bluuebunny/crossref_metadata_2025 huggingface dataset:
Design by Nature: Emerging Applications of Native Liver Extracellular Matrix for Cholangiocyte Organoid-Based Regenerative Medicine
Authors: Willemse Jorke , van der Laan Luc J. W. , de Jonge Jeroen , Verstegen Monique M. A.
Published: March 2022

Organoid technology holds great promise for regenerative medicine. Recent studies show feasibility for bile duct tissue repair in humans by successfully transplanting cholangiocyte organoids in liver grafts during perfusion. Large-scale expansion of cholangiocytes is essential for extending these regenerative medicine applications. Human cholangiocyte organoids have a high and stable proliferation capacity, making them an attractive source of cholangiocytes. Commercially available basement membrane extract (BME) is used to expand the organoids. BME allows the cells to self-organize into 3D structures and stimulates cell proliferation. However, the use of BME is limiting the clinical applications of the organoids. There is a need for alternative tissue-specific and clinically relevant culture substrates capable of supporting organoid proliferation. Hydrogels prepared from decellularized and solubilized native livers are an attractive alternative for BME. These hydrogels can be used for the culture and expansion of cholangiocyte organoids in a clinically relevant manner. Moreover, the liver-derived hydrogels retain tissue-specific aspects of the extracellular microenvironment. They are composed of a complex mixture of bioactive and biodegradable extracellular matrix (ECM) components and can support the growth of various hepatobiliary cells. In this review, we provide an overview of the clinical potential of native liver ECM-based hydrogels for applications with human cholangiocyte organoids. We discuss the current limitations of BME for the clinical applications of organoids and how native ECM hydrogels can potentially overcome these problems in an effort to unlock the full regenerative clinical potential of the organoids.
Unmutated IGHV1-69 CLL Clone Displays a Distinct Gene Expression Profile by a Comparative qRT-PCR Assay
Authors: Mimmi Selena , Maisano Domenico , Dattilo Vincenzo , Gentile Massimo , Chiurazzi Federico , D’Ambrosio Alessandro , Zimbo Annamaria , Nisticò Nancy , Aloisio Annamaria , Vecchio Eleonora , Fiume Giuseppe , Iaccino Enrico , Quinto Ileana
Published: March 2022

Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease characterized by variable clinical courses among different patients. This notion was supported by the possible coexistence of two or more independent CLL clones within the same patients, identified by the characterization of the B cell receptor immunoglobulin (BcR IG) idiotypic sequence. By using the antigen-binding site of the BcR IG as bait, the identification and isolation of aggressive and drug-resistance leukemic B-cell clones could allow a deeper biological and molecular investigation. Indeed, by the screening of phage display libraries, we previously selected a peptide binder of the idiotypic region of CLL BCR IGs expressing the unmutated rearrangement IGHV1-69 and used it as a probe to perform a peptide-based cell sorting by flow cytometry in peripheral blood samples from patients with CLL. Since the IGHV1-69 clones persisted during the follow-up time in both patients, we explored the possibility of these clones having acquired an evolutive advantage compared to the other coexisting clones in terms of a higher expression of genes involved in the survival and apoptosis escape processes. To this end, we studied the expression patterns of a panel of genes involved in apoptosis regulation and in NF-kB-dependent pro-survival signals by comparative qRT-PCR assays. According to the results, IGHV1-69 clones showed a higher expression of pro-survival and anti-apoptotic genes as compared to the other CLL clones with different immunogenetic characteristics. Moreover, these IGHV1-69 clones did not carry any characteristic genetic lesions, indicating the relevance of our approach in performing a comprehensive molecular characterization of single tumor clones, as well as for designing new personalized therapeutic approaches for the most aggressive and persistent tumor clones.
Plasma Metabolomic Profiling Reveals Four Possibly Disrupted Mechanisms in Systemic Sclerosis
Authors: Bögl Thomas , Mlynek Franz , Himmelsbach Markus , Sepp Norbert , Buchberger Wolfgang , Geroldinger-Simić Marija
Published: March 2022

Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical mechanisms relevant to the pathophysiology of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry technology. The investigation of plasma samples from SSc patients (n = 52) compared to a control group (n = 48) allowed us to identify four different dysfunctional metabolic mechanisms, which can be assigned to the kynurenine pathway, the urea cycle, lipid metabolism, and the gut microbiome. These significantly altered metabolic pathways are associated with inflammation, vascular damage, fibrosis, and gut dysbiosis and might be relevant for the pathophysiology of SSc. Further studies are needed to explore the role of these metabolomic networks as possible therapeutic targets of SSc.
Triiodothyronine (T3) Induces Limited Transcriptional and DNA Methylation Reprogramming in Human Monocytes
Authors: Shepherd Rebecca , Kim Bowon , Saffery Richard , Novakovic Boris
Published: March 2022

