bluuebunny/crossref_metadata_2025 huggingface dataset:
Recognition Memory Induces Natural LTP-like Hippocampal Synaptic Excitation and Inhibition
Authors: Sánchez-Rodríguez Irene , Temprano-Carazo Sara , Jeremic Danko , Delgado-Garcia Jose Maria , Gruart Agnès , Navarro-López Juan D. , Jiménez-Díaz Lydia
Published: September 2022

Synaptic plasticity is a cellular process involved in learning and memory by which specific patterns of neural activity adapt the synaptic strength and efficacy of the synaptic transmission. Its induction is governed by fine tuning between excitatory/inhibitory synaptic transmission. In experimental conditions, synaptic plasticity can be artificially evoked at hippocampal CA1 pyramidal neurons by repeated stimulation of Schaffer collaterals. However, long-lasting synaptic modifications studies during memory formation in physiological conditions in freely moving animals are very scarce. Here, to study synaptic plasticity phenomena during recognition memory in the dorsal hippocampus, field postsynaptic potentials (fPSPs) evoked at the CA3–CA1 synapse were recorded in freely moving mice during object-recognition task performance. Paired pulse stimuli were applied to Schaffer collaterals at the moment that the animal explored a new or a familiar object along different phases of the test. Stimulation evoked a complex synaptic response composed of an ionotropic excitatory glutamatergic fEPSP, followed by two inhibitory responses, an ionotropic, GABAA-mediated fIPSP and a metabotropic, G-protein-gated inwardly rectifying potassium (GirK) channel-mediated fIPSP. Our data showed the induction of LTP-like enhancements for both the glutamatergic and GirK-dependent components of the dorsal hippocampal CA3–CA1 synapse during the exploration of novel but not familiar objects. These results support the contention that synaptic plasticity processes that underlie hippocampal-dependent memory are sustained by fine tuning mechanisms that control excitatory and inhibitory neurotransmission balance.
Fatty Acids and Lipid Paradox-Neuroprotective Biomarkers in Ischemic Stroke
Authors: Andone Sebastian , Farczádi Lénárd , Imre Silvia , Bălașa Rodica
Published: September 2022

Stroke is the primary cause of death and disability worldwide, with ischemic stroke up to 80% of the total cases. Lipid profile was established as a major risk factor for stroke, but recent studies show a paradoxical relationship between serum values and the outcome of stroke patients. Our study aims to analyze the impact of the classic extended lipid profile, including fatty acids as potential neuroprotective biomarkers for the outcome of ischemic stroke patients. We included 298 patients and collected clinical, paraclinical, and outcome parameters. We used a method consisting of high-performance liquid chromatography coupled with mass spectrometry to quantify serum fatty acids. We observed a negative correlation between National Institutes of Health Stroke Scale (NIHSS) at admission and total cholesterol (p = 0.040; r = −0.120), respectively triglycerides (p = 0.041; r = −0.122). The eicosapentaenoic to arachidonic acid ratio has a negative correlation, while the docosahexaenoic to eicosapentaenoic acid ratio positively correlates with all the prognostic parameters, showing a potential neuroprotective role for eicosapentaenoic acid in preventing severe ischemic stroke. The impact of the lipid profile paradox and the dependency relationship with the fatty acids represent a significant predictive factor for the functional and disability prognostic of ischemic stroke patients.
Bifidobacterium longum subsp. infantis CECT 7210 Reduces Inflammatory Cytokine Secretion in Caco-2 Cells Cultured in the Presence of Escherichia coli CECT 515
Authors: Álvarez-Mercado Ana I. , Plaza-Díaz Julio , de Almagro M. Cristina , Gil Ángel , Moreno-Muñoz José Antonio , Fontana Luis
Published: September 2022

Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects.
Alteration of Fatty Acid Profile in Fragile X Syndrome
Authors: Abolghasemi Armita , Carullo Maria Paulina , Aguilera Ester Cisneros , Laroui Asma , Plantefeve Rosalie , Rojas Daniela , Benachenhou Serine , Ramírez María Victoria , Proteau-Lemieux Mélodie , Lepage Jean-François , Corbin François , Plourde Mélanie , Farez Mauricio , Cogram Patricia , Çaku Artuela
Published: September 2022

Fragile X Syndrome (FXS) is the most prevalent monogenic cause of Autism Spectrum Disorders (ASDs). Despite a common genetic etiology, the affected individuals display heterogenous metabolic abnormalities including hypocholesterolemia. Although changes in the metabolism of fatty acids (FAs) have been reported in various neuropsychiatric disorders, it has not been explored in humans with FXS. In this study, we investigated the FA profiles of two different groups: (1) an Argentinian group, including FXS individuals and age- and sex-matched controls, and (2) a French-Canadian group, including FXS individuals and their age- and sex-matched controls. Since phospholipid FAs are an indicator of medium-term diet and endogenous metabolism, we quantified the FA profile in plasma phospholipids using gas chromatography. Our results showed significantly lower levels in various plasma FAs including saturated, monosaturated, ω-6 polyunsaturated, and ω-3 polyunsaturated FAs in FXS individuals compared to the controls. A decrease in the EPA/ALA (eicosapentaenoic acid/alpha linoleic acid) ratio and an increase in the DPA/EPA (docosapentaenoic acid/eicosapentaenoic acid) ratio suggest an alteration associated with desaturase and elongase activity, respectively. We conclude that FXS individuals present an abnormal profile of FAs, specifically FAs belonging to the ω-3 family, that might open new avenues of treatment to improve core symptoms of the disorder.
Identification of Quantitative Trait Locus and Candidate Genes for Drought Tolerance in a Soybean Recombinant Inbred Line Population
Authors: Ouyang Wenqi , Chen Limiao , Ma Junkui , Liu Xiaorong , Chen Haifeng , Yang Hongli , Guo Wei , Shan Zhihui , Yang Zhonglu , Chen Shuilian , Zhan Yong , Zhang Hengbin , Cao Dong , Zhou Xinan
Published: September 2022

