bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Biodegradation of BTEX and Stress Response in a Bio-Permeable Reactive Barrier Using Compound-Specific Isotope Analysis
Authors: Chen Tianyu , Wu Yan , Wang Jinnan , Philippe Corvini François-Xavier
Published: July 2022

By using compound-specific isotope analysis (CSIA) in combination with high-throughput sequencing analysis (HTS), we successfully evaluated the benzene and toluene biodegradation in a bio-permeable reactive barrier (bio-PRB) and the stress response of the microbial community. Under stress conditions, a greater decline in the biodegradation rate of BTEX was observed compared with the apparent removal rate. Both an increase in the influent concentration and the addition of trichloroethylene (TCE) inhibited benzene biodegradation, while toluene biodegradation was inhibited by TCE. Regarding the stress response, the relative abundance of the dominant bacterial community responsible for the biodegradation of BTEX increased with the influent concentration. However, the dominant bacterial community did not change, and its relative abundance was restored after the influent concentration decreased. On the contrary, the addition of TCE significantly changed the bacterial community, with Aminicenantes becoming the dominant phyla for co-metabolizing TCE and BTEX. Thus, TCE had a more significant influence on the bio-PRB than an increasing influent concentration, although these two stress conditions showed a similar degree of influence on the apparent removal rate of benzene and toluene. The present work not only provides a new method for accurately evaluating the biodegradation performance and microbial community in a bio-PRB, but also expands the application of compound-specific isotope analysis in the biological treatment of wastewater.
Health-Related Quality of Life of Moroccan COVID-19 Survivors: A Case-Control Study
Authors: Azizi Asmaa , Achak Doha , Saad Elmadani , Hilali Abderraouf , Nejjari Chakib , Khalis Mohamed , Youlyouz-Marfak Ibtissam , Marfak Abdelghafour
Published: July 2022

Background: Research on COVID-19 has mostly focused on transmission, mortality and morbidity associated with the virus. However, less attention has been given to its impact on health-related quality of life (HRQoL) of patients with COVID-19. Therefore, this study aimed to determine the demographic and clinical risk factors associated with COVID-19 and evaluate its impact on the HRQoL of COVID-19 survivors. Methods: A case-control study was carried out between September 2021 and March 2022 on 1105 participants. A total of 354 were COVID-19 survivors and 751 were the control group. The HRQoL was assessed using both EQ-5D-5L and SF-6D generic instruments. Results: The average age of all participants was 56.17 ± 15.46. Older age, urban area, tobacco use, presence of chronic diseases especially type 1 diabetes, kidney and cardiovascular diseases were significantly associated with COVID-19. The COVID-19 survivors had significantly lower HRQoL (EQ-VAS = 50.89) compared to the control group (EQ-VAS = 63.36) (p-value < 0.0001). Pain/ discomfort and anxiety/depression were the most negatively affected by COVID-19 (p-value < 0.0001). Conclusions: The findings from this study could help healthcare professionals and policy makers to better understand the HRQoL sequelae among the COVID-19 survivors and contribute to develop tailored interventions.
Understanding Social Media Literacy: A Systematic Review of the Concept and Its Competences
Authors: Polanco-Levicán Karina , Salvo-Garrido Sonia
Published: July 2022

Nowadays, people spend long periods on social media, ignoring the implications this carries in daily life. In this context, the concept of social media literacy, an emerging concept scarcely developed in the literature, is relevant. This study sought to analyze, descriptively, the main definitions and competences of the concept of social media literacy. The methodology included a systematic search of literature in the databases Web of Science, PubMed, and Scopus between 2010 and 2021, applying filters for English and Spanish, including only scientific articles. A total of 1093 articles were obtained. An article selection process took place, applying the inclusion and exclusion criteria, resulting in a total of 15 articles being selected. The findings indicate that the concept of social media literacy is based on media literacy to then integrate the characteristics and the implications of digital platforms. This is linked to the development of cognitive competences, where critical thinking, socio-emotional competences, and technical competences are fundamental, considering the social context. The development of socio-emotional competences stands out since social media are a frequent place of interaction between people.
Urban–Rural Comparison of the Association between Unsupportive Relationships, Perceived Stress, Authentic Self-Presentation, and Loneliness among Young Adults in Taiwan
Authors: Sun Yuting , Liang Chaoyun
Published: July 2022

This study examined and compared how unsupportive relationships, perceived stress, and authentic self-presentation influence loneliness and what differences exist between these relationships across urban and rural young adults in Taiwan. In total, 356 young adults (188 urban and 168 rural) were investigated, and partial least squares structural equation modelling was used in this study. The results indicated that authentic self-presentation directly and negatively affects loneliness in the urban group, but only indirectly affects loneliness in the rural group through unsupportive relationships and perceived stress. Unsupportive relationships and perceived stress in both the urban and rural groups positively affect their loneliness. In addition, multiple group analysis revealed that significant differences only existed between the effects of authentic self-presentation on unsupportive relationships between urban and rural young adults.
Investigations Concerning the Influence of Sleep Disorders on Postural Stability in Young Men
Authors: Tetych Anna , Olchowik Grażyna , Warchoł Jan
Published: July 2022

