bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of microRNA-135b Enhances Bone Metastasis in Prostate Cancer and Predicts Aggressiveness in Human Prostate Samples
Authors: Olivan Mireia , Garcia Marta , Suárez Leticia , Guiu Marc , Gros Laura , Méndez Olga , Rigau Marina , Reventós Jaume , Segura Miguel F. , de Torres Inés , Planas Jacques , de la Cruz Xavier , Gomis Roger R. , Morote Juan , Rodríguez-Barrueco Ruth , Santamaria Anna
Published: December 2021

About 70% of advanced-stage prostate cancer (PCa) patients will experience bone metastasis, which severely affects patients’ quality of life and progresses to lethal PCa in most cases. Hence, understanding the molecular heterogeneity of PCa cell populations and the signaling pathways associated with bone tropism is crucial. For this purpose, we generated an animal model with high penetrance to metastasize to bone using an intracardiac percutaneous injection of PC3 cells to identify PCa metastasis-promoting factors. Using genomic high-throughput analysis we identified a miRNA signature involved in bone metastasis that also presents potential as a biomarker of PCa progression in human samples. In particular, the downregulation of miR-135b favored the incidence of bone metastases by significantly increasing PCa cells’ migratory capacity. Moreover, the PLAG1, JAKMIP2, PDGFA, and VTI1b target genes were identified as potential mediators of miR-135b’s role in the dissemination to bone. In this study, we provide a genomic signature involved in PCa bone growth, contributing to a better understanding of the mechanisms responsible for this process. In the future, our results could ultimately translate into promising new therapeutic targets for the treatment of lethal PCa.
The Role of Breast Cancer Stem Cells in Chemoresistance and Metastasis in Triple-Negative Breast Cancer
Authors: He Lin , Wick Neda , Germans Sharon Koorse , Peng Yan
Published: December 2021

Triple negative breast cancer (TNBC) remains an aggressive disease due to the lack of targeted therapies and low rate of response to chemotherapy that is currently the main treatment modality for TNBC. Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors and recognized as drivers of tumorigenesis. TNBC tumors are characterized as being enriched for BCSCs. Studies have demonstrated the role of BCSCs as the source of metastatic disease and chemoresistance in TNBC. Multiple targets against BCSCs are now under investigation, with the considerations of either selectively targeting BCSCs or co-targeting BCSCs and non-BCSCs (majority of tumor cells). This review article provides a comprehensive overview of recent advances in the role of BCSCs in TNBC and the identification of cancer stem cell biomarkers, paving the way for the development of new targeted therapies. The review also highlights the resultant discovery of cancer stem cell targets in TNBC and the ongoing clinical trials treating chemoresistant breast cancer. We aim to provide insights into better understanding the mutational landscape of BCSCs and exploring potential molecular signaling pathways targeting BCSCs to overcome chemoresistance and prevent metastasis in TNBC, ultimately to improve the overall survival of patients with this devastating disease.
Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre
Authors: Gee Caroline , Fleuret Catherine , Wilson Ana , Levine Daniel , Elhusseiny Ramy , Muls Ann , Cunningham David , Kohoutova Darina
Published: December 2021

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019–January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 females, 66%) were diagnosed with BAM. Mean age was 59 +/− 12 years. The largest group were females with gynaecological cancer (35), followed by haematology group (15), colorectal/anal (13), prostate (9), upper gastrointestinal cancer (6), another previous malignancy (9). Severe BAM was most common in haematology (10/15; 67%) and gynaecological group (21/35; 60%). Medication and low-fat diet were commenced in 65/87 (75%), medication in 10/87 (11%), diet in 6/87 (7%). Colesevelam was used in 71/75 (95%). Symptoms improved in 74/87 (85%) patients. Vitamin D insufficiency/deficiency was diagnosed in 62/87 (71%), vitamin B12 deficiency in 39/87 (45%). BAM is a common condition in this cohort however treatments are highly effective.
Increased Replication Stress Determines ATR Inhibitor Sensitivity in Neuroblastoma Cells
Authors: King David , Southgate Harriet E. D. , Roetschke Saskia , Gravells Polly , Fields Leona , Watson Jessica B. , Chen Lindi , Chapman Devon , Harrison Daniel , Yeomanson Daniel , Curtin Nicola J. , Tweddle Deborah A. , Bryant Helen E.
Published: December 2021

Despite intensive high-dose multimodal therapy, high-risk neuroblastoma (NB) confers a less than 50% survival rate. This study investigates the role of replication stress in sensitivity to inhibition of Ataxia telangiectasia and Rad3-related (ATR) in pre-clinical models of high-risk NB. Amplification of the oncogene MYCN always imparts high-risk disease and occurs in 25% of all NB. Here, we show that MYCN-induced replication stress directly increases sensitivity to the ATR inhibitors VE-821 and AZD6738. PARP inhibition with Olaparib also results in replication stress and ATR activation, and sensitises NB cells to ATR inhibition independently of MYCN status, with synergistic levels of cell death seen in MYCN expressing ATR- and PARP-inhibited cells. Mechanistically, we demonstrate that ATR inhibition increases the number of persistent stalled and collapsed replication forks, exacerbating replication stress. It also abrogates S and G2 cell cycle checkpoints leading to death during mitosis in cells treated with an ATR inhibitor combined with PARP inhibition. In summary, increased replication stress through high MYCN expression, PARP inhibition or chemotherapeutic agents results in sensitivity to ATR inhibition. Our findings provide a mechanistic rationale for the inclusion of ATR and PARP inhibitors as a potential treatment strategy for high-risk NB.
The Novel Monoacylglycerol Lipase Inhibitor MJN110 Suppresses Neuroinflammation, Normalizes Synaptic Composition and Improves Behavioral Performance in the Repetitive Traumatic Brain Injury Mouse Model
Authors: Selvaraj Prabhuanand , Tanaka Mikiei , Wen Jie , Zhang Yumin
Published: December 2021

