bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuronal Nitric Oxide Synthase as a Shared Target for the Effects of Adiponectin and Resistin on the Mechanical Responses of the Mouse Gastric Fundus
Authors: Idrizaj Eglantina , Nistri Silvia , Zizi Virginia , Baccari Maria Caterina
Published: December 2022

It has been reported that adiponectin (ADPN) and resistin are co-secreted by white mouse adipocytes and exert similar inhibitory effects in the mouse gastric fundus, in which resistin was observed to increase neuronal nitric oxide synthase (nNOS) expression. On these grounds, the present work aimed to investigate whether the effects of the two adipokines on the neurally-induced relaxant responses potentiate each other and whether there is a possible correlation with changes in nNOS expression in preparations from the mouse gastric fundus. In carbachol (CCh)-precontracted strips, electrical field stimulation elicited nitrergic relaxant responses, whose amplitude was increased by ADPN or resistin, but no additional enhancements were observed in their concomitant presence. Western blot and immunofluorescence analyses revealed that ADPN, like resistin, was able to up-regulate nNOS expression and to increase the percentage of nNOS-positive neurons in the myenteric plexus: co-treatment with the two adipokines did not induce additional changes. The results indicate that the two adipokines modulate nitrergic neurotransmission, and both do so by up-regulating nNOS expression. Therefore, nNOS appears to be a shared target for the two adipokines’ effects, which, rather than mutually reinforcing each other, may represent a dual physiological control mechanism to guarantee gastric fundus relaxation.
PHF21A Related Disorder: Description of a New Case
Authors: Butera Ambra , Nicotera Antonio Gennaro , Di Rosa Gabriella , Musumeci Sebastiano Antonino , Vitello Girolamo Aurelio , Musumeci Antonino , Vinci Mirella , Gloria Angelo , Federico Concetta , Saccone Salvatore , Calì Francesco
Published: December 2022

PHF21A (PHD finger protein 21A) gene, located in the short arm of chromosome 11, encodes for BHC80, a component of the Lysine Specific Demethylase 1, Corepressor of REST (LSD1-CoREST) complex. BHC80 is mainly expressed in the human fetal brain and skeletal muscle and acts as a modulator of several neuronal genes during embryogenesis. Data from literature relates PHF21A variants with Potocki–Shaffer Syndrome (PSS), a contiguous gene deletion disorder caused by the haploinsufficiency of PHF21A, ALX4, and EXT2 genes. Clinical cardinal features of PSS syndrome are multiple exostoses (due to the EXT2 involvement), biparietal foramina (due to the ALX4 involvement), intellectual disability, and craniofacial anomalies (due to the PHF21A involvement). To date, to the best of our knowledge, a detailed description of PHF21A-related disorder clinical phenotype is not described in the literature; in fact, only 14 subjects with microdeletion frameshift or nonsense variants concerning only PHF21A gene have been reported. All reported cases did not present ALX4 or EXT2 variants, and their clinical features did not fit with PSS diagnosis. Herein, by using Exome sequencing, and Sanger sequencing of the region of interest, we describe a case of a child with a paternally inherited (mosaicism of 5%) truncating variant of the PHF21A gene (c.649_650del; p.Gln217ValfsTer6), and discuss the new evidence. In conclusion, these patients showed varied clinical expressions, mainly including the presence of intellectual disability, epilepsy, hypotonia, and dysmorphic features. Our study contributes to describing the genotype–phenotype spectrum of patients with PHF21A-related disorder; however, the limited data in the literature have been unable to provide a precise diagnostic protocol for patients with PHF21A-related disorder.
Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
Authors: Calderón-Montaño José Manuel , Guillén-Mancina Emilio , Jiménez-Alonso Julio José , Jiménez-González Víctor , Burgos-Morón Estefanía , Mate Alfonso , Pérez-Guerrero María Concepción , López-Lázaro Miguel
Published: December 2022

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.
HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia
Authors: Lei Ling , Feng Jun , Wu Gang , Wei Zhen , Wang Jian-Zhi , Zhang Bin , Liu Rong , Liu Fei , Wang Xiaochuan , Li Hong-Lian
Published: December 2022

Chronic hypoxia is a risk factor for Alzheimer’s disease (AD), and the neurofibrillary tangle (NFT) formed by hyperphosphorylated tau is one of the two major pathological changes in AD. However, the effect of chronic hypoxia on tau phosphorylation and its mechanism remains unclear. In this study, we investigated the role of HIF-1α (the functional subunit of hypoxia-inducible factor 1) in tau pathology. It was found that in Sprague-Dawley (SD) rats, global hypoxia (10% O2, 6 h per day) for one month induced cognitive impairments. Meanwhile it induced HIF-1α increase, tau hyperphosphorylation, and protein phosphatase 2A (PP2A) deficiency with leucine carboxyl methyltransferase 1(LCMT1, increasing PP2A activity) decrease in the rats’ hippocampus. The results were replicated by hypoxic treatment in primary hippocampal neurons and C6/tau cells (rat C6 glioma cells stably expressing human full-length tau441). Conversely, HIF-1α silencing impeded the changes induced by hypoxia, both in primary neurons and SD rats. The result of dual luciferase assay proved that HIF-1α acted as a transcription factor of LCMT1. Unexpectedly, HIF-1α decreased the protein level of LCMT1. Further study uncovered that both overexpression of HIF-1α and hypoxia treatment resulted in a sizable degradation of LCMT1 via the autophagy–-lysosomal pathway. Together, our data strongly indicated that chronic hypoxia upregulates HIF-1α, which obviously accelerated LCMT1 degradation, thus counteracting its transcriptional expression. The increase in HIF-1α decreases PP2A activity, finally resulting in tau hyperphosphorylation and cognitive dysfunction. Lowering HIF-1α in chronic hypoxia conditions may be useful in AD prevention.
Phellinus baumii Polyphenol: A Potential Therapeutic Candidate against Lung Cancer Cells
Authors: Liu Xue , Cui Shiyao , Dan Caiyun , Li Wenle , Xie Hongqing , Li Conghui , Shi Liangen
Published: December 2022

