bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Adsorption of Cd on Iron–Organic Associations Formed by Laccase-Mediated Modification: Implications for the Immobilization of Cadmium in Paddy Soil
Authors: Yang Weilin , Huang Chunlei , Wan Xiang , Zhao Yunyun , Bao Zhengyu , Xiang Wu
Published: November 2022

The objectives of this study were to evaluate the cadmium adsorption capacity of iron–organic associations (Fe-OM) formed by laccase-mediated modification and assess the effect of Fe-OM on the immobilization of cadmium in paddy soil. Leaf organic matter (OM) was extracted from Changshan grapefruit leaves, and then dissolved organic matter (Lac-OM) and precipitated organic matter (Lac-P) were obtained by laccase catalytic modification. Different Fe-OM associations were obtained by co-precipitation of Fe with OM, Lac-OM, and Lac-P, respectively, and the adsorption kinetics, adsorption edge, and isothermal adsorption experiments of Cd on Fe-OM were carried out. Based on the in situ generation of Fe-OM, passivation experiments on Cd-contaminated soils with a high geological background were carried out. All types of Fe-OM have a better Cd adsorption capacity than ferrihydrite (FH). The theoretical maximum adsorption capacity of the OM-FH, Lac-OM-FH, and Lac-P-FH were 2.2, 2.53, and 2.98 times higher than that of FH, respectively. The adsorption of Cd on Fe-OM is mainly chemisorption, and the -OH moieties on the Fe-OM surface form an inner-sphere complex with the Cd ions. Lac-OM-FH showed a higher Cd adsorption capacity than OM-FH, which is related to the formation of more oxygen-containing groups in the organic matter modified by laccase. The immobilization effect of Lac-OM-FH on active Cd in soil was also higher than that of OM-FH. The Lac-OM-FH formed by laccase-mediated modification has better Cd adsorption performance, which can effectively inactivate the activity of Cd in paddy soil.
Sport Participation and Academic Performance in Young Elite Athletes
Authors: Pinto-Escalona Tania , Valenzuela Pedro L. , Esteban-Cornejo Irene , Martínez-de-Quel Óscar
Published: November 2022

Strong evidence supports physical activity and fitness levels being positively associated with cognitive performance and overall academic performance in youth. This also applies to sports participation. However, whether participation in sports at the elite level is associated with greater academic performance remains unknown. Thus, the present study aimed to compare the academic performance of young elite athletes to that of control students, as well as to analyze whether the type of sport mediates these results. Between 2010 and 2019, all students from the last Baccalaureate course of the Spanish Elite Sport High School—which also includes non-elite athletes and recreational athlete students, who were categorized as controls—participated in this study. Academic performance was assessed through both the grade point average of the two last Baccalaureate courses and through the average grades from the University Entrance Examinations. Athletes were categorized attending to different sport classifications. A total of 1126 adolescents (570 girls, 18.2 ± 0.6 years) participated in the study, of which 483 and 643 were categorized as elite athletes and control students, respectively. Elite athletes attained a lower overall academic performance than controls (p < 0.001), which was confirmed for both sexes (p < 0.001). These differences were separately confirmed for most academic subjects (p < 0.05), as well as when attending to different sport classifications (all p > 0.05). Young elite athletes attained a lower academic performance than their non-elite peers, regardless of their type of sport. These findings highlight the importance of programs aimed at facilitating dual careers among young elite athletes.
Sexual Orientation and Infidelity-Related Behaviors on Social Media Sites
Authors: Șerban Ionela , Salvati Marco , Enea Violeta
Published: November 2022

Little research has been focused on offline or online infidelity in GL dating relationships, especially in a post-communist socio-cultural context. Infidelity–related (IR) behaviors on social media sites might be as hurtful to relationships as offline infidelity, both in gay, lesbian (GL) and heterosexual romantic monogamous relationships. In this cross-sectional study, we aimed to examine the associations between dyadic satisfaction, attitudes toward infidelity, and problematic internet usage, with IR behaviors on social media sites among GL and heterosexual unmarried individuals in Romanian sexual minority communities. Results showed that GL respondents did not significantly differ from heterosexual participants regarding IR behaviors. Furthermore, we found the main effect of attitudes toward infidelity and problematic internet use on IR behaviors. Sexual orientation highlights the main effect of IR behaviors when analyzed with dyadic satisfaction. The current study may be a precursor to further research investigating correlations in online IR behavior among lesbian and gay individuals engaging in consensual nonmonogamy. Implications of the findings are discussed in the social context of a post-communist country where GL individuals may face discrimination and stigma because of their sexual orientation.
Gradual Strength Training Improves Sleep Quality, Physical Function and Pain in Women with Fibromyalgia
Authors: Maestre-Cascales Cristina , Castillo-Paredes Antonio , Romero-Parra Nuria , Adsuar José Carmelo , Carlos-Vivas Jorge
Published: November 2022

