bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Potency of Induced Pluripotent Stem-Cell-Derived Corneal Endothelial-like Cells for Corneal Endothelial Dysfunction
Authors: So Seongjun , Park Yoonkyung , Kang Soon Suk , Han Jongsuk , Sunwoo Jeong Hye , Lee Whanseo , Kim Jin , Ye Eun Ah , Kim Jae Yong , Tchah Hungwon , Kang Eunju , Lee Hun
Published: January 2023

Corneal endothelial cells (CECs) do not proliferate or recover after illness or injury, resulting in decreased cell density and loss of pump/barrier function. Considering the shortage of donor cornea, it is vital to establish robust methods to generate CECs from induced pluripotent stem cells (iPSCs). We investigated the efficacy and safety of transplantation of iPSC-derived CECs into a corneal endothelial dysfunction (CED) rabbit model. iPSCs were generated from human fibroblasts. We characterized iPSCs by demonstrating the gene expression of the PSC markers OCT4, SOX2, TRA-1-60, and NANOG, teratoma formation, and differentiation into three germ layers. Differentiation of iPSCs into CECs was induced via neural crest cell (NCC) induction. CEC markers were detected using immunofluorescence and gene expression was analyzed using quantitative real-time PCR (qRT-PCR). After culturing iPSC-derived NCCs, we found the expression of zona occludens-1 (ZO-1) and Na+/K+ ATPase and a hexagonal morphology. ATP1A1, COL8A1, and AQP1 mRNA expression was higher in iPSC-derived CECs than in iPSCs and NCCs. We performed an injection of iPSC-derived CECs into the anterior chamber of a CED rabbit model and found improved levels of corneal transparency. We also found increased numbers of ZO-1- and ATP1A1-positive cells in rabbit corneas in the iPSC-derived CEC transplantation group. Usage of the coating material vitronectin (VTN) and fasudil resulted in good levels of CEC marker expression, demonstrated with Western blotting and immunocytochemistry. Combination of the VTN coating material and fasudil, instead of FNC mixture and Y27632, afforded the best results in terms of CEC differentiation’s in vitro and in vivo efficacy. Successful transplantation of CEC-like cells into a CED animal model confirms the therapeutic efficacy of these cells, demonstrated by the restoration of corneal clarity. Our results suggest that iPSC-derived CECs can be a promising cellular resource for the treatment of CED.
Silver Nanoparticles Alone or in Combination with Calcium Hydroxide Modulate the Viability, Attachment, Migration, and Osteogenic Differentiation of Human Mesenchymal Stem Cells
Authors: Algazlan Almaha S. , Almuraikhi Nihal , Muthurangan Manikandan , Balto Hanan , Alsalleeh Fahd
Published: January 2023

This study aimed to evaluate the effect of silver nanoparticles (AgNPs) alone or in combination with calcium hydroxide (Ca(OH)2) on the proliferation, viability, attachment, migration, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Different concentrations of AgNPs alone or mixed with Ca(OH)2 were prepared. Cell proliferation was measured using AlamarBlue, and hMSCs attachment to dentin disks was evaluated using scanning electron microscopy. Live–dead imaging was performed to assess apoptosis. Wound healing ability was determined using the scratch-migration assay. To evaluate osteogenic differentiation, the expression of Runt-related transcription factor (RUNX2), Transforming growth factor beta-1 (TGF-β1), Alkaline Phosphatase (ALP), and Osteocalcin (OCN) were measured using real-time reverse transcriptase polymerase chain reaction. ALP staining and activity were also performed as indicators of osteogenic differentiation. AgNPs alone seemed to favor cell attachment. Lower concentrations of AgNPs enhanced cell proliferation. AgNP groups showed markedly less apoptosis. None of the medicaments had adverse effects on wound closure. The expression of TGF-β1 was significantly upregulated in all groups, and OCN was highly expressed in the AgNP groups. AgNPs 0.06% showed the most enhanced ALP gene expression levels, activity, and marked cytochemical staining. In conclusion, AgNPs positively affect hMSCs, making them a potential biomaterial for various clinical applications.
Fecal Volatile Organic Compounds and Microbiota Associated with the Progression of Cognitive Impairment in Alzheimer’s Disease
Authors: Ubeda Cristina , Vázquez-Carretero María D. , Luque-Tirado Andrea , Ríos-Reina Rocío , Rubio-Sánchez Ricardo , Franco-Macías Emilio , García-Miranda Pablo , Calonge María L. , Peral María J.
Published: January 2023

