bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear α-Synuclein-Derived Cytotoxic Effect via Altered Ribosomal RNA Processing in Primary Mouse Embryonic Fibroblasts
Authors: Ho Dong Hwan , Kim Hyejung , Nam Daleum , Heo Jinju , Son Ilhong
Published: January 2023

α-Synuclein (αSyn) is an important player in Parkinson’s disease (PD) pathogenesis. The aggregation of αSyn is mainly formed in the cytoplasm, whereas some αSyn accumulation has also been found in the nuclei of neurons. To assess the effect of nuclear αSyn, we generated αSyn conjugated with a nuclear export signal (NES) or a nuclear localization signal (NLS), and compared them with wild-type αSyn in primary mouse embryonic fibroblasts (MEF) using DNA transfection. Overexpression of NLS-αSyn increased cytotoxicity. The levels of apoptotic markers were increased by NLS-αSyn in MEF. Interestingly, an increase in the levels of 40S ribosomal protein 15 was observed in MEF expressing NLS-αSyn. These MEF also showed a higher 28S/18S rRNA ratio. Intriguingly, the expression of NLS-αSyn in MEF enhanced segmentation of nucleolin (NCL)-positive nucleolar structures. We also observed that the downregulation of NCL, using shRNA, promoted a relatively higher 28S/18S rRNA ratio. The reduction in NCL expression accelerated the accumulation of αSyn, and NCL transfection enhanced the degradation of αSyn. These results suggest that nuclear αSyn contributes to the alteration in ribosomal RNA processing via NCL malfunction-mediated nucleolar segmentation, and that NCL is a key factor for the degradation of αSyn.
Cell-Cycle Dysregulation in the Pathogenesis of Diabetic Kidney Disease: An Update
Authors: Deng Bowen , Song Anni , Zhang Chun
Published: January 2023

In the last few decades, the prevalence of diabetes mellitus (DM) has increased rapidly. Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD) globally, attributed to hemodynamic changes and chronic hyperglycemia. Recent findings have emphasized the role of cell-cycle dysregulation in renal fibrosis and ESRD. Under normal physiological conditions, most mature renal cells are arrested in the G0 phase of the cell cycle, with a rather low rate of renewal. However, renal cells can bypass restriction points and re-enter the cell cycle under stimulation of injuries induced via metabolic disorders. Mild injuries activate proliferation of renal cells to compensate for cell loss and reinstate renal function, while severe or repeated injuries will lead to DNA damage and maladaptive repair which ultimately results in cell-cycle arrest or overproliferation, and eventually promote renal fibrosis and ESRD. In this review, we focus on the role of cell-cycle dysregulation in DKD and discuss new, emerging pathways that are implicated in the process.
Sustainable Vegetable Oil-Based Biomaterials: Synthesis and Biomedical Applications
Authors: Nurchi Chiara , Buonvino Silvia , Arciero Ilaria , Melino Sonia
Published: January 2023

One of the main criteria for ecological sustainability is that the materials produced for common use are green. This can include the use of biomaterials and materials that are environmentally friendly, biodegradable and produced at low cost. The exploration of natural resources as sustainable precursors leads to the production of biopolymers that are useful for 3D printing technology. Recently, waste vegetable oils have been found to be a good alternative source for the production of biopolymers in various applications from the engineering to the biomedicine. In this review, the processes for the synthesis of vegetable oil-based biomaterials are described in detail. Moreover, the functionalization strategies to improve the mechanical properties of these materials and the cell-material interaction for their potential use as micro-structured scaffolds in regenerative medicine are discussed.
Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation
Authors: Tovar Lina Mariana , Burgos Carlos Felipe , Yévenes Gonzalo E. , Moraga-Cid Gustavo , Fuentealba Jorge , Coddou Claudio , Bascunan-Godoy Luisa , Catrupay Claudio , Torres Angel , Castro Patricio A.
Published: January 2023

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.
Stabilization of Monomeric Tau Protein by All D-Enantiomeric Peptide Ligands as Therapeutic Strategy for Alzheimer’s Disease and Other Tauopathies
Authors: Altendorf Tim , Gering Ian , Santiago-Schübel Beatrix , Aghabashlou Saisan Selma , Tamgüney Gültekin , Tusche Markus , Honold Dominik , Schemmert Sarah , Hoyer Wolfgang , Mohrlüder Jeannine , Willbold Dieter
Published: January 2023

Alzheimer’s disease and other tauopathies are the world’s leading causes of dementia and memory loss. These diseases are thought to be caused by the misfolding and aggregation of the intracellular tau protein, ultimately leading to neurodegeneration. The tau protein is involved in a multitude of different neurodegenerative diseases. During the onset of tauopathies, tau undergoes structural changes and posttranslational modifications and aggregates into amyloid fibrils that are able to spread with a prion-like behavior. Up to now, there is no therapeutic agent which effectively controls or reverses the disease. Most of the therapeutics that were developed and underwent clinical trials targeted misfolded or aggregated forms of tau. In the current manuscript, we present the selection and characterization of two all D-enantiomeric peptides that bind monomeric tau protein with a low nanomolar KD, stabilize tau in its monomeric intrinsically disordered conformation, and stop the conversion of monomers into aggregates. We show that the effect of the two all D-enantiomeric peptides is strong enough to stop ongoing tau aggregation in vitro and is able to significantly reduce tau fibril assembly in cell culture. Both compounds may serve as new lead components for the development of therapeutic agents against Alzheimer’s disease and other tauopathies.
Enantioselective Human Serum Albumin Binding of Apremilast: Liquid Chromatographic, Fluorescence and Molecular Docking Study
Authors: Dombi Gergely , Horváth Péter , Fiser Béla , Mirzahosseini Arash , Dobó Máté , Szabó Zoltán-István , Tóth Gergő
Published: January 2023