Background: Fibromyalgia (FM) is characterized by chronic and generalized musculoskeletal pain. There is currently no cure for FM, but alternative treatments are available. Among them, gradual strength training programs (ST) which on daily activities are a valid option to improve some of the pronounced symptoms of FM that affect quality of life, such as fatigue, pain, sleep quality, and physical function. However, there is a need for more information on optimal training programs to improve anxiety and fatigue symptoms. Aim: To analyze the effects of a 24-week gradual and progressive ST on sleep quality, fatigue, pain domains, physical function, and anxiety-state. Methods: 41 women with FM participated in the 24 weeks of intervention based on gradual and progressive ST. Two, 60 min, training sessions per week were con-ducted. Participants were evaluated before the ST program (week 0), in week 12 and at the end of the ST program (week 24). The Revised Fibromyalgia Impact Questionnaire was used to assess sleep quality and fatigue scales. Anxiety-state was evaluated with the State Anxiety Inventory, and pain domains by means of the Brief Pain Inventory. Senior Fitness Test was used for physical function measurements. One-way analysis of variance (ANOVA) was applied to assess the mean differences between phases, and Spearman’s correlations were used to assess the associations between physical and psychological symptoms, and physical function. Results: The results demonstrated that 24 weeks of ST improves physical function, sleep quality and pain domains (p ≤ 0.05). Higher anxiety and pain interference scores were related to worsening physical function. Conclusions: Gradual ST significantly improves sleep quality, pain, and physical function, but not anxiety and fatigue.
Detection and Analysis of Clostridioides difficile Spores in a Hospital Environment
Authors: Kiersnowska Zofia Maria , Lemiech-Mirowska Ewelina , Michałkiewicz Michał , Sierocka Aleksandra , Marczak Michał
Published: November 2022

Clostridioides difficile, due to its long survival time in a hospital environment, is considered to be one of the most frequent factors in healthcare-associated infections. Patient care requires not only rapid and accurate diagnosis, but also knowledge of individual risk factors for infections, e.g., with C. difficile, in various clinical conditions. The goal of this study was to analyse the degree of contamination of a hospital environment with C. difficile spores. Culturing was performed using C diff Banana BrothTM medium, which enables germination of the spores of these bacteria. Samples were collected from inanimate objects within a hospital environment in a specialist hospital in Poland. The results of the study demonstrated the presence of 18 positive samples of Clostridioides spp. (15.4%). Of these, C. difficile spores were detected in six samples, Clostridioides perfringens in eight samples, Clostridioides sporogenes in two samples and Clostridioides innocuum and Clostridioides baratii in one sample each. Among the six samples of C. difficile, a total of four strains which produce the B toxin were cultured. The binary toxin related to ribotype 027 was not detected in our study. Nosocomial infection risk management is a significant problem, mainly concerning the issues of hygiene maintenance, cleaning policy and quality control, and awareness of infection risk.
Correlation between Land Use Pattern and Urban Rail Ridership Based on Bicycle-Sharing Trajectory
Authors: Li Xiangyu , Sinniah Gobi Krishna , Li Ruiwei , Li Xiaoqing
Published: November 2022

As a form of rapid mass transportation, urban rail systems have always been widely used to alleviate urban traffic congestion and reconstruct urban structures. Land use characteristics are indispensable to this system and correlate with urban ridership. Dock-less bicycle-sharing expands the station service coverage range because it integrates public transportation with an urban rail system to create a convenient travel model. Consequently, the land use pattern with dock-less bicycle-sharing is associated with urban rail ridership. This paper measures the correlation between land use and urban rail ridership based on the trajectory of dock-less bicycle-sharing, which precisely reflects the travel behavior of passengers along the trip chain. The specific relationship has been determined using the random forest model. This paper found that the land use pattern could better explain the egress ridership during morning peak hours. In particular, it could explain 48.46% of the urban rail ridership in terms of egress, but the explicability for the ingress ridership slightly decreased to 36.88%. This suggests that the land use pattern is related to urban rail ridership. However, the impact situation varies, so we should understand this relationship with greater care.
Molecular Background of Toxic-Substances-Induced Morphological Alterations in the Umbilical Cord Vessels and Fetal Red Blood Cells
Authors: Zahorán Szabolcs , Márton Ágnes , Dugmonits Krisztina , Chakraborty Payal , Khamit Ali , Hegyi Péter , Orvos Hajnalka , Hermesz Edit
Published: November 2022

The relationship between smoking and human health has been investigated mostly in adults, despite the fact that the chemicals originating from sustained maternal smoking disrupt the carefully orchestrated regulatory cascades in the developing fetus. In this study, we followed molecular alterations in the umbilical cord (UC) vessels and fetal red blood cells (RBCs), which faithfully reflect the in vivo status of the fetus. We showed evidence for the decreased level of DNA-PKcs-positive nuclei in samples with smoking origin, which is associated with the impaired DNA repair system. Furthermore, we pointed out the altered ratio of MMP-9 metalloproteinase and its endogenous inhibitor TIMP-1, which might be a possible explanation for the morphological abnormalities in the UC vessels. The presented in vivo dataset emphasizes the higher vulnerability of the veins, as the primary target for the toxic materials unfiltered by the placenta. All these events become amplified by the functionally impaired fetal RBC population via a crosstalk mechanism between the vessel endothelium and the circulating RBCs. In our ex vivo approach, we looked for the molecular explanation of metal-exposure-induced alterations, where expressions of the selected genes were upregulated in the control group, while samples with smoking origin showed a lack of response, indicative of prior long-term in utero exposure.
Glutathione Plays a Positive Role in the Proliferation of Pinus koraiensis Embryogenic Cells
Authors: Gao Fang , Peng Chunxue , Zhang Yue , Wang Hao , Shen Hailong , Yang Ling
Published: November 2022

