bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Cutting Methods Affect the Quality of Fresh-Cut Cucumbers by Regulating ROS Metabolism
Authors: Guan Yuge , Hu Wenzhong , Wang Lei , Yang Bailu
Published: April 2023

Fresh-cut cucumbers (Cucumis sativus L.) are appreciated by consumers for their convenience and freshness. In the process of home cooking and in the food industry, different cutting methods for cucumbers are needed. In order to explore the effect of cutting methods on the quality of fresh-cut cucumbers, cucumbers were cut into slices, pieces, and strips and whole cucumbers were used as the control. The results indicate that the vitamin C content of the sliced, pieced, and stripped cucumbers was gradually reduced, while the glutathione content increased significantly (p < 0.05) compared with the whole cucumbers. Furthermore, this study reveals that the fresh-cutting operation induced the production of ROS (O2−· and H2O2). Simultaneously, cutting activates phenylalanine ammonia-lyase and peroxidase activity, which enhanced the total phenol content by 1.35 times, 1.51 times, and 1.78 times in the pieced, stripped, and sliced cucumbers, respectively. This combines with the enhancement in the ascorbate peroxidase, glutathione reductase, superoxide dismutase, and catalase activity, contributing to the antioxidant capacity increasing by 1.14–1.95 times compared with the control. In conclusion, the degree of quality indexes was sliced > pieced > stripped. Therefore, this study provides useful information to illuminate the mechanism of the quality change in fresh-cut cucumbers subjected to different cutting methods and makes suggestions on the appropriate cutting style for the commercial or home use of cucumbers.
Rainfall Partitioning in Amazon Forest: Implications of Reduced Impact Logging on Litter Water Conservation
Authors: de Lima Jeferson Alberto , Tonello Kelly Cristina
Published: April 2023

This study aimed to investigate how sustainable forest management can affect litter hydrological properties. We investigated the net precipitation, litter mass, water-holding capacity, effective water-holding and retention capacity, maximum water retention and water content in unlogged and logged forests over 13 months in the Amazon Forest, where reduced-impact logging is allowed. The mean litter mass was similar for unlogged and logged forests. The litter water-holding capacity was 220% for unlogged and 224% for logged forests, and for fractions followed: unstructured > leaves > seeds > branches for both forests. The effective water-holding capacity was 48.7% and 49.3% for unlogged and logged, respectively, and the effective water retention was 10.3 t·ha−1 for both forests. The effective water retention in the rainy and dry seasons accounted for 12.5 t ha−1 and 7.2 t ha−1 for unlogged and logged, respectively. The maximum water retention was slightly greater for logged forests (16.7 t ha−1) than unlogged (16.3 t ha−1). The litter water content had 40% less water in the dry season than in the rainy in both forests. In general, there were no significant differences in litter storage and hydrological properties between stands. This suggests that reduced-impact logging did not significantly affect the hydrological dynamics of the litter layer in the Amazonian forests studied.
Thermally Enhanced Spreading of Miscible Plumes in Porous Media
Authors: Tigera Ryan G. , Benson Whitney L. , Mays David C.
Published: April 2023

In situ groundwater remediation often calls for a chemical or biological amendment to be injected as an aqueous solution into a contaminated groundwater aquifer. Accordingly, remediation depends on mixing the amendment into the contaminated groundwater, which, in turn, depends on spreading the plume of the injected amendment effectively. Here, we present proof-of-principle results from a laboratory study showing that amendment plume spreading can be enhanced by heating the injected water, which is consistent with the mechanism of miscible viscous fingering. The heated water has a lower viscosity, rendering a mobility ratio (i.e., log viscosity ratio) of 1.2 that generates elongated plume perimeters for essentially consistent plume areas. Using a quasi-two-dimensional apparatus and recording photographs after each increment of the injection volume, two image analysis techniques were employed to measure the area and perimeter of the injected plume, and the results are compared to isothermal controls, showing that the plume perimeter increased by 47% when determined by binary image analysis or 56% when determined by morphological image analysis. Accordingly, this study offers evidence that heating the injected water enhances miscible plume spreading in porous media.
Longitudinal SARS-CoV-2 Seroprevalence among Employees in Outpatient Care Services in Hamburg
Authors: Schablon Anja , Harth Volker , Terschüren Claudia , Kleinmüller Olaf , Wohlert Claudia , Schnabel Claudia , Brehm Thomas Theo , Schulze zur Wiesch Julian , Kersten Jan Felix , Nienhaus Albert
Published: April 2023

