bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Polymersome-Based Nanomedicine for Chemotherapeutic and Sonodynamic Combination Therapy
Authors: Kim Mingyun , Kim Doyeon , Jang Yongho , Han Hyounkoo , Lee Seonock , Moon Hyungwon , Kim Jungho , Kim Hyuncheol
Published: January 2023

In anticancer therapy, combination therapy has been suggested as an alternative to the insufficient therapeutic efficacy of single therapy. Among combination therapies, combination chemo- and photodynamic therapy are actively investigated. However, photodynamic therapy shows a limitation in the penetration depth of the laser. Therefore, sonodynamic therapy (SDT), using ultrasound instead of a laser as a trigger, is an upcoming strategy for deep tumors. Additionally, free drugs are easily degraded by enzymes, have difficulty in reaching the target site, and show side effects after systemic administration; therefore, the development of drug delivery systems is desirable for sufficient drug efficacy for combination therapy. However, nanocarriers, such as microbubbles, and albumin nanoparticles, are unstable in the body and show low drug-loading efficiency. Here, we propose polylactide (PLA)-poly (ethylene glycol) (PEG) polymersomes (PLs) with a high drug loading rate of doxorubicin (DOX) and verteporfin (VP) for effective combination therapy in both in vitro and in vivo experiments. The cellular uptake efficiency and cytotoxicity test results of VP-DOX-PLs were higher than that of single therapy. Moreover, in vivo biodistribution showed the accumulation of the VP-DOX-PLs in tumor regions. Therefore, VP-DOX-PLs showed more effective anticancer efficacy than either single therapy in vivo. These results suggest that the combination therapy of SDT and chemotherapy could show novel anticancer effects using VP-DOX-PLs.
Cysteamine/Cystamine Exert Anti-Mycobacterium abscessus Activity Alone or in Combination with Amikacin
Authors: Palucci Ivana , Salustri Alessandro , De Maio Flavio , Pereyra Boza Maria del Carmen , Paglione Francesco , Sali Michela , Occhigrossi Luca , D’Eletto Manuela , Rossin Federica , Goletti Delia , Sanguinetti Maurizio , Piacentini Mauro , Delogu Giovanni
Published: January 2023

Host-directed therapies are emerging as a promising tool in the curing of difficult-to-treat infections, such as those caused by drug-resistant bacteria. In this study, we aim to test the potential activity of the FDA- and EMA-approved drugs cysteamine and cystamine against Mycobacterium abscessus. In human macrophages (differentiated THP-1 cells), these drugs restricted M. abscessus growth similar to that achieved by amikacin. Here, we use the human ex vivo granuloma-like structures (GLS) model of infection with the M. abscessus rough (MAB-R) and smooth (MAB-S) variants to study the activity of new therapies against M. abscessus. We demonstrate that cysteamine and cystamine show a decrease in the number of total GLSs per well in the MAB-S and MAB-R infected human peripheral blood mononuclear cells (PBMCs). Furthermore, combined administration of cysteamine or cystamine with amikacin resulted in enhanced activity against the two M. abscessus morpho variants compared to treatment with amikacin only. Treatment with cysteamine and cystamine was more effective in reducing GLS size and bacterial load during MAB-S infection compared with MAB-R infection. Moreover, treatment with these two drugs drastically quenched the exuberant proinflammatory response triggered by the MAB-R variant. These findings showing the activity of cysteamine and cystamine against the R and S M. abscessus morphotypes support the use of these drugs as novel host-directed therapies against M. abscessus infections.
Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells
Authors: Diaz-Ruano Ana Belén , Martinez-Alarcon Nuria , Perán Macarena , Benabdellah Karim , Garcia-Martinez María de los Ángeles , Preda Ovidiu , Ramirez-Tortosa César , Gonzalez-Hernandez Andrea , Marchal Juan Antonio , Picon-Ruiz Manuel
Published: January 2023

In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17β-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases.
Polyploid/Multinucleated Giant and Slow-Cycling Cancer Cell Enrichment in Response to X-ray Irradiation of Human Glioblastoma Multiforme Cells Differing in Radioresistance and TP53/PTEN Status
Authors: Alhaddad Lina , Chuprov-Netochin Roman , Pustovalova Margarita , Osipov Andreyan N. , Leonov Sergey
Published: January 2023

Radioresistance compromises the efficacy of radiotherapy for glioblastoma multiforme (GBM), the most devastating and common brain tumor. The present study investigated the relationship between radiation tolerance and formation of polyploid/multinucleated giant (PGCC/MGCC) and quiescent/senescent slow-cycling cancer cells in human U-87, LN-229, and U-251 cell lines differing in TP53/PTEN status and radioresistance. We found significant enrichment in MGCC populations of U-87 and LN-229 cell lines, and generation of numerous small mononuclear (called Raju cells, or RJ cells) U-87-derived cells that eventually form cell colonies, in a process termed neosis, in response to X-ray irradiation (IR) at single acute therapeutic doses of 2–6 Gy. For the first time, single-cell high-content imaging and analysis of Ki-67- and EdU-coupled fluorescence demonstrated that the IR exposure dose-dependently augments two distinct GBM cell populations. Bifurcation of Ki-67 staining suggests fast-cycling and slow-cycling populations with a normal-sized nuclear area, and with an enlarged nuclear area, including one resembling the size of PGCC/MGCCs, that likely underlie the highest radioresistance and propensity for repopulation of U-87 cells. Proliferative activity and anchorage-independent survival of GBM cell lines seem to be related to neosis, low level of apoptosis, fraction of prematurely stress-induced senescent MGCCs, and the expression of p63 and p73, members of p53 family transcription factors, but not to the mutant p53. Collectively, our data support the importance of the TP53wt/PTENmut genotype for the maintenance of cycling radioresistant U-87 cells to produce a significant amount of senescent MGCCs as an IR stress-induced adaptation response to therapeutic irradiation doses.
Genetic Regulation Mechanism of Cadmium Accumulation and Its Utilization in Rice Breeding
Authors: Chen Guang , Du Ruiying , Wang Xu
Published: January 2023

