bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a Simulation Model to Numerically Estimate Energy Parameters and Wave Energy Converter Efficiency of a Floating Wave Power Plant
Authors: Zhelonkin Maxim , Kurkin Andrey , Loskutov Alexey , Plekhov Alexander , Malyarov Dmitry , Kryukov Evgeny
Published: May 2023

The significance of coastal zone object protection using wave electrical energy complexes (WEECs) is dealt with. The authors suggest using a floating wave power plant (FWPP), which comprises electrical energy functions and provides coastal zone protection. Features of simulating FWPP in computational fluid dynamics (CFD) modules are considered. The main simulation stages, construction order, the necessary initial and boundary conditions, calculation objectives and results are described and analyzed. Analysis and adjustment of input parameters (wave amplitude, wave disturbance frequency, FWPP geometric parameters) determining the FWPP fluid flow output parameters (dynamic, total pressure, flow rate, flow velocity) were carried out. Calculation process optimization was carried out by comparing the data obtained using a 2-D solver. The main stages of wave disturbances-with-FWPP-structure interaction have been determined. Epures of flow velocity, pressure, flow path and volume flow rate were constructed and analyzed.
An Enhanced Path Planner for Electric Vehicles Considering User-Defined Time Windows and Preferences
Authors: Cubillos Maximiliano , Dell’Amico Mauro , Jabali Ola , Malucelli Federico , Tresoldi Emanuele
Published: May 2023

A number of decision support tools facilitating the use of Electric Vehicles (EVs) have been recently developed. Due to the EVs’ limited autonomy, routing and path planning are the main challenges treated in such tools. Specifically, determining at which Charging Stations (CSs) to stop, and how much the EV should charge at them is complex. This complexity is further compounded by the fact that charging times depend on the CS technology, the EV characteristics, and follow a nonlinear function. Considering these factors, we propose a path-planning methodology for EVs with user preferences, where charging is performed at public CSs. To achieve this, we introduce the Electric Vehicle Shortest Path Problem with time windows and user preferences (EVSPPWP) and propose an efficient heuristic algorithm for it. Given an origin and a destination, the algorithm prioritizes CSs close to Points of Interest (POIs) that match user inputted preferences, and user-defined time windows are considered for activities such as lunch and spending the night at hotels. The algorithm produces flexible solutions by considering clusters of charging points (CPs) as separate CSs. Furthermore, the algorithm yields resilient paths by ensuring that recommended paths have a minimum number of CSs in their vicinity. The main contributions of our methodology are the following: modeling user-defined time windows, including user-defined weights for different POI categories, creating CSs based on clusters of CPs with sufficient proximity, using resilient paths, and proposing an efficient algorithm for solving the EVSPPWP. To facilitate the use of our methodology, the algorithm was integrated into a web interface. We demonstrate the use of the web interface, giving usage examples and comparing different settings.
Innovative Pathways for the Valorization of Biomass Gasification Char: A Systematic Review
Authors: Abdelaal Ali , Benedetti Vittoria , Villot Audrey , Patuzzi Francesco , Gerente Claire , Baratieri Marco
Published: May 2023

The thermochemical process of gasification is widely utilized for bioenergy production and is particularly attractive due to its high conversion efficiency. However, a gasification byproduct, known as char, is commonly treated as industrial waste despite its attractive qualities. Indeed, due to its high carbon content (up to 91%) and well-developed porosity (specific surface areas up to 1253 m2 g−1), gasification char could be considered a cost-effective substitute for activated carbon in various applications, such as catalysis and adsorption. However, its properties are highly dependent on the gasification parameters and the initial feedstock selected, and thus a careful characterization of the material is needed to find the most suitable applications. This review can act as a preliminary assessment of the gasification along with the expected char properties, aiding in the selection of the most appropriate valorization pathways. In particular, different application areas, their relation to the gasification process, and the char properties are extensively discussed.
Microseismic Monitoring at the Farnsworth CO2-EOR Field
Authors: Qin Yan , Li Jiaxuan , Huang Lianjie , Gao Kai , Li David , Chen Ting , Bratton Tom , El-kaseeh George , Ampomah William , Ispirescu Titus , Cather Martha , Balch Robert , Zheng Yingcai , Tang Shuhang , McCormack Kevin L. , McPherson Brian
Published: May 2023

The Farnsworth Unit in northern Texas is a field site for studying geologic carbon storage during enhanced oil recovery (EOR) using CO2. Microseismic monitoring is essential for risk assessment by detecting fluid leakage and fractures. We analyzed borehole microseismic data acquired during CO2 injection and migration, including data denoising, event detection, event location, magnitude estimation, moment tensor inversion, and stress field inversion. We detected and located two shallow clusters, which occurred during increasing injection pressure. The two shallow clusters were also featured by large b values and tensile cracking moment tensors that are obtained based on a newly developed moment tensor inversion method using single-borehole data. The inverted stress fields at the two clusters showed large deviations from the regional stress field. The results provide evidence for microseismic responses to CO2/fluid injection and migration.
Primary Chondroprogenitors: Standardized & Versatile Allogeneic Cytotherapeutics
Authors: Laurent Alexis , Jeannerat Annick , Peneveyre Cédric , Scaletta Corinne , Philippe Virginie , Abdel-Sayed Philippe , Raffoul Wassim , Martin Robin , Hirt-Burri Nathalie , Applegate Lee Ann
Published: May 2023