The interaction between human serum albumin (HSA) and apremilast (APR), a novel antipsoriatic drug, was characterized by multimodal analytical techniques including high-performance liquid chromatography (HPLC), fluorescence spectroscopy and molecular docking for the first time. Using an HSA chiral stationary phase, the APR enantiomers were well separated, indicating enantioselective binding between the protein and the analytes. The influence of chromatographic parameters—type and concentration of the organic modifier, buffer type, pH, ionic strength of the mobile phase, flow rate and column temperature—on the chromatographic responses (retention factor and selectivity) was analyzed in detail. The results revealed that the eutomer S-APR bound to the protein to a greater extent than the antipode. The classical van ’t Hoff method was applied for thermodynamic analysis, which indicated that the enantioseparation was enthalpy-controlled. The stability constants of the protein–enantiomer complexes, determined by fluorescence spectroscopy, were in accordance with the elution order observed in HPLC (KR-APR-HSA = 6.45 × 103 M−1, KS-APR-HSA = 1.04 × 104 M−1), showing that, indeed, the later-eluting S-APR displayed a stronger binding with HSA. Molecular docking was applied to study and analyze the interactions between HSA and the APR enantiomers at the atomic level. It was revealed that the most favored APR binding occurred at the border between domains I and II of HSA, and secondary interactions were responsible for the different binding strengths of the enantiomers.
Investigations on the Influence of the Axial Ligand in [Salophene]iron(III) Complexes on Biological Activity and Redox Behavior
Authors: Descher Hubert , Strich Sophie Luise , Hermann Martin , Enoh Peter , Kircher Brigitte , Gust Ronald
Published: January 2023

The [N,N′-disalicylidene-1,2-phenylenediamine]iron(III) ([salophene]iron(III)) derivatives 1–4 with anionic axial ligands (A = Cl−, NO3−, SCN−, CH3COO−) and complexes 5 and 6 with neutral ligands (A = imidazole, 1-methylimidazole) as well as the μ-oxo dimer 7 inhibited proliferation, reduced metabolic activity, and increased mitochondrial reactive oxygen species. Ferroptosis as part of the mode of action was identified by inhibitor experiments, together with induction of lipid peroxidation and diminished mitochondrial membrane potential. No differences in activity were observed for all compounds except 4, which was slightly less active. Electrochemical analyses revealed for all compounds a fast attachment of the solvent dimethyl sulfoxide and a release of the axial ligand A. In contrast, in dichloromethane and acetonitrile, ligand exchange did not take place, as analyzed by measurements of the standard potential for the iron(III/II) redox reaction.
Seeds of Stevia rebaudiana Bertoni as a Source of Plant Growth-Promoting Endophytic Bacteria with the Potential to Synthesize Rebaudioside A
Authors: Simlat Magdalena , Ptak Agata , Jaglarz Anita , Szewczyk Agnieszka , Dziurka Michał , Gurgul Artur
Published: January 2023

In this study, a new strain of Pantoea vagans, SRS89, was isolated from surface-sterilized stevia seeds. The isolate was evaluated using morphological, molecular, and biochemical methods. The bacterium was 1.5 μm long, yellowish in color, and classified as Gram-negative. Whole genome sequencing of our strain revealed the presence of a 4,610,019 bp chromosome, and genome annotation resulted in the detection of 4283 genes encoding 4204 putative coding sequences. Phylogenic analysis classified the genome of our strain close to the MP7 and LMG 24199 strains of P. vagans. Functional analysis showed that the highest number of genes within the analyzed bacterium genome were involved in transcription, amino acid transport and metabolism, and carbohydrate transport and metabolism. We also identified genes for enzymes involved in the biosynthesis of carotenoids and terpenoids. Furthermore, we showed the presence of growth regulators, with the highest amount noted for gibberellic acid A3, indole-3-acetic acid, and benzoic acid. However, the most promising property of this strain is its ability to synthesize rebaudioside A; the estimated amount quantified using reversed-phase (RP)-HPLC was 4.39 mg/g of the dry weight of the bacteria culture. The isolated endophytic bacterium may be an interesting new approach to the production of this valuable metabolite.
Transcriptional Analysis of the Differences between ToLCNDV-India and ToLCNDV-ES Leading to Contrary Symptom Development in Cucumber
Authors: Vo Thuy T. B. , Cho Won Kyong , Jo Yeonhwa , Lal Aamir , Nattanong Bupi , Qureshi Muhammad Amir , Tabssum Marjia , Troiano Elisa , Parrella Giuseppe , Kil Eui-Joon , Lee Taek-Kyun , Lee Sukchan
Published: January 2023