Metabolites produced by an altered gut microbiota might mediate the effects in the brain. Among metabolites, the fecal volatile organic compounds (VOCs) are considered to be potential biomarkers. In this study, we examined both the VOCs and bacterial taxa in the feces from healthy subjects and Alzheimer’s disease (AD) patients at early and middle stages. Remarkably, 29 fecal VOCs and 13 bacterial genera were differentiated from the healthy subjects and the AD patients. In general, higher amounts of acids and esters were found in in the feces of the AD patients and terpenes, sulfur compounds and aldehydes in the healthy subjects. At the early stage of AD, the most relevant VOCs with a higher abundance were short-chain fatty acids and their producing bacteria, Faecalibacterium and Lachnoclostridium. Coinciding with the development of dementia in the AD patients, parallel rises of heptanoic acid and Peptococcus were observed. At a more advanced stage of AD, the microbiota and volatiles shifted towards a profile in the feces with increases in hexanoic acid, Ruminococcus and Blautia. The most remarkable VOCs that were associated with the healthy subjects were 4-ethyl-phenol and dodecanol, together with their possible producers Clostridium and Coprococcus. Our results revealed a VOCs and microbiota crosstalk in AD development and their profiles in the feces were specific depending on the stage of AD. Additionally, some of the most significant fecal VOCs identified in our study could be used as potential biomarkers for the initiation and progression of AD.
Profound Modification of Fatty Acid Profile and Endocannabinoid-Related Mediators in PPARα Agonist Fenofibrate-Treated Mice
Authors: Murru Elisabetta , Muntoni Anna Lisa , Manca Claudia , Aroni Sonia , Pistis Marco , Banni Sebastiano , Carta Gianfranca
Published: January 2023

Fenofibrate (FBR), an oral medication used to treat dyslipidemia, is a ligand of the peroxisome proliferator-activated receptor α (PPARα), a nuclear receptor that regulates the expression of metabolic genes able to control lipid metabolism and food intake. PPARα natural ligands include fatty acids (FA) and FA derivatives such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), known to have anti-inflammatory and anorexigenic activities, respectively. We investigated changes in the FA profile and FA derivatives by HPLC and LC-MS in male C57BL/6J mice fed a standard diet with or without 0.2% fenofibrate (0.2% FBR) for 21 days. Induction of PPARα by 0.2% FBR reduced weight gain, food intake, feed efficiency, and liver lipids and induced a profound change in FA metabolism mediated by parallel enhanced mitochondrial and peroxisomal β-oxidation. The former effects led to a steep reduction of essential FA, particularly 18:3n3, with a consequent decrease of the n3-highly unsaturated fatty acids (HUFA) score; the latter effect led to an increase of 16:1n7 and 18:1n9, suggesting enhanced hepatic de novo lipogenesis with increased levels of hepatic PEA and OEA, which may activate a positive feedback and further sustain reductions of body weight, hepatic lipids and feed efficiency.
S100A8 and S100A12 Proteins as Biomarkers of High Disease Activity in Patients with Rheumatoid Arthritis That Can Be Regulated by Epigenetic Drugs
Authors: Roszkowski Leszek , Jaszczyk Bożena , Plebańczyk Magdalena , Ciechomska Marzena
Published: January 2023

Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease that is still not well understood in terms of its pathogenesis and presents diagnostic and therapeutic challenges. Monocytes are key players in initiating and maintaining inflammation through the production of pro-inflammatory cytokines and S100 proteins in RA. This study aimed to test a specific DNA methylation inhibitor (RG108) and activator (budesonide) in the regulation of pro-inflammatory mediators—especially the S100 proteins. We also searched for new biomarkers of high disease activity in RA patients. RNA sequencing analysis of healthy controls (HCs) and RA monocytes was performed. Genes such as the S100 family, TNF, and IL-8 were validated by qRT-PCR following DNA-methylation-targeted drug treatment in a monocytic THP-1 cell line. The concentrations of the S100A8, S100A11, and S100A12 proteins in the sera and synovial fluids of RA patients were tested and correlated with clinical parameters. We demonstrated that RA monocytes had significantly increased levels of S100A8, S100A9, S100A11, S100A12, MYD88, JAK3, and IQGAP1 and decreased levels of IL10RA and TGIF1 transcripts. In addition, stimulation of THP-1 cells with budesonide statistically reduced the expression of the S100 family, IL-8, and TNF genes. In contrast, THP-1 cells treated with RG108 had increased levels of the S100 family and TNF genes. We also revealed a significant upregulation of S100A8, S100A11, and S100A12 in RA patients, especially in early RA compared to HC sera. In addition, protein levels of S100A8, S100A11, and S100A12 in RA synovial fluids compared to HC sera were significantly increased. Overall, our data suggest that the S100A8 and S100A12 proteins are strongly elevated during ongoing inflammation, so they could be used as a better biomarker of disease activity than CRP. Interestingly, epigenetic drugs can regulate these S100 proteins, suggesting their potential use in targeting RA inflammation.
Collagen-Specific Molecular Magnetic Resonance Imaging of Prostate Cancer
Authors: Kader Avan , Kaufmann Jan O. , Mangarova Dilyana B. , Moeckel Jana , Adams Lisa C. , Brangsch Julia , Heyl Jennifer L. , Zhao Jing , Verlemann Christine , Karst Uwe , Collettini Federico , Auer Timo A. , Hamm Bernd , Makowski Marcus R.
Published: January 2023