Modulation of the endocannabinoid system has emerged as an effective approach for the treatment of many neurodegenerative and neuropsychological diseases. However, the underlying mechanisms are still uncertain. Using a repetitive mild traumatic brain injury (mTBI) mouse model, we found that there was an impairment in locomotor function and working memory within two weeks post-injury, and that treatment with MJN110, a novel inhibitor of the principal 2-arachidononyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase dose-dependently ameliorated those behavioral changes. Spatial learning and memory deficits examined by Morris water maze between three and four weeks post-TBI were also reversed in the drug treated animals. Administration of MJN110 selectively elevated the levels of 2-AG and reduced the production of arachidonic acid (AA) and prostaglandin E2 (PGE2) in the TBI mouse brain. The increased production of proinflammatory cytokines, accumulation of astrocytes and microglia in the TBI mouse ipsilateral cerebral cortex and hippocampus were significantly reduced by MJN110 treatment. Neuronal cell death was also attenuated in the drug treated animals. MJN110 treatment normalized the expression of the NMDA receptor subunits NR2A and NR2B, the AMPA receptor subunits GluR1 and GluR2, and the GABAA receptor subunits α1, β2,3 and γ2, which were all reduced at 1, 2 and 4 weeks post-injury. The reduced inflammatory response and restored glutamate and GABA receptor expression likely contribute to the improved motor function, learning and memory in the MJN110 treated animals. The therapeutic effects of MJN110 were partially mediated by activation of CB1 and CB2 cannabinoid receptors and were eliminated when it was co-administered with DO34, a novel inhibitor of the 2-AG biosynthetic enzymes. Our results suggest that augmentation of the endogenous levels of 2-AG can be therapeutically useful in the treatment of TBI by suppressing neuroinflammation and maintaining the balance between excitatory and inhibitory neurotransmission.
MUT-7 Provides Molecular Insight into the Werner Syndrome Exonuclease
Authors: Hsu Tsung-Yuan , Hsu Ling-Nung , Chen Shih-Yu , Juang Bi-Tzen
Published: December 2021

Werner syndrome (WS) is a rare recessive genetic disease characterized by premature aging. Individuals with this disorder develop normally during childhood, but their physiological conditions exacerbate the aging process in late adolescence. WS is caused by mutation of the human WS gene (WRN), which encodes two main domains, a 3′-5′ exonuclease and a 3′-5′ helicase. Caenorhabditis elegans expresses human WRN orthologs as two different proteins: MUT-7, which has a 3′-5′ exonuclease domain, and C. elegans WRN-1 (CeWRN-1), which has only helicase domains. These unique proteins dynamically regulate olfactory memory in C. elegans, providing insight into the molecular roles of WRN domains in humans. In this review, we specifically focus on characterizing the function of MUT-7 in small interfering RNA (siRNA) synthesis in the cytoplasm and the roles of siRNA in directing nuclear CeWRN-1 loading onto a heterochromatin complex to induce negative feedback regulation. Further studies on the different contributions of the 3′-5′ exonuclease and helicase domains in the molecular mechanism will provide clues to the accelerated aging processes in WS.
HOPX Plays a Critical Role in Antiretroviral Drugs Induced Epigenetic Modification and Cardiac Hypertrophy
Authors: Kashyap Shiridhar , Rabbani Maryam , de Lima Isabela , Kondrachuk Olena , Patel Raj , Shafiei Mahnoush Sophia , Mukker Avni , Rajakumar Aishwarya , Gupta Manish Kumar
Published: December 2021

People living with HIV (PLWH) have to take an antiretroviral therapy (ART) for life and show noncommunicable illnesses such as chronic inflammation, immune activation, and multiorgan dysregulation. Recent studies suggest that long-term use of ART induces comorbid conditions and is one of the leading causes of heart failure in PLWH. However, the molecular mechanism of antiretroviral drugs (ARVs) induced heart failure is unclear. To determine the mechanism of ARVs induced cardiac dysfunction, we performed global transcriptomic profiling of ARVs treated neonatal rat ventricular cardiomyocytes in culture. Differentially expressed genes were identified by RNA-sequencing. Our data show that ARVs treatment causes upregulation of several biological functions associated with cardiotoxicity, hypertrophy, and heart failure. Global gene expression data were validated in cardiac tissue isolated from HIV patients having a history of ART. Interestingly, we found that homeodomain-only protein homeobox (HOPX) expression was significantly increased in cardiomyocytes treated with ARVs and in the heart tissue of HIV patients. Furthermore, we found that HOPX plays a crucial role in ARVs mediated cellular hypertrophy. Mechanistically, we found that HOPX plays a critical role in epigenetic regulation, through deacetylation of histone, while the HDAC inhibitor, Trichostatin A, can restore the acetylation level of histone 3 in the presence of ARVs.
Immuno-Metabolic Modulation of Liver Oncogenesis by the Tryptophan Metabolism
Authors: Trézéguet Véronique , Fatrouni Hala , Merched Aksam J.
Published: December 2021