With global warming and regional decreases in precipitation, drought has become a problem worldwide. As the number of arid regions in the world is increasing, drought has become a major factor leading to significant crop yield reductions and food crises. Soybean is a crop that is relatively sensitive to drought. It is also a crop that requires more water during growth and development. The aim of this study was to identify the quantitative trait locus (QTL) that affects drought tolerance in soybean by using a recombinant inbred line (RIL) population from a cross between the drought-tolerant cultivar ‘Jindou21’ and the drought-sensitive cultivar ‘Zhongdou33’. Nine agronomic and physiological traits were identified under drought and well-watered conditions. Genetic maps were constructed with 923,420 polymorphic single nucleotide polymorphism (SNP) markers distributed on 20 chromosomes at an average genetic distance of 0.57 centimorgan (cM) between markers. A total of five QTLs with a logarithm of odds (LOD) value of 4.035–8.681 were identified on five chromosomes. Under well-watered conditions and drought-stress conditions, one QTL related to the main stem node number was located on chromosome 16, accounting for 17.177% of the phenotypic variation. Nine candidate genes for drought resistance were screened from this QTL, namely Glyma.16G036700, Glyma.16G036400, Glyma.16G036600, Glyma.16G036800, Glyma.13G312700, Glyma.13G312800, Glyma.16G042900, Glyma.16G043200, and Glyma.15G100700. These genes were annotated as NAC transport factor, GATA transport factor, and BTB/POZ-MATH proteins. This result can be used for molecular marker-assisted selection and provide a reference for breeding for drought tolerance in soybean.
Biomarkers Related to Synaptic Dysfunction to Discriminate Alzheimer’s Disease from Other Neurological Disorders
Authors: Piccoli Tommaso , Blandino Valeria , Maniscalco Laura , Matranga Domenica , Graziano Fabiola , Guajana Fabrizio , Agnello Luisa , Lo Sasso Bruna , Gambino Caterina Maria , Giglio Rosaria Vincenza , La Bella Vincenzo , Ciaccio Marcello , Colletti Tiziana
Published: September 2022

Recently, the synaptic proteins neurogranin (Ng) and α-synuclein (α-Syn) have attracted scientific interest as potential biomarkers for synaptic dysfunction in neurodegenerative diseases. In this study, we measured the CSF Ng and α-Syn concentrations in patients affected by AD (n = 69), non-AD neurodegenerative disorders (n-AD = 50) and non-degenerative disorders (n-ND, n = 98). The concentrations of CSF Ng and α-Syn were significantly higher in AD than in n-AD and n-ND. Moreover, the Aβ42/Ng and Aβ42/α-Syn ratios showed statistically significant differences between groups and discriminated AD patients from n-AD patients, better than Ng or α-Syn alone. Regression analyses showed an association of higher Ng concentrations with MMSE < 24, pathological Aβ 42/40 ratios, pTau, tTau and the ApoEε4 genotype. Aβ 42/Ng was associated with MMSE < 24, an AD-related FDG-PET pattern, the ApoEε4 genotype, pathological Aβ 42 levels and Aβ 42/40 ratios, pTau, and tTau. Moreover, APO-Eε4 carriers showed higher Ng concentrations than non-carriers. Our results support the idea that the Aβ 42/Ng ratio is a reliable index of synaptic dysfunction/degeneration able to discriminate AD from other neurological conditions.
Engineering Nanofiber Scaffolds with Biomimetic Cues for Differentiation of Skin-Derived Neural Crest-like Stem Cells to Schwann Cells
Authors: Podder Ashis Kumar , Mohamed Mohamed Alaa , Tseropoulos Georgios , Nasiri Bita , Andreadis Stelios T.
Published: September 2022

Our laboratory reported the derivation of neural crest stem cell (NCSC)-like cells from the interfollicular epidermis of the neonatal and adult epidermis. These keratinocyte (KC)-derived Neural Crest (NC)-like cells (KC-NC) could differentiate into functional neurons, Schwann cells (SC), melanocytes, and smooth muscle cells in vitro. Most notably, KC-NC migrated along stereotypical pathways and gave rise to multiple NC derivatives upon transplantation into chicken embryos, corroborating their NC phenotype. Here, we present an innovative design concept for developing anisotropically aligned scaffolds with chemically immobilized biological cues to promote differentiation of the KC-NC towards the SC. Specifically, we designed electrospun nanofibers and examined the effect of bioactive cues in guiding KC-NC differentiation into SC. KC-NC attached to nanofibers and adopted a spindle-like morphology, similar to the native extracellular matrix (ECM) microarchitecture of the peripheral nerves. Immobilization of biological cues, especially Neuregulin1 (NRG1) promoted the differentiation of KC-NC into the SC lineage. This study suggests that poly-ε-caprolactone (PCL) nanofibers decorated with topographical and cell-instructive cues may be a potential platform for enhancing KC-NC differentiation toward SC.
Time-Dependent Sensitivity Tunable pH Sensors Based on the Organic-Inorganic Hybrid Electric-Double-Layer Transistor
Authors: Park Ki-Woong , Cho Won-Ju
Published: September 2022

