bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing Political Polarization on Social Media by Deleting Bot Spamming
Authors: Cantini Riccardo , Marozzo Fabrizio , Talia Domenico , Trunfio Paolo
Published: January 2022

Social media platforms are part of everyday life, allowing the interconnection of people around the world in large discussion groups relating to every topic, including important social or political issues. Therefore, social media have become a valuable source of information-rich data, commonly referred to as Social Big Data, effectively exploitable to study the behavior of people, their opinions, moods, interests and activities. However, these powerful communication platforms can be also used to manipulate conversation, polluting online content and altering the popularity of users, through spamming activities and misinformation spreading. Recent studies have shown the use on social media of automatic entities, defined as social bots, that appear as legitimate users by imitating human behavior aimed at influencing discussions of any kind, including political issues. In this paper we present a new methodology, namely TIMBRE (Time-aware opInion Mining via Bot REmoval), aimed at discovering the polarity of social media users during election campaigns characterized by the rivalry of political factions. This methodology is temporally aware and relies on a keyword-based classification of posts and users. Moreover, it recognizes and filters out data produced by social media bots, which aim to alter public opinion about political candidates, thus avoiding heavily biased information. The proposed methodology has been applied to a case study that analyzes the polarization of a large number of Twitter users during the 2016 US presidential election. The achieved results show the benefits brought by both removing bots and taking into account temporal aspects in the forecasting process, revealing the high accuracy and effectiveness of the proposed approach. Finally, we investigated how the presence of social bots may affect political discussion by studying the 2016 US presidential election. Specifically, we analyzed the main differences between human and artificial political support, estimating also the influence of social bots on legitimate users.
MV1035 Overcomes Temozolomide Resistance in Patient-Derived Glioblastoma Stem Cell Lines
Authors: Malacrida Alessio , Di Domizio Alessandro , Bentivegna Angela , Cislaghi Giacomo , Messuti Eleonora , Tabano Silvia Maria , Giussani Carlo , Zuliani Valentina , Rivara Mirko , Nicolini Gabriella
Published: January 2022

Glioblastoma (GBM, grade IV glioma) represents the most aggressive brain tumor and patients with GBM have a poor prognosis. Until now surgical resection followed by radiotherapy and temozolomide (TMZ) treatment represents the standard strategy for GBM. We showed that the imidazobenzoxazin-5-thione MV1035 is able to significantly reduce GBM U87-MG cells migration and invasiveness through inhibition of the RNA demethylase ALKBH5. In this work, we focus on the DNA repair protein ALKBH2, a further MV1035 target resulting from SPILLO-PBSS proteome-wide scale in silico analysis. Our data demonstrate that MV1035 inhibits the activity of ALKBH2, known to be involved in GBM TMZ resistance. MV1035 was used on both U87-MG and two patient-derived (PD) glioma stem cells (GSCs): in combination with TMZ, it has a significant synergistic effect in reducing cell viability and sphere formation. Moreover, MV1035 induces a reduction in MGMT expression in PD-GSCs cell lines most likely through a mechanism that acts on MGMT promoter methylation. Taken together our data show that MV1035 could act as an inhibitor potentially helpful to overcome TMZ resistance and able to reduce GBM migration and invasiveness.
Construction of Light-Responsive Gene Regulatory Network for Growth, Development and Secondary Metabolite Production in Cordyceps militaris
Authors: In-on Ammarin , Thananusak Roypim , Ruengjitchatchawalya Marasri , Vongsangnak Wanwipa , Laomettachit Teeraphan
Published: January 2022

Cordyceps militaris is an edible fungus that produces many beneficial compounds, including cordycepin and carotenoid. In many fungi, growth, development and secondary metabolite production are controlled by crosstalk between light-signaling pathways and other regulatory cascades. However, little is known about the gene regulation upon light exposure in C. militaris. This study aims to construct a gene regulatory network (GRN) that responds to light in C. militaris. First, a genome-scale GRN was built based on transcription factor (TF)-target gene interactions predicted from the Regulatory Sequence Analysis Tools (RSAT). Then, a light-responsive GRN was extracted by integrating the transcriptomic data onto the genome-scale GRN. The light-responsive network contains 2689 genes and 6837 interactions. From the network, five TFs, Snf21 (CCM_04586), an AT-hook DNA-binding motif TF (CCM_08536), a homeobox TF (CCM_07504), a forkhead box protein L2 (CCM_02646) and a heat shock factor Hsf1 (CCM_05142), were identified as key regulators that co-regulate a large group of growth and developmental genes. The identified regulatory network and expression profiles from our analysis suggested how light may induce the growth and development of C. militaris into a sexual cycle. The light-mediated regulation also couples fungal development with cordycepin and carotenoid production. This study leads to an enhanced understanding of the light-responsive regulation of growth, development and secondary metabolite production in the fungi.
Improvement of Bemisia tabaci (Hemiptera: Aleyrodidae) Fitness on Chinese Kale upon Simultaneous Herbivory by Plutella xylostella (Lepidoptera: Plutellidae)
Authors: Jiang Jun , Xu Li-Li , Yu Wen-Yuan , Zhang Shi-Ze , Liu Tong-Xian
Published: January 2022

