bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of COVID-19 Awareness on Protective Behaviors during the Off-Peak Period: Sex Differences among Chinese Undergraduates
Authors: Zhao Teng
Published: October 2022

COVID-19 remains an extreme threat in higher education settings, even during the off-peak period. Appropriate protective measures have been suggested to prevent the spread of COVID-19 in a large population context. Undergraduate students represent a highly vulnerable fraction of the population, so their COVID-19 protective behaviors play critical roles in enabling successful pandemic prevention. Hence, this study aims to understand what and how individual factors contribute to undergraduate students’ protective behaviors. After building multigroup structural equation models using data acquired from the survey taken by 991 undergraduates at a large research university in eastern China, I found that students’ COVID-19 awareness was positively associated with their protective behaviors, such as wearing a mask, using hand sanitizer, and maintaining proper social distance, but not with getting vaccinated. In addition, I found students with higher COVID-19 awareness were more likely to have more COVID-19 knowledge than those with less awareness. Furthermore, sex differences were observed in the mediation effects of COVID-19 awareness on wearing a mask and getting vaccinated, via COVID-19 knowledge, respectively. The results of this study have implications in helping higher education stakeholders enact effective measures to prevent the spread of the pandemic.
Microbial Contamination in the Coffee Industry: An Occupational Menace besides a Food Safety Concern?
Authors: Viegas Carla , Gomes Bianca , Oliveira Filipe , Dias Marta , Cervantes Renata , Pena Pedro , Gomes Anita Quintal , Caetano Liliana Aranha , Carolino Elisabete , de Andrade Ednilton Tavares , Viegas Susana
Published: October 2022

Respiratory abnormalities among workers at coffee roasting and packaging facilities have already been reported; however, little is known about microbiological contamination inside coffee production facilities. This study intends to assess the microbial contamination (fungi and bacteria) in two coffee industries from Brazil with a multi-approach protocol for sampling and for subsequent analyses using four main sources of samples: filtering respiratory protection devices (FRPD) used by workers, settled dust, electrostatic dust cloths (EDC) and coffee beans. The fungal contamination in the assessed industries was also characterized through the molecular detection of toxigenic species and antifungal resistance. Total bacteria contamination presented the highest values in FRPD collected from both industries (7.45 × 104 CFU·m−2; 1.09 × 104 CFU·m−2). Aspergillus genera was widespread in all the environmental samples collected and sections with clinical relevance (Fumigati) and with toxigenic potential (Nigri and Circumdati) were recovered from FRPD. Circumdati section was observed in 4 mg/mL itraconazole. Sections Circumdati (EDC, coffee beans and settled dust) and Nidulantes (EDC, coffee beans and FRPD) were detected by qPCR. Some of the targeted Aspergillus sections that have been identified microscopically were not detected by qPCR and vice-versa. Overall, this study revealed that microbial contamination is a potential occupational risk in the milling stage and should be tackled when assessing exposure and performing risk assessment. In addition, a multi-sampling campaign should be the approach to follow when assessing microbial contamination and FRPD should be included in this campaign. Occupational exposure to mycotoxins should be considered due to high fungal diversity and contamination. A One Health approach should address these issues in order to prevent consumption of coffee crops and beans infected by fungi and, more specifically, to avoid widespread azole resistance.
Enrichment of High Arsenic Groundwater Controlled by Hydrogeochemical and Physical Processes in the Hetao Basin, China
Authors: Cao Wengeng , Ren Yu , Dong Qiuyao , Li Zeyan , Xiao Shunyu
Published: October 2022

Based on 447 samples collected from a shallow aquifer (depths from 0 to 150 m) in the Hetao Basin, Northern China, an integrated hydrogeochemical approach was used in this study to conceptualize the enrichment of high arsenic groundwater in the Hetao Basin. An unconventional method of distinguishing hydrogeochemical and physical processes from a dataset was tested by investigating the cumulative frequency distribution of ionic ratios expressed on a probability scale. By applying cumulative frequency distribution curves to characterize the distribution of ionic ratios throughout the Hetao Basin, hydrogeochemical indicators were obtained that distinguish the series of hydrogeochemical processes that govern groundwater composition. All hydrogeochemical processes can basically be classified as recharge intensity of groundwater, evaporation concentration intensity, and reductive degree controlling the spatial distribution of arsenic. By considering the three processes, we found that the concentration of arsenic was more than 10 μg/L when the (HCO3−+CO32−)/SO42− ratio was over 4.1 (strong reductive area). As the evaporation concentration intensity increased, the median value of arsenic increased from 10.74 to 382.7 μg/L in the median reductive area and rapidly increased from 89.11 to 461.45 μg/L in the strong reductive area. As the river recharge intensity increased (with the intensity index increasing from 0 to 5), the median value of arsenic dropped from 40.2 to 6.8 μg/L in the median reductive area and decreased more markedly from 219.85 to 23.73 μg/L in the strong reductive area. The results provide a new insight into the mechanism of As enrichment in groundwater.
Impacts of Astaxanthin Supplementation on Walking Capacity by Reducing Oxidative Stress in Nursing Home Residents
Authors: Nakanishi Ryosuke , Kanazashi Miho , Tanaka Masayuki , Tanaka Minoru , Fujino Hidemi
Published: October 2022

