bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Modeling of Algol-Type Binaries
Authors: van Rensbergen Walter , de Greve Jean-Pierre
Published: March 2021

In earlier papers, we presented a binary evolutionary code for the purpose of reproducing the orbital parameters, masses, radii, and location in the Hertzsprung Russell diagram (abbreviated as HRD) of well-observed Algol systems. In subsequent versions, the effects of mass and angular momentum losses and tidal coupling were included in order to produce the observed distributions of orbital periods and mass ratios of Algol-type binaries. The mass loss includes stellar wind and possible liberal evolution, when the gainer star is not capable to absorb all of the matter during mass transfer from the donor star. We added magnetic braking to our code to better reproduce the observed equatorial velocities. Large equatorial velocities of mass-gaining stars are now lowered by tidal interaction and magnetic braking. Tides are mainly at work at short orbital periods, leaving magnetic braking alone at work during longer orbital periods. The observed values of the equatorial velocities of mass gainers in Algol-type binaries are mostly well reproduced by our code. According to our models, Algols have short periods with a strong magnetic field.
Recent Shoreline Changes Due to High-Angle Wave Instability along the East Coast of Lingayen Gulf in the Philippines
Authors: Uda Takaaki , Noshi Yasuhito
Published: March 2021

A small perturbation on the shoreline may develop under high-angle wave conditions, resulting in the formation of sand spits along the shoreline. Serizawa et al. explained the development of sand spits caused by the instability mechanism using the BG model (a model for predicting 3-D beach changes based on Bagnold’s concept). However, examples of the development of sand spits caused by this mechanism in the field are limited in number. Lingayen Gulf in the Philippines has a large aspect ratio, so shoreline instability occurs along the coastline, significantly affecting the shore protection along the coast. In this study, the shoreline instability along the river delta coasts around the Balili and Aringay Rivers flowing into Lingayen Gulf and a sand spit were investigated using satellite images together with field observation. The shoreline changes observed south of the Aringay River mouth were compared with those observed in a previous study on the development of a sand spit by San-nami et al. The rate of longshore sand transport to form a sand spit at Santo Tomas in Lingayen Gulf was estimated to be approximately 1.3 × 105 m3/yr, which is in good agreement with the value measured on the Shimizu coast in Suruga Bay, with a comparable aspect ratio of 1.2 relative to 1.3 in Lingayen Gulf. It was concluded that shoreline undulations have evolved downcoast of two river deltas owing to high-angle wave instability along the east coast of Lingayen Gulf and the formation of a sand spit has occurred. A soft measure, such as sand bypassing, would be better to be adopted along the coasts in Lingayen Gulf instead of hard measures against erosion, to prevent rapid expansion of an artificial, protected coastline.
Influencing Factors of Acceptance and Use Behavior of Mobile Health Application Users: Systematic Review
Authors: Wang Chen , Qi Huiying
Published: March 2021

Purpose/Significance: Mobile health applications provide a convenient way for users to obtain health information and services. Studying the factors that influence users’ acceptance and use of mobile health applications (apps or Apps) will help to improve users’ actual usage behavior. Method/Process: Based on the literature review method and using the Web of Science core database as the data source, this paper summarizes the relevant research results regarding the influencing factors of the acceptance and use behavior of mobile health application users and makes a systematic review of the influencing factors from the perspectives of the individual, society, and application (app or App) design. Result/Conclusion: In terms of the individual dimension, the users’ behavior is influenced by demographic characteristics and motivations. Social attributes, source credibility, and legal issues all affect user behavior in the social dimension. In the application design dimension, functionality, perceived ease of use and usefulness, security, and cost are the main factors. At the end of the paper, suggestions are given to improve the users’ acceptability of mobile health applications and improve their use behavior.
Using Environmental Tracers to Characterize Groundwater Flow Mechanisms in the Fractured Crystalline and Karst Aquifers in Upper Crocodile River Basin, Johannesburg, South Africa
Authors: Leketa Khahliso , Abiye Tamiru
Published: March 2021

Environmental isotope tracers were applied in the Upper Crocodile River Basin, Johannesburg, South Africa, to understand the groundwater recharge conditions, flow mechanisms and interactions between surface and subsurface water. Stable isotope analysis indicated that recharge into the fractured quartzite aquifer occurs through direct mechanisms. The high variability in the stable isotope signature of temporal samples from Albert Farm spring indicated the importance of multiple samples for groundwater characterization, and that using a single sample may be yielding biased conclusions. The observed inverse relationship between spring discharge and isotope signature indicated the traces of rainfall amount effect during recharge, thereby suggesting piston groundwater flow. It is deduced that a measured discharge value can be used in this relationship to calculate the isotopic signature, which resembles effective rainfall. In the shallow alluvial deposits that overlie the granitic bed-rock, piezometer levels and stable isotopes revealed an interaction between Montgomery stream and interflow, which regulates streamflow throughout the year. This suggests that caution should be taken where hydrograph separation is applied for baseflow estimates, because the stream flow that overlies such geology may include significant interflow. The hydrochemistry evolution was observed in a stream fed by karst springs. As pH rises due to CO2 degassing, CaCO3 precipitates, thereby forming travertine moulds. The values of saturation indices that were greater than zero in all samples indicated supersaturation by calcite and dolomite and hence precipitation. Through 14C analysis, groundwater flow rate in the karst aquifer was estimated as 11 km/year, suggesting deep circulation in karst structures.
A Comparison Method for 3D Laser Point Clouds in Displacement Change Detection for Arch Dams
Authors: Li Yijing , Liu Ping , Li Huokun , Huang Faming
Published: March 2021