Cadmium (Cd) is a heavy metal whose pollution in rice fields leads to varying degrees of Cd accumulation in rice. Furthermore, the long-term consumption of Cd-contaminated rice is harmful to human health. Therefore, it is of great theoretical significance and application value to clarify the genetic regulation mechanism of Cd accumulation in rice and cultivate rice varieties with low Cd accumulation for the safe use of Cd-contaminated soils. This review summarizes the effects of Cd on rice growth, yield, and quality; the physiological and molecular mechanisms of Cd absorption in the roots, loading, and transport of Cd in the xylem, the distribution of Cd in nodes, redistribution of Cd in leaves, and accumulation of Cd in the grains; the regulation mechanism of the Cd stress response; and the breeding of rice with low Cd accumulation. Future directions on the genetic regulation of Cd in rice and application are also discussed. This review provides a theoretical basis for studies exploring the genetic regulation of Cd stress in rice. It also offers a basis for formulating effective strategies to reduce the Cd content in rice.
The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis
Authors: Bondue Tjessa , Kouraich Anas , Berlingerio Sante Princiero , Veys Koenraad , Marie Sandrine , Alsaad Khaled O. , Al-Sabban Essam , Levtchenko Elena , van den Heuvel Lambertus
Published: January 2023

Cystinosis is an autosomal recessive lysosomal storage disease, caused by mutations in the CTNS gene, resulting in multi-organ cystine accumulation. Three forms of cystinosis are distinguished: infantile and juvenile nephropathic cystinosis affecting kidneys and other organs such as the eyes, endocrine system, muscles, and brain, and adult ocular cystinosis affecting only the eyes. Currently, elevated white blood cell (WBC) cystine content is the gold standard for the diagnosis of cystinosis. We present a patient with proteinuria at adolescent age and corneal cystine crystals, but only slightly elevated WBC cystine levels (1.31 ½ cystine/mg protein), precluding the diagnosis of nephropathic cystinosis. We demonstrate increased levels of cystine in skin fibroblasts and urine-derived kidney cells (proximal tubular epithelial cells and podocytes), that were higher than the values observed in the WBC and healthy control. CTNS gene analysis shows the presence of a homozygous missense mutation (c.590 A > G; p.Asn177Ser), previously described in the Arab population. Our observation underlines that low WBC cystine levels can be observed in patients with juvenile cystinosis, which may delay the diagnosis and timely administration of cysteamine. In such patients, the diagnosis can be confirmed by cystine measurement in slow-dividing cells and by molecular analysis of the CTNS gene.
The LIV-1 Subfamily of Zinc Transporters: From Origins to Present Day Discoveries
Authors: Taylor Kathryn M.
Published: January 2023

This review explains the origin of the LIV-1 family of zinc transporters, paying attention to how this family of nine human proteins was originally discovered. Structural and functional differences between these nine human LIV-1 family members and the five other ZIP transporters are examined. These differences are both related to aspects of the protein sequence, the conservation of important motifs and to the effect this may have on their overall function. The LIV-1 family are dependent on various post-translational modifications, such as phosphorylation and cleavage, which play an important role in their ability to transport zinc. These modifications and their implications are discussed in detail. Some of these proteins have been implicated in cancer which is examined. Furthermore, some additional areas of potential fruitful discovery are discussed and suggested as worthy of examination in the future.
Analysis of Changes in the Expression of Selected Genes from the ABC Family in Patients with Triple-Negative Breast Cancer
Authors: Makuch-Kocka Anna , Kocki Janusz , Brzozowska Anna , Bogucki Jacek , Kołodziej Przemysław , Bogucka-Kocka Anna
Published: January 2023

Triple-negative breast cancer (TNBC) is characterized by a lack of expression of hormone receptors (estrogen and progesterone), as cancer cells also do not overexpress the HER2 receptor. Due to their molecular profile, treatments for this type of breast cancer are limited. In some cases, the pharmacotherapy of patients with TNBC is hindered by the occurrence of multidrug resistance, which is largely conditioned by proteins encoded by genes from the ABC family. The aim of our study was to determine the expression profile of 14 selected genes from the ABC family using real-time PCR in 68 patients with TNBC by comparing the obtained results with clinical data and additionally using bioinformatics tools (Ualcan and The Breast Cancer Gene Expression Miner v4.8 (bc -GenExMiner v4.8)), as well as by comparing experimental data with data in the Cancer Genome Atlas (TCGA) database. Based on the conducted studies, we found different levels of gene expression depending on the age of patients, tumor sizes, metastases to lymph nodes, cell infiltration into adipose tissue, tumor stages, or lymphovascularinvasion. The results of the presented studies demonstrate the effect of the expression level of the studied genes on the clinical course and prognosis of patients with TNBC, and suggest how profiling the expression level of genes from the ABC family may be a useful tool in determining personalized TNBC treatment.
Platelet–Neutrophil Crosstalk in Thrombosis
Authors: Mereweather Laura J. , Constantinescu-Bercu Adela , Crawley James T. B. , Salles-Crawley Isabelle I.
Published: January 2023