Lack of sleep is a factor that disrupts the receptors’ reception of information from the environment and contributes to the emergence of problems with maintaining balance. The main aim of the study was to determine whether sleep disorders affect postural stability in young men. The study participants were 76 male students who were divided into groups with good and poor sleep quality. The division was made based on the results obtained from the questionnaire of the Pittsburgh Sleep Quality Index (PSQI). In each group, postural stability had been tested using three main tests: Sensory Organization Test (SOT); Motor Control Test (MCT); and Adaptation Test (ADT). The results of the analysis show that the obtained results differ in the examined groups under the SOT test. Different values of the tested parameters were noted among people with poor sleep quality and compared with the values of those who sleep well, which translates into a difference in the ability to maintain balance. The greatest impact is observed when using visual and a vestibular system to maintain a stable posture. It was confirmed that the lack of sleep significantly disturbs postural stability.
Introduction to the Special Issue of IJERPH Entitled “Prenatal Exposure to Environmental Pollutants and Other Stressors: Impacts on Fetal Development, Birth Outcomes, Children’s Health and Beyond”
Authors: Röllin Halina B.
Published: July 2022

Environmental pollution is a major cause of global diseases, death and disability, with a toll greater than that caused by communicable diseases, such as HIV/AIDS, malaria and tuberculosis, combined [...]
The Importance of Post-Mortem Investigations in Stillbirths: Case Studies and a Review of the Literature
Authors: Scalise Carmen , Cordasco Fabrizio , Sacco Matteo Antonio , Ricci Pietrantonio , Aquila Isabella
Published: July 2022

Stillbirth has an important economic and social impact, though it remains “inexplicable” in many cases. We report the analysis of 11 cases of intrauterine fetal death carried out through a retrospective study conducted in the period between 2014 and 2017. The purpose of the study is to quantify the contribution of the autopsy and placental examination in identifying the cause of stillbirths. For each case, the medical record was analyzed with the relative maternal and partner data, the results of the external fetal and autopsy examination as well as the macroscopic and histological placental examination. The peak of stillbirth was found in a maternal age group between 30 and 39 years, below the 32nd week and above the 37th week of gestation. The results obtained from the clinical history and external fetal examination make it possible to trace the cause of death in only 18.2% of cases. By adding to these data, the results of the fetal autopsy and the placental examination, it is possible to establish the cause of death in 90.9% of cases. The most frequent abnormalities found in the placenta and cord were short or hypercoiled cord, umbilical cord vascular thrombosis, turns around the neck or stretching of the funiculus, placental infarction and placental insufficiency; also, amniotic fluid abnormalities, such as suspected oligohydramnios and chorioamniositi, were found. The accurate analysis of post-mortem placental and fetal examination is essential to reduce the number of unresponsive intrauterine fetal deaths. Determining the cause of fetal death must help clinicians and parents in better management and care in future pregnancies.
A Commentary on the Healthy Community Stores Case Study Project: Implications for Retailers, Policy, and Future Research
Authors: Sundermeir Samantha M. , Winkler Megan R. , John Sara , Colón-Ramos Uriyoán , Kaur Ravneet , Hickson Ashley , Dombrowski Rachael D. , Hill Alex B. , Bode Bree , DeAngelo Julia , Gittelsohn Joel
Published: July 2022

In the United States, low-income, underserved rural and urban settings experience poor access to healthy, affordable food. Introducing new food outlets in these locations has shown mixed results for improving healthy food consumption. The Healthy Community Stores Case Study Project (HCSCSP) explored an alternative strategy: supporting mission-driven, locally owned, healthy community food stores to improve healthy food access. The HCSCSP used a multiple case study approach, and conducted a cross-case analysis of seven urban healthy food stores across the United States. The main purpose of this commentary paper is to summarize the main practice strategies for stores as well as future directions for researchers and policy-makers based on results from the prior cross-case analyses. We organize these strategies using key concepts from the Retail Food Environment and Customer Interaction Model. Several key strategies for store success are presented including the use of non-traditional business models, focus on specific retail actors such as store champions and multiple vendor relationships, and a stores’ role in the broader community context, as well as the striking challenges faced across store locations. Further exploration of these store strategies and how they are implemented is needed, and may inform policies that can support these types of healthy retail sites and sustain their efforts in improving healthy food access in their communities.
Civilian Military Security Coordinators Coping with Frequent Traumatic Events: Spirituality, Community Resilience, and Emotional Distress
Authors: Weinberg Michael , Kimchy Elimellech Adi
Published: July 2022