The risk of SARS-CoV-2 infection is particularly high for healthcare workers during the pandemic. Home care workers visit many different households per shift. Encounters with mostly elderly patients and their relatives increase the potential for the undetected spread of SARS-CoV-2. In order to gain insight into the seroprevalence of SARS-CoV-2 antibodies and possible transmission risks in outpatient care, this follow-up study was conducted with nursing services in Hamburg. The aim was to estimate the dynamics of seroprevalence in this occupational group over a 12-month period, to identify occupation-specific risk factors, and to collect information on the vaccination status of the surveyed nursing staff. Antibody testing for SARS-CoV-2 IgG against the S1 domain (EUROIMUN Analyser I® Lübeck, Germany) was performed on participating healthcare workers with patient contact at a total of four time points within one year from July 2020 to October 2021 (baseline, follow-up after three, six and twelve months). The data were mostly analysed descriptively. Differences in IgG titres were analysed using variance analysis methods, particularly Tukey’s range test. The seroprevalence was 1.2% (8/678) at baseline and 1.5% (9/581) at the three-month follow-up (T1). At the second follow-up (T2) after six months, vaccination against SARS-CoV-2 was available from January 2021 onwards. The prevalence rate of positive IgG antibodies relative to the S1 domain of the spike protein test among unvaccinated individuals was 6.5%. At (T3) after twelve months (July to October 2021), 482 participants were enrolled, and 85.7% of the workers were considered fully vaccinated at this time point, while 51 individuals were unvaccinated. The prevalence was 13.7% (7/51). In our study, a low seroprevalence was found among home care workers, which was lower than in our studies conducted in the clinical setting. Therefore, it can be assumed that the occupational risk of infection is rather low for both the nursing staff and the patients/clients cared for in the outpatient setting. The good provision of protective equipment and the high vaccination rate of the staff probably had a positive influence.
Reducing Plastic Pollution by Recovery and Recycling: Evidence from a “Blue Economy” Project Impacting Policy-Making in Italy
Authors: Vassallo Lorenzo , Appolloni Andrea , Fantauzzi Chiara , Frondizi Rocco
Published: April 2023

This paper recognizes the relevance of the Seabed Cleaning Project, created by the Angelo Vassallo Sindaco Pescatore Foundation in 2010, and presents it as a tool to achieve benefits in environmental, social, and economic terms, in line with the innovative framework of the Blue Economy. The project suggests a practical, feasible, and scalable solution to plastic pollution that can be obtained thanks to the activity performed by fishermen in cooperation with the municipality and local community (in a multi-level cooperation perspective). The data show a significant reduction of plastic on the seafloor thanks to the project, but further research is needed in order to collect further positive outcomes from different applications of the project. In 2022, the “Salva Mare” Law was approved in the Senate, extending the good practices proposed by the Foundation nationwide and showing how small gestures and concrete actions can provide significant improvements in pursuit of a healthier, safer, greener, and smarter city for the future.
White Spots: Prevention in Orthodontics—Systematic Review of the Literature
Authors: Patano Assunta , Malcangi Giuseppina , Sardano Roberta , Mastrodonato Antonio , Garofoli Grazia , Mancini Antonio , Inchingolo Alessio Danilo , Di Venere Daniela , Inchingolo Francesco , Dipalma Gianna , Inchingolo Angelo Michele
Published: April 2023

Early-stage dental demineralization, called white spots (WS), get their name from the characteristic colour that enamel takes on due to the acid attack of salivary cariogenic bacteria. They are often associated with fixed orthodontic therapy (FOT) and, if left untreated, evolve into caries with repercussions on oral health and dental aesthetics. This review aims to identify the most effective prophylaxis strategies to prevent WS during FOT. The search for the reviewed studies was conducted on the Pubmed, Scopus, and Web of Science databases, selecting English-only articles published in the 5 years from January 2018 to January 2023. The keywords used were “WS” and “fixed orthodontic*”, using “AND” as the Boolean operator. A total of 16 studies were included for qualitative analysis. Prevention begins with maintaining proper oral hygiene; fluoride in toothpaste, mouthwashes, gels, varnishes, and sealants can be added to prophylaxis and used regularly. Using a laser in combination with fluoride helps prevent the occurrence of WS and assists in the repair processes of initial lesions. Further studies are needed to establish international guidelines for preventing WS in orthodontically treated patients.
Investigating Geomorphic Change Using a Structure from Motion Elevation Model Created from Historical Aerial Imagery: A Case Study in Northern Lake Michigan, USA
Authors: DeWitt Jessica D. , Ashland Francis X.
Published: April 2023

South Manitou Island, part of Sleeping Bear Dunes National Lakeshore in northern Lake Michigan, is a post-glacial lacustrine landscape with substantial geomorphic changes including landslides, shoreline and bluff retreat, and sand dune movement. These changes involve interrelated processes, and are influenced to different extents by lake level, climate change, and land use patterns, among other factors. The utility of DEM of Difference (DoD) and other terrain analyses were investigated as a means of understanding interrelated geomorphologic changes and processes across multiple decades and at multiple scales. A 1m DEM was developed from 1955 historical aerial imagery using Structure from Motion Multi-View Stereo (SfM-MVS) and compared to a 2016 lidar-based DEM to quantify change. Landslides, shoreline erosion, bluff retreat, and sand dune movement were investigated throughout South Manitou Island. While the DoD indicates net loss or gain, interpretation of change must take into consideration the SfM-MVS source of the historical DEM. In the case of landslides, where additional understanding may be gleaned through review of the timing of lake high- and lowstands together with DoD values. Landscape-scale findings quantified cumulative feedbacks between interrelated processes. These findings could be upscaled to assess changes across the entire park, informing future change investigations and land management decisions.
Cisplatin in Ovarian Cancer Treatment—Known Limitations in Therapy Force New Solutions
Authors: Zoń Aleksandra , Bednarek Ilona
Published: April 2023