Platelets are essential for the formation of a haemostatic plug to prevent bleeding, while neutrophils are the guardians of our immune defences against invading pathogens. The interplay between platelets and innate immunity, and subsequent triggering of the activation of coagulation is part of the host system to prevent systemic spread of pathogen in the blood stream. Aberrant immunothrombosis and excessive inflammation can however, contribute to the thrombotic burden observed in many cardiovascular diseases. In this review, we highlight how platelets and neutrophils interact with each other and how their crosstalk is central to both arterial and venous thrombosis and in COVID-19. While targeting platelets and coagulation enables efficient antithrombotic treatments, they are often accompanied with a bleeding risk. We also discuss how novel approaches to reduce platelet-mediated recruitment of neutrophils could represent promising therapies to treat thrombosis without affecting haemostasis.
Comparison of Virulence-Factor-Encoding Genes and Genotype Distribution amongst Clinical Pseudomonas aeruginosa Strains
Authors: Bogiel Tomasz , Depka Dagmara , Kruszewski Stanisław , Rutkowska Adrianna , Kanarek Piotr , Rzepka Mateusz , Leitão Jorge H. , Deptuła Aleksander , Gospodarek-Komkowska Eugenia
Published: January 2023

Pseudomonas aeruginosa is an opportunistic pathogen encoding several virulence factors in its genome, which is well-known for its ability to cause severe and life-threatening infections, particularly among cystic fibrosis patients. The organism is also a major cause of nosocomial infections, mainly affecting patients with immune deficiencies and burn wounds, ventilator-assisted patients, and patients affected by other malignancies. The extensively reported emergence of multidrug-resistant (MDR) P. aeruginosa strains poses additional challenges to the management of infections. The aim of this study was to compare the incidence rates of selected virulence-factor-encoding genes and the genotype distribution amongst clinical multidrug-sensitive (MDS) and MDR P. aeruginosa strains. The study involved 74 MDS and 57 MDR P. aeruginosa strains and the following virulence-factor-encoding genes: lasB, plC H, plC N, exoU, nan1, pilA, and pilB. The genotype distribution, with respect to the antimicrobial susceptibility profiles of the strains, was also analyzed. The lasB and plC N genes were present amongst several P. aeruginosa strains, including all the MDR P. aeruginosa, suggesting that their presence might be used as a marker for diagnostic purposes. A wide variety of genotype distributions were observed among the investigated isolates, with the MDS and MDR strains exhibiting, respectively, 18 and 9 distinct profiles. A higher prevalence of genes determining the virulence factors in the MDR strains was observed in this study, but more research is needed on the prevalence and expression levels of these genes in additional MDR strains.
Mechanistic Investigation of the Androgen Receptor DNA-Binding Domain and Modulation via Direct Interactions with DNA Abasic Sites: Understanding the Mechanisms Involved in Castration-Resistant Prostate Cancer
Authors: Xu Shangze , Kondal Matthew D. , Ahmad Ayaz , Zhu Ruidi , Fan Lanyu , Zaborniak Piotr , Madden Katrina S. , de Souza João V. , Bronowska Agnieszka K.
Published: January 2023

The androgen receptor (AR) is an important drug target in prostate cancer and a driver of castration-resistant prostate cancer (CRPC). A significant challenge in designing effective drugs lies in targeting constitutively active AR variants and, most importantly, nearly all AR variants lacking the ligand-binding domain (LBD). Recent findings show that an AR’s constitutive activity may occur in the presence of somatic DNA mutations within non-coding regions, but the role of these mutations remains elusive. The discovery of new drugs targeting CRPC is hampered by the limited molecular understanding of how AR binds mutated DNA sequences, frequently observed in prostate cancer, and how mutations within the protein and DNA regulate AR-DNA interactions. Using atomistic molecular dynamics (MD) simulations and quantum mechanical calculations, we focused our efforts on (i) rationalising the role of several activating DBD mutations linked to prostate cancer, and (ii) DBD interactions in the presence of abasic DNA lesions, which frequently occur in CRPC. Our results elucidate the role of mutations within DBD through their modulation of the intrinsic dynamics of the DBD-DNA ternary complex. Furthermore, our results indicate that the DNA apurinic lesions occurring in the androgen-responsive element (ARE) enhance direct AR-DNA interactions and stabilise the DBD homodimerisation interface. Moreover, our results strongly suggest that those abasic lesions may form reversible covalent crosslinks between DNA and lysine residues of an AR via a Schiff base. In addition to providing an atomistic model explaining how protein mutations within the AR DNA-binding domain affect AR dimerisation and AR-DNA interactions, our findings provide insight into how somatic mutations occurring in DNA non-coding regions may activate ARs. These mutations are frequently observed in prostate cancer and may contribute to disease progression by enhancing direct AR-DNA interactions.
Endothelin-1 as a Biomarker of Idiopathic Pulmonary Fibrosis and Interstitial Lung Disease Associated with Autoimmune Diseases
Authors: Pulito-Cueto Verónica , Genre Fernanda , López-Mejías Raquel , Mora-Cuesta Víctor Manuel , Iturbe-Fernández David , Portilla Virginia , Sebastián Mora-Gil María , Ocejo-Vinyals Javier Gonzalo , Gualillo Oreste , Blanco Ricardo , Corrales Alfonso , Ferraz-Amaro Iván , Castañeda Santos , Cifrián Martínez José Manuel , Atienza-Mateo Belén , Remuzgo-Martínez Sara , González-Gay Miguel Ángel
Published: January 2023