In this study, we propose tunable pH sensors based on the electric-double-layer transistor (EDLT) with time-dependent sensitivity characteristics. The EDLT is able to modulate the drain current by using the mobile ions inside the electrolytic gate dielectric. This property allows the implementation of a device with sensitivity characteristics that are simply adjusted according to the measurement time. An extended gate-type, ion-sensitive, field-effect transistor consisting of a chitosan/Ta2O5 hybrid dielectric EDLT transducer, and an SnO2 sensing membrane, were fabricated to evaluate the sensing behavior at different buffer pH levels. As a result, we were able to achieve tunable sensitivity by only adjusting the measurement time by using a single EDLT and without additional gate electrodes. In addition, to demonstrate the unique sensing behavior of the time-dependent tunable pH sensors based on organic–inorganic hybrid EDLT, comparative sensors consisting of a normal FET with a SiO2 gate dielectric were prepared. It was found that the proposed pH sensors exhibit repeatable and stable sensing operations with drain current deviations <1%. Therefore, pH sensors using a chitosan electrolytic EDLT are suitable for biosensor platforms, possessing tunable sensitivity and high-reliability characteristics.
Endurance Training Increases the Running Performance of Untrained Men without Changing the Mitochondrial Volume Density in the Gastrocnemius Muscle
Authors: Zoladz Jerzy A. , Majerczak Joanna , Galganski Lukasz , Grandys Marcin , Zapart-Bukowska Justyna , Kuczek Piotr , Kołodziejski Leszek , Walkowicz Lucyna , Szymoniak-Chochół Dorota , Kilarski Wincenty , Jarmuszkiewicz Wieslawa
Published: September 2022

The activity and quantity of mitochondrial proteins and the mitochondrial volume density (MitoVD) are higher in trained muscles; however, the underlying mechanisms remain unclear. Our goal was to determine if 20 weeks’ endurance training simultaneously increases running performance, the amount and activity of mitochondrial proteins, and MitoVD in the gastrocnemius muscle in humans. Eight healthy, untrained young men completed a 20-week moderate-intensity running training program. The training increased the mean speed of a 1500 m run by 14.0% (p = 0.008) and the running speed at 85% of maximal heart rate by 9.6% (p = 0.008). In the gastrocnemius muscle, training significantly increased mitochondrial dynamics markers, i.e., peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) by 23%, mitochondrial transcription factor A (TFAM) by 29%, optic artrophy-1 (OPA1) by 31% and mitochondrial fission factor (MFF) by 44%, and voltage-dependent anion channel 1 (VDAC1) by 30%. Furthermore, training increased the amount and maximal activity of citrate synthase (CS) by 10% and 65%, respectively, and the amount and maximal activity of cytochrome c oxidase (COX) by 57% and 42%, respectively, but had no effect on the total MitoVD in the gastrocnemius muscle. We concluded that not MitoVD per se, but mitochondrial COX activity (reflecting oxidative phosphorylation activity), should be regarded as a biomarker of muscle adaptation to endurance training in beginner runners.
Experimental Crossing Confirms Reproductive Isolation between Cryptic Species within Eulimnogammarus verrucosus (Crustacea: Amphipoda) from Lake Baikal
Authors: Drozdova Polina , Saranchina Alexandra , Madyarova Ekaterina , Gurkov Anton , Timofeyev Maxim
Published: September 2022

Ancient lakes are known speciation hotspots. One of the most speciose groups in the ancient Lake Baikal are gammaroid amphipods (Crustacea: Amphipoda: Gammaroidea). There are over 350 morphological species and subspecies of amphipods in Baikal, but the extent of cryptic variation is still unclear. One of the most common species in the littoral zone of the lake, Eulimnogammarus verrucosus (Gerstfeldt, 1858), was recently found to comprise at least three (pseudo)cryptic species based on molecular data. Here, we further explored these species by analyzing their mitogenome-based phylogeny, genome sizes with flow cytometry, and their reproductive compatibility. We found divergent times of millions of years and different genome sizes in the three species (6.1, 6.9 and 8 pg), further confirming their genetic separation. Experimental crossing of the western and southern species, which are morphologically indistinguishable and have adjacent ranges, showed their separation with a post-zygotic reproductive barrier, as hybrid embryos stopped developing roughly at the onset of gastrulation. Thus, the previously applied barcoding approach effectively indicated the separate biological species within E. verrucosus. These results provide new data for investigating genome evolution and highlight the need for precise tracking of the sample origin in any studies in this morphospecies.
Inhibition of FGFR Signaling by Targeting FGF/FGFR Extracellular Interactions: Towards the Comprehension of the Molecular Mechanism through NMR Approaches
Authors: Pagano Katiuscia , Longhi Elisa , Molinari Henriette , Taraboletti Giulia , Ragona Laura
Published: September 2022