Oxidative stress is associated with deterioration of endurance and muscle strength, which are mostly accompanied by aging. Astaxanthin supplement has excellent antioxidant activity without any pro-oxidative properties. In this study, we investigated how astaxanthin supplementation affects walking endurance and muscle strength in nursing home residents. Healthy elderly individuals (age: 67 to 94) were divided into two groups: 13 subjects received a daily dose of 24 mg of astaxanthin for 16 weeks (astaxanthin group) and 11 subjects received a placebo (placebo group). These subjects were compared using body component measurements, serum d-ROM levels, the distance of 6-min walking, blood lactate levels after the 6-min walking test, and muscle strength. After supplementation, the levels of d-ROMs and blood lactate after the 6-min walking test in the astaxanthin group significantly decreased compared with the placebo group (p < 0.05). Additionally, the walking distance was significantly higher in the astaxanthin group than in the placebo group (p < 0.05), despite a significant reduction in lactate levels after 6-MWT (p < 0.05). However, no significant intergroup differences were observed in muscle mass and strength. Astaxanthin supplement for 16 weeks is effective to increase the endurance capacity of the elderly. Astaxanthin supplement suppresses d-ROMs at rest and lactic acid production after the 6-min walk test. In contrast, astaxanthin supplement did not show significant intergroup differences in the muscle mass and strength. Therefore, the effect was most likely accompanied by an increase in endurance instead of an increase in muscle strength.
Personality Traits, Personal Values, and Life Satisfaction among Polish Nurses
Authors: Zalewska Anna M. , Zwierzchowska Marta
Published: October 2022

Nurses’ life satisfaction (LS) predicts their health and the level of care they provide to patients, thus policies for promoting quality of nurses’ work require actions to increase their LS. The aim of this study was to examine relations between LS and two levels of personality (traits and values) among Polish nurses, including joint effects of traits and values in a model integrating all variables to check whether meta-values can mediate trait–LS relationships. Nurses (N = 155) aged 23–64 completed the NEO-FFI, Satisfaction with Life Scale, and PVQ40. LS correlated with all traits, with openness higher than usual (0.34), and positively associated with meta-values: openness to change (0.23), self-transcendence (0.30), and (‘unhealthy’) conservation (0.19). Trait–value consistency was insufficient to explain some trait–value associations. In the SEM analysis, 23.3% of LS variance was explained. LS was related directly to neuroticism negatively and positively not only to extraversion, but also to openness, and self-transcendence meta-value (that increased value-environment congruence), and indirectly positively (through self-transcendence) to openness, agreeableness, conscientiousness, and even neuroticism. These results indicate that promoting nurses’ health and quality of work by enhancing their LS requires supporting and increasing their identification with self-transcendence values and encourage research on factors that can increase it.
Beyond Blue and Green Spaces: Identifying and Characterizing Restorative Environments on Sichuan Technology and Business University Campus
Authors: Du Yue , Zou Zan , He Yaodong , Zhou Yongge , Luo Shixian
Published: October 2022

Undergraduates commonly suffer from stress and anxiety; therefore, it is imperative to find restorative places on campus. Although blue and green spaces are good for recovery and stress relief, previous studies have failed to determine other types of restorative spaces on campuses. Using a bottom-up participatory smartphone photo survey, this study recruited a sample of 243 students from Sichuan Technology and Business University in China, and the results were as follows: (1) potential restorative spaces on campus were grouped into five categories: green, blue, gray, living, and study space; (2) no significant differences were found in the assessment of the five restorative spaces, all of which showed positive effects; (3) the five restorative spaces were linked with four restorative characteristics in different ways, with green, blue, gray, and living space showing the “being away” characteristic (refuges from the hassles of everyday life, indicate geographical or psychological distance), and gray and study spaces showing the “fascination” characteristic (effortless attention); (4) visit duration played an important role in the environment’s potential to promote recovery. A shorter visit duration owing to a lack of infrastructure and interest points may contribute to reduced benefits. This study has important implications for the design and management of restorative environments on college campuses.
Application of Social Network Analysis in the Economic Connection of Urban Agglomerations Based on Nighttime Lights Remote Sensing: A Case Study in the New Western Land-Sea Corridor, China
Authors: Zhang Bin , Yin Jian , Jiang Hongtao , Qiu Yuanhong
Published: October 2022

Nighttime lights remote sensing has a significant advantage in exploring the economic development of cities. Based on nighttime lighting data, this study employed spatial direction analysis, exploratory spatial data analysis, and social network analysis to explore the spatial characteristics of economic development and analyzed the economic connection network structures within urban agglomerations in the New Western Land-sea Corridor (NWLSC) in western China. The results show that the spatial pattern of the Tianshan North slope urban agglomeration, Guanzhong Plain urban agglomeration, and Lanzhou–Xining urban agglomeration shrank, while other urban agglomerations expanded. The city economy of the Chengdu–Chongqing urban agglomeration (CCUA) and the Beibu Gulf urban agglomeration varied dramatically according to a LISA space-time transition analysis, which indicates a strong spatial dependence between cities in the local space. Within urban agglomerations, the economic connection between cities increased significantly, and central cities were at the core of the network and significantly influenced other cities. Among the urban agglomerations, economic connections among neighboring urban agglomerations in geographic space increased during the study period. The CCUA gradually developed into the center of the economic network in the NWLSC. Network density positively influenced economic connections. The degree centrality, closeness centrality, and betweenness centrality significantly enhanced the economic connections between city agglomerations. The study’s conclusions and methods can serve as the policy support for the cooperative development of urban agglomerations in NWLSC serve as a guideline for the development of other economically underdeveloped regions in the world.
Comparative Genomic and Expression Analysis Insight into Evolutionary Characteristics of PEBP Genes in Cultivated Peanuts and Their Roles in Floral Induction
Authors: Zhong Chao , Li Zhao , Cheng Yunlian , Zhang Haina , Liu Yu , Wang Xiaoguang , Jiang Chunji , Zhao Xinhua , Zhao Shuli , Wang Jing , Zhang He , Liu Xibo , Yu Haiqiu
Published: October 2022