Metabolic rewiring in tumor cells is a major hallmark of oncogenesis. Some of the oncometabolites drive suppressive and tolerogenic signals from the immune system, which becomes complicit to the advent and the survival of neoplasia. Tryptophan (TRP) catabolism through the kynurenine (KYN) pathway was reported to play immunosuppressive actions across many types of cancer. Extensive debate of whether the culprit of immunosuppression was the depletion of TRP or rather KYN accumulation in the tumor microenvironment has been ongoing for years. Results from clinical trials assessing the benefit of inhibiting key limiting enzymes of this pathway such as indoleamine 2,3-dioxygenase (IDO1) or tryptophan 2,3-dioxygenase (TDO2) failed to meet the expectations. Bearing in mind the complexity of the tumoral terrain and the existence of different cancers with IDO1/TDO2 expressing and non-expressing tumoral cells, here we present a comprehensive analysis of the TRP global metabolic hub and the driving potential of the process of oncogenesis with the main focus on liver cancers.
A Promising Combination: PACAP and PARP Inhibitor Have Therapeutic Potential in Models of Diabetic and Hypertensive Retinopathies
Authors: Pöstyéni Etelka , Szabadfi Krisztina , Sétáló György , Gabriel Robert
Published: December 2021

Diabetes and hypertension are complex pathologies with increasing prevalence nowadays. Their interconnected pathways are frequently manifested in retinopathies. Severe retinal consequences and their tight connections as well as their possible treatments are particularly important to retinal research. In the present, work we induced diabetes with streptozotocin in spontaneously hypertensive rats and treated them either with PACAP or olaparib and alternatively with both agents. Morphological and immunohistochemical analyses were carried out to describe cell-specific changes during pathologies and after different treatments. Diabetes and hypertension caused massive structural and cellular changes especially when they were elicited together. Hypertension was crucial in the formation of ONL and OPL damage while diabetes caused significant differences in retinal thickness, OPL thickness and in the cell number of the GCL. In diabetes, double neuroprotective treatment ameliorated changes of calbindin-positive cells, rod bipolar cells and dopaminergic amacrine cells. Double treatment was curative in hypertensive diabetic rat retinas, especially in the case of rod bipolar and parvalbumin-positive cells compared to untreated or single-treated retinas. Our results highlighted the promising therapeutic benefits of olaparib and PACAP in these severe metabolic retinal disorders.
Long-Term Treatment with Atypical Antipsychotic Iloperidone Modulates Cytochrome P450 2D (CYP2D) Expression and Activity in the Liver and Brain via Different Mechanisms
Authors: Danek Przemysław J. , Daniel Władysława A.
Published: December 2021

CYP2D enzymes engage in the synthesis of endogenous neuroactive substances (dopamine, serotonin) and in the metabolism of neurosteroids. The present work investigates the effect of iloperidone on CYP2D enzyme expression and activity in rat brains and livers. Iloperidone exerted a weak direct inhibitory effect on CYP2D activity in vitro in the liver and brain microsomes (Ki = 11.5 μM and Ki = 462 μM, respectively). However, a two-week treatment with iloperidone (1 mg/kg ip.) produced a significant decrease in the activity of liver CYP2D, which correlated positively with the reduced CYP2D1, CYP2D2 and CYP2D4 protein and mRNA levels. Like in the liver, iloperidone reduced CYP2D activity and protein levels in the frontal cortex and cerebellum but enhanced these levels in the nucleus accumbens, striatum and substantia nigra. Chronic iloperidone did not change the brain CYP2D4 mRNA levels, except in the striatum, where they were significantly increased. In conclusion, by affecting CYP2D activity in the brain, iloperidone may modify its pharmacological effect, via influencing the rate of dopamine and serotonin synthesis or the metabolism of neurosteroids. By elevating the CYP2D expression/activity in the substantia nigra and striatum (i.e., in the dopaminergic nigrostriatal pathway), iloperidone may attenuate extrapyramidal symptoms, while by decreasing the CYP2D activity and metabolism of neurosteroiods in the frontal cortex and cerebellum, iloperidone can have beneficial effects in the treatment of schizophrenia. In the liver, pharmacokinetic interactions involving chronic iloperidone and CYP2D substrates are likely to occur.
Repeated Low-Dose Acrolein Triggers Irreversible Lamina Propria Edema in Urinary Bladder, Transient Voiding Behavior and Widening of Eyes to Mechanical Stimuli
Authors: Lee Sanghee , Lee Jiwoo , Khimji Chandresh , Lee Jaebeom , Malkmus Shelle , Albo Michael , Yaksh Tony , Chiang George
Published: December 2021

