bluuebunny/crossref_metadata_2025 huggingface dataset:
What Else Can Be Done by the Spinal Cord? A Review on the Effectiveness of Transpinal Direct Current Stimulation (tsDCS) in Stroke Recovery
Authors: Marangolo Paola , Vasta Simona , Manfredini Alessio , Caltagirone Carlo
Published: June 2023

Since the spinal cord has traditionally been considered a bundle of long fibers connecting the brain to all parts of the body, the study of its role has long been limited to peripheral sensory and motor control. However, in recent years, new studies have challenged this view pointing to the spinal cord’s involvement not only in the acquisition and maintenance of new motor skills but also in the modulation of motor and cognitive functions dependent on cortical motor regions. Indeed, several reports to date, which have combined neurophysiological techniques with transpinal direct current stimulation (tsDCS), have shown that tsDCS is effective in promoting local and cortical neuroplasticity changes in animals and humans through the activation of ascending corticospinal pathways that modulate the sensorimotor cortical networks. The aim of this paper is first to report the most prominent tsDCS studies on neuroplasticity and its influence at the cortical level. Then, a comprehensive review of tsDCS literature on motor improvement in animals and healthy subjects and on motor and cognitive recovery in post-stroke populations is presented. We believe that these findings might have an important impact in the future making tsDCS a potential suitable adjunctive approach for post-stroke recovery.
The Role of Erythrocyte Membrane Protein Band 4.1-like 3 in Idiopathic Pulmonary Fibrosis
Authors: Kim Min Kyung , Lee Jong-Uk , Lee Sun Ju , Chang Hun Soo , Park Jong-Sook , Park Choon-Sik
Published: June 2023

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that erythrocyte membrane protein band 4.1-like 3 (EPB41L3) increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing the EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of epithelial–mesenchymal transition (EMT) in an epithelial cell line (A549) and fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5) by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured using RT-PCR, real-time PCR, and Western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated the mRNA and protein expression of FN1, COL1A1, and VIM. In conclusion, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest the therapeutic potential of EPB41L3 as an anti-fibrotic mediator.
Uncharacterized Proteins CxORFx: Subinteractome Analysis and Prognostic Significance in Cancers
Authors: Ershov Pavel , Yablokov Evgeniy , Mezentsev Yuri , Ivanov Alexis
Published: June 2023

Functions of about 10% of all the proteins and their associations with diseases are poorly annotated or not annotated at all. Among these proteins, there is a group of uncharacterized chromosome-specific open-reading frame genes (CxORFx) from the ‘Tdark’ category. The aim of the work was to reveal associations of CxORFx gene expression and ORF proteins’ subinteractomes with cancer-driven cellular processes and molecular pathways. We performed systems biology and bioinformatic analysis of 219 differentially expressed CxORFx genes in cancers, an estimation of prognostic significance of novel transcriptomic signatures and analysis of subinteractome composition using several web servers (GEPIA2, KMplotter, ROC-plotter, TIMER, cBioPortal, DepMap, EnrichR, PepPSy, cProSite, WebGestalt, CancerGeneNet, PathwAX II and FunCoup). The subinteractome of each ORF protein was revealed using ten different data sources on physical protein–protein interactions (PPIs) to obtain representative datasets for the exploration of possible cellular functions of ORF proteins through a spectrum of neighboring annotated protein partners. A total of 42 out of 219 presumably cancer-associated ORF proteins and 30 cancer-dependent binary PPIs were found. Additionally, a bibliometric analysis of 204 publications allowed us to retrieve biomedical terms related to ORF genes. In spite of recent progress in functional studies of ORF genes, the current investigations aim at finding out the prognostic value of CxORFx expression patterns in cancers. The results obtained expand the understanding of the possible functions of the poorly annotated CxORFx in the cancer context.
A Comprehensive Look at the -13910 C>T LCT Gene Polymorphism as a Molecular Marker for Vitamin D and Calcium Levels in Young Adults in Central and Eastern Europe: A Preliminary Study
Authors: Kowalówka Magdalena , Kosewski Grzegorz , Lipiński Daniel , Przysławski Juliusz
Published: June 2023

Intolerance to dairy products resulting from the abnormal digestion of milk sugar (lactose) is a common cause of human gastrointestinal disorders. The aim of this study was to show that the -13910 C>T LCT gene polymorphism, together with genotypes of selected VDR gene polymorphisms and diet and nutritional status parameters, can impact the prevalence of vitamin D and calcium deficiency in young adults. This study was conducted on a group of 63 people, which comprised 21 individuals with primary adult lactase deficiency, and a control group of 42 individuals with no hypolactasia. The LCT and VDR gene genotypes were assessed using PCR restriction fragment length polymorphism (PCR-RFLP) analysis. A validated HPLC method was used to determine serum concentrations of 25(OH)D2 and 25(OH)D3. Atomic absorption spectrometry was used to determine calcium levels. Their diets (self-reported 7-day estimated food record), estimated calcium intakes based on the ADOS-Ca questionnaire and basic anthropometric parameters were assessed. The CC genotype associated with hypolactasia was found in 33.3% of the subjects. The presence of the CC variant of the LCT gene polymorphism in the study group of young Polish adults was found to be associated with significantly lower milk (134.7 ± 66.7 g/d vs. 342.5 ± 176 g/d; p = 0.012) and dairy product consumption (78.50 ± 36.2 g/d vs. 216.3 ± 102 g/d; p = 0.008) compared with lactase persistence. At the same time, people with adult-type primary intolerance were found to have statistically significant lower serum levels of vitamin D and calcium (p < 0.05). There was a higher chance of vitamin D and calcium deficiency and a lower intake in the group exhibiting lactase non-persistence (OR > 1). The AA variant of the VDR gene’s BsmI polymorphism present in people with hypolactasia may further contribute to an increased risk of vitamin D deficiency. Exclusion of lactose from the diet, combined with impaired vitamin D metabolism, may also lead to inhibited calcium absorption by the body. Further research should be carried out on a larger group of subjects to clarify the relationship between lactase activity and vitamin D and calcium levels in young adults.
Milk Exosomes: Next-Generation Agents for Delivery of Anticancer Drugs and Therapeutic Nucleic Acids
Authors: Timofeeva Anna M. , Paramonik Anastasia P. , Sedykh Sergey S. , Nevinsky Georgy A.
Published: June 2023