Cisplatin is one of the most commonly used anticancer drugs worldwide. It is mainly used in the treatment of ovarian cancer, but also used in testicular, bladder and lung cancers. The significant advantage of this drug is the multidirectional mechanism of its anticancer action, with the most important direction being damaging the DNA of cancer cells. Unfortunately, cisplatin displays a number of serious disadvantages, including toxicity to the most important organs, such as kidneys, heart, liver and inner ear. Moreover, a significant problem among patients with ovarian cancer, treated with cisplatin, is the development of numerous resistance mechanisms during therapy, including changes in the processes of cellular drug import and export, changes in the DNA damage repair mechanisms, as well as numerous changes in the processes of apoptosis and autophagy. Due to all of the mentioned problems, strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer are intensively sought. The most important strategy includes the development of less toxic cisplatin analogs. Another important direction is combination therapy, involving the simultaneous use of cisplatin with different anticancer drugs, substances derived from plants, temperature or radiotherapy. Many years of observations accompanying the presence of cisplatin in the therapy made it possible to provide a series of verifiable, statistically significant data, but also to show how, over time, with the new information and scientific discoveries, it is possible to describe and understand the therapeutic problems observed in practice, such as the acquisition of drug resistance by tumor cells or induction of changes in the tumor microenvironment. According to the authors, confronting what we knew so far with what new trends offer has a profound meaning. This paper presents information on the history of cisplatin and describes the molecular mechanisms of its action and the development of resistance by cancer cells. In addition, our goal was to highlight a number of therapeutic strategies to increase the effectiveness of cisplatin in the treatment of ovarian cancer, as well as to identify methods to eliminate problems associated with the use of cisplatin.
Microbial Transformations of Halolactones and Evaluation of Their Antiproliferative Activity
Authors: Mazur Marcelina , Zych Karolina Maria , Obmińska-Mrukowicz Bożena , Pawlak Aleksandra
Published: April 2023

The microbial transformations of lactones with a halogenoethylocyclohexane moiety were performed in a filamentous fungi culture. The selected, effective biocatalyst for this process was the Absidia glauca AM177 strain. The lactones were transformed into the hydroxy derivative, regardless of the type of halogen atom in the substrate structure. For all lactones, the antiproliferative activity was determined toward several cancer cell lines. The antiproliferative potential of halolactones was much broader than that observed for the hydroxyderivative. According to the presented results, the most potent was chlorolactone, which exhibited significant activity toward the T-cell lymphoma line (CL-1) cell line. The hydroxyderivative obtained through biotransformation was not previously described in the literature.
A Comparative Analysis to Dissect the Histological and Molecular Differences among Lipedema, Lipohypertrophy and Secondary Lymphedema
Authors: von Atzigen Julia , Burger Anna , Grünherz Lisanne , Barbon Carlotta , Felmerer Gunther , Giovanoli Pietro , Lindenblatt Nicole , Wolf Stefan , Gousopoulos Epameinondas
Published: April 2023

Lipedema, lipohypertrophy and secondary lymphedema are three conditions characterized by disproportionate subcutaneous fat accumulation affecting the extremities. Despite the apparent similarities and differences among their phenotypes, a comprehensive histological and molecular comparison does not yet exist, supporting the idea that there is an insufficient understanding of the conditions and particularly of lipohypertrophy. In our study, we performed histological and molecular analysis in anatomically-, BMI- and gender-matched samples of lipedema, lipohypertrophy and secondary lymphedema versus healthy control patients. Hereby, we found a significantly increased epidermal thickness only in patients with lipedema and secondary lymphedema, while significant adipocyte hypertrophy was identified in both lipedema and lipohypertrophy. Interestingly, the assessment of lymphatic vessel morphology showed significantly decreased total area coverage in lipohypertrophy versus the other conditions, while VEGF-D expression was significantly decreased across all conditions. The analysis of junctional genes often associated with permeability indicated a distinct and higher expression only in secondary lymphedema. Finally, the evaluation of the immune cell infiltrate verified the increased CD4+ cell and macrophage infiltration in lymphedema and lipedema respectively, without depicting a distinct immune cell profile in lipohypertrophy. Our study describes the distinct histological and molecular characteristics of lipohypertrophy, clearly distinguishing it from its two most important differential diagnoses.
Exome-Based Genomic Markers Could Improve Prediction of Checkpoint Inhibitor Efficacy Independently of Tumor Type
Authors: Dalens Lorraine , Lecuelle Julie , Favier Laure , Fraisse Cléa , Lagrange Aurélie , Kaderbhai Courèche , Boidot Romain , Chevrier Sandy , Mananet Hugo , Derangère Valentin , Truntzer Caroline , Ghiringhelli François
Published: April 2023