Constant interactions between tumor cells and the extracellular matrix (ECM) influence the progression of prostate cancer (PCa). One of the key components of the ECM are collagen fibers, since they are responsible for the tissue stiffness, growth, adhesion, proliferation, migration, invasion/metastasis, cell signaling, and immune recruitment of tumor cells. To explore this molecular marker in the content of PCa, we investigated two different tumor volumes (500 mm3 and 1000 mm3) of a xenograft mouse model of PCa with molecular magnetic resonance imaging (MRI) using a collagen-specific probe. For in vivo MRI evaluation, T1-weighted sequences before and after probe administration were analyzed. No significant signal difference between the two tumor volumes could be found. However, we detected a significant difference between the signal intensity of the peripheral tumor area and the central area of the tumor, at both 500 mm3 (p < 0.01, n = 16) and at 1000 mm3 (p < 0.01, n = 16). The results of our histologic analyses confirmed the in vivo studies: There was no significant difference in the amount of collagen between the two tumor volumes (p > 0.05), but within the tumor, higher collagen expression was observed in the peripheral area compared with the central area of the tumor. Laser ablation with inductively coupled plasma mass spectrometry further confirmed these results. The 1000 mm3 tumors contained 2.8 ± 1.0% collagen and the 500 mm3 tumors contained 3.2 ± 1.2% (n = 16). There was a strong correlation between the in vivo MRI data and the ex vivo histological data (y = −0.068x + 1.1; R2 = 0.74) (n = 16). The results of elemental analysis by inductively coupled plasma mass spectrometry supported the MRI data (y = 3.82x + 0.56; R2 = 0.79; n = 7). MRI with the collagen-specific probe in PCa enables differentiation between different tumor areas. This may help to differentiate tumor from healthy tissue, potentially identifying tumor areas with a specific tumor biology.
Impact of Layered Perovskite Oxide La0.85Yb0.15AlO3 on Structure and Transport Properties of Polyetherimide
Authors: Pulyalina Alexandra , Rostovtseva Valeriia , Faykov Ilya , Saprykina Natalia , Golikova Alexandra , Fedorova Anna , Polotskaya Galina , Novikov Alexander
Published: January 2023

This study aims to improve properties of Ultem® polyetherimide (PEI) by incorporating up to 2 wt% additives of the perovskite oxide La0.85Yb0.15AlO3 (LYA). The structure of dense PEI/LYA films was characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) in combination with an analysis of their elemental composition using energy-dispersive spectroscopy (EDS). The PEI/LYA films exhibit a two-layer structure. Contact angle measurements revealed hydrophilization of the membrane surface enriched with the perovskite. The transport properties were tested via gas separation and pervaporation processes. The separation selectivity of He/N2 and O2/N2 gas pairs increased with the growth of the LYA content in the membranes. Pervaporation of a methanol(MeOH)–cyclohexane(CH) mixture was effective due to the high sorption of MeOH in the PEI/LYA membranes. The maximal pervaporation separation index was found for the PEI/LYA(2%) membrane.
Modelling the Transitioning of SARS-CoV-2 nsp3 and nsp4 Lumenal Regions towards a More Stable State on Complex Formation
Authors: Klatte Nele , Shields Denis C. , Agoni Clement
Published: January 2023

During coronavirus infection, three non-structural proteins, nsp3, nsp4, and nsp6, are of great importance as they induce the formation of double-membrane vesicles where the replication and transcription of viral gRNA takes place, and the interaction of nsp3 and nsp4 lumenal regions triggers membrane pairing. However, their structural states are not well-understood. We investigated the interactions between nsp3 and nsp4 by predicting the structures of their lumenal regions individually and in complex using AlphaFold2 as implemented in ColabFold. The ColabFold prediction accuracy of the nsp3–nsp4 complex was increased compared to nsp3 alone and nsp4 alone. All cysteine residues in both lumenal regions were modelled to be involved in intramolecular disulphide bonds. A linker region in the nsp4 lumenal region emerged as crucial for the interaction, transitioning to a structured state when predicted in complex. The key interactions modelled between nsp3 and nsp4 appeared stable when the transmembrane regions of nsp3 and nsp4 were added to the modelling either alone or together. While molecular dynamics simulations (MD) demonstrated that the proposed model of the nsp3 lumenal region on its own is not stable, key interactions between nsp and nsp4 in the proposed complex model appeared stable after MD. Together, these observations suggest that the interaction is robust to different modelling conditions. Understanding the functional importance of the nsp4 linker region may have implications for the targeting of double membrane vesicle formation in controlling coronavirus infection.
The Potential Role of Regulated Cell Death in Dry Eye Diseases and Ocular Surface Dysfunction
Authors: Scarpellini Camilla , Ramos Llorca Alba , Lanthier Caroline , Klejborowska Greta , Augustyns Koen
Published: January 2023

The research on new treatments for dry eye diseases (DED) has exponentially grown over the past decades. The increased prevalence of dry eye conditions, particularly in the younger population, has received much attention. Therefore, it is of utmost importance to identify novel therapeutical targets. Regulated cell death (RCD) is an essential process to control the biological homeostasis of tissues and organisms. The identification of different mechanisms of RCD stimulated the research on their involvement in different human pathologies. Whereas apoptosis has been widely studied in DED and included in the DED vicious cycle, the role of RCD still needs to be completely elucidated. In this review, we will explore the potential roles of different types of RCD in DED and ocular surface dysfunction. Starting from the evidence of oxidative stress and inflammation in dry eye pathology, we will analyse the potential therapeutic applications of the following principal RCD mechanisms: ferroptosis, necroptosis, and pyroptosis.
Study of Seed Ageing in lpa1-1 Maize Mutant and Two Possible Approaches to Restore Seed Germination
Authors: Colombo Federico , Pagano Andrea , Sangiorgio Stefano , Macovei Anca , Balestrazzi Alma , Araniti Fabrizio , Pilu Roberto
Published: January 2023

