bluuebunny/crossref_metadata_2025 huggingface dataset:
Coffee Polyphenol, Chlorogenic Acid, Suppresses Brain Aging and Its Effects Are Enhanced by Milk Fat Globule Membrane Components
Authors: Unno Keiko , Taguchi Kyoko , Hase Tadashi , Meguro Shinichi , Nakamura Yoriyuki
Published: May 2022

Mice feed with coffee polyphenols (CPP, chlorogenic acid) and milk fat globule membrane (MFGM) has increased survival rates and helps retain long-term memory. In the cerebral cortex of aged mice, CPP intake decreased the expression of the proinflammatory cytokine TNF-α, and lysosomal enzyme cathepsin B. The suppression of inflammation in the brain during aging was thought to result in the suppression of the repressor element 1-silencing transcription factor (REST) and prevention of brain aging. In contrast, CPP increased the expression of REST, cAMP-responsive element binding (CREB) and transforming growth factor β1 (TGF-β1) in the young hippocampus. The increased expression of these factors may contribute to the induction of neuronal differentiation and the suppression of memory decline with aging. Taken together, these results suggest that CPP increases CREB in the young hippocampus and suppresses inflammation in the old brain, resulting in a preventive effect on brain aging. The endotoxin levels were not elevated in the serum of aged mice. Although the mechanism of action of MFGM has not yet been elucidated, the increase in survival rate with both CPP and MFGM intake suggests that adding milk to coffee may improve not only the taste, but also the function.
Short-Term Exposure Effects of the Environmental Endocrine Disruptor Benzo(a)Pyrene on Thyroid Axis Function in Zebrafish
Authors: Rurale Giuditta , Gentile Ilaria , Carbonero Camilla , Persani Luca , Marelli Federica
Published: May 2022

Benzo(a)Pyrene (BaP) is one of the most widespread polycyclic aromatic hydrocarbons (PAHs) with endocrine disrupting properties and carcinogenic effects. In the present study, we tested the effect of BaP on thyroid development and function, using zebrafish as a model system. Zebrafish embryos were treated with 50 nM BaP from 2.5 to 72 h post fertilization (hpf) and compared to 1.2% DMSO controls. The expression profiles of markers of thyroid primordium specification, thyroid hormone (TH) synthesis, hypothalamus-pituitary-thyroid (HPT) axis, TH transport and metabolism, and TH action were analyzed in pools of treated and control embryos at different developmental stages. BaP treatment did not affect early markers of thyroid differentiation but resulted in a significant decrease of markers of TH synthesis (tg and nis) likely secondary to defective expression of the central stimulatory hormones of thyroid axis (trh, tshba) and of TH metabolism (dio2). Consequently, immunofluorescence of BaP treated larvae showed a low number of follicles immunoreactive to T4. In conclusion, our results revealed that the short-term exposure to BaP significantly affects thyroid function in zebrafish, but the primary toxic effects would be exerted at the hypothalamic-pituitary level thus creating a model of central hypothyroidism.
Biophysical Study of the Structure, Dynamics, and Function of Nucleic Acids
Authors: Lee Joon-Hwa , Katahira Masato
Published: May 2022

Nucleic acids have essential roles in all biological processes related to genetic information, such as replication, transcription, translation, repair, and recombination [...]
PD-1/PD-L1, MDSC Pathways, and Checkpoint Inhibitor Therapy in Ph(-) Myeloproliferative Neoplasm: A Review
Authors: Wang Jen-Chin , Sun Lishi
Published: May 2022

There has been significant progress in immune checkpoint inhibitor (CPI) therapy in many solid tumor types. However, only a single failed study has been published in treating Ph(-) myeloproliferative neoplasm (MPN). To make progress in CPI studies on this disease, herein, we review and summarize the mechanisms of activation of the PD-L1 promoter, which are as follows: (a) the extrinsic mechanism, which is activated by interferon gamma (IFN γ) by tumor infiltration lymphocytes (TIL) and NK cells; (b) the intrinsic mechanism of EGFR or PTEN loss resulting in the activation of the MAPK and AKT pathways and then stat 1 and 3 activation; and (c) 9p24 amplicon amplification, resulting in PD-L1 and Jak2 activation. We also review the literature and postulate that many of the failures of CPI therapy in MPN are likely due to excessive MDSC activities. We list all of the anti-MDSC agents, especially those with ruxolitinib, IMID compounds, and BTK inhibitors, which may be combined with CPI therapy in the future as part of clinical trials applying CPI therapy to Ph(-) MPN.
The Increase of miR-195-5p Reduces Intestinal Permeability in Ulcerative Colitis, Modulating Tight Junctions’ Expression
Authors: Scalavino Viviana , Piccinno Emanuele , Bianco Giusy , Schena Nicolò , Armentano Raffaele , Giannelli Gianluigi , Serino Grazia
Published: May 2022