Exosomes are nanovesicles 40–120 nm in diameter secreted by almost all cell types and providing humoral intercellular interactions. Given the natural origin and high biocompatibility, the potential for loading various anticancer molecules and therapeutic nucleic acids inside, and the surface modification possibility for targeted delivery, exosomes are considered to be a promising means of delivery to cell cultures and experimental animal organisms. Milk is a unique natural source of exosomes available in semi-preparative and preparative quantities. Milk exosomes are highly resistant to the harsh conditions of the gastrointestinal tract. In vitro studies have demonstrated that milk exosomes have an affinity to epithelial cells, are digested by cells by endocytosis mechanism, and can be used for oral delivery. With milk exosome membranes containing hydrophilic and hydrophobic components, exosomes can be loaded with hydrophilic and lipophilic drugs. This review covers a number of scalable protocols for isolating and purifying exosomes from human, cow, and horse milk. Additionally, it considers passive and active methods for drug loading into exosomes, as well as methods for modifying and functionalizing the surface of milk exosomes with specific molecules for more efficient and specific delivery to target cells. In addition, the review considers various approaches to visualize exosomes and determine cellular localization and bio-distribution of loaded drug molecules in tissues. In conclusion, we outline new challenges for studying milk exosomes, a new generation of targeted delivery agents.
The Lack of Synergy between Carvedilol and the Preventive Effect of Dexrazoxane in the Model of Chronic Anthracycline-Induced Cardiomyopathy
Authors: Szponar Jaroslaw , Ciechanski Erwin , Ostrowska-Lesko Marta , Gorska Agnieszka , Tchorz Michal , Dabrowska Anna , Dudka Jaroslaw , Murias Marek , Kowalczyk Michał , Korga-Plewko Agnieszka , Mandziuk Slawomir
Published: June 2023

The anticancer efficacy of doxorubicin (DOX) is dose-limited because of cardiomyopathy, the most significant adverse effect. Initially, cardiotoxicity develops clinically silently, but it eventually appears as dilated cardiomyopathy with a very poor prognosis. Dexrazoxane (DEX) is the only FDA-approved drug to prevent the development of anthracycline cardiomyopathy, but its efficacy is insufficient. Carvedilol (CVD) is another product being tested in clinical trials for the same indication. This study’s objective was to evaluate anthracycline cardiotoxicity in rats treated with CVD in combination with DEX. The studies were conducted using male Wistar rats receiving DOX (1.6 mg/kg b.w. i.p., cumulative dose: 16 mg/kg b.w.), DOX and DEX (25 mg/kg b.w. i.p.), DOX and CVD (1 mg/kg b.w. i.p.), or a combination (DOX + DEX + CVD) for 10 weeks. Afterward, in the 11th and 21st weeks of the study, echocardiography (ECHO) was performed, and the tissues were collected. The addition of CVD to DEX as a cardioprotective factor against DOX had no favorable advantages in terms of functional (ECHO), morphological (microscopic evaluation), and biochemical alterations (cardiac troponin I and brain natriuretic peptide levels), as well as systemic toxicity (mortality and presence of ascites). Moreover, alterations caused by DOX were abolished at the tissue level by DEX; however, when CVD was added, the persistence of DOX-induced unfavorable alterations was observed. The addition of CVD normalized the aberrant expression of the vast majority of indicated genes in the DOX + DEX group. Overall, the results indicate that there is no justification to use a simultaneous treatment of DEX and CVD in DOX-induced cardiotoxicity.
IGF-1 Stimulates Glycolytic ATP Production in MCF-7L Cells
Authors: Rajoria Bhumika , Zhang Xihong , Yee Douglas
Published: June 2023

The Insulin-like Growth Factor (IGF) system in breast cancer progression has been a matter of interest for decades, but targeting this system did not result in a successful clinical strategy. The system’s complexity and homology of its two receptors—insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF-1R)—are possible causes. The IGF system maintains cell proliferation and also regulates metabolism, making it a pathway to explore. To understand the metabolic phenotype of breast cancer cells, we quantified their real-time ATP production rate upon acute stimulation with ligands—insulin-like growth factor 1 (1GF-1) and insulin. MCF-7L cells express both IGF-1R and IR, while tamoxifen-resistant MCF-7L (MCF-7L TamR) cells have downregulated IGF-1R with unchanged IR levels. Treating MCF-7L cells with 5 nM IGF-1 increased the glycolytic ATP production rate, while 10 nM insulin did not affect metabolism when compared with the control. Neither treatment altered ATP production in MCF-7L TamR cells. This study provides evidence of the relationship between metabolic dysfunction, cancer, and the IGF axis. In these cells, IGF-1R, and not IR, regulates ATP production.
Characterizing the Protein Isoforms of foraging (for), the PKGI Ortholog in Drosophila melanogaster
Authors: Vasquez Oscar E. , Allen Aaron M. , So Anthony K.-C. , Nguyen Quynh H. , Krause Henry M. , Levine Joel D. , Sokolowski Marla B.
Published: June 2023