Acrolein is a metabolite of cyclophosphamide (CYP), an alkylating agent used for a wide range of benign and malignant diseases. CYP treatments are known to trigger hemorrhagic cystitis in patients and animals. Significant effort has been made to prevent CYP/acrolein-induced cystitis, while still maintaining its therapeutic benefits. As a result, supplementary therapeutic options to mediate the protective role against CYP/acrolein and lower doses of CYP are currently given to targeted patients, as compared to past treatments. There is still a need to further study the effects of the repeated low-dose CYP/acrolein on the pathophysiology of the urinary bladder. In our study, a one-time treatment of acrolein and repeated low-dose acrolein triggered the thickening of the smooth muscle and lamina propria in the urinary bladder of C57BL/6J mice, respectively. The first dose of acrolein did not trigger voiding dysfunction, but the second dose triggered high-volume low-frequency voiding. Interestingly, our new scoring criteria and concurrent behavioral assessment revealed that mice with repeated low-dose acrolein had a wider opening of eyes in response to mechanical stimuli. Our study suggests that clinical symptoms among patients undergoing prolonged low-dose CYP may differ from previously reported symptoms of CYP-induced hemorrhagic cystitis.
Transcriptome Analysis of Induced Pluripotent Stem Cells and Neuronal Progenitor Cells, Derived from Discordant Monozygotic Twins with Parkinson’s Disease
Authors: Vlasov Ivan N. , Alieva Anelya Kh. , Novosadova Ekaterina V. , Arsenyeva Elena L. , Rosinskaya Anna V. , Partevian Suzanna A. , Grivennikov Igor A. , Shadrina Maria I.
Published: December 2021

Parkinson’s Disease (PD) is a widespread severe neurodegenerative disease that is characterized by pronounced deficiency of the dopaminergic system and disruption of the function of other neuromodulator systems. Although heritable genetic factors contribute significantly to PD pathogenesis, only a small percentage of sporadic cases of PD can be explained using known genetic risk factors. Due to that, it could be inferred that changes in gene expression could be important for explaining a significant percentage of PD cases. One of the ways to investigate such changes, while minimizing the effect of genetic factors on experiment, are the study of PD discordant monozygotic twins. In the course of the analysis of transcriptome data obtained from IPSC and NPCs, 20 and 1906 differentially expressed genes were identified respectively. We have observed an overexpression of TNF in NPC cultures, derived from twin with PD. Through investigation of gene interactions and gene involvement in biological processes, we have arrived to a hypothesis that TNF could play a crucial role in PD-related changes occurring in NPC derived from twins with PD, and identified INHBA, WNT7A and DKK1 as possible downstream effectors of TNF.
Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase
Authors: Franck Thierry , Ceusters Justine , Graide Hélène , Mouithys-Mickalad Ange , Serteyn Didier
Published: December 2021

Mesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodelling and wound healing, reducing tissue damage. Upon neutrophil activation, there is a release of myeloperoxidase (MPO), an oxidant enzyme. But little is known about the direct role of MSCs on MPO activity. The aim of this study was to investigate the effect of equine mesenchymal stem cells derived from muscle microinvasive biopsy (mdMSC) on the oxidant response of neutrophils and particularly on the activity of the myeloperoxidase released by stimulated equine neutrophils. After specific treatment (trypsin and washings in phosphate buffer saline), the mdMSCs were exposed to isolated neutrophils. The effect of the suspended mdMSCs was studied on the ROS production and the release of total and active MPO by stimulated neutrophils and specifically on the activity of MPO in a neutrophil-free model. Additionally, we developed a model combining adherent mdMSCs with neutrophils to study total and active MPO from the neutrophil extracellular trap (NET). Our results show that mdMSCs inhibited the ROS production, the activity of MPO released by stimulated neutrophils and the activity of MPO bound to the NET. Moreover, the co-incubation of mdMSCs directly with MPO results in a strong inhibition of the peroxidase activity of MPO, probably by affecting the active site of the enzyme. We confirm the strong potential of mdMSCs to lower the oxidant response of neutrophils. The novelty of our study is an evident inhibition of the activity of MPO by MSCs. The results indicated a new potential therapeutic approach of mdMSCs in the inhibition of MPO, which is considered as a pro-oxidant actor in numerous chronic and acute inflammatory pathologies.
Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma
Authors: Barr Jeffrey , Kruse Allison , Restaino Anthony , Tulina Natalia , Stuckelberger Sarah , Vermeer Samuel , Williamson Caitlin , Vermeer Daniel , Madeo Marianna , Stamp Jillian , Bell Maria , Morgan Mark , Yoon Ju-Yoon , Mitchell Marilyn , Budina Anna , Omran Dalia , Schwartz Lauren , Drapkin Ronny , Vermeer Paola
Published: December 2021

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular–nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics.
Wnt Inhibitory Factor 1 Binds to and Inhibits the Activity of Sonic Hedgehog
Authors: Kerekes Krisztina , Trexler Mária , Bányai László , Patthy László
Published: December 2021

The hedgehog (Hh) and Wnt pathways, crucial for the embryonic development and stem cell proliferation of Metazoa, have long been known to have similarities that argue for their common evolutionary origin. A surprising additional similarity of the two pathways came with the discovery that WIF1 proteins are involved in the regulation of both the Wnt and Hh pathways. Originally, WIF1 (Wnt Inhibitory Factor 1) was identified as a Wnt antagonist of vertebrates, but subsequent studies have shown that in Drosophila, the WIF1 ortholog serves primarily to control the distribution of Hh. In the present, work we have characterized the interaction of the human WIF1 protein with human sonic hedgehog (Shh) using Surface Plasmon Resonance spectroscopy and reporter assays monitoring the signaling activity of human Shh. Our studies have shown that human WIF1 protein binds human Shh with high affinity and inhibits its signaling activity efficiently. Our observation that the human WIF1 protein is a potent antagonist of human Shh suggests that the known tumor suppressor activity of WIF1 may not be ascribed only to its role as a Wnt inhibitor.
Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway
Authors: Kim So-Yeon , Oh Younseo , Jo Sungsin , Ji Jong-Dae , Kim Tae-Hwan
Published: December 2021

Aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor and regulates differentiation and function of various immune cells such as dendritic cells, Th17, and regulatory T cells. In recent studies, it was reported that AhR is involved in bone remodeling through regulating both osteoblasts and osteoclasts. However, the roles and mechanisms of AhR activation in human osteoclasts remain unknown. Here we show that AhR is involved in human osteoclast differentiation. We found that AhR expressed highly in the early stage of osteoclastogenesis and decreased in mature osteoclasts. Kynurenine (Kyn), formylindolo[3,4-b] carbazole (FICZ), and benzopyrene (BaP), which are AhR agonists, inhibited osteoclast formation and Kyn suppressed osteoclast differentiation at an early stage. Furthermore, blockade of AhR signaling through CH223191, an AhR antagonist, and knockdown of AhR expression reversed Kyn-induced inhibition of osteoclast differentiation. Overall, our study is the first report that AhR negatively regulates human osteoclast differentiation and suggests that AhR could be good therapeutic molecule to prevent bone destruction in chronic inflammatory diseases such as rheumatoid arthritis (RA).
Electrochemical Sensing of Interactions between DNA and Charged Macrocycles
Authors: Kulikova Tatjana , Padnya Pavel , Shiabiev Igor , Rogov Alexey , Stoikov Ivan , Evtugyn Gennady
Published: December 2021

In this work, we investigated aggregation of native DNA and thiacalix[4]arene derivative bearing eight terminal amino groups in cone configuration using various redox probes on the glassy carbon electrode. It was shown that sorption transfer of the aggregates on the surface of the electrode covered with carbon black resulted in changes in electrostatic interactions and diffusional permeability of the surface layer. Such changes alter the signals of ferricyanide ion, methylene green and hydroquinone as redox probes to a degree depending on their specific interactions with DNA and own charge. Inclusion of DNA in the surface layer was independently confirmed by scanning electron microscopy, electrochemical impedance spectroscopy and experiments with doxorubicin as a model intercalator. Thermal denaturing of DNA affected the charge separation on the electrode interface and the signals of redox probes. Using hydroquinone, less sensitive to electrostatic interactions, made it possible to determine from 10 pM to 1.0 nM doxorubicin (limit of detection 3 pM) after 10 min incubation. Stabilizers present in the commercial medications did not alter the signal. The DNA sensors developed can find future application in the assessment of the complexes formed by DNA and macrocycles as delivery agents for small chemical species.
Characteristics of Giant Cell Tumor of the Bone in Pediatric Patients: Our 18-Year, Single-Center Experience
Authors: Kim Woo-Jong , Kim Sungmin , Choi Dae-Woong , Lim Gil-Hwan , Jung Sung-Taek
Published: December 2021

A giant cell tumor (GCT) of the bone is characteristically found in skeletally mature patients. The tumor is rare in pediatric patients, and incidence reported in literature varies from 1.8% to 10.6%. We performed a retrospective study addressing symptoms, treatment, and outcome in pediatric patients who were diagnosed with GCT between March 1997 and January 2015 at our hospital. Fourteen (11.1%) of 126 surgically treated patients with histologically proven GCT were <19 years of age. We confirmed skeletal maturity using magnetic resonance imaging (MRI). Fourteen patients from 8 to 19 years old were identified. Sixteen lesions (76.2%) were found in long bones and 5 lesions (23.8%) in short bones. The most common site was around the knee in 8 patients (38%). GCTs mostly occur at the epi-metaphysis in 11 patients (52.3%). Regardless of the openness of epiphyseal plate, we observed GCT of bone in the epiphysis. Further study will be needed to prove the association between the presence of epiphyseal plate and location of tumor. Three patients (21.4%) had multicentric lesions, and four patients (28.5%) had local recurrence. Multicentric giant cell tumor and local recurrence occur more often in pediatric patients. The characteristics of GCT in pediatric patients do not differ from what is reported for GCT in adults.
Exploring the Outcomes That Matter Most to Young People Treated for Chronic Pain: A Qualitative Study
Authors: Joslin Rhiannon , Donovan-Hall Maggie , Roberts Lisa
Published: December 2021