Defects in the intestinal epithelial barrier functions characterize inflammatory conditions such as Inflammatory Bowel Disease (IBD). Overexpression of pro-inflammatory cytokines such as TNF-α, IL-1B, IL-6 and INF-γ trigger epithelial damage. These cytokines are due to upregulation of claudin-2 (CLDN2) that form a pore channel, resulting in redistribution of TJs and an alteration of barrier permeability. Recently, we demonstrated that miR-195-5p is able to regulate CLDN2 and indirectly also CLDN1 in intestinal epithelial cells. Now, we aimed to investigate the modulation of miR-195-5p on the expression of CLDN2 and other TJs under inflammatory conditions induced by TNF-α. We demonstrated that miR-195-5p also modulated the expression of CLDN2 levels after stimulation with TNF-α. In addition, we discovered the role of miR-195-5p in the integrity of the intestinal barrier and in promoting the restoration of the intestinal epithelial. Moreover, we established that replacement of miR-195-5p attenuated the colonic inflammatory response in DSS-induced, colitis and it reduced colonic permeability. In conclusion, our data revealed the role of miR-195-5p in intestinal inflammation in ulcerative colitis, suggesting a potential pharmacological target for new therapeutic approaches.
Neuropathological Features of Gaucher Disease and Gaucher Disease with Parkinsonism
Authors: Furderer Makaila L. , Hertz Ellen , Lopez Grisel J. , Sidransky Ellen
Published: May 2022

Deficient acid β-glucocerebrosidase activity due to biallelic mutations in GBA1 results in Gaucher disease (GD). Patients with this lysosomal storage disorder exhibit a wide range of associated manifestations, spanning from virtually asymptomatic adults to infants with severe neurodegeneration. While type 1 GD (GD1) is considered non-neuronopathic, a small subset of patients develop parkinsonian features. Variants in GBA1 are also an important risk factor for several common Lewy body disorders (LBDs). Neuropathological examinations of patients with GD, including those who developed LBDs, are rare. GD primarily affects macrophages, and perivascular infiltration of Gaucher macrophages is the most common neuropathologic finding. However, the frequency of these clusters and the affected anatomical region varies. GD affects astrocytes, and, in neuronopathic GD, neurons in cerebral cortical layers 3 and 5, layer 4b of the calcarine cortex, and hippocampal regions CA2–4. In addition, several reports describe selective degeneration of the cerebellar dentate nucleus in chronic neuronopathic GD. GD1 is characterized by astrogliosis without prominent neuronal loss. In GD-LBD, widespread Lewy body pathology is seen, often involving hippocampal regions CA2–4. Additional neuropathological examinations in GD are sorely needed to clarify disease-specific patterns and elucidate causative mechanisms relevant to GD, and potentially to more common neurodegenerative diseases.
Molecular and Physiological Responses of Citrus sinensis Leaves to Long-Term Low pH Revealed by RNA-Seq Integrated with Targeted Metabolomics
Authors: Lai Ning-Wei , Zheng Zhi-Chao , Hua Dan , Zhang Jiang , Chen Huan-Huan , Ye Xin , Huang Zeng-Rong , Guo Jiuxin , Yang Lin-Tong , Chen Li-Song
Published: May 2022

Low pH-induced alterations in gene expression profiles and organic acids (OA) and free amino acid (FAA) abundances were investigated in sweet orange [Citrus sinensis (L.) Osbeck cv. Xuegan] leaves. We identified 503 downregulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OA biosynthesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen compounds, proteins, and FAAs in leaves, which might be conducive to maintaining energy homeostasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses to phosphate starvation, including phosphate recycling, lipid remodeling, and phosphate transport, thus enhancing leaf acid-tolerance. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid, and pyroglutamic acid), but it impaired the pentose phosphate pathway and VE and secondary metabolite biosynthesis and downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase, and 2-alkenal reductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.
A Structural Potential of Rare Trinucleotide Repeat Tracts in RNA
Authors: Magner Dorota , Nowak Rafal , Lenartowicz Onyekaa Elzbieta , Pasternak Anna , Kierzek Ryszard
Published: May 2022

Among types of trinucleotide repeats, there is some disproportion in the frequency of their occurrence in the human exome. This research presents new data describing the folding and thermodynamic stability of short, tandem RNA repeats of 23 types, focusing on the rare, yet poorly analyzed ones. UV-melting experiments included the presence of PEG or potassium and magnesium ions to determine their effect on the stability of RNA repeats structures. Rare repeats predominantly stayed single-stranded but had the potential for base pairing with other partially complementary repeat tracts. A coexistence of suitably complementary repeat types in a single RNA creates opportunities for interaction in the context of the secondary structure of RNA. We searched the human transcriptome for model RNAs in which different, particularly rare trinucleotide repeats coexist and selected the GABRA4 and CHIC1 RNAs to study intramolecular interactions between the repeat tracts that they contain. In vitro secondary structure probing results showed that the UAA and UUG repeat tracts, present in GABRA4 3′ UTR, form a double helix, which separates one of its structural domains. For the RNA CHIC1 ORF fragment containing four short AGG repeat tracts and the CGU tract, we proved the formation of quadruplexes that blocked reverse transcription.
Atomistic-Level Description of the Covalent Inhibition of SARS-CoV-2 Papain-like Protease
Authors: Hognon Cécilia , Marazzi Marco , García-Iriepa Cristina
Published: May 2022