The foraging (for) gene of Drosophila melanogaster encodes a cGMP-dependent protein kinase (PKG), which is a major effector of the cGMP signaling pathway involved in the regulation of behaviour and metabolic traits. Despite being well studied at the transcript level, little is known about the for gene at the protein level. Here, we provide a detailed characterization of the for gene protein (FOR) products and present new tools for their study, including five isoform-specific antibodies and a transgenic strain that carries an HA-labelled for allele (forBAC::HA). Our results showed that multiple FOR isoforms were expressed in the larval and adult stages of D. melanogaster and that the majority of whole-body FOR expression arises from three (P1, P1α, and P3) of eight putative protein isoforms. We found that FOR expression differed between the larval and adult stages and between the dissected larval organs we analyzed, which included the central nervous system (CNS), fat body, carcass, and intestine. Moreover, we showed that the FOR expression differed between two allelic variants of the for gene, namely, fors (sitter) and forR (rover), that are known to differ in many food-related traits. Together, our in vivo identification of FOR isoforms and the existence of temporal, spatial, and genetic differences in their expression lay the groundwork for determining their functional significance.
Exploring the Inhibitory Effect of AgBiS2 Nanoparticles on Influenza Viruses
Authors: Yang Junlei , Yue Lihuan , Shen Bei , Yang Zhu , Shao Jiang , Miao Yuqing , Ouyang Ruizhuo , Hu Yihong
Published: June 2023

Influenza viruses are respiratory pathogens that are major threats to human health. Due to the emergence of drug-resistant strains, the use of traditional anti-influenza drugs has been hindered. Therefore, the development of new antiviral drugs is critical. In this article, AgBiS2 nanoparticles were synthesized at room temperature, using the bimetallic properties of the material itself to explore its inhibitory effect on the influenza virus. By comparing the synthesized Bi2S3 and Ag2S nanoparticles, it is found that after adding the silver element, the synthesized AgBiS2 nanoparticles have a significantly better inhibitory effect on influenza virus infection than Bi2S3 and Ag2S nanoparticles. Recent studies have shown that the inhibitory effect of AgBiS2 nanoparticles on the influenza virus mainly occurs in the stages of influenza virus-cell internalization and intracellular replication. In addition, it is found that AgBiS2 nanoparticles also have prominent antiviral properties against α and β coronaviruses, indicating that AgBiS2 nanoparticles have significant potential in inhibiting viral activity.
Wheat Susceptibility Genes TaCAMTA2 and TaCAMTA3 Negatively Regulate Post-Penetration Resistance against Blumeria graminis forma specialis tritici
Authors: Li Mengmeng , Yang Zige , Liu Jiao , Chang Cheng
Published: June 2023

Blumeria graminis forma specialis tritici (B.g. tritici) is the airborne fungal pathogen that causes powdery mildew disease on hexaploid bread wheat. Calmodulin-binding transcription activators (CAMTAs) regulate plant responses to environments, but their potential functions in the regulation of wheat–B.g. tritici interaction remain unknown. In this study, the wheat CAMTA transcription factors TaCAMTA2 and TaCAMTA3 were identified as suppressors of wheat post-penetration resistance against powdery mildew. Transient overexpression of TaCAMTA2 and TaCAMTA3 enhanced the post-penetration susceptibility of wheat to B.g. tritici, while knockdown of TaCAMTA2 and TaCAMTA3 expression using transient- or virus-induced gene silencing compromised wheat post-penetration susceptibility to B.g. tritici. In addition, TaSARD1 and TaEDS1 were characterized as positive regulators of wheat post-penetration resistance against powdery mildew. Overexpressing TaSARD1 and TaEDS1 confers wheat post-penetration resistance against B.g. tritici, while silencing TaSARD1 and TaEDS1 enhances wheat post-penetration susceptibility to B.g. tritici. Importantly, we showed that expressions of TaSARD1 and TaEDS1 were potentiated by silencing of TaCAMTA2 and TaCAMTA3. Collectively, these results implicated that the Susceptibility genes TaCAMTA2 and TaCAMTA3 contribute to the wheat–B.g. tritici compatibility might via negative regulation of TaSARD1 and TaEDS1 expression.
Epidermal Loss of RORα Enhances Skin Inflammation in a MC903-Induced Mouse Model of Atopic Dermatitis
Authors: Hua Xiangmei , Blosch Conrad Dean , Dorsey Hannah , Ficaro Maria K. , Wallace Nicole L. , Hsung Richard P. , Dai Jun
Published: June 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease featuring skin barrier dysfunction and immune dysregulation. Previously, we reported that the retinoid-related orphan nuclear receptor RORα was highly expressed in the epidermis of normal skin. We also found that it positively regulated the expression of differentiation markers and skin barrier-related genes in human keratinocytes. In contrast, epidermal RORα expression was downregulated in the skin lesions of several inflammatory skin diseases, including AD. In this study, we generated mouse strains with epidermis-specific Rora ablation to understand the roles of epidermal RORα in regulating AD pathogenesis. Although Rora deficiency did not cause overt macroscopic skin abnormalities at the steady state, it greatly amplified MC903-elicited AD-like symptoms by intensifying skin scaliness, increasing epidermal hyperproliferation and barrier impairment, and elevating dermal immune infiltrates, proinflammatory cytokines, and chemokines. Despite the normal appearance at the steady state, Rora-deficient skin showed microscopic abnormalities, including mild epidermal hyperplasia, increased TEWL, and elevated mRNA expression of Krt16, Sprr2a, and Tslp genes, indicating subclinical impairment of epidermal barrier functions. Our results substantiate the importance of epidermal RORα in partially suppressing AD development by maintaining normal keratinocyte differentiation and skin barrier function.
Dexamethasone Inhibits Heparan Sulfate Biosynthetic System and Decreases Heparan Sulfate Content in Orthotopic Glioblastoma Tumors in Mice
Authors: Sokolov Dmitry K. , Shevelev Oleg B. , Khotskina Anna S. , Tsidulko Alexandra Y. , Strokotova Anastasia V. , Kazanskaya Galina M. , Volkov Alexander M. , Kliver Evgenii E. , Aidagulova Svetlana V. , Zavjalov Evgenii L. , Grigorieva Elvira V.
Published: June 2023

Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These systemic drugs affect the glycosylated components of brain tissue involved in GB development; however, their effects on heparan sulfate (HS) remain unknown. Here, we used an animal model of GB relapse in which SCID mice first received TMZ and/or DXM (simulating postoperative treatment) with a subsequent inoculation of U87 human GB cells. Control, peritumor and U87 xenograft tissues were investigated for HS content, HS biosynthetic system and glucocorticoid receptor (GR, Nr3c1). In normal and peritumor brain tissues, TMZ/DXM administration decreased HS content (5–6-fold) but did not affect HS biosynthetic system or GR expression. However, the xenograft GB tumors grown in the pre-treated animals demonstrated a number of molecular changes, despite the fact that they were not directly exposed to TMZ/DXM. The tumors from DXM pre-treated animals possessed decreased HS content (1.5–2-fold), the inhibition of HS biosynthetic system mainly due to the -3–3.5-fold down-regulation of N-deacetylase/N-sulfotransferases (Ndst1 and Ndst2) and sulfatase 2 (Sulf2) expression and a tendency toward a decreased expression of the GRalpha but not the GRbeta isoform. The GRalpha expression levels in tumors from DXM or TMZ pre-treated mice were positively correlated with the expression of a number of HS biosynthesis-involved genes (Ext1/2, Ndst1/2, Glce, Hs2st1, Hs6st1/2), unlike tumors that have grown in intact SCID mice. The obtained data show that DXM affects HS content in mouse brain tissues, and GB xenografts grown in DXM pre-treated animals demonstrate attenuated HS biosynthesis and decreased HS content.
Association of the rs3864283 Polymorphism Located in the HINT1 Gene with Cigarette Use and Personality Traits
Authors: Suchanecka Aleksandra , Boroń Agnieszka , Chmielowiec Krzysztof , Strońska-Pluta Aleksandra , Masiak Jolanta , Lachowicz Milena , Chmielowiec Jolanta , Grzywacz Anna
Published: June 2023

Nicotine is the major reinforcing component of tobacco and it is believed that the pharmacological effects of nicotine motivate the initiation and maintenance of a smoking habit. HINT1 appears to play a role in the modulation of the effects of drug abuse. Hence, the aim of this study was the analysis of the association between the rs3864283 polymorphism of the HINT1 gene and cigarette use; the analysis of personality traits assessed by the means of the NEO-FFI Inventory; the analysis of anxiety measured by the STAI questionnaire; and the analysis of the interactions between the rs3864283 and both personality traits and anxiety. The study group consisted of 522 volunteers. Of these, 371 were cigarette users and 151 were never-smokers. The genomic DNA was isolated from venous blood using standard procedures. The results of both inventories, i.e., NEO-FFI and STAI., were reported as the sten scores. Genotyping was conducted with the real-time PCR method. Statistically significant differences were found in the frequency of rs3864283 genotypes and alleles in the tested sample of Cigarette Users when compared to the control group. The Cigarette Users compared to the control group obtained higher scores in the assessment of NEO-FFI extraversion scale, and significantly lower results were obtained for the NEO-FFI openness scale, the agreeableness scale, and the conscientiousness scale. There was a statistically significant effect of rs3864283 genotype interaction and Cigarette Use or not using (control group) on the extraversion scale. There was also a statistically significant effect of Cigarette Users or the control group on the extraversion scale score. The results obtained in the presented study indicated a significant association between the HINT1 rs3864283 variant and smoking status. Moreover, this is the first study incorporating genetic association of above-mentioned polymorphic site with interaction analysis of personality traits and anxiety. Overall, the results of this study suggest that HINT1 is an important genetic component associated with nicotine usage mechanisms.
Genome-Wide Analysis of the PHT Gene Family and Its Response to Mycorrhizal Symbiosis in Tomatoes under Phosphate Starvation Conditions
Authors: Rui Wenjing , Ma Jing , Wei Ning , Zhu Xiaoya , Li Zhifang
Published: June 2023