Primary chondroprogenitors obtained from standardized cell sources (e.g., FE002 clinical grade cell sources) may be cultured in vitro and may be cytotherapeutically applied in allogeneic musculoskeletal regenerative medicine. Multicentric translational research on FE002 human primary chondroprogenitors under the Swiss progenitor cell transplantation program has notably validated their robustness and high versatility for therapeutic formulation in clinically compatible prototypes, as well as a good safety profile in diverse in vivo preclinical models. Therein, stringently controlled primary cell source establishment and extensive cell manufacturing optimization have technically confirmed the adequation of FE002 primary chondroprogenitors with standard industrial biotechnology workflows for consistent diploid cell biobanking under GMP. Laboratory characterization studies and extensive qualification work on FE002 progenitor cell sources have elucidated the key and critical attributes of the cellular materials of interest for potential and diversified human cytotherapeutic uses. Multiple formulation studies (i.e., hydrogel-based standardized transplants, polymeric-scaffold-based tissue engineering products) have shown the high versatility of FE002 primary chondroprogenitors, for the obtention of functional allogeneic cytotherapeutics. Multiple in vivo preclinical studies (e.g., rodent models, GLP goat model) have robustly documented the safety of FE002 primary chondroprogenitors following implantation. Clinically, FE002 primary chondroprogenitors may potentially be used in various forms for volumetric tissue replacement (e.g., treatment of large chondral/osteochondral defects of the knee) or for the local management of chondral affections and pathologies (i.e., injection use in mild to moderate osteoarthritis cases). Overall, standardized FE002 primary chondroprogenitors as investigated under the Swiss progenitor cell transplantation program were shown to constitute tangible contenders in novel human musculoskeletal regenerative medicine approaches, for versatile and safe allogeneic clinical cytotherapeutic management.
Treated Waste Tire Using Cement Coating as Coarse Aggregate in the Production of Sustainable Green Concrete
Authors: Paul Suvash Chandra , Islam Shamsul , Mamun Abdullah Al , Islam Naymul , Babafemi Adewumi John , Kong Sih Ying , Miah Md Jihad
Published: May 2023

Waste tire rubber is one of the most concerning environmental pollution issues. With the increasing demand for automobile production, the rate of waste tire generation has also increased. However, these tires often end up stockpiled and not properly disposed of. This non-biodegradable waste poses severe fire, environmental, and health risks. Due to the progressively severe environmental problems caused by the disposal of waste tires, the feasibility of using such elastic waste materials as an alternative to natural aggregates has become a research topic. The main objective of this research is to investigate the changes in the mechanical and durability properties of concrete with the inclusion of waste tire rubber at specific contents. A total of 80 cylinders measuring 100 mm × 200 mm were cast with waste tire aggregate as a partial replacement for natural coarse aggregate (5% and 10% by weight of natural coarse aggregate). A surface treatment of tire aggregate using a cement coating was performed to study its effect on concrete properties. This research indicates a noticeable reduction in the compressive and split tensile strength of concrete containing untreated waste tire rubber compared to normal concrete made with natural aggregates. However, an improvement was observed when the surface of tire aggregates was coated with cement grout. Additionally, it was noted that the slump value, water absorption, and porosity increased as the percentage of rubber increased. Nevertheless, unlike normal concrete, the failure pattern in tire-mixed concrete occurs gently and uniformly, indicating ductile behavior.
Shelf-Life and Quality of Anchovies (Engraulis encrasicolus) Refrigerated Using Different Packaging Materials
Authors: Dambrosio Angela , Quaglia Nicoletta Cristiana , Colonna Maria Antonietta , Capuozzo Flavia , Giannico Francesco , Tarricone Simona , Caputi Jambrenghi Anna , Ragni Marco
Published: May 2023

The identification of sustainable materials as an alternative to plastic is fundamental for the protection of the environment and for the safeguard of marine ecosystems. The replacement of plastic with organic materials for fish storage might affect its shelf-life due to the high concentration of oxidizable fatty acids in fish flesh. This study investigated the effectiveness of two organic packaging materials, namely coconut fiber (Coc) and paper (Pap), as alternatives to the conventionally used polystyrene (Pol), on the shelf-life, hygienic parameters, and quality traits of anchovies refrigerated for one (T0), three (T1), or seven (T2) days. The hygienic quality of anchovies packaged in the organic Pap and Coc boxes was better than the traditional Pol, probably due to the higher porosity of the packaging, which allows a higher bacterial proliferation. Results of the T-BARS test showed a lower (p < 0.05) malondialdehyde concentration in fillets from the Pap group, which increased (p < 0.05) from the first to the seventh day of storage. The polyunsaturated fatty acids concentration did not differ between groups, but it decreased (p < 0.05) from T0 to T2. Coconut fiber and paper are worthy of further investigation since these packaging materials did not affect the shelf-life and fatty acid profile of anchovies during storage.
Microbial Transglutaminase Cross-Linking Enhances the Textural and Rheological Properties of the Surimi-like Gels Made from Alkali-Extracted Protein Isolate from Catfish Byproducts and the Role of Disulfide Bonds in Gelling
Authors: Zhang Yan , Chang Sam K.C.
Published: May 2023

