bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the JAK/STAT Signaling Pathway in the Pathogenesis of Alzheimer’s Disease: New Potential Treatment Target
Authors: Rusek Marta , Smith Joanna , El-Khatib Kamel , Aikins Kennedy , Czuczwar Stanisław J. , Pluta Ryszard
Published: January 2023

Alzheimer’s disease is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, emerging evidence suggests that neuroinflammation, mediated notably by activated neuroglial cells, neutrophils, and macrophages, also plays an important role in the pathogenesis of Alzheimer’s disease. Therefore, understanding the interplay between the nervous and immune systems might be the key to the prevention or delay of Alzheimer’s disease progression. One of the most important mechanisms determining gliogenic cell fate is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway that is influenced by the overactivation of microglia and astrocytes. The JAK/STAT signaling pathway is one of the critical factors that promote neuroinflammation in neurodegenerative diseases such as Alzheimer’s disease by initiating innate immunity, orchestrating adaptive immune mechanisms, and finally, constraining neuroinflammatory response. Since a chronic neuroinflammatory environment in the brain is a hallmark of Alzheimer’s disease, understanding the process would allow establishing the underlying role of neuroinflammation, then estimating the prognosis of Alzheimer’s disease development and finding a new potential treatment target. In this review, we highlight the recent advances in the potential role of JAK/STAT signaling in neurological diseases with a focus on discussing future research directions regarding novel therapeutic approaches and predictive biomarkers for Alzheimer’s disease.
Microglia in Cultured Porcine Retina: Qualitative Immunohistochemical Analyses of Reactive Microglia in the Outer Retina
Authors: Johansson Kjell , Mohlin Camilla
Published: January 2023

A late stage of several retinal disorders is retinal detachment, a complication that results in rapid photoreceptor degeneration and synaptic damages. Experimental retinal detachment in vivo is an invasive and complicated method performed on anesthetized animals. As retinal detachment may result in visual impairment and blindness, research is of fundamental importance for understanding degenerative processes. Both morphological and ethical issues make the porcine retina a favorable organotypic model for studies of the degenerative processes that follow retinal detachment. In the cultured retina, photoreceptor degeneration and synaptic injuries develop rapidly and correlate with resident microglial cells’ transition into a reactive phenotype. In this immunohistochemical study, we have begun to analyze the transition of subsets of reactive microglia which are known to localize close to the outer plexiform layer (OPL) in degenerating in vivo and in vitro retina. Biomarkers for reactive microglia included P2Ry12, CD63 and CD68 and the general microglial markers were CD11b, Iba1 and isolectin B4 (IB4). The reactive microglia markers labeled microglia subpopulations, suggesting that protective or harmful reactive microglia may be present simultaneously in the injured retina. Our findings support the usage of porcine retina cultures for studies of photoreceptor injuries related to retinal detachment.
Genome Assembly of a Relict Arabian Species of Daphnia O. F. Müller (Crustacea: Cladocera) Adapted to the Desert Life
Authors: Hamza Waleed , Hazzouri Khaled M. , Sudalaimuthuasari Naganeeswaran , Amiri Khaled M. A. , Neretina Anna N. , Al Neyadi Shamma E. S. , Kotov Alexey A.
Published: January 2023

The water flea Daphnia O.F. Müller 1776 (Crustacea: Cladocera) is an important model of recent evolutionary biology. Here, we report a complete genome of Daphnia (Ctenodaphnia) arabica (Crustacea: Cladocera), recently described species endemic to deserts of the United Arab Emirates. In this study, genome analysis of D. arabica was carried out to investigate its genomic differences, complexity as well as its historical origins within the subgenus Daphnia (Ctenodaphnia). Hybrid genome assembly of D. arabica resulted in ~116 Mb of the assembled genome, with an N50 of ~1.13 Mb (BUSCO score of 99.2%). From the assembled genome, in total protein coding, 5374 tRNA and 643 rRNA genes were annotated. We found that the D. arabica complete genome differed from those of other Daphnia species deposited in the NCBI database but was close to that of D. cf. similoides. However, its divergence time estimate sets D. arabica in the Mesozoic, and our demographic analysis showed a great reduction in its genetic diversity compared to other Daphnia species. Interestingly, the population expansion in its diversity occurred during the megadrought climate around 100 Ka ago, reflecting the adaptive feature of the species to arid and drought-affected environments. Moreover, the PFAM comparative analysis highlights the presence of the important domain SOSS complex subunit C in D. arabica, which is missing in all other studied species of Daphnia. This complex consists of a few subunits (A, B, C) working together to maintain the genome stability (i.e., promoting the reparation of DNA under stress). We propose that this domain could play a role in maintaining the fitness and survival of this species in the desert environment. The present study will pave the way for future research to identify the genes that were gained or lost in this species and identify which of these were key factors to its adaptation to the harsh desert environment.
Higher Oxidative Stress in Endometriotic Lesions Upregulates Senescence-Associated p16ink4a and β-Galactosidase in Stromal Cells
Authors: Malvezzi Helena , Cestari Bruna Azevedo , Meola Juliana , Podgaec Sérgio
Published: January 2023