NMR-based approaches play a pivotal role in providing insight into molecular recognition mechanisms, affording the required atomic-level description and enabling the identification of promising inhibitors of protein–protein interactions. The aberrant activation of the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor (FGFR) signaling pathway drives several pathologies, including cancer development, metastasis formation, resistance to therapy, angiogenesis-driven pathologies, vascular diseases, and viral infections. Most FGFR inhibitors targeting the intracellular ATP binding pocket of FGFR have adverse effects, such as limited specificity and relevant toxicity. A viable alternative is represented by targeting the FGF/FGFR extracellular interactions. We previously identified a few small-molecule inhibitors acting extracellularly, targeting FGFR or FGF. We have now built a small library of natural and synthetic molecules that potentially act as inhibitors of FGF2/FGFR interactions to improve our understanding of the molecular mechanisms of inhibitory activity. Here, we provide a comparative analysis of the interaction mode of small molecules with the FGF2/FGFR complex and the single protein domains. DOSY and residue-level NMR analysis afforded insights into the capability of the potential inhibitors to destabilize complex formation, highlighting different mechanisms of inhibition of FGF2-induced cell proliferation.
Pattern of Mitochondrial Respiration in Peripheral Blood Cells of Patients with Parkinson’s Disease
Authors: Schirinzi Tommaso , Salvatori Illari , Zenuni Henri , Grillo Piergiorgio , Valle Cristiana , Martella Giuseppina , Mercuri Nicola , Ferri Alberto
Published: September 2022

Mitochondria are central in the pathogenesis of Parkinson’s disease (PD), as they are involved in oxidative stress, synaptopathy, and other immunometabolic pathways. Accordingly, they are emerging as a potential neuroprotection target, although further human-based evidence is needed for therapeutic advancements. This study aims to shape the pattern of mitochondrial respiration in the blood leukocytes of PD patients in relation to both clinical features and the profile of cerebrospinal fluid (CSF) biomarkers of neurodegeneration. Mitochondrial respirometry on the peripheral blood mononucleate cells (PBMCs) of 16 PD patients and 14 controls was conducted using Seahorse Bioscience technology. Bioenergetic parameters were correlated either with standard clinical scores for motor and non-motor disturbances or with CSF levels of α-synuclein, amyloid-β peptides, and tau proteins. In PD, PBMC mitochondrial basal respiration was normal; maximal and spare respiratory capacities were both increased; and ATP production was higher, although not significantly. Maximal and spare respiratory capacity was directly correlated with disease duration, MDS-UPDRS part III and Hoehn and Yahr motor scores; spare respiratory capacity was correlated with the CSF amyloid-β-42 to amyloid-β-42/40 ratio. We provided preliminary evidence showing that mitochondrial respiratory activity increases in the PBMCs of PD patients, probably following the compensatory adaptations to disease progression, in contrast to the bases of the neuropathological substrate.
MLK3 Regulates Inflammatory Response via Activation of AP-1 Pathway in HEK293 and RAW264.7 Cells
Authors: Ha Anh Thu , Cho Jae Youl , Kim Daewon
Published: September 2022

Inflammation is a critically important barrier found in innate immunity. However, severe and sustained inflammatory conditions are regarded as causes of many different serious diseases, such as cancer, atherosclerosis, and diabetes. Although numerous studies have addressed how inflammatory responses proceed and what kinds of proteins and cells are involved, the exact mechanism and protein components regulating inflammatory reactions are not fully understood. In this paper, to determine the regulatory role of mixed lineage kinase 3 (MLK3), which functions as mitogen-activated protein kinase kinase kinase (MAP3K) in cancer cells in inflammatory response to macrophages, we employed an overexpression strategy with MLK3 in HEK293 cells and used its inhibitor URMC-099 in lipopolysaccharide (LPS)-treated RAW264.7 cells. It was found that overexpressed MLK3 increased the mRNA expression of inflammatory genes (COX-2, IL-6, and TNF-α) via the activation of AP-1, according to a luciferase assay carried out with AP-1-Luc. Overexpression of MLK3 also induced phosphorylation of MAPKK (MEK1/2, MKK3/6, and MKK4/7), MAPK (ERK, p38, and JNK), and AP-1 subunits (c-Jun, c-Fos, and FRA-1). Phosphorylation of MLK3 was also observed in RAW264.7 cells stimulated by LPS, Pam3CSK, and poly(I:C). Finally, inhibition of MLK3 by URMC-099 reduced the expression of COX-2 and CCL-12, phosphorylation of c-Jun, luciferase activity mediated by AP-1, and phosphorylation of MAPK in LPS-treated RAW264.7 cells. Taken together, our findings strongly suggest that MLK3 plays a central role in controlling AP-1-mediated inflammatory responses in macrophages and that this enzyme can serve as a target molecule for treating AP-1-mediated inflammatory diseases.
Different Approaches for the Profiling of Cancer Pathway-Related Genes in Glioblastoma Cells
Authors: Majercikova Zuzana , Dibdiakova Katarina , Gala Michal , Horvath Denis , Murin Radovan , Zoldak Gabriel , Hatok Jozef
Published: September 2022