Inhibition of the papain-like protease (PLpro) of SARS-CoV-2 has been demonstrated to be a successful target to prevent the spreading of the coronavirus in the infected body. In this regard, covalent inhibitors, such as the recently proposed VIR251 ligand, can irreversibly inactivate PLpro by forming a covalent bond with a specific residue of the catalytic site (Cys111), through a Michael addition reaction. An inhibition mechanism can therefore be proposed, including four steps: (i) ligand entry into the protease pocket; (ii) Cys111 deprotonation of the thiol group by a Brønsted–Lowry base; (iii) Cys111-S− addition to the ligand; and (iv) proton transfer from the protonated base to the covalently bound ligand. Evaluating the energetics and PLpro conformational changes at each of these steps could aid the design of more efficient and selective covalent inhibitors. For this aim, we have studied by means of MD simulations and QM/MM calculations the whole mechanism. Regarding the first step, we show that the inhibitor entry in the PLpro pocket is thermodynamically favorable only when considering the neutral Cys111, that is, prior to the Cys111 deprotonation. For the second step, MD simulations revealed that His272 would deprotonate Cys111 after overcoming an energy barrier of ca. 32 kcal/mol (at the QM/MM level), but implying a decrease of the inhibitor stability inside the protease pocket. This information points to a reversible Cys111 deprotonation, whose equilibrium is largely shifted toward the neutral Cys111 form. Although thermodynamically disfavored, if Cys111 is deprotonated in close proximity to the vinylic carbon of the ligand, then covalent binding takes place in an irreversible way (third step) to form the enolate intermediate. Finally, due to Cys111-S− negative charge redistribution over the bound ligand, proton transfer from the initially protonated His272 is favored, finally leading to an irreversibly modified Cys111 and a restored His272. These results elucidate the selectivity of Cys111 to enable formation of a covalent bond, even if a weak proton acceptor is available, as His272.
NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme
Authors: Murad Shafiq , Michen Susanne , Becker Alexander , Füssel Monika , Schackert Gabriele , Tonn Torsten , Momburg Frank , Temme Achim
Published: May 2022

In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas.
Meta-Analysis of Immune Induced Gene Expression Changes in Diverse Drosophila melanogaster Innate Immune Responses
Authors: Waring Ashley L. , Hill Joshua , Allen Brooke M. , Bretz Nicholas M. , Le Nguyen , Kr Pooja , Fuss Dakota , Mortimer Nathan T.
Published: May 2022

Organisms are commonly infected by a diverse array of pathogens and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression, however, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. To examine this, we performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens. Our study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction.
Efficacy of Continuous Glucose Monitoring on Glycaemic Control in Pregnant Women with Gestational Diabetes Mellitus—A Systematic Review
Authors: Majewska Agata , Stanirowski Paweł Jan , Wielgoś Mirosław , Bomba-Opoń Dorota
Published: May 2022

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, affecting up to 14% of pregnant women. The population of patients with risk factors of GDM is increasing; thus, it is essential to improve management of this condition. One of the key factors affecting perinatal outcomes in GDM is glycaemic control. Until recently, glucose monitoring was only available with self-monitoring of blood glucose (SMBG). However, nowadays, there is a new method, continuous glucose monitoring (CGM), which has been shown to be safe in pregnancy. Since proper glycaemia assessment has been shown to affect perinatal outcomes, we decided to perform a systematic review to analyse the role of CGM in glycaemic control in GDM. We conducted a web search of the MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science databases according to the PRISMA guidelines. The web search was performed by two independent researchers and resulted in 14 articles included in the systematic review. The study protocol was registered in the PROSPERO database with registration number CRD42021289883. The main outcome of the systematic review was determining that, when compared, CGM played an important role in better glycaemic control than SMBG. Furthermore, glycaemic control with CGM improved qualification for insulin therapy. However, most of the articles did not reveal CGM’s role in improving neonatal outcomes. Therefore, more studies are needed to analyse the role of CGM in affecting perinatal outcomes in GDM.
Do Oral Pathogens Inhabit the Eye and Play a Role in Ocular Diseases?
Authors: Arjunan Pachiappan , Swaminathan Radhika
Published: May 2022

Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD.
Preoperative Imaging with [18F]-Fluorocholine PET/CT in Primary Hyperparathyroidism
Authors: Dekorsy Franziska J. , Beyer Leonie , Spitzweg Christine , Schmidmaier Ralf , Todica Andrei , Trupka Arnold , Cyran Clemens C. , Berger Frank , Ladurner Roland , Zimmermann Petra , Knösel Thomas , Bartenstein Peter , Lottspeich Christian , Wenter Vera
Published: May 2022