The texture of surimi-like gels made from the protein isolate extracted from catfish byproducts has been proven to be brittle and lack elasticity. To address this issue, varying levels of microbial transglutaminase (MTGase) from 0.1 to 0.6 units/g were applied. MTGase had little effect on the color profile of gels. When MTGase at 0.5 units/g was employed, hardness, cohesiveness, springiness, chewiness, resilience, fracturablity, and deformation were increased by 218, 55, 12, 451, 115, 446, and 71%, respectively. A further increase in added MTGase did not lead to any textural improvement. In comparison to the gels made from fillet mince, the gels made from protein isolate were still lower in cohesiveness. Due to the activated endogenous transglutaminase, a setting step enhanced the textural properties of gels made from fillet mince. However, because of the endogenous proteases-induced protein degradation, the setting step led to a texture deterioration of the gels made from protein isolate. Gels made from protein isolate showed 23–55% higher solubility in reducing solution than in non-reducing solution, suggesting the vital role of disulfide bonds in the gelation process. Due to the different protein composition and conformation, fillet mince and protein isolate exhibited distinct rheological properties. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed the highly denatured protein isolate was susceptible to proteolysis and prone to disulfide formation during the gelation process. It also revealed that MTGase had an inhibitory effect on the proteolysis induced by endogenous enzymes. In view of the susceptibility of the protein isolate to proteolysis during gelation, future research should consider including other enzyme inhibitory agents in the presence of MTGase to improve the gel texture.
Comparison of Derivatization Methods for Groomed Latent Print Residues Analysis via Gas Chromatography
Authors: Kindell Jessica , Bridge Candice
Published: May 2023

The practice of latent print analysis is comprised of a visual examination and the comparison of the fingerprint pattern from a questioned print to an exemplar(s). When a questioned print is either smudged or contains little pattern detail, the print comparison would be considered an inconclusive determination. However, in these scenarios, the latent print residues (LPRs) could provide associative information to supplement the current ACE-V (Analysis, Comparison, Examination-Verification) process. Advancements using analytical techniques allow for the analysis of LPR chemistry; however, derivatization is generally required to increase the abundance of components not traditionally observed in gas chromatography. This study aimed to determine whether two derivatization reagents, boron trifluoride in methanol (BF3-MeOH) and N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA), provide a better recovery of LPR components from a porous or non-porous substrate. Five volunteers deposited groomed latent print samples onto two substrates: a microfiber filter (porous) and a microscope slide (non-porous). The residues were derivatized or evaporated prior to the gas chromatography-mass spectrometry (GC-MS) analysis. The percent recoveries were higher, >83%, in the DCM extracted samples for both substrates compared to those samples prepared in hexanes. DCM/MSTFA derivatization provided the recovery of fatty acids that ranged from 20 to 30% for both substrates and a recovery of squalene at a rate of 2.37% for the filter sample and 4.2% for the slide sample. These rates were higher than the recovery rates obtained for the hexanes/BF3-MeOH-derivatized samples, with a range of 1–8% for the fatty acids recovery rates and 0.6–0.85% for squalene from both substrates. Overall, the MSTFA derivatization reagent produced higher recoveries for LPR on porous and non-porous substrates while providing a LPR chromatographic profile similar to that of a non-derivatized sample. The use of DCM as a solvent provided a wider range of LPR components recovered than hexanes and, thus, should be used as the extraction solvent when derivatizing samples, regardless of the substrate.
Hospital Admission Profile Related to Inner Ear Diseases in England and Wales
Authors: Taybeh Esra’ O. , Naser Abdallah Y.
Published: May 2023

Background: Due to an expansion in the usage of medications (such as anticancer therapies), increased exposure to noise, and an increase in life expectancy, the prevalence of inner ear disease-related hearing loss is rising. Diseases of the inner ear are frequently accompanied by other conditions, such as chronic heart failure, systemic inflammation, arterial hypertension, and cerebrovascular disease. The aim of this study was to investigate the profile of hospital admissions linked to inner ear diseases in England and Wales. Method: This was an ecological descriptive study using public medical databases in England and Wales. Diagnostic codes for diseases of the inner ear (H80–H83) were used to identify all hospital admissions. Between 1999 and 2020, the chi-squared test was used to assess the difference between the admission rates. Results: From 5704 in 1999 to 19,097 in 2020, the total annual number of hospital admissions increased by 234.8%, which corresponds to a 192.3% increase in the admission rate [from 10.94 (95% CI 10.66–11.22) in 1999 to 31.98 (95% CI 31.52–32.43) in 2020 per 100,000 people, p < 0.01]. “Disorders of vestibular function” and “other inner ear diseases” were the most frequent causes of hospital admissions due to inner ear diseases, accounting for 47.6% and 43.6%, respectively. The age range of 15 to 59 years accounted for 42.3% of all diseases of the inner ear hospital admissions. Around 59.6% of all admissions were made by females. The female admission rate increased by 210.1% (from 12.43 (95% CI 12.01–12.85) in 1999 to 38.54 (95% CI 37.84–39.24) in 2020 per 100,000 people). The male admission rate for diseases of the inner ear increased by 169.6% [from 9.37 (95% CI 9.00–9.75) in 1999 to 25.26 (95% CI 24.69–25.84) per 100,000 people] in 2020. Conclusion: Inner ear disease admissions increased markedly in England and Wales during the past two decades. Females and the middle-aged population were at higher risk of being admitted for inner ear diseases. Further cohort studies are warranted to identify other risk factors and develop effective prevention strategies.
Fear and Stigma of COVID-19 Reinfection Scale (FSoCOVID-19RS): New Scale Development and Validation
Authors: Albikawi Zainab Fatehi , Abuadas Mohammad Hamdi , Alalyani Mesheil M. , Zahrani Yousef , Aqel Emad , Safi Raid
Published: May 2023

