bluuebunny/crossref_metadata_2025 huggingface dataset:
Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway
Authors: Su Hui-Yuan , Tsai Yi-Cheng , Tsai Hung-Pei , Lin Chih-Lung
Published: April 2022

M1 microglia induce neuroinflammation-related neuronal death in animal models of spontaneous subarachnoid haemorrhage. Zileuton is a 5-lipoxygenase inhibitor that reduces the levels of downstream pro-inflammatory cytokines. This study aimed to investigate whether zileuton inhibits microglial activation and describe its underlying mechanisms. BV-2 cells were exposed to 1 mg/mL haemolysate for 30 min, followed by treatment with different concentrations (5, 10, 15, or 20 μM) of zileuton for 24 h. The cells were then assessed for viability, polarisation, and protein expression levels. Haemolysate increases the viability of BV-2 cells and induces M1 polarisation. Subsequent exposure to high concentrations of zileuton decreased the viability of BV-2 cells, shifted the polarisation to the M2 phenotype, suppressed the expression of 5-lipoxygenase, decreased tumour necrosis factor α levels, and increased interleukin-10 levels. Furthermore, high concentrations of zileuton suppressed the expression of myeloid differentiation primary response protein 88 and reduced the phosphorylated-nuclear factor-kappa B (NF-kB)/NF-kB ratio. Therefore, phenotype reversal from M1 to M2 is a possible mechanism by which zileuton attenuates haemolysate-induced neuroinflammation after spontaneous subarachnoid haemorrhage.
A Single-Cell Raman Spectroscopy Analysis of Bone Marrow Mesenchymal Stem/Stromal Cells to Identify Inter-Individual Diversity
Authors: Kukolj Tamara , Lazarević Jasmina , Borojević Ana , Ralević Uroš , Vujić Dragana , Jauković Aleksandra , Lazarević Nenad , Bugarski Diana
Published: April 2022

The heterogeneity of stem cells represents the main challenge in regenerative medicine development. This issue is particularly pronounced when it comes to the use of primary mesenchymal stem/stromal cells (MSCs) due to a lack of identification markers. Considering the need for additional approaches in MSCs characterization, we applied Raman spectroscopy to investigate inter-individual differences between bone marrow MSCs (BM-MSCs). Based on standard biological tests, BM-MSCs of analyzed donors fulfill all conditions for their characterization, while no donor-related specifics were observed in terms of BM-MSCs morphology, phenotype, multilineage differentiation potential, colony-forming capacity, expression of pluripotency-associated markers or proliferative capacity. However, examination of BM-MSCs at a single-cell level by Raman spectroscopy revealed that despite similar biochemical background, fine differences in the Raman spectra of BM-MSCs of each donor can be detected. After extensive principal component analysis (PCA) of Raman spectra, our study revealed the possibility of this method to diversify BM-MSCs populations, whereby the grouping of cell populations was most prominent when cell populations were analyzed in pairs. These results indicate that Raman spectroscopy, as a label-free assay, could have a huge potential in understanding stem cell heterogeneity and sorting cell populations with a similar biochemical background that can be significant for the development of personalized therapy approaches.
Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea
Authors: Renko Miha , Zupan Tanja , Plaza David F. , Schmieder Stefanie S. , Perišić Nanut Milica , Kos Janko , Turk Dušan , Künzler Markus , Sabotič Jerica
Published: April 2022

We introduce a new family of fungal protease inhibitors with β-trefoil fold from the mushroom Coprinopsis cinerea, named cocaprins, which inhibit both cysteine and aspartic proteases. Two cocaprin-encoding genes are differentially expressed in fungal tissues. One is highly transcribed in vegetative mycelium and the other in the stipes of mature fruiting bodies. Cocaprins are small proteins (15 kDa) with acidic isoelectric points that form dimers. The three-dimensional structure of cocaprin 1 showed similarity to fungal β-trefoil lectins. Cocaprins inhibit plant C1 family cysteine proteases with Ki in the micromolar range, but do not inhibit the C13 family protease legumain, which distinguishes them from mycocypins. Cocaprins also inhibit the aspartic protease pepsin with Ki in the low micromolar range. Mutagenesis revealed that the β2-β3 loop is involved in the inhibition of cysteine proteases and that the inhibitory reactive sites for aspartic and cysteine proteases are located at different positions on the protein. Their biological function is thought to be the regulation of endogenous proteolytic activities or in defense against fungal antagonists. Cocaprins are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, and demonstrate the incredible plasticity of loop functionalization in fungal proteins with β-trefoil fold.
Aqueous-Deficient Dry Eye Exacerbates Signs and Symptoms of Allergic Conjunctivitis in Mice
Authors: Kishimoto Tatsuma , Ishida Waka , Nakajima Isana , Fukuda Ken , Yamashiro Kenji
Published: April 2022