Phytic acid (PA) is a strong anti-nutritional factor with a key antioxidant role in countering reactive oxygen species. Despite the potential benefits of low phytic acid (lpa) mutants, the reduction of PA causes pleiotropic effects, e.g., reduced seed germination and viability loss related to seed ageing. The current study evaluated a historical series of naturally aged seeds and showed that lpa1-1 seeds aged faster as compared to wildtype. To mimic natural ageing, the present study set up accelerated ageing treatments at different temperatures. It was found that incubating the seeds at 57 °C for 24 h, the wildtype germinated at 82.4% and lpa1-1 at 40%. The current study also hypothesized two possible solutions to overcome these problems: (1) Classical breeding was used to constitute synthetic populations carrying the lpa1-1 mutation, with genes pushing anthocyanin accumulation in the embryo (R-navajo allele). The outcome showed that the presence of R-navajo in the lpa1-1 genotype was not able to improve the germinability (−20%), but this approach could be useful to improve the germinability in non-mutant genotypes (+17%). (2) In addition, hydropriming was tested on lpa1-1 and wildtype seeds, and germination was improved by 20% in lpa1-1, suggesting a positive role of seed priming in restoring germination. Moreover, the data highlighted metabolic differences in the metabolome before and after hydropriming treatment, suggesting that the differences in germination could also be mediated by differences in the metabolic composition induced by the mutation.
Genome-Wide Identification and Characterization of Auxin Response Factor (ARF) Gene Family Involved in Wood Formation and Response to Exogenous Hormone Treatment in Populus trichocarpa
Authors: Liu Yingying , Wang Ruiqi , Yu Jiajie , Huang Shan , Zhang Yang , Wei Hairong , Wei Zhigang
Published: January 2023

Auxin is a key regulator that virtually controls almost every aspect of plant growth and development throughout its life cycle. As the major components of auxin signaling, auxin response factors (ARFs) play crucial roles in various processes of plant growth and development. In this study, a total of 35 PtrARF genes were identified, and their phylogenetic relationships, chromosomal locations, synteny relationships, exon/intron structures, cis-elements, conserved motifs, and protein characteristics were systemically investigated. We also analyzed the expression patterns of these PtrARF genes and revealed that 16 of them, including PtrARF1, 3, 7, 11, 13–17, 21, 23, 26, 27, 29, 31, and 33, were preferentially expressed in primary stems, while 15 of them, including PtrARF2, 4, 6, 9, 10, 12, 18–20, 22, 24, 25, 28, 32, and 35, participated in different phases of wood formation. In addition, some PtrARF genes, with at least one cis-element related to indole-3-acetic acid (IAA) or abscisic acid (ABA) response, responded differently to exogenous IAA and ABA treatment, respectively. Three PtrARF proteins, namely PtrARF18, PtrARF23, and PtrARF29, selected from three classes, were characterized, and only PtrARF18 was a transcriptional self-activator localized in the nucleus. Moreover, Y2H and bimolecular fluorescence complementation (BiFC) assay demonstrated that PtrARF23 interacted with PtrIAA10 and PtrIAA28 in the nucleus, while PtrARF29 interacted with PtrIAA28 in the nucleus. Our results provided comprehensive information regarding the PtrARF gene family, which will lay some foundation for future research about PtrARF genes in tree development and growth, especially the wood formation, in response to cellular signaling and environmental cues.
Progress in the Structural Basis of thermoTRP Channel Polymodal Gating
Authors: Fernández-Ballester Gregorio , Fernández-Carvajal Asia , Ferrer-Montiel Antonio
Published: January 2023

The thermosensory transient receptor potential (thermoTRP) family of ion channels is constituted by several nonselective cation channels that are activated by physical and chemical stimuli functioning as paradigmatic polymodal receptors. Gating of these ion channels is achieved through changes in temperature, osmolarity, voltage, pH, pressure, and by natural or synthetic chemical compounds that directly bind to these proteins to regulate their activity. Given that thermoTRP channels integrate diverse physical and chemical stimuli, a thorough understanding of the molecular mechanisms underlying polymodal gating has been pursued, including the interplay between stimuli and differences between family members. Despite its complexity, recent advances in cryo-electron microscopy techniques are facilitating this endeavor by providing high-resolution structures of these channels in different conformational states induced by ligand binding or temperature that, along with structure-function and molecular dynamics, are starting to shed light on the underlying allosteric gating mechanisms. Because dysfunctional thermoTRP channels play a pivotal role in human diseases such as chronic pain, unveiling the intricacies of allosteric channel gating should facilitate the development of novel drug-based resolving therapies for these disorders.
The Role of Hyperexcitability in Gliomagenesis
Authors: Goethe Eric A. , Deneen Benjamin , Noebels Jeffrey , Rao Ganesh
Published: January 2023