Tomato leaf curl New Delhi virus-ES (ToLCNDV-ES), a high threat to cucurbits in the Mediterranean Basin, is listed as a different strain from the Asian ToLCNDV isolates. In this study, the infectivity of two clones previously isolated from Italy and Pakistan were compared in cucumbers, which resulted in the opposite symptom appearance. The swapping subgenome was processed; however, the mechanisms related to the disease phenotype remain unclear. To identify the disease-associated genes that could contribute to symptom development under the two ToLCNDV infections, the transcriptomes of ToLCNDV-infected and mock-inoculated cucumber plants were compared 21 days postinoculation. The number of differentially expressed genes in ToLCNDV-India-infected plants was 10 times higher than in ToLCNDV-ES-infected samples. The gene ontology (GO) and pathway enrichment were analyzed using the Cucurbits Genomics Database. The flavonoid pathway-related genes were upregulated in ToLCNDV-ES, but some were downregulated in ToLCNDV-India infection, suggesting their role in resistance to the two ToLCNDV infections. The relative expression levels of the selected candidate genes were validated by qRT-PCR under two ToLCNDV-infected conditions. Our results reveal the different infectivity of the two ToLCNDVs in cucumber and also provide primary information based on RNA-seq for further analysis related to different ToLCNDV infections.
The Role of Membrane-Type 1 Matrix Metalloproteinase–Substrate Interactions in Pathogenesis
Authors: Lee Hyun , Ibrahimi Lucas , Azar Dimitri T. , Han Kyu-Yeon
Published: January 2023

A protease is an enzyme with a proteolytic activity that facilitates the digestion of its substrates. Membrane-type I matrix metalloproteinase (MT1-MMP), a member of the broader matrix metalloproteinases (MMP) family, is involved in the regulation of diverse cellular activities. MT1-MMP is a very well-known enzyme as an activator of pro-MMP-2 and two collagenases, MMP-8 and MMP-13, all of which are essential for cell migration. As an anchored membrane enzyme, MT1-MMP has the ability to interact with a diverse group of molecules, including proteins that are not part of the extracellular matrix (ECM). Therefore, MT1-MMP can regulate various cellular activities not only by changing the extra-cellular environment but also by regulating cell signaling. The presence of both intracellular and extra-cellular portions of MT1-MMP can allow it to interact with proteins on both sides of the cell membrane. Here, we reviewed the MT1-MMP substrates involved in disease pathogenesis.
Correlations between the NMR Lipoprotein Profile, APOE Genotype, and Cholesterol Efflux Capacity of Fasting Plasma from Cognitively Healthy Elderly Adults
Authors: de Rojas Itziar , del Barrio Laura , Hernández Isabel , Montrreal Laura , García-González Pablo , Marquié Marta , Valero Sergi , Cano Amanda , Orellana Adelina , Boada Mercè , Mañes Santos , Ruiz Agustín
Published: January 2023

Cholesterol efflux capacity (CEC) is of interest given its potential relationship with several important clinical conditions including Alzheimer’s disease. The inactivation of the APOE locus in mouse models supports the idea that it is involved in determining the CEC. With that in mind, we examine the impact of the plasma metabolome profile and the APOE genotype on the CEC in cognitively healthy elderly subjects. The study subjects were 144 unrelated healthy individuals. The plasma CEC was determined by exposing cultured mouse macrophages treated with BODIPY-cholesterol to human plasma. The metabolome profile was determined using NMR techniques. Multiple regression was performed to identify the most important predictors of CEC, as well as the NMR features most strongly associated with the APOE genotype. Plasma 3-hydroxybutyrate was the variable most strongly correlated with the CEC (r = 0.365; p = 7.3 × 10−6). Male sex was associated with a stronger CEC (r = −0.326, p = 6.8 × 10−5). Most of the NMR particles associated with the CEC did not correlate with the APOE genotype. The NMR metabolomics results confirmed the APOE genotype to have a huge effect on the concentration of plasma lipoprotein particles as well as those of other molecules including omega-3 fatty acids. In conclusion, the CEC of human plasma was associated with ketone body concentration, sex, and (to a lesser extent) the other features of the plasma lipoprotein profile. The APOE genotype exerted only a weak effect on the CEC via the modulation of the lipoprotein profile. The APOE locus was associated with omega-3 fatty acid levels independent of the plasma cholesterol level.
Artificial Infestation of Sarcoptes scabiei (Acari: Sarcoptidae) in Rabbits Exhibits Progressive Pathological Changes, Apoptosis, and Keratinization in the Skin
Authors: Guan Ke , Xu Jing , Gu Xiaobin , He Ran , Xie Yue , Jing Bo , Peng Xuerong , Yang Guangyou
Published: January 2023