Phosphatidyl ethanolamine-binding proteins (PEBPs) are involved in regulating flowering time and various developmental processes. Functions and expression patterns in cultivated peanuts (Arachis hypogaea L.) remain unknown. In this study, 33 PEBP genes in cultivated peanuts were identified and divided into four subgroups: FT, TFL, MFT and FT-like. Gene structure analysis showed that orthologs from A and B genomes in cultivated peanuts had highly similar structures, but some orthologous genes have subgenomic dominance. Gene collinearity and phylogenetic analysis explain that some PEBP genes play key roles in evolution. Cis-element analysis revealed that PEBP genes are mainly regulated by hormones, light signals and stress-related pathways. Multiple PEPB genes had different expression patterns between early and late-flowering genotypes. Further detection of its response to temperature and photoperiod revealed that PEBPs ArahyM2THPA, ArahyEM6VH3, Arahy4GAQ4U, ArahyIZ8FG5, ArahyG6F3P2, ArahyLUT2QN, ArahyDYRS20 and ArahyBBG51B were the key genes controlling the flowering response to different flowering time genotypes, photoperiods and temperature. This study laid the foundation for the functional study of the PEBP gene in cultivated peanuts and the adaptation of peanuts to different environments.
Comprehensive Empirical Model of Substitution—Influence on Hydrogen Bonding in Aromatic Schiff Bases
Authors: Krupka Katarzyna M. , Pocheć Michał , Panek Jarosław J. , Jezierska Aneta
Published: October 2022

In this work, over 500 structures of tri-ring aromatic Schiff bases with different substitution patterns were investigated to develop a unified description of the substituent effect on the intramolecular hydrogen bridge. Both proximal and distal effects were examined using Density Functional Theory (DFT) in the gas phase and with solvent reaction field (Polarizable Continuum Model (PCM) and water as the solvent). In order to investigate and characterize the non-covalent interactions, a topological analysis was performed using the Quantum Theory of Atoms In Molecules (QTAIM) theory and Non-Covalent Interactions (NCI) index. The obtained results were summarized as the generalized, empirical model of the composite substituent effect, assessed using an additional group of simple ring-based Schiff bases. The composite substituent effect has been divided into separate increments describing the different interactions of the hydrogen bridge and the substituent: the classical substituent effect, involving resonance and induction mediated through the ring, steric increment based on substituent proximity to the bridge elements, and distal increment, derived from substitution on the distal ring.
In Vitro Assessment of Poly-N-Vinylpyrrolidone/Acrylic Acid Nanoparticles Biocompatibility in a Microvascular Endothelium Model
Authors: Berdiaki Aikaterini , Kuskov Andrey N. , Kulikov Pavel P. , Thrapsanioti Lydia-Nefeli , Giatagana Eirini-Maria , Stivaktakis Polychronis , Shtilman Mikhail I. , Tsatsakis Aristidis , Nikitovic Dragana
Published: October 2022

An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid—namely, p(VP-AA)-OD6000 (p(VP-AA))—was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells’ viability at the higher concentrations of 0.033 and 0.066 mg/mL (p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized (p = NS) did not affect individual adhesion molecules’ expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations.
Two Ligand-Binding Sites on SARS-CoV-2 Non-Structural Protein 1 Revealed by Fragment-Based X-ray Screening
Authors: Ma Shumeng , Damfo Shymaa , Lou Jiaqi , Pinotsis Nikos , Bowler Matthew W. , Haider Shozeb , Kozielski Frank
Published: October 2022

The regular reappearance of coronavirus (CoV) outbreaks over the past 20 years has caused significant health consequences and financial burdens worldwide. The most recent and still ongoing novel CoV pandemic, caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has brought a range of devastating consequences. Due to the exceptionally fast development of vaccines, the mortality rate of the virus has been curbed to a significant extent. However, the limitations of vaccination efficiency and applicability, coupled with the still high infection rate, emphasise the urgent need for discovering safe and effective antivirals against SARS-CoV-2 by suppressing its replication or attenuating its virulence. Non-structural protein 1 (nsp1), a unique viral and conserved leader protein, is a crucial virulence factor for causing host mRNA degradation, suppressing interferon (IFN) expression and host antiviral signalling pathways. In view of the essential role of nsp1 in the CoV life cycle, it is regarded as an exploitable target for antiviral drug discovery. Here, we report a variety of fragment hits against the N-terminal domain of SARS-CoV-2 nsp1 identified by fragment-based screening via X-ray crystallography. We also determined the structure of nsp1 at atomic resolution (0.99 Å). Binding affinities of hits against nsp1 and potential stabilisation were determined by orthogonal biophysical assays such as microscale thermophoresis and thermal shift assays. We identified two ligand-binding sites on nsp1, one deep and one shallow pocket, which are not conserved between the three medically relevant SARS, SARS-CoV-2 and MERS coronaviruses. Our study provides an excellent starting point for the development of more potent nsp1-targeting inhibitors and functional studies on SARS-CoV-2 nsp1.
Epigenetic Regulation by microRNAs in Hyperhomocysteinemia-Accelerated Atherosclerosis
Authors: Griñán Raquel , Escolà-Gil Joan Carles , Julve Josep , Benítez Sonia , Rotllan Noemí
Published: October 2022