Civilian military security coordinators are a unique kind of first responders. They live in communities that are close to the border and are responsible for the security of their community in routine and emergency situations until the arrival of the army or the police. Their role puts them at an elevated risk of experiencing emotional distress and developing PTSD. The present study, which was conducted in Israel following terror incidents over the year 2018, aimed to examine the relationships between spirituality and perceived community resilience, on the one hand, and PTSD symptoms and stress, on the other, among civilian military security coordinators. One hundred and thirteen (n = 113) civilian military security coordinators living up to 12.4 miles from the border who are routinely exposed to terror and other traumatic events completed demographic, spirituality, community resilience, PTSD, and stress questionnaires. Structural-equation-model analyses showed that spirituality was negatively associated with PTSD symptoms and stress. However, perceived community resilience was not associated with PTSD symptoms or stress. In addition, age was negatively associated with PTSD symptoms and stress. Financial situation was also negatively associated with PTSD symptoms and stress and incidence of exposure to terror and security threats was associated only with PTSD symptoms. Theoretical and practical implications are discussed.
Integrated Payment, Fragmented Realities? A Discourse Analysis of Integrated Payment in the Netherlands
Authors: Reindersma Thomas , Fabbricotti Isabelle , Ahaus Kees , Sülz Sandra
Published: July 2022

The current models used for paying for health and social care are considered a major barrier to integrated care. Despite the implementation of integrated payment schemes proving difficult, such initiatives are still widely pursued. In the Netherlands, this development has led to a payment architecture combining traditional and integrated payment models. To gain insight into the justification for and future viability of integrated payment, this paper’s purpose is to explain the current duality by identifying discourses on integrated payment models, determining which discourses predominate, and how they have changed over time and differ among key stakeholders in healthcare. The discourse analysis revealed four discourses, each with its own underlying assumptions and values regarding integrated payment. First, the Quality-of-Care discourse sees integrated payment as instrumental in improving care. Second, the Affordability discourse emphasizes how integrated payment can contribute to the financial sustainability of the healthcare system. Third, the Bureaucratization discourse highlights the administrative burden associated with integrated payment models. Fourth, the Strategic discourse stresses micropolitical and professional issues that come into play when implementing such models. The future viability of integrated payment depends on how issues reflected in the Bureaucratization and Strategic discourses are addressed without losing sight of quality-of-care and affordability, two aspects attracting significant public interest in The Netherlands.
Health and Wellbeing in Aging
Authors: Plácido Ana Isabel , Herdeiro Maria Teresa , Roque Fátima
Published: July 2022

Good health and wellbeing while aging is an ambitious goal proposed by the World Health Organization (WHO) and a core value for most governments [...]
Study of Novel Furocoumarin Derivatives on Anti-Vitiligo Activity, Molecular Docking and Mechanism of Action
Authors: Niu Chao , Zang Deng , Aisa Haji Akber
Published: July 2022

Vitiligo is a common chronic dermatological abnormality that afflicts tens of millions of people. Furocoumarins isolated from Uygur traditional medicinal material Psoralen corylifolia L. have been proven to be highly effective for the treatment of vitiligo. Although many furocoumarin derivatives with anti-vitiligo activity have been synthesized, their targets with respect to the disease are still ambiguous. Fortunately, the JAKs were identified as potential targets for the disease and its inhibitors have been proved to be effective in the treatment of vitiligo in many clinical trials. Thus, sixty-five benzene sulfonate and benzoate derivatives of furocoumarins (7a–7ad, 8a–8ag) with superior anti-vitiligo activity targeting JAKs were designed and synthesized based on preliminary research. The SAR was characterized after the anti-vitiligo-activity evaluation in B16 cells. Twenty-two derivatives showed more potent effects on melanin synthesis in B16 cells than the positive control (8-MOP). Among them, compounds 7y and 8 not only could increase melanin content, but they also improved the catecholase activity of tyrosinase in a concentration-dependent manner. The docking studies indicated that they were able to interact with amino acid residues in JAK1 and JAK2 via hydrogen bonds. Furthermore, candidate 8 showed a moderate inhibition of CXCL−10, which plays an important role in JAK–STAT signaling. The RT-PCR and Western blotting analyses illustrated that compounds 7y and 8 promoted melanogenesis by activating the p38 MAPK and Akt/GSK-3β/β-catenin pathways, as well as increasing the expressions of the MITF and tyrosinase-family genes. Finally, furocoumarin derivative 8 was recognized as a promising candidate for the fight against the disease and worthy of further research in vivo.
The Potential Application of Starch and Walnut Shells as Biofillers for Natural Rubber (NR) Composites
Authors: Sowińska-Baranowska Anna , Maciejewska Magdalena , Duda Paulina
Published: July 2022