Phellinus baumii, a fungus that grows on mulberry trees and is used in traditional Chinese medicine, exerts therapeutic effects against various diseases, including cancer. Polyphenols, generally considered to be antioxidants, have antitumor and proapoptotic effects. In this study, we identified the composition of Phellinus baumii polyphenol (PBP) and characterized its 17 chemical components by UPLC–ESI–QTOF–MS. Furthermore, to clarify the potential mechanism of PBP against Lung Cancer Cells, network pharmacology and experimental verification were combined. Molecular docking elucidated the binding conformation and mechanism of the primary active components (Osmundacetone and hispidin) to the core targets CASP3, PARP1 and TP53. In addition, potential molecular mechanisms of PBP predicted by network pharmacology analysis were validated in vitro. PBP significantly inhibited the human lung cancer A549 cells and showed typical apoptotic characteristics, without significant cytotoxicity to normal human embryonic kidney (HEK293) cells. Analysis using flow cytometry and western blot indicated that PBP caused apoptosis, cell cycle arrest, reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (MMP) depression in A549 cells to exercise its antitumor effects. These results reveal that PBP has great potential for use as an active ingredient for antitumor therapy.
Electroretinography as a Biomarker to Monitor the Progression of Stargardt Disease
Authors: Sajovic Jana , Meglič Andrej , Hawlina Marko , Fakin Ana
Published: December 2022

The aim of the present study is to determine how electroretinographic (ERG) responses reflect age-related disease progression in the Stargardt disease (STGD1). The prospective comparative cohort study included 8 patients harboring two null ABCA4 variants (Group 1) and 34 patients with other ABCA4 genotypes (Group 2). Age at exam, age at onset, visual acuity (VA) and ERG responses were evaluated. The correlation between ERG responses and age in each patient group was determined using linear regression. A Mann-Whitney U Test was used to compare the median values between the groups. Age of onset was significantly earlier in Group 1 than in Group 2 (8 vs. 18), while disease duration was similar (13 vs. 12 years, i.e., advanced stage). Group 1 had significantly worse VA and lower ERG responses. ERG responses that significantly correlated with age in Group 1 were DA 0.01 and 3.0 ERG, which represented a retinal rod system response. The only ERG response that significantly correlated with age in Group 2 was the S-cone ERG. The observed difference was likely due to early cone loss occurring in double-null patients and slower photoreceptor loss in patients with other genotypes. The results suggest that specific ERG responses may be used to detect double-null patients at an early stage and monitor STGD1 disease progression in patients with specific genotypes.
Allosteric Inhibition of c-Abl to Induce Unfolded Protein Response and Cell Death in Multiple Myeloma
Authors: Kosako Hideki , Yamashita Yusuke , Morita Shuhei , Iwabuchi Sadahiro , Hashimoto Shinichi , Matsuoka Taka-Aki , Sonoki Takashi , Tamura Shinobu
Published: December 2022

Endoplasmic reticulum stress activates inositol-requiring enzyme 1α (IRE1α) and protein kinase, R-like endoplasmic reticulum kinase (PERK), the two principal regulators of the unfolded protein response (UPR). In multiple myeloma, adaptive IRE1α signaling is predominantly activated and regulates cell fate along with PERK. Recently, we demonstrated that GNF-2, an allosteric c-Abl inhibitor, rheostatically enhanced IRE1α activity and induced apoptosis through c-Abl conformational changes in pancreatic β cells. Herein, we analyzed whether the pharmacological modulation of c-Abl conformation resulted in anti-myeloma effects. First, we investigated the effects of GNF-2 on IRE1α activity and cell fate, followed by an investigation of the anti-myeloma effects of asciminib, a new allosteric c-Abl inhibitor. Finally, we performed RNA sequencing to characterize the signaling profiles of asciminib. We observed that both GNF-2 and asciminib decreased cell viability and induced XBP1 mRNA splicing in primary human myeloma cells and myeloma cell lines. RNA sequencing identified the induction of UPR- and apoptosis-related genes by asciminib. Asciminib re-localized c-Abl to the endoplasmic reticulum, and its combination with a specific IRE1α inhibitor, KIRA8, enhanced cell death with the reciprocal induction of CHOP mRNA expression. Together, the allosteric inhibition of c-Abl-activated UPR with anti-myeloma effects; this could be a novel therapeutic target for multiple myeloma.
Validation of Six Commercial Antibodies for the Detection of Heterologous and Endogenous TRPM8 Ion Channel Expression
Authors: Hernández-Ortego Pablo , Torres-Montero Remedios , de la Peña Elvira , Viana Félix , Fernández-Trillo Jorge
Published: December 2022