Bemisia tabaci and the diamondback moth (DBM), Plutella xylostella, are two major cosmopolitan pests that often occur together and cause severe economic losses to cruciferous crops. However, little is known about how they interact with each other. To determine the effects of defense responses induced by the two pests on the biology and population dynamics of the herbivores, we studied the performance and fitness of B. tabaci and DBM when they damaged Chinese kale simultaneously and in different orders. The results showed that DBM pre-infestation shortened the developmental duration, increased longevity, oviposition days, and fecundity of B. tabaci. Meanwhile, the intrinsic rate of increase (r), net reproductive rate (R0) and finite rate of increase (λ) of B. tabaci increased significantly with dual infection as compared with only B. tabaci infestation. In contrast, B. tabaci pre-infestation reduced the longevity and oviposition days of DBM, but the population parameters r, R0, and λ did not vary significantly compared with only DBM infestation. Thus, co-infestation of B. tabaci and DBM was beneficial to the performance of the B. tabaci population. The present findings highlight that B. tabaci has become a dominant competitor when mixing with DBM on the same host plant.
Early Starvation Contributes to the Adaptive Capacity of Corythucha marmorata (Uhler), an Emerging Pest in China
Authors: Zhou Wei , Chen Wenlong
Published: January 2022

Food shortages severely reduce the prospects of insect survival in natural settings, including in the case of herbivorous insects. However, the early starvation experience of some insects has positive effects throughout their entire lifespan. It is important to discuss the effects of refeeding and host plants on the capacity of herbivorous insects to adapt to starvation and low temperatures, considering that starvation resistance is expected to show some degree of adaptive phenotypic plasticity. We tested the relationship between host plant, starvation, and the supercooling capacity of the invasive pest Corythucha marmorata. In particular, we highlighted how early starvation affects the refeeding and recovery phases. Among the various range of hosts, the chrysanthemum lace bug has the fastest growth rate on Helianthus annuus, and the strongest supercooling capacity on Symphyotrichum novi-belgii. Especially, starvation for 2 days increases the rates of survival, development, and number of eggs upon refeeding, in comparison to no starvation. A 3-day starvation period in the nymphal stage significantly increased the supercooling capacity of 5th instar nymphs and adults, as observed in our study.
Function and Plasticity of Electrical Synapses in the Mammalian Brain: Role of Non-Junctional Mechanisms
Authors: Curti Sebastian , Davoine Federico , Dapino Antonella
Published: January 2022

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals, they are mostly composed of the protein connexin36. Circuits of electrically coupled neurons are widespread in these animals. Plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations such as lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on the gap junction resistance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage and ligand gated channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here, we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.
Role of Natural Killer Cells during Pregnancy and Related Complications
Authors: Mahajan Deviyani , Sharma Neeta Raj , Kancharla Sudhakar , Kolli Prachetha , Tripathy Ashutosh , Sharma Amarish Kumar , Singh Sanjeev , Kumar Sudarshan , Mohanty Ashok Kumar , Jena Manoj Kumar
Published: January 2022

A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual natural killer (dNK) cells are the most common type of natural killer (NK) cells in the uterus. The increase in the number of uterine NK (uNK) cells during the mid-secretory phase of the menstrual cycle, followed by further increase of dNK cells in early pregnancy, has heightened interest in their involvement during pregnancy. Extensive research has revealed various roles of dNK cells during pregnancy including the formation of new blood vessels, migration of trophoblasts, and immunological tolerance. The present review article is focused on the significance of NK cells during pregnancy and their role in pregnancy-related diseases. The article will provide an in-depth review of cellular and molecular interactions during pregnancy and related disorders, with NK cells playing a pivotal role. Moreover, this study will help researchers to understand the physiology of normal pregnancy and related complications with respect to NK cells, so that future research work can be designed to alleviate the complications.
The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment
Authors: Ferreira-Gonçalves Tânia , Gaspar Maria Manuela , Coelho João M. P. , Marques Vanda , Viana Ana S. , Ascensão Lia , Carvalho Lina , Rodrigues Cecília M. P. , Ferreira Hugo Alexandre , Ferreira David , Reis Catarina Pinto
Published: January 2022

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer.
Androgen Receptor as an Emerging Feasible Biomarker for Breast Cancer
Authors: You Chan-Ping , Leung Man-Hong , Tsang Wai-Chung , Khoo Ui-Soon , Tsoi Ho
Published: January 2022