Increased serum levels of homocysteine (Hcy) is a risk factor for cardiovascular disease and is specifically linked to various diseases of the vasculature such as atherosclerosis. However, the precise mechanisms by which Hcy contributes to this condition remain elusive. During the development of atherosclerosis, epigenetic modifications influence gene expression. As such, epigenetic modifications are an adaptive response to endogenous and exogenous factors that lead to altered gene expression by methylation and acetylation reactions of different substrates and the action of noncoding RNA including microRNAs (miRNAs). Epigenetic remodeling modulates cell biology in both physiological and physiopathological conditions. DNA and histone modification have been identified to have a crucial role in the progression of atherosclerosis. However, the potential role of miRNAs in hyperHcy (HHcy)-related atherosclerosis disease remains poorly explored and might be essential as well. There is no review available yet summarizing the contribution of miRNAs to hyperhomocystein-mediated atherogenicity or their potential as therapeutic targets even though their important role has been described in numerous studies. Specifically, downregulation of miR-143 or miR-125b has been shown to regulate VSCMs proliferation in vitro. In preclinical studies, downregulation of miR-92 or miR195-3p has been shown to increase the accumulation of cholesterol in foam cells and increase macrophage inflammation and atherosclerotic plaque formation, respectively. Another preclinical study found that there is a reciprocal regulation between miR-148a/152 and DNMT1 in Hcy-accelerated atherosclerosis. Interestingly, a couple of studies have shown that miR-143 or miR-217 may be used as potential biomarkers in patients with HHcy that may develop atherosclerosis. Moreover, the current review will also update current knowledge on miRNA-based therapies, their challenges, and approaches to deal with Hcy-induced atherosclerosis.
Nr1d1 Mediated Cell Senescence in Mouse Heart-Derived Sca-1+CD31− Cells
Authors: Pu Shiming , Wang Qian , Liu Qin , Zhao Hongxia , Zhou Zuping , Wu Qiong
Published: October 2022

Aim: Sca-1+CD31− cells are resident cardiac progenitor cells, found in many mammalian tissues including the heart, and able to differentiate into cardiomyocytes in vitro and in vivo. Our previous work indicated that heart-derived Sca-1+CD31− cells increased the Nr1d1 mRNA level of Nr1d1 with aging. However, how Nr1d1 affects the senescence of Sca-1+CD31− cells. Methods: Overexpression and knockdown of Nr1d1 in Sca-1+CD31− cells and mouse cardiac myocyte (MCM) cell lines were performed by lentiviral transduction. The effects of Nr1d1 abundance on cell differentiation, proliferation, apoptosis, cell cycle, and transcriptomics were evaluated. Moreover, binding of Nr1d1 to the promoter region of Nr4a3 and Serpina3 was examined by a luciferase reporter assay. Results and Conclusions: Upregulation Nr1d1 in young Sca-1+CD31− cells inhibited cell proliferation and promoted apoptosis. However, depletion of Nr1d1 in aged Sca-1+CD31− cells promoted cell proliferation and inhibited apoptosis. Furthermore, Nr1d1 was negatively associated with cell proliferation, promoting apoptosis and senescence-associated beta-galactosidase production in MCMs. Our findings show that Nr1d1 stimulates Serpina3 expression through its interaction with Nr4a3. Nr1d1 may therefore act as a potent anti-aging receptor that can be a therapeutic target for aging-related diseases.
Genomic Basis for Individual Differences in Susceptibility to the Neurotoxic Effects of Diesel Exhaust
Authors: Noël Alexandra , Ashbrook David G. , Xu Fuyi , Cormier Stephania A. , Lu Lu , O’Callaghan James P. , Menon Shyam K. , Zhao Wenyuan , Penn Arthur L. , Jones Byron C.
Published: October 2022

Air pollution is a known environmental health hazard. A major source of air pollution includes diesel exhaust (DE). Initially, research on DE focused on respiratory morbidities; however, more recently, exposures to DE have been associated with neurological developmental disorders and neurodegeneration. In this study, we investigated the effects of sub-chronic inhalation exposure to DE on neuroinflammatory markers in two inbred mouse strains and both sexes, including whole transcriptome examination of the medial prefrontal cortex. We exposed aged male and female C57BL/6J (B6) and DBA/2J (D2) mice to DE, which was cooled and diluted with HEPA-filtered compressed air for 2 h per day, 5 days a week, for 4 weeks. Control animals were exposed to HEPA-filtered air on the same schedule as DE-exposed animals. The prefrontal cortex was harvested and analyzed for proinflammatory cytokine gene expression (Il1β, Il6, Tnfα) and transcriptome-wide response by RNA-seq. We observed differential cytokine gene expression between strains and sexes in the DE-exposed vs. control-exposed groups for Il1β, Tnfα, and Il6. For RNA-seq, we identified 150 differentially expressed genes between air and DE treatment related to natural killer cell-mediated cytotoxicity per Kyoto Encyclopedia of Genes and Genomes pathways. Overall, our data show differential strain-related effects of DE on neuroinflammation and neurotoxicity and demonstrate that B6 are more susceptible than D2 to gene expression changes due to DE exposures than D2. These results are important because B6 mice are often used as the default mouse model for DE studies and strain-related effects of DE neurotoxicity warrant expanded studies.
Estimating the Similarity between Protein Pockets
Authors: Eguida Merveille , Rognan Didier
Published: October 2022