Background: The advent of COVID-19 and its impacts have prompted fear and stigma among people all across the world. Because of stigma, there was often a delay in diagnosis and treatment, which resulted in a poor prognosis. As a result, a reliable scale is required to measure the level of fear and stigma of COVID-19 reinfection. Aim: To develop and validate a scale for determining the level of fear and stigma of COVID-19 reinfection. Methods: A cross-sectional study including 200 nursing-college students who had previously tested positive for COVID-19 was conducted. The scale’s reliability was evaluated by external and internal consistency methods. Construct, convergent, and discriminant validity were evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Results: The scale’s mean score was 24.85 ± 11.35, and no floor or ceiling effects were detected. The scale items’ reliability, measured by Cronbach’s alpha coefficient if an item was deleted, ranged from 0.76 to 0.95, with a total score value of 0.86. The range of convergent validity coefficients was between 0.37 and 0.64. Pearson’s correlation coefficients for test–retest validity ranged from 0.71 to 0.93, with a total score of 0.82. The coefficient of split-half correlation was 0.87, while the coefficient of reliability was 0.93. According to the factor analysis, two components had latent roots larger than 1. The rotated component matrix of the two factors revealed that all items had R values over 0.30, indicating that none of them should be excluded. In addition, CFA results revealed that χ2 = 3524, df = 1283, χ2/df ratio = 2.74, p < 0.001, GFI = 0.86, CFI = 0.92, AGFI = 0.88, and RMSEA = 0.05. The scale’s convergent and discriminant validity was confirmed. Conclusions: The 14-item, two-dimensional Fear and Stigma of COVID-19 Reinfection Scale (FSoCOVID-19 RS) was demonstrated to have reliable psychometric properties.
Reliability and Validity of a Portable Traction Dynamometer in Knee-Strength Extension Tests: An Isometric Strength Assessment in Recreationally Active Men
Authors: Garcia Danielle , de Sousa Neto Ivo Vieira , de Souza Monteiro Yuri , Magalhães Denis Pinheiro , Ferreira Gleison Miguel Lissemerki , Grisa Roberto , Prestes Jonato , Rosa Bruno Viana , Abrahin Odilon , Martins Tatiane Meire , Vidal Samuel Estevam , de Moura Andrade Rosimeire , Celes Rodrigo Souza , Rolnick Nicholas , da Cunha Nascimento Dahan
Published: May 2023

Background: the study determined the validity and reliability of measurements obtained using the portable traction dynamometer (PTD) (E-Lastic, E-Sports Solutions, Brazil) and the reproducibility between evaluators (precision) in the evaluation of the isometric muscle strength of the knee extensors of healthy male adults, compared to measurements obtained with the “gold standard” computerized dynamometer (CD) (Biodex System 3, Nova York, NY, USA). Methods: we evaluated sixteen recreationally active men (29.50 ± 7.26 years). The test–retest reliability of both equipment to determine quadriceps strength, agreement analysis, and the minimal important difference were verified. Results: excellent test–retest interrater reliability was observed for absolute and relative measurements, with a low absolute error for both sets of equipment and excellent validity of the PTD against the CD, as verified by linear regression and Pearson’s correlation coefficient. Conclusions: PTD is a valid and reliable instrument for assessing the isometric strength of knee extensors, with results similar to the isometric CD “gold standard”.
Making Sense of Antisense lncRNAs in Hepatocellular Carcinoma
Authors: Mosca Nicola , Russo Aniello , Potenza Nicoletta
Published: May 2023

Transcriptome complexity is emerging as an unprecedented and fascinating domain, especially by high-throughput sequencing technologies that have unveiled a plethora of new non-coding RNA biotypes. This review covers antisense long non-coding RNAs, i.e., lncRNAs transcribed from the opposite strand of other known genes, and their role in hepatocellular carcinoma (HCC). Several sense–antisense transcript pairs have been recently annotated, especially from mammalian genomes, and an understanding of their evolutionary sense and functional role for human health and diseases is only beginning. Antisense lncRNAs dysregulation is significantly involved in hepatocarcinogenesis, where they can act as oncogenes or oncosuppressors, thus playing a key role in tumor onset, progression, and chemoradiotherapy response, as deduced from many studies discussed here. Mechanistically, antisense lncRNAs regulate gene expression by exploiting various molecular mechanisms shared with other ncRNA molecules, and exploit special mechanisms on their corresponding sense gene due to sequence complementarity, thus exerting epigenetic, transcriptional, post-transcriptional, and translational controls. The next challenges will be piecing together the complex RNA regulatory networks driven by antisense lncRNAs and, ultimately, assigning them a function in physiological and pathological contexts, in addition to defining prospective novel therapeutic targets and innovative diagnostic tools.
Nanomaterials Based on Collaboration with Multiple Partners: Zn3Nb2O8 Doped with Eu3+ and/or Amino Substituted Porphyrin Incorporated in Silica Matrices for the Discoloration of Methyl Red
Authors: Birdeanu Mihaela , Fratilescu Ion , Epuran Camelia , Mocanu Liviu , Ianasi Catalin , Lascu Anca , Fagadar-Cosma Eugenia
Published: May 2023