In the large-scale breeding of conifers, cultivating embryogenic cells with good proliferative capacity is crucial in the process of somatic embryogenesis. In the same cultural environment, the proliferative capacity of different cell lines is significantly different. To reveal the regulatory mechanism of proliferation in woody plant cell lines with different proliferative potential, we used Korean pine cell lines with high proliferative potential 001#–001 (Fast) and low proliferative potential 001#–010 (Slow) for analysis. A total of 17 glutathione-related differentially expressed genes was identified between F and S cell lines. A total of 893 metabolites was obtained from the two cell lines in the metabolomic studies. A total of nine metabolites related to glutathione was significantly upregulated in the F cell line compared with the S cell line. The combined analyses revealed that intracellular glutathione might be the key positive regulator mediating the difference in proliferative capacity between F and S cell lines. The qRT-PCR assay validated 11 differentially expressed genes related to glutathione metabolism. Exogenous glutathione and its synthase inhibitor L-buthionine-sulfoximine treatment assay demonstrated the positive role of glutathione in the proliferation of Korean pine embryogenic cells.
Development of the Periventricular Nucleus as a Brain Center, Containing Dopaminergic Neurons and Neurons Expressing Individual Enzymes of Dopamine Synthesis
Authors: Pronina Tatiana , Pavlova Ekaterina , Dil’mukhametova Liliya , Ugrumov Michael
Published: November 2022

We have recently shown that the periventricular nucleus (PeVN) of adult rats is a “mixed dopaminergic (DAergic) center” containing three thousand neurons: DAergic neurons and those expressing one of the dopamine (DA)-synthesizing enzymes. This study aims to evaluate the development of the PeVN as a mixed DAergic center in rats in the perinatal period, critical for brain morphogenesis. During this period, the PeVN contains DAergic neurons and monoenzymatic neurons expressing individual enzymes of DA synthesis: tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). In the perinatal period, the total number of such neurons triples, mainly due to monoenzymatic neurons; the content of L-DOPA, the end product of monoenzymatic TH neurons, doubles; and the content of DA, the end product of monoenzymatic AADC neurons and DAergic neurons, increases sixfold. Confocal microscopy has shown that, in the PeVN, all types of neurons and their processes are in close relationships, which suggests their mutual regulation by L-DOPA and DA. In addition, monoenzymatic and DAergic fibers are close to the third cerebral ventricle, located in the subependymal zone, between ependymal cells and in the supraependymal zone. These observations suggest that these fibers deliver L-DOPA and DA to the cerebrospinal fluid, participating in the neuroendocrine regulation of the brain.
Prediction of Recurrent Mutations in SARS-CoV-2 Using Artificial Neural Networks
Authors: Saldivar-Espinoza Bryan , Macip Guillem , Garcia-Segura Pol , Mestres-Truyol Júlia , Puigbò Pere , Cereto-Massagué Adrià , Pujadas Gerard , Garcia-Vallve Santiago
Published: November 2022

Predicting SARS-CoV-2 mutations is difficult, but predicting recurrent mutations driven by the host, such as those caused by host deaminases, is feasible. We used machine learning to predict which positions from the SARS-CoV-2 genome will hold a recurrent mutation and which mutations will be the most recurrent. We used data from April 2021 that we separated into three sets: a training set, a validation set, and an independent test set. For the test set, we obtained a specificity value of 0.69, a sensitivity value of 0.79, and an Area Under the Curve (AUC) of 0.8, showing that the prediction of recurrent SARS-CoV-2 mutations is feasible. Subsequently, we compared our predictions with updated data from January 2022, showing that some of the false positives in our prediction model become true positives later on. The most important variables detected by the model’s Shapley Additive exPlanation (SHAP) are the nucleotide that mutates and RNA reactivity. This is consistent with the SARS-CoV-2 mutational bias pattern and the preference of some host deaminases for specific sequences and RNA secondary structures. We extend our investigation by analyzing the mutations from the variants of concern Alpha, Beta, Delta, Gamma, and Omicron. Finally, we analyzed amino acid changes by looking at the predicted recurrent mutations in the M-pro and spike proteins.
Different Types of Chronic Inflammation Engender Distinctive Immunosenescent Profiles in Affected Patients
Authors: Moysidou Eleni , Lioulios Georgios , Xochelli Aliki , Nikolaidou Vasiliki , Christodoulou Michalis , Mitsoglou Zoi , Stai Stamatia , Fylaktou Asimina , Papagianni Aikaterini , Stangou Maria
Published: November 2022