Global and national policies state that all children and young people should be part of decision making and that outcomes that matter to them should take priority, yet patient-centred outcomes have been identified as a gap in the paediatric chronic pain literature. This study gave youths experiencing chronic pain a platform to have their views heard. Using novel methods, twenty-one young people, aged 11 to 18 years old, completed a semi-structured interview in which they constructed a timeline drawing to symbolise their treatment. They identified when aspects of their life changed (outcomes) and described the importance of these changes. Thematic analysis identified four themes that emerged at different stages of the treatment: “perfect storm”; “turning points”; “disconnect”; and; “free”. “Turning points” were points in time when the narrative of the young person took a turn in a different direction. At these points, the outcomes important to them also changed. Youths initially prioritised outcomes related to pain, then during treatment the focus became their emotional functioning, with role functioning and “going out” becoming the focus at the end. The stage of treatment as perceived by the young person impacted which outcomes mattered most.
Recent Climate Change in the Lake Kyoga Basin, Uganda: An Analysis Using Short-Term and Long-Term Data with Standardized Precipitation and Anomaly Indexes
Authors: Obubu John Peter , Mengistou Seyoum , Fetahi Tadesse , Alamirew Tena , Odong Robinson , Ekwacu Samuel
Published: December 2021

Climate change (CC) is now a global challenge due to uncertainties on the drivers and the multifaceted nature of its impacts. It impacts many sectors such as agriculture, water supply, and global economies through temperature and precipitation, affecting many livelihoods. Although there are global, regional, and national studies on CC, their application to determine local CC occurence mitigation and adaptation measures is not ideal. Therefore, this study aimed to determine climate change trends in Lake Kyoga Basin using standardized precipitation and anomaly indexes. Short-term (39 years, 1981–2020) and long-term (59 years, 1961–2020) monthly data from eight strategic meteorological stations were acquired from the Uganda National Meteorological Authority and supplemented with satellite and model reanalysis climate datasets. Change in precipitation was determined by SPI-6, while SAI determined change in temperature. The Mann–Kendall test was used to determine the trend significance. Whereas two (Serere and Lira) long-term data stations showed significant changes in precipitation, all the short-term data stations showed a significant increasing trend. Decadal relative rainfall anomaly increased from 85.6–105 in 1981–1990 to 92.0–120.9 in 2011–2020, while mean temperature anomaly increased from 0.2–0.6 °C to 1.0–1.6 °C in the same period. The frequency of severe wet weather events was more than for dry weather events in many stations, indicating an increase in precipitation. Maximum, mean, and minimum temperatures increased, with resultant warmer nights. The findings showed that the Lake Kyoga basin is experiencing climate change, with both temperature and rainfall increasing spatially and temporarily. Climate change affects agriculture, which is the main economic activity, and causes the destruction of infrastructure from floods, landslides, and mudslides. The results of this study are helpful in pointing out climate change-affected areas, and hence for designing mitigation and adaption strategies for local communities by policy and decision-makers from relevant stakeholders.
Enhancing Wear Resistance and Cutting Performance of a Long-Life Micro-Groove Tool in Turning AISI 201
Authors: Wu Jinxing , He Lin , Wu Yanying , Zhou Chaobiao , Zou Zhongfei , Zhan Gang , Zhou Tao , Du Feilong , Tian Pengfei , Zou Zichuan , Zhang Xiuhua
Published: December 2021

Tool-chip friction increases cutting temperature, aggravates tool wear, and shortens the service life of cutting tools. A micro-groove design of the rake face can improve the wear performance of the tool. In this study, we used the finite element simulation “Deform” to obtain the temperature field distribution of the tool rake face. The size of the micro-groove was determined by selecting a suitable temperature field combined with the characteristics of tool–chip flow in the cutting process, and the tool was prepared using powder metallurgy. The three-direction cutting forces and tool tip temperature were obtained by a cutting test. Compared with the original turning tool, the cutting force and cutting temperature of the micro-groove tool were reduced by more than 20%, the friction coefficient was reduced by more than 14%, the sliding energy was reduced and the shear energy was greatly decreased. According to the analysis of tool wear by SEM (scanning electron microscope) and EDS (energy dispersive X-ray spectroscopy), the crater wear, adhesive wear and oxidation wear of the micro-groove tool were lower than those of the original turning tool. In particular, the change in the crater wear area on the rake face of the original tool and the micro-groove tool was consistent with the cutting temperature and the wear width of the flank face. On the whole, the crater wear area and the change rate of the crater wear area of the micro-groove tool were smaller. Due to the proper microgroove structure of the rake face, the tool-chip contact area decreased, and the second rake angle of the tool became larger. Hence, the tool-chip friction, cutting forces, cutting energy consumption were reduced, tool wear was improved, and the service life of the micro-groove tool was five times longer than that of the original tool.
In Situ Polymerization to Boron Nitride-Fluorinated Poly Methacrylate Composites as Thin but Robust Anti-Corrosion Coatings
Authors: Hu Qingqing , Lv Aijuan , Ma Yukang , Wang Yan , Zhang Haoyi , Mi Xin , Xiao Qiang
Published: December 2021