The aim of this study was to determine the role of endothelin-1 (ET-1), a molecule involved in multiple vascular and fibrosing abnormalities, as a biomarker of interstitial lung disease (ILD), as well as its use for the differential diagnosis between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD), using a large and well-defined cohort of patients with ILD. A total of 112 patients with IPF, 91 patients with AD-ILD (28 rheumatoid arthritis (RA), 26 systemic sclerosis, 20 idiopathic inflammatory myositis and 17 interstitial pneumonia with autoimmune features) and 44 healthy controls were included. ET-1 serum levels were determined by enzyme-linked immunosorbent assay. A significant increase in ET-1 levels was found in patients with IPF compared to controls. Likewise, AD-ILD patients also showed higher ET-1 levels than controls when the whole cohort was stratified by the type of AD. Similar ET-1 levels were found in IPF and AD-ILD patients, regardless of the underlying AD. Interestingly, increased ET-1 levels were correlated with worse lung function in IPF and RA-ILD patients. Our study supports that serum ET-1 may be useful as a biomarker of ILD, although it could not help in the differential diagnosis between IPF and AD-ILD. Moreover, ET-1 levels may be associated with ILD severity.
A Genome-Wide Functional Screen Identifies Enhancer and Protective Genes for Amyloid Beta-Peptide Toxicity
Authors: Picón-Pagès Pol , Bosch-Morató Mònica , Subirana Laia , Rubio-Moscardó Francisca , Guivernau Biuse , Fanlo-Ucar Hugo , Zeylan Melisa Ece , Senyuz Simge , Herrera-Fernández Víctor , Vicente Rubén , Fernández-Fernández José M. , García-Ojalvo Jordi , Gursoy Attila , Keskin Ozlem , Oliva Baldomero , Posas Francesc , de Nadal Eulàlia , Muñoz Francisco J.
Published: January 2023

Alzheimer’s disease (AD) is known to be caused by amyloid β-peptide (Aβ) misfolded into β-sheets, but this knowledge has not yet led to treatments to prevent AD. To identify novel molecular players in Aβ toxicity, we carried out a genome-wide screen in Saccharomyces cerevisiae, using a library of 5154 gene knock-out strains expressing Aβ1–42. We identified 81 mammalian orthologue genes that enhance Aβ1–42 toxicity, while 157 were protective. Next, we performed interactome and text-mining studies to increase the number of genes and to identify the main cellular functions affected by Aβ oligomers (oAβ). We found that the most affected cellular functions were calcium regulation, protein translation and mitochondrial activity. We focused on SURF4, a protein that regulates the store-operated calcium channel (SOCE). An in vitro analysis using human neuroblastoma cells showed that SURF4 silencing induced higher intracellular calcium levels, while its overexpression decreased calcium entry. Furthermore, SURF4 silencing produced a significant reduction in cell death when cells were challenged with oAβ1–42, whereas SURF4 overexpression induced Aβ1–42 cytotoxicity. In summary, we identified new enhancer and protective activities for Aβ toxicity and showed that SURF4 contributes to oAβ1–42 neurotoxicity by decreasing SOCE activity.
Approaching the Dimerization Mechanism of Small Molecule Inhibitors Targeting PD-L1 with Molecular Simulation
Authors: Liang Jianhuai , Wang Bingfeng , Yang Yang , Liu Boping , Jin Yulong
Published: January 2023

Inhibitors blocking the PD-1/PD-L1 immune checkpoint demonstrate impressive anti-tumor immunity, and small molecule inhibitors disclosed by the Bristol-Myers Squibb (BMS) company have become a hot topic. In this work, by modifying the carbonyl group of BMS-202 into a hydroxyl group to achieve two enantiomers (MS and MR) with a chiral center, we found that this is an effective way to regulate its hydrophobicity and thus to reduce the negative effect of polar solvation free energy, which enhances the stability of PD-L1 dimer/inhibitor complexes. Moreover, we studied the binding modes of BMS-200 and BMS-202-related small molecule inhibitors by molecular dynamics simulation to explore their inhibitory mechanism targeting PD-L1 dimerization. The results showed that the size exclusion effect of the inhibitors triggered the rearrangement of the residue ATyr56, leading to the formation of an axisymmetric tunnel-shaped pocket, which is an important structural basis for improving the binding affinity of symmetric inhibitors with PD-L1. Furthermore, after inhibitor dissociation, the conformation of ATyr123 and BMet115 rearranged, which blocked the entrance of the binding pocket, while the reverse rearrangements of the same residues occurred when the PD-L1 monomer was complexed with the inhibitors, preparing PD-L1 for dimerization. Overall, this study casts a new light on the inhibitory mechanism of BMS inhibitors targeting PD-L1 dimerization and provides an idea for designing novel small molecule inhibitors for future cancer immunotherapy.
Recent Advances in Protein–Protein Interactions
Authors: Sedov Igor A. , Zuev Yuriy F.
Published: January 2023