Dam deformation monitoring can directly identify the safe operation state of a dam in advance, which plays an important role in dam safety management. Three-dimensional (3D) terrestrial laser scanning technology is widely used in the field of deformation monitoring due to its fast, complete, and high-density 3D data acquisition capabilities. However, 3D point clouds are characterized by rough surfaces, discrete distributions, which affect the accuracy of deformation analysis of two states data. In addition, it is impossible to directly extract the correspondence points from an irregularly distributed point cloud to unify the coordinates of the two states’ data, and the correspondence lines and planes are often difficult to obtain in the natural environment. To solve the above problems, this paper studies a displacement change detection method for arch dams based on two-step point cloud registration and contour model comparison method. In the environment around a dam, the stable rock is used as the correspondence element to improve the registration accuracy, and a two-step registration method from rough to fine using the iterative closest point algorithm is present to describe the coordinate unification of the two states’ data without control network and target. Then, to analyze the displacement variation of an arch dam surface in two states and improve the accuracy of comparing the two surfaces without being affected by the roughness of the point cloud, the contour model fitting the point clouds is used to compare the change in distance between models. Finally, the method of this paper is applied to the Xiahuikeng Arch Dam, and the displacement changes of the entire dam in different periods are visualized by comparing with the existing methods. The results show that the displacement change in the middle area of the dam is generally greater than that of the two banks, increasing with the increase in elevation, which is consistent with the displacement change behavior of the arch dam during operation and can reach millimeter-level accuracy.
Ring-Selective Fragmentation in the Tirapazamine Molecule upon Low-Energy Electron Attachment
Authors: Arthur-Baidoo Eugene , Ameixa Joao , Ončák Milan , Denifl Stephan
Published: March 2021

We investigate dissociative electron attachment to tirapazamine through a crossed electron–molecule beam experiment and quantum chemical calculations. After the electron is attached and the resulting anion reaches the first excited state, D1, we suggest a fast transition into the ground electronic state through a conical intersection with a distorted triazine ring that almost coincides with the minimum in the D1 state. Through analysis of all observed dissociative pathways producing heavier ions (90–161 u), we consider the predissociation of an OH radical with possible roaming mechanism to be the common first step. This destabilizes the triazine ring and leads to dissociation of highly stable nitrogen-containing species. The benzene ring is not altered during the process. Dissociation of small anionic fragments (NO2−, CN2−, CN−, NH2−, O−) cannot be conclusively linked to the OH predissociation mechanism; however, they again do not require dissociation of the benzene ring.
PAI-1 in Diabetes: Pathophysiology and Role as a Therapeutic Target
Authors: Altalhi Rawan , Pechlivani Nikoletta , Ajjan Ramzi A.
Published: March 2021

Hypofibrinolysis is a key abnormality in diabetes and contributes to the adverse vascular outcome in this population. Plasminogen activator inhibitor (PAI)-1 is an important regulator of the fibrinolytic process and levels of this antifibrinolytic protein are elevated in diabetes and insulin resistant states. This review describes both the physiological and pathological role of PAI-1 in health and disease, focusing on the mechanism of action as well as protein abnormalities in vascular disease with special focus on diabetes. Attempts at inhibiting protein function, using different techniques, are also discussed including direct and indirect interference with production as well as inhibition of protein function. Developing PAI-1 inhibitors represents an alternative approach to managing hypofibrinolysis by targeting the pathological abnormality rather than current practice that relies on profound inhibition of the cellular and/or acellular arms of coagulation, and which can be associated with increased bleeding events. The review offers up-to-date knowledge on the mechanisms of action of PAI-1 together with the role of altering protein function to improve hypofirbinolysis. Developing PAI-1 inhibitors may form for the basis of future new class of antithrombotic agents that reduce vascular complications in diabetes.
Intense Pulsed Light Attenuates UV-Induced Hyperimmune Response and Pigmentation in Human Skin Cells
Authors: Kim Juewon , Lee Jeongin , Choi Hyunjung
Published: March 2021

