bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond
Authors: Chen Shang-Der , Yang Jenq-Lin , Hsieh Yi-Heng , Lin Tsu-Kung , Lin Yi-Chun , Chao A-Ching , Yang Ding-I
Published: September 2021

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.
Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy
Authors: Di Somma Sarah , Napolitano Fabiana , Portella Giuseppe , Malfitano Anna Maria
Published: September 2021

Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the interplay in tumor microenvironment between macrophages and mesenchymal stem cells and macrophages and fibroblasts. In particular, cell–cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumor phenotypes induced in macrophages. Nonetheless, in the context of virotherapy, the response of macrophages as a consequence of treatment with oncolytic viruses will be analyzed regarding their polarization status and their pro/anti-tumor response.
Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer’s and Parkinson’s Diseases
Authors: Lam Simon , Hartmann Nils , Benfeitas Rui , Zhang Cheng , Arif Muhammad , Turkez Hasan , Uhlén Mathias , Englert Christoph , Knight Robert , Mardinoglu Adil
Published: September 2021

Neurodegenerative diseases, including Alzheimer’s (AD) and Parkinson’s diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analysed transcriptomic data from AD and PD patients, and stratified these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identified retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrated that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.
Bio-Specific Au/Fe3+ Porous Spongy Nanoclusters for Sensitive SERS Detection of Escherichia coli O157:H7
Authors: Li Yuzhi , Gao Fei , Lu Chang , Fauconnier Marie-Laure , Zheng Jinkai
Published: September 2021

For sensitive and fast detection of Escherichia coli O157:H7, organic and inorganic hybrid Au/Fe3+ nanoclusters (NCs) were synthesized for the first time using gold nanoparticles (GNPs), bovine serum albumin, ferric chloride, phosphate-buffered saline, and antibodies. The Au/Fe3+ porous spongy NCs with large surface area showed excellent bio-specific capability for E. coli O157:H7. GNPs in Au/Fe3+ NCs functioned as signal enhancers, significantly increasing the Raman signal via the metathesis reaction product of Prussian blue and obviously improving the detection sensitivity. We combined the novel Au/Fe3+ NCs with antibody-modified magnetic nanoparticles to create a biosensor capable of sensitive detection of E. coli O157:H7, which showed a good linear response (101 to 106 cfu/mL), high detection sensitivity (2 cfu/mL), and good recovery rate (93.60–97.50%) in spiked food samples. These results make the biosensor well-suited for food safety monitoring. This strategy achieves the goal of sensitive and quantitative detection of E. coli O157:H7.
The Regional EEG Pattern of the Sleep Onset Process in Older Adults
Authors: Gorgoni Maurizio , Scarpelli Serena , Annarumma Ludovica , D’Atri Aurora , Alfonsi Valentina , Ferrara Michele , De Gennaro Luigi
Published: September 2021

Healthy aging is characterized by macrostructural sleep changes and alterations of regional electroencephalographic (EEG) sleep features. However, the spatiotemporal EEG pattern of the wake-sleep transition has never been described in the elderly. The present study aimed to assess the topographical and temporal features of the EEG during the sleep onset (SO) in a group of 36 older participants (59–81 years). The topography of the 1 Hz bins’ EEG power and the time course of the EEG frequency bands were assessed. Moreover, we compared the delta activity and delta/beta ratio between the older participants and a group of young adults. The results point to several peculiarities in the elderly: (a) the generalized post-SO power increase in the slowest frequencies did not include the 7 Hz bin; (b) the alpha power revealed a frequency-specific pattern of post-SO modifications; (c) the sigma activity exhibited only a slight post-SO increase, and its highest bins showed a frontotemporal power decrease. Older adults showed a generalized reduction of delta power and delta/beta ratio in both pre- and post-SO intervals compared to young adults. From a clinical standpoint, the regional EEG activity may represent a target for brain stimulation techniques to reduce SO latency and sleep fragmentation.
State Attachment Variability: Between- and within-Person Level Associations with Trait Attachment and Psychological Problems
Authors: Verhees Martine W. F. T. , Ceulemans Eva , Bakermans-Kranenburg Marian J. , Bosmans Guy
Published: September 2021

Research suggests that inter-individual differences in the degree of state attachment variability are related to differences in trait attachment and psychological problems between children. In this study, we tested whether such associations are also relevant at a within-person level, and if so, whether intra-individual fluctuations in the degree of variability were predictive of or predicted by intra-individual fluctuations in trait attachment and psychological problems. Children (N = 152; Mage = 10.41 years, SDage = 0.60 at time 1) were tested three times over a period of one year. At each timepoint, children reported on their expectations of maternal support in different distressing situations. Additionally, we administered measures of trait attachment to children and psychological problems to children and their mothers. We used Random-Intercept Cross-Lagged Panel Models to distinguish between-person from within-person associations between these constructs over time. The results revealed that the degree of state attachment variability was mainly relevant to understand differences between children in trait attachment and psychological problems: children who overall showed more state attachment variability were overall less securely attached at a trait-level and reported more psychological problems. Although evidence for within-person associations was less robust, there was some indication that the degree of state attachment variability might be related to the development of trust and psychological problems at a within-person level.
The Association between a MAOB Variable Number Tandem Repeat Polymorphism and Cocaine and Opiate Addictions in Polyconsumers
Authors: Mateu César , Rodríguez-Arias Marta , Gil-Miravet Isis , Benito Ana , Tomás José M. , Haro Gonzalo
Published: September 2021