Phosphate is one of the essential mineral nutrients. Phosphate transporter genes (PHTs) play an important role in Pi acquisition and homeostasis in tomato plants. However, basic biological information on PHT genes and their responses of symbiosis with arbuscular mycorrhizal in the genome remains largely unknown. We analyzed the physiological changes and PHT gene expression in tomatoes (Micro-Tom) inoculated with arbuscular mycorrhizal (AM) fungi (Funneliformis mosseae) under different phosphate conditions (P1: 0 µM, P2: 25 µM, and P3: 200 µM Pi). Twenty-three PHT genes were identified in the tomato genomics database. Protein sequence alignment further divided the 23 PHT genes into three groups, with similar classifications of exons and introns. Good colonization of plants was observed under low phosphate conditions (25 µM Pi), and Pi stress and AM fungi significantly affected P and N accumulation and root morphological plasticity. Moreover, gene expression data showed that genes in the SlPHT1 (SlPT3, SlPT4, and SlPT5) gene family were upregulated by Funneliformis mosseae under all conditions, which indicated that these gene levels were significantly increased with AM fungi inoculation. None of the analyzed SlPHT genes in the SlPH2, SlPHT3, SlPHT4, and SlPHO gene families were changed at any Pi concentration. Our results indicate that inoculation with AM fungi mainly altered the expression of the PHT1 gene family. These results will lay a foundation for better understanding the molecular mechanisms of inorganic phosphate transport under AM fungi inoculation.
Multi-Omics Identification of Genetic Alterations in Head and Neck Squamous Cell Carcinoma and Therapeutic Efficacy of HNC018 as a Novel Multi-Target Agent for c-MET/STAT3/AKT Signaling Axis
Authors: Khedkar Harshita Nivrutti , Chen Lung-Ching , Kuo Yu-Cheng , Wu Alexander T. H. , Huang Hsu-Shan
Published: June 2023

Amongst the most prevalent malignancies worldwide, head and neck squamous cell carcinoma (HNSCC) is characterized by high morbidity and mortality. The failure of standard treatment modalities, such as surgery, radiotherapy, and chemotherapy, demands the need for in-depth understanding of the complex signaling networks involved in the development of treatment resistance. A tumor’s invasive growth and high levels of intrinsic or acquired treatment resistance are the primary causes of treatment failure. This may be a result of the presence of HNSCC’s cancer stem cells, which are known to have self-renewing capabilities that result in therapeutic resistance. Using bioinformatics methods, we discovered that elevated expressions of MET, STAT3, and AKT were associated with poor overall survival in HNSCC patients. We then evaluated the therapeutic potential of our newly synthesized small molecule HNC018 towards its potential as a novel anticancer drug. Our computer-aided structure characterization and target identification study predicted that HNC018 could target these oncogenic markers implicated in HNSCC. Subsequently, the HNC018 has demonstrated its anti-proliferative and anticancer activities towards the head and neck squamous cell carcinoma cell lines, along with displaying the stronger binding affinities towards the MET, STAT3, and AKT than the standard drug cisplatin. Reduction in the clonogenic and tumor-sphere-forming ability displays HNC018’s role in decreasing the tumorigenicity. Importantly, an vivo study has shown a significant delay in tumor growth in HNC018 alone or in combination with cisplatin-treated xenograft mice model. Collectively with our findings, HNC018 highlights the desirable properties of a drug-like candidate and could be considered as a novel small molecule for treating head and neck squamous cell carcinoma.
Dynomics: A Novel and Promising Approach for Improved Breast Cancer Prognosis Prediction
Authors: Inglese Marianna , Ferrante Matteo , Boccato Tommaso , Conti Allegra , Pistolese Chiara A. , Buonomo Oreste C. , D’Angelillo Rolando M. , Toschi Nicola
Published: June 2023

Traditional imaging techniques for breast cancer (BC) diagnosis and prediction, such as X-rays and magnetic resonance imaging (MRI), demonstrate varying sensitivity and specificity due to clinical and technological factors. Consequently, positron emission tomography (PET), capable of detecting abnormal metabolic activity, has emerged as a more effective tool, providing critical quantitative and qualitative tumor-related metabolic information. This study leverages a public clinical dataset of dynamic 18F-Fluorothymidine (FLT) PET scans from BC patients, extending conventional static radiomics methods to the time domain—termed as ‘Dynomics’. Radiomic features were extracted from both static and dynamic PET images on lesion and reference tissue masks. The extracted features were used to train an XGBoost model for classifying tumor versus reference tissue and complete versus partial responders to neoadjuvant chemotherapy. The results underscored the superiority of dynamic and static radiomics over standard PET imaging, achieving accuracy of 94% in tumor tissue classification. Notably, in predicting BC prognosis, dynomics delivered the highest performance, achieving accuracy of 86%, thereby outperforming both static radiomics and standard PET data. This study illustrates the enhanced clinical utility of dynomics in yielding more precise and reliable information for BC diagnosis and prognosis, paving the way for improved treatment strategies.
Electrospinning Preparation, Structure, and Properties of Fe3O4/Tb(acac)3phen/Polystyrene Bifunctional Microfibers
Authors: Liu Lina , Qin Ruifei , Fan Xiaofeng , Wang Kexin , Wang Xiujie , Wang Hao , Chen Yongjun , Wang Jintao , Wang Yi
Published: June 2023