Primary hyperparathyroidism (pHPT) is a common endocrine disorder due to hyperfunctioning parathyroid glands. To date, the only curing therapy is surgical removal of the dysfunctional gland, making correct detection and localization crucial in order to perform a minimally invasive parathyroidectomy. 18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) has shown promising results for the detection of pHPT, suggesting superiority over conventional imaging with ultrasounds or scintigraphy. A total of 33 patients with pHPT who had negative or equivocal findings in conventional imaging received 18F-FCH PET/CT preoperatively and were retrospectively included. A pathological hyperfunctional parathyroid gland was diagnosed in 24 cases (positive PET, 72.7%), 4 cases showed equivocal choline uptake (equivocal PET, 12.1%), and in 5 cases, no enhanced choline uptake was evident (negative PET, 15.2%). Twelve of the twenty-four detected adenoma patients underwent surgery, and in all cases, a pathological parathyroid adenoma was resected at the site detected by PET/CT. Two of the six patients without pathological choline uptake who received a parathyroidectomy revealed no evidence of parathyroid adenoma tissue in the histopathological evaluation. This retrospective study analyzes 18F-FCH PET/CT in a challenging patient cohort with pHPT and negative or equivocal conventional imaging results and supports the use of 18F-FCH for the diagnosis of hyperfunctional parathyroid tissue, especially in this patient setting, with a 100% true positive and true negative detection rate. Our study further demonstrates the importance of 18F-FCH PET/CT for successful surgical guidance.
Characterization of Retinal Drusen in Subjects at High Genetic Risk of Developing Sporadic Alzheimer’s Disease: An Exploratory Analysis
Authors: López-Cuenca Inés , Salobrar-García Elena , Gil-Salgado Inés , Sánchez-Puebla Lidia , Elvira-Hurtado Lorena , Fernández-Albarral José A. , Ramírez-Toraño Federico , Barabash Ana , de Frutos-Lucas Jaisalmer , Salazar Juan J. , Ramírez José M. , Ramírez Ana I. , de Hoz Rosa
Published: May 2022

Having a family history (FH+) of Alzheimer’s disease (AD) and being a carrier of at least one ɛ4 allele of the ApoE gene are two of the main risk factors for the development of AD. AD and age-related macular degeneration (AMD) share one of the main risk factors, such as age, and characteristics including the presence of deposits (Aβ plaques in AD and drusen in AMD); however, the role of apolipoprotein E isoforms in both pathologies is controversial. We analyzed and characterized retinal drusen by optical coherence tomography (OCT) in subjects, classifying them by their AD FH (FH- or FH+) and their allelic characterization of ApoE ɛ4 (ApoE ɛ4- or ApoE ɛ4+) and considering cardiovascular risk factors (hypercholesterolemia, hypertension, and diabetes mellitus). In addition, we analyzed the choroidal thickness by OCT and the area of the foveal avascular zone with OCTA. We did not find a relationship between a family history of AD or any of the ApoE isoforms and the presence or absence of drusen. Subjects with drusen show choroidal thinning compared to patients without drusen, and thinning could trigger changes in choroidal perfusion that may give rise to the deposits that generate drusen.
Gender-Specific Differences in the Intensive Care Treatment of COVID-19 Patients
Authors: Jirak Peter , Mirna Moritz , Van Almsick Vincent , Shomanova Zornitsa , Mahringer Magdalena , Lichtenauer Michael , Kopp Kristen , Topf Albert , Sieg Franz , Kraus Johannes , Gharibeh Sarah X. , Hoppe Uta C. , Fiedler Lukas , Larbig Robert , Pistulli Rudin , Motloch Lukas J. , Dieplinger Anna-Maria
Published: May 2022

Background: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive. Methods: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were screened for the study. After propensity score matching for gender, 40 men and 40 women were included in the study. Comparative analysis was conducted for laboratory parameters, ICU therapy and complications (pulmonary embolism, thrombosis, stroke, and ventricular arrhythmias), and outcome (mortality). Results: Male patients had significantly higher levels of CRP (p = 0.012), interleukin-6 (p = 0.020) and creatinine (p = 0.027), while pH levels (p = 0.014) were significantly lower compared to females. Male patients had longer intubation times (p = 0.017), longer ICU stays (p = 0.022) and higher rates of catecholamine dependence (p = 0.037). Outcome, complications and ICU therapy did not differ significantly between both groups. Conclusion: The present study represents the first matched comparison of male and female COVID-19 patients requiring intensive care treatment. After propensity matching, male patients still displayed a higher disease severity. This was reflected in higher rates of vasopressors, duration of ICU stay and duration of intubation. In contrast, no significant differences were observed in mortality rates, organ replacement therapy and complications during ICU stay.
Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells
Authors: Chang Jia-Feng , Kuo Hsiao-Ling , Liu Shih-Hao , Hsieh Chih-Yu , Hsu Chih-Ping , Hung Kuo-Chin , Wang Ting-Ming , Wu Chang-Chin , Lu Kuo-Cheng , Lin Wei-Ning , Hung Chi-Feng , Ko Wen-Chin
Published: May 2022