Protein-protein interactions (PPIs) lead to formation of complexes and aggregates between a pair or multiple protein molecules [...]
Suppression of RBFox2 by Multiple MiRNAs in Pressure Overload-Induced Heart Failure
Authors: Gu Mingyao , Zhao Yuying , Wang Hong , Cheng Wanwen , Liu Jie , Ouyang Kunfu , Wei Chaoliang
Published: January 2023

Heart failure is the final stage of various cardiovascular diseases and seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including the RNA binding protein RBFox2. It participates in multiple aspects of the regulation of cardiac function and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures, including mRNAs and miRNAs, in a mouse model of heart failure after TAC surgery. A global analysis showed that an asymmetric alternation in gene expression and a large-scale upregulation of miRNAs occurred in heart failure. An association analysis revealed that the latter not only contributed to the degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBFox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBFox2 was targeted by multiple miRNAs, including Let-7, miR-16, and miR-200b, which were significantly upregulated in heart failure. The overexpression of these miRNAs suppressed the RBFox2 protein and its downstream effects in cardiomyocytes, which was evidenced by the suppressed alternative splicing of the Enah gene and impaired E–C coupling via the repression of the Jph2 protein. The inhibition of Let-7, the most abundant miRNA family targeting RBFox2, could restore the RBFox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. In all, these findings revealed the molecular mechanism leading to RBFox2 depression in heart failure, and provided an approach to rescue RBFox2 through miRNA inhibition for the treatment of heart failure.
Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations
Authors: Filkina Maria E. , Baray Daria N. , Beloglazkina Elena K. , Grishin Yuri K. , Roznyatovsky Vitaly A. , Kukushkin Maxim E.
Published: January 2023

Nitrile imine cycloaddition to hydantoins containing an exocyclic C=C double bond has been previously described in a very limited number of examples. In this work, regioselective synthesis of spiro-pyrazoline-imidazolidine-2,4-diones based on a 1,3-dipolar cycloaddition reaction of nitrile imines to 5-methylidene-3-phenyl-hydantoin have been proposed. It was found that, regardless of the nature of the aryl substituents at the terminal C and N atoms of the C-N-N fragment of nitrile imine (electron donor or electron acceptor), cycloaddition to the 5-methylidenhydantoin exocyclic C=C bond proceeds regioselectively, and the terminal nitrogen atom of the nitrile imine connects to the more sterically hindered carbon atom of the double bond, which leads to the formation of a 5-disubstituted pyrazoline ring. The observed cycloaddition regioselectivity was rationalized using DFT calculations of frontier molecular orbital interactions, global CDFT reactivity indices, and minimum energy paths.
Carboxyl Functionalization of N-MWCNTs with Stone–Wales Defects and Possibility of HIF-1α Wave-Diffusive Delivery
Authors: Shunaev Vladislav V. , Bobenko Nadezhda G. , Korusenko Petr M. , Egorushkin Valeriy E. , Glukhova Olga E.
Published: January 2023

Nitrogen-doped multi-walled carbon nanotubes (N-MWCNTs) are widely used for drug delivery. One of the main challenges is to clarify their interaction with hypoxia-inducible factor 1 alpha (HIF-1α), the lack of which leads to oncological and cardiovascular diseases. In the presented study, N-MWCNTs were synthesized by catalytic chemical vapor deposition and irradiated with argon ions. Their chemical state, local structure, interfaces, Stone–Wales defects, and doping with nitrogen were analyzed by high resolution transmission electron microscopy (HRTEM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy. Using experimental data, supercells of functionalized N-MWCNTs with an oxygen content of 2.7, 4 and 6 at. % in carboxyl groups were built by quantum chemical methods. Our analysis by the self-consistent charge density functional tight-binding (SCC DFTB) method shows that a key role in the functionalization of CNTs with carboxyl groups belongs to Stone–Wales defects. The results of research in the decoration of CNTs with HIF-1α demonstrate the possibility of wave-diffusion drug delivery. The nature of hybridization and relaxation determines the mechanism of oxygen regulation with HIF-1α molecules, namely, by OH-(OH–C) and OH-(O=C) chemical bonds. The concentration dependence of drug release in the diffusion mode suggests that the best pattern for drug delivery is provided by the tube with a carboxylic oxygen content of 6 at. %.
FPGA-Based Decision Support System for ECG Analysis
Authors: Giorgio Agostino , Guaragnella Cataldo , Rizzi Maria
Published: January 2023