High-performance anti-corrosion coatings featuring easy processability and thin thickness are highly desired in industry. Yet, solution process coating often faces a sedimentation problem with particles which are used as reinforcement in coatings. In this contribution, boron nitride (BN) was modified by an acrylate silane coupling agent (KH-570) to obtain acrylated BN flakes. Afterwards, the acrylated BN flakes were in situ copolymerized with 2-(perfluorohexyl)ethyl methacrylate to synthesize BN-fluorinated poly methacrylate (PFBP) composites. The as-obtained PFBP composites can form stable coating solutions, in which sedimentation of BN flakes seldom happens. The coating solution can easily form uniform coatings on various substrates with nanoscale thickness, confirmed by scanning electron microscope (SEM). The corrosion resistance of the samples coated PFBP coatings in 3.5 wt.% sodium chloride solution was evaluated by electrochemical impedance spectroscopy (EIS). It is indicated that the incorporation of BN flakes greatly reduce the corrosion rate. Adhesion measurements and abrasion resistance test indicate the PFBP coating performs good adhesion to substrate and robustness. Through the in situ polymerization, acrylated BN flakes are connected with the polymer chain, which inhibits the sedimentation of BN in the coating solution. Additionally, the BN flakes dispersed in the fluorinated polymer act as barriers, improving the corrosion resistance of the coated samples.
TS Fuzzy Robust Sampled-Data Control for Nonlinear Systems with Bounded Disturbances
Authors: Poongodi Thangavel , Mishra Prem Prakash , Lim Chee Peng , Saravanakumar Thangavel , Boonsatit Nattakan , Hammachukiattikul Porpattama , Rajchakit Grienggrai
Published: December 2021

We investigate robust fault-tolerant control pertaining to Takagi–Sugeno (TS) fuzzy nonlinear systems with bounded disturbances, actuator failures, and time delays. A new fault model based on a sampled-data scheme that is able to satisfy certain criteria in relation to actuator fault matrix is introduced. Specifically, we formulate a reliable controller with state feedback, such that the resulting closed-loop-fuzzy system is robust, asymptotically stable, and able to satisfy a prescribed H∞ performance constraint. Linear matrix inequality (LMI) together with a proper construction of the Lyapunov–Krasovskii functional is leveraged to derive delay-dependent sufficient conditions with respect to the existence of robust H∞ controller. It is straightforward to obtain the solution by using the MATLAB LMI toolbox. We demonstrate the effectiveness of the control law and less conservativeness of the results through two numerical simulations.
Enhanced X-ray Attenuating Efficiency of Silicon Dioxide Nanoparticles with Cesium Lead Bromide and 2,5-Diphenyloxazole Co-Embedded Therein
Authors: Choe Geunpyo , Kwon Hyemin , Ryu Ilhwan , Yim Sanggyu
Published: December 2021

An X-ray-attenuation-based in vivo imaging can be a promising candidate for real-time detection of cancer in an early stage due to its significantly longer penetration depth compared to currently investigated fluorescence-emission-based imaging techniques. It has recently been demonstrated that this novel concept of imaging is feasible using cesium lead bromide (CPB) quantum dots (QDs) stably embedded in silicon dioxide (SiO2) nanoparticles (NPs). However, further improvements are necessary to realize its practical use, especially in terms of X-ray attenuation efficiency. In this study, we have found that the X-ray attenuation capability of CPB/SiO2 NPs was significantly enhanced by embedding an organic X-ray scintillator, 2,5-diphenyloxazole (PPO), together with CPB QDs in the NPs. The embedment not only solved the water dispersibility and stability problem of PPO, but also significantly increased the Hounsfield unit of the NPs, which was proportional to the degree of X-ray attenuation, by 2.7 times.
The Role of Cations of the Precipitant in the Interaction of Protein Molecules in the Lysozyme Oligomers in Crystallization Solutions
Authors: Kordonskaya Yuliya V. , Timofeev Vladimir I. , Dyakova Yulia A. , Marchenkova Margarita A. , Pisarevsky Yury V. , Kovalchuk Mikhail V.
Published: December 2021

At the moment, the main opinion is that protein crystallization depends mainly on the the precipitant anions, therefore, there have been only few works devoted to the problem of the influence of its cations. Using the molecular dynamics method, we investigated the stability, changes in the compactness and structural transformations of lysozyme dimers and octamers in solutions with different precipitants (LiCl, NaCl, KCl and CuCl2) in order to study the contribution of cations during crystal formation in more detail. As a result, we found that cations have a rather noticeable effect on the behavior of oligomers: the higher the atomic mass of the cation, the greater the changes in the dimers structures during its dynamics and, according to the data of SAXS experiments, the lower the concentration of dimers. However, for octamers, this dependence is more complicated.
Assessment of Globularity of Protein Structures via Minimum Volume Ellipsoids and Voxel-Based Atom Representation
Authors: Banach Mateusz
Published: December 2021

A computer algorithm for assessment of globularity of protein structures is presented. By enclosing the input protein in a minimum volume ellipsoid (MVEE) and calculating a profile measuring how voxelized space within this shape (cubes on a uniform grid) is occupied by atoms, it is possible to estimate how well the molecule resembles a globule. For any protein to satisfy the proposed globularity criterion, its ellipsoid profile (EP) should first confirm that atoms adequately fill the ellipsoid’s center. This property should then propagate towards the surface of the ellipsoid, although with diminishing importance. It is not required to compute the molecular surface. Globular status (full or partial) is assigned to proteins with values of their ellipsoid profiles, called here the ellipsoid indexes (EI), above certain levels. Due to structural outliers which may considerably distort the measurements, a companion method for their detection and reduction of their influence is also introduced. It is based on kernel density estimation and is shown to work well as an optional input preparation step for MVEE. Finally, the complete workflow is applied to over two thousand representatives of SCOP 2.08 domain superfamilies, surveying the landscape of tertiary structure of proteins from the Protein Data Bank.
Grain Boundary Wetting Phenomena in High Entropy Alloys Containing Nitrides, Carbides, Borides, Silicides, and Hydrogen: A Review
Authors: Straumal Boris , Rabkin Eugen , Lopez Gabriel A. , Korneva Anna , Kuzmin Alexei , Gornakova Alena , Straumal Alexander , Baretzky Brigitte
Published: December 2021