Biomarkers can be used for diagnosis, prognosis, and prediction in targeted therapy. The estrogen receptor α (ERα) and human epidermal growth factor receptor 2 (HER2) are standard biomarkers used in breast cancer for guiding disease treatment. The androgen receptor (AR), a nuclear hormone receptor, contributes to the development and progression of prostate tumors and other cancers. With increasing evidence to support that AR plays an essential role in breast cancer, AR has been considered a useful biomarker in breast cancer, depending on the context of breast cancer sub-types. The existing survival analyses suggest that AR acts as a tumor suppressor in ER + ve breast cancers, serving as a favorable prognostic marker. However, AR functions as a tumor promoter in ER-ve breast cancers, including HER2 + ve and triple-negative (TNBC) breast cancers, serving as a poor prognostic factor. AR has also been shown to be predictive of the potential of response to adjuvant hormonal therapy in ER + ve breast cancers and to neoadjuvant chemotherapy in TNBC. However, conflicting results do exist due to intrinsic molecular differences between tumors and the scoring method for AR positivity. Applying AR expression status to guide treatment in different breast cancer sub-types has been suggested. In the future, AR will be a feasible biomarker for breast cancer. Clinical trials using AR antagonists in breast cancer are active. Targeting AR alone or other therapeutic agents provides alternatives to existing therapy for breast cancer. Therefore, AR expression will be necessary if AR-targeted treatment is to be used.
Influence of Particle Size on Ecotoxicity of Low-Density Polyethylene Microplastics, with and without Adsorbed Benzo-a-Pyrene, in Clam Scrobicularia plana
Authors: Rodrigues Ana Rita , Mestre Nélia C. C. , Fonseca Tainá Garcia da , Pedro Paulo Z. , Carteny Camilla C. , Cormier Bettie , Keiter Steffen , Bebianno Maria João
Published: January 2022

This study investigated the ecotoxicological effects of differently sized (4–6 µm and 20–25 µm) low-density polyethylene (LDPE) microplastics (MPs), with and without adsorbed benzo-a-pyrene (BaP), in clam Scrobicularia plana. Biomarkers of oxidative stress (superoxide dismutase—SOD; catalase—CAT), biotransformation (glutathione-S-transferases—GST), oxidative damage (lipid peroxidation—LPO) and neurotoxicity (acetylcholinesterase—AChE) were analysed in gills and digestive glands at different time intervals for a total of 14 days of exposure. In order to have a better impact perspective of these contaminants, an integrated biomarker response index (IBR) and Health Index were applied. Biomarker alterations are apparently more related to smaller sized (4–6 µm) MPs in gills and to virgin LDPE MPs in the digestive gland according to IBR results, while the digestive gland was more affected by these MPs according to the health index.
Breast Cancer Treatment: The Case of Gold(I)-Based Compounds as a Promising Class of Bioactive Molecules
Authors: Galassi Rossana , Luciani Lorenzo , Wang Junbiao , Vincenzetti Silvia , Cui Lishan , Amici Augusto , Pucciarelli Stefania , Marchini Cristina
Published: January 2022

Breast cancers (BCs) may present dramatic diagnoses, both for ineffective therapies and for the limited outcomes in terms of lifespan. For these types of tumors, the search for new drugs is a primary necessity. It is widely recognized that gold compounds are highly active and extremely potent as anticancer agents against many cancer cell lines. The presence of the metal plays an essential role in the activation of the cytotoxicity of these coordination compounds, whose activity, if restricted to the ligands alone, would be non-existent. On the other hand, gold exhibits a complex biochemistry, substantially variable depending on the chemical environments around the central metal. In this review, the scientific findings of the last 6–7 years on two classes of gold(I) compounds, containing phosphane or carbene ligands, are reviewed. In addition to this class of Au(I) compounds, the recent developments in the application of Auranofin in regards to BCs are reported. Auranofin is a triethylphosphine-thiosugar compound that, being a drug approved by the FDA—therefore extensively studied—is an interesting lead gold compound and a good comparison to understand the activities of structurally related Au(I) compounds.
Nrf2-Related Therapeutic Effects of Curcumin in Different Disorders
Authors: Ghafouri-Fard Soudeh , Shoorei Hamed , Bahroudi Zahra , Hussen Bashdar Mahmud , Talebi Seyedeh Fahimeh , Taheri Mohammad , Ayatollahi Seyed Abdulmajid
Published: January 2022

Curcumin is a natural polyphenol with antioxidant, antibacterial, anti-cancer, and anti-inflammation effects. This substance has been shown to affect the activity of Nrf2 signaling, a pathway that is activated in response to stress and decreases levels of reactive oxygen species and electrophilic substances. Nrf2-related effects of curcumin have been investigated in different contexts, including gastrointestinal disorders, ischemia-reperfusion injury, diabetes mellitus, nervous system diseases, renal diseases, pulmonary diseases, cardiovascular diseases as well as cancers. In the current review, we discuss the Nrf2-mediated therapeutic effects of curcumin in these conditions. The data reviewed in the current manuscript indicates curcumin as a potential activator of Nrf2 and a therapeutic substance for the protection of cells in several pathological conditions.
The Biomolecules Journal Club: Highlights on Recent Papers—1
Authors: Rabanal Francesc , Johnson Mark S. , Alaimo Alessandro , Bolanos-Garcia Victor M. , Beddoe Travis
Published: January 2022