The high mortality rate associated with cardiac abnormalities highlights the need of accurately detecting heart disorders in the early stage so to avoid severe health consequence for patients. Health trackers have become popular in the form of wearable devices. They are aimed to perform cardiac monitoring outside of medical clinics during peoples’ daily lives. Our paper proposes a new diagnostic algorithm and its implementation adopting a FPGA-based design. The conceived system automatically detects the most common arrhythmias and is also able to evaluate QT-segment lengthening and pulmonary embolism risk often caused by myocarditis. Debug and simulations have been carried out firstly in Matlab environment and then in Quartus IDE by Intel. The hardware implementation of the embedded system and the test for the functional accuracy verification have been performed adopting the DE1_SoC development board by Terasic, which is equipped with the Cyclone V 5CSEMA5F31C6 FPGA by Intel. Properly modified real ECG signals corrupted by a mixture of muscle noise, electrode movement artifacts, and baseline wander are used as a test bench. A value of 99.20% accuracy is achieved by taking into account 0.02 mV for the root mean square value of noise voltage. The implemented low-power circuit is suitable as a wearable decision support device.
Analyzing the Connection between Customary Land Rights and Land Grabbing: A Case Study of Zambia
Authors: Bae Yuh Jin
Published: January 2023

Since the global crises in the 2000s, many foreign and domestic actors have acquired large tracts of land for food and biofuel crop cultivation and other purposes in Africa, often leading to the displacement of the African people living on customary land. The weak customary land rights of ordinary African people have been viewed as one of the main factors making it possible for various land-grabbers to exploit customary land with different purposes. However, it would be insufficient to conclude that the weak customary land rights are the only factor leading to land grabbing in Africa as such land rights give the inheritors the rights to use the land permanently. Therefore, the main objective of this research is to identify a more specific factor leading to land grabbing in Africa, which this article refers to as a ‘land-grabbing-friendly legal environment’. To achieve the main goal, by considering the case of Zambia, this research aims to: (1) analyze the main areas and regions where land grabbing occurs in Zambia and the land-grabbers involved; and (2) analyze the main uses of customary land and changes in tenure systems applied to customary land from the colonial era up to the present day, through a legal history research approach. The main findings of this research are as follows: (1) land-grabbing incidences have often been linked to the government-led agricultural program, involving both internal and external land-grabbers, and (2) the creation of the dual-tenure system during the colonial era and its continuation to the present day have led to the poor financial status of ordinary Zambians living on customary land, contributing to their weak customary land rights. By examining the main results, this research concludes that it is crucial for the Zambian government to bring about reasonable fees for land-titling registration for the ordinary Zambians living on customary land, as well as to separate development aspects from land laws. These steps will strengthen the land rights of the ordinary Zambians and prevent land grabbing.
A Register-Based Study of Interior Monologue in James Joyce’s Ulysses
Authors: Gast Volker , Wehmeier Christian , Vanderbeke Dirk
Published: January 2023

While fictional orality (spoken language in fictional texts) has received some attention in the context of quantitative register studies at the interface of linguistics and literature, only a few attempts have been made so far to apply the quantitative methods of register studies to interior monologues (and other forms of inner speech or thought representation). This article presents a case study of the three main characters of James Joyce’s Ulysses whose thoughts are presented extensively in the novel, i.e., Leopold and Molly Bloom and Stephen Dedalus. Making use of quantitative, corpus-based methods, the thoughts of these characters are compared to fictional direct speech and (literary and non-literary) reference texts. We show that the interior monologues of Ulysses span a range of non-narrative registers with varying degrees of informational density and involvement. The thoughts of one character, Leopold Bloom, differ substantially from that character’s speech. The relative heterogeneity across characters is taken as an indication that interior monologue is used as a means of perspective taking and implicit characterization.
2,7-Bis(pyridin-3-ylethynyl)fluoren-9-one
Authors: Podda Enrico , Arca Massimiliano , Pintus Anna , Demontis Valentina , Lippolis Vito , Ferino Giulio , Orton James B. , Coles Simon J. , Aragoni Maria Carla
Published: January 2023

2,7-bis(pyridin-3-ylethynyl)fluoren-9-one [(3-PyE)2FO] was synthesized in one step by the Sonogashira coupling reaction between 3-ethynylpyridine and 2,7-dibromofluoren-9-one. The title compound was fully characterized, and its crystal structure was determined through single-crystal XRD analysis.
1,1′-Dibromo-2,2′,5,5′-tetrakis(methylthio)ferrocene
Authors: Blockhaus Tobias , Zott Fabian , Sünkel Karlheinz
Published: January 2023

The reaction of 1,1′-dibromoferrocene with three equivalents of LiTMP and Me2S2 produces a product mixture, from which 1,1′-dibromo-2,2′-bis(methylthio)ferrocene (4) can be isolated in moderate yield. Further treatment of the isolated compound 4 with two equivalents of LiTMP and Me2S2 also produced a mixture, from which the title compound 7 could be isolated. A crystal structure determination of 7 shows that the two cyclopentadienyl rings are oriented in such a way that a maximum number of S…Br contacts results. Intermolecular S…Br contacts, supported by S…S contacts, lead to a 1D-chain polymer in [1 0 0] direction.
Chitin-Derived Nanocatalysts for Reductive Amination Reactions
Authors: Polidoro Daniele , Rodriguez-Padron Daily , Perosa Alvise , Luque Rafael , Selva Maurizio
Published: January 2023