Dry eye disease (DED) and allergic conjunctivitis affect a large number of patients, and many patients usually have both symptoms. We investigated the interactions between DED and allergic conjunctivitis in mice. Four experimental groups were compared: control, DED, allergy, and allergy with DED. DED was induced by removing the extraorbital lacrimal glands of the mice. Allergic conjunctivitis was induced by intraperitoneal administration of ovalbumin and antigen eye drops. The early phase reaction of the allergy was evaluated using the clinical score, scratching behavior, and vascular permeability in the conjunctiva. Epithelial barrier function was assessed by an LC-biotin assay. Tear fluid volume and corneal fluorescein staining decreased in the DED and allergy with DED groups. LC-biotin penetrated the entire epithelium of both the cornea and conjunctiva in DED mice. The clinical score of the early phase reaction was higher in allergy-induced mice than in non-allergy mice. Edema of the eyelid and conjunctiva were aggravated in mice with DED. The number of scratching episodes and leakage of Evans blue into the conjunctiva were higher in allergy-induced DED mice than in control mice. The presence of aqueous-deficient dry eye caused ocular surface epithelial damage and exacerbated allergic signs and symptoms.
Gene Expression of Pregnancy Neutrophils Differs for Protease versus Lipopolysaccharide Stimulation
Authors: Walsh Scott W. , Al Dulaimi Marwah , Strauss Jerome F.
Published: April 2022

Neutrophils, which extensively infiltrate maternal systemic blood vessels in preeclampsia, express protease-activated receptor 1 (PAR-1) but only during pregnancy. Neutrophils are generally considered to be non-specific in their response, but the pregnancy-specific expression of PAR-1 could result in a gene expression profile unique to pregnancy, which could help explain why the maternal inflammatory response in preeclampsia is systemic rather than localized. We sought to determine if gene expression of pregnancy neutrophils would differ if stimulated by a protease versus bacterial lipopolysaccharide (LPS). We isolated neutrophils from normal pregnant women at 30 weeks’ gestation and cultured them with elastase or LPS. We used elastase because it is a protease elevated in women with preeclampsia, and it activates pregnancy neutrophils via PAR-1. RNA was isolated from the neutrophils for sequencing of the transcriptomes. We discovered many differences in the gene expression profiles. For example, exposure to elastase resulted in three times more uniquely expressed genes than LPS, and the number of significantly differentially upregulated and downregulated genes was greater for elastase. Analysis of canonical pathways revealed similarities for innate immunity but also differences. LPS treatment enriched more pathways, but elastase activated more genes in each pathway. Elastase treatment enriched the MAPK signaling pathway, whereas LPS did not. This is significant because MAPK is a key mediator of transcriptional responses. These findings indicate that protease stimulation of pregnancy neutrophils results in a different profile than stimulation with LPS, which may help explain why the sterile inflammatory response of preeclampsia is systemic and unique to pregnancy.
At Embryo Implantation Site IL-35 Secreted by Trophoblast, Polarizing T Cells towards IL-35+ IL-10+ IL-4+ Th2-Type Cells, Could Favour Fetal Allograft Tolerance and Pregnancy Success
Authors: Lombardelli Letizia , Logiodice Federica , Kullolli Ornela , Haller Herman , Agostinis Chiara , Bulla Roberta , Rukavina Daniel , Piccinni Marie-Pierre
Published: April 2022

We investigated the role of rhIL-35, at low concentrations compatible with those produced by human trophoblast cells (less than 1 ng/mL), on human T helper (Th) cell functions and the presence of decidual IL-35-producing Th cells in human pregnancy. We found that human trophoblast cells produced IL-35 but not IL-4 or IL-10. RhIL-35, at concentrations produced by human trophoblasts, polarized T cells towards IL-35+, IL-10+, IL-4+ Th2-type cells and to Foxp3+ EBI3+ p35+ T reg cells producing IL-35 but not IL-10 and IL-4. Moreover, rhIL-35 at low concentrations did not suppress the proliferation of Th cells but stimulated IL-4 and IL-10 production by established Th clones. In particular, Th1-type clones acquired the capacity to produce IL-4. In addition, purified human trophoblast cell supernatants containing IL-35 upregulated IL-4 and IL-10 production by Th clones. Finally, IL-35+, IL-10+, IL-4+ Th2-type cells, which were found to be induced by low concentrations of IL-35 compatible with those produced by human trophoblasts, are exclusively present in the decidua of a successful pregnancy and at the embryo implantation site, suggesting their stringent dependence on trophoblast cells. Thus, the proximity of Th cells to IL-35-producing trophoblasts could be the determining factor for the differentiation of IL-35+, IL-10+, IL-4+ Th2-type cells that are crucial for human pregnancy success.
Effects of Trichoderma harzianum Strain T22 on the Arthropod Community Associated with Tomato Plants and on the Crop Performance in an Experimental Field
Authors: Caccavo Vittoria , Forlano Pierluigi , Mang Stefania , Fanti Paolo , Nuzzaci Maria , Battaglia Donatella , Trotta Vincenzo
Published: April 2022

Fungi belonging to the genus Trichoderma have received much attention in recent years due to their beneficial effects on crop health and their use as pest control agents. Trichoderma activates direct plant defenses against phytophagous arthropods and reinforces indirect plant defense through the attraction of predators. Although the plant defenses against insect herbivores were demonstrated in laboratory experiments, little attention has been paid to the use of Trichoderma spp. in open field conditions. In the present study, we investigated the effects of the inoculation of the commercial Trichoderma harzianum strain T22 on the arthropod community associated with tomato plants and on the crop performance in an experimental field located in South Italy. Our results showed that inoculation with T. harzianum could alter the arthropod community and reduce the abundance of specific pests under field conditions with respect to the sampling period. The present study also confirmed the beneficial effect of T. harzianum against plant pathogens and on tomato fruit. The complex tomato–arthropod–microorganism interactions that occurred in the field are discussed to enrich our current information on the possibilities of using Trichoderma as a green alternative agent in agriculture.
Safety and Efficacy of the Nit-Occlud® Coil for Percutaneous Closure of Various Sizes of PDA
Authors: Jung Seyong , Seol Jaehee , Choi Jaeyoung , Ha Keesoo
Published: April 2022