The goal of this study was application of corn starch and ground walnut shells in various amounts by weight as biofillers of natural rubber (NR) biocomposites. Additionally, ionic liquid 1-butyl-3-methylimidazolium chloride (BmiCl) and (3-aminopropyl)-triethoxysilane (APTES) were used to increase the activity of biofillers and to improve the curing characteristics of NR composites. The effect of biofillers used and their modification with aminosilane or ionic liquid on the curing characteristics of NR composites and their functional properties, including crosslink density, mechanical properties in static and dynamic conditions, hardness, thermal stability and resistance to thermo-oxidative aging were investigated. Starch and ground walnut shells were classified as inactive fillers, which can be used alternatively to commercial inactive fillers, e.g., chalk. BmiCl and APTES were successfully used to support the vulcanization and to improve the dispersion of biofillers in NR elastomer matrix. Vulcanizates with starch, especially those containing APTES and BmiCl, exhibited improved tensile properties due to the higher crosslink density and homogenous dispersion of starch, which resulted from BmiCl addition. NR filled with ground walnut shells demonstrated improved resistance to thermo-oxidative aging. It resulted from lignin present in walnut shells, the components of which belong to polyphenols, that have an antioxidant activity.
Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma
Authors: Lim Jin Hong , Park Keunwan , Choi Kyung Hwa , Kim Chan Wung , Lee Jae Ha , Weicker Raymond , Pan Cheol-Ho , Kim Seok-Mo , Park Ki Cheong
Published: July 2022

Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells.
Organotypic Culture of Testicular Tissue from Infant Boys with Cryptorchidism
Authors: Wang Danyang , Hildorf Simone , Ntemou Elissavet , Mamsen Linn Salto , Dong Lihua , Pors Susanne Elisabeth , Fedder Jens , Clasen-Linde Erik , Cortes Dina , Thorup Jørgen , Andersen Claus Yding
Published: July 2022

Organotypic culture of human fetal testis has achieved fertilization-competent spermatids followed by blastocysts development. This study focuses on whether the organotypic culture of testicular tissue from infant boys with cryptorchidism could support the development of spermatogonia and somatic cells. Frozen-thawed tissues were cultured in two different media, with or without retinoic acid (RA), for 60 days and evaluated by tissue morphology and immunostaining using germ and somatic cell markers. During the 60-day culture, spermatocytes stained by boule-like RNA-binding protein (BOLL) were induced in biopsies cultured with RA. Increased AR expression (p < 0.001) and decreased AMH expression (p < 0.001) in Sertoli cells indicated advancement of Sertoli cell maturity. An increased number of SOX9-positive Sertoli cells (p < 0.05) was observed, while the percentage of tubules with spermatogonia was reduced (p < 0.001). More tubules with alpha-smooth muscle actin (ACTA, peritubular myoid cells (PTMCs) marker) were observed in an RA-absent medium (p = 0.02). CYP17A1/STAR-positive Leydig cells demonstrated sustained steroidogenic function. Our culture conditions support the initiation of spermatocytes and enhanced maturation of Sertoli cells and PTMCs within infant testicular tissues. This study may be a basis for future studies focusing on maintaining and increasing the number of spermatogonia and identifying different factors and hormones, further advancing in vitro spermatogenesis.
Genome-Wide Identification and Characterization of RNA/DNA Differences Associated with Fusarium graminearum Infection in Wheat
Authors: Yang Guang , Pan Yan , Zhao Qinlong , Huang Jiaqian , Pan Wenqiu , Cui Licao , Song Weining , Ouellet Therese , Pan Youlian , Nie Xiaojun
Published: July 2022

RNA/DNA difference (RDD) is a post-transcriptional modification playing a crucial role in regulating diverse biological processes in eukaryotes. Although it has been extensively studied in plant chloroplast and mitochondria genomes, RDDs in plant nuclear genomes are not well studied at present. Here, we investigated the RDDs associated with fusarium head blight (FHB) through a novel method by comparing the RNA-seq data between Fusarium-infected and control samples of four wheat genotypes. A total of 187 high-confidence unique RDDs in 36 genes were identified, representing the first landscape of the FHB-responsive RDD in wheat. The majority (26) of these 36 RDD genes were correlated either positively or negatively with FHB levels. Effects of these RDDs on RNA and protein sequences have been identified, their editing frequency and the expression level of the corresponding genes provided, and the prediction of the effect on the minimum folding free energy of mRNA, miRNA binding, and colocation of RDDs with conserved domains presented. RDDs were predicted to induce modifications in the mRNA and protein structures of the corresponding genes. In two genes, TraesCS1B02G294300 and TraesCS3A02G263900, editing was predicted to enhance their affinity with tae-miR9661-5p and tae-miR9664-3p, respectively. To our knowledge, this study is the first report of the association between RDD and FHB in wheat; this will contribute to a better understanding of the molecular basis underlying FHB resistance, and potentially lead to novel strategies to improve wheat FHB resistance through epigenetic methods.
Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence, Severity, and Treatment Response
Authors: Cederberg Katie L. J. , Hanif Umaer , Peris Sempere Vicente , Hédou Julien , Leary Eileen B. , Schneider Logan D. , Lin Ling , Zhang Jing , Morse Anne M. , Blackman Adam , Schweitzer Paula K. , Kotagal Suresh , Bogan Richard , Kushida Clete A. , Ju Yo-El S. , Petousi Nayia , Turnbull Chris D. , Mignot Emmanuel ,   The STAGES Cohort Investigator Group
Published: July 2022