Genetic analysis of the association between alcohol, cocaine, and opiate addiction and variable number tandem repeat (VNTR) polymorphisms in monoamine oxidase B (MAOB) and serotonergic 5-hydroxytryptamine (serotonin) receptor 1B and 2C (HTR1B 21 and HTR2C) pathway genes was performed in a sample of 302 polyconsumers. Our genetic association analysis revealed a significant association between a 184 base pair (bp) VNTR polymorphism in the MAOB gene and addiction to cocaine and opiates. This work highlights new genetic marker associations in cocaine and opiate polyconsumer addictions. These data help to clarify and quantify the complex role of genetics in addictive disorders, as well as their future contribution to the prevention (genetic counselling), diagnosis (genetic diagnosis of vulnerability), and treatment (pharmacogenomics) of these disorders.
On the Specificity and Permanence of Electroencephalography Functional Connectivity
Authors: Zhang Yibo , Li Ming , Shen Hui , Hu Dewen
Published: September 2021

Functional connectivity, representing a statistical coupling relationship between different brain regions or electrodes, is an influential concept in clinical medicine and cognitive neuroscience. Electroencephalography-derived functional connectivity (EEG-FC) provides relevant characteristic information about individual differences in cognitive tasks and personality traits. However, it remains unclear whether these individual-dependent EEG-FCs remain relatively permanent across long-term sessions. This manuscript utilizes machine learning algorithms to explore the individual specificity and permanence of resting-state EEG connectivity patterns. We performed six recordings at different intervals during a six-month period to examine the variation and permanence of resting-state EEG-FC over a long period. The results indicated that the EEG-FC networks are quite subject-specific with a high-precision identification accuracy of greater than 90%. Meanwhile, the individual specificity remained stable and only varied slightly after six months. Furthermore, the specificity is mainly derived from the internal connectivity of the frontal lobe. Our work demonstrates the existence of specific and permanent EEG-FC patterns in the brain, providing potential information for biometric applications.
Brain Region and Cell Compartment Dependent Regulation of Electron Transport System Components in Huntington’s Disease Model Mice
Authors: Burtscher Johannes , Pepe Giuseppe , Marracino Federico , Capocci Luca , Giova Susy , Millet Grégoire P. , Di Pardo Alba , Maglione Vittorio
Published: September 2021

Huntington’s disease (HD) is a rare hereditary neurodegenerative disorder characterized by multiple metabolic dysfunctions including defects in mitochondrial homeostasis and functions. Although we have recently reported age-related changes in the respiratory capacities in different brain areas in HD mice, the precise mechanisms of how mitochondria become compromised in HD are still poorly understood. In this study, we investigated mRNA and protein levels of selected subunits of electron transport system (ETS) complexes and ATP-synthase in the cortex and striatum of symptomatic R6/2 mice. Our findings reveal a brain-region-specific differential expression of both nuclear and mitochondrial-encoded ETS components, indicating defects of transcription, translation and/or mitochondrial import of mitochondrial ETS components in R6/2 mouse brains.
Ottoman Mosques in Albania: Building Acoustic Exploration inside Five Case Studies
Authors: Sukaj Silvana , Bevilacqua Antonella , Ciaburro Giuseppe , Iannace Gino , Trematerra Amelia
Published: September 2021

The Ottoman mosques of the 15th and 16th centuries represent an architectural typology that has been replicated in territories out of the Middle East for as long as Islam spread its influence on other countries. This paper deals with the determination of the acoustic properties inside a few Ottoman mosques located in different cities of Albania, specifically in Elbasan, Berat, Kavaja, Tirana and Shkodra. A comparison between the prayer rooms of these five mosques has been undertaken in terms of the main acoustic parameters by following the standard requirements outlined in ISO 3382-1. The architectural characteristics of the single-unit mosques chosen for this research study are determined by the domed-square musalla, which has a comparable volume size among all five mosques. Results gathered by the acoustic measurements undertaken in unoccupied conditions highlight an overall lack of speech understanding given the values of some acoustic parameters fairly acceptable. This outcome is justified by the geometrical configuration, worsened by the presence of a dome that creates a focusing effect of the sound rays, and by the reflecting finish materials applied to walls and roof that facilitate the build-up defect of echoes.
Imaging-Guided Evaluation of the Novel Small-Molecule Benzosuberene Tubulin-Binding Agent KGP265 as a Potential Therapeutic Agent for Cancer Treatment
Authors: Guo Yihang , Wang Honghong , Gerberich Jeni L. , Odutola Samuel O. , Charlton-Sevcik Amanda K. , Li Maoping , Tanpure Rajendra P. , Tidmore Justin K. , Trawick Mary Lynn , Pinney Kevin G. , Mason Ralph P. , Liu Li
Published: September 2021