We formerly proved that uremic vascular calcification (UVC) correlates tightly with oxidative elastic lamina (EL) injury and two cell fates (apoptosis and osteocytic conversion) in smooth muscle cells (SMC) of chronic kidney disease (CKD) patients and eliminating p-cresyl sulfate (PCS)-activated intracellular ROS ameliorates the MAPK signaling pathway in a human arterial SMC (HASMC) model. Nonetheless, whether ROS scavenger attenuates PCS-triggered inflammasome activation and eicosanoid inflammation in the UVC process remains unknown. Patients with lower extremity amputation were categorized into CKD and normal control group according to renal function. We used immunohistochemistry stain to analyze UVC in arterial specimens, including oxidative injury (8-hydroxy-2′-deoxyguanosine (8-OHdG) and internal EL disruption), cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX2), interleukin-1 beta (IL-1β), caspase-1 and NLRP3. To simulate the patho-mechanism of human UVC, the therapeutic effects of ROS scavenger on PCS-triggered inflammatory pathways was explored in a HASMC model. We found CKD patients had higher circulating levels of PCS and an increase in medial arterial calcification than the control group. In CKD arteries, the severity of UVC corresponded with expressions of oxidative EL disruption and 8-OHdG. Furthermore, coupling expressions of cPLA2 and COX2 were accentuated in CKD arteries, indicative of eicosanoid inflammation. Notably, tissue expressions of IL-1β, caspase-1 and NLRP3 were enhanced in parallel with UVC severity, indicative of inflammasome activation. From bedside to bench, ROS scavenger attenuates PCS-activated expressions of cPLA2/COX2, pro-caspase-1 and NLRP3 in the HASMC model. UVC as an inevitable outcome is predictive of death in CKD patients. Nonetheless, UVC remain pharmacoresistant despite the evolution of treatment for mineral-parathyroid hormone-vitamin D axis. Beyond the mineral dysregulation, the stimulation of pro-oxidant PCS alone results in eicosanoid inflammation and inflammasome activation. Concerning the key role of Caspase-1 in pyroptosis, cell fates of HASMC in uremic milieu are not limited to apoptosis and osteogenesis. In view of this, reducing ROS and PCS may act as a therapeutic strategy for UVC-related cardiovascular events in CKD patients.
Smoothing the Undersampled Carpal Bone Model with Small Volume and Large Curvature: A Feasibility Study
Authors: Ji Chengcheng , Li Jianzhang , Praster Maximilian , Rath Björn , Hildebrand Frank , Eschweiler Jörg
Published: May 2022

The carpal bones are eight small bones with irregularities and high curvature on their surfaces. The 3D model of the carpal bone serves as the foundation of further clinical applications, e.g., wrist kinematic behavior. However, due to the limitation of the Magnetic Resonance Imaging (MRI) technique, reconstructed carpal bone models are discretely undersampled, which has dramatic stair-step effects and leads to abnormal meshes on edges or surfaces, etc. Our study focuses on determining the viability of various smoothing techniques for a carpal model reconstructed by in vivo gathered MR images. Five algorithms, namely the Laplacian smoothing algorithm, the Laplacian smoothing algorithm with pre-dilation, the scale-dependent Laplacian algorithm, the curvature flow algorithm, and the inverse distance algorithm, were chosen for evaluation. The assessment took into account the Relative Volume Difference and the Hausdorff Distance as well as the surface quality and the preservation of morphological and morphometric properties. For the five algorithms, we analyzed the Relative Volume Difference and the Hausdorff Distance for all eight carpal bones. Among all the algorithms, the scale-dependent Laplacian method processed the best result regarding surface quality and the preservation of morphological and morphometric properties. Based on our extensive examinations, the scale-dependent Laplacian algorithm is suitable for the undersampled carpal bone model with small volume and large curvature.
Influence of Elbow Angle on Erosion-Corrosion of 1018 Steel for Gas–Liquid–Solid Three Phase Flow
Authors: Khan Rehan , Ya Hamdan H. , Shah Imran , Niazi Usama Muhammad , Ahmed Bilal Anjum , Irfan Muhammad , Glowacz Adam , Pilch Zbigniew , Brumercik Frantisek , Azeem Mohammad , Alam Mohammad Azad , Ahmed Tauseef
Published: May 2022

Erosive wear due to the fact of sand severely affects hydrocarbon production industries and, consequently, various sectors of the mineral processing industry. In this study, the effect of the elbow geometrical configuration on the erosive wear of carbon steel for silt–water–air flow conditions were investigated using material loss analysis, surface roughness analysis, and microscopic imaging technique. Experiments were performed under the plug flow conditions in a closed flow loop at standard atmospheric pressure. Water and air plug flow and the disperse phase was silt (silica sand) with a 2.5 wt % concentration, and a silt grain size of 70 µm was used for performing the tests. The experimental analysis showed that silt impact increases material disintegration up to 1.8 times with a change in the elbow configuration from 60° to 90° in plug flow conditions. The primary erosive wear mechanisms of the internal elbow surface were sliding, cutting, and pit propagation. The maximum silt particle impaction was located at the outer curvature in the 50° position in 60° elbows and the 80° position in 90° elbows in plug flow. The erosion rate decreased from 10.23 to 5.67 mm/year with a change in the elbow angle from 90° to 60°. Moreover, the microhardness on the Vickers scale increased from 168 to 199 in the 90° elbow and from 168 to 184 in the 60° elbow.
An Evaluation of 3D-Printed Materials’ Structural Properties Using Active Infrared Thermography and Deep Neural Networks Trained on the Numerical Data
Authors: Szymanik Barbara
Published: May 2022