Endometriosis affects a significant proportion of women worldwide; however, no definitive cure for this disease has been discovered to date. Oxidative stress promotes endometriotic lesion maintenance in the peritoneal cavity in women. Furthermore, there is evidence of the mitogen-activated protein kinase (MAPK) signaling pathway and senescence involvement in the physiopathogenesis of endometriosis. Reactive oxygen species (ROS) cause oxidative damage and are expected to trigger senescence in the endometrium while also causing alterations in MAPK signaling. However, the role of ROS in the senescence-associated phenotype in endometriosis remains unknown. In this context, this study attempted to delineate the pathways linking ROS to senescence in endometrial and endometriotic lesions of healthy individuals and those with endometriosis. Our results indicate a higher presence of ROS in endometriotic lesions, and the upregulation of MAPK. Furthermore, we show that endometriotic lesions in stromal cells stimulated with hydrogen peroxide develop more senescence traits than eutopic and non-endometriosis endometrium. Overall, endometriotic cells respond differently to extracellular distress. Our contribution to further research in this field contributed to the roadmap of endometriosis’ search for alternative treatments.
MitoQ Protects Ovarian Organoids against Oxidative Stress during Oogenesis and Folliculogenesis In Vitro
Authors: Wang Jiapeng , Du Hua , Ma Lixin , Feng Mingqian , Li Liping , Zhao Xiaorong , Dai Yanfeng
Published: January 2023

Ovarian organoids, based on mouse female germline stem cells (FGSCs), have great value in basic research and are a vast prospect in pre-clinical drug screening due to their properties, but the competency of these in vitro-generated oocytes was generally low, especially, in vitro maturation (IVM) rate. Recently, it has been demonstrated that the 3D microenvironment triggers mitochondrial dysfunction during follicle growth in vitro. Therefore, therapies that protect mitochondria and enhance their function in oocytes warrant investigation. Here, we reported that exposure to 100 nM MitoQ promoted follicle growth and maturation in vitro, accompanied by scavenging ROS, reduced oxidative injury, and restored mitochondrial membrane potential in oocytes. Mechanistically, using mice granulosa cells (GCs) as a cellular model, it was shown that MitoQ protects GCs against H2O2-induced apoptosis by inhibiting the oxidative stress pathway. Together, these results reveal that MitoQ reduces oxidative stress in ovarian follicles via its antioxidative action, thereby protecting oocytes and granulosa cells and providing an efficient way to improve the quality of in vitro-generated oocytes.
A Low-Fat/Sucrose Diet Rich in Complex Carbohydrates Reverses High-Fat/Sucrose Diet-Induced Corneal Dysregulation
Authors: Akowuah Prince K. , Lema Carolina , Rumbaut Rolando E. , Burns Alan R.
Published: January 2023

High-fat/sucrose diet feeding in mice causes loss of corneal nerve function and impairs corneal wound healing. While changing to a diet with a low fat/sugar composition and enrichments in complex carbohydrates mitigates the reduction in nerve function, it remains to be determined if it has an effect on corneal wound healing. In this study, 6-week-old C57BL/6 male mice were fed either a normal diet or a high-fat/sucrose diet for 20 weeks. A third group (diet reversal) was placed on a high-fat/sucrose diet for 10 weeks followed by a normal diet for an additional 10 weeks. A central corneal epithelial abrasion wound was created, and wound closure was monitored. Neutrophil and platelet recruitment was assessed by immunofluorescence microscopy. Mice fed the high-fat/sucrose diet-only had greater adiposity (p < 0.005) than normal diet-only fed mice; diet reversal markedly reduced adiposity. Following corneal abrasion, wound closure was delayed by ~6 h (p ≤ 0.01) and, at 30 h post-wounding, fewer neutrophils reached the wound center and fewer extravascular platelets were present at the limbus (p < 0.05). Diet restored normal wound closure and neutrophil and platelet influx in the injured cornea. These data suggest compositional changes to the diet may be an effective diet-based therapeutic strategy for maintaining or restoring corneal health.
DHCR24, a Key Enzyme of Cholesterol Synthesis, Serves as a Marker Gene of the Mouse Adrenal Gland Inner Cortex
Authors: Zheng Huifei Sophia , Kang Yuan , Lyu Qiongxia , Junghans Kristina , Cleary Courtney , Reid Olivia , Cauthen Greer , Laprocina Karly , Huang Chen-Che Jeff
Published: January 2023

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by DHCR24). In humans and rats, DHCR24 is highly expressed in the adrenal gland, especially in the zona fasciculata. We recently reported that DHCR24 was expressed in the mouse adrenal gland’s inner cortex and also found that thyroid hormone treatment significantly upregulated the expression of Dhcr24 in the mouse adrenal gland. In the present study, we showed the cellular expression of DHCR24 in mouse adrenal glands in early postnatal stages. We found that the expression pattern of DHCR24 was similar to the X-zone marker gene 20αHSD in most developmental stages. This finding indicates that most steroidogenic adrenocortical cells in the mouse adrenal gland do not synthesize cholesterol locally. Unlike the 20αHSD-positive X-zone regresses during pregnancy, some DHCR24-positive cells remain present in parous females. Conditional knockout mice showed that the removal of Dhcr24 in steroidogenic cells did not affect the overall development of the adrenal gland or the secretion of corticosterone under acute stress. Whether DHCR24 plays a role in conditions where a continuous high amount of corticosterone production is needed requires further investigation.
SHIP1 Controls Internal Platelet Contraction and αIIbβ3 Integrin Dynamics in Early Platelet Activation
Authors: Severin Sonia , Consonni Alessandra , Chicanne Gaëtan , Allart Sophie , Payrastre Bernard , Gratacap Marie-Pierre
Published: January 2023

The Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP1) is known to dephosphorylate PtdIns(3,4,5)P3 into PtdIns(3,4)P2 and to interact with several signaling proteins though its docking functions. It has been shown to negatively regulate platelet adhesion and spreading on a fibrinogen surface and to positively regulate thrombus growth. In the present study, we have investigated its role during the early phase of platelet activation. Using confocal-based morphometric analysis, we found that SHIP1 is involved in the regulation of cytoskeletal organization and internal contractile activity in thrombin-activated platelets. The absence of SHIP1 has no significant impact on thrombin-induced Akt or Erk1/2 activation, but it selectively affects the RhoA/Rho-kinase pathway and myosin IIA relocalization to the cytoskeleton. SHIP1 interacts with the spectrin-based membrane skeleton, and its absence induces a loss of sustained association of integrins to this network together with a decrease in αIIbβ3 integrin clustering following thrombin stimulation. This αIIbβ3 integrin dynamics requires the contractile cytoskeleton under the control of SHIP1. RhoA activation, internal platelet contraction, and membrane skeleton integrin association were insensitive to the inhibition of PtdIns(3,4,5)P3 synthesis or SHIP1 phosphatase activity, indicating a role for the docking properties of SHIP1 in these processes. Altogether, our data reveal a lipid-independent function for SHIP1 in the regulation of the contractile cytoskeleton and integrin dynamics in platelets.
Top-Down Proteomics Detection of Potential Salivary Biomarkers for Autoimmune Liver Diseases Classification
Authors: Olianas Alessandra , Guadalupi Giulia , Cabras Tiziana , Contini Cristina , Serrao Simone , Iavarone Federica , Castagnola Massimo , Messana Irene , Onali Simona , Chessa Luchino , Diaz Giacomo , Manconi Barbara
Published: January 2023

(1) Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases characterized by chronic hepatic inflammation and progressive liver fibrosis. The possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. The use of proteomics for personalized medicine is a rapidly emerging field. (2) Salivary proteomic data of 36 healthy controls (HCs), 36 AIH and 36 PBC patients, obtained by liquid chromatography/mass spectrometry top-down pipeline, were analyzed by multiple Mann—Whitney test, Kendall correlation, Random Forest (RF) analysis and Linear Discriminant Analysis (LDA); (3) Mann—Whitney tests provided indications on the panel of differentially expressed salivary proteins and peptides, namely cystatin A, statherin, histatin 3, histatin 5 and histatin 6, which were elevated in AIH patients with respect to both HCs and PBC patients, while S100A12, S100A9 short, cystatin S1, S2, SN and C showed varied levels in PBC with respect to HCs and/or AIH patients. RF analysis evidenced a panel of salivary proteins/peptides able to classify with good accuracy PBC vs. HCs (83.3%), AIH vs. HCs (79.9%) and PBC vs. AIH (80.2%); (4) RF appears to be an attractive machine-learning tool suited for classification of AIH and PBC based on their different salivary proteomic profiles.
The Genome of Fusarium oxysporum f. sp. phaseoli Provides Insight into the Evolution of Genomes and Effectors of Fusarium oxysporum Species
Authors: Hao Yali , Li Yan , Ping Xingxing , Yang Qihong , Mao Zhenchuan , Zhao Jianlong , Lu Xiaofei , Xie Bingyan , Yang Yuhong , Ling Jian
Published: January 2023

Fusarium oxysporum f. sp. phaseoli, the causal agent of cowpea fusarium wilt, is a serious threat to cowpea production in China. In this study, a sample of cowpea fusarium wilt was identified as Fusarium oxysporum f. sp. phaseoli using the methods of morphological characters and molecular detection. We further reported the first genome assembly for Fusarium oxysporum f. sp. phaseoli, with 53.7 Mb genome sequence comprising 14,694 genes. Comparative genomic analysis among five Fusarium oxysporum genomes showed that four accessory chromosomes in the five Fusarium oxysporum display similar characteristics, with low sequence similarity (55.35%, vs. overall average of 81.76%), low gene density (2.18 genes/10 kb vs. 3.02 genes/Mb) and highly transposable element density (TEs) (15.01/100 kb vs. 4.89/100 kb), indicating that variable accessory chromosomes are the main source of Fusarium oxysporum evolution. We identified a total of 100 Fusarium oxysporum f. sp. phaseoli-specific effectors in the genome and found 13 specific effector genes located in large insertion or deletion regions, suggesting that insertion or deletion events can cause the emergence of species-specific effectors in Fusarium oxysporum. Our genome assembly of Fusarium oxysporum f. sp. phaseoli provides a valuable resource for the study of cowpea fusarium wilt, and the comparative genomic study of Fusarium oxysporum could contribute to the knowledge of genome and effector-associated pathogenicity evolution in Fusarium oxysporum study.
Similar Pro- and Antiangiogenic Profiles Close to Delivery in Different Clinical Presentations of Two Pregnancy Syndromes: Preeclampsia and Fetal Growth Restriction
Authors: Dymara-Konopka Weronika , Laskowska Marzena , Grywalska Ewelina , Hymos Anna , Błażewicz Anna , Leszczyńska-Gorzelak Bożena
Published: January 2023