The skin of an organism is affected by various environmental factors and fights against aging stress via mechanical and biochemical responses. Photoaging induced by ultraviolet B (UVB) irradiation is common and is the most vital factor in the senescence phenotype of skin, and so, suppression of UVB stress-induced damage is critical. To lessen the UVB-induced hyperimmune response and hyperpigmentation, we investigated the ameliorative effects of intense pulsed light (IPL) treatment on the photoaged phenotype of skin cells. Normal human epidermal keratinocytes and human epidermal melanocytes were exposed to 20 mJ/cm2 of UVB. After UVB irradiation, the cells were treated with green (525–530 nm) and yellow (585–592 nm) IPL at various time points prior to the harvest step. Subsequently, various signs of excessive immune response, including expression of proinflammatory and melanogenic genes and proteins, cellular oxidative stress level, and antioxidative enzyme activity, were examined. We found that IPL treatment reduced excessive cutaneous immune reactions by suppressing UVB-induced proinflammatory cytokine expression. IPL treatment prevented hyperpigmentation, and combined treatment with green and yellow IPL synergistically attenuated both processes. IPL treatment may exert protective effects against UVB injury in skin cells by attenuating inflammatory cytokine and melanogenic gene overexpression, possibly by reducing intracellular oxidative stress. IPL treatment also preserves antioxidative enzyme activity under UVB irradiation. This study suggests that IPL treatment is a useful strategy against photoaging, and provides evidence supporting clinical approaches with non-invasive light therapy.
A Bioinformatics Systems Biology Analysis of the Current Oral Proteomic Biomarkers and Implications for Diagnosis and Treatment of External Root Resorption
Authors: Mona Mahmoud , Abbasi Zunnaira , Kobeissy Firas , Chahbandar Abdulrahman , Pileggi Roberta
Published: March 2021

External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to the loss of the tooth or multiple teeth. Traditionally, clinicians have relied on radiographs and cone beam computed tomography (CBCT) images for the diagnosis of ERR; however, these techniques are not often precise or definitive and may require exposure of patients to more ionizing radiation than necessary. To overcome these shortcomings, there is an immense need to develop non-invasive approaches such as biomarker screening methods for rapid and precise diagnosis for ERR. In this review, we performed a literature survey for potential salivary or gingival crevicular fluid (GCF) proteomic biomarkers associated with ERR and analyzed the potential pathways leading to ERR. To the best of our knowledge, this is the first proteomics biomarker survey that connects ERR to body biofluids which represents a novel approach to diagnose and even monitor treatment progress for ERR.
Magnoliae Cortex Alleviates Muscle Wasting by Modulating M2 Macrophages in a Cisplatin-Induced Sarcopenia Mouse Model
Authors: Hong Minwoo , Han Ik-Hwan , Choi Ilseob , Cha Nari , Kim Woojin , Kim Sun Kwang , Bae Hyunsu
Published: March 2021

Cachexia causes high mortality, low quality of life, and rapid weight loss in cancer patients. Sarcopenia, a condition characterized by the loss of muscle, is generally present in cachexia and is associated with inflammation. M2 macrophages, also known as an anti-inflammatory or alternatively activated macrophages, have been shown to play a role in muscle repair. Magnoliae Cortex (M.C) is a widely used medicinal herb in East Asia reported to have a broad range of anti-inflammatory activities; however, the effects of M.C on sarcopenia and on M2 macrophage polarization have to date not been studied. This study was designed to investigate whether the oral administration of M.C could decrease cisplatin-induced sarcopenia by modulating M2 macrophage polarization in mice. C57BL/6 mice were injected intraperitoneally with cisplatin (2.5 mg/kg) to mimic chemotherapy-induced sarcopenia. M.C extract (50, 100, and 200 mg/kg) was administered orally every 3 days (for a total of 12 times). M.C (100 and 200 mg/kg) significantly alleviated the cisplatin-induced loss of body mass, skeletal muscle weight, and grip strength. In addition, M.C increased the expression of M2 macrophage markers, such as MRC1, CD163, TGF-β, and Arg-1, and decreased the expression of M1-specific markers, including NOS2 and TNF-α, in skeletal muscle. Furthermore, the levels of like growth factor-1(IGF-1), as well as the number of M2a and M2c macrophages, significantly increased in skeletal muscle after M.C administration. M.C did not interfere with the anticancer effect of cisplatin in colon cancer. Our results demonstrated that M.C can alleviate cisplatin-induced sarcopenia by increasing the number of M2 macrophages. Therefore, our findings suggest that M.C could be used as an effective therapeutic agent to reverse or prevent cisplatin-induced sarcopenia.
Genetics of Host Protection against Helicobacter pylori Infections
Authors: Capparelli Rosanna , Iannelli Domenico
Published: March 2021