Chitin, the second most abundant biopolymer in the planet after cellulose, represents a renewable carbon and nitrogen source. A thrilling opportunity for the valorization of chitin is focused on the preparation of biomass-derived N-doped carbonaceous materials. In this contribution, chitin-derived N-doped carbons were successfully prepared and functionalized with palladium metal nanoparticles. The physicochemical properties of these nanocomposites were investigated following a multi-technique strategy and their catalytic activity in reductive amination reactions was explored. In particular, a biomass-derived platform molecule, namely furfural, was upgraded to valuable bi-cyclic compounds under continuous flow conditions.
Kinetics Study of Polypropylene Pyrolysis by Non-Isothermal Thermogravimetric Analysis
Authors: Dubdub Ibrahim
Published: January 2023

Polypropylene (PP) is considered as one of six polymers representative of plastic wastes. This paper attempts to obtain information on PP polymer pyrolysis kinetics with the help of thermogravimetric analysis (TGA). TGA is used to measure the weight of the sample with temperature increases at different heating rates—5, 10, 20, 30, and 40 K min−1—in inert nitrogen. The pyrolytic kinetics have been analyzed by four model-free methods—Friedman (FR), Flynn–Wall–Qzawa (FWO), Kissinger–Akahira–Sunose (KAS) and Starnik (STK)—and by two model-fitting methods—Coats–Redfern (CR) and Criado methods. The values of activation energies of PP polymer pyrolysis at different conversions are in good agreement with the average of (141, 112, 106, 108 kJ mol−1) for FR, FWO, KAS and STK, respectively. Criado methods have been implemented with the CR method to obtain the reaction mechanism model. As per Criado’s method, the most controlling reaction mechanism has been identified as the geometrical contraction models—cylinder model.
Influence of Pre-Strain on Static and Fatigue Properties of S420M Steel
Authors: Mroziński Stanisław , Lipski Adam , Piotrowski Michał , Egner Halina
Published: January 2023

This paper reports the results of static tensile and low-cycle fatigue tests on S420M steel specimens. As-received (unstrained) and pre-strained specimens were used during the tests. Based on the static tensile tests carried out, no effect of pre-strain on the basic strength parameters of the S420M steel was found. Low-cycle fatigue tests showed that the pre-strain of the specimens causes a change in the cyclic properties of the steel and a slight increase in fatigue life compared to that of the as-received specimens. The greatest increase in durability was observed at the lowest strain levels.
Measurement of Optical Properties of CH3NH3PbX3 (X = Br, I) Single Crystals Using Terahertz Time-Domain Spectroscopy
Authors: Konda Srinivasa Rao , Lin Yucai , Rajan Rahul A. , Yu Weili , Li Wei
Published: January 2023

Organometallic lead bromide and iodide perovskite single crystals (PSCs) are potential candidates for terahertz applications. Herein, we performed terahertz time-domain spectroscopy (THz-TDS) in the frequency range of 0.1–3.0 THz on different thicknesses of MAPbBr3 (0.3, 0.6, and 0.8 mm) and MAPbI3 (0.6, 0.8, 0.9, 1.3, and 2.3 mm). The measurements were carried out with respect to the position (along the focal area), azimuthal rotation of the PSCs, and incidence angles of the reference THz pulse on the PSCs’ surface. Based on the transmitted THz pulses from PSCs from the above measurements, we calculated the real and imaginary parts of the refractive index, dielectric constants, absorption coefficients, and dark conductivity. These optical parameters tend to increase with decreases in the PSCs’ thicknesses. The transmission spectra of the terahertz electric field indicate that the measured optical properties do not vary significantly with the position and orientation of PSCs. The real parts of the refractive index and dielectric constants are higher than the imaginary values for both PSCs. On the other hand, a slight blueshift in the optical phonon vibrations corresponding to Pb-Br/I-Pb and Pb-Br/I bonds is observed with an increase in thickness. Interestingly, the phonon vibrations do not vary with the incidence angle of the THz pulses on the same crystal’s surface. The optical parameters based on THz-TDS reveal that the PSCs satisfy the requirement for tunable THz devices which need suitable, sensitive, and stable absorption properties between 0.1 and 3 THz.
Qualitative and Quantitative Investigations on the Failure Effect of Critical Fissures in Rock Specimens under Plane Strain Compression
Authors: Wen Jiaqi , Tang Lei , Zhang Shenghang , Zhan Qibing , Wang Yukun
Published: January 2023

To investigate the failure effects of critical fissures in rock specimens subjected to plane strain compression (PSC), five types of internal fissures in rock specimens were designed and twelve PSC tests were conducted for two lithologies based on the discrete element method (DEM). The results were analyzed in terms of the fracture mode, data characteristics, and crack evolution. The results indicated the following. (1) The rock samples with a critical fissure under PSC showed a weak face shear fracture mode, which was influenced by lithology, fissure angle, and fissure surface direction. (2) There were four critical expansion points (CEPs) of axial stress of the rocks under PSC, which were the stage signs of rock materials from local damage to complete fracture. The rock-bearing capacity index (RockBCI) was further proposed. (3) The bearing capacity of rock samples with horizontal fissures, fissures whose angles coincided with the fracture surface, and fissures whose surface was perpendicular to the lateral confine direction was the worst; their BCI2 values were found to be 80.6%, 70.8%, and 56.9% of the rock samples without any fissures, respectively. The delayed fracture situation under PSC was identified and analyzed. (4) The crack evolution followed the unified law of localization, and the fissures in the rocks changed the mode of crack development and the path of the deepening and connecting of crack clusters, as well as affecting the time process from damage to collapse. This research innovatively investigated the behavior characteristics of rock samples with a fissure under PSC, and it qualitatively and quantitatively analyzed the bearing capacity of rock mass from local damage to fracture.
Environmental Impact of Concrete Slab Made of Recycled Aggregate Concrete Based on Limit States of Load-Bearing Capacity and Serviceability—LCA Case Study
Authors: Pavlů Tereza , Pešta Jan , Vlach Tomáš , Fořtová Kristina
Published: January 2023