Deregulation of signalling pathways that regulate cell growth, survival, metabolism, and migration can frequently lead to the progression of cancer. Brain tumours are a large group of malignancies characterised by inter- and intratumoral heterogeneity, with glioblastoma (GBM) being the most aggressive and fatal. The present study aimed to characterise the expression of cancer pathway-related genes (n = 84) in glial tumour cell lines (A172, SW1088, and T98G). The transcriptomic data obtained by the qRT-PCR method were compared to different control groups, and the most appropriate control for subsequent interpretation of the obtained results was chosen. We analysed three widely used control groups (non-glioma cells) in glioblastoma research: Human Dermal Fibroblasts (HDFa), Normal Human Astrocytes (NHA), and commercially available mRNAs extracted from healthy human brain tissues (hRNA). The gene expression profiles of individual glioblastoma cell lines may vary due to the selection of a different control group to correlate with. Moreover, we present the original multicriterial decision making (MCDM) for the possible characterization of gene expression profiles. We observed deregulation of 75 genes out of 78 tested in the A172 cell line, while T98G and SW1088 cells exhibited changes in 72 genes. By comparing the delta cycle threshold value of the tumour groups to the mean value of the three controls, only changes in the expression of 26 genes belonging to the following pathways were identified: angiogenesis FGF2; apoptosis APAF1, CFLAR, XIAP; cellular senescence BM1, ETS2, IGFBP5, IGFBP7, SOD1, TBX2; DNA damage and repair ERCC5, PPP1R15A; epithelial to mesenchymal transition SNAI3, SOX10; hypoxia ADM, ARNT, LDHA; metabolism ATP5A1, COX5A, CPT2, PFKL, UQCRFS1; telomeres and telomerase PINX1, TINF2, TNKS, and TNKS2. We identified a human astrocyte cell line and normal human brain tissue as the appropriate control group for an in vitro model, despite the small sample size. A different method of assessing gene expression levels produced the same disparities, highlighting the need for caution when interpreting the accuracy of tumorigenesis markers.
Immuno-Mediated Inflammation in Hypertensive Patients with 1-h Post-Load Hyperglycemia
Authors: Perticone Maria , Maio Raffaele , Gigliotti Simona , Arturi Franco , Succurro Elena , Sciacqua Angela , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco
Published: September 2022

Inflammation plays a key role in the pathogenesis/progression of atherosclerosis, and inflammatory molecules contribute to the progression of cardiovascular disease. Subjects with normal post-load glucose tolerance and 1-h post-load plasma glucose >155 mg/dL have an increased risk of subclinical target organ damage and incident diabetes. We aimed to test possible differences in immune-mediated inflammatory parameters in newly-diagnosed hypertensives with or without 1-h post-load hyperglycemia. We enrolled 25 normotensives (NGT) and 50 hypertensives normotolerant on oral glucose tolerance test, further divided into two groups based on 1-h post-load plasma glucose: NGT 1-h ≥ 155 (n = 25) and NGT 1-h < 155 (n = 25). We measured toll-like receptor (TLR) 2, TLR4, nuclear factor kβ (NF-kβ), interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α. Hypertensives showed significantly worse metabolic and lipid profiles, and higher values of body mass ass index (BMI), creatinine, and inflammatory parameters, compared to controls. NGT 1-h ≥ 155 had a worse glycometabolic profile and higher values of TLR2 (9.4 ± 4.2 vs. 5.9 ± 2.6 MFI), TLR4 (13.1 ± 3.9 vs. 7.8 ± 2.3 MFI), NF-kβ (0.21 ± 0.07 vs. 0.14 ± 0.04), IL-1β (6.9 ± 3.4 vs. 3.2 ± 2.1 pg/mL), IL-6 (10.8 ± 2.6 vs. 4.1 ± 1.6 pg/mL), IL-8 (27.6 ± 9.3 vs. 13.3 ± 5.6 pg/mL), TNF-α (6.4 ± 2.9 vs. 3.3 ± 1.4 pg/mL), and high-sensitivity C-reactive protein (hs-CRP) (4.8 ± 1.5 vs. 2.7 ± 1.0 mg/dL) in comparison with NGT 1-h < 155. Matsuda-index and 1-h post-load glycemia were retained as major predictors of TLRs and NF-kβ. These results contribute to better characterizing cardiovascular risk in hypertensives.
CTLA4-Linked Autoimmunity in the Pathogenesis of Endometriosis and Related Infertility: A Systematic Review
Authors: Mikuš Mislav , Goldštajn Marina Šprem , Brlečić Ivan , Dumančić Stipe , Laganà Antonio Simone , Chiantera Vito , Vujić Goran , Ćorić Mario
Published: September 2022

Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.
Heat Stress Decreases Rice Grain Weight: Evidence and Physiological Mechanisms of Heat Effects Prior to Flowering
Authors: Wu Chao , Cui Kehui , Fahad Shah
Published: September 2022