TRPM8 is a non-selective cation channel expressed in primary sensory neurons and other tissues, including the prostate and urothelium. Its participation in different physiological and pathological processes such as thermoregulation, pain, itch, inflammation and cancer has been widely described, making it a promising target for therapeutic approaches. The detection and quantification of TRPM8 seems crucial for advancing the knowledge of the mechanisms underlying its role in these pathophysiological conditions. Antibody-based techniques are commonly used for protein detection and quantification, although their performance with many ion channels, including TRPM8, is suboptimal. Thus, the search for reliable antibodies is of utmost importance. In this study, we characterized the performance of six TRPM8 commercial antibodies in three immunodetection techniques: Western blot, immunocytochemistry and immunohistochemistry. Different outcomes were obtained for the tested antibodies; two of them proved to be successful in detecting TRPM8 in the three approaches while, in the conditions tested, the other four were acceptable only for specific techniques. Considering our results, we offer some insight into the usefulness of these antibodies for the detection of TRPM8 depending on the methodology of choice.
Gamma-Tocotrienol Modulates Total-Body Irradiation-Induced Hematopoietic Injury in a Nonhuman Primate Model
Authors: Garg Tarun K. , Garg Sarita , Miousse Isabelle R. , Wise Stephen Y. , Carpenter Alana D. , Fatanmi Oluseyi O. , van Rhee Frits , Singh Vijay K. , Hauer-Jensen Martin
Published: December 2022

Radiation exposure causes acute damage to hematopoietic and immune cells. To date, there are no radioprotectors available to mitigate hematopoietic injury after radiation exposure. Gamma-tocotrienol (GT3) has demonstrated promising radioprotective efficacy in the mouse and nonhuman primate (NHP) models. We determined GT3-mediated hematopoietic recovery in total-body irradiated (TBI) NHPs. Sixteen rhesus macaques divided into two groups received either vehicle or GT3, 24 h prior to TBI. Four animals in each treatment group were exposed to either 4 or 5.8 Gy TBI. Flow cytometry was used to immunophenotype the bone marrow (BM) lymphoid cell populations, while clonogenic ability of hematopoietic stem cells (HSCs) was assessed by colony forming unit (CFU) assays on day 8 prior to irradiation and days 2, 7, 14, and 30 post-irradiation. Both radiation doses showed significant changes in the frequencies of B and T-cell subsets, including the self-renewable capacity of HSCs. Importantly, GT3 accelerated the recovery in CD34+ cells, increased HSC function as shown by improved recovery of CFU-granulocyte macrophages (CFU-GM) and burst-forming units erythroid (B-FUE), and aided the recovery of circulating neutrophils and platelets. These data elucidate the role of GT3 in hematopoietic recovery, which should be explored as a potential medical countermeasure to mitigate radiation-induced injury to the hematopoietic system.
Insight into Different Stages of Steroid Degradation in Thermophilic Saccharopolyspora hirsuta VKM Ac-666T Strain
Authors: Lobastova Tatyana , Fokina Victoria , Pozdnyakova-Filatova Irina , Tarlachkov Sergey , Shutov Andrey , Donova Marina
Published: December 2022

Steroids are abundant molecules in nature, and various microorganisms evolved to utilize steroids. Thermophilic actinobacteria play an important role in such processes. However, very few thermophiles have so far been reported capable of degrading or modifying natural sterols. Recently, genes putatively involved in the sterol catabolic pathway have been revealed in the moderately thermophilic actinobacterium Saccharopolyspora hirsuta VKM Ac-666T, but peculiarities of strain activity toward sterols are still poorly understood. S. hirsuta catalyzed cholesterol bioconversion at a rate significantly inferior to that observed for mesophilic actinobacteria (mycobacteria and rhodococci). Several genes related to different stages of steroid catabolism increased their expression in response to cholesterol as was shown by transcriptomic studies and verified by RT–qPCR. Sequential activation of genes related to the initial step of cholesterol side chain oxidation (cyp125) and later steps of steroid core degradation (kstD3, kshA, ipdF, and fadE30) was demonstrated for the first time. The activation correlates with a low cholesterol conversion rate and intermediate accumulation by the strain. The transcriptomic analyses revealed that the genes involved in sterol catabolism are linked functionally, but not transcriptionally. The results contribute to the knowledge on steroid catabolism in thermophilic actinobacteria and could be used at the engineering of microbial catalysts.
Divergent Contribution of the Golgi Apparatus to Microtubule Organization in Related Cell Lines
Authors: Brodsky Ilya B. , Fokin Artem I. , Efremov Aleksei A. , Nadezhdina Elena S. , Burakov Anton V.
Published: December 2022