With the exponential increase in publicly available protein structures, the comparison of protein binding sites naturally emerged as a scientific topic to explain observations or generate hypotheses for ligand design, notably to predict ligand selectivity for on- and off-targets, explain polypharmacology, and design target-focused libraries. The current review summarizes the state-of-the-art computational methods applied to pocket detection and comparison as well as structural druggability estimates. The major strengths and weaknesses of current pocket descriptors, alignment methods, and similarity search algorithms are presented. Lastly, an exhaustive survey of both retrospective and prospective applications in diverse medicinal chemistry scenarios illustrates the capability of the existing methods and the hurdle that still needs to be overcome for more accurate predictions.
Sensitivity of Cutaneous T-Cell Lymphoma Cells to the Mcl-1 Inhibitor S63845 Correlates with the Lack of Bcl-w Expression
Authors: Sumarni Uly , Zhu Jiaqi , Sinnberg Tobias , Eberle Jürgen
Published: October 2022

Long-term, curative treatment of cutaneous T-cell lymphomas (CTCL) remains a major challenge. Therapy resistance is often based on apoptosis deficiency, and may depend on antiapoptotic Bcl-2 proteins, such as Bcl-2, Bcl-xL, Bcl-w and Mcl-1. For their targeting, several antagonists have been generated, which mimic the Bcl-2 homology domain 3 (BH3 mimetics). As dysregulation and overexpression of Mcl-1 has been reported in CTCL, the use of Mcl-1 inhibitors appears as an attractive strategy. Here, we investigated the effects of the selective Mcl-1 inhibitor S63845 in a series of four CTCL cell lines, in comparison to ABT-263 and ABT-737 (inhibitors of Bcl-2, Bcl-xL and Bcl-w). In two cell lines (HH, HuT-78), S63845 resulted in significant apoptosis induction, decrease in cell viability, loss of mitochondrial membrane potential and caspase activation, while two other cell lines (MyLa, SeAx) remained completely resistant. An inverse correlation was found, as S63845-resistant cells were highly sensitive to ABT-263/-737, and S63845-sensitive cells showed only moderate sensitivity to ABTs. Combinations of S63845 and ABT-263 partially yielded synergistic effects. As concerning Bcl-2 protein expression, weaker Mcl-1 expression was found in S63845-resistant MyLa and SeAx, while for Bcl-2 and Bcl-xL, the lowest expression was found in the highly sensitive cell line HH. The most striking difference between S63845-resistant and -sensitive cells was identified for Bcl-w, which was exclusively expressed in S63845-resistant cells. Thus, CTCL may be efficiently targeted by BH3 mimetics, providing the right target is preselected, and Bcl-w expression may serve as a suitable marker.
Antithrombin as Therapeutic Intervention against Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation: Lessons Learned from COVID-19-Associated Coagulopathy
Authors: Wiedermann Christian J.
Published: October 2022

Recent research has contributed significantly to our understanding of the pathogenesis of acute disseminated intravascular coagulation. COVID-19 can be considered as a new underlying condition of disseminated intravascular coagulation. In this narrative review, current evidence is presented regarding biomarker differences between sepsis-induced and COVID-19-associated coagulopathies, supporting the importance of acquired antithrombin deficiency in the early differential diagnosis of septic coagulopathy and its potential impact on treatment with endogenous anticoagulants. Establishing new scoring systems for septic coagulopathy in combination with endogenous anticoagulant biomarker activities may allow for the identification of those in the heterogeneous population of sepsis patients who are more likely to benefit from targeted specific treatment interventions.
Tryptophan Modulatory Role in European Seabass (Dicentrarchus labrax) Immune Response to Acute Inflammation under Stressful Conditions
Authors: Machado Marina , Peixoto Diogo , Santos Paulo , Ricardo Ana , Duarte Inês , Carvalho Inês , Aragão Cláudia , Azeredo Rita , Costas Benjamín
Published: October 2022