Designing appropriate materials destined for the removal of dyes from waste waters represents a great challenge for achieving a sustainable society. Three partnerships were set up to obtain novel adsorbents with tailored optoelectronic properties using silica matrices, Zn3Nb2O8 oxide doped with Eu3+, and a symmetrical amino-substituted porphyrin. The pseudo-binary oxide with the formula Zn3Nb2O8 was obtained by the solid-state method. The doping of Zn3Nb2O8 with Eu3+ ions was intended in order to amplify the optical properties of the mixed oxide that are highly influenced by the coordination environment of Eu3+ ions, as confirmed by density functional theory (DFT) calculations. The first proposed silica material, based solely on tetraethyl orthosilicate (TEOS) with high specific surface areas of 518–726 m2/g, offered better performance as an adsorbent than the second one, which also contained 3-aminopropyltrimethoxysilane (APTMOS). The contribution of amino-substituted porphyrin incorporated into silica matrices resides both in providing anchoring groups for the methyl red dye and in increasing the optical properties of the whole nanomaterial. Two different types of methyl red adsorption mechanisms can be reported: one based on surface absorbance and one based on the dye entering the pores of the adsorbents due to their open groove shape network.
Metabolic Engineering and Synthetic Biology Approaches for the Heterologous Production of Aromatic Polyketides
Authors: Yang Dongsoo , Eun Hyunmin , Prabowo Cindy Pricilia Surya
Published: May 2023

Polyketides are a diverse set of natural products with versatile applications as pharmaceuticals, nutraceuticals, and cosmetics, to name a few. Of several types of polyketides, aromatic polyketides comprising type II and III polyketides contain many chemicals important for human health such as antibiotics and anticancer agents. Most aromatic polyketides are produced from soil bacteria or plants, which are difficult to engineer and grow slowly in industrial settings. To this end, metabolic engineering and synthetic biology have been employed to efficiently engineer heterologous model microorganisms for enhanced production of important aromatic polyketides. In this review, we discuss the recent advancement in metabolic engineering and synthetic biology strategies for the production of type II and type III polyketides in model microorganisms. Future challenges and prospects of aromatic polyketide biosynthesis by synthetic biology and enzyme engineering approaches are also discussed.
The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review
Authors: Thoene Michael , Bejer-Olenska Ewa , Wojtkiewicz Joanna
Published: May 2023

Articular cartilage has very low metabolic activity. While minor injuries may be spontaneously repaired within the joint by chondrocytes, there is very little chance of a severely impaired joint regenerating itself when damaged. Therefore, any significant joint injury has little chance of spontaneously healing without some type of therapy. This article is a review that will examine the causes of osteoarthritis, both acute and chronic, and how it may be treated using traditional methods as well as with the latest stem cell technology. The latest regenerative therapy is discussed, including the use and potential risks of mesenchymal stem cells for tissue regeneration and implantation. Applications are then discussed for the treatment of OA in humans after using canine animal models. Since the most successful research models of OA were dogs, the first applications for treatment were veterinary. However, the treatment options have now advanced to the point where patients suffering from osteoarthritis may be treated with this technology. A survey of the literature was performed in order to determine the current state of stem cell technology being used in the treatment of osteoarthritis. Then, the stem cell technology was compared with traditional treatment options.
Early Clinical Outcomes of the First Commercialized Human Autologous Ex Vivo Cultivated Oral Mucosal Epithelial Cell Transplantation for Limbal Stem Cell Deficiency: Two Case Reports and Literature Review
Authors: Toshida Hiroshi , Kasahara Tomoto , Kiriyama Masamichi , Iwasaki Yuma , Sugita Jobu , Ichikawa Kohei , Ohta Toshihiko , Miyahara Katsumi
Published: May 2023

The first product in the world for ex vivo cultivated oral mucosal epithelial cell transplantation (COMET) to treat limbal stem cell deficiency (LSCD), named Ocural®, was launched in June 2021 in Japan. COMET was performed on two patients, including the first case in the post-marketing phase of Ocural®. Pathological and immunohistochemical examinations were also carried out using specimens obtained before and after COMET and the spare cell sheet. In case 1, the ocular surface remained free from epithelial defects for approximately six months. In case 2, although defect of the cornea-like epithelia was observed after COMET for one month, it was resolved after the insertion of lacrimal punctal plugs. In case 1, adjuvant treatment was interrupted due to an accident during the second month after COMET, resulting in conjunctival ingrowth and corneal opacity. Eventually, a lamellar keratoplasty was required at six months after COMET. Immunohistochemistry revealed the presence of markers for stem cells (p63, p75), proliferation (Ki-67), and differentiation (Keratin-3, -4, and -13) in both the cornea-like tissue after COMET and a cultivated oral mucosal epithelial cell sheet. In conclusion, Ocural® can be accomplished without major complications, and the stem cells derived from oral mucosa might be successfully engrafted.
Synthesis, Antimicrobial, and Antibiofilm Activities of Some Novel 7-Methoxyquinoline Derivatives Bearing Sulfonamide Moiety against Urinary Tract Infection-Causing Pathogenic Microbes
Authors: Ghorab Mostafa M. , M. Soliman Aiten , El-Sayyad Gharieb S. , Abdel-Kader Maged S. , El-Batal Ahmed I.
Published: May 2023