Heat stress during the preflowering panicle initiation stage seriously decreases rice grain weight in an invisible way and has not been given enough attention. The current review aims to (i) specify the heat effects on rice grain weight during the panicle initiation stage compared with the most important grain-filling stage; and (ii) discuss the physiological mechanisms of the decreased rice grain weight induced by heat during panicle initiation in terms of assimilate supply and phytohormone regulation, which are key physiological processes directly regulating rice grain weight. We emphasize that the effect of heat during the panicle initiation stage on rice grain weight is more serious than that during the grain-filling stage. Heat stress during the panicle initiation stage induces alterations in endogenous phytohormones, leading to the inhibition of the photosynthesis of functional leaves (source) and the formation of vascular bundles (flow), thus reducing the accumulation and transport of nonstructural carbohydrates and the growth of lemmata and paleae. The disruptions in the “flow” and restrictions in the preanthesis “source” tissue reduce grain size directly and decrease grain plumpness indirectly, resulting in a reduction in the final grain weight, which could be the direct physiological causes of the lower rice grain weight induced by heat during the panicle initiation stage. We highlight the seriousness of preflowering heat stress on rice grain weight, which can be regarded as an invisible disaster. The physiological mechanisms underlying the lower grain weight induced by heat during panicle initiation show a certain novelty because they distinguish this stage from the grain-filling stage. Additionally, a number of genes that control grain size through phytohormones have been summarized, but their functions have not yet been fully tested under heat conditions, except for the Grain Size and Abiotic stress tolerance 1 (GSA1) and BRASSINOSTEROID INSENSITIVE1 (OsBRI1) genes, which are reported to respond rapidly to heat stress. The mechanisms of reduced rice grain weight induced by heat during the panicle initiation stage should be studied in more depth in terms of molecular pathways.
Dual Mode of Mitochondrial ROS Action during Reprogramming to Pluripotency
Authors: Skvortsova Elena V. , Nazarov Igor B. , Tomilin Alexey N. , Sinenko Sergey A.
Published: September 2022

Essential changes in cell metabolism and redox signaling occur during the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). In this paper, using genetic and pharmacological approaches, we have investigated the role of electron transport chain (ETC) complex-I (CI) of mitochondria in the process of cell reprogramming to pluripotency. Knockdown of NADH-ubiquinone oxidoreductase core subunits S1 (Ndufs1) or subunit B10 (Ndufb10) of the CI or inhibition of this complex with rotenone during mouse embryonic fibroblast (MEF) reprogramming resulted in a significantly decreased number of induced pluripotent stem cells (iPSCs). We have found that mitochondria and ROS levels due course of the reprogramming tightly correlate with each other, both reaching peak by day 3 and significantly declining by day 10 of the process. The transient augmentation of mitochondrial reactive oxygen species (ROS) could be attenuated by antioxidant treatment, which ameliorated overall reprogramming. However, ROS scavenging after day 3 or during the entire course of reprogramming was suppressive for iPSC formation. The ROS scavenging within the CI-deficient iPSC-precursors did not improve, but further suppressed the reprogramming. Our data therefore point to distinct modes of mitochondrial ROS action during the early versus mid and late stages of reprogramming. The data further substantiate the paradigm that balanced levels of oxidative phosphorylation have to be maintained on the route to pluripotency.
Zearalenone Promotes LPS-Induced Oxidative Stress, Endoplasmic Reticulum Stress, and Accelerates Bovine Mammary Epithelial Cell Apoptosis
Authors: Fu Yurong , Jin Yongcheng , Tian Yue , Yu Hao , Wang Ruqi , Qi Huiyu , Feng Bo , Zhang Jing
Published: September 2022

Both zearalenone (ZEA) and lipopolysaccharide (LPS) can induce oxidative stress, and even apoptosis in bovine mammary epithelial cells (MAC-T), but not much attention has been given to the synergistic effect of ZEA and LPS. In this study, we treated MAC-T cells with different concentrations of LPS (1, 10, 50, and 100 μg/mL) and ZEA (5, 15, and 30 μM) to induce cell damage. Previous results show that MAC-T cell viability decreases with increasing LPS concentration. Meanwhile, 1 µg/mL LPS and ZEA were selected for combined treatment in subsequent studies. It was found that co-treatment with ZEA and LPS increases the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), decreases mitochondrial membrane potential (MMP), and superoxide dismutase (SOD), and reduces glutathione (GSH). ZEA and LPS are found to activate endoplasmic reticulum (ER) stress by increasing the expression of glucose-regulated protein 78 kDa (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP). It increases cell apoptosis by suppressing the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), indicated by up-regulation of Bcl2-associated X protein (Bax) and Cysteinyl aspartate-specific proteinases 3 (caspase-3) expression. The above results suggest that the synergistic effect of ZEA and LPS aggravate cytotoxicity.
Fluorine Atoms on C6H5-Corrole Affect the Interaction with Mpro and PLpro Proteases of SARS-CoV-2: Molecular Docking and 2D-QSAR Approaches
Authors: Chaves Otávio Augusto , Rodrigues-Santos Cláudio Eduardo , Echevarria Áurea , Sacramento Carolina Q. , Fintelman-Rodrigues Natalia , Temerozo Jairo R. , Castro-Faria-Neto Hugo Caire , Souza Thiago Moreno Lopes e
Published: September 2022

