bluuebunny/crossref_metadata_2025 huggingface dataset:
Variety of Surgical Guides and Protocols for Bone Reduction Prior to Implant Placement: A Narrative Review
Authors: Mijiritsky Eitan , Ben Zaken Hadar , Shacham Maayan , Cinar Ihsan Caglar , Tore Cem , Nagy Katalin , Ganz Scott D.
Published: February 2021

Edentulism and terminal dentition are still considered significant problems in the dental field, posing a great challenge for surgical and restorative solutions especially with immediate loading protocols. When the implant placement is planned immediately after extraction with irregular bone topography or there is an un-leveled alveolar ridge topography for any other reason, bone reduction may be required to level the alveolar crest in order to create the desired bone architecture allowing for sufficient bone width for implant placement and to insure adequate inter-arch restorative space. Bone reduction protocols exist in analog and digitally planned methodologies, with or without surgical guides to achieve the desired bone level based upon the desired position of the implants with regard to the restorative outcome. The objective of this paper was to scrutinize the literature regarding the practice of bone reduction in conjunction with implant placement, and to review different types of bone reduction surgical guides. Results: The literature reveals different protocols that provide for bone reduction with a variety of bone reduction methods. The digitally-planned surgical guide based on Cone-Beam computerized tomography (CBCT) scan reconstructed data can improve accuracy, reduce surgical time, and deliver the desired bone level for the implant placement with fewer surgical and restorative complications. The clinician’s choice is based on personal experience, training, and comfort with a specific guide type. Conclusions: Bone reduction, when required, is an indispensable step in the surgical procedure to attain suitable width of bone in anticipation of implant placement ideally determined by the desired tooth position and required restorative space based on material selection for the chosen framework design, i.e., hybrid, monolithic zirconia. Additionally, bone reduction and implant placement can be accomplished in the same surgical procedure, minimizing trauma and the need for two separate interventions.
Late Menarche, Not Reproductive Period, Is Associated with Poor Cognitive Function in Postmenopausal Women in Taiwan
Authors: Chou Hung-Tse , Wu Pei-Yu , Huang Jiun-Chi , Chen Szu-Chia , Ho Wan-Yi
Published: February 2021

Female sex hormones such as estrogen and progesterone play an important role in the regulation of a woman’s body, including cognition and neurogenesis. However, the effects of age at menarche and reproductive period on cognitive function are still controversial. The aim of this study was to investigate the relationships between age at menarche and reproductive period with cognitive impairment. Data were obtained from the Taiwan Biobank. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and its five subdomains. Multivariable linear regression analysis revealed that an old age at menarche (per one year; coefficient β, −0.189; p = 0.020) was significantly associated with a low total MMSE score, whereas reproductive period (p = 0.733) was not significantly associated with total MMSE score. Furthermore, an old age at menarche was significantly associated with low MMSE G2 (registration) (per one year; coefficient β, −0.022; p = 0.035) and G5 (language, construction and obey) scores (per one year; coefficient β, −0.054; p = 0.047). However, age at menarche was not significantly associated with MMSE G1 (orientation), G3 (attention and calculation) and G4 (recall) scores. In addition, reproductive period was not significantly associated with any MMSE subscores. Late menarche was associated with poor cognitive function, including low total MMSE score and low MMSE G2 and G5 scores. However, reproductive period was not associated with cognitive function in postmenopausal women.
An Improved Stress-Scale Specifically Designed to Measure Stress of Women with Newly Diagnosed Breast Cancer
Authors: Lee Tso-Ying , Hsing Shih-Chun , Li Chin-Ching
Published: February 2021

Most breast cancer patients are middle-aged women actively involved in establishing a family, developing a career, or raising children. With the exception of the Newly Diagnosed Breast Cancer Stress Scale (NDBCSS), few stress scales have been designed for women with breast cancer. This study checked the dimensionality of the NDBCSS by confirmatory factor analysis (CFA) and the results showed a poor fit, indicating an urgent need for improvement. Exploratory factor analysis (EFA) using the varimax rotation method was performed to improve the model, the revised NDBCSS (NDBCSS-R), which showed a good Kaiser-Meyer-Olkin value, Bartlett’s test of sphericity, and internal consistency reliability. The NDBCSS-R showed improved indices compared with NDBCSS, including: chi-square fit statistics/degree of freedom (CMIN/DF), goodness-of-fit index (GFI), adjusted goodness of fit index (AGFI), normed fix index (NFI), relative fit index (RFI), incremental fix index (IFI), Tucker–Lewis index (TLI), comparative fix index (CFI), root mean square error of approximation (RMSEA), root mean square residual (RMR), parsimonious goodness-fit-index (PGFI), and parsimonious normed fit index (PNFI). In conclusion, the improved NDBCSS-R can provide health professionals with an early understanding of the stress levels of women with breast cancer so that they can provide immediate medical intervention to prevent vicious cycles in a timely manner.
A Data-Driven Quasi-Dynamic Traffic Assignment Model Integrating Multi-Source Traffic Sensor Data on the Expressway Network
Authors: Zeng Xing , Guan Xuefeng , Wu Huayi , Xiao Heping
Published: February 2021