The present work aimed to study the role of dietary tryptophan supplementation in modulating the European seabass (Dicentrarchus labrax) immune condition during stressful rearing conditions (i.e., 15 days exposure to high density), as well as the immune response to acute inflammation after intraperitoneal injection of a bacterial pathogen. Stress alone did not compromise seabass health indicators. In contrast, a clear peripheral and local inflammatory response was observed in response to the inoculated bacteria. Moreover, exposure to a high stocking density seemed to exacerbate the inflammatory response at early sampling points, compared to fish stocked at a lower density. In contrast, stressed fish presented some immune-suppressing effects on the T-cell surface glycoprotein receptor expressions at a late sampling point following inflammation. Regarding the effects of dietary tryptophan, no changes were observed on seabass immune indicators prior to inflammation, while a small number of immunosuppressive effects were observed in response to inflammation, supporting tryptophan’s role in the promotion of immune-tolerance signals during inflammation. Nonetheless, tryptophan dietary supplementation improved the inflammatory response against a bacterial pathogen during stressful conditions, supported by a reduction of plasma cortisol levels, an up-regulation of several immune-related genes at 48 h, and an inversion of the previously observed, stress-induced T-cell suppression. Finally, the involvement of tryptophan catabolism in macrophages was confirmed by the up-regulation of genes involved in the kynurenine pathway. The present study brings new insights regarding the immune modulatory role of tryptophan during stressful conditions in fish, thus allowing for the development of novel prophylactic protocols during vaccination by intraperitoneal injection in the European seabass.
TSPO PET Imaging as a Potent Non-Invasive Biomarker for Diffuse Intrinsic Pontine Glioma in a Patient-Derived Orthotopic Rat Model
Authors: Chevaleyre Céline , Kereselidze Dimitri , Caillé Fabien , Tournier Nicolas , Olaciregui Nagore G. , Winkeler Alexandra , Declèves Xavier , Jego Benoit , Cisternino Salvatore , Auvity Sylvain , Truillet Charles
Published: October 2022

Diffuse intrinsic pontine gliomas (DIPG), the first cause of cerebral pediatric cancer death, will greatly benefit from specific and non-invasive biomarkers for patient follow-up and monitoring of drug efficacy. Since biopsies are challenging for brain tumors, molecular imaging may be a technique of choice to target and follow tumor evolution. So far, MR remains the imaging technique of reference for DIPG, although it often fails to define the extent of tumors, an essential parameter for therapeutic efficacy assessment. Thanks to its high sensitivity, positron emission tomography (PET) offers a unique way to target specific biomarkers in vivo. We demonstrated in a patient-derived orthotopic xenograft (PDOX) model in the rat that the translocator protein of 18 kDa (TSPO) may be a promising biomarker for monitoring DIPG tumors. We studied the distribution of 18F-DPA-714, a TSPO radioligand, in rats inoculated with HSJD-DIPG-007 cells. The primary DIPG human cell line HSJD-DIPG-007 highly represents this pediatric tumor, displaying the most prevalent DIPG mutations, H3F3A (K27M) and ACVR1 (R206H). Kinetic modeling and parametric imaging using the brain 18F-DPA-714 PET data enabled specific delineation of the DIPG tumor area, which is crucial for radiotherapy dose management.
Early Doxorubicin Myocardial Injury: Inflammatory, Oxidative Stress, and Apoptotic Role of Galectin-3
Authors: Al-Salam Suhail , Kandhan Karthishwaran , Sudhadevi Manjusha , Yasin Javed , Tariq Saeed
Published: October 2022

Doxorubicin (DOXO) is an effective drug that is used in the treatment of a large number of cancers. Regardless of its important chemotherapeutic characteristics, its usage is restricted because of its serious side effects; the most obvious is cardiotoxicity, which can manifest acutely or years after completion of treatment, leading to left ventricular dysfunction, dilated cardiomyopathy, and heart failure. Galectin 3 (Gal-3) is a beta galactoside binding lectin that has different roles in normal and pathophysiological conditions. Gal-3 was found to be upregulated in animal models, correlating with heart failure, atherosclerosis, and myocardial infarction. Male C57B6/J and B6.Cg-Lgals3 /J Gal-3 knockout (KO) mice were used for a mouse model of acute DOXO-induced cardiotoxicity. Mice were given DOXO or vehicle (normal saline), after which the mice again had free access to food and water. Heart and plasma samples were collected 5 days after DOXO administration and were used for tissue processing, staining, electron microscopy, and enzyme-linked immunosorbent assay (ELISA). There was a significant increase in the heart concentration of Gal-3 in Gal-3 wild type DOXO-treated mice when compared with the sham control. There were significantly higher concentrations of heart cleaved caspase-3, plasma troponin I, plasma lactate dehydrogenase, and plasma creatine kinase in Gal-3 KO DOXO-treated mice than in Gal-3 wild type DOXO-treated mice. Moreover, there were significantly higher heart antioxidant proteins and lower oxidative stress in Gal-3 wild type DOXO-treated mice than in Gal-3 KO DOXO-treated mice. In conclusion, Gal-3 can affect the redox pathways and regulate cell survival and death of the myocardium following acute DOXO injury.
Long-Term Adverse Effect of Liver Stiffness on Glycaemic Control in Type 2 Diabetic Patients with Nonalcoholic Fatty Liver Disease: A Pilot Study
Authors: Mantovani Alessandro , Taverna Antonio , Cappelli Davide , Beatrice Giorgia , Csermely Alessandro , Sani Elena , Byrne Christopher D. , Targher Giovanni
Published: October 2022