Immunosenescence encompasses a spectrum of lymphocyte phenotypic alterations. The aim of the study was to evaluate immunosenescent effect of two different forms of chronic inflammation, Systemic Lupus Erythematosous (SLE), a systemic autoimmune disease, and End-Stage Kidney Disease (ESKD), a chronic inflammatory disorder. Certain lymphocyte surface molecules, including CD31, CD45RA, CCR7, CD28, CD57, for T, and IgD, CD27 for B lymphocytes, were analyzed by flow cytometry in 30 SLE and 53 ESKD patients on hemodialysis (HD), and results were compared to 31 healthy controls (HC) of similar age, gender, and nationality. Significant Lymphopenia was evident in both SLE and ESKD-HD patients, compared to HC, affecting B cells 75.4 (14.4–520.8), 97 (32–341), and 214 (84–576) cells/μL, respectively, p < 0.0001, and CD4 cells 651.2 (71.1–1478.2), 713 (234–1509), and 986 (344–1591) cells/μL, respectively, p < 0.0001. The allocation of B cell subpopulations was remarkably different between SLE and ESKD-HD patients. SLE showed a clear shift to senescence (CD19IgD-CD27−) cells, compared to ESKD-HD and HC, 11.75 (10)% vs. 8 (6) vs. 8.1 (10), respectively. Regarding T lymphocytes, Central Memory CD8 cells predominated in both SLE and ESKD-HD patients compared to HC, 53 (50)%, 52 (63), and 24 (64)%, respectively, while ESKD-HD but not SLE patients also had increased expression of CD4CD28− and CD8CD28− cells. In conclusion, both diseases are followed by significant lymphopenia; however, the senescent phenomenon affects the B lymphocyte compartment in SLE patients and T lymphocytes in ESKD-HD patients.
A New Role of NAP1L1 in Megakaryocytes and Human Platelets
Authors: Freitag Martin , Schwertz Hansjörg
Published: November 2022

Platelets (PLTs) are anucleate and considered incapable of nuclear functions. Contrastingly, nuclear proteins were detected in human PLTs. For most of these proteins, it is unclear if nuclear or alternatively assigned functions are performed, a question we wanted to address for nuclear assembly protein 1like 1 (NAP1L1). Using a wide array of molecular methods, including RNAseq, co-IP, overexpression and functional assays, we explored expression pattern and functionality of NAP1L1 in PLTs, and CD34+-derived megakaryocytes (MKs). NAP1L1 is expressed in PLTs and MKs. Co-IP experiments revealed that dihydrolipolylysine-residue acetyltransferase (DLAT encoded protein PDC-E2, ODP2) dynamically interacts with NAP1L1. PDC-E2 is part of the mitochondrial pyruvate-dehydrogenase (PDH) multi-enzyme complex, playing a crucial role in maintaining cellular respiration, and promoting ATP-synthesis via the respiratory chain. Since altered mitochondrial function is a hallmark of infectious syndromes, we analyzed PDH activity in PLTs from septic patients demonstrating increased activity, paralleling NAP1L1 expression levels. MKs PDH activity decreased following an LPS-challenge. Furthermore, overexpression of NAP1L1 significantly altered the ability of MKs to form proplatelet extensions, diminishing thrombopoiesis. These results indicate that NAP1L1 performs in other than nucleosome-assembly functions in PTLs and MKs, binding a key mitochondrial protein as a potential chaperone, and gatekeeper, influencing PDH activity and thrombopoiesis.
MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes
Authors: Ramanjaneya Manjunath , Bettahi Ilham , Pawar Krunal , Halabi Najeeb M. , Moin Abu Saleh Md , Sathyapalan Thozhukat , Abou-Samra Abdul Badi , Atkin Stephen L. , Butler Alexandra E.
Published: November 2022

Hypoglycemia, as a complication of type 2 diabetes (T2D), causes increased morbidity and mortality but the physiological response underlying hypoglycemia has not been fully elucidated. Small noncoding microRNA (miRNA) have multiple downstream biological effects. This pilot exploratory study was undertaken to determine if induced miRNA changes would persist and contribute to effects seen 24 h post-hypoglycemia. A parallel, prospective study design was employed, involving T2D (n = 23) and control (n = 23) subjects. The subjects underwent insulin-induced hypoglycemia (2 mmol/L; 36 mg/dL); blood samples were drawn at baseline, upon the induction of hypoglycemia, and 4 h and 24 h post-hypoglycemia, with a quantitative polymerase chain reaction analysis of miRNA undertaken. The baseline miRNAs did not differ. In the controls, 15 miRNAs were downregulated and one was upregulated (FDR < 0.05) from the induction of hypoglycemia to 4 h later while, in T2D, only four miRNAs were altered (downregulated), and these were common to both cohorts (miR-191-5p; miR-143-3p; let-7b-5p; let-7g-5p), correlated with elevated glucagon levels, and all were associated with energy balance. From the induction of hypoglycemia to 24 h, 14 miRNAs were downregulated and 5 were upregulated (FDR < 0.05) in the controls; 7 miRNAs were downregulated and 7 upregulated (FDR < 0.05) in T2D; a total of 6 miRNAs were common between cohorts, 5 were downregulated (miR-93-5p, let-7b-5p, miR-191-5p, miR-185-5p, and miR-652-3p), and 1 was upregulated (miR-369-3p). An ingenuity pathway analysis indicated that many of the altered miRNAs were associated with metabolic and coagulation pathways; however, of the inflammatory proteins expressed, only miR-143-3p at 24 h correlated positively with tumor necrosis factor-α (TNFa; p < 0.05 and r = 0.46) and negatively with toll-like receptor-4 (TLR4; p < 0.05 and r = 0.43). The MiRNA levels altered by hypoglycemia reflected changes in counter-regulatory glucagon and differed between cohorts, and their expression at 24 h suggests miRNAs may potentiate and prolong the physiological response. Trial registration: ClinicalTrials.gov NCT03102801.
Chlamydial Infection-Dependent Synthesis of Sphingomyelin as a Novel Anti-Chlamydial Target of Ceramide Mimetic Compounds
Authors: Kumagai Keigo , Sakai Shota , Ueno Masaharu , Kataoka Michiyo , Kobayashi Shu , Hanada Kentaro
Published: November 2022