Static traffic assignment (STA) models have been widely utilized in the field of strategic transport planning. However, STA models cannot fully represent the dynamic road conditions and suffer from inaccurate assignment during traffic congestion. At the same time, an increasing number of installed sensors have become an important means of detecting dynamic road conditions. To address the shortcomings of STA models, we integrate multi-source traffic sensor datasets and propose a novel data-driven quasi-dynamic traffic assignment model, named DQ-DTA. In this model, records of toll stations are used for time-varying travel demand estimation. GPS trajectory datasets of vehicles are further used to calculate the dynamic link costs of the road network, replacing the imprecise Bureau of Public Roads (BPR) function. Moreover, license plate recognition (LPR) data are used to design a statistical probability-based multipath assignment method to capture travelers’ route choices. The expressway network in the Hunan province is selected as the study area, and several classic STA models are also chosen for performance comparison. Experimental results demonstrate that the accuracy of the proposed DQ-DTA model is about 6% higher than that of the chosen STA models.
Landslide Susceptibility Mapping and Assessment Using Geospatial Platforms and Weights of Evidence (WoE) Method in the Indian Himalayan Region: Recent Developments, Gaps, and Future Directions
Authors: Batar Amit Kumar , Watanabe Teiji
Published: February 2021

The Himalayan region and hilly areas face severe challenges due to landslide occurrences during the rainy seasons in India, and the study area, i.e., the Rudraprayag district, is no exception. However, the landslide related database and research are still inadequate in these landslide-prone areas. The main purpose of this study is: (1) to prepare the multi-temporal landslide inventory map using geospatial platforms in the data-scarce environment; (2) to evaluate the landslide susceptibility map using weights of evidence (WoE) method in the Geographical Information System (GIS) environment at the district level; and (3) to provide a comprehensive understanding of recent developments, gaps, and future directions related to landslide inventory, susceptibility mapping, and risk assessment in the Indian context. Firstly, 293 landslides polygon were manually digitized using the BHUVAN (Indian earth observation visualization) and Google Earth® from 2011 to 2013. Secondly, a total of 14 landslide causative factors viz. geology, geomorphology, soil type, soil depth, slope angle, slope aspect, relative relief, distance to faults, distance to thrusts, distance to lineaments, distance to streams, distance to roads, land use/cover, and altitude zones were selected based on the previous study. Then, the WoE method was applied to assign the weights for each class of causative factors to obtain a landslide susceptibility map. Afterward, the final landslide susceptibility map was divided into five susceptibility classes (very high, high, medium, low, and very low classes). Later, the validation of the landslide susceptibility map was checked against randomly selected landslides using IDRISI SELVA 17.0 software. Our study results show that medium to very high landslide susceptibilities had occurred in the non-forest areas, mainly scrubland, pastureland, and barren land. The results show that medium to very high landslide susceptibilities areas are in the upper catchment areas of the Mandakini river and adjacent to the National Highways (107 and 07). The results also show that landslide susceptibility is high in high relative relief areas and shallow soil, near thrusts and faults, and on southeast, south, and west-facing steep slopes. The WoE method achieved a prediction accuracy of 85.7%, indicating good accuracy of the model. Thus, this landslide susceptibility map could help the local governments in landslide hazard mitigation, land use planning, and landscape protection.
Correlation Analysis and Reconstruction of the Geometric Evaluation Indicator System of the Discrete Global Grid
Authors: Wang Zheng , Zhao Xuesheng , Sun Wenbin , Luo Fuli , Li Yalu , Duan Yuanzheng
Published: February 2021

Although a Discrete Global Grid (DGG) is uniform in its initial subdivision, its geometric deformation increases with the level of subdivisions. The Goodchild Criteria are often used to evaluate the quality of DGGs. However, some indicators in these criteria are mutually incompatible and overlap. If the criteria are used directly, the evaluation of the DGGs is inaccurate or unreliable. In this paper, we calculated and analyzed the correlation between the evaluation indicators of the DGG and reconstructed a quality evaluation system of DGGs with independent indicators. Firstly, we classified the Goodchild Criteria into quantitative and qualitative indicators. Then, we calculated the correlation among the quantitative indicators and extracted the independent evaluation factors and related weights of the observed values by factor analysis. After eliminating or merging the incompatible and overlapping quantitative indicators and performing a logical reasoning of the qualitative indicators, we reconstructed a comprehensive evaluation system with independent indicators. Finally, taking the Quaternary Triangular Mesh (QTM) model as an example, we verified the independence of the indicators and the feasibility of the evaluation system. The new indicator system ensures the reliability of the evaluation of DGGs in many fields.
Distribution of Lightning Accidents in Sri Lanka from 1974 to 2019 Using the DesInventar Database
Authors: Edirisinghe Mahesh , Maduranga Uruvitiya Gamage Dilaj
Published: February 2021