Sarcoptes scabiei (S. scabiei) is an ectoparasite that can infest humans and 150 mammalian host species, primarily causing pruritus, crust, and alopecia. However, neither the pathological process of host skin under S. scabiei infection nor the mechanism of S. scabiei infection in regulating apoptosis and keratinization of host skin has been studied yet. In this study, a total of 56 rabbits were artificially infested with S. scabiei, and the skin samples were collected at seven different time points, including 6 h, 12 h, day 1, day 3, 1 week, 4 weeks, and 8 weeks, whereas a group of eight rabbits served as controls. We measured epidermal thickness by H&E staining, observed the skin ultrastructure by electron microscopy, and detected the degree of skin apoptosis by TUNEL staining. The level of transcription of genes related to apoptosis and keratinization was detected by quantitative real-time PCR (qRT-PCR), and the level of Bcl-2 protein expression was further detected using immunohistochemistry. Our results showed that, with increased infestation time, the epidermal layer of the rabbit skin exhibited significant thickening and keratinization, swollen mitochondria in the epidermal cells, and increased skin apoptosis. The level of caspase-1, 3, 8, 10, 14, and Bcl-2 mRNA expression was increased, whereas the level of keratin 1 and 5 was decreased after S. scabiei infestation. In conclusion, S. scabiei infestation causes thickening of the epidermis, which may be related to apoptosis-induced proliferation and skin keratinization.
Antimicrobial Natural Hydrogels in Biomedicine: Properties, Applications, and Challenges—A Concise Review
Authors: Kapusta Oliwia , Jarosz Anna , Stadnik Katarzyna , Giannakoudakis Dimitrios A. , Barczyński Bartłomiej , Barczak Mariusz
Published: January 2023

Natural hydrogels are widely used as biomedical materials in many areas, including drug delivery, tissue scaffolds, and particularly wound dressings, where they can act as an antimicrobial factor lowering the risk of microbial infections, which are serious health problems, especially with respect to wound healing. In this review article, a number of promising strategies in the development of hydrogels with biocidal properties, particularly those originating from natural polymers, are briefly summarized and concisely discussed. Common strategies to design and fabricate hydrogels with intrinsic or stimuli-triggered antibacterial activity are exemplified, and the mechanisms lying behind these properties are also discussed. Finally, practical antibacterial applications are also considered while discussing the current challenges and perspectives.
Synthesis, Crystal, and Electronic Structure of (HpipeH2)2[Sb2I10](I2), with I2 Molecules Linking Sb2X10 Dimers into a Polymeric Anion: A Strategy for Optimizing a Hybrid Compound’s Band Gap
Authors: Bykov Andrey V. , Shestimerova Tatiana A. , Bykov Mikhail A. , Osminkina Liubov A. , Kuznetsov Alexey N. , Gontcharenko Victoria E. , Shevelkov Andrei V.
Published: January 2023

In searching for a tool for optimizing the band gap of a hybrid compound capable of serving as a light-harvesting material in lead-free photovoltaics, we synthesized a new polyiodoantimonate (HpipeH2)2[Sb2I10](I2) and analyzed its crystal and electronic structure by application of X-ray crystal structure analysis, Raman and diffuse reflectance spectroscopies, and quantum chemical calculations. It was demonstrated that I2 molecules link Sb2I10 edge-sharing octahedra into zig-zag chains, whereas the organic cations link inorganic anionic chains into a 3D structure featuring a complex pattern of covalent bonds and non-covalent interactions. Overall, these features provide the background for forming the electronic structure with a narrow band gap of 1.41 eV, therefore being a versatile tool for optimizing the band gap of a potential light-harvesting hybrid compound.
Genome-Wide Analyses of Thaumatin-like Protein Family Genes Reveal the Involvement in the Response to Low-Temperature Stress in Ammopiptanthus nanus
Authors: Liu Qi , Sui Xiangyu , Wang Ying , Zhu Ming , Zhou Yijun , Gao Fei
Published: January 2023

Thaumatin-like proteins (TLPs), a family of proteins with high sequence similarity to thaumatin, are shown to be involved in plant defense, and are thus classified into the pathogenesis related protein family 5. Ammopiptanthus nanus is a rare evergreen broad-leaved shrub distributed in the temperate zone of Central Asia, which has a high tolerance to low-temperature stress. To characterize A. nanus TLPs and understand their roles in low-temperature response in A. nanus, a comprehensive analysis of the structure, evolution, and expression of TLP family proteins was performed. A total of 31 TLP genes were detected in the A. nanus genome, and they were divided into four groups based on their phylogenetic positions. The majority of the AnTLPs contained the conserved cysteine residues and were predicted to have the typical three-dimensional structure of plant TLPs. The primary modes of gene duplication of the AnTLP family genes were segmental duplication. The promoter regions of most AnTLP genes contain multiple cis-acting elements related to environmental stress response. Gene expression analysis based on transcriptome data and fluorescence quantitative PCR analysis revealed that several AnTLP genes were involved in cold-stress response. We further showed that a cold-induced AnTLP gene, AnTLP13, was localized in apoplast, and heterologous expression of the AnTLP13 in Escherichia coli and yeast cells and tobacco leaves enhanced low-temperature stress tolerance when compared with the control cells or seedlings. Our study provided important data for understanding the roles of TLPs in plant response to abiotic stress.
Wheat Long Noncoding RNAs from Organelle and Nuclear Genomes Carry Conserved microRNA Precursors Which May Together Comprise Intricate Networks in Insect Responses
Authors: Akpinar Bala Ani , Muslu Tugdem , Reddy Gadi V. P. , Dogramaci Munevver , Budak Hikmet
Published: January 2023