The obligate intracellular bacterium Chlamydia trachomatis is the major causative agent of bacterial sexually transmitted diseases worldwide. In infected cells, the ceramide transport protein (CERT) is recruited to inclusions, where C. trachomatis replicates using host-synthesized ceramide. The ceramide is converted to sphingomyelin (SM) by a chlamydial infection-dependent SM synthesis (cidSM-synthesis) pathway, which occurs even in the absence of the SM synthases (SMS)-1 and -2 of host cells. The ceramide mimetic compound (1R,3S)-HPA-12 and the nonmimetic compound E16A, both of which are potent inhibitors of CERT, repressed the proliferation of C. trachomatis in HeLa cells. Unexpectedly, (1R,3R)-HPA-12, a ceramide mimetic compound that lacks CERT inhibitory activity, also exhibited potent anti-chlamydial activity. Using endogenous SMS-knockout mutant HeLa cells, we revealed that (1R,3R)-HPA-12 mildly inhibited cidSM-synthesis. In addition, LC-MS analysis revealed that (1R,3R)-HPA-12 is converted to a phosphocholine-conjugated metabolite in an infection-dependent manner. Imaging analysis with a fluorescent analog of ceramide suggested that cidSM-synthesis occurs in the bacterial bodies and/or inclusions. Collectively, these results suggested that (1R,3R)-HPA-12 exerts its anti-chlamydia activity not only as an inhibitor of cidSM-synthesis, but also via putative toxic effects of its phosphocholine adduct, which is most likely produced by the cidSM-synthesis route.
Seasonal Change in Adiponectin Associated with Ovarian Morphology and Function in Wild Ground Squirrels (Citellus dauricus Brandt)
Authors: Fan Sijie , Lu Wenjing , Zhang Haolin , Yuan Zhengrong , Han Yingying , Weng Qiang
Published: November 2022

The goal of this study is to explore the relationship between altered circulating adiponectin concentration, ovarian tissue morphology, ovarian steroidogenesis, and sex hormone production in ovaries of wild ground squirrels. The ovarian mass differed significantly during the breeding and non-breeding seasons, and the circulating estradiol and progesterone concentrations were significantly higher in the breeding season, while the circulating adiponectin level was significantly lower. The expression levels of gonadotropin receptors (FSHR and LHR) and steroidogenic enzymes (StAR, P450scc, P450arom, and 3β-HSD) were significantly higher during the breeding season. Comparing the ovarian transcriptome data of wild ground squirrels between the two periods, we found that some differentially expressed genes were enriched for ovarian steroidogenesis and the adipocytokine signaling pathway, which correlated with our present results. Notably, the MAPK signaling pathway was also enriched and its related genes (Erk1, p38 Mapk, Jnk) were up-regulated by qPCR during the non-breeding season. These findings suggested that adiponectin may be involved in the regulation of seasonal changes in the ovarian function of wild ground squirrels, possibly by acting on the MAPK signaling pathway to regulate sex steroidogenesis in the ovaries.
Treadmill Exercise Prevents Cognitive Impairments in Adolescent Intermittent Ethanol Rats by Reducing the Excessive Activation of Microglia Cell in the Hippocampus
Authors: Guo Yanxia , Yan Min , Li Li , Zhao Li , Li Yan
Published: November 2022

The excessive activation of microglia cell induced by adolescent intermittent ethanol (AIE) leads to neuroinflammation in the hippocampus. The endocannabinoid system plays a key role in the modulation of microglia activation. Accumulating evidence suggests that regular exercise improves learning and memory deficits in AIE models. The purpose of this study was to explore the effects of treadmill exercise intervention on the cognitive performance, activation of microglia cells and the expression of monoacylglycerol lipase (MAGL), cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R) in the hippocampus of AIE rats. Here, we show that AIE rats exhibited cognitive impairments, whereas the treadmill exercise improves the cognitive performance in AIE rats. In order to explore the possible mechanisms for the exercise-induced attenuation of cognitive disorder, we examined the neuroinflammation in the hippocampus. We found that treadmill exercise led to the decrease in the level of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and the increase in the level of anti-inflammatory cytokine (IL-10). In addition, we found that treadmill exercise reduced the excessive activation of the microglia cell in the hippocampus of AIE rats. Finally, we found that AIE led to a decrease in the expression of CB1R and CB2R in the hippocampus; however, the treadmill exercise further decreased the expression of CB2R in the hippocampus of AIE rats. Our results suggest that treadmill exercise attenuates AIE-induced neuroinflammation and the excessive activation of hippocampus microglial cells, which may contribute to the exercise-induced improvement of cognitive performance in AIE rats.
TOLLIP Protein Expression Predicts Unfavorable Outcome in Renal Cell Carcinoma
Authors: Kowalewski Adam , Jaworski Damian , Borowczak Jędrzej , Maniewski Mateusz , Szczerbowski Krzysztof , Antosik Paulina , Durślewicz Justyna , Smolińska Marta , Ligmanowska Joanna , Grzanka Dariusz , Szylberg Łukasz
Published: November 2022

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.
Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction
Authors: Bronisz Elżbieta , Cudna Agnieszka , Wierzbicka Aleksandra , Kurkowska-Jastrzębska Iwona
Published: November 2022