Immune checkpoint inhibitors (ICIs) have improved the care of patients in multiple cancer types. However, PD-L1 status, high Tumor Mutational Burden (TMB), and mismatch repair deficiency are the only validated biomarkers of efficacy for ICIs. These markers remain imperfect, and new predictive markers represent an unmet medical need. Whole-exome sequencing was carried out on 154 metastatic or locally advanced cancers from different tumor types treated by immunotherapy. Clinical and genomic features were investigated using Cox regression models to explore their capacity to predict progression-free survival (PFS). The cohort was split into training and validation sets to assess validity of observations. Two predictive models were estimated using clinical and exome-derived variables, respectively. Stage at diagnosis, surgery before immunotherapy, number of lines before immunotherapy, pleuroperitoneal, bone or lung metastasis, and immune-related toxicity were selected to generate a clinical score. KRAS mutations, TMB, TCR clonality, and Shannon entropy were retained to generate an exome-derived score. The addition of the exome-derived score improved the prediction of prognosis compared with the clinical score alone. Exome-derived variables could be used to predict responses to ICI independently of tumor type and might be of value in improving patient selection for ICI therapy.
A Multigene-Panel Study Identifies Single Nucleotide Polymorphisms Associated with Prostate Cancer Risk
Authors: Manca Maria Antonietta , Scarpa Fabio , Cossu Davide , Simula Elena Rita , Sanna Daria , Ruberto Stefano , Noli Marta , Ashraf Hajra , Solinas Tatiana , Madonia Massimo , Cusano Roberto , Sechi Leonardo A.
Published: April 2023

The immune system plays a critical role in modulating cancer development and progression. Polymorphisms in key genes involved in immune responses are known to affect susceptibility to cancer. Here, we analyzed 35 genes to evaluate the association between variants of genes involved in immune responses and prostate cancer risk. Thirty-five genes were analyzed in 47 patients with prostate cancer and 43 healthy controls using next-generation sequencing. Allelic and genotype frequencies were calculated in both cohorts, and a generalized linear mixed model was applied to test the relationship between prostate cancer risk and nucleotide substitution. Odds ratios were calculated to describe the association between each single nucleotide polymorphism (SNP) and prostate cancer risk. Significant changes in allelic and genotypic distributions were observed for IL4R, IL12RB1, IL12RB2, IL6, TMPRSS2, and ACE2. Furthermore, a generalized linear mixed model identified statistically significant associations between prostate cancer risk and SNPs in IL12RB2, IL13, IL17A, IL4R, MAPT, and TFNRS1B. Finally, a statistically significant association was observed between IL2RA and TNFRSF1B and Gleason scores, and between SLC11A1, TNFRSF1B and PSA values. We identified SNPs in inflammation and two prostate cancer-associated genes. Our results provide new insights into the immunogenetic landscape of prostate cancer and the impact that SNPs on immune genes may have on affecting the susceptibility to prostate cancer.
Differential Early Mechanistic Frontal Lobe Responses to Choline Chloride and Soy Isoflavones in an Experimental Model of Fetal Alcohol Spectrum Disorder
Authors: de la Monte Suzanne M. , Tong Ming , Delikkaya Busra
Published: April 2023

Fetal alcohol spectrum disorder (FASD) is the most common preventable cause of neurodevelopmental defects, and white matter is a major target of ethanol neurotoxicity. Therapeutic interventions with choline or dietary soy could potentially supplement public health preventive measures. However, since soy contains abundant choline, it would be important to know if its benefits are mediated by choline or isoflavones. We compared early mechanistic responses to choline and the Daidzein+Genistein (D+G) soy isoflavones in an FASD model using frontal lobe tissue to assess oligodendrocyte function and Akt-mTOR signaling. Long Evans rat pups were binge administered 2 g/Kg of ethanol or saline (control) on postnatal days P3 and P5. P7 frontal lobe slice cultures were treated with vehicle (Veh), Choline chloride (Chol; 75 µM), or D+G (1 µM each) for 72 h without further ethanol exposures. The expression levels of myelin oligodendrocyte proteins and stress-related molecules were measured by duplex enzyme-linked immunosorbent assays (ELISAs), and mTOR signaling proteins and phosphoproteins were assessed using 11-plex magnetic bead-based ELISAs. Ethanol’s main short-term effects in Veh-treated cultures were to increase GFAP and relative PTEN phosphorylation and reduce Akt phosphorylation. Chol and D+G significantly modulated the expression of oligodendrocyte myelin proteins and mediators of insulin/IGF-1-Akt-mTOR signaling in both control and ethanol-exposed cultures. In general, the responses were more robust with D+G; the main exception was that RPS6 phosphorylation was significantly increased by Chol and not D+G. The findings suggest that dietary soy, with the benefits of providing complete nutrition together with Choline, could be used to help optimize neurodevelopment in humans at risk for FASD.
Colorectal Cancer Chemoprevention: A Dream Coming True?
Authors: Lepore Signorile Martina , Grossi Valentina , Fasano Candida , Simone Cristiano
Published: April 2023

Colorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC.
A Review of CRISPR Tools for Treating Usher Syndrome: Applicability, Safety, Efficiency, and In Vivo Delivery
Authors: Major Lauren , McClements Michelle E. , MacLaren Robert E.
Published: April 2023