Compared to single functional materials, multifunctional materials with magnetism and luminescence are more attractive and promising; Thus, it has become an important subject. In our work, bifunctional Fe3O4/Tb(acac)3phen/polystyrene) microfibers with magnetic and luminescent properties (acac: acetylacetone, phen: 1,10-phenanthroline) were synthesized by simple electrospinning process. The doping of Fe3O4 and Tb(acac)3phen made the fiber diameter larger. The surface of pure polystyrene microfibers and microfibers doped only with Fe3O4 nanoparticles were chapped similar to bark, whereas the surface of the microfibers was smoother after doping with Tb(acac)3phen complexes. The luminescent properties of the composite microfibers were systematically studied in contrast to pure Tb(acac)3phen complexes, including excitation and emission spectra, fluorescence dynamics, and the temperature dependence of intensity. Compared with the pure complexes, the thermal activation energy and thermal stability of composite microfiber was significantly improved, and the luminescence of the unit mass of Tb(acac)3phen complexes in composite microfibers was stronger than that in pure Tb(acac)3phen complexes. The magnetic properties of the composite microfibers were also investigated using hysteresis loops, and an interesting experimental phenomenon was found that the saturation magnetization of the composite microfibers gradually increased with the increase in the doping proportion of terbium complexes.
Porous Talcum-Based Steatite Ceramics Fabricated by the Admixture of Organic Particles: Experimental Characterization and Effective Medium/Field Modeling of Thermo-Mechanical Properties
Authors: Pichler Christian , Perfler Lukas , Traxl Roland , Lackner Roman
Published: June 2023

In this paper, an experimental campaign, as regards the thermo-mechanical properties (heat capacity, thermal conductivity, Young’s modulus, and tensile (bending) strength) of talcum-based steatite ceramics with artificially introduced porosity, is presented. The latter has been created by adding various amounts of an organic pore-forming agent, almond shell granulate, prior to compaction and sintering of the green bodies. The so-obtained porosity-dependent material parameters have been represented by homogenization schemes from effective medium/effective field theory. As regards the latter, thermal conductivity and elastic properties are well described by the self-consistent estimate, with effective material properties scaling in a linear manner with porosity, with the latter in the range of 1.5 vol-%, representing the intrinsic porosity of the ceramic material, to 30 vol-% in this study. On the other hand, strength properties are, due to the localization of the failure mechanism in the quasi-brittle material, characterized by a higher-order power-law dependency on porosity.
Effect of Peel Ply on Resin Flow during Vacuum Infusion
Authors: An Sehun , Kim Jung-soo , Roh Hyung Doh , Kim Wie-Dae , Lee Jungwan , Um Moon-Kwang
Published: June 2023

Although various simulations have been conducted for the vacuum infusion process, most of the studies have considered only fabrics and flow medium and ignored the effect of peel ply. However, peel ply can affect resin flow because it is placed between the fabrics and flow medium. To verify this, permeability of two types of peel plies was measured, and it was found that the permeability between the peel plies differed significantly. Moreover, the permeability of the peel plies was lower than that of the carbon fabric; thus, peel ply can cause a bottleneck in the flow in the out-of-plane direction. Some 3D flow simulations were conducted in cases of no peel ply and for two types of the peel plies to confirm the effect of peel ply, and experiments were also conducted for two types of the peel plies. It was observed that filling time and flow pattern were highly dependent on the peel plies. The smaller permeability of peel ply has, the greater effect of peel ply is. These results indicate that the permeability of peel ply is one of the dominant factors and should be considered in process design in vacuum infusion. Additionally, by adding one layer of peel ply and applying permeability, the accuracy of flow simulations can be improved for filling time and pattern.
Preparation of HfCxN1−x Nanoparticles Derived from a Multifunction Precursor with Hf-O and Hf-N Bonds
Authors: Zeng Guang , Xu Ping , Zeng Chen , Huang Qizhong , Su Zhean
Published: June 2023

HfCxN1−x nanoparticles were synthesized using the urea-glass route, employing hafnium chloride, urea, and methanol as raw materials. The synthesis process, polymer-to-ceramic conversion, microstructure, and phase evolution of HfCxN1−x/C nanoparticles were thoroughly investigated across a wide range of molar ratios between the nitrogen source and the hafnium source. Upon annealing at 1600 °C, all precursors demonstrated remarkable translatability to HfCxN1−x ceramics. Under high nitrogen source ratios, the precursor exhibited complete transformation into HfCxN1−x nanoparticles at 1200 °C, with no observed presence of oxidation phases. In comparison to HfO2, the carbothermal reaction of HfN with C significantly reduced the preparation temperature required for HfC. By increasing the urea content in the precursor, the carbon content of the pyrolyzed products increased, leading to a substantial decrease in the electrical conductivity of HfCxN1−x/C nanoparticle powders. Notably, as the urea content in the precursor increased, a significant decrease in average electrical conductivity values was observed for the R4-1600, R8-1600, R12-1600, and R16-1600 nanoparticles measured at a pressure of 18 MPa, yielding values of 225.5, 59.1, 44.8, and 46.0 S·cm−1, respectively.
Meta-Structure Hull Design with Periodic Layered Phononic Crystals Theory for Wide-Band Low-Frequency Sound Insolation
Authors: Zhang Fuxi , Sun Xinyi , Tao Wei , Wang Shiming , Flowers George T. , Hu Qingsong , Gaidai Oleg
Published: June 2023