We are glad to share with you our first Journal Club and to highlight some of the most interesting papers published recently [...]
Characterisation of Congolese Aquatic Biomass and Their Potential as a Source of Bioenergy
Authors: Mayala Tania S. , Ngavouka Maryse D. Nkoua , Douma Dick H. , Hammerton James M. , Ross Andrew B. , Brown Aaron E. , M’Passi-Mabiala Bernard , Lovett Jon C.
Published: January 2022

This study assesses the bioenergy potential of two types of aquatic biomass found in the Republic of Congo: the green macroalgae Ulva lactuca (UL) and Ledermanniella schlechteri (LS). Their combustion behaviour was assessed using elemental and biochemical analysis, TGA, bomb calorimetry and metal analysis. Their anaerobic digestion behaviour was determined using biochemical methane potential (BMP) tests. The average HHV for LS is 14.1 MJ kg−1, whereas UL is lower (10.5 MJ kg−1). Both biomasses have high ash contents and would be problematic during thermal conversion due to unfavourable ash behaviour. Biochemical analysis indicated high levels of carbohydrate and protein and low levels of lipids and lignin. Although the lipid profile is desirable for biodiesel production, the levels are too low for feasible extraction. High levels of carbohydrates and protein make both biomasses suitable for anaerobic digestion. BMP tests showed that LS and UL have an average of 262 and 161 mL CH4 gVS−1, respectively. The biodegradability (BI) of LS and UL had an average value of 76.5% and 43.5%, respectively. The analysis indicated that these aquatic biomasses are unsuitable for thermal conversion and lipid extraction; however, conversion through anaerobic digestion is promising.
The Salutary Effects of Catalpol on Diesel Exhaust Particles-Induced Thrombogenic Changes and Cardiac Oxidative Stress, Inflammation and Apoptosis
Authors: Nemmar Abderrahim , Beegam Sumaya , Zaaba Nur Elena , Alblooshi Salem , Alseiari Saleh , Ali Badreldin H.
Published: January 2022

Inhaled particulate air pollution exerts pulmonary inflammation and cardiovascular toxicity through secondary systemic effects due to oxidative stress and inflammation. Catalpol, an iridiod glucoside, extracted from the roots of Rehmannia glutinosa Libosch, has been reported to possess anti-inflammatory and antioxidant properties. Yet, the potential ameliorative effects of catalpol on particulate air pollution—induced cardiovascular toxicity, has not been studied so far. Hence, we evaluated the possible mitigating mechanism of catalpol (5 mg/kg) which was administered to mice by intraperitoneal injection one hour before the intratracheal (i.t.) administration of a relevant type of pollutant particle, viz. diesel exhaust particles (DEPs, 30 µg/mouse). Twenty-four hours after the lung deposition of DEPs, several cardiovascular endpoints were evaluated. DEPs caused a significant shortening of the thrombotic occlusion time in pial microvessels in vivo, induced platelet aggregation in vitro, and reduced the prothrombin time and the activated partial thromboplastin time. All these actions were effectively mitigated by catalpol pretreatment. Likewise, catalpol inhibited the increase of the plasma concentration of C-reactive proteins, fibrinogen, plasminogen activator inhibitor-1 and P- and E-selectins, induced by DEPs. Moreover, in heart tissue, catalpol inhibited the increase of markers of oxidative (lipid peroxidation and superoxide dismutase) and nitrosative (nitric oxide) stress, and inflammation (tumor necrosis factor α, interleukin (IL)-6 and IL-1β) triggered by lung exposure to DEPs. Exposure to DEPs also caused heart DNA damage and increased the levels of cytochrome C and cleaved caspase, and these effects were significantly diminished by the catalpol pretreatment. Moreover, catalpol significantly reduced the DEPs-induced increase of the nuclear factor κB (NFκB) in the heart. In conclusion, catalpol significantly ameliorated DEPs–induced procoagulant events and heart oxidative and nitrosative stress, inflammation, DNA damage and apoptosis, at least partly, through the inhibition of NFκB activation.
Endovascular Management of Hemorrhagic Stroke
Authors: Musmar Basel , Adeeb Nimer , Ansari Junaid , Sharma Pankaj , Cuellar Hugo H.
Published: January 2022

Significant advances in endovascular neurosurgery tools, devices, and techniques are changing the approach to the management of acute hemorrhagic stroke. The endovascular treatment of intracranial aneurysms emerged in the early 1990s with Guglielmi detachable coils, and since then, it gained rapid popularity that surpassed open surgery. Stent-assisted coiling and balloon remodeling techniques have made the treatment of wide-necked aneurysms more durable. With the introduction of flow diverters and flow disrupters, many aneurysms with complex geometrics can now be reliably managed. Arteriovenous malformations and fistulae can also benefit from endovascular therapy by embolization using n-butyl cyanoacrylate (NBCA), Onyx, polyvinyl alcohol (PVA), and coils. In this article, we describe the role of endovascular treatment for the most common causes of intracerebral and subarachnoid hemorrhages, particularly ruptured aneurysms and vascular malformations.
Dopamine D2L Receptor Deficiency Alters Neuronal Excitability and Spine Formation in Mouse Striatum
Authors: Govindaiah Gubbi , Liu Rong-Jian , Wang Yanyan
Published: January 2022