Currently, there are limited data regarding the long-term effect of liver stiffness on glycaemic control in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). We prospectively followed an outpatient sample of 61 consecutive postmenopausal women with T2DM and NAFLD who had baseline data on liver ultrasonography and Fibroscan®-assessed liver stiffness measurement (LSM) in 2017 and who underwent follow-up in 2022. Haemoglobin A1c (HbA1c) was measured both at baseline and follow-up. At baseline, 52 patients had NAFLD (hepatic steatosis) alone, and 9 had NAFLD with coexisting clinically significant fibrosis (defined as LSM ≥ 7 kPa on Fibroscan®). At follow-up, 16 patients had a worsening of glycaemic control (arbitrarily defined as HbA1c increase ≥ 0.5% from baseline). The prevalence of NAFLD and coexisting clinically significant fibrosis at baseline was at least three times greater among patients who developed worse glycaemic control at follow-up, compared with those who did not (31.3% vs. 8.9%; p = 0.030). In logistic regression analysis, the presence of NAFLD and clinically significant fibrosis was associated with an approximately 4.5-fold increased likelihood of developing worse glycaemic control at follow-up (odds ratio 4.66, 95% confidence interval 1.07–20.3; p = 0.041), even after adjustment for baseline confounding factors, such as age, body mass index, haemoglobin A1c (or HOMA-estimated insulin resistance) and use of some glucose-lowering agents that may positively affect NAFLD and liver fibrosis. In conclusion, our results suggest that the presence of Fibroscan®-assessed significant fibrosis was associated with a higher risk of developing worse glycaemic control in postmenopausal women with T2DM and NAFLD.
Molecular and Genetic Events Determining the Softening of Fleshy Fruits: A Comprehensive Review
Authors: Peng Zhenzhen , Liu Gangshuai , Li Hongli , Wang Yunxiang , Gao Haiyan , Jemrić Tomislav , Fu Daqi
Published: October 2022

Fruit softening that occurs during fruit ripening and postharvest storage determines the fruit quality, shelf life and commercial value and makes fruits more attractive for seed dispersal. In addition, over-softening results in fruit eventual decay, render fruit susceptible to invasion by opportunistic pathogens. Many studies have been conducted to reveal how fruit softens and how to control softening. However, softening is a complex and delicate life process, including physiological, biochemical and metabolic changes, which are closely related to each other and are affected by environmental conditions such as temperature, humidity and light. In this review, the current knowledge regarding fruit softening mechanisms is summarized from cell wall metabolism (cell wall structure changes and cell-wall-degrading enzymes), plant hormones (ETH, ABA, IAA and BR et al.), transcription factors (MADS-Box, AP2/ERF, NAC, MYB and BZR) and epigenetics (DNA methylation, histone demethylation and histone acetylation) and a diagram of the regulatory relationship between these factors is provided. It will provide reference for the cultivation of anti-softening fruits.
Importance of FaWRKY71 in Strawberry (Fragaria × ananassa) Fruit Ripening
Authors: Yue Maolan , Jiang Leiyu , Zhang Nating , Zhang Lianxi , Liu Yongqiang , Wang Yan , Li Mengyao , Lin Yuanxiu , Zhang Yunting , Zhang Yong , Luo Ya , Wang Xiaorong , Chen Qing , Tang Haoru
Published: October 2022

WRKY transcription factors play a nonnegligible role in plant growth and development, but little is known about the involvement of WRKY transcription factors in the regulation of fruit ripening. In this study, FaWRKY71 was identified to be closely related to fruit maturation in octoploid strawberry. FaWRKY71 protein localized in the nucleus and responded to cold, salt, low phosphate, ABA, and light quality in strawberry seedlings. The temporal and spatial pattern expression analysis indicated that FaWRKY71 was expressed in all the detected tissues, especially in the full red fruits. In addition, FaWRKY71 gave rise to the accumulation of anthocyanin content by promoting the expression of structural genes FaF3’H, FaLAR, FaANR, and transport factors FaTT19 and FaTT12 in the flavonoid pathway, and softening the texture of strawberry via up-regulating the abundance of FaPG19 and FaPG21. Furthermore, FaWRKY71 was a positive regulator that mediated resistance against reactive oxygen species by enhancing the enzyme activities of SOD, POD, and CAT, reducing the amount of MDA. Altogether, this study provides new and comprehensive insight into the regulatory mechanisms facilitating fruit ripening in strawberry.
The Role of Cryoprotective Agents in Liposome Stabilization and Preservation
Authors: Boafo George Frimpong , Magar Kosheli Thapa , Ekpo Marlene Davis , Qian Wang , Tan Songwen , Chen Chuanpin
Published: October 2022

To improve liposomes’ usage as drug delivery vehicles, cryoprotectants can be utilized to prevent constituent leakage and liposome instability. Cryoprotective agents (CPAs) or cryoprotectants can protect liposomes from the mechanical stress of ice by vitrifying at a specific temperature, which forms a glassy matrix. The majority of studies on cryoprotectants demonstrate that as the concentration of the cryoprotectant is increased, the liposomal stability improves, resulting in decreased aggregation. The effectiveness of CPAs in maintaining liposome stability in the aqueous state essentially depends on a complex interaction between protectants and bilayer composition. Furthermore, different types of CPAs have distinct effective mechanisms of action; therefore, the combination of several cryoprotectants may be beneficial and novel attributed to the synergistic actions of the CPAs. In this review, we discuss the use of liposomes as drug delivery vehicles, phospholipid–CPA interactions, their thermotropic behavior during freezing, types of CPA and their mechanism for preventing leakage of drugs from liposomes.
IsomiR-eQTL: A Cancer-Specific Expression Quantitative Trait Loci Database of miRNAs and Their Isoforms
Authors: Moradi Afshin , Whatmore Paul , Farashi Samaneh , Barrero Roberto A. , Batra Jyotsna
Published: October 2022

