bayley Scales of Infant Development-III (BSID-III, cognitive, language, and motor skills) were administered to the infants and several obstetrical data were recorded. In the multivariable models, medium maternal first-trimester vitamin B12 levels (312 to 408 pg/mL, tertile 2) were associated with better neonatal performance in the motor, gross motor, language, and cognitive skills with respect to tertile 1 (<312 pg/mL). The probability of obtaining a neonatal motor, gross motor, and receptive language score >75th percentile was significantly higher also in the tertile 2 group. In summary, good maternal vitamin B12 status in the early stage of pregnancy appears to be associated with better infant motor, language, and cognitive performance at 40 days postpartum.
Systematic Literature Review of the Nutrient Status, Intake, and Diet Quality of Chinese Children across Different Age Groups
Authors: Ayling Katie , Li Rongrong , Muhardi Leilani , Melse-Boonstra Alida , Sun Ye , Chen Wei , Kudla Urszula
Published: March 2023

There is a lack of comprehensive reports on nutrient deficiencies and dietary intake among various age groups of children in China. The objective of this review is to provide an overview of the nutrient status, intake, and diet adequacy of Chinese children (0–18 years old). PubMed and Scopus were searched for literature published between January 2010 and July 2022. A systematic review approach with a quality assessment was performed to analyze 2986 identified articles in English and Chinese. Eighty-three articles were included in the analysis. In younger children, anemia and iron and Vitamin A deficiencies remain severe public health problems, despite high Vitamin A and adequate iron intake. In older children, a high prevalence of selenium; Vitamin A and D deficiencies; and inadequate intakes of Vitamins A, D, B, C, selenium, and calcium were reported. Intakes of dairy, soybeans, fruits, and vegetables were below recommended levels. High intakes of iodine, total and saturated fat, and sodium and low dietary diversity scores were also reported. As nutritional concerns vary with age and region, future nutrition interventions should be tailored accordingly.
Physical Activity, Sedentary Behaviour and Cardiovascular Risk Factors in Overweight Low-Income Schoolchildren: A Complex System Perspective
Authors: Bezerra Thaynã , Souza Filho Anastácio , Quirino Natália , Bandeira Paulo , Cabral Luciana , Reuter Cézane , Martins Clarice , Carvalho Ferdinando
Published: March 2023

Background: This study analysed through the perspective of networks the association between physical activity (PA), sedentary behaviour (SB), and cardiovascular risk factors in overweight low-income schoolchildren from the perspective of complex systems. Methods: The sample consisted of 41 overweight children between 6 and 10 years old (56% girls). PA and SB were analysed by accelerometer, and the measures of cardiovascular factor risk were: anthropometric and hemodynamic measurements, body fat, lipid profile and glucose, cardiorespiratory fitness (CRF), left ventricular mass (LVM), and Sokolow–Lyon. Network analysis with Bootstrap-1000 was performed to analyse the association between PA, SB and the cardiovascular risk factors. Results: Moderate-to-vigorous PA was positive related to waist circumference (WC; 0.499), HDL-C (0.307), and CRF (0.276), and negatively associated with BMI (−0.251) and Fat (−0.341). For SB, positive associations were seen with WC (0.326), CRF (0.296), LVM (0.250) and Sokolow (0.215). In addition, the centrality indicators highlighted WC as the most important variable in the network. Conclusion: Interventions that aim to mitigate the harmful effects of obesity on cardiovascular risk factors in overweight children should consider WC as an important variable in the system.
HAM/TSP Pathogenesis: The Transmigration Activity of HTLV-1-Infected T Cells into Tissues
Authors: Nakamura Tatsufumi
Published: March 2023

Slowly progressive spastic paraparesis with bladder dysfunction, the main clinical feature of human T-cell leukemia virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is induced by chronic inflammation in the spinal cord, mainly the lower thoracic cord. A long-standing bystander mechanism, such as the destruction of surrounding tissues by inflammatory cytokines, etc., induced under the interaction between infiltrated HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ cytotoxic T cells, has been considered implicated for the induction of chronic inflammation. As this bystander mechanism is triggered conceivably by the transmigration of HTLV-1-infected CD4+ T cells to the spinal cord, heightened transmigrating activity of HTLV-1-infected CD4+ T cells to the spinal cord might play a crucial role as the first responder in the development of HAM/TSP. This review evaluated the functions of HTLV-1-infected CD4+ T cells in HAM/TSP patients as the prerequisite for the acquisition of the activity such as adhesion molecule expression changes, small GTPases activation, and expression of mediators involved in basement membrane disruption. The findings suggest that HTLV-1-infected CD4+ T cells in HAM/TSP patients have enough potential to facilitate transmigration into the tissues. Future HAM/TSP research should clarify the molecular mechanisms leading to the establishment of HTLV-1-infected CD4+ T cells as the first responder in HAM/TSP patients. In addition, a regimen with an inhibitory activity against the transmigration of HTLV-1-infected CD4+ T cells into the spinal cord might be recommended as one of the therapeutic strategies against HAM/TSP patients.
Assembly and Analysis of Haemonchus contortus Transcriptome as a Tool for the Knowledge of Ivermectin Resistance Mechanisms
Authors: Reyes-Guerrero David Emanuel , Jiménez-Jacinto Verónica , Alonso-Morales Rogelio Alejandro , Alonso-Díaz Miguel Ángel , Maza-Lopez Jocelyn , Camas-Pereyra René , Olmedo-Juárez Agustín , Higuera-Piedrahita Rosa Isabel , López-Arellano María Eugenia
Published: March 2023