The selective disruption of tumor-associated vasculature represents an attractive therapeutic approach. We have undertaken the first in vivo evaluation of KGP265, a water-soluble prodrug of a benzosuberene-based tubulin-binding agent, and found promising vascular-disrupting activity in three distinct tumor types. Dose escalation in orthotopic MDA-MB-231-luc breast tumor xenografts in mice indicated that higher doses produced more effective vascular shutdown, as revealed by dynamic bioluminescence imaging (BLI). In syngeneic orthotopic 4T1-luc breast and RENCA-luc kidney tumors, dynamic BLI and oxygen enhanced multispectral optoacoustic tomography (OE-MSOT) were used to compare vascular shutdown following the administration of KGP265 (7.5 mg/kg). The BLI signal and vascular oxygenation response (ΔsO2) to a gas breathing challenge were both significantly reduced within 2 h, indicating vascular disruption, which continued over 24 h. A correlative histology confirmed increased necrosis and hemorrhage. Twice-weekly doses of KGP265 caused significant growth delay in both MDA-MB-231 and 4T1 breast tumors, with no obvious systemic toxicity. A combination with carboplatin produced significantly greater tumor growth delay than carboplatin alone, though significant carboplatin-associated toxicity was observed (whole-body weight loss). KGP265 was found to be effective at low concentrations, generating long-term vascular shutdown and tumor growth delay, thus providing strong rationale for further development, particularly in combination therapies.
The Role of the Hedgehog Pathway in Cholangiocarcinoma
Authors: Anichini Giulia , Carrassa Laura , Stecca Barbara , Marra Fabio , Raggi Chiara
Published: September 2021

Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.
HER2 Signaling and Breast Cancer Stem Cells: The Bridge behind HER2-Positive Breast Cancer Aggressiveness and Therapy Refractoriness
Authors: Pupa Serenella M. , Ligorio Francesca , Cancila Valeria , Franceschini Alma , Tripodo Claudio , Vernieri Claudio , Castagnoli Lorenzo
Published: September 2021

HER2 overexpression/amplification occurs in 15–20% of breast cancers (BCs) and identifies a highly aggressive BC subtype. Recent clinical progress has increased the cure rates of limited-stage HER2-positive BC and significantly prolonged overall survival in patients with advanced disease; however, drug resistance and tumor recurrence remain major concerns. Therefore, there is an urgent need to increase knowledge regarding HER2 biology and implement available treatments. Cancer stem cells (CSCs) represent a subset of malignant cells capable of unlimited self-renewal and differentiation and are mainly considered to contribute to tumor onset, aggressiveness, metastasis, and treatment resistance. Seminal studies have highlighted the key role of altered HER2 signaling in the maintenance/enrichment of breast CSCs (BCSCs) and elucidated its bidirectional communication with stemness-related pathways, such as the Notch and Wingless/β-catenin cascades. d16HER2, a splice variant of full-length HER2 mRNA, has been identified as one of the most oncogenic HER2 isoform significantly implicated in tumorigenesis, epithelial-mesenchymal transition (EMT)/stemness and the response to targeted therapy. In addition, expression of a heterogeneous collection of HER2 truncated carboxy-terminal fragments (CTFs), collectively known as p95HER2, identifies a peculiar subgroup of HER2-positive BC with poor prognosis, with the p95HER2 variants being able to regulate CSC features. This review provides a comprehensive overview of the current evidence regarding HER2-/d16HER2-/p95HER2-positive BCSCs in the context of the signaling pathways governing their properties and describes the future prospects for targeting these components to achieve long-lasting tumor control.
Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development
Authors: Kowalczyk Wojciech , Waliszczak Grzegorz , Jach Robert , Dulińska-Litewka Joanna
Published: September 2021

Breast cancer remains one of the most important health problems worldwide. The family of steroid receptors (SRs), which comprise estrogen (ER), progesterone (PR), androgen (AR), glucocorticoid (GR) and mineralocorticoid (MR) receptors, along with a receptor for a secosteroid—vitamin D, play a crucial role in the pathogenesis of the disease. They function predominantly as nuclear receptors to regulate gene expression, however, their full spectrum of action reaches far beyond this basic mechanism. SRs are involved in a vast variety of interactions with other proteins, including extensive crosstalk with each other. How they affect the biology of a breast cell depends on such factors as post-translational modifications, expression of coregulators, or which SR isoform is predominantly synthesized in a given cellular context. Although ER has been successfully utilized as a breast cancer therapy target for years, research on therapeutic application of other SRs is still ongoing. Designing effective hormone therapies requires thorough understanding of the molecular function of the SRs. Over the past decades, huge amount of data was obtained in multiple studies exploring this field, therefore in this review we attempt to summarize the current knowledge in a comprehensive way.
Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC
Authors: Mann Jacqueline E , Ludwig Megan L , Kulkarni Aditi , Scheftz Erin B , Murray Isabel R , Zhai Jingyi , Gensterblum-Miller Elizabeth , Jiang Hui , Brenner J Chad
Published: September 2021