This article describes an approach to evaluating the structural properties of samples manufactured through 3D printing via active infrared thermography. The mentioned technique was used to test the PETG sample, using halogen lamps as an excitation source. First, a simplified, general numerical model of the phenomenon was prepared; then, the obtained data were used in a process of the deep neural network training. Finally, the network trained in this manner was used for the material evaluation on the basis of the original experimental data. The described methodology allows for the automated assessment of the structural state of 3D−printed materials. The usage of a generalized model is an innovative method that allows for greater product assessment flexibility.
Fluidized ZnO@BCFPs Particle Electrodes for Efficient Degradation and Detoxification of Metronidazole in 3D Electro-Peroxone Process
Authors: Yuan Dan , Wan Shungang , Liu Rurong , Wang Mengmeng , Sun Lei
Published: May 2022

A novel material of self-shaped ZnO-embedded biomass carbon foam pellets (ZnO@BCFPs) was successfully synthesized and used as fluidized particle electrodes in three-dimensional (3D) electro-peroxone systems for metronidazole degradation. Compared with 3D and 2D + O3 systems, the energy consumption was greatly reduced and the removal efficiencies of metronidazole were improved in the 3D + O3 system. The degradation rate constants increased from 0.0369 min−1 and 0.0337 min−1 to 0.0553 min−1, respectively. The removal efficiencies of metronidazole and total organic carbon reached 100% and 50.5% within 60 min under optimal conditions. It indicated that adding ZnO@BCFPs particle electrodes was beneficial to simultaneous adsorption and degradation of metronidazole due to improving mass transfer of metronidazole and forming numerous tiny electrolytic cells. In addition, the process of metronidazole degradation in 3D electro-peroxone systems involved hydroxyethyl cleavage, hydroxylation, nitro-reduction, N-denitrification and ring-opening. The active species of ·OH and ·O2− played an important role. Furthermore, the acute toxicity LD50 and the bioconcentration factor of intermediate products decreased with the increasing reaction time.
Estimating Structural Shocks with the GVAR-DSGE Model: Pre- and Post-Pandemic
Authors: Kwok Chunyeung
Published: May 2022

This paper investigates the possibility of using the global VAR (GVAR) model to estimate a simple New Keynesian DSGE-type multi-country model. The long-run forecasts from an estimated GVAR model were used to calculate the steady-states of macro variables as differences. The deviations from the long-run forecasts were taken as the deviation from the steady-states and were used to estimate a simple NK open economy model with an IS curve, Philips curve, Taylor rule, and an exchange rate equation. The shocks to these equations were taken as the demand shock, supply shock, monetary shock, and exchange rate shock, respectively. An alternative model was constructed to compare the results from GVAR long-run forecasts. The alternative model used a Hodrick–Prescott (HP) filter to derive deviations from the steady-states. The impulsive response functions from the shocks were then compared to results from other DSGE models in the literature. Both GVAR and HP estimates produced dissimilar results, although the GVAR managed to capture more from the data, given the explicit co-integration relationships. For the IRFs, both GVAR and HP estimated DSGE models appeared to be as expected before the pandemic; however, if we include the pandemic data, i.e., 2020, the IRFs are very different, due to the nature of the policy actions. In general, DSGE–GVAR models appear to be much more versatile, and are able to capture dynamics that HP filters are not.
Surface Residual Stress Analysis in GMAW and LBW of the Dissimilar TRIP-DP Steels Joint: An Experimental Approach
Authors: Baltazar-Hernández Víctor H. , López-Baltazar Enrique A. , Alvarado-Hernández Francisco , Gómez-Jiménez Salvador , Ruiz-Mondragón José Jorge , Biro Elliot , Zhou Norman
Published: May 2022

A transformation-induced plasticity (TRIP) steel and a dual-phase (DP) steel were paired together by employing gas metal arc welding (GMAW) and laser beam welding (LBW) processes. The post-weld microstructure, the hardness profile, and the uniaxial tensile behavior of the welded steels have been analyzed in detail. The experimental surface residual stress distribution across the weldment was measured through the X-ray diffraction sin2Ψ technique. The results indicate that although a harder microstructure composed of predominant martensite was observed along the weldment, the uniaxial tensile behavior resulted in better elongation properties and a higher UTS in the LBW specimen as compared to the GMAW specimen. The resultant residual stress distribution in the heat-affected zone (HAZ) had an increase to a maximum value, followed by a steady decrease up to the base metal following the trend: upper-critical UC-HAZ (maximum) → inter-critical IC-HAZ (moderated) → subcritical SC-HAZ (lowered), which was particularly more evident on the GMAW specimen. Overall, the resultant residual stresses along the weldment were lower on the LBW specimen (172 MPa maximum) which clearly contrasts to the GMAW specimen (421 MPa maximum). Finally, the tensile residual stresses in both the GMAW or LBW did not influence the overall tensile properties of the weldments.
Influence of Supersaturation on Growth Behavior and Mechanical Properties of Polycrystalline 3C-SiC on W Wire Substrate
Authors: Liu Shuai , Luo Xian , Huang Bin , Yang Yanqing
Published: May 2022