Membrane trafficking in interphase animal cells is accomplished mostly along the microtubules. Microtubules are often organized radially by the microtubule-organizing center to coordinate intracellular transport. Along with the centrosome, the Golgi often serves as a microtubule-organizing center, capable of nucleating and retaining microtubules. Recent studies revealed the role of a special subset of Golgi-derived microtubules, which facilitates vesicular traffic from this central transport hub of the cell. However, proteins essential for microtubule organization onto the Golgi might be differentially expressed in different cell lines, while many potential participants remain undiscovered. In the current work, we analyzed the involvement of the Golgi complex in microtubule organization in related cell lines. We studied two cell lines, both originating from green monkey renal epithelium, and found that they relied either on the centrosome or on the Golgi as a main microtubule-organizing center. We demonstrated that the difference in their Golgi microtubule-organizing activity was not associated with the well-studied proteins, such as CAMSAP3, CLASP2, GCC185, and GMAP210, but revealed several potential candidates involved in this process.
Huperzine—A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation
Authors: Zhang Hongyu , Wang Danjie , Sun Jingxian , Wang Yumeng , Wu Shuai , Wang Jun
Published: December 2022

Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1β, IL-18, CD16, and TNF-α). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation.
Acylcarnitines in Ophthalmology: Promising Emerging Biomarkers
Authors: Theodoridis Konstantinos , Gika Helen , Kotali Antigoni
Published: December 2022

Several common ocular diseases are leading causes of irreversible visual impairment. Over the last decade, various mainly untargeted metabolic studies have been performed to show that metabolic dysfunction plays an important role in the pathogenesis of ocular diseases. A number of metabolites in plasma/serum, aqueous or vitreous humor, or in tears have been found to differ between patients and controls; among them are L-carnitine and acylcarnitines, which are essential for mitochondrial fatty acid oxidation. The metabolic profile of carnitines regarding a variety of diseases has attracted researchers’ interest. In this review, we present and discuss recent advances that have been made in the identification of carnitines as potential metabolic biomarkers in common ocular diseases, such as age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion, primary open-angle glaucoma, rhegmatogenous retinal detachment, and dry eye syndrome.
Advances in NURR1-Regulated Neuroinflammation Associated with Parkinson’s Disease
Authors: Al-Nusaif Murad , Lin Yushan , Li Tianbai , Cheng Cheng , Le Weidong
Published: December 2022

Neuroinflammation plays a crucial role in the progression of neurodegenerative disorders, particularly Parkinson’s disease (PD). Glial cell activation and subsequent adaptive immune involvement are neuroinflammatory features in familial and idiopathic PD, resulting in the death of dopaminergic neuron cells. An oxidative stress response, inflammatory mediator production, and immune cell recruitment and activation are all hallmarks of this activation, leading to chronic neuroinflammation and progressive neurodegeneration. Several studies in PD patients’ cerebrospinal fluid and peripheral blood revealed alterations in inflammatory markers and immune cell populations that may lead to or exacerbate neuroinflammation and perpetuate the neurodegenerative process. Most of the genes causing PD are also expressed in astrocytes and microglia, converting their neuroprotective role into a pathogenic one and contributing to disease onset and progression. Nuclear receptor-related transcription factor 1 (NURR1) regulates gene expression linked to dopaminergic neuron genesis and functional maintenance. In addition to playing a key role in developing and maintaining neurotransmitter phenotypes in dopaminergic neurons, NURR1 agonists have been shown to reverse behavioral and histological abnormalities in animal PD models. NURR1 protects dopaminergic neurons from inflammation-induced degeneration, specifically attenuating neuronal death by suppressing the expression of inflammatory genes in microglia and astrocytes. This narrative review highlights the inflammatory changes in PD and the advances in NURR1-regulated neuroinflammation associated with PD. Further, we present new evidence that targeting this inflammation with a variety of potential NURR1 target therapy medications can effectively slow the progression of chronic neuroinflammation-induced PD.
Removal of Pb2+, CrT, and Hg2+ Ions from Aqueous Solutions Using Amino-Functionalized Magnetic Nanoparticles
Authors: Allwin Mabes Raj A. F. P. , Bauman Maja , Lakić Marijana , Dimitrušev Nena , Lobnik Aleksandra , Košak Aljoša
Published: December 2022

In this paper, a circular economy approach with the adsorption and desorption of heavy metal (HM) ions—i.e., lead (Pb2+), chromium (CrT), and mercury (Hg2+)—from aqueous solutions was studied. Specific and selective binding of HM ions was performed on stabilized and amino-functionalized iron oxide magnetic nanoparticles (γ-Fe2O3@NH2 NPs) from an aqueous solution at pH 4 and 7. For this purpose, γ-Fe2O3@NH2 NPs were characterized by thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), specific surface area (BET), transmission electron microscopy (TEM), EDXS, and zeta potential measurements (ζ). The effects of different adsorbent amounts (mads = 20/45/90 mg) and the type of anions (NO3−, Cl−, SO42−) on adsorption efficiency were also tested. The desorption was performed with 0.1 M HNO3. The results showed improvement of adsorption efficiency for CrT, Pb2+, and Hg2+ ions at pH 7 by 45 mg of g-Fe2O3@NH2 NPs, and the sequence was as follows: CrT > Hg2+ > Pb2+, with adsorption capacities of 90.4 mg/g, 85.6 mg/g, and 83.6 mg/g, respectively. The desorption results showed the possibility for the reuse of γ-Fe2O3@NH2 NPs with HNO3, as the desorption efficiency was 100% for Hg2+ ions, 96.7% for CrT, and 91.3% for Pb2+.
Genome-Wide Identification of Aquaporin Genes in Adzuki Bean (Vigna angularis) and Expression Analysis under Drought Stress
Authors: Tayade Rupesh , Rana Varnika , Shafiqul Mohammad , Nabi Rizwana Begum Syed , Raturi Gaurav , Dhar Hena , Thakral Vandana , Kim Yoonha
Published: December 2022