As immunotherapies targeting the PDL1 checkpoint have become a mainstay of treatment for a subset of head and neck squamous cell carcinoma (HNSCC) patients, a detailed understanding of the mechanisms underlying PDL1-mediated immune evasion is needed. To elucidate factors regulating expression of PDL1 in HNSCC cells, a genome-wide CRISPR profiling approach was implemented to identify genes and pathways conferring altered PDL1 expression in an HNSCC cell line model. Our screen nominated several candidate PDL1 drivers, including Toll-like Receptor 2 (TLR2). Depletion of TLR2 blocks interferon-γ-induced PDL1 expression, and stimulation of TLR2 with either Staphylococcus aureus or a bacterial lipopeptide mimetic, Pam3CSK4, enhanced PDL1 expression in multiple models. The data herein demonstrate a role for TLR2 in modulating the expression of PDL1 in HNSCC models and suggest that microbiota may directly modulate immunosuppression in cancer cells. Our study represents a step toward disentangling the diverse pathways and stimuli regulating PDL1 expression in HNSCC and underscores a need for future work to characterize the complex microbiome in HNSCC patients treated with immunotherapy.
MEIS2 Is an Adrenergic Core Regulatory Transcription Factor Involved in Early Initiation of TH-MYCN-Driven Neuroblastoma Formation
Authors: De Wyn Jolien , Zimmerman Mark W. , Weichert-Leahey Nina , Nunes Carolina , Cheung Belamy B. , Abraham Brian J. , Beckers Anneleen , Volders Pieter-Jan , Decaesteker Bieke , Carter Daniel R. , Look Alfred Thomas , De Preter Katleen , Van Loocke Wouter , Marshall Glenn M. , Durbin Adam D. , Speleman Frank , Durinck Kaat
Published: September 2021

Roughly half of all high-risk neuroblastoma patients present with MYCN amplification. The molecular consequences of MYCN overexpression in this aggressive pediatric tumor have been studied for decades, but thus far, our understanding of the early initiating steps of MYCN-driven tumor formation is still enigmatic. We performed a detailed transcriptome landscaping during murine TH-MYCN-driven neuroblastoma tumor formation at different time points. The neuroblastoma dependency factor MEIS2, together with ASCL1, was identified as a candidate tumor-initiating factor and shown to be a novel core regulatory circuit member in adrenergic neuroblastomas. Of further interest, we found a KEOPS complex member (gm6890), implicated in homologous double-strand break repair and telomere maintenance, to be strongly upregulated during tumor formation, as well as the checkpoint adaptor Claspin (CLSPN) and three chromosome 17q loci CBX2, GJC1 and LIMD2. Finally, cross-species master regulator analysis identified FOXM1, together with additional hubs controlling transcriptome profiles of MYCN-driven neuroblastoma. In conclusion, time-resolved transcriptome analysis of early hyperplastic lesions and full-blown MYCN-driven neuroblastomas yielded novel components implicated in both tumor initiation and maintenance, providing putative novel drug targets for MYCN-driven neuroblastoma.
Targeting Acute Myeloid Leukemia Using the RevCAR Platform: A Programmable, Switchable and Combinatorial Strategy
Authors: Kittel-Boselli Enrico , Soto Karla Elizabeth González , Loureiro Liliana Rodrigues , Hoffmann Anja , Bergmann Ralf , Arndt Claudia , Koristka Stefanie , Mitwasi Nicola , Kegler Alexandra , Bartsch Tabea , Berndt Nicole , Altmann Heidi , Fasslrinner Frederick , Bornhäuser Martin , Bachmann Michael Philipp , Feldmann Anja
Published: September 2021

Clinical translation of novel immunotherapeutic strategies such as chimeric antigen receptor (CAR) T-cells in acute myeloid leukemia (AML) is still at an early stage. Major challenges include immune escape and disease relapse demanding for further improvements in CAR design. To overcome such hurdles, we have invented the switchable, flexible and programmable adaptor Reverse (Rev) CAR platform. This consists of T-cells engineered with RevCARs that are primarily inactive as they express an extracellular short peptide epitope incapable of recognizing surface antigens. RevCAR T-cells can be redirected to tumor antigens and controlled by bispecific antibodies cross-linking RevCAR T- and tumor cells resulting in tumor lysis. Remarkably, the RevCAR platform enables combinatorial tumor targeting following Boolean logic gates. We herein show for the first time the applicability of the RevCAR platform to target myeloid malignancies like AML. Applying in vitro and in vivo models, we have proven that AML cell lines as well as patient-derived AML blasts were efficiently killed by redirected RevCAR T-cells targeting CD33 and CD123 in a flexible manner. Furthermore, by targeting both antigens, a Boolean AND gate logic targeting could be achieved using the RevCAR platform. These accomplishments pave the way towards an improved and personalized immunotherapy for AML patients.
Recent Manganese Oxide Octahedral Molecular Sieves (OMS–2) with Isomorphically Substituted Cationic Dopants and Their Catalytic Applications
Authors: Sabaté Ferran , Sabater María J.
Published: September 2021