A new series of 4-((7-methoxyquinolin-4-yl) amino)-N-(substituted) benzenesulfonamide 3(a–s) was synthesized via the reaction of 4-chloro-7-methoxyquinoline 1 with various sulfa drugs. The structural elucidation was verified based on spectroscopic data analysis. All the target compounds were screened for their antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and unicellular fungi. The results revealed that compound 3l has the highest effect on most tested bacterial and unicellular fungal strains. The highest effect of compound 3l was observed against E. coli and C. albicans with MIC = 7.812 and 31.125 µg/mL, respectively. Compounds 3c and 3d showed broad-spectrum antimicrobial activity, but the activity was lower than that of 3l. The antibiofilm activity of compound 3l was measured against different pathogenic microbes isolated from the urinary tract. Compound 3l could achieve biofilm extension at its adhesion strength. After adding 10.0 µg/mL of compound 3l, the highest percentage was 94.60% for E. coli, 91.74% for P. aeruginosa, and 98.03% for C. neoformans. Moreover, in the protein leakage assay, the quantity of cellular protein discharged from E. coli was 180.25 µg/mL after treatment with 1.0 mg/mL of compound 3l, which explains the creation of holes in the cell membrane of E. coli and proves compound 3l’s antibacterial and antibiofilm properties. Additionally, in silico ADME prediction analyses of compounds 3c, 3d, and 3l revealed promising results, indicating the presence of drug-like properties.
Regulation of the Cell Cycle by ncRNAs Affects the Efficiency of CDK4/6 Inhibition
Authors: Hu Qingyi , Huang Tao
Published: May 2023

Cyclin-dependent kinases (CDKs) regulate cell division at multiple levels. Aberrant proliferation induced by abnormal cell cycle is a hallmark of cancer. Over the past few decades, several drugs that inhibit CDK activity have been created to stop the development of cancer cells. The third generation of selective CDK4/6 inhibition has proceeded into clinical trials for a range of cancers and is quickly becoming the backbone of contemporary cancer therapy. Non-coding RNAs, or ncRNAs, do not encode proteins. Many studies have demonstrated the involvement of ncRNAs in the regulation of the cell cycle and their abnormal expression in cancer. By interacting with important cell cycle regulators, preclinical studies have demonstrated that ncRNAs may decrease or increase the treatment outcome of CDK4/6 inhibition. As a result, cell cycle-associated ncRNAs may act as predictors of CDK4/6 inhibition efficacy and perhaps present novel candidates for tumor therapy and diagnosis.
Deletion of the foxO4 Gene Increases Hypoxia Tolerance in Zebrafish
Authors: Shi Linlin , Zhang Axin , Liu Hong , Wang Huanling
Published: May 2023

Oxygen homeostasis is an important organizing principle for understanding development, physiology, disease, and evolution. Under various physiological and pathological states, organisms experience oxygen deficiency or hypoxia. FoxO4 has been recognized as an important transcriptional regulator involved in a variety of cellular functions, including proliferation, apoptosis, differentiation, and stress resistance, but its role in hypoxia adaptation mechanisms in animals is not so clear. To explore the role of foxO4 in the hypoxia response, we detected the expression of foxO4 and the regulatory relationship between Hif1α and foxO4 under hypoxic conditions. It was found that the expression of foxO4 was up-regulated in ZF4 cells and zebrafish tissues after hypoxia treatment, and Hif1α could directly target the HRE of the foxO4 promoter to regulate foxO4 transcription, indicating that foxO4 was involved in the hypoxia response by the Hif1α-mediated pathway. Furthermore, we obtained foxO4 knockout zebrafish and found that the disruption of foxO4 increased the tolerance to hypoxia. Further research found that the oxygen consumption and locomotor activity of foxO4−/− zebrafish were lower than those of WT zebrafish, as was true for NADH content, NADH/NAD+ rate, and expression of mitochondrial respiratory chain complex-related genes. This suggests that disruption of foxO4 reduced the oxygen demand threshold of the organism, which explained why the foxO4−/− zebrafish were more tolerant to hypoxia than WT zebrafish. These results will provide a theoretical basis for further study of the role of foxO4 in the hypoxia response.
Chloroplast Pan-Genomes and Comparative Transcriptomics Reveal Genetic Variation and Temperature Adaptation in the Cucumber
Authors: Xia Lei , Wang Han , Zhao Xiaokun , Obel Hesbon Ochieng , Yu Xiaqing , Lou Qunfeng , Chen Jinfeng , Cheng Chunyan
Published: May 2023