Haemonchus contortus (Hc) is an important parasitic nematode of small ruminants. In this study we assembled the transcriptome of Hc as a model to contribute to the knowledge about the profile of the differential gene expression between two Mexican Hc strains under different anthelmintic resistance statuses, one susceptible and the other resistant to ivermectin (IVMs and IVMr, respectively), in order to improve and/or to have new strategies of control and diagnosis. The transcript sequence reads were assembled and annotated. Overall, ~127 Mbp were assembled and distributed into 77,422 transcript sequences, and 4394 transcripts of the de novo transcriptome were matched base on at least one of the following criteria: (1) Phylum Nemathelminthes and Platyhelminthes, important for animal health care, and (2) ≥55% of sequence identity with other organisms. The gene ontology (GO) enrichment analysis (GOEA) was performed to study the level of gene regulation to IVMr and IVMs strains using Log Fold Change (LFC) filtering values ≥ 1 and ≥ 2. The upregulated-displayed genes obtained via GOEA were: 1993 (for LFC ≥ 1) and 1241 (for LFC ≥ 2) in IVMr and 1929 (for LFC ≥ 1) and 835 (for LFC ≥ 2) in IVMs. The enriched GO terms upregulated per category identified the intracellular structure, intracellular membrane-bounded organelle and integral component of the cell membrane as some principal cellular components. Meanwhile, efflux transmembrane transporter activity, ABC-type xenobiotic transporter activity and ATPase-coupled transmembrane transporter activity were associated with molecular function. Responses to nematicide activity, pharyngeal pumping and positive regulation of synaptic assembly were classified as biological processes that might be involved in events related to the anthelmintic resistance (AR) and nematode biology. The filtering analysis of both LFC values showed similar genes related to AR. This study deepens our knowledge about the mechanisms behind the processes of H. contortus in order to help in tool production and to facilitate the reduction of AR and promote the development of other control strategies, such as anthelmintic drug targets and vaccines.
Successful Prenatal Treatment of Cardiac Rhabdomyoma in a Fetus with Tuberous Sclerosis
Authors: Will Joachim , Siedentopf Nina , Schmid Oliver , Gruber Teresa , Henrich Wolfgang , Hertzberg Christoph , Weschke Bernhard
Published: March 2023

Cardiac rhabdomyomas are a possible early manifestation of the Tuberous Sclerosis Complex (TSC). They often regress spontaneously but may grow and cause cardiac dysfunction, threatening the child’s life. Treatment with rapalogs can stop the growth of these cardiac tumors and even make them shrink. Here, we present the case of a successful treatment of a cardiac rhabdomyoma in a fetus with TSC by administering sirolimus to the mother. The child’s father carries a TSC2 mutation and the family already had a child with TSC. After we confirmed the TSC diagnosis and growth of the tumor with impending heart failure, we started treatment at 27 weeks of gestation. Subsequently, the rhabdomyoma shrank and the ventricular function improved. The mother tolerated the treatment very well. Delivery was induced at 39 weeks and 1 day of gestation and proceeded without complications. The length, weight, and head circumference of the newborn were normal for the gestational age. Rapalog treatment was continued with everolimus. Metoprolol and vigabatrin were added because of ventricular preexcitation and epileptic discharges in the EEG, respectively. We provide the follow-up data on the child’s development in her first two years of life and discuss the efficacy and safety of this treatment.
Plasma and Cerebrospinal Fluid Concentrations of Micafungin Administered at High Doses in Critically Ill Infants with Systemic Candidiasis: A Pooled Analysis of Two Studies
Authors: De Rose Domenico Umberto , Bersani Iliana , Ronchetti Maria Paola , Piersigilli Fiammetta , Cairoli Sara , Dotta Andrea , Desai Amit , Kovanda Laura Lynn , Goffredo Bianca Maria , Auriti Cinzia
Published: March 2023