The present report describes the structural and physical–chemical variations of the potassium manganese oxide mineral, α–MnO2, which is a specific manganese octahedral molecular sieve (OMS) named cryptomelane (K–OMS–2), with different transition metal cations. We will describe some frequently used synthesis methods to obtain isomorphic substituted materials [M]–K–OMS–2 by replacing the original manganese cationic species in a controlled way. It is important to note that one of the main effects of doping is related to electronic environmental changes, as well as to an increase of oxygen species mobility, which is ultimately related to the creation of new vacancies. Given the interest and the importance of these materials, here, we collect the most recent advances in [M]–K–OMS–2 oxides (M = Ag, Ce, Mo, V, Nb, W, In, Zr and Ru) that have appeared in the literature during the last ten years, leaving aside other metal–doped [M]–K–OMS–2 oxides that have already been treated in previous reviews. Besides showing the most important structural and physic-chemical features of these oxides, we will highlight their applications in the field of degradation of pollutants, fine chemistry and electrocatalysis, and will suggest potential alternative applications.
Driver Genetic Mutations in Spinal Cord Gliomas Direct the Degree of Functional Impairment in Tumor-Associated Spinal Cord Injury
Authors: Nagashima Yoshitaka , Nishimura Yusuke , Ohka Fumiharu , Eguchi Kaoru , Aoki Kosuke , Ito Hiroshi , Nishii Tomoya , Oyama Takahiro , Hara Masahito , Kitano Yotaro , Masaki Hirano , Wakabayashi Toshihiko , Natsume Atsushi
Published: September 2021

Genetic analysis in glioma has been developed recently. Spinal cord glioma is less common than intracranial glioma. Thus, the clinical significance of genetic mutations in spinal cord gliomas remains unclear. Furthermore, because the spinal cord is an important communication channel between the brain and the rest of the body, increased attention should be paid to its functional prognosis. In this study, we investigated the functional prognosis and driver genetic mutations in eight patients with spinal cord gliomas (World Health Organization grade I, three cases; grade II, two cases; grade III/IV, three cases). IDH mutations were detected in all grade II cases and H3F3A mutations were detected in all grade III/IV cases. The functional status of grade I and II gliomas remained unchanged or improved 1 year after surgery, whereas grade III/IV gliomas remained unchanged or deteriorated. Spinal glioma progenitor cells with H3F3A mutations were associated with accelerated tumor-associated spinal cord injury, which led to functional impairment. Conversely, the presence of IDH mutations, which are rarely reported in spinal gliomas, indicated a relatively favorable functional prognosis.
Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death
Authors: Ahn Yu-Jeong , Shin Hyun-Joo , Jeong Eun-Ae , An Hyeong-Seok , Lee Jong-Youl , Jang Hye-Min , Kim Kyung-Eun , Lee Jaewoong , Shin Meong-Cheol , Roh Gu-Seob
Published: September 2021

Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that protects against brain injury. However, little is known about the effect of Ex-4 on kainic acid (KA)-induced seizures and hippocampal cell death. Therefore, this study evaluated the neuroprotective effects of Ex-4 pretreatment in a mouse model of KA-induced seizures. Three days before KA treatment, mice were intraperitoneally injected with Ex-4. We found that Ex-4 pretreatment reversed KA-induced reduction of GLP-1R expression in the hippocampus and attenuated KA-induced seizure score, hippocampal neuronal death, and neuroinflammation. Ex-4 pretreatment also dramatically reduced hippocampal lipocalin-2 protein in KA-treated mice. Furthermore, immunohistochemical studies showed that Ex-4 pretreatment significantly alleviated blood–brain barrier leakage. Finally, Ex-4 pretreatment stimulated hippocampal expression of phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), a known target of GLP-1/GLP-1R signaling. These findings indicate that Ex-4 pretreatment may protect against KA-induced neuronal damage by regulating GLP-1R/CREB-mediated signaling pathways.
Altered Brain Cholinergic and Synaptic Markers in Obese Zucker Rats
Authors: Martinelli Ilenia , Tomassoni Daniele , Roy Proshanta , Amenta Francesco , Tayebati Seyed Khosrow
Published: September 2021