The chymotrypsin-like cysteine protease (3CLpro, also known as main protease—Mpro) and papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been used as the main targets for screening potential synthetic inhibitors for posterior in vitro evaluation of the most promising compounds. In this sense, the present work reports for the first time the evaluation of the interaction between Mpro/PLpro with a series of 17 porphyrin analogues-corrole (C1), meso-aryl-corrole (C2), and 15 fluorinated-meso-aryl-corrole derivatives (C3–C17) via molecular docking calculations. The impact of fluorine atoms on meso-aryl-corrole structure was also evaluated in terms of binding affinity and physical-chemical properties by two-dimensional quantitative structure–activity relationship (2D-QSAR). The presence of phenyl moieties increased the binding capacity of corrole for both proteases and depending on the position of fluorine atoms might impact positively or negatively the binding capacity. For Mpro the para-fluorine atoms might decrease drastically the binding capacity, while for PLpro there was a certain increase in the binding affinity of fluorinated-corroles with the increase of fluorine atoms into meso-aryl-corrole structure mainly from tri-fluorinated insertions. The 2D-QSAR models indicated two separated regions of higher and lower affinity for Mpro:C1–C17 based on dual electronic parameters (σI and σR), as well as one model was obtained with a correlation between the docking score value of Mpro:C2–C17 and the corresponding 13C nuclear magnetic resonance (NMR) chemical shifts of the sp2 carbon atoms (δC-1 and δC-2) of C2–C17. Overall, the fluorinated-meso-aryl-corrole derivatives showed favorable in silico parameters as potential synthetic compounds for future in vitro assays on the inhibition of SARS-CoV-2 replication.
Ellagic Acid and Its Anti-Aging Effects on Central Nervous System
Authors: Zhu Heyu , Yan Yuanmei , Jiang Yi , Meng Xianfang
Published: September 2022

Aging is an unavoidable biological process that leads to the decline of human function and the reduction in people’s quality of life. Demand for anti-aging medicines has become very urgent. Many studies have shown that ellagic acid (EA), a phenolic compound widely distributed in dicotyledonous plants, has powerful anti-inflammation and antioxidant properties. Moreover, it has been demonstrated that EA can enhance neuronal viability, reduce neuronal defects, and alleviate damage in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. This paper reviews the biochemical functions and neuroprotective effects of EA, showing the clinical value of its application.
Clevis-Grip Tensile Tests on Basalt, Carbon and Steel FRCM Systems Realized with Customized Cement-Based Matrices
Authors: De Domenico Dario , Maugeri Natale , Longo Paolo , Ricciardi Giuseppe , Gullì Giuseppe , Calabrese Luigi
Published: September 2022

The tensile properties of fabric-reinforced cementitious matrix (FRCM) composites are experimentally investigated through clevis-grip tensile tests (according to AC434 provisions) on FRCM coupons realized with customized (ad hoc developed in this paper) cement-based matrices. The tested FRCM coupons are reinforced with basalt, carbon, or steel fabrics, and are prepared with three different matrices: one-component mortar incorporating dispersible copolymer powders of vinyl acetate and ethylene (matrices A and B) and two-component mortar with carboxylated styrene–butadiene copolymer liquid resin (matrix C). This has made it possible to investigate the mechanical compatibility between different mortar matrices and fabrics and the resulting tensile properties of FRCM composites in the uncracked, cracking, and fully cracked phases. Experimental results are critically analyzed in terms of stress–strain curves and failure mechanisms comparatively for the analyzed FRCM systems. It has been shown that the matrix B exhibits a good compatibility with the basalt pre-impregnated fabric, while the matrix C appears to be the most suitable candidate to optimize the interfacial stress transfer at the fiber–matrix interface for all fabrics, thus exalting the mechanical performances in terms of tensile strength and ultimate strain. The results of this experimental program can be useful for designing optimized mortar mixes aimed at realizing novel FRCM composites or at improving existing FRCM systems by suitably accounting for compatibility behavior and slippage at the fabric–matrix interface.
Simulated Short- and Long-Term Deformation in Coastal Karst Caves
Authors: Lin Chunxiu , Xia Chang , Zhang Hong , Liu Zhen , Zhou Cuiying
Published: September 2022

The self-balanced pressure arch theory is an important basis for excavation support in karst caves, but it is difficult to quantify the empirical theory in coastal areas. In addition, the rheological effects of karst strata could pose a hazard to engineering. Therefore, this study investigated the rheological mechanism under the self-balanced pressure arch effect, and we proposed a mesoscopic unit rheological model for clay minerals in a water-rich environment. With the discrete element method (DEM), we realized the numerical modeling of the rheological model. Then, the proposed model is validated by a case study of foundation excavation in the coastal karst area of China. The mesoscopic mechanical characteristics of caves considering the influence of pressure arch are analyzed. The results show that the self-balance of the caverns mainly lies in the mesoscopic mineral strength and local stress. With the rheological controlled model, the final predicted convergent deformation of the foundation has an error of less than 10% compared with the field monitoring data. In this study, we can quantitively describe the self-balance effect of the pressure arch surrounding the caves and reveal the rheological mechanism. The proposed model can be applied to similar engineering with careful calibration and provide safety guidance.
The Immune System as a Therapeutic Target for Alzheimer’s Disease
Authors: Zieneldien Tarek , Kim Janice , Sawmiller Darrell , Cao Chuanhai
Published: September 2022

Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder and is the most common cause of dementia. Furthermore, aging is considered the most critical risk factor for AD. However, despite the vast amount of research and resources allocated to the understanding and development of AD treatments, setbacks have been more prominent than successes. Recent studies have shown that there is an intricate connection between the immune and central nervous systems, which can be imbalanced and thereby mediate neuroinflammation and AD. Thus, this review examines this connection and how it can be altered with AD. Recent developments in active and passive immunotherapy for AD are also discussed as well as suggestions for improving these therapies moving forward.
Parametric Optimisation of Friction-Stir-Spot-Welded Al 6061-T6 Incorporated with Silicon Carbide Using a Hybrid WASPAS–Taguchi Technique
Authors: Chaudhary Neeru , Singh Sarbjit , Garg Mohinder Pal , Garg Harish Kumar , Sharma Shubham , Li Changhe , Tag Eldin Elsayed Mohamed , El-Khatib Samah
Published: September 2022