Most interventionalists use the Amplatzer Duct Occluder (ADO) or the Nit-Occlud® Coils (NOC) to close patent ductus arteriosus (PDA). Data regarding the success and effect of NOCs in the occlusion of large PDAs are insufficient. We aimed to investigate whether the PDA occlusion of large PDAs using NOC is safe and efficient for all ages. This was a retrospective study involving 361 pediatric and adult patients who underwent the transcatheter closure of PDA using NOC over the past 21 years for all PDA sizes and ages. The sizes of PDA were classified as small, moderate, and large. A comparison of the aortic pressure before and after PDA occlusion using NOC showed significant differences in terms of systolic and pulse pressures for all age groups (p < 0.05). The rate of the residual shunts of NOC was 2%, while the rate of complete occlusions of NOC was 98% at 12 months after occlusion regardless of the shape of PDA. The complication rate with PDA occlusion using NOC was 5%. PDA occlusion using NOC is as effective and safe as ADO for the occlusion of PDA of all sizes. Therefore, PDA occlusion using NOC can be a safe and feasible procedure to close various sizes and types of PDA without complications.
Soluble Urokinase Plasminogen Activator Receptor Levels Are Associated with Severity of Fibrosis in Patients with Primary Sclerosing Cholangitis
Authors: Özdirik Burcin , Maibier Martin , Scherf Maria , Nicklaus Jule Marie , Frohme Josephine , Puengel Tobias , Meyer zum Büschenfelde Dirk , Tacke Frank , Mueller Tobias , Sigal Michael
Published: April 2022

The soluble urokinase-type plasminogen activator receptor (suPAR) has evolved as a useful biomarker for different entities of chronic liver disease. However, its role in patients with primary sclerosing cholangitis (PSC) is obscure. We analyzed plasma levels of suPAR in 84 patients with PSC and compared them to 68 patients with inflammatory bowel disease (IBD) without PSC and to 40 healthy controls. Results are correlated with clinical records. suPAR concentrations were elevated in patients with PSC compared to patients with IBD only and to healthy controls (p < 0.001). Elevated suPAR levels were associated with the presence of liver cirrhosis (p < 0.001) and signs of portal hypertension (p < 0.001). suPAR revealed a high accuracy for the discrimination of the presence of liver cirrhosis comparable to previously validated noninvasive fibrosis markers (area under the curve (AUC) 0.802 (95%CI: 0.702–0.902)). Further, we demonstrated that suPAR levels may indicate the presence of acute cholangitis episodes (p < 0.001). Finally, despite the high proportion of PSC patients with IBD, presence of IBD and its disease activity did not influence circulating suPAR levels. suPAR represents a previously unrecognized biomarker for diagnosis and liver cirrhosis detection in patients with PSC. However, it does not appear to be confounded by intestinal inflammation in the context of IBD.
Initial Experience with Left Bundle Branch Area Pacing with Conventional Stylet-Driven Extendable Screw-In Leads and New Pre-Shaped Delivery Sheaths
Authors: Byeon Kyeongmin , Kim Hye Ree , Park Seung-Jung , Park Young Jun , Choi Ji-Hoon , Kim Ju Youn , Park Kyoung-Min , On Young Keun , Kim June Soo
Published: April 2022

Until recently, left bundle branch area pacing (LBBAp) has mostly been performed using lumen-less fixed screw leads. There are limited data on LBBAp with conventional style-driven extendable screw-in (SDES) leads, particularly data performed by operators with no previous experience with LBBAp procedures. In total, 42 consecutive patients undergoing LBBAp using SDES leads and newly designed delivery sheaths (LBBAp group) were compared with those treated with conventional right ventricular pacing (RVp) for atrioventricular block (RVp group, n = 84) using propensity score matching (1:2 ratio). The LBBAp was successful in 83% (35/42) of patients, with satisfactory pacing thresholds (0.8 ± 0.2 V at 0.4 ms). In the LBBAp group, the mean paced-QRS duration obtained during RV apical pacing (173 ± 18 ms) was significantly reduced by LBBAp (116 ± 14 ms, p < 0.001). Compared with the RVp group, the LBBAp group showed more physiological pacing, suggested by a much narrower paced-QRS duration (116 ± 14 vs. 151 ± 21 ms, p < 0.001). The pacing threshold was comparable in both groups. The LBBAp group revealed stable pacing thresholds for 6.8 ± 4.8 months post-implant and no serious complications including lead dislodgement or septal perforation. The novel approach of LBBAp using SDES leads and the new dedicated pre-shaped delivery sheaths was effectively and safely performed, even by inexperienced operators with LBBAp procedures.
Integrated Transcriptomics and Nontargeted Metabolomics Analysis Reveal Key Metabolic Pathways in Ganoderma lucidum in Response to Ethylene
Authors: Meng Li , Zhou Ruyue , Lin Jialong , Wang Qingji , Wang Panmeng , Wang Wei , Wang Li , Li Zhuang
Published: April 2022