The striatum contains several types of neurons including medium spiny projection neurons (MSNs), cholinergic interneurons (ChIs), and fast-spiking interneurons (FSIs). Modulating the activity of these neurons by the dopamine D2 receptor (D2R) can greatly impact motor control and movement disorders. D2R exists in two isoforms: D2L and D2S. Here, we assessed whether alterations in the D2L and D2S expression levels affect neuronal excitability and synaptic function in striatal neurons. We observed that quinpirole inhibited the firing rate of all three types of striatal neurons in wild-type (WT) mice. However, in D2L knockout (KO) mice, quinpirole enhanced the excitability of ChIs, lost influence on spike firing of MSNs, and remained inhibitory effect on spike firing of FSIs. Additionally, we showed mIPSC frequency (but not mIPSC amplitude) was reduced in ChIs from D2L KO mice compared with WT mice, suggesting spontaneous GABA release is reduced at GABAergic terminals onto ChIs in D2L KO mice. Furthermore, we found D2L deficiency resulted in reduced dendritic spine density in ChIs, suggesting D2L activation plays a role in the formation/maintenance of dendritic spines of ChIs. These findings suggest new molecular and cellular mechanisms for causing ChIs abnormality seen in Parkinson’s disease or drug-induced dyskinesias.
Neuroprotective Role of Hypothermia in Acute Spinal Cord Injury
Authors: Al-Nashash Hasan , ALL Angelo H.
Published: January 2022

Even nowadays, the question of whether hypothermia can genuinely be considered therapeutic care for patients with traumatic spinal cord injury (SCI) remains unanswered. Although the mechanisms of hypothermia action are yet to be fully explored, early hypothermia for patients suffering from acute SCI has already been implemented in clinical settings. This article discusses measures for inducing various forms of hypothermia and summarizes several hypotheses describing the likelihood of hypothermia mechanisms of action. We present our objective neuro-electrophysiological results and demonstrate that early hypothermia manifests neuroprotective effects mainly during the first- and second-month post-SCI, depending on the severity of the injury, time of intervening, duration, degree, and modality of inducing hypothermia. Nevertheless, eventually, its beneficial effects gradually but consistently diminish. In addition, we report potential complications and side effects for the administration of general hypothermia with a unique referment to the local hypothermia. We also provide evidence that instead of considering early hypothermia post-SCI a therapeutic approach, it is more a neuroprotective strategy in acute and sub-acute phases of SCI that mostly delay, but not entirely avoid, the natural history of the pathophysiological events. Indeed, the most crucial rationale for inducing early hypothermia is to halt these devastating inflammatory and apoptotic events as early and as much as possible. This, in turn, creates a larger time-window of opportunity for physicians to formulate and administer a well-designed personalized treatment for patients suffering from acute traumatic SCI.
News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments
Authors: Meldolesi Jacopo
Published: January 2022

Upon its discovery, Alzheimer’s, the neurodegenerative disease that affects many millions of patients in the world, remained without an effective therapy. The first drugs, made available near the end of last century, induced some effects, which remained only marginal. More promising effects are now present, induced by two approaches. Blockers of the enzyme BACE-1 induce, in neurons and glial cells, decreased levels of Aβ, the key peptide of the Alzheimer’s disease. If administered at early AD steps, the BACE-1 blockers preclude further development of the disease. However, they have no effect on established, irreversible lesions. The extracellular vesicles secreted by mesenchymal stem cells induce therapy effects analogous, but more convenient, than the effects of their original cells. After their specific fusion to target cells, the action of these vesicles depends on their ensuing release of cargo molecules, such as proteins and many miRNAs, active primarily on the cell cytoplasm. Operationally, these vesicles exhibit numerous advantages: they exclude, by their accurate selection, the heterogeneity of the original cells; exhibit molecular specificity due to their engineering and drug accumulation; and induce effective actions, mediated by variable concentrations of factors and molecules and by activation of signaling cascades. Their strength is reinforced by their combination with various factors and processes. The recent molecular and operations changes, induced especially by the stem cell target cells, result in encouraging and important improvement of the disease. Their further development is expected in the near future.
Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis
Authors: Li Hui , Wen Wen , Luo Jia
Published: January 2022

Pancreatitis and alcoholic pancreatitis are serious health concerns with an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here, we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR in developing novel therapeutic strategies for the disease.
Taurine Grafted Micro-Implants Improved Functions without Direct Dependency between Interleukin-6 and the Bile Acid Lithocholic Acid in Plasma
Authors: Mooranian Armin , Ionescu Corina Mihaela , Wagle Susbin Raj , Kovacevic Bozica , Walker Daniel , Jones Melissa , Chester Jacqueline , Foster Thomas , Johnston Edan , Kojic Sanja , Stojanovic Goran , Mikov Momir , Al-Salami Hani
Published: January 2022