Background: Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods: Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine®) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC0–24, plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions: The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood–brain barrier reaching therapeutic levels in CSF.
DLin-MC3-Containing mRNA Lipid Nanoparticles Induce an Antibody Th2-Biased Immune Response Polarization in a Delivery Route-Dependent Manner in Mice
Authors: Yavuz Altan , Coiffier Céline , Garapon Cynthia , Gurcan Serra , Monge Claire , Exposito Jean-Yves , Arruda Danielle Campiol , Verrier Bernard
Published: March 2023

mRNA-based vaccines have made a leap forward since the SARS-CoV-2 pandemic and are currently used to develop anti-infectious therapies. If the selection of a delivery system and an optimized mRNA sequence are two key factors to reach in vivo efficacy, the optimal administration route for those vaccines remains unclear. We investigated the influence of lipid components and immunization route regarding the intensity and quality of humoral immune responses in mice. The immunogenicity of HIV-p55Gag encoded mRNA encapsulated into D-Lin-MC3-DMA or GenVoy-ionizable lipid-based LNPs was compared after intramuscular or subcutaneous routes. Three sequential mRNA vaccines were administrated followed by a heterologous boost composed of p24-HIV protein antigen. Despite equivalent IgG kinetic profiles of general humoral responses, IgG1/IgG2a ratio analysis showed a Th2/Th1 balance toward a Th1-biased cellular immune response when both LNPs were administrated via the intramuscular route. Surprisingly, a Th2-biased antibody immunity was observed when DLin-containing vaccine was injected subcutaneously. A protein-based vaccine boost appeared to reverse this balance to a cellular-biased response correlated to an increase in antibody avidity. Our finding suggests that the intrinsic adjuvant effect of ionizable lipids appears to be dependent on the delivery route used, which could be relevant to reach potent and long-lasting immunity after mRNA-based immunization.
Use of a Cellulase from Trichoderma reesei as an Adjuvant for Enterococcus faecalis Biofilm Disruption in Combination with Antibiotics as an Alternative Treatment in Secondary Endodontic Infection
Authors: Velázquez-Moreno Selene , González-Amaro Ana Maria , Aragón-Piña Antonio , López-López Lluvia Itzel , Sánchez-Sánchez Roberto , Pérez-Díaz Mario Alberto , Oliva Rodríguez Ricardo , Lorenzo-Leal Ana C. , González-Ortega Omar , Martinez-Gutierrez Fidel , Bach Horacio
Published: March 2023

Apical periodontitis is an inflammation leading to the injury and destruction of periradicular tissues. It is a sequence of events that starts from root canal infection, endodontic treatment, caries, or other dental interventions. Enterococcus faecalis is a ubiquitous oral pathogen that is challenging to eradicate because of biofilm formation during tooth infection. This study evaluated a hydrolase (CEL) from the fungus Trichoderma reesei combined with amoxicillin/clavulanic acid as a treatment against a clinical E. faecalis strain. Electron microscopy was used to visualize the structure modification of the extracellular polymeric substances. Biofilms were developed on human dental apices using standardized bioreactors to evaluate the antibiofilm activity of the treatment. Calcein and ethidium homodimer assays were used to evaluate the cytotoxic activity in human fibroblasts. In contrast, the human-derived monocytic cell line (THP-1) was used to evaluate the immunological response of CEL. In addition, the secretion of the pro-inflammatory cytokines IL-6 and TNF-α and the anti-inflammatory cytokine IL-10 were measured by ELISA. The results demonstrated that CEL did not induce the secretion of IL-6 and TNF-α when compared with lipopolysaccharide used as a positive control. Furthermore, the treatment combining CEL with amoxicillin/clavulanic acid showed excellent antibiofilm activity, with a 91.4% reduction in CFU on apical biofilms and a 97.6% reduction in the microcolonies. The results of this study could be used to develop a treatment to help eradicate persistent E. faecalis in apical periodontitis.
In Silico Pharmacology for Evidence-Based and Precision Medicine
Authors: Spanakis Marios
Published: March 2023

Personalized/precision medicine (PM) originates from the application of molecular pharmacology in clinical practice, representing a new era in healthcare that aims to identify and predict optimum treatment outcomes for a patient or a cohort with similar genotype/phenotype characteristics [...]
The Delivery and Activation of Growth Factors Using Nanomaterials for Bone Repair
Authors: Li Yiwei , Xu Chun , Lei Chang
Published: March 2023

Bone regeneration is a comprehensive process that involves different stages, and various growth factors (GFs) play crucial roles in the entire process. GFs are currently widely used in clinical settings to promote bone repair; however, the direct application of GFs is often limited by their fast degradation and short local residual time. Additionally, GFs are expensive, and their use may carry risks of ectopic osteogenesis and potential tumor formation. Nanomaterials have recently shown great promise in delivering GFs for bone regeneration, as they can protect fragile GFs and control their release. Moreover, functional nanomaterials can directly activate endogenous GFs, modulating the regeneration process. This review provides a summary of the latest advances in using nanomaterials to deliver exogenous GFs and activate endogenous GFs to promote bone regeneration. We also discuss the potential for synergistic applications of nanomaterials and GFs in bone regeneration, along with the challenges and future directions that need to be addressed.