As an important reinforcement for metal matrix composites, the microstructure and mechanical properties of W-core SiC filament have drawn increasing attentions among researchers. In this work, the growth behavior of polycrystalline 3C-SiC on W-wire substrate in the chemical vapor deposition (CVD) process and the evolution of mechanical properties in preparation of W-core SiC filament, were investigated as a function of gas-phase supersaturation. Kinetic studies revealed that the growth of 3C-SiC grains was limited by surface reactions at both 850 °C and 1050 °C, and the deposit experienced similar morphological changes from a porous structure to large clusters, with the increase in supersaturation. Structural analyses and mechanical tests show that the production of pores and the amorphous phase with a low supersaturation, of 9.6 × 107 at 850 °C, resulted in a reduction in the modulus and hardness of the polycrystalline deposits, to 270.3 GPa and 33.9 GPa, while the reduced structural defects (e.g., stacking faults and twins) in highly (111) orientated 3C-SiC grains, as well as the improved surface quality obtained with the medium supersaturation of 1.6 × 107 at 1050 °C, enhanced the tensile strength and the Weibull modulus of W-core SiC filament to 2.88 GPa and 11.2, respectively. During the growth of 3C-SiC grains, the variation in structural defects density is controlled by the critical nucleation energy of the two-dimensional (2D) nucleus.
Study of Heat Source Model and Residual Stress Caused by Welding in GMAW of Al Alloy
Authors: Yi Myung-Su , Park Joo-Shin
Published: May 2022

An important trend in recent ships and offshore structures is that they require high strength as well as light weight. Due to this trend, various materials are being used to replace existing carbon steel, with aluminum alloys being used frequently. In particular, this trend is conspicuous in outfitting rather than in traditional structural strength members. As a typical example, the use of aluminum alloys is increasing in helideck structures and handrails, which are tertiary components. In order to make the example structures above, welding is absolutely necessary. There are various welding methods used for aluminum alloy, with gas metal arc welding (GMAW) the most widely used. It is very important to be able to simulate welding and to predict various physical quantities of this welding technique in the production of aluminum alloy structures. In particular, welding-induced residual stresses are always generated in a structure that has been welded, and can greatly influence structural stability. Therefore, this paper proposes a method to simulate the welding phenomenon using a precise welding heat source for various aluminum alloys. Additionally, the validity of the proposed finite element (FE) analysis method is verified by measuring the residual stress of the representative aluminum alloy.
Zircon U-Pb-Hf Isotopes, Biotite 40Ar/39Ar Geochronology, and Whole-Rock Geochemistry of the Baogeqi Gabbro in the Northern Alxa, Southernmost Central Asian Orogenic Belt
Authors: Zhang Shaohua , Liu Chiyang , Wang Jianqiang , Bai Jianke , Zhao Xiaochen , Zhang Long , Jia Nan , Song Lijun , Peng Heng
Published: May 2022

The final closure time of the Paleo-Asian Ocean and the Permo-Carboniferous tectonic settings in the northern Alxa are very important but controversial tectonic issues. The geochronology and petrogenesis of mafic igneous rocks are superior in clarifying regional tectonic settings. Here, we report on zircon U-Pb-Hf isotopes, biotite 40Ar/39Ar geochronology and whole-rock geochemical data of the hornblende gabbro from the Baogeqi gabbro pluton in the northern Alxa. The LA-ICP MS U-Pb analysis of zircon grains from the hornblende gabbro yield a weighted mean age of 262.7 ± 2.3 Ma (2σ, MSWD = 0.74), manifesting that the Baogeqi gabbro pluton emplacement was during the late Middle Permian (Capitanian). The 40Ar/39Ar dating of biotite grains from the hornblende gabbro yields a plateau age of 231.3 ± 1.6 Ma (2σ, MSWD = 0.55), indicating that the Baogeqi gabbro pluton cooled to below 300 ℃ in the Triassic. The hornblende gabbro samples are calc-alkaline with metaluminous character, and show enrichment in large ion lithophile elements (e.g., Rb, Ba, Sr, and K) but depletion in Nb, Ta, P, Th, and Ti relative to primitive mantle. Combined with the positive zircon εHf(t) values (+4.9–+9.4), we suggest that the magmas formed from the partial melting of depleted mantle were metasomatized by slab-derived fluids. Together with regional geology, these geochemical data suggest that the Baogeqi gabbro pluton was formed in an intracontinental extension setting, further indicating that the Paleo-Asian Ocean in the northern Alxa was closed prior to the late Middle Permian (Capitanian), and this region was in a post-collision extensional setting during the Capitanian-Late Permian. In addition, the Triassic cooling of the gabbro pluton may be a record of the decline of the Capitanian-Late Permian post-collisional extension basin due to the far-field effect of subduction-collision during the closure of the Paleo-Tethys Ocean.
Functional Characterization of Flavanone 3-Hydroxylase (F3H) and Its Role in Anthocyanin and Flavonoid Biosynthesis in Mulberry
Authors: Dai Mingjie , Kang Xiaoru , Wang Yuqiong , Huang Shuai , Guo Yangyang , Wang Rufeng , Chao Nan , Liu Li
Published: May 2022