A recent study showed an association between diabetes development and the bile acid lithocholic acid (LCA), while another study demonstrated positive biological effects of the conjugated bile acid, taurocholic acid (TCA), on pancreatic cells. Thus, this study aimed to encapsulate TCA with primary islets (graft) and study the biological effects of the graft, post-transplantation, in diabetic mice, including effects on LCA concentrations. Sixteen mature adult mice were made diabetic and randomly divided into two equal groups, control and test (transplanted encapsulated islets without or with TCA). Graft pharmaceutical features pre-transplantation, and biological effects including on LCA concentrations post-transplantation, were measured. TCA-microcapsules had an oval shape and similar size compared with the control. The treatment group survived longer, showed improved glucose and interleukin-6 concentrations, and lower LCA concentrations in plasma, large intestine, faeces, liver and spleen, compared with control. Results suggest that TCA incorporation with islets encapsulated graft exerted beneficial effects, but there was no direct and significant dependency between concentrations of interleukin-6 and LCA.
The Activation of Mesenchymal Stem Cells by Glioblastoma Microvesicles Alters Their Exosomal Secretion of miR-100-5p, miR-9-5p and let-7d-5p
Authors: Garnier Delphine , Ratcliffe Edward , Briand Joséphine , Cartron Pierre-François , Oliver Lisa , Vallette François M.
Published: January 2022

Glioblastoma (GBM) is the most aggressive brain tumor, and despite initial response to chemo- and radio-therapy, the persistence of glioblastoma stem cells (GSCs) unfortunately always results in tumor recurrence. It is now largely admitted that tumor cells recruit normal cells, including mesenchymal stem cells (MSCs), and components of their environment, to participate in tumor progression, building up what is called the tumor microenvironment (TME). While growth factors and cytokines constitute essential messengers to pass on signals between tumor and TME, recent uncovering of extracellular vesicles (EVs), composed of microvesicles (MVs) and exosomes, opened new perspectives to define the modalities of this communication. In the GBM context particularly, we investigated what could be the nature of the EV exchange between GSCs and MSCs. We show that GSCs MVs can activate MSCs into cancer-associated fibroblasts (CAFs)-like cells, that subsequently increase their secretion of exosomes. Moreover, a significant decrease in anti-tumoral miR-100-5p, miR-9-5p and let-7d-5p was observed in these exosomes. This clearly suggests a miRNA-mediated GBM tumor promotion by MSCs exosomes, after their activation by GBM MVs.
Bioinspired Granular Media Friction Pad: A Universal System for Friction Enhancement on Variety of Substrates
Authors: Tramsen Halvor T. , Heepe Lars , Gorb Stanislav N.
Published: January 2022

The granular media friction pad (GMFP) inspired by the biological smooth attachment pads of cockroaches and grasshoppers employs passive jamming, to create high friction forces on a large variety of substrates. The granular medium inside the pad is encased by a flexible membrane which at contact formation greatly adapts to the substrate profile. Upon applying load, the granular medium undergoes the jamming transition and changes from fluid-like to solid-like properties. The jammed granular medium, in combination with the deformation of the encasing elastic membrane, results in high friction forces on a multitude of substrate topographies. Here we explore the effect of elasticity variation on the generation of friction by varying granular media filling quantity as well as membrane modulus and thickness. We systematically investigate contact area and robustness against substrate contamination, and we also determine friction coefficients for various loading forces and substrates. Depending on the substrate topography and loading forces, a low filling quantity and a thin, elastic membrane can be favorable, in order to generate the highest friction forces.
AuNP Aptasensor for Hodgkin Lymphoma Monitoring
Authors: Slyusarenko Maria , Shalaev Sergey , Valitova Alina , Zabegina Lidia , Nikiforova Nadezhda , Nazarova Inga , Rudakovskaya Polina , Vorobiev Maxim , Lezov Alexey , Filatova Larisa , Yevlampieva Natalia , Gorin Dmitry , Krzhivitsky Pavel , Malek Anastasia
Published: January 2022