In this review, we analyze the structure of multicomponent alloys without principal components (they are also called high entropy alloys—HEAs), containing not only metals but also hydrogen, nitrogen, carbon, boron, or silicon. In particular, we discuss the phenomenon of grain boundary (GB) wetting by the melt or solid phase. The GB wetting can be complete or incomplete (partial). In the former case, the grains of the matrix are completely separated by the continuous layer of the second phase (solid or liquid). In the latter case of partial GB wetting, the second solid phase forms, between the matrix grains, a chain of (usually lenticular) precipitates or droplets with a non-zero value of the contact angle. To deal with the morphology of GBs, the new GB tie-lines are used, which can be constructed in the two- or multiphase areas of the multidimensional HEAs phase diagrams. The GBs in HEAs in the case of complete or partial wetting can also contain hydrides, nitrides, carbides, borides, or silicides. Thus, GB wetting by the hydrides, nitrides, carbides, borides, or silicides can be used in the so-called grain boundary chemical engineering in order to improve the properties of respective HEAs.
The Application of Organic Phosphate Nucleating Agents in Polypropylene with Different Molecular Weights
Authors: Li Juan , Liang Zhaohua , Gao Chengtao , Luo Shanshan , Huang Shaowen , Zhang Daohai , Qin Shuhao
Published: December 2021

Two kinds of organic phosphate nucleating agent (NA-11 and NA-21) were used in PP with different molecular weights through the melt extrusion method. The dispersibility of the nucleating agents in PP, and the effect of the nucleating agents on the molecular weight, rheological behavior and crystallization behavior of PP were investigated. SEM and TEM analysis showed that the average radius of the dispersed particles (nucleating agents) was larger in LPP than that in HPP. The good dispersion of NA-21 also created more nucleation embryos for the adsorption of polypropylene molecules than the agglomerated NA-11. The gel permeation chromatography (GPC) analysis showed that the average molecular weight of HPP and LPP both decreased with the addition of a nucleating agent. The rotational rheometer and capillary rheometer analysis showed that the effect of NA-21 on reducing intermolecular entanglement was more significant, whether in HPP or LPP. The addition of NA-21 had less elastic energy storage and better flow stability, and could be processed at a higher speed. Simultaneously, the relaxation time in the blends with LPP was shorter than that with HPP. It was found that the crystallinity and nucleation efficiency of HPP/nucleating agent blends increased remarkably, while there was a barely perceptible increase in LPP/nucleating agent blends.
Modification of FA0.85MA0.15Pb(I0.85Br0.15)3 Films by NH2-POSS
Authors: Zhang Yangyang , Liu Na , Xie Haipeng , Liu Jia , Yuan Pan , Wei Junhua , Zhao Yuan , Yang Baopeng , Zhang Jianhua , Wang Shitan , Huang Han , Niu Dongmei , Chen Qi , Gao Yongli
Published: December 2021

The surface composition and morphology of FA0.85MA0.15Pb(I0.85Br0.15)3 films fabricated by the spin-coating method with different concentrations of NH2-POSS were investigated with atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), angle-resolved X-ray photoelectron spectroscopy (AR-XPS), and Fourier transform infrared spectroscopy (FTIR). It was found that the surface composition of the FA0.85MA0.15Pb(I0.85Br0.15)3 films was changed regularly through the interaction between NH2-POSS and the perovskite film. The corresponding surface morphological changes were also observed. When the concentration of NH2-POSS exceeded 10 mg/mL, a lot of cracks on the surface of the perovskite film were observed and the surface morphology was damaged. The surface composition and its distribution can be adjusted by changing the concentration of NH2-POSS and the proper concentration of NH2-POSS can substantially improve the quality of perovskite film.
Tuning Charge Order in (TMTTF)2X by Partial Anion Substitution
Authors: Pustogow Andrej , Dizdarevic Daniel , Erfort Sebastian , Iakutkina Olga , Merkl Valentino , Untereiner Gabriele , Dressel Martin
Published: December 2021

In the quasi-one-dimensional (TMTTF)2X compounds with effectively quarter-filled bands, electronic charge order is stabilized from the delicate interplay of Coulomb repulsion and electronic bandwidth. The correlation strength is commonly tuned by physical pressure or chemical substitution with stoichiometric ratios of anions and cations. Here, we investigate the charge-ordered state through partial substitution of the anions in (TMTTF)2[AsF6]1−x[SbF6]x with x≈0.3, determined from the intensity of infrared vibrations, which is sufficient to suppress the spin-Peierls state. Our dc transport experiments reveal a transition temperature TCO = 120 K and charge gap ΔCO=430 K between the values of the two parent compounds (TMTTF)2AsF6 and (TMTTF)2SbF6. Upon plotting the two parameters for different (TMTTF)2X, we find a universal relationship between TCO and ΔCO yielding that the energy gap vanishes for transition temperatures TCO≤60 K. While these quantities indicate that the macroscopic correlation strength is continuously tuned, our vibrational spectroscopy results probing the local charge disproportionation suggest that 2δ is modulated on a microscopic level.