Thyroid hormones have immunomodulatory roles, but their effects on the transcriptome and epigenome of innate immune cell types remain unexplored. In this study, we investigate the effects of triiodothyronine (T3) on the transcriptome and methylome of human monocytes in vitro, both in resting and lipopolysaccharide (LPS)-stimulated conditions. In resting monocytes, 5 µM T3 affected the expression of a small number of monocyte-to-macrophage differentiation-associated genes, including TLR4 (p-value < 0.05, expression fold change >1.5). T3 attenuated a small proportion of monocyte-to-macrophage differentiation-associated DNA methylation changes, while specifically inducing DNA methylation changes at several hundred differentially methylated CpG probes (DMPs) (p-value < 0.05, Δβ > 0.05). In LPS-stimulated monocytes, the presence of T3 attenuated the effect of 27% of LPS-induced DMPs (p-value < 0.05, Δβ > 0.05). Interestingly, co-stimulation with T3 + LPS induced a unique DNA methylation signature that was not observed in the LPS-only or T3-only exposure groups. Our results suggest that T3 induces limited transcriptional and DNA methylation remodeling in genes enriched in metabolism and immune processes and alters the normal in vitro LPS response. The overlap between differentially expressed genes and genes associated with DMPs was minimal; thus, other epigenetic mechanisms may underpin the expression changes. This research provides insight into the complex interplay between thyroid hormones, epigenetic remodeling, and transcriptional dynamics in monocytes.
Checkpoint Inhibitors and Induction of Celiac Disease-like Condition
Authors: Lerner Aaron , Benzvi Carina
Published: March 2022

Immune checkpoint inhibitors herald a new era in oncological therapy-resistant cancer, thus bringing hope for better outcomes and quality of life for patients. However, as with other medications, they are not without serious side effects over time. Despite this, their advantages outweigh their disadvantages. Understanding the adverse effects will help therapists locate, apprehend, treat, and perhaps diminish them. The major ones are termed immune-related adverse events (irAEs), representing their auto-immunogenic capacity. This narrative review concentrates on the immune checkpoint inhibitors induced celiac disease (CD), highlighting the importance of the costimulatory inhibitors in CD evolvement and suggesting several mechanisms for CD induction. Unraveling those cross-talks and pathways might reveal some new therapeutic strategies.
High-Density Lipoproteins and Cardiovascular Disease: The Good, the Bad, and the Future II
Authors: Julve Josep , Escolà-Gil Joan Carles
Published: March 2022

The notion that high-density lipoproteins (HDL) are atheroprotective is supported by different lines of evidence [...]
Cancer Detection Using an Artificial Secretable MicroRNA Found in Blood and Urine
Authors: Shueng Pei-Wei , Shih Kuang-Chung , Gambhir Sanjiv , Kuo Deng-Yu , Chuang Hui-Yen
Published: March 2022

Biomarkers can potentially help in the detection and prognosis of diseases such as cancer, its recurrence, predicting response to therapy, and monitoring of response during and/or after treatment. Endogenous tumor blood biomarkers suffer from low concentrations that are not distinguishable from background noise and, if identified, the localization of the biomarker production site is not known. The use of exogenously introduced or artificial biomarkers can eliminate these issues. In this study, we show that cancer cells can be made to produce an artificial secreted microRNA (Sec-miR) that can be detected in media from cells in culture, and from both blood and urine in living mice. In culture, we show that chaining a number of Sec-miR sequences in a plasmid and transfecting cells with the plasmids could increase Sec-miR secretion as the number of sequences increases. Tumor induction in mice with a stably transfected HeLa cell line shows the presence and significant increase in the Sec-miR with time and tumor growth in plasma (p < 0.001, R2 = 0.5542). The relative half-life of the Sec-miR was seen to be 1.2 h in the plasma of living mice and was seen to appear in urine within 12 h. The transgene for the Sec-miR within a minicircle was introduced via the tail-vein into subcutaneous tumor-bearing mice. As the tumor growth increased with time, further in vivo transfection of the Sec-miR minicircles showed an increase in Sec-miR in both plasma and urine (R2 = 0.4546). This study demonstrated that an exogenous Sec-miR biomarker would allow for early tumor detection using in vitro diagnostics techniques.
Self-Powered Wearable Biosensor in a Baby Diaper for Monitoring Neonatal Jaundice through a Hydrovoltaic-Biosensing Coupling Effect of ZnO Nanoarray
Authors: Ning Zirui , Long Zhihe , Yang Guangyou , Xing Lili , Xue Xinyu
Published: March 2022