Glioblastoma is the most common malignant primary brain tumor. Recent studies have demonstrated that excitatory or activity-dependent signaling—both synaptic and non-synaptic—contribute to the progression of glioblastoma. Glutamatergic receptors may be stimulated via neuron–tumor synapses or release of glutamate by the tumor itself. Ion currents generated by these receptors directly alter the structure of membrane adhesion molecules and cytoskeletal proteins to promote migratory behavior. Additionally, the hyperexcitable milieu surrounding glioma increases the rate at which tumor cells proliferate and drive recurrent disease. Inhibition of excitatory signaling has shown to effectively reduce its pro-migratory and -proliferative effects.
Snap29 Is Dispensable for Self-Renewal Maintenance but Required for Proper Differentiation of Mouse Embryonic Stem Cells
Authors: Jia Yumei , Guo Zhaoyuan , Zhu Jiahao , Qin Guanyu , Sun Wenwen , Yin Yu , Wang Haiying , Guo Renpeng
Published: January 2023

Pluripotent embryonic stem cells (ESCs) can self-renew indefinitely and are able to differentiate into all three embryonic germ layers. Synaptosomal-associated protein 29 (Snap29) is implicated in numerous intracellular membrane trafficking pathways, including autophagy, which is involved in the maintenance of ESC pluripotency. However, the function of Snap29 in the self-renewal and differentiation of ESCs remains elusive. Here, we show that Snap29 depletion via CRISPR/Cas does not impair the self-renewal and expression of pluripotency-associated factors in mouse ESCs. However, Snap29 deficiency enhances the differentiation of ESCs into cardiomyocytes, as indicated by heart-like beating cells. Furthermore, transcriptome analysis reveals that Snap29 depletion significantly decreased the expression of numerous genes required for germ layer differentiation. Interestingly, Snap29 deficiency does not cause autophagy blockage in ESCs, which might be rescued by the SNAP family member Snap47. Our data show that Snap29 is dispensable for self-renewal maintenance, but required for the proper differentiation of mouse ESCs.
Identification of NPF Family Genes in Brassica rapa Reveal Their Potential Functions in Pollen Development and Response to Low Nitrate Stress
Authors: Yang Xiaoshuang , Han Wenyu , Qi Jiao , Li Yueying , Chen Xingbo , Zhang Yiwen , Wu Jingyu , Li Genze , Gao Jing , Dong Xiangshu
Published: January 2023

Nitrate Transporter 1/Peptide Transporter Family (NPF) genes encode membrane transporters involved in the transport of diverse substrates. However, little is known about the diversity and functions of NPFs in Brassica rapa. In this study, 85 NPFs were identified in B. rapa (BrNPFs) which comprised eight subfamilies. Gene structure and conserved motif analysis suggested that BrNFPs were conserved throughout the genus. Stress and hormone-responsive cis-acting elements and transcription factor binding sites were identified in BrNPF promoters. Syntenic analysis suggested that tandem duplication contributed to the expansion of BrNPFs in B. rapa. Transcriptomic profiling analysis indicated that BrNPF2.6, BrNPF2.15, BrNPF7.6, and BrNPF8.9 were expressed in fertile floral buds, suggesting important roles in pollen development. Thirty-nine BrNPFs were responsive to low nitrate availability in shoots or roots. BrNPF2.10, BrNPF2.19, BrNPF2.3, BrNPF5.12, BrNPF5.16, BrNPF5.8, and BrNPF6.3 were only up-regulated in roots under low nitrate conditions, indicating that they play positive roles in nitrate absorption. Furthermore, many genes were identified in contrasting genotypes that responded to vernalization and clubroot disease. Our results increase understanding of BrNPFs as candidate genes for genetic improvement studies of B. rapa to promote low nitrate availability tolerance and for generating sterile male lines based on gene editing methods.
Metformin and Its Immune-Mediated Effects in Various Diseases
Authors: Nojima Ichiro , Wada Jun
Published: January 2023

Metformin has been a long-standing prescribed drug for treatment of type 2 diabetes (T2D) and its beneficial effects on virus infection, autoimmune diseases, aging and cancers are also recognized. Metformin modulates the differentiation and activation of various immune-mediated cells such as CD4+ and CD+8 T cells. The activation of adenosine 5′-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1) pathway may be involved in this process. Recent studies using Extracellular Flux Analyzer demonstrated that metformin alters the activities of glycolysis, oxidative phosphorylation (OXPHOS), lipid oxidation, and glutaminolysis, which tightly link to the modulation of cytokine production in CD4+ and CD+8 T cells in various disease states, such as virus infection, autoimmune diseases, aging and cancers.
Identification and Functional Validation of Auxin-Responsive Tabzip Genes from Wheat Leaves in Arabidopsis
Authors: Jia Ziyao , Zhang Mengjie , Ma Can , Wang Zanqiang , Wang Zhonghua , Fang Yan , Wang Jun
Published: January 2023