A liquid biopsy based on circulating small extracellular vesicles (SEVs) has not yet been used in routine clinical practice due to the lack of reliable analytic technologies. Recent studies have demonstrated the great diagnostic potential of nanozyme-based systems for the detection of SEV markers. Here, we hypothesize that CD30-positive Hodgkin and Reed–Sternberg (HRS) cells secrete CD30 + SEVs; therefore, the relative amount of circulating CD30 + SEVs might reflect classical forms of Hodgkin lymphoma (cHL) activity and can be measured by using a nanozyme-based technique. A AuNP aptasensor analytics system was created using aurum nanoparticles (AuNPs) with peroxidase activity. Sensing was mediated by competing properties of DNA aptamers to attach onto surface of AuNPs inhibiting their enzymatic activity and to bind specific markers on SEVs surface. An enzymatic activity of AuNPs was evaluated through the color reaction. The study included characterization of the components of the analytic system and its functionality using transmission and scanning electron microscopy, nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and spectrophotometry. AuNP aptasensor analytics were optimized to quantify plasma CD30 + SEVs. The developed method allowed us to differentiate healthy donors and cHL patients. The results of the CD30 + SEV quantification in the plasma of cHL patients were compared with the results of disease activity assessment by positron emission tomography/computed tomography (PET-CT) scanning, revealing a strong positive correlation. Moreover, two cycles of chemotherapy resulted in a statistically significant decrease in CD30 + SEVs in the plasma of cHL patients. The proposed AuNP aptasensor system presents a promising new approach for monitoring cHL patients and can be modified for the diagnostic testing of other diseases.
An Ultrasensitive Silicon-Based Electrolyte-Gated Transistor for the Detection of Peanut Allergens
Authors: Kim Donghoon , Jin Bo , Kim Sol-A , Choi Wonyeong , Shin Seonghwan , Park Jiwon , Shim Won-Bo , Kim Kihyun , Lee Jeong-Soo
Published: January 2022

The highly sensitive detection of peanut allergens (PAs) using silicon-based electrolyte-gated transistors (Si-EGTs) was demonstrated. The Si-EGT was made using a top-down technique. The fabricated Si-EGT showed excellent intrinsic electrical characteristics, including a low threshold voltage of 0.7 V, low subthreshold swing of <70 mV/dec, and low gate leakage of <10 pA. Surface functionalization and immobilization of antibodies were performed for the selective detection of PAs. The voltage-related sensitivity (SV) showed a constant behavior from the subthreshold regime to the linear regime. The current-related sensitivity (SI) was high in the subthreshold regime and then significantly decreased as the drain current increased. The limit of detection (LOD) was calculated to be as low as 25 pg/mL based on SI characteristics, which is the lowest value reported to date in the literature for various sensor methodologies. The Si-EGT showed selective detection of PA through a non-specific control test. These results confirm that Si-EGT is a high-sensitivity and low-power biosensor for PA detection.
Substituent Effects Impact Surface Charge and Aggregation of Thiophenol-Labeled Gold Nanoparticles for SERS Biosensors
Authors: File Nolan , Carmicheal Joseph , Krasnoslobodtsev Alexey V. , Japp Nicole C. , Souchek Joshua J. , Chakravarty Sudesna , Hollingsworth Michael A. , Sasson Aaron A. , Natarajan Gopalakrishnan , Kshirsagar Prakash G. , Jain Maneesh , Hayashi Chihiro , Junker Wade M. , Kaur Sukhwinder , Batra Surinder K.
Published: January 2022

SERS immunoassay biosensors hold immense potential for clinical diagnostics due to their high sensitivity and growing interest in multi-marker panels. However, their development has been hindered by difficulties in designing compatible extrinsic Raman labels. Prior studies have largely focused on spectroscopic characteristics in selecting Raman reporter molecules (RRMs) for multiplexing since the presence of well-differentiated spectra is essential for simultaneous detection. However, these candidates often induce aggregation of the gold nanoparticles used as SERS nanotags despite their similarity to other effective RRMs. Thus, an improved understanding of factors affecting the aggregation of RRM-coated gold nanoparticles is needed. Substituent electronic effects on particle stability were investigated using various para-substituted thiophenols. The inductive and resonant effects of functional group modifications were strongly correlated with nanoparticle surface charge and hence their stability. Treatment with thiophenols diminished the negative surface charge of citrate-stabilized gold nanoparticles, but electron-withdrawing substituents limited the magnitude of this diminishment. It is proposed that this phenomenon arises by affecting the interplay of competing sulfur binding modes. This has wide-reaching implications for the design of biosensors using thiol-modified gold surfaces. A proof-of-concept multiplexed SERS biosensor was designed according to these findings using the two thiophenol compounds with the most electron-withdrawing substitutions: NO2 and CN.
Electroanalysis of Fentanyl and Its New Analogs: A Review
Authors: Choińska Marta Katarzyna , Šestáková Ivana , Hrdlička Vojtěch , Skopalová Jana , Langmaier Jan , Maier Vítězslav , Navrátil Tomáš
Published: January 2022

The review describes fentanyl and its analogs as new synthetic opioids and the possibilities of their identification and determination using electrochemical methods (e.g., voltammetry, potentiometry, electrochemiluminescence) and electrochemical methods combined with various separation methods. The review also covers the analysis of new synthetic opioids, their parent compounds, and corresponding metabolites in body fluids, such as urine, blood, serum, and plasma, necessary for a fast and accurate diagnosis of intoxication. Identifying and quantifying these addictive and illicit substances and their metabolites is necessary for clinical, toxicological, and forensic purposes. As a reaction to the growing number of new synthetic opioid intoxications and increasing fatalities observed over the past ten years, we provide thorough background for developing new biosensors, screen-printed electrodes, or other point-of-care devices.
Optimal Scaling Approaches for Perfusion MRI with Distorted Arterial Input Function (AIF) in Patients with Ischemic Stroke
Authors: Bal Sukhdeep Singh , Yang Fan Pei Gloria , Sung Yueh-Feng , Chen Ke , Yin Jiu-Haw , Peng Giia-Sheun
Published: January 2022