This narrative review discusses the genetics of protection against Helicobacter pylori (Hp) infection. After a brief overview of the importance of studying infectious disease genes, we provide a detailed account of the properties of Hp, with a view to those relevant for our topic. Hp displays a very high level of genetic diversity, detectable even between single colonies from the same patient. The high genetic diversity of Hp can be evaded by stratifying patients according to the infecting Hp strain. This approach enhances the power and replication of the study. Scanning for single nucleotide polymorphisms is generally not successful since genes rarely work alone. We suggest selecting genes to study from among members of the same family, which are therefore inclined to cooperate. Further, extending the analysis to the metabolism would significantly enhance the power of the study. This combined approach displays the protective role of MyD88, TIRAP, and IL1RL1 against Hp infection. Finally, several studies in humans have demonstrated that the blood T cell levels are under the genetic control of the CD39+ T regulatory cells (TREGS).
Global Changes of 5-mC/5h-mC Ratio and Methylation of Adiponectin and Leptin Gene in Placenta Depending on Mode of Delivery
Authors: Słabuszewska-Jóźwiak Aneta , Malinowska Marcelina , Kloska Anna , Jakóbkiewicz-Banecka Joanna , Gujski Mariusz , Bojar Iwona , Raczkiewicz Dorota , Jakiel Grzegorz
Published: March 2021

It was suggested that the epigenetic alterations of the placenta are associated with obesity, as well as the delivery mode. This study aimed to assess the effect of maternal outcome and delivery procedure on global placental DNA methylation status, as well as selected 5’-Cytosine-phosphate-Guanine-3’ (CpG) sites in ADIPOQ and LEP genes. Global DNA methylation profile in the placenta was assessed using the 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) ratio evaluated with the ELISA, followed by target gene methylation patterns at selected gene regions which were determined using methylation-specific qPCR in 70 placentas from healthy, pregnant women with single pregnancy. We found no statistically significant differences in 5-mC/5-hmC ratio between intrapartum cesarean sections (CS) and vaginal deliveries (p = 0.214), as well as between elective cesarean sections and vaginal deliveries (p = 0.221). In intrapartum cesarean sections, the ADIPOQ demethylation index was significantly higher (the average: 1.75) compared to elective cesarean section (the average: 1.23, p = 0.010) and vaginal deliveries (the average: 1.23, p = 0.011). The LEP demethylation index did not significantly differ among elective CS, intrapartum CS, and vaginal delivery groups. The demethylation index of ADIPOQ correlated negatively with LEP in the placenta in the vaginal delivery group (r = −0.456, p = 0.017), but not with the global methylation. The methylation of a singular locus might be different depending on the mode of delivery and uterine contractions. Further studies should be conducted with locus-specific analysis of the whole genome to detect the methylation index of specific genes involved in metabolism.
SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome
Authors: Sisto Margherita , Ribatti Domenico , Lisi Sabrina
Published: March 2021

There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.
The Role of Endoglin in Hepatocellular Carcinoma
Authors: Jeng Kuo-Shyang , Sheen I-Shyan , Lin Shu-Sheng , Leu Chuen-Miin , Chang Chiung-Fang
Published: March 2021

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.
Utilization of Isoflavones in Soybeans for Women with Menopausal Syndrome: An Overview
Authors: Chen Li-Ru , Chen Kuo-Hu
Published: March 2021

Based on their nutrient composition, soybeans and related foods have been considered to be nutritious and healthy for humans. Particularly, the biological activity and subsequent benefits of soy products may be associated with the presence of isoflavone in soybeans. As an alternative treatment for menopause-related symptoms, isoflavone has gained much popularity for postmenopausal women who have concerns related to undergoing hormone replacement therapy. However, current research has still not reached a consensus on the effects of isoflavone on humans. This overview is a summary of the current literature about the processing of soybeans and isoflavone types (daidzein, genistein, and S-equol) and supplements and their extraction and analysis as well as information about the utilization of isoflavones in soybeans. The processes of preparation (cleaning, drying, crushing and dehulling) and extraction of soybeans are implemented to produce refined soy oil, soy lecithin, free fatty acids, glycerol and soybean meal. The remaining components consist of inorganic constituents (minerals) and the minor components of biologically interesting small molecules. Regarding the preventive effects on diseases or cancers, a higher intake of isoflavones is associated with a moderately lower risk of developing coronary heart disease. It may also reduce the risks of breast and colorectal cancer as well as the incidence of breast cancer recurrence. Consumption of isoflavones or soy foods is associated with reduced risks of endometrial and bladder cancer. Regarding the therapeutic effects on menopausal syndrome or other diseases, isoflavones have been found to alleviate vasomotor syndromes even after considering placebo effects, reduce bone loss in the spine and ameliorate hypertension and in vitro glycemic control. They may also alleviate depressive symptoms during pregnancy. On the other hand, isoflavones have not shown definitive effects regarding improving cognition and urogenital symptoms. Because of lacking standardization in the study designs, such as the ingredients and doses of isoflavones and the durations and outcomes of trials, it currently remains difficult to draw overall conclusions for all aspects of isoflavones. These limitations warrant further investigations of isoflavone use for women’s health.
DHA and Its Metabolites Have a Protective Role against Methylmercury-Induced Neurotoxicity in Mouse Primary Neuron and SH-SY5Y Cells
Authors: Oguro Ami , Fujita Kenta , Ishihara Yasuhiro , Yamamoto Megumi , Yamazaki Takeshi
Published: March 2021