Ganoderic acid (GA) is an important secondary metabolite of Ganoderma lucidum with a diverse array of pharmacological properties. In this study, we found that exogenous ethylene increased the production of endogenous ethylene and ganoderic acid in G. lucidum. However, the mechanism by which ethylene is regulated remains unclear. As a result, we performed a combined transcriptomics and nontargeted metabolomics analysis to evaluate the regulatory mechanism of ethylene. A total of 4070 differentially expressed genes (1835 up-regulated and 2235 down-regulated) and 378 differentially accumulated metabolites (289 up-regulated and 89 down-regulated) were identified in all groups. The transcriptomics and nontargeted metabolomics data revealed that genes involved in the tricarboxylic acid (TCA) cycle, polyamine metabolic pathway, acetyl-CoA carboxylase (ACC) pathway, and triterpenoid metabolism were up-regulated, whereas the metabolic intermediates involved in these metabolic pathways were down-regulated. These findings imply that ethylene potentially accelerates normal glucose metabolism, hence increasing the number of intermediates available for downstream biological processes, including polyamine metabolism, ethylene synthesis pathway, and ganoderic acid biosynthesis. The findings will contribute significantly to our understanding of secondary metabolites biosynthesis in fungi.
Improving the Safety of DIEP Flap Transplantation: Detailed Perforator Anatomy Study Using Preoperative CTA
Authors: Frank Katharina , Ströbel Armin , Ludolph Ingo , Hauck Theresa , May Matthias S. , Beier Justus P. , Horch Raymund E. , Arkudas Andreas
Published: April 2022

Background: Deep inferior epigastric perforator and muscle sparing transverse rectus abdominis muscle flaps are commonly used flaps for autologous breast reconstruction. CT-angiography allows to analyse the perforator course preoperatively. Our aim was to compare the different aspects of perforator anatomy in the most detailed study. Methods: CT-angiographies of 300 female patients with autologous breast reconstruction of 10 years were analysed regarding the anatomy of the deep inferior epigastric artery and every perforator. Results: Overall, 2260 perforators were included. We identified correlations regarding the DIEA branching point and number of perforators and their intramuscular course. The largest perforator emerged more often from the medial branch of the DIEA than the smaller perforators (70% (416/595) vs. 54% (878/1634), p < 0.001) and more often had a direct connection to the SIEV (large 67% (401/595) vs. small 39% (634/1634), p < 0.01). Medial row perforators were larger than the laterals (lateral 1.44 mm ± 0.43 (n = 941) vs. medial 1.58 mm ± 0.52 (n = 1304) (p < 0.001)). The larger and more medial the perforator, the more likely it was connected to the SIEV: perforators with direct connection to the SIEV had a diameter of 1.65 mm ± 0.53 (n = 1050), perforators with indirect connection had a diameter of 1.43 ± 0.43 (n = 1028), perforators without connection had a diameter of 1.31 mm ± 0.37 (n = 169) (p < 0.001). Medial perforators were more often directly connected to the SIEV than lateral perforators (medial 56% (723/1302) vs. lateral 35% (327/941), p < 0.001). A lateral perforator more often had a short intramuscular course than medial perforators (69% (554/800) vs. 45% (474/1055), p < 0.001), which was also more often observed in the case of a small perforator and a caudal exit of the rectus sheath. Conclusion: The largest perforator emerges more often from the medial branch of the DIEA and frequently has a direct connection to the SIEV, making medial row perforators ideal for DIEP flap transplantation.
Development and Assessment of the Validity and Reliability of the Short-Form Life Satisfaction Index (LSI-SF) among the Elderly Population
Authors: Li Pei-Shan , Hsieh Chia-Jung , Tallutondok Eva Berthy , Shih Ya-Ling , Liu Chieh-Yu
Published: April 2022

Background: Elderly care should focus on not only prolonging life but also satisfaction with elderly life. Our study investigated the reliability and validity of the Short-Form Life Satisfaction Index (LSI-SF). Method: Data were drawn from the 2015 Taiwan Longitudinal Study on Aging. Internal consistency reliability was used to confirm that the items measured the targeted characteristics. Construct validity was established by confirmatory factor analysis (CFA). Criterion-related validity was examined with the WHO-5 Well-Being Index as an indicator of quality of life. Known-group validity was determined from the difference between frailty stage and quality of life. Results: The high consistency reliability supported the reliability of the LSI-SF. Rigorous CFA validated the construct validity of the LSI-SF. Perfect convergent and discriminant validity supported the validity of the LSI-SF. In addition, there was a significant correlation between the LSI-SF and the WHO-5 Well-Being Index. The LSI-SF appears to be a reliable measure of quality of life in the elderly. We found that frailty status was associated with lower life satisfaction, which supported the known-group validity. Life satisfaction was highest in the non-frailty stage and lowest in the frailty stage. Conclusions: The LSI-SF appears to be a valid and reliable measure of satisfaction with elderly life.
Lymphatic and Blood Endothelial Extracellular Vesicles: A Story Yet to Be Written
Authors: Trisko Johanna , Fleck Johanna , Kau Silvio , Oesterreicher Johannes , Holnthoner Wolfgang
Published: April 2022

Extracellular vesicles (EVs), such as exosomes, microvesicles, and apoptotic bodies, are cell-derived, lipid bilayer-enclosed particles mediating intercellular communication and are therefore vital for transmitting a plethora of biological signals. The vascular endothelium substantially contributes to the circulating particulate secretome, targeting important signaling pathways that affect blood cells and regulate adaptation and plasticity of endothelial cells in a paracrine manner. Different molecular signatures and functional properties of endothelial cells reflect their heterogeneity among different vascular beds and drive current research to understand varying physiological and pathological effects of blood and lymphatic endothelial EVs. Endothelial EVs have been linked to the development and progression of various vascular diseases, thus having the potential to serve as biomarkers and clinical treatment targets. This review aims to provide a brief overview of the human vasculature, the biology of extracellular vesicles, and the current knowledge of endothelium-derived EVs, including their potential role as biomarkers in disease development.
Smart Bone Graft Composite for Cancer Therapy Using Magnetic Hyperthermia
Authors: Santana Geovana L. , Crovace Murilo C. , Mazón Ernesto E. , de Oliveira Adilson J. A. , Pavan Theo Z. , Zanotto Edgar D.
Published: April 2022