Friction stir spot welding (FSSW) is one of the most popular fusion joining processes. The process is a solid-state welding process that allows welding of weldable as well as non-weldable materials. As a part of this investigation, weld samples of Al6061-T6 were reinforced with silicon carbide (SiC) powder with an average particle size of 45 µm. Initially, a Taguchi L9 orthogonal array was developed with three factors, i.e., rotational speed of the tool, pre-dwelling time, and diameter of the hole that was filled with SiC before welding. The effects of the SiC particles and process parameters were investigated as tensile–shear load and micro-hardness. The optimisation of parameters in order to maximise the output responses—i.e., strength and hardness of the welded joints—was performed using a hybrid WASPAS–Taguchi method. The optimised process parameters obtained were a 3.5 mm guiding hole diameter, 1700 rpm tool rotation speed, and 14 s of pre-dwelling time.
Influence Factors in the Wide Application of Alkali-Activated Materials: A Critical Review about Efflorescence
Authors: Liang Kaikang , Cui Kai , Sabri Mohanad Muayad Sabri , Huang Jiandong
Published: September 2022

Applications related to alkali-activated materials (AAMs) have received much attention due to their excellent mechanical properties and low-energy production. Although much research has focused on developing AAMs, their application is still limited. One of the primary reasons is the efflorescence. Not only does efflorescence affect the material aesthetics, but it also affects the mechanical performance, leading to a decrease in material quality. This paper first summarizes the current research on AAMs efflorescence. The formation process of efflorescence is divided into three parts: alkaline cation leaching, air carbonation, and efflorescence formation. Furthermore, the influences caused by different factors, including raw materials, curing conditions, AAMs modalities, etc., on the efflorescence are proposed. This paper highlights the solutions for efflorescence by avoiding free alkaline cation leaching and preventing air carbonation. The advantages and disadvantages of efflorescence are discussed in-depth, showing that it can be exploited under certain conditions, such as in wastewater treatment. This paper has important implications for the practical preparation and application of AAMs.
Orthotropic Behavior of Twin-Roll-Cast and Hot-Rolled Magnesium ZAX210 Sheet
Authors: Ullmann Madlen , Kaden Christoph , Kittner Kristina , Prahl Ulrich
Published: September 2022

Magnesium sheet metal alloys offer a deformation asymmetry, which is strongly related to grain size and texture. In order to predict deformation behavior as well as to provide methods to eliminate anisotropy and yield asymmetry, a lot of effort is invested in studying the tension–compression asymmetry of magnesium alloys. However, only a few studies deal with the characterization of the yield asymmetry of magnesium wrought alloys, especially Ca-containing alloys, related to temperature and strain. In this study, the orthotropic behavior of a twin-roll-cast, homogenized, rolled and finish-annealed Mg-2Zn-1Al-0.3Ca (ZAX210) magnesium alloy was investigated by tensile testing at room temperature, 150 °C and 250 °C. The r-values were determined and the Hill’48 yield criterion was used for the constitutive formulation of the plastic yielding and deformation. The yield loci calculated using Mises and Hill’48 as well as the determined r-values reveal an almost isotropic behavior of the ZAX210 alloy. The r-value increases with increasing logarithmic strain. At 0.16 logarithmic strain the r-values at room temperature vary between 1 (0°) and 1.5 (45° and 90°). At higher temperatures (250 °C), r-values close to 1 at all tested directions are attained. The enhanced yield asymmetry can be attributed to the weaker basal texture that arises during hot rolling and final annealing of the twin-roll-cast ZAX210 magnesium alloy. In comparison to AZ31, the ZAX210 alloy shows a yield behavior close to transversal isotropy. Finally, responsible mechanisms for this behavior are discussed.
Blast Resistance of Reinforced Concrete Slabs Based on Residual Load-Bearing Capacity
Authors: Wang Lijun , Cheng Shuai , Liao Zhen , Yin Wenjun , Liu Kai , Ma Long , Wang Tao , Zhang Dezhi
Published: September 2022

In this paper, the blast-loading experiment and numerical simulation are carried out for RC slabs with two typical reinforcement ratios. The time history of reflected shockwave pressures and displacement responses at different positions on the impact surface of the specimens are obtained, and the influence of the reinforcement ratio on the dynamic responses and failure modes of the RC slabs is analyzed. Based on the experimental data, the simulation model of the RC slab is verified, and the results indicate good agreement between the two methods. On this basis, the residual load-bearing capacity of the damaged RC slabs is analyzed. The results show that the load distribution on the impact surface of the slab is extremely uneven under close-in blast loading. The resistance curve shape of the RC slabs varies markedly before and after blast loading, and its load bearing capacity and bending stiffness deteriorate irreversibly. Increasing the reinforcement ratio can impede crack extension, reduce the slab’s residual displacement, and, at the same time, reduce the decrease of the damaged slab’s load-bearing capacity. The findings of this study will provide insights into the anti-explosion design and damage evaluation of RC slabs.