The consumption of fish now involves a risk of methylmercury (MeHg) exposure but also provides the benefit of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) such as docosahexaenoic acid (DHA). Some epidemiological studies have suggested that the intake of DHA can alleviate the neurotoxicity of MeHg, but the underlying mechanism is not known. Herein, we observed that pretreatment with 0.1–1 µM DHA suppressed MeHg-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells and mouse primary neuronal cells. These effects of DHA were canceled in the presence of the retinoid X receptor (RXR) antagonist UVI3003. An RXR agonist, bexarotene, suppressed the cytotoxicity of MeHg. DHA also suppressed the MeHg-induced production of reactive oxygen species (ROS) via an induction of antioxidant genes (catalase and SOD1). Pretreatment with DHA did not change the incorporation of MeHg. We showed previously that in the brain, the intake of DHA increased the level of 19,20-DHDP, which is the metabolite produced by cytochrome P450 and soluble epoxide hydrolase from DHA. In the present study, we observed that 19,20-DHDP also suppressed neurotoxicity from MeHg. These results indicate that DHA and its metabolites have a protective role in MeHg-induced neurotoxicity.
(Pro)renin Receptor Is Present in Human Sperm and It Adversely Affects Sperm Fertility Ability
Authors: Gianzo Marta , Urizar-Arenaza Itziar , Muñoa-Hoyos Iraia , Larreategui Zaloa , Garrido Nicolás , Irazusta Jon , Subirán Nerea
Published: March 2021

Sperm fertility ability may be modulated by different molecular systems, such as the renin-angiotensin system (RAS). Although renin is one of its most relevant peptides, the presence and role of the (pro)renin receptor (PRR) is completely unknown. We have proved for the first time the existence of PRR and its transcript in human sperm by western blot and RT-PCR. Immunofluorescence studies showed that this receptor is mainly located in the apical region over the acrosome and in the postacrosomal region of the sperm head and along the sperm tail. In addition, this prospective cohort study also proves that semen samples with higher percentages of PRR-positive spermatozoa are associated with poor sperm motility, worse blastocyst development and no-viable blastocysts. Our results provide insight into how PRR play a negative role in sperm physiology that it may condition human embryo quality and development. An in-depth understanding of the role of PRR in sperm fertility can help elucidate its role in male infertility, as well as establish biomarkers for the diagnosis or selection of sperm to use during assisted reproductive techniques.
Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration
Authors: Tellman Tristen V. , Cruz Lissette A. , Grindel Brian J. , Farach-Carson Mary C.
Published: March 2021

The Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex at the cell surface of prostate cancer (PCa) cells influences cell–cell cohesion and dyscohesion. We investigated matrix metalloproteinase-7/matrilysin (MMP-7)’s ability to digest components of the PSPN Complex in bone metastatic PCa cells using in silico analyses and in vitro experiments. Results demonstrated that in addition to the heparan sulfate proteoglycan, perlecan, all components of the PSPN Complex were degraded by MMP-7. To investigate the functional consequences of PSPN Complex cleavage, we developed a preformed microtumor model to examine initiation of cell dispersion after MMP-7 digestion. We found that while perlecan fully decorated with glycosaminoglycan limited dispersion of PCa microtumors, MMP-7 initiated rapid dyscohesion and migration even with perlecan present. Additionally, we found that a bioactive peptide (PLN4) found in perlecan domain IV in a region subject to digestion by MMP-7 further enhanced cell dispersion along with MMP-7. We found that digestion of the PSPN Complex with MMP-7 destabilized cell–cell junctions in microtumors evidenced by loss of co-registration of E-cadherin and F-actin. We conclude that MMP-7 plays a key functional role in PCa cell transition from a cohesive, indolent phenotype to a dyscohesive, migratory phenotype favoring production of circulating tumor cells and metastasis to bone.
CRISPR/Cas9 Guided Mutagenesis of Grain Size 3 Confers Increased Rice (Oryza sativa L.) Grain Length by Regulating Cysteine Proteinase Inhibitor and Ubiquitin-Related Proteins
Authors: Usman Babar , Zhao Neng , Nawaz Gul , Qin Baoxiang , Liu Fang , Liu Yaoguang , Li Rongbai
Published: March 2021