The reported lightning accidents that are available in the DesInventar database—which consist of 549 deaths, 498 injured people, 39 destroyed houses, and 741 damaged houses—were analyzed in terms of their geographical and temporal variation. The average lightning flash densities were calculated using zonal statistics using the geographic information system (GIS), referring to the respective raster maps generated based on Lightning Imaging Sensor (LIS) data from the Tropical Rainfall Measurement Mission (TRMM) Satellite. Hence, the variations of the lightning accidents—monthly and climate season-wise—in response to the lightning flash density were also reported. The calculated average lightning flash density in Sri Lanka is 8.26 flashes km−2 year−1, and the maximum average lightning flash density of 31.33 flashes km−2 year−1 is observed in April in a calendar year. April seems to be more vulnerable to lightning accidents, as the maximum number of deaths (150 deaths) and injuries (147 injuries) were recorded in this month. Most of the high-risk lightning accident regions that were identified in Sri Lanka are well known for agricultural activities, and those activities will eventually create the platform for lightning victims. In Sri Lanka, in a year, 12 people were killed and 11 people were injured, based on the reported accidents from 1974 to 2019. Conversely, a substantial increase in the number of deaths, injuries, and incidents of property damage has been observed in the last two decades (2000–2019). On average, for the period from 2000 to 2019, 18 people were killed and 16 people were injured per year. Furthermore, considering the population of the country, 0.56 people per million per year were killed, and 0.51 people per million per year were injured due to lightning accidents based on the reported accidents from 1974 to 2019. Moreover, for the 2000–2019 period, these estimated values are significantly higher; 0.86 people per million per year were killed, and 0.77 people per million per year were injured.
Assessment of Neotectonic Landscape Deformation in Evia Island, Greece, Using GIS-Based Multi-Criteria Analysis
Authors: Valkanou Kanella , Karymbalis Efthimios , Papanastassiou Dimitris , Soldati Mauro , Chalkias Christos , Gaki-Papanastassiou Kalliopi
Published: February 2021

This study deals with the assessment and mapping of neotectonic landscape deformation in the northern part of the Evia Island (Central Greece). Multi-Criteria Decision Analysis (MCDA) utilizing Analytic Hierarchy Process (AHP) and Weighted Linear Combination (WLC) procedures were conducted for the calculation of the Neotectonic Landscape Deformation Index (NLDI). The study is based on the combination of morphotectonic, geomorphological and geological parameters. The GIS-based spatial MCDA led to the classification of the study area into five classes of neotectonic deformation (from very low to very high) and to a neotectonic deformation map. The results were compared with the outputs of a relative tectonic activity classification approach based on quantitative geomorphic analysis at a regional scale, including site-specific field observations. Areas of high and very high deformation are related to the major active faults of Dirfis, Kandili and Gregolimano–Telethrio. Other minor active normal faults of medium to high seismic risk level, affecting the northern and northeastern parts of the island, are also associated with areas of intense landscape neotectonic deformation.
Integration of an InSAR and ANN for Sinkhole Susceptibility Mapping: A Case Study from Kirikkale-Delice (Turkey)
Authors: Nefeslioglu Hakan A. , Tavus Beste , Er Melahat , Ertugrul Gamze , Ozdemir Aybuke , Kaya Alperen , Kocaman Sultan
Published: February 2021

Suitable route determination for linear engineering structures is a fundamental problem in engineering geology. Rapid evaluation of alternative routes is essential, and novel approaches are indispensable. This study aims to integrate various InSAR (Interferometric Synthetic Aperture Radar) techniques for sinkhole susceptibility mapping in the Kirikkale-Delice Region of Turkey, in which sinkhole formations have been observed in evaporitic units and a high-speed train railway route has been planned. Nine months (2019–2020) of ground deformations were determined using data from the European Space Agency’s (ESA) Sentinel-1A/1B satellites. A sinkhole inventory was prepared manually using satellite optical imagery and employed in an ANN (Artificial Neural Network) model with topographic conditioning factors derived from InSAR digital elevation models (DEMs) and morphological lineaments. The results indicate that high deformation areas on the vertical displacement map and sinkhole-prone areas on the sinkhole susceptibility map (SSM) almost coincide. InSAR techniques are useful for long-term deformation monitoring and can be successfully associated in sinkhole susceptibility mapping using an ANN. Continuous monitoring is recommended for existing sinkholes and highly susceptible areas, and SSMs should be updated with new results. Up-to-date SSMs are crucial for the route selection, planning, and construction of important transportation elements, as well as settlement site selection, in such regions.
Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa
Authors: Kuehlewein Laura , Zobor Ditta , Stingl Katarina , Kempf Melanie , Nasser Fadi , Bernd Antje , Biskup Saskia , Cremers Frans P.M. , Khan Muhammad Imran , Mazzola Pascale , Schäferhoff Karin , Heinrich Tilman , Haack Tobias B. , Wissinger Bernd , Zrenner Eberhart , Weisschuh Nicole , Kohl Susanne
Published: February 2021