The adzuki bean Vigna angularis (Wild.) is an important leguminous crop cultivated mainly for food purposes in Asian countries; it represents a source of carbohydrates, digestible proteins, minerals, and vitamins. Aquaporins (AQPs) are crucial membrane proteins involved in the transmembrane diffusion of water and small solutes in all living organisms, including plants. In this study, we used the whole genome sequence of the adzuki bean for in silico analysis to comprehensively identify 40 Vigna angularis aquaporin (VaAQP) genes and reveal how these plants react to drought stress. VaAQPs were compared with AQPs from other closely-related leguminous plants, and the results showed that mustard (Brassica rapa) (59), barrel medic (Medicago truncatula) (46), soybean (Glycine max) (66), and common bean (Phaseolus vulgaris L.) (41) had more AQP genes. Phylogenetic analysis revealed that forty VaAQPs belong to five subfamilies, with the VaPIPs (fifteen) subfamily the largest, followed by the VaNIPs (ten), VaTIPs (ten), VaSIPs (three), and VaXIPs (two) subfamilies. Furthermore, all AQP subcellular locations were found at the plasma membrane, and intron–exon analysis revealed a relationship between the intron number and gene expression, duplication, evolution, and diversity. Among the six motifs identified, motifs one, two, five, and six were prevalent in VaTIP, VaNIP, VaPIP, and VaXIP, while motifs one, three, and four were not observed in VaPIP1-3 and VaPIP1-4. Under drought stress, two of the VaAQPs (VaPIP2-1 and VaPIP2-5) showed significantly higher expression in the root tissue while the other two genes (VaPIP1-1 and VaPIP1-7) displayed variable expression in leaf tissue. This finding revealed that the selected VaAQPs might have unique molecular functions linked with the uptake of water under drought stress or in the exertion of osmoregulation to transport particular substrates rather than water to protect plants from drought. This study presents the first thorough investigation of VaAQPs in adzuki beans, and it reveals the transport mechanisms and related physiological processes that may be utilized for the development of drought-tolerant adzuki bean cultivars.
Advanced 3D Magnetic Scaffolds for Tumor-Related Bone Defects
Authors: Cojocaru Florina-Daniela , Balan Vera , Verestiuc Liliana
Published: December 2022

The need for bone substitutes is a major challenge as the incidence of serious bone disorders is massively increasing, mainly attributed to modern world problems, such as obesity, aging of the global population, and cancer incidence. Bone cancer represents one of the most significant causes of bone defects, with reserved prognosis regarding the effectiveness of treatments and survival rate. Modern therapies, such as hyperthermia, immunotherapy, targeted therapy, and magnetic therapy, seem to bring hope for cancer treatment in general, and bone cancer in particular. Mimicking the composition of bone to create advanced scaffolds, such as bone substitutes, proved to be insufficient for successful bone regeneration, and a special attention should be given to control the changes in the bone tissue micro-environment. The magnetic manipulation by an external field can be a promising technique to control this micro-environment, and to sustain the proliferation and differentiation of osteoblasts, promoting the expression of some growth factors, and, finally, accelerating new bone formation. By incorporating stimuli responsive nanocarriers in the scaffold’s architecture, such as magnetic nanoparticles functionalized with bioactive molecules, their behavior can be rigorously controlled under external magnetic driving, and stimulates the bone tissue formation.
Implementation of Copy Number Variations-Based Diagnostics in Morphologically Challenging EWSR1/FUS::NFATC2 Neoplasms of the Bone and Soft Tissue
Authors: Brcic Iva , Scheipl Susanne , Bergovec Marko , Leithner Andreas , Szkandera Joanna , Sotlar Karl , Suda Arnold , Smolle Maria , Kraus Tanja , Rosenberg Andrew , Liegl-Atzwanger Bernadette , Igrec Jasminka
Published: December 2022