Leaves are an essential and unique organ of plants, and many studies have proved that auxin has significant impacts on the architecture of leaves, thus the manipulation of the three-dimensional structure of a leaf could provide potential strategies for crop yields. In this study, 32 basic leucine zipper transcription factors (bZIP TFs) which responded to 50 μM of indole-acetic acid (IAA) were identified in wheat leaves by transcriptome analysis. Phylogenetic analysis indicated that the 32 auxin-responsive TabZIPs were classified into eight groups with possible different functions. Phenotypic analysis demonstrated that knocking out the homologous gene of the most down-regulated auxin-responsive TabZIP6D_20 in Arabidopsis (AtHY5) decreased its sensitivity to 1 and 50 μM IAA, while the TabZIP6D_20/hy5 complementary lines recovered its sensitivity to auxin as a wild type (Wassilewskija), suggesting that the down-regulated TabZIP6D_20 was a negative factor in the auxin-signaling pathway. These results demonstrated that the auxin-responsive TabZIP genes might have various and vital functions in the architecture of a wheat leaf under auxin response.
Activation of β-Adrenoceptors Promotes Lipid Droplet Accumulation in MCF-7 Breast Cancer Cells via cAMP/PKA/EPAC Pathways
Authors: Silva Dany , Kacprzak Katarzyna , Quintas Clara , Gonçalves Jorge , Fresco Paula
Published: January 2023

Physiologically, β-adrenoceptors are major regulators of lipid metabolism, which may be reflected in alterations in lipid droplet dynamics. β-adrenoceptors have also been shown to participate in breast cancer carcinogenesis. Since lipid droplets may be seen as a hallmark of cancer, the present study aimed to investigate the role of β-adrenoceptors in the regulation of lipid droplet dynamics in MCF-7 breast cancer cells. Cells were treated for up to 72 h with adrenaline (an endogenous adrenoceptor agonist), isoprenaline (a non-selective β-adrenoceptor agonist) and salbutamol (a selective β2-selective agonist), and their effects on lipid droplets were evaluated using Nile Red staining. Adrenaline or isoprenaline, but not salbutamol, caused a lipid-accumulating phenotype in the MCF-7 cells. These effects were significantly reduced by selective β1- and β3-antagonists (10 nM atenolol and 100 nM L-748,337, respectively), indicating a dependence on both β1- and β3-adrenoceptors. These effects were dependent on the cAMP signalling pathway, involving both protein kinase A (PKA) and cAMP-dependent guanine-nucleotide-exchange (EPAC) proteins: treatment with cAMP-elevating agents (forskolin or 8-Br-cAMP) induced lipid droplet accumulation, whereas either 1 µM H-89 or 1 µM ESI-09 (PKA or EPAC inhibitors, respectively) abrogated this effect. Taken together, the present results demonstrate the existence of a β-adrenoceptor-mediated regulation of lipid droplet dynamics in breast cancer cells, likely involving β1- and β3-adrenoceptors, revealing a new mechanism by which adrenergic stimulation may influence cancer cell metabolism.
microRNAs Are Abundant and Stable in Platelet-Rich Fibrin and Other Autologous Blood Products of Canines
Authors: Jasineviciute Indre , Hasan Md Nazmul , Grigas Juozas , Pautienius Arnoldas , Stankevicius Arunas , Zymantiene Judita , Miura Naoki
Published: January 2023

Various microRNAs (miRNAs) present in autologous blood products of canines have not been studied recently. We aimed to elucidate the existence of miRNAs in platelet-rich fibrin (PRF) and the stability of canine autologous blood products under various storage conditions. Total RNAs were isolated from PRF and other autologous blood products following newly adapted protocols used in commercial kits for plasma and tissue samples. Quantitative real-time polymerase chain reaction analysis (qPCR) was used to detect miRNAs in autologous blood products. The miR-16, miR-21, miR-155, and miR-146a were abundant in PRF and other autologous blood products of canines. Furthermore, we found they could maintain stability under protracted freezing temperatures of −30 °C for at least one month. Our findings revealed that PRF might be a stable resource for various canine miRNAs.
Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro
Authors: Wu Zong-Han , Chiu Chun-Hung , Chen Chin-Chu , Chyau Charng-Cherng , Cheng Chi-Hung
Published: January 2023

Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity.
The Immunological Microenvironment and the Emerging Role of Stem Cells Therapy in Peyronie’s Disease: A Systematic Narrative Review
Authors: Yang Che-Hsueh , Lin Dian-Yu , Lin Yi-Sheng , Hsu Chao-Yu , Tung Min-Che , Tan Kok-Tong , Ou Yen-Chuan
Published: January 2023

Current literature has indicated that Peyronie’s disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.
Influence of the Hot-Mix Asphalt Production Temperature on the Effectiveness of the Reclaimed Asphalt Rejuvenation Process
Authors: Bocci Edoardo , Prosperi Emiliano , Bocci Maurizio
Published: January 2023