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.
Multiple Myeloma Bone Disease: Implication of MicroRNAs in Its Molecular Background
Authors: Papanota Aristea-Maria , Karousi Paraskevi , Kontos Christos K. , Ntanasis-Stathopoulos Ioannis , Scorilas Andreas , Terpos Evangelos
Published: February 2021

Multiple myeloma (MM) is a common hematological malignancy arising from terminally differentiated plasma cells. In the majority of cases, symptomatic disease is characterized by the presence of bone disease. Multiple myeloma bone disease (MMBD) is a result of an imbalance in the bone-remodeling process that leads to increased osteoclast activity and decreased osteoblast activity. The molecular background of MMBD appears intriguingly complex, as several signaling pathways and cell-to-cell interactions are implicated in the pathophysiology of MMBD. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the expression of their target mRNAs. Numerous miRNAs have been witnessed to be involved in cancer and hematological malignancies and their role has been characterized either as oncogenic or oncosuppressive. Recently, scientific research turned towards miRNAs as regulators of MMBD. Scientific data support that miRNAs finely regulate the majority of the signaling pathways implicated in MMBD. In this review, we provide concise information regarding the molecular pathways with a significant role in MMBD and the miRNAs implicated in their regulation. Moreover, we discuss their utility as molecular biomarkers and highlight the putative usage of miRNAs as novel molecular targets for targeted therapy in MMBD.
RGDS-Modified Superporous Poly(2-Hydroxyethyl Methacrylate)-Based Scaffolds as 3D In Vitro Leukemia Model
Authors: Svozilová Hana , Plichta Zdeněk , Proks Vladimír , Studená Radana , Baloun Jiří , Doubek Michael , Pospíšilová Šárka , Horák Daniel
Published: February 2021

Superporous poly(2-hydroxyethyl methacrylate-co-2-aminoethyl methacrylate) (P(HEMA-AEMA)) hydrogel scaffolds are designed for in vitro 3D culturing of leukemic B cells. Hydrogel porosity, which influences cell functions and growth, is introduced by adding ammonium oxalate needle-like crystals in the polymerization mixture. To improve cell vitality, cell-adhesive Arg-Gly-Asp-Ser (RGDS) peptide is immobilized on the N-(γ-maleimidobutyryloxy)succinimide-activated P(HEMA-AEMA) hydrogels via reaction of SH with maleimide groups. This modification is especially suitable for the survival of primary chronic lymphocytic leukemia cells (B-CLLs) in 3D cell culture. No other tested stimuli (interleukin-4, CD40 ligand, or shaking) can further improve B-CLL survival or metabolic activity. Both unmodified and RGDS-modified P(HEMA-AEMA) scaffolds serve as a long-term (70 days) 3D culture platforms for HS-5 and M2-10B4 bone marrow stromal cell lines and MEC-1 and HG-3 B-CLL cell lines, although the adherent cells retain their physiological morphologies, preferably on RGDS-modified hydrogels. Moreover, the porosity of hydrogels allows direct cell lysis, followed by efficient DNA isolation from the 3D-cultured cells. P(HEMA-AEMA)-RGDS thus serves as a suitable 3D in vitro leukemia model that enables molecular and metabolic assays and allows imaging of cell morphology, interactions, and migration by confocal microscopy. Such applications can prospectively assist in testing of drugs to treat this frequently recurring or refractory cancer.
Peptides from the Intestinal Tract of Breast Milk-Fed Infants Have Antimicrobial and Bifidogenic Activity
Authors: Beverly Robert L. , Woonnimani Prajna , Scottoline Brian P. , Lueangsakulthai Jiraporn , Dallas David C.
Published: February 2021

For bioactive milk peptides to be relevant to infant health, they must be released by gastrointestinal proteolysis and resist further proteolysis until they reach their site of activity. The intestinal tract is the likeliest site for most bioactivities, but it is currently unknown whether bioactive milk peptides are present therein. The purpose of the present study was to identify antimicrobial and bifidogenic peptides in the infant intestinal tract. Milk peptides were extracted from infant intestinal samples, and the activities of the bulk peptide extracts were determined by measuring growth of Escherichia coli, Staphylococcus aureus, and Bifidobacterium longum spp. infantis after incubation with serial dilutions. The peptide profiles of active and inactive samples were determined by peptidomics analysis and compared to identify candidate peptides for bioactivity testing. We extracted peptides from 29 intestinal samples collected from 16 infants. Five samples had antimicrobial activity against S. aureus and six samples had bifidogenic activity for B. infantis. We narrowed down a list of 6645 milk peptides to 11 candidate peptides for synthesis, of which 6 fully inhibited E. coli and S. aureus growth at concentrations of 2500 and 3000 µg/mL. This study provides evidence for the potential bioactivity of milk peptides in the infant intestinal tract.
Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes
Authors: Louwagie Eli J. , Larsen Tricia D. , Wachal Angela L. , Gandy Tyler C.T. , Baack Michelle L.
Published: February 2021

Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer.
High Throughput Proteomic Exploration of Hypothermic Preservation Reveals Active Processes within the Cell Associated with Cold Ischemia Kinetic
Authors: Pasini-Chabot Ophélie , Vincent Julia , Le Pape Sylvain , Lepoittevin Maryne , Kaaki Wassim , Woillard Jean-Baptiste , Giraud Sebastien , Bourmeyster Nicolas , Hauet Thierry , Thuillier Raphael
Published: February 2021

The demand for organs to be transplanted increases pressure on procurement centers, to the detriment of organ quality, increasing complications. New preservation protocols are urgently needed, requiring an in-depth understanding of ischemia-reperfusion mechanisms. We performed a proteomic analysis using LC-MS/MS-TOF data analyzed through R software and Cytoscape’s ClueGO application, comparing the proteome of kidney endothelial cells, key cell type, subjected to 3, 6, 12, 19, and 24 h of cold ischemia and 6 h reperfusion. Critical pathways such as energy metabolism, cytoskeleton structure/transport system, and gene transcription/translation were modulated. Important time windows were revealed: a—during the first 3 h, central proteins were upregulated within these pathways; b—the majority of these upregulations were maintained until 12 h cold ischemia time (CIT); c—after that time, the overall decrease in protein expression was observed; d—at reperfusion, proteins expressed in response to cold ischemia were all downregulated. This shows that cold ischemia is not a simple slowing down of metabolism, as deep changes take place within the proteome on major pathways. Time-sensitive expression of key protein reveals possible quality biomarkers as well as potential targets for new strategies to maintain or optimize organ quality.
Transcription Factor ChbZIP1 from Alkaliphilic Microalgae Chlorella sp. BLD Enhancing Alkaline Tolerance in Transgenic Arabidopsis thaliana
Authors: Qu Dehui , Show Pau-Loke , Miao Xiaoling
Published: February 2021

Saline-alkali soil has become an important environmental problem for crop productivity. One of the most effective approaches is to cultivate new stress-tolerant plants through genetic engineering. Through RNA-seq analysis and RT-PCR validation, a novel bZIP transcription factor ChbZIP1, which is significantly upregulated at alkali conditions, was obtained from alkaliphilic microalgae Chlorella sp. BLD. Overexpression of ChbZIP1 in Saccharomyces cerevisiae and Arabidopsis increased their alkali resistance, indicating ChbZIP1 may play important roles in alkali stress response. Through subcellular localization and transcriptional activation activity analyses, we found that ChbZIP1 is a nuclear-localized bZIP TF with transactivation activity to bind with the motif of G-box 2 (TGACGT). Functional analysis found that genes such as GPX1, DOX1, CAT2, and EMB, which contained G-box 2 and were associated with oxidative stress, were significantly upregulated in Arabidopsis with ChbZIP1 overexpression. The antioxidant ability was also enhanced in transgenic Arabidopsis. These results indicate that ChbZIP1 might mediate plant adaptation to alkali stress through the active oxygen detoxification pathway. Thus, ChbZIP1 may contribute to genetically improving plants’ tolerance to alkali stress.
Cardioprotective Properties of Mannitol—Involvement of Mitochondrial Potassium Channels
Authors: Feige Katharina , Rubbert Janine , Raupach Annika , Stroethoff Martin , Heinen André , Hollmann Markus W. , Huhn Ragnar , Torregroza Carolin
Published: February 2021

Cardiac preconditioning (PC) and postconditioning (PoC) are powerful measures against the consequences of myocardial ischemia and reperfusion (I/R) injury. Mannitol—a hyperosmolar solution—is clinically used for treatment of intracranial and intraocular pressure or promotion of diuresis in renal failure. Next to these clinical indications, different organ-protective properties—e.g., perioperative neuroprotection—are described. However, whether Mannitol also confers cardioprotection via a pre- and/or postconditioning stimulus, possibly reducing consequences of I/R injury, remains to be seen. Therefore, in the present study we investigated whether (1) Mannitol-induced pre- and/or postconditioning induces myocardial infarct size reduction and (2) activation of mitochondrial ATP-sensitive potassium (mKATP) channels is involved in cardioprotection by Mannitol. Experiments were performed on isolated hearts of male Wistar rats via a pressure controlled Langendorff system, randomized into 7 groups. Each heart underwent 33 min of global ischemia and 60 min of reperfusion. Control hearts (Con) received Krebs–Henseleit buffer as vehicle only. Pre- and postconditioning was achieved by administration of 11 mmol/L Mannitol for 10 min before ischemia (Man-PC) or immediately at the onset of reperfusion (Man-PoC), respectively. In further groups, the mKATP channel blocker 5HD, was applied with and without Mannitol, to determine the potential underlying cardioprotective mechanisms. Primary endpoint was infarct size, determined by triphenyltetrazolium chloride staining. Mannitol significantly reduced infarct size both as a pre- (Man-PC) and postconditioning (Man-PoC) stimulus compared to control hearts (Man-PC: 31 ± 4%; Man-PoC: 35 ± 6%, each p < 0.05 vs. Con: 57 ± 9%). The mKATP channel inhibitor completely abrogated the cardioprotective effect of Mannitol-induced pre- (5HD-PC-Man-PC: 59 ± 8%, p < 0.05 vs. Man-PC) and postconditioning (5HD-PoC-Man-PoC: 59 ± 10% vs. p < 0.05 Man-PoC). Infarct size was not influenced by 5HD itself (5HD-PC: 60 ± 14%; 5HD-PoC: 54 ± 14%, each ns vs. Con). This study demonstrates that Mannitol (1) induces myocardial pre- and postconditioning and (2) confers cardioprotection via activation of mKATP channels.
Combined Transcriptomic and Metabolomic Analysis Reveals the Role of Phenylpropanoid Biosynthesis Pathway in the Salt Tolerance Process of Sophora alopecuroides
Authors: Zhu Youcheng , Wang Qingyu , Wang Ying , Xu Yang , Li Jingwen , Zhao Shihui , Wang Doudou , Ma Zhipeng , Yan Fan , Liu Yajing
Published: February 2021