Although whole genome sequencing, genetic variation mapping, and pan-genome studies have been done on a large group of cucumber nuclear genomes, organelle genome information is largely unclear. As an important component of the organelle genome, the chloroplast genome is highly conserved, which makes it a useful tool for studying plant phylogeny, crop domestication, and species adaptation. Here, we have constructed the first cucumber chloroplast pan-genome based on 121 cucumber germplasms, and investigated the genetic variations of the cucumber chloroplast genome through comparative genomic, phylogenetic, haplotype, and population genetic structure analysis. Meanwhile, we explored the changes in expression of cucumber chloroplast genes under high- and low-temperature stimulation via transcriptome analysis. As a result, a total of 50 complete chloroplast genomes were successfully assembled from 121 cucumber resequencing data, ranging in size from 156,616–157,641 bp. The 50 cucumber chloroplast genomes have typical quadripartite structures, consisting of a large single copy (LSC, 86,339–86,883 bp), a small single copy (SSC, 18,069–18,363 bp), and two inverted repeats (IRs, 25,166–25,797 bp). Comparative genomic, haplotype, and population genetic structure results showed that there is more genetic variation in Indian ecotype cucumbers compared to other cucumber cultivars, which means that many genetic resources remain to be explored in Indian ecotype cucumbers. Phylogenetic analysis showed that the 50 cucumber germplasms could be classified into 3 types: East Asian, Eurasian + Indian, and Xishuangbanna + Indian. The transcriptomic analysis showed that matK were significantly up-regulated under high- and low-temperature stresses, further demonstrating that cucumber chloroplasts respond to temperature adversity by regulating lipid metabolism and ribosome metabolism. Further, accD has higher editing efficiency under high-temperature stress, which may contribute to the heat tolerance. These studies provide useful insight into genetic variation in the chloroplast genome, and established the foundation for exploring the mechanisms of temperature-stimulated chloroplast adaptation.
Hfe Actions in Kupffer Cells Are Dispensable for Hepatic and Systemic Iron Metabolism
Authors: Knoop Paul , Yilmaz Dilay , Paganoni Rossana , Steele-Perkins Peter , Gruber Andreas , Akdogan Banu , Zischka Hans , Leopold Kerstin , Vujić Spasić Maja Vujić
Published: May 2023

Mutations in the HFE/Hfe gene cause Hereditary Hemochromatosis (HH), a highly prevalent genetic disorder characterized by elevated iron deposition in multiple tissues. HFE acts in hepatocytes to control hepcidin expression, whereas HFE actions in myeloid cells are required for cell-autonomous and systemic iron regulation in aged mice. To address the role of HFE specifically in liver-resident macrophages, we generated mice with a selective Hfe deficiency in Kupffer cells (HfeClec4fCre). The analysis of the major iron parameters in this novel HfeClec4fCre mouse model led us to the conclusion that HFE actions in Kupffer cells are largely dispensable for cellular, hepatic and systemic iron homeostasis.
Mitochondria in Human Fertility and Infertility
Authors: Tesarik Jan , Mendoza-Tesarik Raquel
Published: May 2023

In human spermatozoa and oocytes (and their surrounding granulosa cells), mitochondria carry out important functions relating to human fertility and infertility. Sperm mitochondria are not transmitted to the future embryo, but are closely related to the generation of energy needed for sperm movement, capacitation, and acrosome reactions, as well as for sperm–oocyte fusion. On the other hand, oocyte mitochondria produce energy required for oocyte meiotic division and their abnormalities can thus cause oocyte and embryo aneuploidy. In addition, they play a role in oocyte calcium metabolism and in essential epigenetic events during the oocyte-to-embryo transition. They are transmitted to the future embryos and may thus cause hereditary diseases in the offspring. Due to the long life span of the female germ cells, the accumulation of mitochondrial DNA abnormalities often causes ovarian aging. Mitochondrial substitution therapy is the only way of dealing with these issues nowadays. New therapies based on mitochondrial DNA editing are under investigation.
Hypoxia Is Associated with Increased Immune Infiltrates and Both Anti-Tumour and Immune Suppressive Signalling in Muscle-Invasive Bladder Cancer
Authors: Smith Vicky , Lee Dave , Reardon Mark , Shabbir Rekaya , Sahoo Sudhakar , Hoskin Peter , Choudhury Ananya , Illidge Timothy , West Catharine M. L.
Published: May 2023

Hypoxia and a suppressive tumour microenvironment (TME) are both independent negative prognostic factors for muscle-invasive bladder cancer (MIBC) that contribute to treatment resistance. Hypoxia has been shown to induce an immune suppressive TME by recruiting myeloid cells that inhibit anti-tumour T cell responses. Recent transcriptomic analyses show hypoxia increases suppressive and anti-tumour immune signalling and infiltrates in bladder cancer. This study sought to investigate the relationship between hypoxia-inducible factor (HIF)-1 and -2, hypoxia, and immune signalling and infiltrates in MIBC. ChIP-seq was performed to identify HIF1α, HIF2α, and HIF1β binding in the genome of the MIBC cell line T24 cultured in 1% and 0.1% oxygen for 24 h. Microarray data from four MIBC cell lines (T24, J82, UMUC3, and HT1376) cultured under 1%, 0.2%, and 0.1% oxygen for 24 h were used. Differences in the immune contexture between high- and low-hypoxia tumours were investigated using in silico analyses of two bladder cancer cohorts (BCON and TCGA) filtered to only include MIBC cases. GO and GSEA were used with the R packages “limma” and “fgsea”. Immune deconvolution was performed using ImSig and TIMER algorithms. RStudio was used for all analyses. Under hypoxia, HIF1α and HIF2α bound to ~11.5–13.5% and ~4.5–7.5% of immune-related genes, respectively (1–0.1% O2). HIF1α and HIF2α both bound to genes associated with T cell activation and differentiation signalling pathways. HIF1α and HIF2α had distinct roles in immune-related signalling. HIF1 was associated with interferon production specifically, whilst HIF2 was associated with generic cytokine signalling as well as humoral and toll-like receptor immune responses. Neutrophil and myeloid cell signalling was enriched under hypoxia, alongside hallmark pathways associated with Tregs and macrophages. High-hypoxia MIBC tumours had increased expression of both suppressive and anti-tumour immune gene signatures and were associated with increased immune infiltrates. Overall, hypoxia is associated with increased inflammation for both suppressive and anti-tumour-related immune signalling and immune infiltrates, as seen in vitro and in situ using MIBC patient tumours.
PSEN1 E280A Cholinergic-like Neurons and Cerebral Spheroids Derived from Mesenchymal Stromal Cells and from Induced Pluripotent Stem Cells Are Neuropathologically Equivalent
Authors: Mendivil-Perez Miguel , Velez-Pardo Carlos , Lopera Francisco , Kosik Kenneth S. , Jimenez-Del-Rio Marlene
Published: May 2023