As 30% of epileptic patients remain drug-resistant, seizure prediction is vital. Induction of epileptic seizure is a complex process that can depend on factors such as intrinsic neuronal excitability, changes in extracellular ion concentration, glial cell activity, presence of inflammation and activation of the blood–brain barrier (BBB). In this study, we aimed to assess if levels of serum proteins associated with BBB can predict seizures. Serum levels of MMP-9, MMP-2, TIMP-1, TIMP-2, S100B, CCL-2, ICAM-1, P-selectin, and TSP-2 were examined in a group of 49 patients with epilepsy who were seizure-free for a minimum of seven days and measured by ELISA. The examination was repeated after 12 months. An extensive medical history was taken, and patients were subjected to a follow-up, including a detailed history of seizures. Serum levels of MMP-2, MMP-9, TIMP-1, CCL-2, and P-selectin differed between the two time points (p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, p = 0.0035, respectively). General linear model analyses determined the predictors of seizures. Levels of MMP-2, MMP-9, and CCL-2 were found to influence seizure count in 1, 3, 6, and 12 months of observation. Serum levels of MMP-2, MMP-9, and CCL-2 may be considered potential biomarkers for seizure prediction and may indicate BBB activation.
Effect and Mechanism Analysis of Pig FUT8 Gene on Resistance to Escherichia coli F18 Infection
Authors: Wu Lisi , Wang Yifu , Wu Shenglong , Wu Zhengchang , Bao Wenbin
Published: November 2022

Post-weaning diarrhea caused by enterotoxigenic Escherichia coli F18 (E. coli F18) causes significant economic losses for pig producers. Fucosyltransferase 8 (FUT8) is a glycosyltransferase that catalyzes core fucosylation; however, its role in mediating the resistance to E. coli F18 infection in pigs remains unknown. In this study, we systematically verified the relationship between FUT8 expression and E. coli resistance. The results showed that FUT8 was expressed in all detected tissues of Meishan piglets and that its expression was significantly increased in the duodenum and jejunum of E. coli F18-sensitive individuals when compared to E. coli F18-resistant individuals. FUT8 expression increased after exposure to E. coli F18 (p < 0.05) and decreased significantly after LPS induction for 6 h (p < 0.01). Then, the IPEC-J2 stable cell line with FUT8 interference was constructed, and FUT8 knockdown decreased the adhesion of E. coli F18ac to IPEC-J2 cells (p < 0.05). Moreover, we performed a comparative transcriptome study of IPEC-J2 cells after FUT8 knockdown via RNA-seq. In addition, further expression verification demonstrated the significant effect of FUT8 on the glycosphingolipid biosynthesis and Toll-like signaling pathways. Moreover, the core promoter of FUT8, which was located at −1213 bp to −673 bp, was identified via luciferase assay. Interestingly, we found a 1 bp C base insertion mutation at the −774 bp region, which could clearly inhibit the transcriptional binding activity of C/EBPα to an FUT8 promoter. Therefore, it is speculated that FUT8 acts in a critical role in the process of E. coli infection; furthermore, the low expression of FUT8 is conducive to the enhancement of E. coli resistance in piglets. Our findings revealed the mechanism of pig FUT8 in regulating E. coli resistance, which provided a theoretical basis for the screening of E. coli resistance in Chinese local pig breeds.
Cell-Specific Response of NSIP- and IPF-Derived Fibroblasts to the Modification of the Elasticity, Biological Properties, and 3D Architecture of the Substrate
Authors: Janiszewska Natalia , Orzechowska Barbara , Awsiuk Kamil , Rysz Jakub , Tymetska Svitlana , Raczkowska Joanna
Published: November 2022

The fibrotic fibroblasts derived from idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP) are surrounded by specific environments, characterized by increased stiffness, aberrant extracellular matrix (ECM) composition, and altered lung architecture. The presented research was aimed at investigating the effect of biological, physical, and topographical modification of the substrate on the properties of IPF- and NSIP-derived fibroblasts, and searching for the parameters enabling their identification. Soft and stiff polydimethylsiloxane (PDMS) was chosen for the basic substrates, the properties of which were subsequently tuned. To obtain the biological modification of the substrates, they were covered with ECM proteins, laminin, fibronectin, and collagen. The substrates that mimicked the 3D structure of the lungs were prepared using two approaches, resulting in porous structures that resemble natural lung architecture and honeycomb patterns, typical of IPF tissue. The growth of cells on soft and stiff PDMS covered with proteins, traced using fluorescence microscopy, confirmed an altered behavior of healthy and IPF- and NSIP-derived fibroblasts in response to the modified substrate properties, enabling their identification. In turn, differences in the mechanical properties of healthy and fibrotic fibroblasts, determined using atomic force microscopy working in force spectroscopy mode, as well as their growth on 3D-patterned substrates were not sufficient to discriminate between cell lines.
Integrated Transcriptome and Metabolome Analysis Reveals the Regulatory Mechanisms of FASN in Geese Granulosa Cells
Authors: Chen Xi , Huang Kailiang , Hu Shenqiang , Lan Gang , Gan Xiang , Gao Shanyan , Deng Yan , Hu Jiwei , Li Liang , Hu Bo , He Hua , Liu Hehe , Xia Lu , Wang Jiwen
Published: November 2022