Salt stress is the main abiotic stress that limits crop yield and agricultural development. Therefore, it is imperative to study the effects of salt stress on plants and the mechanisms through which plants respond to salt stress. In this study, we used transcriptomics and metabolomics to explore the effects of salt stress on Sophora alopecuroides. We found that salt stress incurred significant gene expression and metabolite changes at 0, 4, 24, 48, and 72 h. The integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes (DEGs) and differential metabolites (DMs) obtained in the phenylpropanoid biosynthesis pathway were significantly correlated under salt stress. Of these, 28 DEGs and seven DMs were involved in lignin synthesis and 23 DEGs and seven DMs were involved in flavonoid synthesis. Under salt stress, the expression of genes and metabolites related to lignin and flavonoid synthesis changed significantly. Lignin and flavonoids may participate in the removal of reactive oxygen species (ROS) in the root tissue of S. alopecuroides and reduced the damage caused under salt stress. Our research provides new ideas and genetic resources to study the mechanism of plant responses to salt stress and further improve the salt tolerance of plants.
Molecular Determinants of the Kinetic Binding Properties of Antihistamines at the Histamine H1 Receptors
Authors: Akimoto Hayato , Uesawa Yoshihiro , Hishinuma Shigeru
Published: February 2021

The binding affinity of ligands for their receptors is determined by their kinetic and thermodynamic binding properties. Kinetic analyses of the rate constants of association and dissociation (kon and koff, respectively) of antihistamines have suggested that second-generation antihistamines have a long duration of action owing to the long residence time (1/koff) at the H1 receptors. In this study, we examined the relationship between the kinetic and thermodynamic binding properties of antihistamines, followed by an evaluation of the structural determinants responsible for their kinetic binding properties using quantitative structure–activity relationship (QSAR) analyses. We found that whereas the binding enthalpy and entropy might contribute to the increase and decrease, respectively, in the koff values, there was no significant relationship with the kon values. QSAR analyses indicated that kon and koff values could be determined by the descriptors FASA_H (water-accessible surface area of all hydrophobic atoms divided by total water-accessible surface area) and vsurf_CW2 (a 3D molecular field descriptor weighted by capacity factor 2, the ratio of the hydrophilic surface to the total molecular surface), respectively. These findings provide further insight into the mechanisms by which the kinetic binding properties of antihistamines are regulated by their thermodynamic binding forces and physicochemical properties.
New Era of Immunotherapy in Pediatric Brain Tumors: Chimeric Antigen Receptor T-Cell Therapy
Authors: Wu Wan-Tai , Lin Wen-Ying , Chen Yi-Wei , Lin Chun-Fu , Wang Hsin-Hui , Wu Szu-Hsien , Lee Yi-Yen
Published: February 2021

Immunotherapy, including chimeric antigen receptor (CAR) T-cell therapy, immune checkpoint inhibitors, cancer vaccines, and dendritic cell therapy, has been incorporated as a fifth modality of modern cancer care, along with surgery, radiation, chemotherapy, and target therapy. Among them, CAR T-cell therapy emerges as one of the most promising treatments. In 2017, the first two CAR T-cell drugs, tisagenlecleucel and axicabtagene ciloleucel for B-cell acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL), respectively, were approved by the Food and Drug Administration (FDA). In addition to the successful applications to hematological malignancies, CAR T-cell therapy has been investigated to potentially treat solid tumors, including pediatric brain tumor, which serves as the leading cause of cancer-associated death for children and adolescents. However, the employment of CAR T-cell therapy in pediatric brain tumors still faces multiple challenges, such as CAR T-cell transportation and expansion through the blood–brain barrier, and identification of the specific target antigen on the tumor surface and immunosuppressive tumor microenvironment. Nevertheless, encouraging outcomes in both clinical and preclinical trials are coming to light. In this article, we outline the current propitious progress and discuss the obstacles needed to be overcome in order to unveil a new era of treatment in pediatric brain tumors.
Controlling Ratios of Plasmid-Based Double Cut Donor and CRISPR/Cas9 Components to Enhance Targeted Integration of Transgenes in Chinese Hamster Ovary Cells
Authors: Shin Sung Wook , Kim Dongwoo , Lee Jae Seong
Published: February 2021