In the case of concrete sustainability, two main ways are generally discussed: (1) the reduction of natural raw materials and (2) the reduction of emissions related to concrete production. Following the second point, there have not yet been reported clear results. This problem is not given enough attention in present publications. This study brings a general view of this issue and a basic comparison with common concrete and traditional reinforcement. This case study deals with the life cycle analysis of a concrete slab made of recycled aggregate concrete with a fine recycled aggregate. The concrete slab was designed according to the limit states of load-bearing capacity and serviceability, which is based on the experimental verification of recycled aggregate concrete properties. Two different reinforcements are compared: (1) ordinary reinforcement by steel bars and (2) glass fibers. Furthermore, scenarios vary due to the slab thickness and reinforcement percentage. The results show the positive environmental impact of replacing natural sand with a fine recycled aggregate. The reduction of climate change potential can be almost 40% in some cases.
Engineering, Mechanical and Dynamic Properties of Basalt Fiber Reinforced Concrete
Authors: Wu Han , Qin Xia , Huang Xu , Kaewunruen Sakdirat
Published: January 2023

This study investigates the engineering and mechanical properties of basalt fiber-reinforced (FRF) concrete, giving special attention to residual flexural strength and dynamic modal parameters. These properties, which have not been thoroughly investigated elsewhere, are a precursor to structural design applications for dynamic compliant structures (i.e., bridges, offshore platforms, railways, and airport pavement). Accordingly, the standard notched flexural tests have been carried out to assess the basalt fiber-reinforced concrete’s residual flexural strength with an additional 0.125%, 0.25%, 0.375%, and 0.5% of volume fraction of basalt fiber. In addition, dynamic modal tests were then conducted to determine the dynamic modulus of elasticity (MOE) and damping of the FRF concrete beams. The results indicate that concrete’s toughness and crack resistance performance are significantly improved with added fiber in basalt fiber reinforced concrete, and the optimum fiber content is 0.25%. It also exhibits the highest increment of compressive strength of 4.48% and a dynamic MOE of 13.83%. New insights reveal that although the residual flexural performance gradually improved with the addition of basalt fiber, the damping ratio had an insignificant change.
The Quality of Surgical Instrument Surfaces Machined with Robotic Belt Grinding
Authors: Hamrol Adam , Hoffmann Mateusz , Lisek Marcin , Bozek Jedrzej
Published: January 2023

Belt grinding is commonly used in the finishing of non-functional shaped surfaces of surgical instruments. Most often it is carried out manually. The subject of this article is the possibility of replacing manual belt grinding with robotic grinding. A research stand was built, the machining process was programmed, and a comparative study of manual and robotic grinding was carried out. The subject of the research were the arms of orthodontic forceps. The condition of the treated surface, defined by its structure and roughness and the geometric accuracy and the error of the shape of the arm in the selected cross-section were adopted as the comparative criteria. Research has shown that robotic belt grinding is more efficient in terms of quality and produces more consistent results than manual grinding.
Mechanical and Hydration Characteristics of Stabilized Gold Mine Tailings Using a Sustainable Industrial Waste-Based Binder
Authors: Pan Zhenkai , Hu Shaohua , Zhang Chao , Zhou Tong , Hua Guowei , Li Yuan , Lv Xiaolin
Published: January 2023

Sustainable resource utilization of tailings is a long-term challenge. Therefore, a novel waste-based binder is proposed in this study to stabilize/solidify gold mine tailings (GMTs). This binder is composed of fly ash (FA), ground blast furnace slag (GBFS), and metakaolin (MK) activated with mixed calcium carbide residue (CCR) as well as pure reagent grade chemical, sodium hydroxide (SH, NaOH), and plaster gypsum (PG, CaSO4·2H2O). The mechanical properties and hydration of stabilized tailings with curing period were investigated. Tests included triaxial compression test and nitrogen adsorption to evaluate the strength of the stabilized tailings and microstructure. The results show that the addition of the waste-based binder yields significant improvement in shear strength. Strain softening occurred for all cured samples, and a local shear band can be observed in all failed stabilized samples. Based on the relationship between strength and curing period, it can be speculated that the hydration reaction of the sample ends after around 40 days of curing. A bimodal pore-size distribution was observed in all solidified/stabilized samples. FTIR and 27Al MAS-NMR were used to analyze hydration products. The strength improvement of stabilized tailings was mainly attributed to the formation of ettringite and C–S–H gels after various polymerization reactions. These new hydrates bind tailings particles and fill the pores to form a more stable structure, which supplied superior mechanical properties. This paper can provide a theoretical basis for exploring the application of the industrial waste-based binder to modify the mechanical properties of gold tailings.