FASN plays a critical role in lipid metabolism, which is involved in regulating ovarian follicular development. However, the molecular mechanisms of how FASN regulate the function of ovarian follicular cells still remain elusive. In this study, by overexpression or interference of FASN in pre-hierarchical follicle granulosa cells (phGCs) and hierarchical follicle granulosa cells (hGCs), we analyzed their effects on the granulosa cell transcriptome and metabolome profiles using RNA-Seq and LC-MS/MS, respectively. The results showed that overexpression of FASN promoted proinflammatory factors expression by activating TLR3/IRF7 and TLR3/NF-κB pathways in phGCs, but only by activating TLR3/IRF7 pathways in hGCs. Then, necroptosis and apoptosis were triggered through the JAK/STAT1 pathway (induced by inflammatory factors) and BAK/caspase-7 pathway, respectively. The combined analysis of the metabolome and transcriptome revealed that FASN affected the demand of GCs for 5-hydroxytryptamine (5-HT) by activating the neuroactive ligand-receptor interaction pathway in two categorized GCs and only altering the metabolic pathway of tryptophan in phGCs, and ultimately participated in regulating the physiological function of geese GCs. Taken together, this study showed that the mechanisms of FASN regulating the physiological function of geese phGCs and hGCs were similar, but they also had some different characteristics.
Testing of Exchange-Correlation Functionals of DFT for a Reliable Description of the Electron Density Distribution in Organic Molecules
Authors: Domagała Małgorzata , Jabłoński Mirosław , Dubis Alina T. , Zabel Manfred , Pfitzner Arno , Palusiak Marcin
Published: November 2022

Researchers carrying out calculations using the DFT method face the problem of the correct choice of the exchange-correlation functional to describe the quantities they are interested in. This article deals with benchmark calculations aimed at testing various exchange-correlation functionals in terms of a reliable description of the electron density distribution in molecules. For this purpose, 30 functionals representing all rungs of Jacob’s Ladder are selected and then the values of some QTAIM-based parameters are compared with their reference equivalents obtained at the CCSD/aug-cc-pVTZ level of theory. The presented results show that the DFT method undoubtedly has the greatest problems with a reliable description of the electron density distribution in multiple strongly polar bonds, such as C=O, and bonds associated with large electron charge delocalization. The performance of the tested functionals turned out to be unsystematic. Nevertheless, in terms of a reliable general description of QTAIM-based parameters, the M11, SVWN, BHHLYP, M06-HF, and, to a slightly lesser extent, also BLYP, B3LYP, and X3LYP functionals turned out to be the worst. It is alarming to find the most popular B3LYP functional in this group. On the other hand, in the case of the electron density at the bond critical point, being the most important QTAIM-based parameter, the M06-HF functional is especially discouraged due to the very poor description of the C=O bond. On the contrary, the VSXC, M06-L, SOGGA11-X, M06-2X, MN12-SX, and, to a slightly lesser extent, also TPSS, TPSSh, and B1B95 perform well in this respect. Particularly noteworthy is the overwhelming performance of double hybrids in terms of reliable values of bond delocalization indices. The results show that there is no clear improvement in the reliability of describing the electron density distribution with climbing Jacob’s Ladder, as top-ranked double hybrids are also, in some cases, able to produce poor values compared to CCSD.
Circulating Non-Coding RNA Levels Are Altered in Autosomal Dominant Frontotemporal Dementia
Authors: Fenoglio Chiara , Serpente Maria , Visconte Caterina , Arcaro Marina , Sorrentino Federica , D’Anca Marianna , Arighi Andrea , Rotondo Emanuela , Vimercati Roberto , Rossi Giacomina , Scarpini Elio , Galimberti Daniela
Published: November 2022

Frontotemporal Dementia (FTD) represents a highly heritable neurodegenerative disorder. Most of the heritability is caused by autosomal dominant mutations in the Microtubule-Associated Protein Tau (MAPT), Progranulin (GRN), and the pathologic exanucleotide expansion of C9ORF72 genes. At the pathological level, either the tau or the TAR DNA-binding protein (TDP-43) account for almost all cases of FTD. Pathogenic mechanisms are just arising, and the emerging role of non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long non-coding RNAs (lncRNAs), have become increasingly evident. Using specific arrays, an exploratory analysis testing the expression levels of 84 miRNAs and 84 lncRNAs has been performed in a population consisting of 24 genetic FTD patients (eight GRN, eight C9ORF72, and eight MAPT mutation carriers), eight sporadic FTD patients, and eight healthy controls. The results showed a generalized ncRNA downregulation in patients carrying GRN and C9ORF72 when compared with the controls, with statistically significant results for the following miRNAs: miR-155-5p (Fold Change FC: 0.45, p = 0.037 FDR = 0.52), miR-15a-5p (FC: 0.13, p = 0.027, FDR = 1), miR-222-3p (FC: 0.13, p = 0.027, FDR = 0.778), miR-140-3p (FC: 0.096, p = 0.034, FRD = 0.593), miR-106b-5p (FC: 0.13, p = 0.02, FDR = 0.584) and an upregulation solely for miR-124-3p (FC: 2.1, p = 0.01, FDR = 0.893). Conversely, MAPT mutation carriers showed a generalized robust upregulation in several ncRNAs, specifically for miR-222-3p (FC: 22.3, p = 7 × 10−6, FDR = 0.117), miR-15a-5p (FC: 30.2, p = 0.008, FDR = 0.145), miR-27a-3p (FC: 27.8, p = 6 × 10−6, FDR = 0.0005), miR-223-3p (FC: 18.9, p = 0.005, FDR = 0.117), and miR-16-5p (FC: 10.9, p = 5.26 × 10−5, FDR = 0.001). These results suggest a clear, distinctive pattern of dysregulation among ncRNAs and specific enrichment gene pathways between mutations associated with the TDP-43 and tau pathologies. Nevertheless, these preliminary results need to be confirmed in a larger independent cohort.
Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer
Authors: Singharajkomron Natsaranyatron , Yodsurang Varalee , Seephan Suthasinee , Kungsukool Sakkarin , Petchjorm Supinda , Maneeganjanasing Nara , Promboon Warunyu , Dangwilailuck Wadsana , Pongrakhananon Varisa
Published: November 2022