Magnetic hyperthermia (MHT) is a therapy that uses the heat generated by a magnetic material for cancer treatment. Magnetite nanoparticles are the most used materials in MHT. However, magnetite has a high Curie temperature (Tc~580 °C), and its use may generate local superheating. To overcome this problem, strontium-doped lanthanum manganite could replace magnetite because it shows a Tc near the ideal range (42–45 °C). In this study, we developed a smart composite formed by an F18 bioactive glass matrix with different amounts of Lanthanum-Strontium Manganite (LSM) powder (5, 10, 20, and 30 wt.% LSM). The effect of LSM addition was analyzed in terms of sinterability, magnetic properties, heating ability under a magnetic field, and in vitro bioactivity. The saturation magnetization (Ms) and remanent magnetization (Mr) increased by the LSM content, the confinement of LSM particles within the bioactive glass matrix also caused an increase in Tc. Calorimetry evaluation revealed a temperature increase from 5 °C (composition LSM5) to 15 °C (LSM30). The specific absorption rates were also calculated. Bioactivity measurements demonstrated HCA formation on the surface of all the composites in up to 15 days. The best material reached 40 °C, demonstrating the proof of concept sought in this research. Therefore, these composites have great potential for bone cancer therapy and should be further explored.
Effect of Elevated Temperature on Rhyolitic Rocks’ Properties
Authors: Ahmed Haitham M. , Hefni Mohammed A. , Ahmed Hussin A. M. , Adewuyi Sefiu O. , Hassani Ferri , Sasmito Agus P. , Saleem Hussein A. , Moustafa Essam B. , Hassan Gamal S. A.
Published: April 2022

The effect of high temperatures on rock’s thermophysical and mechanical properties is critical to the design of underground geotechnical applications. The current work investigates the impact of temperature on rhyolitic turf rock’s physical and mechanical properties. Intact cylindrical core rock samples were heated to different temperatures (200, 400, 600, and 800 °C). The uniaxial compressive strength (UCS) and elastic modulus of unheated and heated samples were determined as important mechanical properties. In addition, the effect of temperature on the physical properties of rhyolite rock (density, color, and absorption) was investigated in conjunction with its microstructural properties. The hardening of the rhyolitic rock samples was observed below 600 °C, at which point the UCS and elastic modulus decreased to 78.0% and 75.9%, respectively, at 800 °C. The results also show that heating does not significantly affect the density and volume of permeable pore space, but a color change can be observed at 400 °C and above. A microscopic analysis shows the change in microstructural properties of rhyolite rock after heating to 600 °C. Furthermore, the SEM observations of heated materials show structural particle displacements and microcracking, leading to apparent surface cracks.
Waste Material via Geopolymerization for Heavy-Duty Application: A Review
Authors: Kheimi Marwan , Aziz Ikmal Hakem , Abdullah Mohd Mustafa Al Bakri , Almadani Mohammad , Abd Razak Rafiza
Published: April 2022

Due to the extraordinary properties for heavy-duty applications, there has been a great deal of interest in the utilization of waste material via geopolymerization technology. There are various advantages offered by this geopolymer-based material, such as excellent stability, exceptional impermeability, self-refluxing ability, resistant thermal energy from explosive detonation, and excellent mechanical performance. An overview of the work with the details of key factors affecting the heavy-duty performance of geopolymer-based material such as type of binder, alkali agent dosage, mixing design, and curing condition are reviewed in this paper. Interestingly, the review exhibited that different types of waste material containing a large number of chemical elements had an impact on mechanical performance in military, civil engineering, and road application. Finally, this work suggests some future research directions for the the remarkable of waste material through geopolymerization to be employed in heavy-duty application.
Review on Motion and Load-Bearing Characteristics of the Planetary Roller Screw Mechanism
Authors: Li Xin , Liu Geng , Fu Xiaojun , Ma Shangjun
Published: April 2022

Studying the motion and load-bearing characteristics of the planetary roller screw mechanism is the basis for the structural design and performance optimisation of the mechanism. The mechanical structures and working principles of different kinds of planetary roller screw mechanisms are summarised. Published papers on kinematic, load-bearing and dynamic models of the planetary roller screw mechanism are reviewed. Based on the slip state in point contacts at the screw–roller and the nut–roller interfaces, the kinematic models are divided into three types. The finite element method and numerical theory are the two main methods used to develop the load-bearing models. Current dynamic models differ mainly concerning whether they take the rotation of the screw into consideration. In this work, each kind of model is presented in detail along with relevant literature. The main conclusions for each type of model are discussed, and an overview of the future evolution of motion and load-bearing characteristics of the planetary roller screw mechanism are given.
Algebraic Perspective of Cubic Multi-Polar Structures on BCK/BCI-Algebras
Authors: Al-Masarwah Anas , Alshehri Halimah
Published: April 2022