Alzheimer’s disease (AD) is a chronic neurological condition characterized by the severe loss of cholinergic neurons. Currently, the incomplete understanding of the loss of neurons has prevented curative treatments for familial AD (FAD). Therefore, modeling FAD in vitro is essential for studying cholinergic vulnerability. Moreover, to expedite the discovery of disease-modifying therapies that delay the onset and slow the progression of AD, we depend on trustworthy disease models. Although highly informative, induced pluripotent stem cell (iPSCs)-derived cholinergic neurons (ChNs) are time-consuming, not cost-effective, and labor-intensive. Other sources for AD modeling are urgently needed. Wild-type and presenilin (PSEN)1 p.E280A fibroblast-derived iPSCs, menstrual blood-derived menstrual stromal cells (MenSCs), and umbilical cord-derived Wharton Jelly’s mesenchymal stromal cells (WJ-MSCs) were cultured in Cholinergic-N-Run and Fast-N-Spheres V2 medium to obtain WT and PSEN 1 E280A cholinergic-like neurons (ChLNs, 2D) and cerebroid spheroids (CSs, 3D), respectively, and to evaluate whether ChLNs/CSs can reproduce FAD pathology. We found that irrespective of tissue source, ChLNs/CSs successfully recapitulated the AD phenotype. PSEN 1 E280A ChLNs/CSs show accumulation of iAPPβ fragments, produce eAβ42, present TAU phosphorylation, display OS markers (e.g., oxDJ-1, p-JUN), show loss of ΔΨm, exhibit cell death markers (e.g., TP53, PUMA, CASP3), and demonstrate dysfunctional Ca2+ influx response to ACh stimuli. However, PSEN 1 E280A 2D and 3D cells derived from MenSCs and WJ-MSCs can reproduce FAD neuropathology more efficiently and faster (11 days) than ChLNs derived from mutant iPSCs (35 days). Mechanistically, MenSCs and WJ-MSCs are equivalent cell types to iPSCs for reproducing FAD in vitro.
Medical Genetics, Genomics and Bioinformatics—2022
Authors: Klimontov Vadim V. , Koshechkin Konstantin A. , Orlova Nina G. , Sekacheva Marina I. , Orlov Yuriy L.
Published: May 2023

The analysis of molecular mechanisms of disease progression challenges the development of bioinformatics tools and omics data integration [...]
Fluorescence Resonance Energy Transfer Properties and Auger Recombination Suppression in Supraparticles Self-Assembled from Colloidal Quantum Dots
Authors: Tian Xinhua , Chang Hao , Dong Hongxing , Zhang Chi , Zhang Long
Published: May 2023

Colloid quantum dots (CQDs) are recognized as an ideal material for applications in next-generation optoelectronic devices, owing to their unique structures, outstanding optical properties, and low-cost preparation processes. However, monodisperse CQDs cannot meet the requirements of stability and collective properties for device applications. Therefore, it is urgent to build stable 3D multiparticle systems with collective physical and optical properties, which is still a great challenge for nanoscience. Herein, we developed a modified microemulsion template method to synthesize quantum dot supraparticles (QD-SPs) with regular shapes and a high packing density, which is an excellent research platform for ultrafast optical properties of composite systems. The redshift of the steady-state fluorescence spectra of QD-SPs compared to CQD solutions indicates that fluorescence resonance energy transfer (FRET) occurred between the CQDs. Moreover, we investigated the dynamic processes of energy transfer in QD-SPs by time-resolved ultrafast fluorescence spectroscopy. The dynamic redshift and lifetime changes of the spectra further verified the existence of rapid energy transfer between CQDs with different exciton energies. In addition, compared with CQD solutions, the steady-state fluorescence lifetime of SPs increased and the fluorescence intensity decreased slowly with increasing temperature, which indicates that the SP structure suppressed the Auger recombination of CQDs. Our results provide a practical approach to enhance the coupling and luminescence stability of CQDs, which may enable new physical phenomena and improve the performance of optoelectronic devices.
Analytical Solution for Negative Skin Friction in Offshore Wind Power Pile Foundations on Artificial Islands under the Influence of Soil Consolidation
Authors: Jiang Chong , Shi Zexiong , Pang Li
Published: May 2023

The construction of offshore wind power pile foundations on artificial islands is a challenging task due to soil consolidation and additional loads that result in negative skin friction (NSF). In this study, a comprehensive pile–soil interaction model is established to investigate the development of NSF in artificial islands under the action of self-weight consolidation of fill soil and surcharge load. The one-dimensional consolidation theory and an ideal elastoplastic load transfer model are employed to obtain the analytical solution for skin friction and axial force of the pile with respect to time and depth. The predicted results are in good agreement with the field tests and finite element methods. Finally, a parametric study is conducted to investigate the effect of pile installation time, surcharge load, and pile head load on the development of NSF.