The purpose of this study was to evaluate serum levels of anti- and pro-angiogenic substances measured using enzyme-linked immunosorbent assays and their ratios in pregnancies complicated by different clinical subsets of placental ischemic syndrome: preeclampsia and/or fetal growth restriction. A prospective case-control study was performed consisting of 77 singleton pregnancies complicated by preeclampsia, preeclampsia with concurrent fetal growth restriction (FGR), and isolated normotensive FGR pairwise matched by gestational age with healthy pregnancies. The entire study cohort was analyzed with respect to adverse pregnancy outcomes that occurred. In all investigated subgroups, placental growth factor (PlGF) was lower and soluble endoglin (sEng), the soluble fms-like tyrosine kinase-1—sFlt-1/PlGF and sFlt-1*sEng/PlGF ratios were higher than in the control group. The differences were most strongly pronounced in the PE with concurrent FGR group and in the sFlt-1/PlGF ratio. The highest sFlt-1 values in preeclamptic patients suggest that this substance may be responsible for reaching the threshold needed for PE to develop as a maternal manifestation of ischemic placental disease. The FGR is characterized by an elevated maternal sFlt-1/PlGF ratio, which boosts at the moment of indicated delivery due to fetal risk. We concluded that angiogenic imbalance is reflective of placental disease regardless of its clinical manifestation in the mother, and may be used as support for the diagnosis and prognosis of FGR.
Low Magnesium in Conjunction with High Homocysteine and Less Sleep Accelerates Telomere Attrition in Healthy Elderly Australian
Authors: Dhillon Varinderpal S. , Deo Permal , Thomas Philip , Fenech Michael
Published: January 2023

The relationship between sleep and micronutrients, including magnesium, is implicated in its regulation. The effects of low magnesium and other micronutrients on sleep disruption and telomere loss are not well understood. The present study was carried out in 172 healthy elderly subjects from South Australia. Plasma micronutrients including magnesium were measured. Each participant provided information about their sleep hours (<7 h or ≥7 h). Lymphocyte telomere length (TL) was measured by real-time qPCR assay. Plasma magnesium level was significantly low in subjects who sleep less than 7 h (p = 0.0002). TL was significantly shorter in people who are low in magnesium and sleep less than 7 h (p = 0.01). Plasma homocysteine (Hcy) is negatively associated with magnesium (r = −0.299; p < 0.0001). There is a significant interaction effect of magnesium and Hcy on sleep duration (p = 0.04) and TL (p = 0.003). Our results suggest that inadequate magnesium levels have an adverse impact on sleep and telomere attrition rate in cognitively normal elderly people, and this may be exacerbated by low levels of vitamin B12 and folate that elevate Hcy concentration.
Integrating Common Risk Factors with Polygenic Scores Improves the Prediction of Type 2 Diabetes
Authors: Timasheva Yanina , Balkhiyarova Zhanna , Avzaletdinova Diana , Rassoleeva Irina , Morugova Tatiana V. , Korytina Gulnaz , Prokopenko Inga , Kochetova Olga
Published: January 2023

We tested associations between 13 established genetic variants and type 2 diabetes (T2D) in 1371 study participants from the Volga-Ural region of the Eurasian continent, and evaluated the predictive ability of the model containing polygenic scores for the variants associated with T2D in our dataset, alone and in combination with other risk factors such as age and sex. Using logistic regression analysis, we found associations with T2D for the CCL20 rs6749704 (OR = 1.68, PFDR = 3.40 × 10−5), CCR5 rs333 (OR = 1.99, PFDR = 0.033), ADIPOQ rs17366743 (OR = 3.17, PFDR = 2.64 × 10−4), TCF7L2 rs114758349 (OR = 1.77, PFDR = 9.37 × 10−5), and CCL2 rs1024611 (OR = 1.38, PFDR = 0.033) polymorphisms. We showed that the most informative prognostic model included weighted polygenic scores for these five loci, and non-genetic factors such as age and sex (AUC 85.8%, 95%CI 83.7–87.8%). Compared to the model containing only non-genetic parameters, adding the polygenic score for the five T2D-associated loci showed improved net reclassification (NRI = 37.62%, 1.39 × 10−6). Inclusion of all 13 tested SNPs to the model with age and sex did not improve the predictive ability compared to the model containing five T2D-associated variants (NRI = −17.86, p = 0.093). The five variants associated with T2D in people from the Volga-Ural region are linked to inflammation (CCR5, CCL2, CCL20) and glucose metabolism regulation (TCF7L, ADIPOQ2). Further studies in independent groups of T2D patients should validate the prognostic value of the model and elucidate the molecular mechanisms of the disease development.
A New ABCB1 Inhibitor Enhances the Anticancer Effect of Doxorubicin in Both In Vitro and In Vivo Models of NSCLC
Authors: Adorni Maria Pia , Galetti Maricla , La Monica Silvia , Incerti Matteo , Ruffoni Alessandro , Elviri Lisa , Zanotti Ilaria , Papotti Bianca , Cavallo Delia , Alfieri Roberta , Petronini Pier Giorgio , Bernini Franco
Published: January 2023