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.
Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review
Authors: Ng Chiew Yong , Kee Li Ting , Al-Masawa Maimonah Eissa , Lee Qian Hui , Subramaniam Thayaalini , Kok David , Ng Min Hwei , Law Jia Xian
Published: July 2022

Extracellular vesicles (EVs) are minute vesicles with lipid bilayer membranes. EVs are secreted by cells for intercellular communication. Recently, EVs have received much attention, as they are rich in biological components such as nucleic acids, lipids, and proteins that play essential roles in tissue regeneration and disease modification. In addition, EVs can be developed as vaccines against cancer and infectious diseases, as the vesicle membrane has an abundance of antigenic determinants and virulent factors. EVs for therapeutic applications are typically collected from conditioned media of cultured cells. However, the number of EVs secreted by the cells is limited. Thus, it is critical to devise new strategies for the large-scale production of EVs. Here, we discussed the strategies utilized by researchers for the scalable production of EVs. Techniques such as bioreactors, mechanical stimulation, electrical stimulation, thermal stimulation, magnetic field stimulation, topographic clue, hypoxia, serum deprivation, pH modification, exposure to small molecules, exposure to nanoparticles, increasing the intracellular calcium concentration, and genetic modification have been used to improve the secretion of EVs by cultured cells. In addition, nitrogen cavitation, porous membrane extrusion, and sonication have been utilized to prepare EV-mimetic nanovesicles that share many characteristics with naturally secreted EVs. Apart from inducing EV production, these upscaling interventions have also been reported to modify the EVs’ cargo and thus their functionality and therapeutic potential. In summary, it is imperative to identify a reliable upscaling technique that can produce large quantities of EVs consistently. Ideally, the produced EVs should also possess cargo with improved therapeutic potential.
Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine
Authors: Kolatorova Lucie , Vitku Jana , Suchopar Josef , Hill Martin , Parizek Antonin
Published: July 2022

Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.
Exploring C-to-G and A-to-Y Base Editing in Rice by Using New Vector Tools
Authors: Zeng Dongchang , Zheng Zhiye , Liu Yuxin , Liu Taoli , Li Tie , Liu Jianhong , Luo Qiyu , Xue Yang , Li Shengting , Chai Nan , Yu Suize , Xie Xianrong , Liu Yao-Guang , Zhu Qinlong
Published: July 2022

CRISPR/Cas9-based cytosine base editors (CBEs) and adenine base editors (ABEs) can efficiently mediate C-to-T/G-to-A and A-to-G/T-to-C substitutions, respectively; however, achieving base transversions (C-to-G/C-to-A and A-to-T/A-to-C) is challenging and has been rarely studied in plants. Here, we constructed new plant C-to-G base editors (CGBEs) and new A-to-Y (T/C) base editors and explored their base editing characteristics in rice. First, we fused the highly active cytidine deaminase evoFENRY and the PAM-relaxed Cas9-nickase variant Cas9n-NG with rice and human uracil DNA N-glycosylase (rUNG and hUNG), respectively, to construct CGBE-rUNG and CGBE-hUNG vector tools. The analysis of five NG-PAM target sites showed that these CGBEs achieved C-to-G conversions with monoallelic editing efficiencies of up to 27.3% in T0 rice, with major byproducts being insertion/deletion mutations. Moreover, for the A-to-Y (C or T) editing test, we fused the highly active adenosine deaminase TadA8e and the Cas9-nickase variant SpGn (with NG-PAM) with Escherichia coli endonuclease V (EndoV) and human alkyladenine DNA glycosylase (hAAG), respectively, to generate ABE8e-EndoV and ABE8e-hAAG vectors. An assessment of five NG-PAM target sites showed that these two vectors could efficiently produce A-to-G substitutions in a narrow editing window; however, no A-to-Y editing was detected. Interestingly, the ABE8e-EndoV also generated precise small fragment deletions in the editing window from the 5′-deaminated A base to the SpGn cleavage site, suggesting its potential value in producing predictable small-fragment deletion mutations. Overall, we objectively evaluated the editing performance of CGBEs in rice, explored the possibility of A-to-Y editing, and developed a new ABE8e-EndoV tool, thus providing a valuable reference for improving and enriching base editing tools in plants.
MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer
Authors: Masi Letizia , Capobianco Ivan , Magrì Carlotta , Marafini Irene , Petito Valentina , Scaldaferri Franco
Published: July 2022