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas9)-mediated genome editing has become an important way for molecular breeding in crop plants. To promote rice breeding, we edited the Grain Size 3 (GS3) gene for obtaining valuable and stable long-grain rice mutants. Furthermore, isobaric tags for the relative and absolute quantitation (iTRAQ)-based proteomic method were applied to determine the proteome-wide changes in the GS3 mutants compared with wild type (WT). Two target sites were designed to construct the vector, and the Agrobacterium-mediated method was used for rice transformation. Specific mutations were successfully introduced, and the grain length (GL) and 1000-grain weight (GWT) of the mutants were increased by 31.39% and 27.15%, respectively, compared with WT. The iTRAQ-based proteomic analysis revealed that a total of 31 proteins were differentially expressed in the GS3 mutants, including 20 up-regulated and 11 down-regulated proteins. Results showed that differentially expressed proteins (DEPs) were mainly related to cysteine synthase, cysteine proteinase inhibitor, vacuolar protein sorting-associated, ubiquitin, and DNA ligase. Furthermore, functional analysis revealed that DEPs were mostly enriched in cellular process, metabolic process, binding, transmembrane, structural, and catalytic activities. Pathway enrichment analysis revealed that DEPs were mainly involved in lipid metabolism and oxylipin biosynthesis. The protein-to-protein interaction (PPI) network found that proteins related to DNA damage-binding, ubiquitin-40S ribosomal, and cysteine proteinase inhibitor showed a higher degree of interaction. The homozygous mutant lines featured by stable inheritance and long-grain phenotype were obtained using the CRISPR/Cas9 system. This study provides a convenient and effective way of improving grain yield, which could significantly accelerate the breeding process of long-grain japonica parents and promote the development of high-yielding rice.
Sesquiterpene Lactone Deoxyelephantopin Isolated from Elephantopus scaber and Its Derivative DETD-35 Suppress BRAFV600E Mutant Melanoma Lung Metastasis in Mice
Authors: Cvetanova Biljana , Li Meng-Yi , Yang Chung-Chih , Hsiao Pei-Wen , Yang Yu-Chih , Feng Jia-Hua , Shen Ya-Ching , Nakagawa-Goto Kyoko , Lee Kuo-Hsiung , Shyur Lie-Fen
Published: March 2021

Melanoma is a highly metastatic disease with an increasing rate of incidence worldwide. It is treatment refractory and has poor clinical prognosis; therefore, the development of new therapeutic agents for metastatic melanoma are urgently required. In this study, we created a lung-seeking A375LM5IF4g/Luc BRAFV600E mutant melanoma cell clone and investigated the bioefficacy of a plant sesquiterpene lactone deoxyelephantopin (DET) and its novel semi-synthetic derivative, DETD-35, in suppressing metastatic A375LM5IF4g/Luc melanoma growth in vitro and in a xenograft mouse model. DET and DETD-35 treatment inhibited A375LM5IF4g/Luc cell proliferation, and induced G2/M cell-cycle arrest and apoptosis. Furthermore, A375LM5IF4g/Luc exhibited clonogenic, metastatic and invasive abilities, and several A375LM5IF4g/Luc metastasis markers, N-cadherin, MMP2, vimentin and integrin α4 were significantly suppressed by treatment with either compound. Interestingly, DET- and DETD-35-induced Reactive Oxygen Species (ROS) generation and glutathione (GSH) depletion were found to be upstream events important for the in vitro activities, because exogenous GSH supplementation blunted DET and DETD-35 effects on A375LM5IF4g/Luc cells. DET and DETD-35 also induced mitochondrial DNA mutation, superoxide production, mitochondrial bioenergetics dysfunction, and mitochondrial protein deregulation. Most importantly, DET and DETD-35 inhibited lung metastasis of A375LM5IF4g/Luc in NOD/SCID mice through inhibiting pulmonary vascular permeability and melanoma cell (Mel-A+) proliferation, angiogenesis (VEGF+, CD31+) and EMT (N-cadherin) in the tumor microenvironment in the lungs. These findings indicate that DET and DETD-35 may be useful in the intervention of lung metastatic BRAFV600E mutant melanoma.
Unravelling Regioselectivity of Leuconostoc citreum ABK-1 Alternansucrase by Acceptor Site Engineering
Authors: Wangpaiboon Karan , Sitthiyotha Thassanai , Chunsrivirot Surasak , Charoenwongpaiboon Thanapon , Pichyangkura Rath
Published: March 2021