In tumors, the multi drug resistance phenomenon may occur through the efflux of chemotherapeutic drugs out of cancer cells, impeding their accumulation, and eventually reducing their toxicity. This process is mediated by transporters overexpressed in the plasma membranes of tumor cells, among which is the P-glycoprotein/multidrug resistance 1/ATP-binding cassette B1 (P-gp/MDR1/ABCB1). The aim of this study was to explore the effect of a new molecule, called AIF-1, on ABCB1 activity. In a cellular model of non-small cell lung cancer (NSCLC), AIF-1 significantly inhibited ABCB1 activity, which was evaluated by the fluorimetric measurement of the intracellular accumulation of calcein. AIF-1 also significantly increased the intracellular content of doxorubicin, which was evaluated by confocal microscopy and LC-MS/MS analysis. This effect translated to higher cytotoxicity of doxorubicin and reduced cellular proliferation. Finally, in a murine xenograft model, the tumor volume increased by 267% and 148% on average in mice treated with vehicle and doxorubicin alone, respectively. After the co-administration of doxorubicin with AIF-1, tumor volume increased by only 13.4%. In conclusion, these results suggest enhancement of the efficacy of the chemotherapeutic drug doxorubicin by AIF-1, laying the basis for the future development of new ABCB1 inhibitors for tumor treatment.
Towards Accurate Identification of Antibiotic-Resistant Pathogens through the Ensemble of Multiple Preprocessing Methods Based on MALDI-TOF Spectra
Authors: Chung Chia-Ru , Wang Hsin-Yao , Chou Po-Han , Wu Li-Ching , Lu Jang-Jih , Horng Jorng-Tzong , Lee Tzong-Yi
Published: January 2023

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has been used to identify microorganisms and predict antibiotic resistance. The preprocessing method for the MS spectrum is key to extracting critical information from complicated MS spectral data. Different preprocessing methods yield different data, and the optimal approach is unclear. In this study, we adopted an ensemble of multiple preprocessing methods––FlexAnalysis, MALDIquant, and continuous wavelet transform-based methods––to detect peaks and build machine learning classifiers, including logistic regressions, naïve Bayes classifiers, random forests, and a support vector machine. The aim was to identify antibiotic resistance in Acinetobacter baumannii, Acinetobacter nosocomialis, Enterococcus faecium, and Group B Streptococci (GBS) based on MALDI-TOF MS spectra collected from two branches of a referral tertiary medical center. The ensemble method was compared with the individual methods. Random forest models built with the data preprocessed by the ensemble method outperformed individual preprocessing methods and achieved the highest accuracy, with values of 84.37% (A. baumannii), 90.96% (A. nosocomialis), 78.54% (E. faecium), and 70.12% (GBS) on independent testing datasets. Through feature selection, important peaks related to antibiotic resistance could be detected from integrated information. The prediction model can provide an opinion for clinicians. The discriminative peaks enabling better prediction performance can provide a reference for further investigation of the resistance mechanism.
Cobalt Ferrite/Polyetherimide Composites as Thermally Stable Materials for Electromagnetic Interference Shielding Uses
Authors: Asandulesa Mihai , Hamciuc Corneliu , Pui Aurel , Virlan Constantin , Lisa Gabriela , Barzic Andreea Irina , Oprisan Bogdan
Published: January 2023

The progress of the automated industry has introduced many benefits in our daily life, but it also produces undesired electromagnetic interference (EMI) that distresses the end-users and functionality of electronic devices. This article develops new composites based on a polyetherimide (PEI) matrix and cobalt ferrite (CoFe2O4) nanofiller (10–50 wt%) by mixing inorganic phase in the poly(amic acid) solution, followed by film casting and controlled heating, to acquire the corresponding imide structure. The composites were designed to contain both electric and magnetic dipole sources by including highly polarizable groups (phenyls, ethers, -CN) in the PEI structure and by loading this matrix with magnetic nanoparticles, respectively. The films exhibited high thermal stability, having the temperature at which decomposition begins in the interval of 450–487 °C. Magnetic analyses indicated a saturation magnetization, coercitive force, and magnetic remanence of 27.9 emu g−1, 705 Oe, and 9.57 emu g−1, respectively, for the PEI/CoFe2O4 50 wt%. Electrical measurements evidenced an increase in the conductivity from 4.42 10−9 S/cm for the neat PEI to 1.70 10−8 S/cm for PEI/CoFe2O4 50 wt% at 1 MHz. The subglass γ- and β-relaxations, primary relaxation, and conductivity relaxation were also examined depending on the nanofiller content. These novel composites are investigated from the point of view of their EMI shielding properties, showing that they are capable of attenuating the electric and magnetic parts of electromagnetic waves.
SCOBY Cellulose Modified with Apple Powder—Biomaterial with Functional Characteristics
Authors: Bryszewska Malgorzata Anita , Tabandeh Erfan , Jędrasik Jakub , Czarnecka Maja , Dzierżanowska Julia , Ludwicka Karolina
Published: January 2023