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). These are autoimmune diseases of the gastrointestinal tract with a chronic relapsing and remitting course. Due to complex interactions between multiple factors in the etiology of IBD, the discovery of new predictors of disease course and response to therapy, and the development of effective therapies is a significant challenge. The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules with a length of 18–25 nucleotides, that regulate gene expression by an RNA interference process, is implicated in the complex pathogenetic context of IBD. Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of disease severity of IBD. In this review, we summarize the expressed miRNA profile in blood, mucosal tissue, and stool and highlight the role of miRNAs as biomarkers with potential diagnostic and therapeutic applications in ulcerative colitis and Crohn’s disease. Moreover, we discuss the new perspectives in developing a new screening model for the detection of colorectal cancer (CRC) based on fecal miRNAs.
miR-143-3p Inhibits Aberrant Tau Phosphorylation and Amyloidogenic Processing of APP by Directly Targeting DAPK1 in Alzheimer’s Disease
Authors: Wang Long , Shui Xindong , Mei Yingxue , Xia Yongfang , Lan Guihua , Hu Li , Zhang Mi , Gan Chen-Ling , Li Ruomeng , Tian Yuan , Wang Quling , Gu Xi , Chen Dongmei , Zhang Tao , Lee Tae Ho
Published: July 2022

The neuropathology of Alzheimer’s disease (AD) is characterized by intracellular aggregation of hyperphosphorylated tau and extracellular accumulation of beta-amyloid (Aβ). Death-associated protein kinase 1 (DAPK1), as a novel therapeutic target, shows promise for the treatment of human AD, but the regulatory mechanisms of DAPK1 expression in AD remain unclear. In this study, we identified miR-143-3p as a promising candidate for targeting DAPK1. miR-143-3p directly bound to the 3′ untranslated region of human DAPK1 mRNA and inhibited its translation. miR-143-3p decreased tau phosphorylation and promoted neurite outgrowth and microtubule assembly. Moreover, miR-143-3p attenuated amyloid precursor protein (APP) phosphorylation and reduced the generation of Aβ40 and Aβ42. Furthermore, restoring DAPK1 expression with miR-143-3p antagonized the effects of miR-143-3p in attenuating tau hyperphosphorylation and Aβ production. In addition, the miR-143-3p levels were downregulated and correlated inversely with the expression of DAPK1 in the hippocampus of AD patients. Our results suggest that miR-143-3p might play critical roles in regulating both aberrant tau phosphorylation and amyloidogenic processing of APP by targeting DAPK1 and thus offer a potential novel therapeutic strategy for AD.
Critical Roles of NF-κB Signaling Molecules in Bone Metabolism Revealed by Genetic Mutations in Osteopetrosis
Authors: Jimi Eijiro , Katagiri Takenobu
Published: July 2022

The nuclear factor-κB (NF-κB) transcription factor family consists of five related proteins, RelA (p65), c-Rel, RelB, p50/p105 (NF-κB1), and p52/p100 (NF-κB2). These proteins are important not only for inflammation and the immune response but also for bone metabolism. Activation of NF-κB occurs via the classic and alternative pathways. Inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, activate the former, and cytokines involved in lymph node formation, such as receptor activator of NF-κB ligand (RANKL) and CD40L, activate the latter. p50 and p52 double-knockout mice revealed severe osteopetrosis due to the total lack of osteoclasts, which are specialized cells for bone resorption. This finding suggests that the activation of NF-κB is required for osteoclast differentiation. The NF-κB signaling pathway is controlled by various regulators, including NF-κB essential modulator (NEMO), which is encoded by the IKBKG gene. In recent years, mutant forms of the IKBKG gene have been reported as causative genes of osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-EDA-ID). In addition, a mutation in the RELA gene, encoding RelA, has been reported for the first time in newborns with high neonatal bone mass. Osteopetrosis is characterized by a diffuse increase in bone mass, ranging from a lethal form observed in newborns to an asymptomatic form that appears in adulthood. This review describes the genetic mutations in NF-κB signaling molecules that have been identified in patients with osteopetrosis.
Human Chorionic Villous Differentiation and Placental Development
Authors: Kojima Junya , Ono Masanori , Kuji Naoaki , Nishi Hirotaka
Published: July 2022