The identification of expression quantitative trait loci (eQTL) is an important component in efforts to understand how genetic variants influence disease risk. MicroRNAs (miRNAs) are short noncoding RNA molecules capable of regulating the expression of several genes simultaneously. Recently, several novel isomers of miRNAs (isomiRs) that differ slightly in length and sequence composition compared to their canonical miRNAs have been reported. Here we present isomiR-eQTL, a user-friendly database designed to help researchers find single nucleotide polymorphisms (SNPs) that can impact miRNA (miR-eQTL) and isomiR expression (isomiR-eQTL) in 30 cancer types. The isomiR-eQTL includes a total of 152,671 miR-eQTLs and 2,390,805 isomiR-eQTLs at a false discovery rate (FDR) of 0.05. It also includes 65,733 miR-eQTLs overlapping known cancer-associated loci identified through genome-wide association studies (GWAS). To the best of our knowledge, this is the first study investigating the impact of SNPs on isomiR expression at the genome-wide level. This database may pave the way for researchers toward finding a model for personalised medicine in which miRNAs, isomiRs, and genotypes are utilised.
Targeting CXCR4 and CD47 Receptors: An Overview of New and Old Molecules for a Biological Personalized Anticancer Therapy
Authors: Leo Manuela , Sabatino Lina
Published: October 2022

Biological therapy, with its multifaceted applications, has revolutionized the treatment of tumors, mainly due to its ability to exclusively target cancer cells and reduce the adverse effects on normal tissues. This review focuses on the therapies targeting the CXCR4 and CD47 receptors. We surveyed the results of early clinical trials testing compounds classified as nonpeptides, small peptides, CXCR4 antagonists or specific antibodies whose activity reduces or completely blocks the intracellular signaling pathways and cell proliferation. We then examined antibodies and fusion proteins against CD47, the receptor that acts as a “do not eat me” signal to phagocytes escaping immune surveillance. Despite these molecules being tested in early clinical trials, some drawbacks are emerging that impair their use in practice. Finally, we examined the ImmunoGenic Surrender mechanism that involves crosstalk and co-internalization of CXCR4 and CD47 upon engagement of CXCR4 by ligands or other molecules. The favorable effect of such compounds is dual as CD47 surface reduction impact on the immune response adds to the block of CXCR4 proliferative potential. These results suggest that a combination of different therapeutic approaches has more beneficial effects on patients’ survival and may pave the way for new accomplishments in personalized anticancer therapy.
Generating Fluent Fact Checking Explanations with Unsupervised Post-Editing
Authors: Jolly Shailza , Atanasova Pepa , Augenstein Isabelle
Published: October 2022

Fact-checking systems have become important tools to verify fake and misguiding news. These systems become more trustworthy when human-readable explanations accompany the veracity labels. However, manual collection of these explanations is expensive and time-consuming. Recent work has used extractive summarization to select a sufficient subset of the most important facts from the ruling comments (RCs) of a professional journalist to obtain fact-checking explanations. However, these explanations lack fluency and sentence coherence. In this work, we present an iterative edit-based algorithm that uses only phrase-level edits to perform unsupervised post-editing of disconnected RCs. To regulate our editing algorithm, we use a scoring function with components including fluency and semantic preservation. In addition, we show the applicability of our approach in a completely unsupervised setting. We experiment with two benchmark datasets, namely LIAR-PLUS and PubHealth. We show that our model generates explanations that are fluent, readable, non-redundant, and cover important information for the fact check.
UAVs for Medicine Delivery in a Smart City Using Fiducial Markers
Authors: Innocenti Eros , Agostini Giacomo , Giuliano Romeo
Published: October 2022

Drone delivery has gained increasing importance in the past few years. Recent technology advancements have allowed us to think of systems capable of transporting and delivering goods precisely and efficiently. However, in order to switch from a test environment to a real environment, many open issues need to be addressed. In this paper, we focused on drop-off point localization based on fiducial markers, analyzing different systems and the configuration of different aspects. We tested our system in a real-world environment and drew conclusions which lead us to identify the most reliable fiducial system and family for this use case.
(AI) in Infrastructure Projects—Gap Study
Authors: Abdel-Kader Mohamed Y. , Ebid Ahmed M. , Onyelowe Kennedy C. , Mahdi Ibrahim M. , Abdel-Rasheed Ibrahim
Published: October 2022

Infrastructure projects are usually complicated, expensive, long-term mega projects; accordingly, they are the type of projects that most need optimization in the design, construction and operation stages. A great deal of earlier research was carried out to optimize the performance of infrastructure projects using traditional management techniques. Recently, artificial intelligence (AI) techniques were implemented in infrastructure projects to improve their performance and efficiency due to their ability to deal with fuzzy, incomplete, inaccurate and distorted data. The aim of this research is to collect, classify, analyze and review all of the available previous research related to implementing AI techniques in infrastructure projects to figure out the gaps in the previous studies and the recent trends in this research area. A total of 159 studies were collected since the beginning of the 1990s until the end of 2021. This database was classified based on publishing date, infrastructure subject and the used AI technique. The results of this study show that implementing AI techniques in infrastructure projects is rapidly increasing. They also indicate that transportation is the first and the most AI-using project and that both artificial neural networks (ANN) and particle swarm optimization (PSO) are the most implemented techniques in infrastructure projects. Finally, the study presented some opportunities for farther research, especially in natural gas projects.