The hulls of marine vehicles are generally very effective at attenuating airborne acoustic noise generated by their powertrains. However, conventional hull designs are generally not very effective at attenuating wide-band low-frequency noise. Meta-structure concepts offer an opportunity for the design of laminated hull structures tailored to address this concern. This research proposes a novel meta-structure laminar hull concept using periodic layered Phononic crystals to optimize the sound insolation performance on the air–solid side of the hull structure. The acoustic transmission performance is evaluated using the transfer matrix, the acoustic transmittance, and the tunneling frequencies. The theoretical and numerical models for a proposed thin solid-air sandwiched meta-structure hull indicate ultra-low transmission within a 50-to-800 Hz frequency band and with two predicted sharp tunneling peaks. The corresponding 3D-printed sample experimentally validates the tunneling peaks at 189 Hz and 538 Hz, with 0.38 and 0.56 transmission magnitudes, respectively, with the frequency band between those values showing wide-band mitigation. The simplicity of this meta-structure design provides a convenient way to achieve acoustic band filtering of low frequencies for marine engineering equipment and, accordingly, an effective technique for low-frequency acoustic mitigation.
Kinetic and Thermodynamic Study of Methylene Blue Adsorption on TiO2 and ZnO Thin Films
Authors: Vallejo William , Diaz-Uribe Carlos Enrique , Duran Freider
Published: June 2023

In this work, we fabricated and characterized ZnO and TiO2 thin films, determining their structural, optical, and morphological properties. Furthermore, we studied the thermodynamics and kinetics of methylene blue (MB) adsorption onto both semiconductors. Characterization techniques were used to verify thin film deposition. The semiconductor oxides reached different removal values, 6.5 mg/g (ZnO) and 10.5 mg/g (TiO2), after 50 min of contact. The pseudo-second-order model was suitable for fitting the adsorption data. ZnO had a greater rate constant (45.4 × 10−3) than that of TiO2 (16.8 × 10−3). The removal of MB by adsorption onto both semiconductors was an endothermic and spontaneous process. Finally, the stability of the thin films showed that both semiconductors maintained their adsorption capacity after five consecutive removal tests.
Mechanical Behavior and Crack Evolution of Goaf Surrounding Rock with Different Roof-Contacted Filling Rates
Authors: Wang Jie , Huang Kaifei , Fu Jianxin , Song Weidong
Published: June 2023

The goaf formed by mining is filled and treated, which greatly improves the safety and stability of the surrounding rock. During the filling process, the roof-contacted filling rates (RCFR) of goaf were closely related to the stability control of the surrounding rock. The influence of the roof-contacted filling rate on the mechanical characteristics and crack propagation of the goaf surrounding rock (GSR) has been studied. Biaxial compression experiments and numerical simulation experiments were conducted on samples under different operating conditions. The results were as follows: (1) The peak stress, peak strain, and elastic modulus of the GSR are closely related to the RCFR and the goaf size; they increase with the increase of the RCFR, and decrease with the increase of the goaf size; (2) In the initial loading stage, a small number of cracks are generated, and the acoustic emission ringing count increases slowly. The mid-loading stage is the crack initiation and rapid expansion, and the cumulative ring count curve shows a “stepwise” growth. In the later loading stage, cracks continue to propagate and form macroscopic fractures, but the number of rings significantly decreases; (3) Shear cracks are prone to occur in the rock part of the GSR; tensile cracks are prone to occur in the backfill; and the crack propagation speed in the rock is faster than in the backfill. Stress concentration is the direct cause of GSR failure. The maximum concentrated stress of rock mass and backfill is 1~2.5 times and 0.17~0.7 times of the peak stress of the GSR, respectively.
Experimental and Numerical Investigation of Hot Extruded Inconel 718
Authors: Bacchetti Stefano , Coppola Michele A. , De Bona Francesco , Lanzutti Alex , Miotti Pierpaolo , Salvati Enrico , Sordetti Francesco
Published: June 2023

Inconel 718 is a widely used superalloy, due to its unique corrosion resistance and mechanical strength properties at very high temperatures. Hot metal extrusion is the most widely used forming technique, if the manufacturing of slender components is required. As the current scientific literature does not comprehensively cover the fundamental aspects related to the process–structure relationships, in the present work, a combined numerical and experimental approach is employed. A finite element (FE) model was established to answer three key questions: (1) predicting the required extrusion force at different extrusion speeds; (2) evaluating the influence of the main processing parameters on the formation of surface cracks using the normalized Cockcroft Latham’s (nCL) damage criterion; and (3) quantitatively assessing the amount of recrystallized microstructure through Avrami’s equation. For the sake of modeling validation, several experimental investigations were carried out under different processing conditions. Particularly, it was found that the higher the initial temperature of the billet, the lower the extrusion force, although a trade-off must be sought to avoid the formation of surface cracks occurring at excessive temperatures, while limiting the required extrusion payload. The extrusion speed also plays a relevant role. Similarly to the role of the temperature, an optimal extrusion speed value must be identified to minimize the possibility of surface crack formation (high speeds) and to minimize the melting of intergranular niobium carbides (low speeds).
Multi-Response Optimization of Additively Manufactured Ti6Al4V Component Using Grey Relational Analysis Coupled with Entropy Weights
Authors: Alqahtani Khaled N. , Dabwan Abdulmajeed , Abualsauod Emad Hashiem , Anwar Saqib , Al-Samhan Ali M. , Kaid Husam
Published: June 2023