This review considers research into the treatment of Usher syndrome, a deaf-blindness syndrome inherited in an autosomal recessive manner. Usher syndrome mutations are markedly heterogeneous, involving many different genes, and research grants are limited due to minimal patient populations. Furthermore, gene augmentation therapies are impossible in all but three Usher syndromes as the cDNA sequence exceeds the 4.7 kb AAV packaging limit. It is, therefore, vital to focus research efforts on alternative tools with the broadest applicability. The CRISPR field took off in recent years following the discovery of the DNA editing activity of Cas9 in 2012. New generations of CRISPR tools have succeeded the original CRISPR/Cas9 model to enable more sophisticated genomic amendments such as epigenetic modification and precise sequence alterations. This review will evaluate the most popular CRISPR tools to date: CRISPR/Cas9, base editing, and prime editing. It will consider these tools in terms of applicability (in relation to the ten most prevalent USH2A mutations), safety, efficiency, and in vivo delivery potential with the intention of guiding future research investment.
APC Loss Prevents Doxorubicin-Induced Cell Death by Increasing Drug Efflux and a Chemoresistant Cell Population in Breast Cancer
Authors: Stefanski Casey D. , Arnason Anne , Maloney Sara , Kotsen Janna , Powers Elizabeth , Zhang Jian-Ting , Prosperi Jenifer R.
Published: April 2023

Chemoresistance is a major health concern affecting cancer patients. Resistance is multifactorial, with one mechanism being the increased expression of ABC transporters (such as MDR1 and MRP1), which are drug efflux transporters capable of preventing intracellular accumulation of drugs and cell death. Our lab showed that the loss of Adenomatous Polyposis Coli (APC) caused an intrinsic resistance to doxorubicin (DOX), potentially through an enhanced tumor-initiating cell (TIC) population and the increased activation of STAT3 mediating the expression of MDR1 in the absence of WNT being activated. Here, in primary mouse mammary tumor cells, the loss of APC decreased the accumulation of DOX while increasing the protein levels of MDR1 and MRP1. We demonstrated decreased APC mRNA and protein levels in breast cancer patients compared with normal tissue. Using patient samples and a panel of human breast cancer cell lines, we found no significant trend between APC and either MDR1 or MRP1. Since the protein expression patterns did not show a correlation between the ABC transporters and the expression of APC, we evaluated the drug transporter activity. In mouse mammary tumor cells, the pharmacological inhibition or genetic silencing of MDR1 or MRP1, respectively, decreased the TIC population and increased DOX-induced apoptosis, supporting the use of ABC transporter inhibitors as therapeutic targets in APC-deficient tumors.
Chalcone T4 Inhibits RANKL-Induced Osteoclastogenesis and Stimulates Osteogenesis In Vitro
Authors: de Matos Iolanda Augusta Fernandes , Fernandes Natalie Aparecida Rodrigues , Cirelli Giovani , de Godoi Mariely Araújo , de Assis Letícia Ribeiro , Regasini Luis Octávio , Rossa Junior Carlos , Guimarães-Stabili Morgana Rodrigues
Published: April 2023

Chalcones are phenolic compounds produced during the biosynthesis of flavonoids that have numerous biological activities, including anti-inflammatory, antioxidant and anticancer. In this in vitro study, we investigate a newly synthesized chalcone (Chalcone T4) in the context of bone turnover, specifically on the modulation of osteoclast differentiation and activity and osteoblast differentiation. Murine macrophages (RAW 264.7) and pre-osteoblasts (MC3T3-E1) were used as models of osteoclasts and osteoblasts, respectively. Differentiation and activity osteoclasts were induced by RANKL in the presence and absence of non-cytotoxic concentrations of Chalcone T4, added in different periods during osteoclastogenesis. Osteoclast differentiation and activity were assessed by actin ring formation and resorption pit assay, respectively. Expression of osteoclast-specific markers (Nfatc1, Oscar, Acp5, Mmp-9 and Ctsk) was determined by RT-qPCR, and the activation status of relevant intracellular signaling pathways (MAPK, AKT and NF-kB) by Western blot. Osteoblast differentiation and activity was induced by osteogenic culture medium in the presence and absence of the same concentrations of Chalcone T4. Outcomes assessed were the formation of mineralization nodules via alizarin red staining and the expression of osteoblast-related genes (Alp e Runx2) by RT-qPCR. Chalcone T4 reduced RANKL-induced osteoclast differentiation and activity, suppressed Oscar, Acp5 and Mmp-9 expression, and decreased ERK and AKT activation in a dose-dependent manner. Nfact1 expression and NF-kB phosphorylation were not modulated by the compound. Mineralized matrix formation and the expression of Alp and Runx2 by MC3T3-E1 cells were markedly stimulated by Chalcone T4. Collectively, these results demonstrate that Chalcone T4 inhibits in osteoclast differentiation and activity and stimulates osteogenesis, which indicates a promising therapeutic potential in osteolytic diseases.
Prenatal and Neonatal Pulmonary Thrombosis as a Potential Complication of SARS-CoV-2 Infection in Late Pregnancy
Authors: Abdulaziz-Opiela Gazala , Sobieraj Anna , Sibrecht Greta , Bajdor Julia , Mroziński Bartłomiej , Kozłowska Zuzanna , Iciek Rafał , Wróblewska-Seniuk Katarzyna , Wender-Ożegowska Ewa , Szczapa Tomasz
Published: April 2023