Hot recycling of reclaimed asphalt pavement (RAP) into new hot-mix asphalt (HMA) is a complex process that must be precisely calibrated in the asphalt plants. In particular, temperature is a key parameter that, if inadequately set, can affect the final mix performance as it influences the RAP binder mobilization rate and the severity of bitumen short-term aging. The present paper aims at evaluating the effect of HMA production temperature on the behavior of mixtures including 50% of RAP and two types of rejuvenating agents. In particular, volumetric, mechanical, chemical, and rheological properties of the mixes and binder-aggregate adhesion have been investigated on the HMA produced in the laboratory at 140 °C or 170 °C. The results showed that the adoption of a lower production temperature did not significantly influence the air voids content in the mix, but determined a less stiff, brittle and cracking-prone behavior. Moreover, the decrease of the HMA production temperature was profitable for the increase of bitumen-aggregate adhesion.
Locality of Residential Areas in COVID-19 Pandemic Conditions: Analysis of Neighborhoods and Housing Design in Saudi Arabia
Authors: Aldossary Naief A. , AlQahtany Ali M. , Alyami Saleh H.
Published: January 2023

The current coronavirus COVID-19 pandemic is impacting countries across the world, resulting in governments undertaking a number of precautionary measures for their populations. This raises the issue of the effectiveness of urban design of dwellings to assist with these measures. This study therefore determines the current readiness of local neighborhoods and housing in Saudi Arabia to face epidemics. The study employs an analysis of a public survey achieving a comprehensive (n = 413) across the country to identify: (a) the current situation of local neighborhood and services, including density and the ability to fulfil human needs during periods of quarantine; (b) the ability of housing design to assist with social distancing: (c) appropriate housing design to fulfil social needs; and (d) the design of housing to accommodate the ability for infected household members to self-isolate. The findings identify that neighborhoods in Saudi Arabia meet current social requirements and can assist in avoiding gatherings. In addition, it illustrates the advantages and disadvantages of housing design, revealing that villas tend to be low density, and so facilitate social distancing, but neighborhoods with a high number of residential units face considerable challenges, due to the high density of population, particularly in areas lacking planning.
Execution Time Decrease for Controllers Based on Adaptive Particle Swarm Optimization
Authors: Mînzu Viorel , Rusu Eugen , Arama Iulian
Published: January 2023

Execution time is an important topic when using metaheuristic-based optimization algorithms within control structures. This is the case with Receding Horizon Control, whose controller makes predictions based on a metaheuristic algorithm. Because the closed loop’s main time constraint is that the controller’s run time must be smaller than the sampling period, this paper joins the authors’ previous work in investigating decreasing execution time. In this context, good results have been obtained by introducing the “reference control profile” concept that leads to the idea of adapting the control variables’ domains for each sampling period. This paper continues to address this concept, which is adjusted to harmonize with the Particle Swarm Optimization algorithm. Moreover, besides adapting the control variables’ domains, the proposed controller’s algorithm tunes these domains to avoid losing convergence. A simulation study validates the new techniques using a nontrivial process model and considering three modes in which the controller works. The results showed that the proposed techniques have practical relevance and significantly decrease execution time.
Platelet Concentration and Platelet/Lymphocyte Ratio as Prognostic Indicators in Luminal Breast Cancer
Authors: Rönnau Angela Della’Santa Rubio O. , Berto Maiquidieli Dal , Bica Claudia Giuliano , Alves Rafael Vargas , Rotta Liane Nanci
Published: January 2023

Ratios between the blood cells are indirect measures of the imbalance in the pro-inflammatory status observed in carcinogenesis and have been proposed as accessible and feasible biomarkers to predict cancer prognosis. We aim to evaluate the prognostic significance of neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), and platelet/lymphocyte (PLR) ratios in Brazilian patients with luminal breast cancer (LBC) treated with tamoxifen. A retrospective cohort of 72 operable LBC patients. Preoperative leukocyte and platelet absolute values permitted to calculate NLR, MLR, and PLR. Area under curve (ROC) determined the cutoff value associated with relapse and death. Univariate and multivariate analyses were used to assess the relationship of the platelet and PLR to disease-free survival (DFS) and overall survival (OS). Lower DFS was associated with >297 × 103/mm3 (54 vs. 60.9 months in <297, p = 0.04). Platelet > 279 × 103/mm3 are related to higher OS (p = 0.03). Univariate analysis revealed that platelet concentration was associated with DFS (p = 0.04) and OS (p = 0.04), but not as an independent factor (HR = 1.31, 95%CI: 0.42–4.07, p = 0.65) and OS (HR = 1.64, 95%CI: 0.28–9.52, p = 0.58). Both univariate (p = 0.01) and multivariate analysis revealed that PLR < 191.5 was a significant independent predictor of higher OS/better prognosis (HR = 16.16, 95%CI: 2.83–109.25, p = 0.00). Pretreatment platelet indices (absolute count and PLR) are prognosis predictors in LBC patients. Platelet > 279 × 103/mm3 and PRL < 191.5 was associated with a higher OS, with the PRL being an independent predictor of higher OS.
Influence of Post Processing on Thermal Conductivity of ITO Thin Films
Authors: Kaźmierczak-Bałata Anna , Bodzenta Jerzy , Dehbashi Mohsen , Mayandi Jeyanthinath , Venkatachalapathy Vishnukanthan
Published: January 2023