In the last decade, new tumor entities have been described, including EWSR1/FUS::NFATC2-rearranged neoplasms of different biologic behavior. To gain further insights into the behavior of these tumors, we analyzed a spectrum of EWSR1/FUS::NFATC2-rearranged neoplasms and discuss their key diagnostic and molecular features in relation to their prognosis. We report five patients with EWSR1/FUS::NFATC2-rearranged neoplasms, including one simple bone cyst (SBC), two complex cystic bone lesions lacking morphological characteristics of SBC, and two sarcomas. In three cases, fluorescence in situ hybridization (FISH) and in all cases copy number variation (CNV) profiling and fusion analyses were performed. All patients were male, three cystic lesions occurred in children (aged 10, 14, and 17 years), and two sarcomas in adults (69 and 39 years). Fusion analysis revealed two FUS::NFATC2 rearrangements in two cystic lesions and three EWSR1::NFATC2 rearrangements in one complex cystic lesion and two sarcomas. EWSR1 FISH revealed tumor cells with break-apart signal without amplification in one complex cystic lesion and EWSR1 amplification in both sarcomas was documented. CNV analysis showed simple karyotypes in all cystic lesions, while more complex karyotypes were found in NFATC2-rearranged sarcomas. Our study supports and expands previously reported molecular findings of EWSR1/FUS::NFATC2-rearranged neoplasms. The study highlights the importance of combining radiology and morphologic features with molecular aberrations. The use of additional molecular methods, such as CNV and FISH in the routine diagnostic workup, can be crucial in providing a correct diagnosis and avoiding overtreatment.
Construction of a Compact and High-Precision Classifier in the Inductive Learning Method for Prediction and Diagnostic Problems
Authors: Kuzmich Roman , Stupina Alena , Yasinskiy Andrey , Pokushko Mariia , Tsarev Roman , Boubriak Ivan
Published: December 2022

The study is dictated by the need to make reasonable decisions in the classification of observations, for example, in the problems of medical prediction and diagnostics. Today, as part of the digitalization in healthcare, decision-making by a doctor is carried out using intelligent information systems. The introduction of such systems contributes to the implementation of policies aimed at ensuring sustainable development in the health sector. The paper discusses the method of inductive learning, which can be the algorithmic basis of such systems. In order to build a compact and high-precision classifier for the studied method, it is necessary to obtain a set of informative patterns and to create a method for building a classifier with high generalizing ability from this set of patterns. Three optimization models for the building of informative patterns have been developed, which are based on different concepts. Additionally, two algorithmic procedures have been developed that are used to obtain a compact and high-precision classifier. Experimental studies were carried out on the problems of medical prediction and diagnostics, aimed at finding the best optimization model for the building of informative pattern and at proving the effectiveness of the developed algorithmic procedures.
Investigating Concrete Properties Using Dielectric Constant from Ground Penetrating Radar Scans
Authors: Taylor Jonathan M. , Morris Isabel M.
Published: December 2022

Determining the material properties and existing capacity of concrete infrastructure using nondestructive techniques is challenging due to evolving design requirements, unknown as-built conditions, and ongoing maintenance and deterioration. Concrete’s material properties, including density, porosity, and compressive strength, are usually determined by mechanical testing, but being able to measure these properties noninvasively could aid engineers in maintaining and designing concrete infrastructure. Research into nondestructive methods for determining material properties of concrete has shown relationships between mechanical properties and ground penetrating radar (GPR) properties such as dielectric constant, attenuation, and instantaneous amplitude. We investigated direct relationships between dielectric constant and the density, porosity, and compressive strength of 23 mature concrete samples with varying mix designs using a commercial 1 GHz GPR. In normal-weight concrete, weak trends were seen between a dielectric for compressive strength (R2=0.76) and one for density (R2=0.64), whereas no significant trend was found with porosity (R2=0.52). The GPR unit used provides acceptable data but has limited resolution for analyses and utility. The dielectrics showed distinct clustering by mix type—particularly the inclusion of materials such as blast furnace slag. While demonstrating that the dielectric constant is a candidate for rapid concrete comparisons, there is also a demonstrated need for further investigation of the complex relationships between mechanical and electromagnetic properties in concrete.
Two-Dimensional and Three-Dimensional Coordination Polymers Based on Ln(III) and 2,5-Diiodoterephthalates: Structures and Luminescent Behavior
Authors: Zaguzin Alexander S. , Bondarenko Mikhail A. , Abramov Pavel A. , Rakhmanova Marianna I. , Sokolov Maxim N. , Fedin Vladimir P. , Adonin Sergey A.
Published: December 2022

Five new coordination polymers based on Ln3+ and 2,5-diiodoterephthalates (2,5-I-bdc)— {[La2(2,5-I-bdc)3(DMF)4]}·2DMF (1) and {[Ln2(2,5-I-bdc)3(DMF)4]} (Ln = La (2), Nd (3), Sm (4) and Eu (5))—were prepared and characterized by single crystal and powder X-ray diffractometry. Luminescent behavior was examined (the highest quantum yield is 4.5%); thermal stability was examined using thermogravimetric analysis.
Hydrothermal Synthesized CoS2 as Efficient Co-Catalyst to Improve the Interfacial Charge Transfer Efficiency in BiVO4
Authors: Gao Yangqin , Yang Guoqing , Tian Zhijie , Zhu Hongying , Ma Lianzheng , Li Xuli , Li Ning , Ge Lei
Published: December 2022