The association between obesity and loss of cognitive performance has been recognized. Although there are data regarding the metabolic alterations in obese conditions and the development of neuroinflammation, no clear evidence concerning obesity-related cholinergic and synaptic impairments in the frontal cortex and hippocampus has been reported yet. Here, we investigate different cholinergic and synaptic markers in 12-, 16-, and 20-week-old obese Zucker rats (OZRs) compared with lean littermate rats (LZRs), using immunochemical and immunohistochemical analysis. Consequently, OZRs showed body weight gain, hypertension, and dysmetabolism. In 20-week-old OZRs, the reduction of vesicular acetylcholine transporter (VAChT) and alpha7 nicotinic acetylcholine receptors (α7nAChR) occurred both in the frontal cortex and in the hippocampus, suggesting a cognitive dysfunction due to obesity and aging. Among the muscarinic receptors analyzed, the level of expression of type 1 (mAChR1) was lower in the hippocampus of the older OZRs. Finally, we showed synaptic dysfunctions in OZRs, with a reduction of synaptophysin (SYP) and synaptic vesicle glycoprotein 2B (SV2B) in 20-week-old OZRs, both in the frontal cortex and in the hippocampus. Taken together, our data suggest specific alterations of cholinergic and synaptic markers that can be targeted to prevent cognitive deficits related to obesity and aging.
Impairments in Brain Bioenergetics in Aging and Tau Pathology: A Chicken and Egg Situation?
Authors: Grimm Amandine
Published: September 2021

The brain is the most energy-consuming organ of the body and impairments in brain energy metabolism will affect neuronal functionality and viability. Brain aging is marked by defects in energetic metabolism. Abnormal tau protein is a hallmark of tauopathies, including Alzheimer’s disease (AD). Pathological tau was shown to induce bioenergetic impairments by affecting mitochondrial function. Although it is now clear that mutations in the tau-coding gene lead to tau pathology, the causes of abnormal tau phosphorylation and aggregation in non-familial tauopathies, such as sporadic AD, remain elusive. Strikingly, both tau pathology and brain hypometabolism correlate with cognitive impairments in AD. The aim of this review is to discuss the link between age-related decrease in brain metabolism and tau pathology. In particular, the following points will be discussed: (i) the common bioenergetic features observed during brain aging and tauopathies; (ii) how age-related bioenergetic defects affect tau pathology; (iii) the influence of lifestyle factors known to modulate brain bioenergetics on tau pathology. The findings compiled here suggest that age-related bioenergetic defects may trigger abnormal tau phosphorylation/aggregation and cognitive impairments after passing a pathological threshold. Understanding the effects of aging on brain metabolism may therefore help to identify disease-modifying strategies against tau-induced neurodegeneration.
Extracellular Vesicles (Exosomes) as Immunosuppressive Mediating Variables in Tumor and Chronic Inflammatory Microenvironments
Authors: Awadasseid Annoor , Wu Yanling , Zhang Wen
Published: September 2021

Exosomes are extracellular vesicles released by most of the eukaryotic cells. Exosomes’ components include proteins, lipids, microRNA, circular RNA, long noncoding RNA, DNA, etc. Exosomes may carry both pro and anti-inflammatory cargos; however, exosomes are predominantly filled with immunosuppressive cargos such as enzymes and microRNAs in chronic inflammation. Exosomes have surfaced as essential participants in physiological and pathological intercellular communication. Exosomes may prevent or promote the formation of an aggressive tumor and chronic inflammatory microenvironments, thus influencing tumor and chronic inflammatory progression as well as clinical prognosis. Exosomes, which transmit many signals that may either enhance or constrain immunosuppression of lymphoid and myeloid cell populations in tumors, are increasingly becoming recognized as significant mediators of immune regulation in cancer. In this review, we outline the function of exosomes as mediators of immunosuppression in tumor and chronic inflammatory microenvironments, with the aim to improve cancer therapy.
Fifteen-Years Follow-Up in a Cohort of Children with Functional Gastrointestinal Disorders: Prevalence and Risk Factors to Develop Neuropsychiatric Disorders and Other Comorbidities
Authors: Zanchi Chiara , Pintaldi Stefano , Di Leo Grazia , Ronfani Luca , Zamagni Giulia , Viel Marialuisa , Barbi Egidio , Cozzi Giorgio
Published: September 2021