Alternansucrase (ALT, EC 2.4.1.140) is a glucansucrase that can generate α-(1,3/1,6)-linked glucan from sucrose. Previously, the crystal structure of the first alternansucrase from Leuconostoc citreum NRRL B-1355 was successfully elucidated; it showed that alternansucrase might have two acceptor subsites (W675 and W543) responsible for the formation of alternating linked glucan. This work aimed to investigate the primary acceptor subsite (W675) by saturated mutagenesis using Leuconostoc citreum ABK-1 alternansucrase (LcALT). The substitution of other residues led to loss of overall activity, and formation of an alternan polymer with a nanoglucan was maintained when W675 was replaced with other aromatic residues. Conversely, substitution by nonaromatic residues led to the synthesis of oligosaccharides. Mutations at W675 could potentially cause LcALT to lose control of the acceptor molecule binding via maltose–acceptor reaction—as demonstrated by results from molecular dynamics simulations of the W675A variant. The formation of α-(1,2), α-(1,3), α-(1,4), and α-(1,6) linkages were detected from products of the W675A mutant. In contrast, the wild-type enzyme strictly synthesized α-(1,6) linkage on the maltose acceptor. This study examined the importance of W675 for transglycosylation, processivity, and regioselectivity of glucansucrases. Engineering glucansucrase active sites is one of the essential approaches to green tools for carbohydrate modification.
Molecular Mechanisms Underlying Remodeling of Ductus Arteriosus: Looking beyond the Prostaglandin Pathway
Authors: Hsu Ho-Wei , Lin Ting-Yi , Liu Yi-Ching , Yeh Jwu-Lai , Hsu Jong-Hau
Published: March 2021

The ductus arteriosus (DA) is a physiologic vessel crucial for fetal circulation. As a major regulating factor, the prostaglandin pathway has long been the target for DA patency maintenance or closure. However, the adverse effect of prostaglandins and their inhibitors has been a major unsolved clinical problem. Furthermore, a significant portion of patients with patent DA fail to respond to cyclooxygenase inhibitors that target the prostaglandin pathway. These unresponsive medical patients ultimately require surgical intervention and highlight the importance of exploring pathways independent from this well-recognized prostaglandin pathway. The clinical limitations of prostaglandin-targeting therapeutics prompted us to investigate molecules beyond the prostaglandin pathway. Thus, this article introduces molecules independent from the prostaglandin pathway based on their correlating mechanisms contributing to vascular remodeling. These molecules may serve as potential targets for future DA patency clinical management.
Perirenal Adipose Tissue—Current Knowledge and Future Opportunities
Authors: Grigoraș Adriana , Balan Raluca Anca , Căruntu Irina-Draga , Giușcă Simona Eliza , Lozneanu Ludmila , Avadanei Roxana Elena , Rusu Andreea , Riscanu Laura Adriana , Amalinei Cornelia
Published: March 2021

The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.
Quality of Life and Psychological Impact in Patients with Atopic Dermatitis
Authors: Talamonti Marina , Galluzzo Marco , Silvaggio Dionisio , Lombardo Paolo , Tartaglia Chiara , Bianchi Luca
Published: March 2021

Atopic dermatitis (AD) is a dermatological disorder that affects patients’ mental health and psychological state in complex ways. The importance of understanding the entire scope of this burden is well recognized, but there is limited comprehensive information about the resulting stress on adult patients with AD. This study aimed to determine the degree of psychological stress in patients with AD compared to healthy participants. A total of 352 adult patients participated in this cross-sectional study—174 with AD and 178 healthy participants. Demographic and clinical data were collected. Itch and sleep disturbance were assessed using a numeric rating scale and a visual analogue scale. The 20-item Toronto Alexithymia Scale (TAS-20) and Beck Depression Inventory (BDI) questionnaires were administered to assess the symptoms of alexithymia and depression. Quality of life (QOL) was assessed in AD patients using the Dermatology Quality Index. In our study, we found high TAS-20 and BDI scores among patients with AD. The prevalence of alexithymic personality features was 56.3% in patients with AD versus 21.3% in healthy controls (p < 0.001). Based on BDI scoring (BDI-21 > 13), depression was suspected in a significantly higher number of patients with AD than in the control group (56.9% (99/174) vs. 15.7% (28/178); p < 0.0001). Eczema Area and Severity Index (EASI) score did not show any significant correlations with psychological parameters. Among clinical parameters, only sleep disturbance was positively correlated with depression (R = 0.307, p < 0.005). Our data show that the severity index score as a representative factor of skin involvement has a limited role in predicting the effect of skin diseases on mental status. Screening and assessment for psychiatric disorders, QOL, and sleep disturbance in patients with atopic dermatitis cannot be neglected by physicians and they should be treated in clinical practice with the consideration of psychosomatic approaches.
Special Issue: Diagnosis and Management of Addiction and Other Mental Disorders (Dual Disorders)
Authors: Adan Ana , Torrens Marta
Published: March 2021