Cubic multipolar structure with finite degree (briefly, cubic k-polar (CkP) structure) is a new hybrid extension of both k-polar fuzzy (kPF) structure and cubic structure in which CkP structure consists of two parts; the first one is an interval-valued k-polar fuzzy (IVkPF) structure acting as a membership grade extended from the interval P[0,1] to P[0,1]k (i.e., from interval-valued of real numbers to the k-tuple interval-valued of real numbers), and the second one is a kPF structure acting as a nonmembership grade extended from the interval [0,1] to [0,1]k (i.e., from real numbers to the k-tuple of real numbers). This approach is based on generalized cubic algebraic structures using polarity concepts and therefore the novelty of a CkP algebraic structure lies in its large range comparative to both kPF algebraic structure and cubic algebraic structure. The aim of this manuscript is to apply the theory of CkP structure on BCK/BCI-algebras. We originate the concepts of CkP subalgebras and (closed) CkP ideals. Moreover, some illustrative examples and dominant properties of these concepts are studied in detail. Characterizations of a CkP subalgebra/ideal are given, and the correspondence between CkP subalgebras and (closed) CkP ideals are discussed. In this regard, we provide a condition for a CkP subalgebra to be a CkP ideal in a BCK-algebra. In a BCI-algebra, we provide conditions for a CkP subalgebra to be a CkP ideal, and conditions for a CkP subalgebra to be a closed CkP ideal. We prove that, in weakly BCK-algebra, every CkP ideal is a closed CkP ideal. Finally, we establish the CkP extension property for a CkP ideal.
Credit Card Fraud Detection Using a New Hybrid Machine Learning Architecture
Authors: Malik Esraa Faisal , Khaw Khai Wah , Belaton Bahari , Wong Wai Peng , Chew XinYing
Published: April 2022

The negative effect of financial crimes on financial institutions has grown dramatically over the years. To detect crimes such as credit card fraud, several single and hybrid machine learning approaches have been used. However, these approaches have significant limitations as no further investigation on different hybrid algorithms for a given dataset were studied. This research proposes and investigates seven hybrid machine learning models to detect fraudulent activities with a real word dataset. The developed hybrid models consisted of two phases, state-of-the-art machine learning algorithms were used first to detect credit card fraud, then, hybrid methods were constructed based on the best single algorithm from the first phase. Our findings indicated that the hybrid model Adaboost + LGBM is the champion model as it displayed the highest performance. Future studies should focus on studying different types of hybridization and algorithms in the credit card domain.
Wide Range Applications of Spirulina: From Earth to Space Missions
Authors: Fais Giacomo , Manca Alessia , Bolognesi Federico , Borselli Massimiliano , Concas Alessandro , Busutti Marco , Broggi Giovanni , Sanna Pierdanilo , Castillo-Aleman Yandy Marx , Rivero-Jiménez René Antonio , Bencomo-Hernandez Antonio Alfonso , Ventura-Carmenate Yendry , Altea Michela , Pantaleo Antonella , Gabrielli Gilberto , Biglioli Federico , Cao Giacomo , Giannaccare Giuseppe
Published: April 2022

Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.
Preclinical Development of Seriniquinones as Selective Dermcidin Modulators for the Treatment of Melanoma
Authors: Hirata Amanda S. , La Clair James J. , Jimenez Paula C. , Costa-Lotufo Leticia Veras , Fenical William
Published: April 2022

The bioactive natural product seriniquinone was discovered as a potential melanoma drug, which was produced by the as-yet-undescribed marine bacterium of the rare genus Serinicoccus. As part of a long-term research program aimed at the discovery of new agents for the treatment of cancer, seriniquinone revealed remarkable in vitro activity against a diversity of cancer cell lines in the US National Cancer Institute 60-cell line screening. Target deconvolution studies defined the seriniquinones as a new class of melanoma-selective agents that act in part by targeting dermcidin (DCD). The targeted DCD peptide has been recently examined and defined as a “pro-survival peptide” in cancer cells. While DCD was first isolated from human skin and thought to be only an antimicrobial peptide, currently DCD has been also identified as a peptide associated with the survival of cancer cells, through what is believed to be a disulfide-based conjugation with proteins that would normally induce apoptosis. However, the significantly enhanced potency of seriniquinone was of particular interest against the melanoma cell lines assessed in the NCI 60-cell line panel. This observed selectivity provided a driving force that resulted in a multidimensional program for the discovery of a usable drug with a new anticancer target and, therefore, a novel mode of action. Here, we provided an overview of the discovery and development efforts to date.
Discovery of Anti-MRSA Secondary Metabolites from a Marine-Derived Fungus Aspergillus fumigatus
Authors: Zhang Rui , Wang Haifeng , Chen Baosong , Dai Huanqin , Sun Jingzu , Han Junjie , Liu Hongwei
Published: April 2022

Methicillin-resistant Staphylococcus aureus (MRSA), a WHO high-priority pathogen that can cause great harm to living beings, is a primary cause of death from antibiotic-resistant infections. In the present study, six new compounds, including fumindoline A–C (1–3), 12β, 13β-hydroxy-asperfumigatin (4), 2-epi-tryptoquivaline F (17) and penibenzophenone E (37), and thirty-nine known ones were isolated from the marine-derived fungus Aspergillus fumigatus H22. The structures and the absolute configurations of the new compounds were unambiguously assigned by spectroscopic data, mass spectrometry (MS), electronic circular dichroism (ECD) spectroscopic analyses, quantum NMR and ECD calculations, and chemical derivatizations. Bioactivity screening indicated that nearly half of the compounds exhibit antibacterial activity, especially compounds 8 and 11, and 33–38 showed excellent antimicrobial activities against MRSA, with minimum inhibitory concentration (MIC) values ranging from 1.25 to 2.5 μM. In addition, compound 8 showed moderate inhibitory activity against Mycobacterium bovis (MIC: 25 μM), compound 10 showed moderate inhibitory activity against Candida albicans (MIC: 50 μM), and compound 13 showed strong inhibitory activity against the hatching of a Caenorhabditis elegans egg (IC50: 2.5 μM).
Classical Cerebrospinal Fluid Biomarkers in Dementia with Lewy Bodies
Authors: Foska Aikaterini , Tsantzali Ioanna , Sideri Eleni , Stefanou Maria Ioanna , Bakola Eleni , Kitsos Dimitrios K. , Zompola Christina , Bonakis Anastasios , Giannopoulos Sotirios , Voumvourakis Konstantinos I. , Tsivgoulis Georgios , Paraskevas George P.
Published: April 2022