Background: Functional gastrointestinal disorders (FGIDs) are chronic and recurrent disorders, which affect up to 23% of children and adolescents and represent 50% of gastroenterological accesses. The association between FGIDs diagnosed at paediatric age and the onset of migraine or headache and neuropsychiatric diseases in adolescence and adulthood is widely reported in the literature. However, there is still limited knowledge about the long-term prognosis and risk factors for neuropsychiatric pathologies and other comorbidities. Aim: The aim is to assess the prevalence and persistence of FGIDs as well as the occurrence of migraine or headache and neuropsychiatric disorders in a cohort of patients diagnosed with FGIDs 15 years ago compared with a control group of peers. Materials and methods: We enrolled a group of patients diagnosed with FGIDs at paediatric age, at least 10 years ago (FGIDs group, n = 79; median age 23), and control subjects (control group, n = 201; median age 23). In both groups, an online questionnaire created explicitly for the study was submitted in order to investigate the presence of chronic intestinal diseases, migraine, headache or neuropsychiatric disorders. Results: 45.6% (36 out of 79) of patients previously diagnosed with FGIDs still suffer from FGIDs versus 12% (24 out of 201) of healthy controls (p < 0.0001). The prevalence of chronic organic gastrointestinal disorders was comparable in the two groups (2.5% in FGIDs group versus 1% in healthy group, p = 0.3). Thirty-three percent (26 out of 79) of FGIDs patients reported headache or migraine versus 13% (26 out of 201) of healthy peers (p < 0.001). No differences were found regarding the prevalence of anxiety and depression. Conclusion: The outcome at 15 years of FGIDs was characterized by a high prevalence of persisting functional symptoms along with a significant incidence of headaches and migraines. Abbreviation: FGIDs: Functional gastrointestinal disorders; IBS: Inflammatory Bowel Syndrome.
A National Population Cohort Study Showed That Exposure to General Anesthesia in Early Childhood Is Associated with an Increase in the Risk of Developmental Delay
Authors: Yang Ya-Ling , Wang Liang-Jen , Chang Jung-Chan , Ho Shu-Chen , Kuo Ho-Chang
Published: September 2021

This study investigated the relationship between exposure to general anesthesia (GA) and the risk of cognitive and mental disorders. This study has thus investigated the relationships between exposure to GA before the age of 3 and subsequent cognitive and mental disorders in a national-wide research sample. We obtained our subjects from the National Health Insurance Research Database (NHIRD) of Taiwan, which was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Children in the hospital aged less than 3 years old were included if there was GA exposure or not during the period of year 1997 to 2008. Cox proportional hazard regression models adjusted for potential confounding factors were used to estimate the relative magnitude of the risk associated with GA exposure. The cohort contained 2261 subjects with GA and 4522 children without GA as a comparison group. GA exposure group had a higher rate of developmental delay than in the without GA group (hazard ratio 1.46, p < 0.0001). There was no significant difference in the overall incidence of ADHD, autism and intellectual disability between the GA-exposed group and the comparison cohort. In conclusion, this study reported that children exposed to GA early before the age of three had a small association with increased risk of development delay thereafter.
Vital Pulp Therapy in Primary Dentition: Pulpotomy—A 100-Year Challenge
Authors: Igna Andreea
Published: September 2021

Pulpotomy has long been the most indicated vital pulp procedure in primary molars with extensive caries. The success of a pulpotomy is highly technique sensitive and it depends upon many factors, such as diagnosis accuracy, caries excavation method, pulp dressing material, quality of the final restoration and operator experience. This paper provides an overview of the pulpotomy procedure in primary teeth over a century, with reference to advances in technique, medication and restoration possibilities and challenges and controversies surrounding the subject as well as future directions.
The Physiologic Significance of Early Urinary Intestinal Fatty Acid Binding Protein Levels in Preterm Infants: A Prospective Cohort Study
Authors: Jung Young-Hwa , Kim Ee-Kyung , Shin Seung-Han , Lee Jin-A , Kim Han-Suk , Kim Beyong-Il
Published: September 2021

Intestinal fatty acid binding protein (I-FABP) is released from mature enterocytes when cell membrane integrity is disrupted. This study aimed to prospectively investigate the physiologic significance of early urinary I-FABP and whether it might reflect intestinal compromise in preterm infants. We conducted a prospective cohort study of 100 preterm infants weighing <1250 g and collected serial urine samples at 12, 24, and 48 h after birth. The correlations between initial urinary I-FABP/urinary creatinine (creatinineu) levels and associated factors were analyzed. Among 100 patients, 15 were diagnosed with meconium obstruction of prematurity, and five were diagnosed with necrotizing enterocolitis during the hospital stay. Early urinary I-FABP/creatinineu levels were inversely correlated with both gestational age (Spearman’s rank correlation coefficient (Rs) −0.381, p < 0.01) and birth weight ((Rs) −0.424, p < 0.01). Early urinary I-FABP/creatinineu levels were associated with cord pH ((Rs) −0.436, p < 0.01) and base excess ((Rs) −0.258, p = 0.021). There were significantly positive correlations between early urinary I-FABP/creatinineu levels and the time to full enteral feeding in preterm infants without specific intestinal morbidities. Therefore, a more premature gut with acute perinatal ischemia is expected to exhibit increased I-FABP levels shortly after birth. Because of small sample size, further large-scale studies are needed.
3D Printing in Drug Delivery and Biomedical Applications: A State-of-the-Art Review
Authors: Mahmood Muhammad Arif
Published: September 2021