In humans, the placenta provides the only fetomaternal connection and is essential for establishing a pregnancy as well as fetal well-being. Additionally, it allows maternal physiological adaptation and embryonic immunological acceptance, support, and nutrition. The placenta is derived from extra-embryonic tissues that develop rapidly and dynamically in the first weeks of pregnancy. It is primarily composed of trophoblasts that differentiate into villi, stromal cells, macrophages, and fetal endothelial cells (FEC). Placental differentiation may be closely related to perinatal diseases, including fetal growth retardation (FGR) and hypertensive disorders of pregnancy (HDP), and miscarriage. There are limited findings regarding human chorionic villous differentiation and placental development because conducting in vivo studies is extremely difficult. Placental tissue varies widely among species. Thus, experimental animal findings are difficult to apply to humans. Early villous differentiation is difficult to study due to the small tissue size; however, a detailed analysis can potentially elucidate perinatal disease causes or help develop novel therapies. Artificial induction of early villous differentiation using human embryonic stem (ES) cells/induced pluripotent stem (iPS) cells was attempted, producing normally differentiated villi that can be used for interventional/invasive research. Here, we summarized and correlated early villous differentiation findings and discussed clinical diseases.
Developing New Treatments for COVID-19 through Dual-Action Antiviral/Anti-Inflammatory Small Molecules and Physiologically Based Pharmacokinetic Modeling
Authors: Zagaliotis Panagiotis , Petrou Anthi , Mystridis George , Geronikaki Athina , Vizirianakis Ioannis , Walsh Thomas
Published: July 2022

Broad-spectrum antiviral agents that are effective against many viruses are difficult to develop, as the key molecules, as well as the biochemical pathways by which they cause infection, differ largely from one virus to another. This was more strongly highlighted by the COVID-19 pandemic, which found health systems all over the world largely unprepared and proved that the existing armamentarium of antiviral agents is not sufficient to address viral threats with pandemic potential. The clinical protocols for the treatment of COVID-19 are currently based on the use of inhibitors of the inflammatory cascade (dexamethasone, baricitinib), or inhibitors of the cytopathic effect of the virus (monoclonal antibodies, molnupiravir or nirmatrelvir/ritonavir), using different agents. There is a critical need for an expanded armamentarium of orally bioavailable small-molecular medicinal agents, including those that possess dual antiviral and anti-inflammatory (AAI) activity that would be readily available for the early treatment of mild to moderate COVID-19 in high-risk patients. A multidisciplinary approach that involves the use of in silico screening tools to identify potential drug targets of an emerging pathogen, as well as in vitro and in vivo models for the determination of a candidate drug’s efficacy and safety, are necessary for the rapid and successful development of antiviral agents with potentially dual AAI activity. Characterization of candidate AAI molecules with physiologically based pharmacokinetics (PBPK) modeling would provide critical data for the accurate dosing of new therapeutic agents against COVID-19. This review analyzes the dual mechanisms of AAI agents with potential anti-SARS-CoV-2 activity and discusses the principles of PBPK modeling as a conceptual guide to develop new pharmacological modalities for the treatment of COVID-19.
Total and Plant Protein Consumption: The Role of Inflammation and Risk of Non-Communicable Disease
Authors: Azzini Elena , Peluso Ilaria , Intorre Federica , Barnaba Lorenzo , Venneria Eugenia , Foddai Maria Stella , Ciarapica Donatella , Maiani Francesca , Raguzzini Anna , Polito Angela
Published: July 2022

Background: Inflammatory cytokine levels are associated with Non-Communicable Diseases (NCDs) and can be influenced by a person’s macronutrient profile. This work aims to evaluate the relationship between the compliance with the age-specific recommended protein intake and the levels of inflammatory markers related to the risk of NCDs. Methods: The study participants included 347 participants (119 men and 228 women), ages 18 to 86 years. Cardio-metabolic risk evaluations, including an assessment of the prevalence of Metabolic Syndrome, were performed. Leptin, IL-15, IL-6, and TNF-α levels were measured. Results: The adequacy of the total protein (TP) intake was lower in old people compared to individuals aged <60 years, and only few volunteers consumed the suggested 50% plant protein (PP) for a healthy and sustainable diet. A lower risk of NCDs with a PP consumption above at least 40% was observed only in old individuals. A differential effect on TNF-α and IL-6 was observed for both TP and PP intake by gender and age class, whereas for leptin and IL-15 only significant interactions among sex and the class of age were found. Conclusion: Although our data suggest that consuming more than 40% of PP can reduce the risk of NCDs, the effect of gender differences on cytokine levels should be considered in larger studies.
Detection of Unprecedented CYP74 Enzyme in Mammal: Hydroperoxide Lyase CYP74C44 of the Bat Sturnira hondurensis
Authors: Gorina Svetlana S. , Iljina Tatiana M. , Mukhtarova Lucia S. , Toporkova Yana Y. , Grechkin Alexander N.
Published: July 2022