This work presents the influence of post processing on morphology, thermal and electrical properties of indium tin oxide (ITO) thin films annealed at 400 °C in different atmospheres. The commercially available 170 nm thick ITO layers deposited on glass were used as a starting material. The X-ray diffraction measurements revealed polycrystalline structure with dominant signal from (222) plane for all samples. The annealing reduces the intensity of this peak and causes increase of (221) and (440) peaks. Atomic force microscopy images showed that the surface morphology is typical for polycrystalline layers with roughness not exceeding few nm. Annealing in the oxygen and the nitrogen-hydrogen mixture (NHM) changes shapes of grains. The electrical conductivity decreases after annealing except the one of layer annealed in NHM. Thermal conductivities of annealed ITO thin films were in range from 6.4 to 10.6 W·m−1·K−1, and they were higher than the one for starting material—5.1 W·m−1·K−1. Present work showed that annealing can be used to modify properties of ITO layers to make them useful for specific applications e.g., in ITO based solar cells.
Numerical Study of Casing Microleakage Flow Field Sensitivity and Acoustic Field Characteristics
Authors: Li Jingcui , Wan Jifang , Liu Hangming , Yi Xianzhong , He Yuxian , Chen Kang , Zhao Xinbo
Published: January 2023

The casing leakage phenomenon seriously affects the safety and economic problems of oil and gas production and transportation. In this paper, the numerical simulation study of the casing’s micro-leakage flow field and acoustic field is carried out by taking the oil and gas well casing as the research object. The CFD numerical model of the casing micro-leakage is established, and the influence of the size of the leakage hole, the shape of the leakage hole, and the pressure difference between the inside and outside the casing on the microleakage flow field is analyzed. An acoustic-vibroacoustic coupling calculation model based on Fluent and LMS Virtual LAB is established, and the sound pressure value and distribution at different frequencies are calculated. The results show that the flow rate of the leakage hole increases with the pressure difference between the inside and the outside leakage hole and the area of the leakage hole. Moreover, the flow rate of the circular leakage hole is higher for the same leakage hole area. The simulation model based on the equivalent sound source can be used to calculate and analyze the sound field in the tubing. By sound field computation based on the near-field equivalent sound source, when the frequency is 32,000 Hz, the amplitude of sound pressure is maximum. In addition, the sound pressure is greatly reduced once the sound wave passes through the tubing pipeline. Lastly, the sound pressure is higher at the position facing the leakage hole in the tubing, making detecting the leakage sound field signal easier. The results can provide a reference for further research on oil casing microleakage detection technology.
Magnetic-Field-Induced Improvement of Photothermal Sterilization Performance by Fe3O4@SiO2@Au/PDA Nanochains
Authors: Xu Kezhu , Fang Qunling , Wang Jing , Hui Ailing , Xuan Shouhu
Published: January 2023

Due to the abuse of antibiotics, the sensitivity of patients to antibiotics is gradually reduced. This work develops a Fe3O4@SiO2@Au/PDA nanochain which shows an interesting magnetic-field-induced improvement of its photothermal antibacterial property. First, SiO2 was wrapped on Fe3O4 nanospheres assembled in a chain to form a Fe3O4@SiO2 nanocomposite with a chain-like nanostructure. Then, the magnetic Fe3O4@SiO2@Au/PDA nanochains were prepared using in situ redox-oxidization polymerization. Under the irradiation of an 808 nm NIR laser, the temperature rise of the Fe3O4@SiO2@Au/PDA nanochain dispersion was obvious, indicating that they possessed a good photothermal effect. Originating from the Fe3O4, the Fe3O4@SiO2@Au/PDA nanochain showed a typical soft magnetic behavior. Both the NIR and magnetic field affected the antimicrobial performance of the Fe3O4@SiO2@Au/PDA nanochains. Escherichia coli and Staphylococcus aureus were used as models to verify the antibacterial properties. The experimental results showed that the Fe3O4@SiO2@Au/PDA nanochains exhibited good antibacterial properties under photothermal conditions. After applying a magnetic field, the bactericidal effect was further significantly enhanced. The above results show that the material has a broad application prospect in inhibiting the growth of bacteria.
Finite Element Analysis of Crack Propagation in Adhesive Joints with Notched Adherends
Authors: Qureshi Ayman , Guan Tianyue , Alfano Marco
Published: January 2023

The adherends notching technique has been the subject of a few recent studies and consists of tailoring the geometry of the adjoined layers to mitigate the bondline peak stresses and enhance the joint strength. In the present study, we explored the effect of the adherends notching technique on crack propagation using finite element (FE) simulations based on the cohesive zone model (CZM) of fracture. Double cantilever beam (DCB) adhesive joints subjected to quasistatic loading were considered as a model material system. An array of equally spaced notches was placed on the faying sides of the adherends, oriented perpendicularly to the direction of crack growth. A parametric investigation was carried out to ascertain the role of the notches and the input cohesive properties on various performance metrics, e.g., load–displacement response and dissipated energy. The proposed notching strategy promotes an unstable crack pinning/depinning process, which effectively delays crack growth and increases the effective work of fracture. Additionally, we found that the overall behaviour is tunable by changing geometric (i.e., notch spacing and depth) and bondline material properties.