The bare surface of BiVO4 photoanode usually suffers from extremely low interfacial charge transfer efficiency which leads to a significantly suppressed photoelectrochemical water splitting performance. Various strategies, including surface modification and the loading of co-catalysts, facilitate the interface charge transfer process in BiVO4. In this study, we demonstrate that CoS2 synthesized from the hydrothermal method can be used as a high-efficient co-catalyst to sufficiently improve the interface charge transfer efficiency in BiVO4. The photoelectrochemical water splitting performance of BiVO4 was significantly improved after CoS2 surface modification. The BiVO4/CoS2 photoanode achieved an excellent photocurrent density of 5.2 mA/cm2 at 1.23 V versus RHE under AM 1.5 G illumination, corresponding to a 3.7 times enhancement in photocurrent compared with bare BiVO4. The onset potential of the BiVO4/CoS2 photoanode was also negatively shifted by 210 mV. The followed systematic combined optical and electrochemical characterization results reveal that the interfacial charge transfer efficiency of BiVO4 was largely improved from less than 20% to more than 70% due tor CoS2 surface modification. The further surface carrier dynamics study performed using an intensity modulated photocurrent spectroscopy displayed a 6–10 times suppression in surface recombination rate constants for CoS2 modified BiVO4, which suggests that the key reason for the improved interfacial charge transfer efficiency possibly originates from the passivated surface states due to the coating of CoS2.
Behavior and Bioadhesives: How Bolas Spiders, Mastophora hutchinsoni, Catch Moths
Authors: Diaz Candido , Long John H.
Published: December 2022

Spiders use various combinations of silks, adhesives, and behaviors to ensnare and trap prey. A common but difficult to catch prey in most spider habitats are moths. They easily escape typical orb-webs because their bodies are covered in sacrificial scales that flake off when in contact with the web’s adhesives. This defense is defeated by spiders of the sub-family of Cyrtarachninae, moth-catching specialists who combine changes in orb-web structure, predatory behavior, and chemistry of the aggregate glue placed in those webs. The most extreme changes in web structure are shown by bolas spiders, who create a solitary capture strand containing only one or two glue droplets at the end of a single thread. They prey on male moths by releasing pheromones to draw them within range of their bolas, which they flick to ensnare the moth. We used a high-speed video camera to capture the behavior of the bolas spider Mastophora hutchinsoni. We calculated the kinematics of spiders and moths in the wild to model the physical and mechanical properties of the bolas during prey capture, the behavior of the moth, and how these factors lead to successful prey capture. We created a numerical model to explain the mechanical behavior of the bolas silk during prey capture. Our kinematic analysis shows that the material properties of the aggregate glue bolas of M. hutchinsoni are distinct from that of the other previously analyzed moth-specialist, Cyrtarachne akirai. The spring-like behavior of the M. hutchinsoni bolas suggests it spins a thicker liquid.
Prognostic Value of Admission Peak NT-proBNP Combined with Culprit Plaque Types for Predicting Cardiovascular Risk in ST-Segment Elevated Myocardial Infarction: An Optical Coherence Tomography Study
Authors: Li Jiannan , Chen Runzhen , Zhou Jinying , Wang Ying , Zhao Xiaoxiao , Liu Chen , Zhou Peng , Chen Yi , Song Li , Yan Shaodi , Yan Hongbing , Zhao Hanjun
Published: December 2022

Objective: Different culprit plaque phenotypes including plaque rupture (PR) and non-plaque rupture (NPR), and N-Terminal prohormone of brain natriuretic peptide (NT-proBNP) have been reported to influence clinical outcomes in patients with acute coronary syndrome (ACS). We aimed to investigate the prognostic implication of the peak and baseline values at admission for NT-proBNP for major adverse cardiovascular events (MACE) in ST-Segment Elevated Myocardial Infarction (STEMI) patients with different plaque phenotype. Methods: A total of 428 patients with STEMI undergoing optical coherence tomography (OCT) were enrolled and divided into four groups: PR/Tertile1-2 NT-proBNP (n = 132), PR/Tertile3 NT-proBNP (n = 65), NPR/Tertile1-2 NT-proBNP (n = 154), NPR/Tertlie3 NT-proBNP (n = 77). Baseline and Peak values of NT-proBNP were obtained in the admission period. The MACEs were defined as the composite of all-cause death, recurrence of myocardial infarction and stroke. Results: High levels for peak NT-proBNP were significantly associated with a higher incidence of MACE and death (Log rank p = 0.037 and 0.0012, respectively). In the subgroup with NPR, a high level for peak NT-proBNP was significantly associated with higher incidence of death (Log rank p = 0.0022) but this association was not significant in the subgroup of PR (Log rank p = 0.24). Though plaque types were not associated with adverse event, the combination of NPR and a higher peak value for NT-proBNP indicated higher incidence of death compared with other groups (Log rank p = 0.0017). The area under the receiver operating characteristic curve for predicting death to evaluate the diagnostic value of the peak value for NT-proBNP and plaque types combined with traditional risk factors was 0.843 (95% CI: 0.805–0.876), which is superior to solely traditional risk factors: NRI (26.8% [95% CI: 0.4–53.1%], p = 0.046) and IDI (5.1% [95% CI: 1.0–9.2%], p = 0.016). Conclusion: STEMI patients with NPR and a high level for peak NT-proBNP showed higher incidence of death. The peak value of NT-proBNP in combination with plaque types can be used in risk stratification and prediction of death in patients with STEMI.
Infective Endocarditis: Predictive Factors for Diagnosis and Mortality in Surgically Treated Patients
Authors: Li Jing , Ruegamer Tamara , Brochhausen Christoph , Menhart Karin , Hiergeist Andreas , Kraemer Lukas , Hellwig Dirk , Maier Lars S. , Schmid Christof , Jantsch Jonathan , Schach Christian
Published: December 2022