The need for new non-animal and non-petroleum-based materials is strongly emphasized in the sustainable and green economy. Waste materials have proven a valuable resource in this regard. In fact, there have been quite a large number of goods obtained from wastes called “Vegan leather” that have gained the clothing market’s attention in recent years. In practice, they are mostly composites of waste materials like cactus, pineapples, or, eventually, apples with polymers like polyurethane or polyvinyl chloride. The article presents the results of work aimed at obtaining a material based entirely on natural, biodegradable raw materials. Bacterial cellulose produced as a byproduct of the fermentation carried out by SCOBY was modified with glycerol and then altered by the entrapment of apple powder. The effect of introducing apple powder into the SCOBY culture media on the mechanical properties of the obtained bacterial cellulose was also evaluated The resulting material acquired new mechanical characteristics that are advantageous in terms of strength. Microscopic observation of the apple powder layer showed that the coverage was uniform. Different amounts of apple powder were used to cover the cellulose surface from 10 to 60%, and it was found that the variant with 40% of this powder was the most favorable in terms of mechanical strength. Also, the application of the created material as a card folder showed that it is durable in use and retains its functional characteristics for at least 1 month. The mechanical properties of modified bacterial cellulose were favorably affected by the entrapment of apple powder on its surface, and as a result, a novel material with functional characteristics was obtained.
The Role of Inflammation and Therapeutic Concepts in Diabetic Retinopathy—A Short Review
Authors: Gomułka Krzysztof , Ruta Michał
Published: January 2023

Diabetic retinopathy (DR) as a microangiopathy is the most common complication in patients with diabetes mellitus (DM) and remains the leading cause of blindness among adult population. DM in its complicated pathomechanism relates to chronic hyperglycemia, hypoinsulinemia, dyslipidemia and hypertension—all these components in molecular pathways maintain oxidative stress, formation of advanced glycation end-products, microvascular changes, inflammation, and retinal neurodegeneration as one of the key players in diabetes-associated retinal perturbations. In this current review, we discuss the natural history of DR with special emphasis on ongoing inflammation and the key role of vascular endothelial growth factor (VEGF). Additionally, we provide an overview of the principles of diabetic retinopathy treatments, i.e., in laser therapy, anti-VEGF and steroid options.
Exploring the Effects of Metabolism-Disrupting Chemicals on Pancreatic α-Cell Viability, Gene Expression and Function: A Screening Testing Approach
Authors: Al-Abdulla Ruba , Ferrero Hilda , Boronat-Belda Talía , Soriano Sergi , Quesada Iván , Alonso-Magdalena Paloma
Published: January 2023

Humans are constantly exposed to many environmental pollutants, some of which have been largely acknowledged as key factors in the development of metabolic disorders such as diabetes and obesity. These chemicals have been classified as endocrine-disrupting chemicals (EDCs) and, more recently, since they can interfere with metabolic functions, they have been renamed as metabolism-disrupting chemicals (MDCs). MDCs are present in many consumer products, including food packaging, personal care products, plastic bottles and containers, and detergents. The scientific literature has ever-increasingly focused on insulin-releasing pancreatic β-cells as one of the main targets for MDCs. Evidence highlights that these substances may disrupt glucose homeostasis by altering pancreatic β-cell physiology. However, their potential impact on glucagon-secreting pancreatic α-cells remains poorly known despite the essential role that this cellular type plays in controlling glucose metabolism. In the present study, we have selected seven paradigmatic MDCs representing major toxic classes, including bisphenols, phthalates, perfluorinated compounds, metals, and pesticides. By using an in vitro cell-based model, the pancreatic α-cell line αTC1-9, we have explored the effects of these compounds on pancreatic α-cell viability, gene expression, and secretion. We found that cell viability was moderately affected after bisphenol-A (BPA), bisphenol-F (BPF), and perfluorooctanesulfonic acid (PFOS) exposure, although cytotoxicity was relatively low. In addition, all bisphenols, as well as di(2-ethylhexyl) phthalate (DEHP) and cadmium chloride (CdCl2), promoted a marked decreased on glucagon secretion, together with changes in the expression of glucagon and/or transcription factors involved in cell function and identity, such as Foxo1 and Arx. Overall, our results indicated that most of the selected chemicals studied caused functional alterations in pancreatic α-cells. Moreover, we revealed, for the first time, their direct effects on key molecular aspects of pancreatic α-cell biology.
Anticandidal Activity of Capsaicin and Its Effect on Ergosterol Biosynthesis and Membrane Integrity of Candida albicans
Authors: Behbehani Jawad M. , Irshad Mohammad , Shreaz Sheikh , Karched Maribasappa
Published: January 2023