Long noncoding RNAs (lncRNAs) are a diverse class of noncoding RNAs that are typically longer than 200 nucleotides but lack coding potentials. Advances in deep sequencing technologies enabled a better exploration of this type of noncoding transcripts. The poor sequence conservation, however, complicates the identification and annotation of lncRNAs at a large scale. Wheat is among the leading food staples worldwide whose production is threatened by both biotic and abiotic stressors. Here, we identified putative lncRNAs from durum wheat varieties that differ in stem solidness, a major source of defense against wheat stem sawfly, a devastating insect pest. We also analyzed and annotated lncRNAs from two bread wheat varieties, resistant and susceptible to another destructive pest, orange wheat blossom midge, with and without infestation. Several putative lncRNAs contained potential precursor sequences and/or target regions for microRNAs, another type of regulatory noncoding RNAs, which may indicate functional networks. Interestingly, in contrast to lncRNAs themselves, microRNAs with potential precursors within the lncRNA sequences appeared to be highly conserved at the sequence and family levels. We also observed a few putative lncRNAs that have perfect to near-perfect matches to organellar genomes, supporting the recent observations that organellar genomes may contribute to the noncoding transcript pool of the cell.
Anti-Obesity Effects of Metformin: A Scoping Review Evaluating the Feasibility of Brown Adipose Tissue as a Therapeutic Target
Authors: Ziqubu Khanyisani , Mazibuko-Mbeje Sithandiwe E. , Mthembu Sinenhlanhla X. H. , Mabhida Sihle E. , Jack Babalwa U. , Nyambuya Tawanda M. , Nkambule Bongani B. , Basson Albertus K. , Tiano Luca , Dludla Phiwayinkosi V.
Published: January 2023

Brown adipose tissue (BAT) is increasingly recognized as the major therapeutic target to promote energy expenditure and ameliorate diverse metabolic complications. There is a general interest in understanding the pleiotropic effects of metformin against metabolic complications. Major electronic databases and search engines such as PubMed/MEDLINE, Google Scholar, and the Cochrane library were used to retrieve and critically discuss evidence reporting on the impact of metformin on regulating BAT thermogenic activity to ameliorate complications linked with obesity. The summarized evidence suggests that metformin can reduce body weight, enhance insulin sensitivity, and improve glucose metabolism by promoting BAT thermogenic activity in preclinical models of obesity. Notably, this anti-diabetic agent can affect the expression of major thermogenic transcriptional factors such as uncoupling protein 1 (UCP1), nuclear respiratory factor 1 (NRF1), and peroxisome-proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) to improve BAT mitochondrial function and promote energy expenditure. Interestingly, vital molecular markers involved in glucose metabolism and energy regulation such as AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21) are similarly upregulated by metformin treatment in preclinical models of obesity. The current review also discusses the clinical relevance of BAT and thermogenesis as therapeutic targets. This review explored critical components including effective dosage and appropriate intervention period, consistent with the beneficial effects of metformin against obesity-associated complications.
Comparative Efficacy of ALK Inhibitors for Treatment-Naïve ALK-Positive Advanced Non-Small Cell Lung Cancer with Central Nervous System Metastasis: A Network Meta-Analysis
Authors: Ando Koichi , Manabe Ryo , Kishino Yasunari , Kusumoto Sojiro , Yamaoka Toshimitsu , Tanaka Akihiko , Ohmori Tohru , Sagara Hironori
Published: January 2023

Central nervous system (CNS) metastases and acquired resistance complicate the treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC). Thus, this review aimed to provide a comprehensive overview of brain metastasis, acquired resistance, and prospects for overcoming these challenges. A network meta-analysis of relevant phase III randomized controlled trials was performed to compare the efficacies of multiple ALK inhibitors by drug and generation in overall patients with ALK-p untreated advanced NSCLC and a subgroup of patients with CNS metastases. The primary endpoint was progression-free survival (PFS). Generation-specific comparison results showed that third-generation ALK inhibitors were significantly more effective than second-generation ALK inhibitors in prolonging the PFS of the subgroup of patients with CNS metastases. Drug-specific comparison results demonstrated that lorlatinib was the most effective in prolonging PFS, followed by brigatinib, alectinib, ensartinib, ceritinib, crizotinib, and chemotherapy. While lorlatinib was superior to brigatinib for PFS in the overall patient population, no significant difference between the two was found in the subgroup of patients with CNS metastases. These results can serve as a foundation for basic, clinical, and translational research and guide clinical oncologists in developing individualized treatment strategies for patients with ALK-p, ALK inhibitor-naive advanced NSCLC.
Robustness of Breast Margins with Volumetric Modulated Arc Therapy without a Six-Degrees-of-Freedom Couch: A Dosimetric Evaluation
Authors: Prunaretty Jessica , Mir Nicolas , Tilhac Anaïs , Gouillou Maureen , Azria David , Fenoglietto Pascal , Bourgier Céline
Published: January 2023