Neonatal venous thrombosis is a rare condition that can be iatrogenic or occur due to viral infections or genetic mutations. Thromboembolic complications are also commonly observed as a result of SARS-CoV-2 infections. They can affect pediatric patients, especially the ones suffering from multisystem inflammatory syndrome in children (MIS-C) or multisystem inflammatory syndrome in neonates (MIS-N). The question remains whether the maternal SARS-CoV-2 infection during pregnancy can lead to thromboembolic complications in fetuses and neonates. We report on a patient born with an embolism in the arterial duct, left pulmonary artery, and pulmonary trunk, who presented several characteristic features of MIS-N, suspecting that the cause might have been the maternal SARS-CoV2 infection in late pregnancy. Multiple genetic and laboratory tests were performed. The neonate presented only with a positive result of IgG antibodies against SARS-CoV-2. He was treated with low molecular weight heparin. Subsequent echocardiographic tests showed that the embolism dissolved. More research is necessary to evaluate the possible neonatal complications of maternal SARS-CoV-2 infection.
Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients
Authors: Rodríguez-Jiménez Carmen , de la Peña Gema , Sanguino Javier , Poyatos-Peláez Sara , Carazo Ana , Martínez-Hernández Pedro L. , Arrieta Francisco , Mostaza José M. , Gómez-Coronado Diego , Rodríguez-Nóvoa Sonia
Published: April 2023

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.
Determination and Comparison of Soybean Lecithin and Bovine Brain Plasmalogens Effects in Healthy Male Wistar Rats
Authors: Sidorova Yuliya S. , Sarkisyan Varuzhan A. , Petrov Nikita A. , Frolova Yuliya V. , Kochetkova Alla A.
Published: April 2023

The aim of this study was to investigate the effects of soybean lecithin and plasmalogens concentrating on a variety of physiological tests and biochemical analyses in healthy Wistar rats. For six weeks, male Wistar rats were given a standard diet that included plasmalogens or soybean lecithin. We measured anxiety levels, overall exploratory activity, short- and long-term memory, cognitive abilities, and grip strength. Lecithin increased significantly anxiety and enhanced memory and cognitive functions. Plasmalogens significantly improved appetite and increased grip strength. When compared to plasmalogens, lecithin significantly raised HDL levels while lowering LDL levels. The plasmalogens group showed a significant increase in the C16:0DMA/C16:0 ratio, which led us to assume that plasmalogen consumption could increase their synthesis in neural tissue. The study’s findings imply that, despite their various modes of action, soy lecithin and plasmalogens may both be significant nutritional components for enhancing cognitive functions.
The Wheel of p53 Helps to Drive the Immune System
Authors: Łasut-Szyszka Barbara , Rusin Marek
Published: April 2023

The p53 tumor suppressor protein is best known as an inhibitor of the cell cycle and an inducer of apoptosis. Unexpectedly, these functions of p53 are not required for its tumor suppressive activity in animal models. High-throughput transcriptomic investigations as well as individual studies have demonstrated that p53 stimulates expression of many genes involved in immunity. Probably to interfere with its immunostimulatory role, many viruses code for proteins that inactivate p53. Judging by the activities of immunity-related p53-regulated genes it can be concluded that p53 is involved in detection of danger signals, inflammasome formation and activation, antigen presentation, activation of natural killer cells and other effectors of immunity, stimulation of interferon production, direct inhibition of virus replication, secretion of extracellular signaling molecules, production of antibacterial proteins, negative feedback loops in immunity-related signaling pathways, and immunologic tolerance. Many of these p53 functions have barely been studied and require further, more detailed investigations. Some of them appear to be cell-type specific. The results of transcriptomic studies have generated many new hypotheses on the mechanisms utilized by p53 to impact on the immune system. In the future, these mechanisms may be harnessed to fight cancer and infectious diseases.
Leveraging Exosomes as the Next-Generation Bio-Shuttles: The Next Biggest Approach against Th17 Cell Catastrophe
Authors: Samarpita Snigdha , Li Xiaogang
Published: April 2023