Oral candidiasis is an infection of the oral cavity commonly caused by Candida albicans. Endodontic treatment failure has also been found to be persistent from C. albicans in the root canal system. Despite the availability of antifungal drugs, the management of Candida oral infection is difficult as it exhibits resistance to a different class of antifungal drugs. Therefore, it is necessary to discover new antifungal compounds to cure fungal infections. This study aimed to examine the antifungal susceptibility of Capsaicin, an active compound of chili pepper. The susceptibility of Capsaicin and Fluconazole was tested against the Candida species by the CLSI (M27-A3) method. The effect of Capsaicin on the fungal cell wall was examined by the ergosterol inhibitory assay and observed by the scanning electron micrograph. The MIC range of Capsaicin against Candida isolates from oral (n = 30), endodontic (n = 8), and ATCC strains (n = 2) was 12.5–50 µg/mL. The MIC range of Fluconazole (128- 4 µg/mL) significantly decreased (2- to 4-fold) after the combination with Capsaicin (MIC/4) (p < 0.05). Capsaicin (at MIC) significantly reduced the mature biofilm of C. albicans by 70 to 89% (p < 0.01). The ergosterol content of the cell wall decreased significantly with the increase in the Capsaicin dose (p < 0.01). Capsaicin showed high sensitivity against the hyphae formation and demonstrated a more than 71% reduction in mature biofilm. A fluorescence microscopy revealed the membrane disruption of Capsaicin-treated C. albicans cells, whereas a micrograph of electron microscopy showed the distorted cells’ shape, ruptured cell walls, and shrinkage of cells after the release of intracellular content. The results conclude that Capsaicin had a potential antifungal activity that inhibits the ergosterol biosynthesis in the cell wall, and therefore, the cells’ structure and integrity were disrupted. More importantly, Capsaicin synergistically enhanced the Fluconazole antifungal activity, and the synergistic effect might be helpful in the prevention of Fluconazole resistance development and reduced drug-dosing.
Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome
Authors: He Steven , Chakraborty Rajdeep , Ranganathan Shoba
Published: January 2023

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40–50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.
Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations
Authors: Bobylev Alexander G. , Yakupova Elmira I. , Bobyleva Liya G. , Molochkov Nikolay V. , Timchenko Alexander A. , Timchenko Maria A. , Kihara Hiroshi , Nikulin Alexey D. , Gabdulkhakov Azat G. , Melnik Tatiana N. , Penkov Nikita V. , Lobanov Michail Y. , Kazakov Alexey S. , Kellermayer Miklós , Mártonfalvi Zsolt , Galzitskaya Oxana V. , Vikhlyantsev Ivan M.
Published: January 2023

A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500–1500 kDa. Using various structural-analysis methods, we investigated in vitro nonspecific amyloid aggregation of the high-molecular-weight isoform of chicken smooth-muscle titin (SMTHMW, ~1500 kDa). As confirmed by X-ray diffraction analysis, under near-physiological conditions, the protein formed amorphous amyloid aggregates with a quaternary cross-β structure within a relatively short time (~60 min). As shown by circular dichroism and Fourier-transform infrared spectroscopy, the quaternary cross-β structure—unlike other amyloidogenic proteins—formed without changes in the SMTHMW secondary structure. SMTHMW aggregates partially disaggregated upon increasing the ionic strength above the physiological level. Based on the data obtained, it is not the complete protein but its particular domains/segments that are likely involved in the formation of intermolecular interactions during SMTHMW amyloid aggregation. The discovered properties of titin position this protein as an object of interest for studying amyloid aggregation in vitro and expanding our views of the fundamentals of amyloidogenesis.
Improving Sleep Quality to Prevent Perinatal Depression: The Obstetric Nurse Intervention
Authors: Poeira Ana Filipa , Zangão Maria Otília
Published: January 2023

Throughout their life, women should pay attention to their mental health. Evidence indicates that poor sleep quality is related to depressive symptoms in pregnancy, justifying the intervention of health professionals in improving sleep quality to promote the mental health of pregnant women. The objective of our study is to analyze the relationship between sleep quality and perinatal depression, and to identify the obstetric nurse’s intervention in improving sleep quality in the perinatal period. A total of 53 pregnant women between the 28th week of pregnancy and the 7th day after delivery completed the Edinburgh Postnatal Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI). Women were also asked about the strategies used by the obstetric nurse to improve their quality of sleep. Data analysis was performed using IBM SPSS Statistics software, version 25.0. The Mann–Whitney-U and Kruskal-Wallis tests were carried out. A p-value < 0.05 was considered statistically significant. The median PSQI score was 10 (±3.63), and 9.2% (n = 9) had good quality sleep. The median EPDS score was 12 (±4.43), and 27 participants (50.9%) had probable depression. The women with likely depression had worse sleep quality (p = 0.016). Most participants reported that the obstetric nurse showed no interest in their sleep quality during pregnancy. Women of other nationalities have a higher risk of depression (p = 0.013). Based on our results, it is crucial to assess sleep quality in the perinatal period to promote women’s health during the prenatal and postnatal periods, and more action is needed since we are facing one of the most significant challenges of this century, preventing depression.
Active Turbulence Grid-Controlled Inflow Turbulence and Replication of Heat Exchanger Flow Fields in Fan Applications
Authors: Czwielong Felix , Becker Stefan
Published: January 2023