The term “dual disorder” (DD) refers to the coexistence or concurrence of at least one substance use disorder (SUD) and another mental disorder in the same person, as the World Health Organization established in its lexicon of alcohol and drug terms [...]
Study of the Operating Characteristics for the High-Speed Water Jet Pump Installed on the Underwater Vehicle with Different Cruising Speeds
Authors: Lu Yeming , Liu Haoran , Wang Xiaofang , Wang Hui
Published: March 2021

Due to the higher propulsive efficiency, lesser vibration, and better maneuverability, the water jet pump is widely applied to high-speed underwater vehicles. By taking a newly developed water jet pump system as the object, the corresponding underwater vehicle’s operating characteristics affected by different cruising speeds (15.43, 30.86, and 52.47 m/s) were investigated. The steady results reply that the cruising speed increase will result in the decline of the overall performances comprised of the head, the efficiency, the thrust, and the power. While, by using different analyzing methods, the unsteady results are listed as follows: (1) The energy loss theory denotes that the increasing cruising speed promoted the kinetic energy diffusion from the Reynolds stress and viscous stress and depress the turbulent kinetic energy production and the viscous dissipation. (2) The statistical PLS method reveals that the tip load effect on the leakage flow becomes weaker when the cruising speed becomes larger, while the effect from the scraping pressure has a completely opposite trend. (3) Further unsteady analysis implies that the increasing cruising speed makes the pressure pulsation larger and makes the radial force, the axial force, and the cloudy cavity size smaller.
β-Galactosidase-Producing Isolates in Mucoromycota: Screening, Enzyme Production, and Applications for Functional Oligosaccharide Synthesis
Authors: Volford Bettina , Varga Mónika , Szekeres András , Kotogán Alexandra , Nagy Gábor , Vágvölgyi Csaba , Papp Tamás , Takó Miklós
Published: March 2021

β-Galactosidases of Mucoromycota are rarely studied, although this group of filamentous fungi is an excellent source of many industrial enzymes. In this study, 99 isolates from the genera Lichtheimia, Mortierella, Mucor, Rhizomucor, Rhizopus and Umbelopsis, were screened for their β-galactosidase activity using a chromogenic agar approach. Ten isolates from the best producers were selected, and the activity was further investigated in submerged (SmF) and solid-state (SSF) fermentation systems containing lactose and/or wheat bran substrates as enzyme production inducers. Wheat bran proved to be efficient for the enzyme production under both SmF and SSF conditions, giving maximum specific activity yields from 32 to 12,064 U/mg protein and from 783 to 22,720 U/mg protein, respectively. Oligosaccharide synthesis tests revealed the suitability of crude β-galactosidases from Lichtheimia ramosa Szeged Microbiological Collection (SZMC) 11360 and Rhizomucor pusillus SZMC 11025 to catalyze transgalactosylation reactions. In addition, the crude enzyme extracts had transfructosylation activity, resulting in the formation of fructo-oligosaccharide molecules in a sucrose-containing environment. The maximal oligosaccharide concentration varied between 0.0158 and 2.236 g/L depending on the crude enzyme and the initial material. Some oligosaccharide-enriched mixtures supported the growth of probiotics, indicating the potential of the studied enzyme extracts in future prebiotic synthesis processes.
Characterization of the Ergosterol Biosynthesis Pathway in Ceratocystidaceae
Authors: Sayari Mohammad , van der Nest Magrieta A. , Steenkamp Emma T. , Rahimlou Saleh , Hammerbacher Almuth , Wingfield Brenda D.
Published: March 2021

Terpenes represent the biggest group of natural compounds on earth. This large class of organic hydrocarbons is distributed among all cellular organisms, including fungi. The different classes of terpenes produced by fungi are mono, sesqui, di- and triterpenes, although triterpene ergosterol is the main sterol identified in cell membranes of these organisms. The availability of genomic data from members in the Ceratocystidaceae enabled the detection and characterization of the genes encoding the enzymes in the mevalonate and ergosterol biosynthetic pathways. Using a bioinformatics approach, fungal orthologs of sterol biosynthesis genes in nine different species of the Ceratocystidaceae were identified. Ergosterol and some of the intermediates in the pathway were also detected in seven species (Ceratocystis manginecans, C. adiposa, Huntiella moniliformis, Thielaviopsis punctulata, Bretziella fagacearum, Endoconidiophora polonica and Davidsoniella virescens), using gas chromatography-mass spectrometry analysis. The average ergosterol content differed among different genera of Ceratocystidaceae. We also identified all possible terpene related genes and possible biosynthetic clusters in the genomes used in this study. We found a highly conserved terpene biosynthesis gene cluster containing some genes encoding ergosterol biosynthesis enzymes in the analysed genomes. An additional possible terpene gene cluster was also identified in all of the Ceratocystidaceae. We also evaluated the sensitivity of the Ceratocystidaceae to a triazole fungicide that inhibits ergosterol synthesis. The results showed that different members of this family behave differently when exposed to different concentrations of triazole tebuconazole.