Microtubule-associated proteins (MAPs) play essential roles in cancer development. This study aimed to identify transcriptomic biomarkers among MAP genes for the diagnosis and prognosis of lung cancer by analyzing differential gene expressions and correlations with tumor progression. Gene expression data of patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) from the Cancer Genome Atlas (TCGA) database were used to identify differentially expressed MAP genes (DEMGs). Their prognostic value was evaluated by Kaplan–Meier and Cox regression analysis. Moreover, the relationships between alterations in lung cancer hallmark genes and the expression levels of DEMGs were investigated. The candidate biomarker genes were validated using three independent datasets from the Gene Expression Omnibus (GEO) database and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on clinical samples. A total of 88 DEMGs were identified from TCGA data. The 20 that showed the highest differential expression were subjected to association analysis with hallmark genes. Genetic alterations in TP53, EGFR, PTEN, NTRK1, and PIK3CA correlated with the expression of most of these DEMGs. Of these, six candidates—NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2—were significantly differentially expressed and correlated with the overall survival (OS) of the patients. The mRNA expression profiles of these candidates were consistently verified using three GEO datasets and qRT-PCR on patient lung tissues. The expression levels of NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2 can serve as diagnostic biomarkers for LUAD and LUSC. Moreover, the first five can serve as prognostic biomarkers for LUAD, while LRRK2 can be a prognostic biomarker for LUSC. Our research describes the novel role and potential application of MAP-encoding genes in clinical practice.
Interactions of the Fungal Community in the Complex Patho-System of Esca, a Grapevine Trunk Disease
Authors: Martín Laura , García-García Blanca , Alguacil María del Mar
Published: November 2022

Worldwide, Esca is a complex and devastating Grapevine Trunk Disease (GTD), characterized by inconstant foliar symptoms and internal wood degradation. A large range of fungal taxa have been reported as causal agents. We applied both culture-dependent and culture-independent methods (Illumina Technology and q-PCR) to investigate this concerning disease. Woods from vines with asymptomatic leaves and vines with leaf Esca symptoms were compared. Internally, different types of wood were found, from healthy wood with black necrosis to wood with white rot. A combination of leaf and wood Esca symptoms resulted in four experimental categories. Although there was no relation with symptoms, culture-independent mycobiome composition revealed Phaeomoniella chlamydospora, a GTD pathogen, as the most abundant species (detected in 85.4% of wood samples, with 14.8% relative abundance). Using TaqMan q-PCR, P. chlamydospora DNA was detected in 60.4% of samples (far from the 18.8% of positive results in the culture-dependent approach). There was a predominance of saprotrophs, even if their abundance was not affected by Esca symptoms. Concerning pathotrophs, the white rot development within grapevines was linked to the abundance of fungi belonging to the Hymenochaetaceae family. The Botryosphaeriaceae family was identified as an indicator for expression of Esca foliar symptoms. Lastly, the Aureobasidiaceae family was found to be a potential biocontrol agent for Esca, since it was most abundant in the control asymptomatic plants.
A Benefit Dependency Network for Shadow Information Technology Adoption, Based on Practitioners’ Viewpoints
Authors: Scalabrin Bianchi Isaias , Vaquina António , Pereira Ruben , Dinis Sousa Rui , Dávila Guillermo Antonio
Published: November 2022

Shadow information technology (SIT) revolves around systems that are hidden but are still managed by the same business entities. It consists of the use of devices, software, systems and applications without the information technology (IT) department’s approval. Employees use IT without the knowledge of the IT department, and it creates a gap in communications, as the IT department loses the knowledge of the reality within the company. However, there are benefits involved. In order to take advantage of these benefits, changes have to be implemented in the way that business activities are handled. The benefits should be a direct result of the changes, of the difference between the ongoing and the suggested way that activities should be undertaken, and the levels of efficiency and effectiveness to which people deliver their daily tasks. The objective of this study was to propose a benefit dependency network (BDN) for SIT, and, through its concepts, to synthetize our findings and specify the connections between SIT practices and their benefits. This research was conducted a systematic literature review (SLR) and used a design science research methodology, adopting semi-structured interviews with fourteen interactions to propose a BDN for SIT. We proposed a model with five dimensions related to a BDN for SIT. By understanding the BDN and the benefits of SIT, it is easier to have a better notion of the implications and the factors involved in order to assist the decision-making process. Whether an organization wants to reach innovation, increase revenue or retain clients, the BDN helps with analysis and selection, and is something that organizations should take seriously, as it is essential to have knowledge about what the benefits are and how they can be reached. To the best of the authors’ knowledge, this research included and replaced several processes in the BDN for SIT, in a topic that is still underexplored.