The use and interpretation of diagnostic cerebrospinal fluid (CSF) biomarkers for neurodegenerative disorders, such as Dementia with Lewy bodies (DLB), represent a clinical challenge. According to the literature, the composition of CSF in DLB patients varies. Some patients present with reduced levels of amyloid, others with full Alzheimer Disease CSF profile (both reduced amyloid and increased phospho-tau) and some with a normal profile. Some patients may present with abnormal levels of a-synuclein. Continuous efforts will be required to establish useful CSF biomarkers for the early diagnosis of DLB. Given the heterogeneity of methods and results between studies, further validation is fundamental before conclusions can be drawn.
Diagnostic Accuracy of the RDW for Predicting Death in COVID-19
Authors: Guaní-Guerra Eduardo , Torres-Murillo Brenda , Muñoz-Corona Carolina , Rodríguez-Jiménez José Carlos , Macías Alejandro E. , Scavo-Montes David A. , Alvarez Jose A.
Published: April 2022

Background and Objectives: An association between high red blood cell distribution width (RDW) and mortality has been found in several diseases, including infection and sepsis. Some studies have aimed at determining the association of elevated RDW with adverse prognosis in COVID-19, but its usefulness has not been well established. The objective of this study was to determine the accuracy of the RDW, measured at hospital admission and discharge, for predicting death in patients with COVID-19. Materials andMethods: An observational, retrospective, longitudinal, and analytical study was conducted in two different COVID-19 reference centers in the state of Guanajuato, Mexico. A total of 323 patients hospitalized by COVID-19 were included. Results: We found higher RDW levels at the time of hospital admission in the non-survivors group compared to levels in survivors (median = 13.6 vs. 13.0, p < 0.001). Final RDW levels were even higher in the deceased group when compared with those of survivors (median = 14.6 [IQR, 12.67–15.6] vs. 12.9 [IQR, 12.2–13.5], p < 0.001). For patients who died, an RDW > 14.5% was more common at the time of death than for patients who survived at the time of discharge (81 vs. 13 patients, p < 0.001; RR = 2.3, 95% CI 1.89–2.81). Conclusions: The RDW is an accessible and economical parameter that, together with other characteristics of the presentation and evolution of patients with COVID-19, can be helpful in determining the prognosis. An RDW that increases during hospitalization could be a more important mortality predictor than the RDW at hospital admission.
Functional Brain Asymmetry and Menopausal Treatments: Is There a Link?
Authors: Digesu Giuseppe , Riemma Gaetano , Torella Marco , La Verde Marco , Schiattarella Antonio , Munno Gaetano , Fasulo Diego , Celardo Angela , Vagnetti Primo , Annona Salvatore , Schettino Maria , Guida Maurizio , De Franciscis Pasquale
Published: April 2022

Background and Objectives: The human brain presents a functional asymmetry for every cognitive function, and it is possible that sexual hormones could have an impact on it. Visual–spatial attention, one of the most lateralized functions and one that is mainly dependent on the right hemisphere, represents a sentinel for functional cerebral asymmetry (FCA). The aim of this study was to evaluate whether menopausal hormone therapy (MHT) or phytoestrogens could modulate FCA in postmenopausal women. Materials and Methods: We enrolled postmenopausal women who were taking MHT or soy isoflavones or receiving no therapy and asked them to perform the line bisection test at study enrollment and after 18 and 36 months. Results: Ninety women completed the follow-up. At zero time, women who had not been subjected to therapy showed a leftward deviation (F = −3.0), whereas, after 36 months, the test results showed a rightward deviation (F = 4.5; p < 0.01). Women taking MHT showed a leftward deviation at the start (F = −3.0) and a persistent leftward deviation after 36 months (F = −4.0; p = 0.08). Conversely, women taking soy isoflavones started with a leftward deviation (F = −3.0) that became rightward (F = 3.0), with a significant difference shown after 36 months (p < 0.01). Conclusions: Our data suggest that hormonal modulation improves the interplay between the two hemispheres and reduces FCA. We propose, therefore, that the functions of the right hemisphere are mainly affected by aging and that this could be one of the reasons why the right hemisphere is more susceptible to the effects of MHT.
The Microbial Nitrogen Cycling, Bacterial Community Composition, and Functional Potential in a Natural Grassland Are Stable from Breaking Dormancy to Being Dormant Again
Authors: Das Bikram K. , Ishii Satoshi , Antony Linto , Smart Alexander J. , Scaria Joy , Brözel Volker S.
Published: April 2022