Due to its near-net-shape manufacturing and ability to treat challenging-to-manufacture materials such as titanium alloys, Additive manufacturing (AM) is growing in popularity. However, due to the poor surface quality of AM components, finishing processes such as machining are required. One of the most difficult aspects of finishing AM components is the fact that even when using the same machining parameters, the surface roughness can vary significantly depending on the orientation of the part. In this study, electron beam melting (EBM) Ti6Al4V parts are subjected to the finishing (milling) process in three potential orientations relative to the direction of the tool feed. The impact of the feed rate, radial depth of cut, and cutting speed on the surface roughness and cutting force of the Ti6Al4V EBM part is studied while taking the orientations of the EBM components into consideration. It is found that the machined surface changes in noticeable ways with respect to orientation. A factorial design is used for the experiments, and analysis of variance (ANOVA) is used to evaluate the results. Furthermore, the grey relational analysis (GRA) method coupled with entropy weights is utilized to determine the optimal process variables for machining a Ti6Al4V EBM component. The results show that the feed rate has the greatest impact on the multi-response optimization, followed by the cutting speed, faces, and radial depth of cut.
Notch-Stress S–N Curves for Welded Aluminum-Alloy Components Subjected to Bending
Authors: Matić Tomislav , Vulić Nenad , Kustura Dražen , Peko Ivan
Published: June 2023

Fatigue analysis of aluminum-alloy welded joints based on the linear elastic notch-stress approach is presented in this paper. The International Institute of Welding proposes two variants of the approach, one for thick joints, i.e., joints with a plate thickness of 5 mm or more, with a reference radius rref = 1 mm, using the FAT71 notch-stress design curve, and one for thin joints, i.e., joints with a plate thickness of less than 5 mm, with a reference radius rref = 0.05 mm, using the FAT180 notch-stress design curve. In this work, the feasibility of the proposed S–N curves, obtained mainly by fatigue tests on axially loaded joints, was investigated for 4 mm thick joints subjected to bending. The fatigue analysis was performed for two types of joints: a joint with longitudinal fillet-welded attachment and a joint with round sheet fillet-welded attachment. It was shown that a more accurate estimation of the fatigue life of 4 mm thick aluminum joints loaded in bending can be obtained using the FAT71 notch-stress design curve.
Regulatory Functions of Hypoxia in Host–Parasite Interactions: A Focus on Enteric, Tissue, and Blood Protozoa
Authors: DeMichele Emily , Sosnowski Olivia , Buret Andre G. , Allain Thibault
Published: June 2023

Body tissues are subjected to various oxygenic gradients and fluctuations and hence can become transiently hypoxic. Hypoxia-inducible factor (HIF) is the master transcriptional regulator of the cellular hypoxic response and is capable of modulating cellular metabolism, immune responses, epithelial barrier integrity, and local microbiota. Recent reports have characterized the hypoxic response to various infections. However, little is known about the role of HIF activation in the context of protozoan parasitic infections. Growing evidence suggests that tissue and blood protozoa can activate HIF and subsequent HIF target genes in the host, helping or hindering their pathogenicity. In the gut, enteric protozoa are adapted to steep longitudinal and radial oxygen gradients to complete their life cycle, yet the role of HIF during these protozoan infections remains unclear. This review focuses on the hypoxic response to protozoa and its role in the pathophysiology of parasitic infections. We also discuss how hypoxia modulates host immune responses in the context of protozoan infections.
Editorial for the Special Issue “Petrology and Mineralogy of Pegmatite Deposits”
Authors: Müller Axel , Roda-Robles Encarnación
Published: June 2023

This Special Issue of Minerals, section Mineral Deposits, on the topic of “Petrology and Mineralogy of Pegmatite Deposits”, was inspired by the currently growing scientific and economic interest in pegmatites [...]
Long-Term Leaching Behavior and Geochemical Modeling of Cement Solidified Incineration Fly Ash Containing Waste Tires and Wood Biomass
Authors: Santiago Jose Rodolfo , Sekito Tomoo , Dote Yutaka
Published: June 2023

Waste incineration is a widely used treatment method, and sustainable approaches are required to properly recycle large volumes of incineration ash to reduce environmental impacts and landfill space consumption. Studies have focused on the potential of recycling incineration ash as a replacement for natural aggregates in civil engineering applications, such as road construction. However, industrial waste incineration ash, such as waste tire incineration ash, contains hazardous heavy metals, such as lead and zinc that pose potential environmental threats. Moreover, few studies have investigated the leachability of these hazardous metals after long-term natural aging. This study investigates the long-term evolution of leachate chemistry, mineralogical transformation, and heavy metal fixation performance of a recycled roadbed material using ash from industrial waste incineration of waste tires and biomass (SFA). Additionally, field samples from a five-year pilot test site utilizing SFA were also examined. Regulatory leaching tests showed that the concentrations of Cd, Pb, As, T-Cr, and Ni were all below permissible limits even after five years of utilization. Long-term column leaching experiment results indicated that, compared to the total content of the SFA material, the leaching ratios of Pb, T-Cr, Cu, and Zn were 27%, 12%, 5%, and 0.1%, respectively. The SFA pH-stat leaching test results demonstrated that the mass release of the total content of heavy metals was relatively minimal, even under acidic pH conditions (pH < 4). Finally, profiles of pH and major ions in leachate from the column leaching experiment were simulated using HYDRUS HP1, implementing a dual-porosity modeling approach. In conclusion, despite containing hazardous heavy metals, SFA exhibits significantly low leaching rates over a long-term period.