Personalized medicines are gaining popularity day by day as they empower patient genomics and assist in improved drug design with minimum side effects. Various dosages can be combined into one dose that fits the patient’s requirements. For this purpose, 3D printing is a new technology to produce medicine based on patient needs. It utilizes controlled devices to prepare active pharmaceutical ingredients (API) in a layer-wise fashion to develop an appropriate tailored drug transport structure. It contains numerous methods, including inkjet printing and fused deposition modeling. For this purpose, scientists have used various materials, including polyvinyl alcohol, polylactic acid and polycaprolactone. These materials have been applied to design and develop forms that are suitable for tuning the drug release. Different forms of dosages, including tablets (immediate and pulsatile release) and transdermic dosages, can be produced using the 3D printing technique. Furthermore, the 3D printing technique can also be used to prepare customized medicines to treat life-threatening diseases. In the case of patients needing various medicines, a 3D printer can be used to design and manufacture only one dosage incorporating different medicines. This article reviewed 3D printing utilization for customized medicines based on one’s needs. Various methods and materials used in medicine 3D printing were discussed with their applications.
Blockchain Software Selection as a Fuzzy Multi-Criteria Problem
Authors: Ilieva Galina , Yankova Tania , Radeva Irina , Popchev Ivan
Published: September 2021

Increased consumer requirements for quality, safety and traceability of goods in supply chains has accelerated the implementation of blockchain during the COVID-19 pandemic. The right choice of blockchain software is a complicated task and an important prerequisite for successful deployment. In this study, we propose a conceptual framework for group multi-criteria selection of blockchain software in fuzzy environment according to organization needs and experts’ judgements. The applicability of the new framework has been verified through an illustrative example for ranking blockchain systems. The evaluations of compared alternatives were calculated by using measurement of alternatives and ranking according to the compromise solution (MARCOS) method. The robustness of the new framework was proven by sensitivity analysis in which two (crisp and fuzzy) MARCOS models with two different sets of weighting coefficients were compared.
Synthesis, Single Crystal X-ray, Hirshfeld and DFT Studies of 1,8-Dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic Acid
Authors: Altowyan Mezna , Sultan Mujeeb , Soliman Saied , Yousuf Sammer , Ali Israr , Shawish Ihab , Barakat Assem
Published: September 2021

In this paper, synthesis, single-crystal X-ray structure, Hirshfeld and DFT studies of 1,8-dichloro-9,10-dihydro-9,10-ethanoanthracene-11-carboxylic acid are discussed. Different intermolecular contacts affecting the crystal stability are studied using Hirshfeld calculations. The H…Cl and O…H contacts are the most significant, showing corresponding interaction distances of 2.731 Å (Cl2…H10) and 1.681Å (H1…O1), 2.328 Å (O1…H13), 2.510 Å (O1…H12) based on Hirshfeld calculations. DFT calculations are carried out to study the electronic behavior, as well as the 1H- and 13C-NMR spectra of the synthesized compound. The computed NMR chemical shifts show excellent correlation with the experimental data (R2 = 0.9884–0.9705).
Study on the Synergistic Extraction of Lithium from Spent Lithium Cobalt Oxide Batteries by Molten Salt Electrolysis and Two-Step Precipitation Method
Authors: Li Hui , Li Haotian , Liang Jinglong , Yan Hongyan , Cai Zongying
Published: September 2021

With the continuous development of society, the number of spent lithium-ion batteries has also increased, and the recovery of valuable metals such as Ni, Co, and Li has become the main research direction of many scholars. In this paper, the extraction process of lithium that enters the molten salt after LiCoO2 electrolysis is studied. Oxalic acid and phosphate are added to molten salt containing lithium ions to realize the two-part precipitation method to extract lithium. The influence of pH value, temperature, reaction time, and oxalic acid (or phosphate) addition on the process of oxalic acid calcium removal and phosphate lithium precipitation is analyzed. The results show that the calcium removal rate of oxalic acid has reached 99.72% (Initial conditions: PH = 7.0, T = 70 °C, t = 1.5 h, n(H2C2O4):n(Ca2+) = 1.2:1). The precipitation of Li3PO4 obtained in the phosphate extraction experiment of lithium is as high as 88.44% (Initial conditions: PH = 8.0, T = 70 °C, t = 1.5 h, n(actual dosage of Na3PO4):n(theoretical dosage of Na3PO4) = 1.2:1). The obtained lithium phosphate crystals show regular spherical particles, which can be seen by SEM.
Improving Stability and Colloidal Dispersity of CsPbBr3@SiO2 Nanoparticles Based on In-Situ Synthesis in Entropy Ligands Functionalized SiO2 Nanoreactor
Authors: Chen Tianju , Zhang Peng , Chen Guoliang , Yang Qi , Li Feiming
Published: September 2021

Perovskite nanocrystals (PNCs) have witnessed unprecedented development in optoelectronic fields over the past few years. However, their intrinsic ionic structural instability still dramatically hinders their practical applications. Reliably improving the stability of PNCs while retaining their colloidal dispersity remains a grand challenge. Herein, we report a new strategy whereby CsPbBr3 nanoparticles are grown in situ in an entropy ligand-functionalized SiO2 nanoreactor. Consequently, the as-obtained CsPbBr3@SiO2 NPs show outstanding stability and colloidal dispersity in various non-polar solvents and have good solution processability, which are unattainable by conventional template-assisted methods.