The genome of the neotropical fruit bat Sturnira hondurensis was recently sequenced, revealing an unexpected gene encoding a plant-like protein, CYP74C44, which shares ca. 90% sequence identity with the putative CYP74C of Populus trichocarpa. The preparation and properties of the recombinant CYP74C44 are described in the present work. The CYP74C44 enzyme was found to be active against the 13- and 9-hydroperoxides of linoleic and α-linolenic acids (13-HPOD, 13-HPOT, 9-HPOD, and 9-HPOT, respectively), as well as the 15-hydroperoxide of eicosapentaenoic acid (15-HPEPE). All substrates studied were specifically transformed into chain cleavage products that are typical for hydroperoxide lyases (HPLs). The HPL chain cleavage reaction was validated by the identification of NaBH4-reduced products (Me/TMS) of 15-HPEPE and 13- and 9-hydroperoxides as (all-Z)-14-hydroxy-5,8,11-tetradecatrienoic, (9Z)-12-hydroxy-9-dodecenoic, and 9-hydroxynonanoic acids (Me/TMS), respectively. Thus, CYP74C44 possessed the HPL activity that is typical for the CYP74C subfamily proteins.
Proteome-Wide Differential Effects of Peritoneal Dialysis Fluid Properties in an In Vitro Human Endothelial Cell Model
Authors: Sacnun Juan Manuel , Hoogenboom Robin , Eibensteiner Fabian , Sobieszek Isabel J. , Unterwurzacher Markus , Wagner Anja , Herzog Rebecca , Kratochwill Klaus
Published: July 2022

To replace kidney function, peritoneal dialysis (PD) utilizes hyperosmotic PD fluids with specific physico-chemical properties. Their composition induces progressive damage of the peritoneum, leading to vasculopathies, decline of membrane function, and PD technique failure. Clinically used PD fluids differ in their composition but still remain bioincompatible. We mapped the molecular pathomechanisms in human endothelial cells induced by the different characteristics of widely used PD fluids by proteomics. Of 7894 identified proteins, 3871 were regulated at least by 1 and 49 by all tested PD fluids. The latter subset was enriched for cell junction-associated proteins. The different PD fluids individually perturbed proteins commonly related to cell stress, survival, and immune function pathways. Modeling two major bioincompatibility factors of PD fluids, acidosis, and glucose degradation products (GDPs) revealed distinct effects on endothelial cell function and regulation of cellular stress responses. Proteins and pathways most strongly affected were members of the oxidative stress response. Addition of the antioxidant and cytoprotective additive, alanyl-glutamine (AlaGln), to PD fluids led to upregulation of thioredoxin reductase-1, an antioxidant protein, potentially explaining the cytoprotective effect of AlaGln. In conclusion, we mapped out the molecular response of endothelial cells to PD fluids, and provided new evidence for their specific pathomechanisms, crucial for improvement of PD therapies.
Regiospecific Grafting of Chitosan Oligomers Brushes onto Silicon Wafers
Authors: Garreau Cyrielle , Gablin Corinne , Léonard Didier , Delair Thierry , Sudre Guillaume , Trombotto Stéphane
Published: July 2022

The functionalization of surfaces using chitosan oligomers is of great interest for a wide range of applications in biomaterial and biomedical fields, as chitosan oligomers can provide various functional properties including biocompatibility, wetting, adhesion, and antibacterial activity. In this study, an innovative process for the regiospecific chemical grafting of reducing-end-modified chitosan oligomers brushes onto silicon wafers is described. Chitosan oligomers (COS) with well-defined structural parameters (average DP ~19 and DA ~0%) and bearing a 2,5-anhydro-d-mannofuranose (amf) unit at the reducing end were obtained via nitrous acid depolymerization of chitosan. After a silanization step where silicon wafers were modified with aromatic amine derivatives, grafting conditions were studied to optimize the reductive amination between aldehydes of amf-terminated COS and aromatic amines of silicon wafers. Functionalized surfaces were fully characterized by AFM, ATR-FTIR, ellipsometry, contact angle measurement, and ToF-SIMS techniques. Smooth surfaces were obtained with a COS layer about 3 nm thick and contact angle values between 72° and 76°. Furthermore, it was shown that the addition of the reducing agent NaBH3CN could positively improve the COS grafting density and/or led to a better stability of the covalent grafting to hydrolysis. Finally, this study also showed that this grafting process is also efficient for chitosan oligomers of higher DA (i.e., ~21%).
Genetic and Biochemical Aspects of Floral Scents in Roses
Authors: Shi Shaochuan , Zhang Zhao
Published: July 2022

Floral scents possess high ornamental and economic values to rose production in the floricultural industry. In the past two decades, molecular bases of floral scent production have been studied in the rose as well as their genetic inheritance. Some significant achievements have been acquired, such as the comprehensive rose genome and the finding of a novel geraniol synthase in plants. In this review, we summarize the composition of floral scents in modern roses, focusing on the recent advances in the molecular mechanisms of floral scent production and emission, as well as the latest developments in molecular breeding and metabolic engineering of rose scents. It could provide useful information for both studying and improving the floral scent production in the rose.
Cellular and Molecular Mechanisms in Oxidative Stress-Related Diseases
Authors: Remigante Alessia , Morabito Rossana
Published: July 2022

The redox equilibrium is important in preserving the correct functionality of vital cellular functions [...]