In our hospital, a TrueBeam linear accelerator and the PerfectPitch 6-degrees-of-freedom (6-DOF) couch (Varian), with 7 mm margins, are used for volumetric modulated arc therapy (VMAT) of breast cancer (BC). This study tested whether a 3-degrees-of-freedom (3-DOF) couch, i.e., without rotation compensation (such as the Halcyon couch), affected dose metrics. A total of 446 daily extended cone beam computed tomography (CBCT) data of 20 patients who received VMAT for BC were used to recalculate the treatment plans with the session registration (6-DOF) and a simulated matching with 3-DOF. The initial plan provided significantly better coverage for internal mammary chain and clavicular lymph node clinical target volumes (CTVs) than the 6-DOF and 3-DOF CBCT plans. The volumes receiving 110% of the prescribed dose (V110%) were increased for all CTVs with the 6-DOF and 3-DOF CBCT plans, but the difference was significant only for the breast/chest wall CTV (p < 0.05; paired samples t-test). Protection of the heart and lungs was comparable among plans. The dose volume histograms based on the 6-DOF and 3-DOF data were similar for CTVs and organs at risk. Therefore, with a 7 mm margin, VMAT and a 3-DOF couch can be used for BC treatment without any compromise in delivery accuracy.
(R)-N-Benzyl-N-(1-phenylethyl)cyclohexanamine
Authors: García-González Ángel , Belda Leland , Manchado Alejandro , Nieto Carlos T. , Garrido Narciso Martín
Published: January 2023

The preparation and characterization of a new chiral tertiary dibenzylamine are described. These molecules are well known in the literature for their high neuropharmacological potential. The general synthetic pathway is based on asymmetric Aza–Michael addition of chiral (R)-N-benzyl-N-(α-methylbenzyl)amide to methyl cyclohex-1-en-carboxilate obtaining the β-amino ester, followed by carboxylic acid hydrolysis and subsequent Barton descarboxylation. Interestingly, it is a general synthetic procedure of a wide range of chiral amines by careful choice of insaturated esters and alkylation of the chiral enolate in the initial reaction. The new tertiary dibenzylamine molecule is fully characterized by NMR Spectroscopy (1H and 13C), as well by High-Resolution Mass Spectrometry and Infrared Spectroscopy.
On the Various Numerical Techniques for the Optimization of Bone Scaffold
Authors: Wu Jiongyi , Zhang Youwei , Lyu Yongtao , Cheng Liangliang
Published: January 2023

As the application of bone scaffolds becomes more and more widespread, the requirements for the high performance of bone scaffolds are also increasing. The stiffness and porosity of porous structures can be adjusted as needed, making them good candidates for repairing damaged bone tissues. However, the development of porous bone structures is limited by traditional manufacturing methods. Today, the development of additive manufacturing technology has made it very convenient to manufacture bionic porous bone structures as needed. In the present paper, the current state-of-the-art optimization techniques for designing the scaffolds and the settings of different optimization methods are introduced. Additionally, various design methods for bone scaffolds are reviewed. Furthermore, the challenges in designing high performance bone scaffolds and the future developments of bone scaffolds are also presented.
Experimental Study on the Damage Characteristics and Acoustic Properties of Red Sandstone with Different Water Contents under Microwave Radiation
Authors: Liu Junjun , Xie Jing , Yang Bengao , Li Fei , Deng Huchao , Yang Zundong , Gao Mingzhong
Published: January 2023

Rock breaking is one of the most basic issues in deep underground engineering. Water plays an important role in the rock response under microwave radiation. Consequently, microwave radiation experiments using red sandstone with different water contents were conducted. The damage characteristics and ultrasonic properties of red sandstone after microwave radiation were primarily investigated, and the representative conclusions were drawn as follows: With the increase in water content, the time of complete formation of the rupture surface of the rock sample gradually decreased, and the decreasing range gradually increased. When the fracture surface is completely formed, the samples with a higher water content have more powdery rock cuttings and less surface roughness. The damage degree of the samples does not increase significantly with the increase in the water content when the sample is radiated at the same time. As the microwave radiation time is increased, the damage degree of the sample will increase significantly. Through the ultrasonic velocity test, it can be suggested that the sample exhibits obvious zonal damage characteristics under the action of a microwave. Generally speaking, it is a very effective means of improving the degree of microwave attenuation of the rock by increasing the water content of the rock mass.
Two-Level 3D Column-like Nanofilms with Hexagonally–Packed Tantalum Fabricated via Anodizing of Al/Nb and Al/Ta Layers—A Potential Nano-Optical Biosensor
Authors: Pligovka Andrei , Lazavenka Andrei , Turavets Ulyana , Hoha Alexander , Salerno Marco
Published: January 2023

Reanodizing metal underlayers through porous anodic alumina has already been used extensively to fabricate ordered columns of different metal oxides. Here, we present similar 3D multilayered nanostructures with unprecedented complexity. Two-level 3D column-like nanofilms have been synthesized by anodizing an Al/Nb metal layer in aqueous oxalic acid for forming the first level, and an Al/Ta layer in aqueous tartaric acid for forming the second level of the structure. Both levels were then reanodized in aqueous boric acid. The Ta layer deposited on partially dissolved porous anodic alumina of the first level, with protruding tops of niobia columns, acquired a unique hexagonally-packed structure. The morphology of the first and second levels was determined using scanning electron microscopy. Prolonged etching for 24 h in a 50%wt aqueous phosphoric acid was used to remove the porous anodic alumina. The formation mechanism of aluminum phosphates on the second-level columns in the process of long-time cold etching is considered. The model for the growth of columns on a Ta hexagonally-packed structure of the second level is proposed and described. The described approach can be applied to create 3D two- or three-level column-like systems from various valve metals (Ta, Nb, W, Hf, V, Ti), their combinations and alloys, with adjustable column sizes and scaling. The results of optical simulation show a high sensitivity of two-level column-like 3D nanofilms to biomedical objects and liquids. Among potential applications of these two-level column-like 3D nanofilms are photonic crystals for full-color displays, chemical sensors and biosensor, solar cells and thermoresponsive shape memory polymers.
A Temperature-Dependent Viscoplasticity Model for the Hot Work Steel X38CrMoV5-3, Including Thermal and Cyclic Softening under Thermomechanical Fatigue Loading
Authors: Schlayer Markus , Warwas Marc , Seifert Thomas
Published: January 2023