In recent years, the launch of clinical-grade exosomes is rising expeditiously, as they represent a new powerful approach for the delivery of advanced therapies and for diagnostic purposes for various diseases. Exosomes are membrane-bound extracellular vesicles that can act as biological messengers between cells, in the context of health and disease. In comparison to several lab-based drug carriers, exosome exhibits high stability, accommodates diverse cargo loads, elicits low immunogenicity and toxicity, and therefore manifests tremendous perspectives in the development of therapeutics. The efforts made to spur exosomes in drugging the untreatable targets are encouraging. Currently, T helper (Th) 17 cells are considered the most prominent factor in the establishment of autoimmunity and several genetic disorders. Current reports have indicated the importance of targeting the development of Th17 cells and the secretion of its paracrine molecule, interleukin (IL)-17. However, the present-day targeted approaches exhibit drawbacks, such as high cost of production, rapid transformation, poor bioavailability, and importantly, causing opportunistic infections that ultimately hamper their clinical applications. To overcome this hurdle, the potential use of exosomes as vectors seem to be a promising approach for Th17 cell-targeted therapies. With this standpoint, this review discusses this new concept by providing a snapshot of exosome biogenesis, summarizes the current clinical trials of exosomes in several diseases, analyzes the prospect of exosomes as an established drug carrier and delineates the present challenges, with an emphasis on their practical applications in targeting Th17 cells in diseases. We further decode the possible future scope of exosome bioengineering for targeted drug delivery against Th17 cells and its catastrophe.
Human Embryonic Stem-Cell-Derived Exosomes Repress NLRP3 Inflammasome to Alleviate Pyroptosis in Nucleus Pulposus Cells by Transmitting miR-302c
Authors: Yu Yawen , Li Wenting , Xian Tinghui , Tu Mei , Wu Hao , Zhang Jiaqing
Published: April 2023

Recent studies have shown that the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is extensively activated in the process of intervertebral disc degeneration (IVDD), leading to the pyroptosis of nucleus pulposus cells (NPCs) and the exacerbation of the pathological development of the intervertebral disc (IVD). Exosomes derived from human embryonic stem cells (hESCs-exo) have shown great therapeutic potential in degenerative diseases. We hypothesized that hESCs-exo could alleviate IVDD by downregulating NLRP3. We measured the NLRP3 protein levels in different grades of IVDD and the effect of hESCs-exo on the H2O2-induced pyroptosis of NPCs. Our results indicate that the expression of NLRP3 was upregulated with the increase in IVD degeneration. hESCs-exo were able to reduce the H2O2-mediated pyroptosis of NPCs by downregulating the expression levels of NLRP3 inflammasome-related genes. Bioinformatics software predicted that miR-302c, an embryonic stem-cell-specific RNA, can inhibit NLRP3, thereby alleviating the pyroptosis of NPCs, and this was further verified by the overexpression of miR-302c in NPCs. In vivo experiments confirmed the above results in a rat caudal IVDD model. Our study demonstrates that hESCs-exo could inhibit excessive NPC pyroptosis by downregulating the NLRP3 inflammasome during IVDD, and miR-302c may play a key role in this process.
Impact Assessment of Implementing Several Retrofitting Strategies on the Air-Conditioning Energy Demand of an Existing University Office Building in Santiago, Chile
Authors: Venegas Tomás P. , Espinosa Byron A. , Cataño Francisco A. , Vasco Diego A.
Published: April 2023

This work analyzed the thermal behavior of an existing building, considering different retrofitting strategies. The methodology starts with an in-situ survey that allowed for obtaining information about occupation, work schedules, envelope materials, lighting, and equipment, which was vital to develop an energy model of the building. Then, the thermal analysis, employing simulations, demonstrates a higher relevance of heat flows through the building’s envelope than internal loads and higher cooling rather than heating demands. Afterward, several retrofit strategies focusing on modifying architectural elements were assessed. Finally, these strategies were compared based on their impact on the air-conditioning energy demand. A systematic review identified a lack of studies relating certification and energy policies to buildings retrofitting. Therefore, we assessed the energy performance of the building, when modified to meet the baseline requirements set on the Chilean certification requirements for sustainable buildings, to verify if the certification is a suitable method to assess the energy efficiency of an office building. Although the study only involves a single building, it aims to illustrate identified limitations using the energy policies for Chilean public buildings. The Chilean certification for sustainable buildings seems not to be suitable for the evaluation of energy consumption for the retrofit of existing buildings. Although this study does not demonstrate general trends, it presents a precedent for subsequent studies to evaluate the relevance of the Chilean certification guidelines.
High Poisonous Cd Ions Removal by Ru-ZnO-g-C3N4 Nanocomposite: Description and Adsorption Mechanism
Authors: Ismail Mukhtar , Albadri Abuzar , Ben Aissa Mohamed Ali , Modwi Abueliz , Saleh Sayed M.
Published: April 2023

Ru-ZnO-g-C3N4 nanocomposite was made using a straightforward ultrasonication method and evaluated for its potential to remove Cd ions from aqueous environments. X-ray diffraction analysis confirms composite production with an average crystalline size of 6.61 nm, while transmission electron microscopy results indicate nanosheet-like nanomaterials with uniform elements distribution. Measurements of N2 adsorption–desorption reveal the creation of a mesoporous structure with a BET surface area of approximately 257 m2/g. Fourier converted infrared reveals vibrational modes for O-H, amino groups, triazine, and Ru-ZnO. In contrast, X-ray photoelectron spectroscopy investigation reveals the presence of the elements Ru, Zn, O, N, and C. Ru-ZnO-g-C3N4 nanocomposite has remarkable adsorption efficiency for aqueous Cd ions, achieving 475.5 mg/g in 18 min. This study reveals that the Ru-ZnO-g-C3N4 nanocomposite may be used as an effective and reusable adsorbent for removing Cd ions during wastewater treatment and, possibly, for eliminating other toxic metal ions.
Evaluating the Sublethal Effects of Origanum vulgare Essential Oil and Carvacrol on the Biological Characteristics of Culex pipiens biotype molestus (Diptera: Culicidae)
Authors: Giatropoulos Athanasios , Koliopoulos George , Pantelakis Pavlos-Nektarios , Papachristos Dimitrios , Michaelakis Antonios
Published: April 2023