Chinese hamster ovary (CHO) cells are the most valuable expression host for the commercial production of biotherapeutics. Recent trends in recombinant CHO cell-line development have focused on the site-specific integration of transgenes encoding recombinant proteins over random integration. However, the low efficiency of homology-directed repair upon transfection of Cas9, single-guide RNA (sgRNA), and the donor template has limited its feasibility. Previously, we demonstrated that a double-cut donor (DCD) system enables highly efficient CRISPR/Cas9-mediated targeted integration (TI) in CHO cells. Here, we describe several CRISPR/Cas9 vector systems based on DCD templates using a promoter trap-based TI monitoring cell line. Among them, a multi-component (MC) system consisting of an sgRNA/DCD vector and Cas9 expression vector showed an approximate 1.5-fold increase in knock-in (KI) efficiency compared to the previous DCD system, when a systematically optimized relative ratio of sgRNA/DCD and Cas9 vector was applied. Our optimization efforts revealed that concurrently increasing sgRNA and DCD components relative to Cas9 correlated positively with KI efficiency at a single KI site. Furthermore, we explored component bottlenecks, such as effects of sgRNA components and applicability of the MC system on simultaneous double KI. Taken together, we improved the DCD vector design by tailoring plasmid constructs and relative component ratios, and this system can be widely used in the TI strategy of transgenes, particularly in CHO cell line development and engineering.
Progress in the Development of Eukaryotic Elongation Factor 2 Kinase (eEF2K) Natural Product and Synthetic Small Molecule Inhibitors for Cancer Chemotherapy
Authors: Zhang Bin , Zou Jiamei , Zhang Qiting , Wang Ze , Wang Ning , He Shan , Zhao Yufen , Naman C. Benjamin
Published: February 2021

Eukaryotic elongation factor 2 kinase (eEF2K or Ca2+/calmodulin-dependent protein kinase, CAMKIII) is a new member of an atypical α-kinase family different from conventional protein kinases that is now considered as a potential target for the treatment of cancer. This protein regulates the phosphorylation of eukaryotic elongation factor 2 (eEF2) to restrain activity and inhibit the elongation stage of protein synthesis. Mounting evidence shows that eEF2K regulates the cell cycle, autophagy, apoptosis, angiogenesis, invasion, and metastasis in several types of cancers. The expression of eEF2K promotes survival of cancer cells, and the level of this protein is increased in many cancer cells to adapt them to the microenvironment conditions including hypoxia, nutrient depletion, and acidosis. The physiological function of eEF2K and its role in the development and progression of cancer are here reviewed in detail. In addition, a summary of progress for in vitro eEF2K inhibitors from anti-cancer drug discovery research in recent years, along with their structure–activity relationships (SARs) and synthetic routes or natural sources, is also described. Special attention is given to those inhibitors that have been already validated in vivo, with the overall aim to provide reference context for the further development of new first-in-class anti-cancer drugs that target eEF2K.
An Update on the Role of Leptin in the Immuno-Metabolism of Cartilage
Authors: Cordero-Barreal Alfonso , González-Rodríguez María , Ruiz-Fernández Clara , Eldjoudi Djedjiga Ait , AbdElHafez Yousof Ramadan Farrag , Lago Francisca , Conde Javier , Gómez Rodolfo , González-Gay Miguel Angel , Mobasheri Ali , Pino Jesus , Gualillo Oreste
Published: February 2021

Since its discovery in 1994, leptin has been considered as an adipokine with pleiotropic effects. In this review, we summarize the actual information about the impact of this hormone on cartilage metabolism and pathology. Leptin signalling depends on the interaction with leptin receptor LEPR, being the long isoform of the receptor (LEPRb) the one with more efficient intracellular signalling. Chondrocytes express the long isoform of the leptin receptor and in these cells, leptin signalling, alone or in combination with other molecules, induces the expression of pro-inflammatory molecules and cartilage degenerative enzymes. Leptin has been shown to increase the proliferation and activation of immune cells, increasing the severity of immune degenerative cartilage diseases. Leptin expression in serum and synovial fluid are related to degenerative diseases such as osteoarthritis (OA), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Inhibition of leptin signalling showed to have protective effects in these diseases showing the key role of leptin in cartilage degeneration.
Microbial Production of Melanin Pigments from Caffeic Acid and L-Tyrosine Using Streptomyces glaucescens and FCS-ECH-Expressing Escherichia coli
Authors: Ahn Soo-Yeon , Jang Seyoung , Sudheer Pamidimarri D. V. N. , Choi Kwon-Young
Published: February 2021