Mulberry (Morus spp., Moraceae) is an important economic crop plant and is rich in flavonoids and anthocyanidins in ripe fruits. Anthocyanins are glycosides of anthocyanidins. Flavanone 3-hydroxylase (F3H) catalyzes the conversion of naringenin into dihydroflavonols and is responsible for the biosynthesis of flavonols and anthocyanidins. In this study, MazsF3H was cloned and characterized from Morus atropurpurea var. Zhongshen 1. Conserved motif analysis based on alignment and phylogenetic analysis indicated that MazsF3H belonged to 2-oxoglutarate-dependent dioxygenase and MazsF3H clustered with F3Hs from other plants. MazsF3H was located in both nucleus and cytosol. MazsF3H was expressed in stems, leaves, stigmas and ovaries, except buds. F3H expression levels showed a positive and close relationship with anthocyanin content during the anthocyanin-rich fruit ripening process, while it showed a negative correlation with anthocyanin content in LvShenZi, whose fruits are white and would not experience anthocyanin accumulation during fruit ripening. Significantly different F3H expression levels were also found in different mulberry varieties that have quite different anthocyanin contents in ripe fruits. Overexpression MazsF3H in tobacco showed unexpected results, including decreased anthocyanin content. Down-regulation of F3H expression levels resulted in co-expression of the genes involved in anthocyanin biosynthesis and a significant decrease in anthocyanin content, but the change in total flavonoid content was subtle. Our results indicated that F3H may play quite different roles in different varieties that have quite different fruit colors. In addition, possible complex regulation of flavonoid biosynthesis should be further explored in some of the featured plant species.
Iminosugar Amino Acid idoBR1 Reduces Inflammatory Responses in Microglia
Authors: Olajide Olumayokun A. , Iwuanyanwu Victoria U. , Banjo Owolabi W. , Kato Atsushi , Penkova Yana B. , Fleet George W. J. , Nash Robert J.
Published: May 2022

(1) Background. Inflammation is reported to be a key factor in neurodegeneration. The microglia are immune cells present in the central nervous system; their activation results in the release of inflammatory cytokines and is thought to be related to aging and neurodegenerative disorders, such as Alzheimer’s disease. (2) Methods. A mouse BV-2 microglia cell line was activated using LPS and the anti-inflammatory cucumber-derived iminosugar amino acid idoBR1, (2R,3R,4R,5S)-3,4,5-trihydroxypiperidine-2-carboxylic acid, was used alongside dexamethasone as the control to determine whether it could reduce the inflammatory responses. (3) Results. A dose-dependent reduction in the LPS-induced production of the proinflammatory factors TNFα, IL-6, and nitric oxide and the transcription factor NF-κB was found. (4) Conclusions. Further investigations of the anti-inflammatory effects of idoBR1 in other models of neurodegenerative diseases are warranted.
Degradation of Benzotriazole UV Stabilizers in PAA/d-Electron Metal Ions Systems—Removal Kinetics, Products and Mechanism Evaluation
Authors: Kiejza Dariusz , Karpińska Joanna , Kotowska Urszula
Published: May 2022

Benzotriazole UV stabilizers (BUVs) have gained popularity, due to their absorption properties in the near UV range (200–400 nm). They are used in the technology for manufacturing plastics, protective coatings, and cosmetics, to protect against the destructive influence of UV radiation. These compounds are highly resistant to biological and chemical degradation. As a result of insufficient treatment by sewage treatment plants, they accumulate in the environment and in the tissues of living organisms. BUVs have adverse effects on living organisms. This work presents the use of peracetic acid in combination with d-electron metal ions (Fe2+, Co2+), for the chemical oxidation of five UV filters from the benzotriazole group: 2-(2-hydroxy-5-methylphenyl)benzotriazole (UV-P), 2-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)-4-methylphenol (UV-326), 2,4-di-tert-butyl-6-(5-chloro-2H-benzotriazol-2-yl)phenol (UV-327), 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV-328), and 2-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol (UV-329). The oxidation procedure has been optimized based on the design of experiments (DoE) methodology. The oxidation of benzotriazoles follows first order kinetics. The oxidation products of each benzotriazole were investigated, and the oxidation mechanisms of the tested compounds were proposed.