Background: Diagnosis of infective endocarditis (IE) often is challenging, and mortality is high in such patients. Our goal was to characterize common diagnostic tools to enable a rapid and accurate diagnosis and to correlate these tools with mortality outcomes. Methods: Because of the possibility of including perioperative diagnostics, only surgically treated patients with suspected left-sided IE were included in this retrospective, monocentric study. A clinical committee confirmed the diagnosis of IE. Results: 201 consecutive patients (age 64 ± 13 years, 74% male) were finally diagnosed with IE, and 14 patients turned out IE-negative. Preoperative tests with the highest sensitivity for IE were positive blood cultures (89.0%) and transesophageal echocardiography (87.5%). In receiver operating characteristics, vegetation size revealed high predictive power for IE (AUC 0.800, p < 0.001) with an optimal cut-off value of 11.5 mm. Systemic embolism was associated with mortality, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) had predictive power for mortality. Conclusion: If diagnostic standard tools remain inconclusive, we suggest employing novel cut-off values to increase diagnostic accuracy and accelerate diagnosis. Patients with embolism or elevated NT-proBNP deserve a closer follow-up.
User Reputation on E-Commerce: Blockchain-Based Approaches
Authors: Gonçalves Maria José Angélico , Pereira Rui Humberto , Coelho Marta Alexandra Guerra Magalhães
Published: December 2022

User trust is a fundamental issue in e-commerce. To address this problem, recommendation systems have been widely used in different application domains including social media healthcare, e-commerce, and others. In this paper, we present a systematic review of the literature in the area of blockchain-based reputation models and we discuss the obtained results, answering the initial research questions. These findings lead us to conclude that the existing systems are based on a trusted third party (TTP) to collect and store reputation data, which does not provide transparency on users’ reputation scores. In the recent literature, on the one hand, blockchain-based reputation systems have been highlighted as possible solutions to effectively provide the necessary transparency, as well as effective identity management. On the other hand, new challenges are posed in terms of user privacy and performance, due to the specific characteristics of the blockchain. According to the literature, two major approaches have been proposed based on public and permissioned blockchains. Each approach applies adjusted models for calculating reputation scores. Despite the undoubted advantages added by a blockchain, the problem is only partially solved since there is no effective way to prevent blockchain oracles from feeding the chain with false, unfair, or biased data. In our future work, we intend to explore the two approaches discussed in the literature in order to propose a new blockchain-based model for deriving user reputation scores.
Effects of Image Quality on the Accuracy Human Pose Estimation and Detection of Eye Lid Opening/Closing Using Openpose and DLib
Authors: Ye Run Zhou , Subramanian Arun , Diedrich Daniel , Lindroth Heidi , Pickering Brian , Herasevich Vitaly
Published: December 2022

Objective: The application of computer models in continuous patient activity monitoring using video cameras is complicated by the capture of images of varying qualities due to poor lighting conditions and lower image resolutions. Insufficient literature has assessed the effects of image resolution, color depth, noise level, and low light on the inference of eye opening and closing and body landmarks from digital images. Method: This study systematically assessed the effects of varying image resolutions (from 100 × 100 pixels to 20 × 20 pixels at an interval of 10 pixels), lighting conditions (from 42 to 2 lux with an interval of 2 lux), color-depths (from 16.7 M colors to 8 M, 1 M, 512 K, 216 K, 64 K, 8 K, 1 K, 729, 512, 343, 216, 125, 64, 27, and 8 colors), and noise levels on the accuracy and model performance in eye dimension estimation and body keypoint localization using the Dlib library and OpenPose with images from the Closed Eyes in the Wild and the COCO datasets, as well as photographs of the face captured at different light intensities. Results: The model accuracy and rate of model failure remained acceptable at an image resolution of 60 × 60 pixels, a color depth of 343 colors, a light intensity of 14 lux, and a Gaussian noise level of 4% (i.e., 4% of pixels replaced by Gaussian noise). Conclusions: The Dlib and OpenPose models failed to detect eye dimensions and body keypoints only at low image resolutions, lighting conditions, and color depths. Clinical Impact: Our established baseline threshold values will be useful for future work in the application of computer vision in continuous patient monitoring.
Students Can (Mostly) Recognize Effective Learning, So Why Do They Not Do It?
Authors: Rea Stephany Duany , Wang Lisi , Muenks Katherine , Yan Veronica X.
Published: December 2022

Cognitive psychology research has emphasized that the strategies that are effective and efficient for fostering long-term retention (e.g., interleaved study, retrieval practice) are often not recognized as effective by students and are infrequently used. In the present studies, we use a mixed-methods approach and challenge the rhetoric that students are entirely unaware of effective learning strategies. We show that whether being asked to describe strategies used by poor-, average-, and high-performing students (Study 1) or being asked to judge vignettes of students using different strategies (Study 2), participants are generally readily able to identify effective strategies: they were able to recognize the efficacy of explanation, pretesting, interpolated retrieval practice, and even some interleaving. Despite their knowledge of these effective strategies, they were still unlikely to report using these strategies themselves. In Studies 2 and 3, we also explore the reasons why students might not use the strategies that they know are effective. Our findings suggest that interventions to improve learners’ strategy use might focus less on teaching them about what is effective and more on increasing self-efficacy, reducing the perceived costs, and establishing better habits.