In this paper, a temperature-dependent viscoplasticity model is presented that describes thermal and cyclic softening of the hot work steel X38CrMoV5-3 under thermomechanical fatigue loading. The model describes the softening state of the material by evolution equations, the material properties of which can be determined on the basis of a defined experimental program. A kinetic model is employed to capture the effect of coarsening carbides and a new isotropic cyclic softening model is developed that takes history effects during thermomechanical loadings into account. The temperature-dependent material properties of the viscoplasticity model are determined on the basis of experimental data measured in isothermal and thermomechanical fatigue tests for the material X38CrMoV5-3 in the temperature range between 20 and 650 ∘C. The comparison of the model and an existing model for isotropic softening shows an improved description of the softening behavior under thermomechanical fatigue loading. A good overall description of the experimental data is possible with the presented viscoplasticity model, so that it is suited for the assessment of operating loads of hot forging tools.
Effect of Bi Addition on the Heat Resistance of As-Extruded AZ31 Magnesium Alloy
Authors: Wang Qinghang , Zhai Haowei , Wang Li , Huang Lixin , Zhao Jun , Gao Yuyang , Jiang Bin
Published: January 2023

In this work, we investigate the impact of Bi addition on the heat resistance of as-extruded AZ31 alloy during high-temperature annealing and hot compression. Electron backscattered diffraction (EBSD) technique and quasi in situ scanning electron microscopy (SEM) are used to analyze the evolution of microstructures during high-temperature annealing and hot compression, respectively. The test results show that with a prolonged annealing time, the as-extruded AZB313 alloy exhibited a lower grain growth rate, due to the pinning effect of Mg3Bi2 phases distributed at grain boundaries. On the other hand, as the compressive temperature increased, the downtrend of strength is delayed in the as-extruded AZB313 alloy. Thermally stable Mg3Bi2 phases dispersed within the grains act as barriers, hindering the motion of dislocations, which not only provides a more effective precipitation strengthening effect, but also increases the resistance to deformation of grains. Moreover, grain boundary sliding can also be restricted by Mg3Bi2 phases located at grain boundaries. This work provides a new idea for the development of heat-resistant wrought Mg alloys.
Experimental Study on Different Improvement Schemes of EICP-Lignin Solidified Silt
Authors: Sun Yongshuai , Zhong Xinyan , Lv Jianguo , Wang Guihe , Hu Ruilin
Published: January 2023

In practical engineering applications, silt is prone to liquefaction and quicksand. This paper mainly studies the improvement effects of urease, lignin and their mixture on the strength and liquefaction resistance of silt. Based on the results and phenomena of an unconfined compressive strength and dynamic triaxial test, the improvement effects of the compressive strength, deformation resistance and liquefaction resistance of silt under different improvement schemes are analyzed, and the optimal values of the cement or lignin when enzyme-induced calcium carbonate precipitation (EICP) technology, lignin alone or EICP and lignin are obtained. The results show that the optimum concentration of the constant temperature and humidity sample (referred to as the constant humidity sample) and the constant temperature immersion sample (referred to as the soaking sample) of urease in the unconfined compressive strength test is 1.0 mol/L, and the compressive strength of the soaking sample is 4.9 MPa, which is 1.56 times that of the constant humidity sample; the optimum addition ratio of the lignin-improved constant humidity sample is 3%, and its compressive strength is 2.07 Mpa; the optimum addition ratio of the samples immersed at constant temperature is 4%, and the compressive strength is 3.05 MPa; when urease combines with lignin to improve silt, 4% is the best lignin addition ratio, the compressive strength of the constant humidity sample reaches 1.57 Mpa and the compressive strength of the soaking sample reaches 3.75 MPa; in the dynamic triaxial multi-stage cyclic load test, all samples were cured at constant humidity sample, and in the urease modified silt scheme, 1.0 mol/L was the optimal cement concentration; in the scheme of improving silt with lignin, 3% is the optimal addition ratio; when 1.25 mol/L cementation solution plus urease crude extract is combined with different ratios of lignin in the experimental scheme, 3% is the best lignin addition ratio.
Improving the p-Type CuCrO2 Thin Film’s Electrical and Optical Properties
Authors: Jiang Jiaxin , You Yu-Feng , Vasu Dhanapal , Chen Sheng-Chi , Chiu Te-Wei , Prashanth Gopi , Chen Po Chou
Published: January 2023