The quantity of grass-root exudates varies by season, suggesting temporal shifts in soil microbial community composition and activity across a growing season. We hypothesized that bacterial community and nitrogen cycle-associated prokaryotic gene expressions shift across three phases of the growing season. To test this hypothesis, we quantified gene and transcript copy number of nitrogen fixation (nifH), ammonia oxidation (amoA, hao, nxrB), denitrification (narG, napA, nirK, nirS, norB, nosZ), dissimilatory nitrate reduction to ammonia (nrfA), and anaerobic ammonium oxidation (hzs, hdh) using the pre-optimized Nitrogen Cycle Evaluation (NiCE) chip. Bacterial community composition was characterized using V3-V4 of the 16S rRNA gene, and PICRUSt2 was used to draw out functional inferences. Surprisingly, the nitrogen cycle genes and transcript quantities were largely stable and unresponsive to seasonal changes. We found that genes and transcripts related to ammonia oxidation and denitrification were different for only one or two time points across the seasons (p < 0.05). However, overall, the nitrogen cycling genes did not show drastic variations. Similarly, the bacterial community also did not vary across the seasons. In contrast, the predicted functional potential was slightly low for May and remained constant for other months. Moreover, soil chemical properties showed a seasonal pattern only for nitrate and ammonium concentrations, while ammonia oxidation and denitrification transcripts were strongly correlated with each other. Hence, the results refuted our assumptions, showing stability in N cycling and bacterial community across growing seasons in a natural grassland.
Epidemics of Crimean-Congo Hemorrhagic Fever (CCHF) in Sudan between 2010 and 2020
Authors: Ahmed Ayman , Ali Yousif , Salim Bashir , Dietrich Isabelle , Zinsstag Jakob
Published: April 2022

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral disease that poses a great threat to global health in the Old World, and it is endemic in Europe, Asia, and Africa, including Sudan. In this retrospective study, we reviewed previous epidemiological reports about the major epidemics of CCHF throughout Sudan between 2010 and 2020. During these epidemics, the infection of humans with Crimean-Congo hemorrhagic fever virus (CCHFV), the causative agent of CCHF, was diagnosed using qRT-PCR. We have identified 88 cases of CCHF, including 13 fatalities reported during five epidemics that occurred in 2010, 2011, 2015, 2019, and 2020. The two epidemics in 2010 and 2011 were by far the largest, with 51 and 27 cases reported, respectively. The majority of cases (78%) were reported in the endemic region of Kordofan. Here, we document that the first emergence of CCHFV in the Darfur region, West Sudan, occurred in 2010. We were not able to investigate outbreak dynamics through phylogenetic analysis due to the limited diagnostic capacity and the lack of sequencing services in the country. These findings call for establishing a genomic-based integrated One Health surveillance and response system for the early preparedness, prevention, and control of CCHF in the country.
Fusion of Lineament Factor (LF) Map Analysis and Multifractal Technique for Massive Sulfide Copper Exploration: The Sahlabad Area, East Iran
Authors: Shirazi Aref , Hezarkhani Ardeshir , Pour Amin Beiranvand
Published: April 2022

Fault systems are characteristically one of the main factors controlling massive sulfide mineralization. The main objective of this study was to investigate the relationship between fault systems and host lithology with massive sulfide copper mineralization in the Sahlabad area, South Khorasan province, east of Iran. Subsequently, the rose diagram analysis, Fry analysis, lineament factor (LF) map analysis and multifractal technique were implemented for geological and geophysical data. Airborne geophysical analysis (aeromagnetometric data) was executed to determine the presence of intrusive and extrusive masses associated with structural systems. Accordingly, the relationship between the formation boundaries and the fault system was understood. Results indicate that the NW-SE fault systems are controlling the lithology of the host rock for copper mineralization in the Sahlabad area. Hence, the NW-SE fault systems are consistent with the main trend of lithological units related to massive sulfide copper mineralization in the area. Additionally, the distance of copper deposits, mines and indices in the Sahlabad area with fault systems was calculated and interpreted. Fieldwork results confirm that the NW-SE fault systems are entirely matched with several massive sulfide copper mineralizations in the area. This study demonstrates that the fusion of lineament factor (LF) map analysis and multifractal technique is a valuable and inexpensive approach for exploring massive sulfide mineralization in metallogenic provinces.
Enhanced Extraction Efficiency of Flavonoids from Pyrus ussuriensis Leaves with Deep Eutectic Solvents
Authors: Lee Jong Woo , Park Hye Yoon , Park Junseong
Published: April 2022

In this study, deep eutectic solvents (DESs) were synthesized using different ratios of choline chloride (CC) and dicarboxylic acids, and their eutectic temperatures were determined. The DES synthesized using CC and glutaric acid (GA), which showed a higher extraction efficiency than conventional solvents, was used for the extraction of flavonoid components from Pyrus ussuriensis leaves (PUL), and the extraction efficiency was evaluated using the response surface methodology. The flavonoid components rutin, hyperoside, and isoquercitrin were identified through high-performance liquid chromatography (HPLC), equipped with a Waters 2996 PDA detector, and HPLC mass spectrometry (LC-MS/MS) analyses. The optimum extraction was achieved at a temperature of 30 °C using DES in a concentration of 30.85 wt.% at a stirring speed of 1113 rpm and an extraction time of 1 h. The corresponding flavonoid content was 217.56 μg/mL. The results were verified by performing three reproducibility experiments, and a high significance, with a confidence range of 95%, was achieved. In addition, the PUL extracts exhibited appreciable antioxidant activity. The results showed that the extraction process using the DES based on CC and GA in a 1:1 molar ratio could effectively improve the yield of flavonoids from PUL.