Culex pipiens is a mosquito species complex spread worldwide that poses a serious threat to human health as the primary vector of West Nile virus. Its control is mainly based on larvicidal applications with synthetic insecticides on mosquito breeding sites. However, the excessive use of synthetic larvicides may provoke mosquito resistance issues and negative side effects to the aquatic environment and human health. Plant-derived essential oils, including those from the Lamiaceae family, can be eco-friendly alternative larvicidal agents causing acute larval toxicity and/or growth inhibitory effects on the developmental stages of mosquitoes through different modes of action. In the current laboratory study, we evaluated the sublethal effects of carvacrol-rich oregano essential oil and pure carvacrol on Cx. pipiens biotype molestus, the autogenous member of the Cx. pipiens species complex, after the exposure of 3rd–4th instar larvae to LC50 concentrations. The short-term (24 h) larvicidal treatment with the sublethal concentrations of both tested materials exhibited an acute lethal effect on the exposed larvae as well as significant delayed mortality for surviving larvae and pupae. Larvicidal treatment with carvacrol reduced the longevity of the emerged males. In addition, the morphological abnormalities that were observed at the larval and pupal stage along with failed adult emergence indicate the potential growth inhibitory properties of the tested bioinsecticides. Our findings suggest that carvacrol and carvacrol-rich oregano oil are effective plant-based larvicides at doses lower than the acute lethal ones, thus promoting an environmentally friendly and more affordable perspective for their use against the WNV vector Cx. pipiens biotype molestus.
Research on the Design of Virtual Reality Online Education Information Presentation Based on Multi-Sensory Cognition
Authors: Wu Wen-Yu , Guo Jia-Yu , Li Ying-Jing , Sun Ying-Liang
Published: April 2023

The popularity of the online teaching model increased during the COVID-19, and virtual reality online education is now firmly established as a future trend in educational growth. Human–computer interaction and collaboration between virtual models and physical entities, as well as virtual multi-sensory cognition, have become the focus of research in the field of online education. In this paper, we analyze the mapping form of teaching information and cue information on users’ cognition through an experimental system and investigate the effects of the presentation form of online virtual teaching information, the length of the material, users’ memory of the information, and the presentation form of information cues on users’ cognitive performance. The experimental results show that different instructional information and cue presentation designs have significant effects on users’ learning performance, with relatively longer instructional content being more effective and users being more likely to mechanically remember the learning materials. By studying the impact of multi-sensory information presentation on users’ cognition, the output design of instructional information can be optimized, cognitive resources can be reasonably allocated, and learning effectiveness can be ensured, which is of great significance for virtual education research in digital twins.
Left Ventricle Segmental Longitudinal Strain and Regional Myocardial Work Index Could Help Determine Mitral Valve Prolapse Patients with Increased Risk of Ventricular Arrhythmias
Authors: Daniłowicz-Szymanowicz Ludmiła , Zienciuk-Krajka Agnieszka , Wabich Elżbieta , Fijałkowski Marcin , Fijałkowska Jadwiga , Młodziński Krzysztof , Raczak Grzegorz
Published: April 2023

Mitral valve prolapse (MVP) could associate with malignant ventricular arrhythmias (VAs). Mitral annular disjunction, a putative mechanism for an arrhythmic substrate, leads to excessive mobility, stretch, and damage of some segments. Speckle tracking echocardiography (STE), with particular attention to the segmental longitudinal strain and myocardial work index (MWI), could be an indicator of the segments we aimed to check. Seventy-two MVP patients and twenty controls underwent echocardiography. Complex VAs documented prospectively after the enrollment was qualified as the primary endpoint, which was noticed in 29 (40%) patients. Pre-specified cut-off values for peak segmental longitudinal strain (PSS) and segmental MWI for basal lateral (−25%, 2200 mmHg%), mid-lateral (−25%, 2500 mmHg%), mid-posterior (−25%, 2400 mmHg%), and mid-inferior (−23%, 2400 mmHg%) segments were accurate predictors of complex VAs. A combination of PSS and MWI increased the probability of the endpoint, reaching the highest predictive value for the basal lateral segment: odds ratio 32.15 (3.78–273.8), p < 0.001 for PSS ≥ −25% and MWI ≥ 2200 mmHg%. STE may be a valuable tool for assessing the arrhythmic risk in MVP patients. Excessively increased segmental longitudinal strain with an augmented regional myocardial work index identifies patients with the highest risk of complex VAs.