In this research, we studied the functional properties of CuCrO2, which is the most promising p-type transparent conductive oxide (TCO). The thin films were fabricated using a spin coating technique. The diffraction patterns were obtained with the help of X-ray diffractions, and the optical properties of absorption characteristics were studied using UV-visible absorption. The physical properties of film formation and surface morphology were analyzed using FESEM analysis. The aging properties were also analyzed with the help of various precursors with different aging times. The CuCrO2 thin films’ functional properties were determined by using chelating agent and precursor solution aging times. The CuCrO2 thin films have better transmittance, resistance, figure of merit (FOM), and electrical conductivity. Moreover, the resistivity values of the CuCrO2 thin films are 7.01, 9.90, 12.54, 4.10, 2.42, and 0.35 Ω cm. The current research article covers the preparation of copper chromium delafossite thin films. These thin films can be suitable for hole transport layers in transparent optoelectronic devices.
Investigation of the Tribological Behaviour of Various AMC Surfaces against Brake Lining Material
Authors: Hirsch Sarah Johanna , Eiselt Patrick , Ozdemir Ismail , Grund Thomas , Nestler Andreas , Lampke Thomas , Schubert Andreas
Published: January 2023

AlSi7Mg/SiCp aluminium matrix composites (AMCs) with a high ceramic content (35 vol.%) that were produced by using the field-assisted sintering technique (FAST) were subjected to tribological preconditioning and evaluated as a potential lightweight material to substitute grey cast iron brake discs. However, since an uncontrolled running-in process of the AMC surface can lead to severe wear and thus to failure of the friction system, AMC surfaces cannot be used directly after finishing and have to be preconditioned. A defined generation of a tribologically conditioned surface (tribosurface) is necessary, as was the aim in this study. To simulate tribological conditions in automotive brake systems, the prepared AMC samples were tested in a pin-on-disc configuration against conventional brake lining material under dry sliding conditions. The influence of the surface topography generated by face turning using different indexable inserts and feeds or an additional plasma electrolytic treatment was investigated at varied test pressures and sliding distances. The results showed that the coefficient of friction remained nearly constant when the set pressure was reached, whereas the initial topography of the samples studied by SEM varied substantially. A novel approach based on analysing the material ratio determined by 3D surface measurement was developed in order to obtain quantitative findings for industrial application.
Effect of Short-Term Ageing Treatment on Bending Force Behavior of Commercial Nickel-Titanium Archwire
Authors: Munir Asad , Razali Muhammad Fauzinizam , Hassan Muhammad Hafiz , Franz Gérald
Published: January 2023

Superelastic nickel–titanium (NiTi) archwires have become the preferred archwire for orthodontic alignment and the levelling stage due to their ability to exert a light force on teeth throughout a wide range of tooth movement. The magnitude and trend of the force exerted on the malposed tooth is influenced by the orthodontist’s consideration of the size and geometry of the NiTi archwire during orthodontic therapy. In this work, a novel approach of a short-term ageing treatment was utilized to modify the magnitude and trend of the bending force of a commercial superelastic NiTi archwire. The bending behavior of the superelastic NiTi archwire was altered by subjecting it to different temperatures in an ageing treatment for 15 min. The bending behavior of the aged NiTi archwire was examined using a three-point and three-bracket setup. The commercial NiTi archwire’s bending forces in both the three-point and three-bracket configurations were successfully altered by the 15 min ageing treatment. During unloading in the three-bracket arrangement, the NiTi archwires aged at 490 °C or 520 °C exhibited a lower magnitude and more consistent force compared to the NiTi archwires aged at 400 °C or 430 °C. Ageing the archwire for 15 min at 490 °C produced a suitable size of Ni4Ti3 precipitate, which makes the wire more flexible during bending and reduces the unloading force in the three-bracket bending configuration. The short-term aged NiTi archwire could be used to enhance the force delivery trend to the malposed tooth by lowering the amplitude of the force delivered and sustaining that force throughout the orthodontic treatment duration.
Classification of Thermally Degraded Concrete by Acoustic Resonance Method and Image Analysis via Machine Learning
Authors: Dvořák Richard , Chobola Zdeněk , Plšková Iveta , Hela Rudolf , Bodnárová Lenka
Published: January 2023

The study of the resistance of plain concrete to high temperatures is a current topic across the field of civil engineering diagnostics. It is a type of damage that affects all components in a complex way, and there are many ways to describe and diagnose this degradation process and the resulting condition of the concrete. With regard to resistance to high temperatures, phenomena such as explosive spalling or partial creep of the material may occur. The resulting condition of thermally degraded concrete can be assessed by a number of destructive and nondestructive methods based on either physical or chemical principles. The aim of this paper is to present a comparison of nondestructive testing of selected concrete mixtures and the subsequent classification of the condition after thermal degradation. In this sense, a classification model based on supervised machine learning principles is proposed, in which the thermal degradation of the selected test specimens are known classes. The whole test set was divided into five mixtures, each with seven temperature classes in 200 °C steps from 200 °C up to 1200 °C. The output of the paper is a comparison of the different settings of the classification model and validation algorithm in relation to the observed parameters and the resulting model accuracy. The classification is done by using parameters obtained by the acoustic NDT Impact-Echo method and image-processing tools.