Background: Diagnosis and timely treatment of ischemic stroke depends on the fast and accurate quantification of perfusion parameters. Arterial input function (AIF) describes contrast agent concentration over time as it enters the brain through the brain feeding artery. AIF is the central quantity required to estimate perfusion parameters. Inaccurate and distorted AIF, due to partial volume effects (PVE), would lead to inaccurate quantification of perfusion parameters. Methods: Fifteen patients suffering from stroke underwent perfusion MRI imaging at the Tri-Service General Hospital, Taipei. Various degrees of the PVE were induced on the AIF and subsequently corrected using rescaling methods. Results: Rescaled AIFs match the exact reference AIF curve either at peak height or at tail. Inaccurate estimation of CBF values estimated from non-rescaled AIFs increase with increasing PVE. Rescaling of the AIF using all three approaches resulted in reduced deviation of CBF values from the reference CBF values. In most cases, CBF map generated by rescaled AIF approaches show increased CBF and Tmax values on the slices in the left and right hemispheres. Conclusion: Rescaling AIF by VOF approach seems to be a robust and adaptable approach for correction of the PVE-affected multivoxel AIF. Utilizing an AIF scaling approach leads to more reasonable absolute perfusion parameter values, represented by the increased mean CBF/Tmax values and CBF/Tmax images.
Differential Effects of Exercise on fMRI of the Midbrain Ascending Arousal Network Nuclei in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Gulf War Illness (GWI) in a Model of Postexertional Malaise (PEM)
Authors: Baraniuk James N. , Amar Alison , Pepermitwala Haris , Washington Stuart D.
Published: January 2022

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Gulf War Illness (GWI) and control subjects underwent fMRI during difficult cognitive tests performed before and after submaximal exercise provocation (Washington 2020). Exercise caused increased activation in ME/CFS but decreased activation for GWI in the dorsal midbrain, left Rolandic operculum and right middle insula. Midbrain and isthmus nuclei participate in threat assessment, attention, cognition, mood, pain, sleep, and autonomic dysfunction. Methods: Activated midbrain nuclei were inferred by a re-analysis of data from 31 control, 36 ME/CFS and 78 GWI subjects using a seed region approach and the Harvard Ascending Arousal Network. Results: Before exercise, control and GWI subjects showed greater activation during cognition than ME/CFS in the left pedunculotegmental nucleus. Post exercise, ME/CFS subjects showed greater activation than GWI ones for midline periaqueductal gray, dorsal and median raphe, and right midbrain reticular formation, parabrachial complex and locus coeruleus. The change between days (delta) was positive for ME/CFS but negative for GWI, indicating reciprocal patterns of activation. The controls had no changes. Conclusions: Exercise caused the opposite effects with increased activation in ME/CFS but decreased activation in GWI, indicating different pathophysiological responses to exertion and mechanisms of disease. Midbrain and isthmus nuclei contribute to postexertional malaise in ME/CFS and GWI.
Multi-Modal Feature Selection with Feature Correlation and Feature Structure Fusion for MCI and AD Classification
Authors: Jiao Zhuqing , Chen Siwei , Shi Haifeng , Xu Jia
Published: January 2022

Feature selection for multiple types of data has been widely applied in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) classification research. Combining multi-modal data for classification can better realize the complementarity of valuable information. In order to improve the classification performance of feature selection on multi-modal data, we propose a multi-modal feature selection algorithm using feature correlation and feature structure fusion (FC2FS). First, we construct feature correlation regularization by fusing a similarity matrix between multi-modal feature nodes. Then, based on manifold learning, we employ feature matrix fusion to construct feature structure regularization, and learn the local geometric structure of the feature nodes. Finally, the two regularizations are embedded in a multi-task learning model that introduces low-rank constraint, the multi-modal features are selected, and the final features are linearly fused and input into a support vector machine (SVM) for classification. Different controlled experiments were set to verify the validity of the proposed method, which was applied to MCI and AD classification. The accuracy of normal controls versus Alzheimer’s disease, normal controls versus late mild cognitive impairment, normal controls versus early mild cognitive impairment, and early mild cognitive impairment versus late mild cognitive impairment achieve 91.85 ± 1.42%, 85.33 ± 2.22%, 78.29 ± 2.20%, and 77.67 ± 1.65%, respectively. This method makes up for the shortcomings of the traditional multi-modal feature selection based on subjects and fully considers the relationship between feature nodes and the local geometric structure of feature space. Our study not only enhances the interpretation of feature selection but also improves the classification performance, which has certain reference values for the identification of MCI and AD.