In this study, synthetic allomelanin was prepared from wild-type Streptomyces glaucescens and recombinant Escherichia coli BL21(DE3) strains. S. glaucescens could produce 125.25 ± 6.01 mg/L of melanin with a supply of 5 mM caffeic acid within 144 h. The ABTS radical scavenging capacity of S. glaucescens melanin was determined to be approximately 7.89 mg/mL of IC50 value, which was comparable to L-tyrosine-based eumelanin. The isolated melanin was used in cotton fabric dyeing, and the effect of copper ions, laccase enzyme treatment, and the dyeing cycle on dyeing performance was investigated. Interestingly, dyeing fastness was greatly improved upon treatment with the laccase enzyme during the cotton dyeing process. Besides, the supply of C5-diamine, which was reported to lead to more complex crosslinking between melanin units, to caffeic acid-based melanin synthesis was also investigated for higher production and novel functionalities. To facilitate the supply of caffeic acid and C5-diamine, E. coli strains expressing each or combinations of tyrosine ammonia lyase/p-coumarate 3-hydroxylase, feruloyl-CoA synthetase/enoyl-CoA hydratase/aldolase, and tyrosinase/lysine decarboxylase enzymes were prepared and investigated for their eumelanin, C5-diamine, and allomelanin production from L-tyrosine and L-lysine, respectively. Finally, H-NMR, FT-IR, and MALDI-TOF analysis of the synthetic melanin pigments were attempted to obtain the chemical information.
Downstream Changes in Odonate (Insecta: Odonata) Communities along a Suburban to Urban Gradient: Untangling Natural and Anthropogenic Effects
Authors: Worthen Wade B. , Fravel R. Kile , Horne Connor P.
Published: February 2021

The community structure of lotic odonates (Insecta: Odonata) changes downstream, but it is difficult to untangle natural and anthropogenic causes. We surveyed larvae and adults at 15 sites along the Reedy River in Greenville Co., SC, USA, from sites in forested suburban landscapes through the urban core of the city of Greenville. We used principal component analyses and Akaike information criteria models to describe the relationships between larval and adult community descriptors (abundance, richness, and diversity) and habitat characteristics at several spatial scales, including water chemistry, sediment and detritus, aquatic and streamside vegetation, and the percent cover of landforms in the surrounding landscape. At all scales, larval abundance, richness, and diversity correlated with the amount of detritus. At a small scale, adult indices correlated with the amount of sunlight and streamside vegetation. Zygopteran community composition was nested at a large scale; richness and diversity did not correlate with changes in the landscape but increased downstream. Anisopteran composition was also nested, but richness correlated with the percent cover of field, wetland, and open water in the habitat and was unrelated to downstream site position. Landscape transformation affected anisopterans more than zygopterans by opening habitats that facilitate these generalist heliotherms.
Wastewater Refinery: Producing Multiple Valuable Outputs from Wastewater
Authors: Kusch-Brandt Sigrid , Alsheyab Mohammad A. T.
Published: February 2021

A wastewater refinery is a multifunctional solution that combines different technologies and processing schemes to recover a spectrum of valuable materials from municipal or industrial wastewater. The concept of wastewater refinery introduces a new perspective on wastewater treatment and management. It aims at making the most of wastewater constituents by co-producing different worthful outputs, such as water, energy, nitrogen, sulfide, and phosphorous. This can turn the treatment of wastewater from a major cost into a source of profit. The wastewater refinery approach is well aligned with the concept of the circular economy. A case study on Qatar’s wastewater revealed the potential recovery of significant quantities of valuable resources embodied in the country’s wastewater. Valorization of organic constituents and the recovery of nitrogen, phosphorus, and sulfide should be given priority. To facilitate the adoption of the wastewater refinery concept, research is required to explore technical and economic bottlenecks.
Challenges and Innovations in Osteochondral Regeneration: Insights from Biology and Inputs from Bioengineering toward the Optimization of Tissue Engineering Strategies
Authors: Morouço Pedro , Fernandes Cristiana , Lattanzi Wanda
Published: February 2021

Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone (corresponding to a IV grade according to the conventional radiographic classification by Berndt and Harty). Therefore, strategies for functional tissue regeneration should also aim at healing the subchondral bone and joint interface, besides hyaline cartilage. With the ambition of contributing to solving this problem, several research groups have been working intensively on the development of tailored implants that could promote that complex osteochondral regeneration. These implants may be manufactured through a wide variety of processes and use a wide variety of (bio)materials. This review aimed to examine the state of the art regarding the challenges, advantages, and drawbacks of the current strategies for osteochondral regeneration. One of the most promising approaches relies on the principles of additive manufacturing, where technologies are used that allow for the production of complex 3D structures with a high level of control, intended and predefined geometry, size, and interconnected pores, in a reproducible way. However, not all materials are suitable for these processes, and their features should be examined, targeting a successful regeneration.