A novel active turbulence grid of the Institute of Fluid Mechanics at FAU Erlangen-Nuremberg is introduced. The focus of this grid is not on basic investigations of fluid mechanics, as is usually the case with active turbulence grids, but the generation of defined inflow conditions for axial fans. Thus, by means of the active turbulence grid, individual turbulence characteristics in the flow to the fan can be changed; therefore, fundamental interactions between the flow mechanics at the axial fan and the sound radiation can be analyzed. In addition, the replication of the flow fields of heat exchangers by the active turbulence grid is the focus of the investigations. The investigations showed that it is possible to use the active turbulence grid to generate defined inflow conditions for axial fans. It was also possible to reproduce the heat exchanger flow fields both for the mean turbulence values and for the spatial distributions. It was found that the grid induces tonal components due to the drive motors, but also that the inherent noise has no significant influence on the spectrum of the fans under investigation. Based on selected turbulence characteristics, direct correlations were found between the spatial distribution of the turbulence level and sound radiation at the first blade passing frequency of the axial fan. As the variance of the turbulence level increases, the sound radiation of the tonal components becomes more pronounced. The total sound pressure level, however, is mainly determined by the low-frequency broadband sound. A linear relationship between the spatial mean value of the turbulence level and the total sound pressure level was found for the investigated axial fan.
Analysis of Diabetic Retinopathy (DR) Based on the Deep Learning
Authors: Fayyaz Abdul Muiz , Sharif Muhammad Imran , Azam Sami , Karim Asif , El-Den Jamal
Published: January 2023

If Diabetic Retinopathy (DR) patients do not receive quick diagnosis and treatment, they may lose vision. DR, an eye disorder caused by high blood glucose, is becoming more prevalent worldwide. Once early warning signs are detected, the severity of the disease must be validated before choosing the best treatment. In this research, a deep learning network is used to automatically detect and classify DR fundus images depending on severity using AlexNet and Resnet101-based feature extraction. Interconnected layers helps to identify the critical features or characteristics; in addition, Ant Colony systems also help choose the characteristics. Passing these chosen attributes through SVM with multiple kernels yielded the final classification model with promising accuracy. The experiment based on 750 features proves that the proposed approach has achieved an accuracy of 93%.
Vehicular Networks Dynamic Grouping and Re-Orchestration Scenarios
Authors: Al-Hamid Duaa Zuhair , Al-Anbuky Adnan
Published: January 2023

The topological structure in vehicular communication networks presents challenges for sustaining network connectivity on the road. Highway dynamics, for example, encourage the need for an adaptive and flexible structure to handle the rapid events of vehicles joining and leaving the road. Such demand aligns with the advancement made in software-defined networks and related dynamic network re-orchestration. This paper discusses the development of a virtual model that represents the operation of an autonomous vehicular network. It also investigates the ability to re-orchestrate the topology through software definition while running the various operational phases. Network self-formation, network expansion, retraction via vehicular members joining and leaving, and network self-healing when a topological rupture occurs as a result of a key member leaving the network are the key grouping phases. The communication approach is analyzed based on the status of network members and their ability to assume the various network roles. The concept is tested using both a Contiki–Cooja network simulator and a MATLAB analytical modeling tool to reflect the operation and performance of the grouping approach under various road scenarios. The outcome of the analysis reflects the ability of the group to be formulated within a measured latency considering the various network parameters such as communication message rate. The approach offers tools for managing the dynamic connectivity of vehicular groups and may also be extended to assume the function of an on-road network digital twin during the lifetime of a given group.
Knockdown of the Sodium/Potassium ATPase Subunit Beta 2 Reduces Egg Production in the Dengue Vector, Aedes aegypti
Authors: Martinez Nathan P. , Pinch Matthew , Kandel Yashoda , Hansen Immo A.
Published: January 2023

The Na+/K+ ATPase (NKA) is present in the cellular membrane of most eukaryotic cells. It utilizes energy released by ATP hydrolysis to pump sodium ions out of the cell and potassium ions into the cell, which establishes and controls ion gradients. Functional NKA pumps consist of three subunits, alpha, beta, and FXYD. The alpha subunit serves as the catalytic subunit while the beta and FXYD subunits regulate the proper folding and localization, and ion affinity of the alpha subunit, respectively. Here we demonstrate that knockdown of NKA beta subunit 2 mRNA (nkaβ2) reduces fecundity in female Ae. aegypti. We determined the expression pattern of nkaβ2 in several adult mosquito organs using qRT-PCR. We performed RNAi-mediated knockdown of nkaβ2 and assayed for lethality, and effects on female fecundity. Tissue expression levels of nkaβ2 mRNA were highest in the ovaries with the fat body, midgut and thorax having similar expression levels, while Malpighian tubules had significantly lower expression. Survival curves recorded post dsRNA injection showed a non-significant decrease in survival of nkaβ2 dsRNA-injected mosquitoes compared to GFP dsRNA-injected mosquitoes. We observed a significant reduction in the number of eggs laid by nkaβ2 dsRNA-injected mosquitoes compared to control mosquitoes. These results, coupled with the tissue expression profile of nkaβ2, indicate that this subunit plays a role in normal female Ae. aegypti fecundity. Additional research needs to be conducted to determine the exact role played by NKAβ2 in mosquito post-blood meal nutrient sensing, transport, yolk precursor protein (YPP) synthesis and yolk deposition.