Neonatal jaundice refers to the abnormality of bilirubin metabolism for newborns, and wearable transcutaneous bilirubin meters for real-time measuring the bilirubin concentration is an insistent demand for the babies’ parents and doctors. In this paper, a self-powered wearable biosensor in a baby diaper for real-time monitoring neonatal jaundice has been realized by the hydrovoltaic-biosensing coupling effect of ZnO nanoarray. Without external power supply, the system can work independently, and the hydrovoltaic output can be treated as both the power source and biosensing signal. The working mechanism is that the hydrovoltaic output arises from the urine flowing on ZnO nanoarray and the enzymatic reaction on the surface can influence the output. The sensing information can be transmitted through a wireless transmitter, and thus the parents and doctors can treat the neonatal jaundice of babies in time. This work can potentially promote the development of next generation of biosensors and physiological monitoring system, and expand the scope of self-powered technique and smart healthcare area.
Cognitive Considerations in Major Depression: Evaluating the Effects of Pharmacotherapy and ECT on Mood and Executive Control Deficits
Authors: Spagna Alfredo , Wang Jason , Rosario Isabella Elaine , Zhang Li , Zu Meidan , Wang Kai , Tian Yanghua
Published: March 2022

Deficits in the executive control of attention greatly impact the quality of life of patients diagnosed with major depressive disorder (MDD). However, attentional deficits are often underemphasized in clinical contexts compared with mood-based symptoms, and a comprehensive approach for specifically evaluating and treating them has yet to be developed. The present study evaluates the efficacy of bifrontal electroconvulsive therapy (ECT) combined with drug therapy (DT) in alleviating mood-related symptomatology and executive control deficits in drug-refractory MDD patients and compares these effects with those observed in MDD patients undergoing DT only. The Hamilton Rating Scale for Depression and the Lateralized Attentional Network Test-Revised were administered across two test sessions to assess treatment-related changes in mood-based symptoms and conflict processing, respectively, in patients undergoing ECT + DT (n = 23), patients undergoing DT (n = 33), and healthy controls (n = 40). Although both groups showed an improvement in mood-based symptoms following treatment and a deficit in conflict processing estimated on error rate, a post-treatment reduction of an executive control deficit estimated on RT was solely observed in the ECT + DT patient group. Furthermore, Bayesian correlational analyses confirmed the dissociation of mood-related symptoms and of executive control measures, supporting existing literature proposing that attentional deficits and mood symptoms are independent aspects of MDD. The cognitive profile of MDD includes executive control deficits, and while both treatments improved mood-based symptoms, only ECT + DT exerted an effect on both measures of the executive control deficit. Our findings highlight the importance of considering the improvement in both mood and cognitive deficits when determining the efficacy of therapeutic approaches for MDD.
Factors Influencing High-Rise Gated Community Collective Action Effectiveness: Conceptualization of the Social-Ecological System (SES) Framework
Authors: Shi Xuerui , Ling Gabriel Hoh Teck
Published: March 2022

Managing common property in gated communities is challenging. Although numerous studies have demonstrated that there are several determinants of collective action effectiveness and performances in gated communities, empirical research drawing on a multidimensional social-ecological system (SES) framework in quantitatively exploring relationships between institutional–physical–social factors and gated community collective action remains lacking. Therefore, based on Ostrom’s social-ecological system (SES) framework, this study attempts to identify factors influencing the self-organizing system (collective action) of gated communities in China. Using stratified purposive sampling, ten gated communities with various characteristics in the Taigu district were selected, in which questionnaires were then distributed to 414 households to collect valid data within the communities. Taking the ridge regression as a more robust predictive SES model with a penalty value of k = 0.1 and regularization, R Square of 0.882, this study, among 14 factors, ultimately identified six key institutional–social–ecological factors based on the descending standardized effect size, and they are: (i) types of community; (ii) presence of leaders; (iii) exclusiveness systems of a gated community; (iv) age of gated community; (v) strict enforcement of rules; and (vi) number of households that affect residents’ collective action in terms of community security, hygiene and cleanliness, and facility quality. The research findings provide urban managers and communities novel insights to formulate strategic policies towards sustainable housing and building management.
Tumor-Tissue Expression of the Hyaluronic Acid Receptor RHAMM Predicts Histological Transformation in Follicular Lymphoma Patients
Authors: Enemark Marie Beck , Hybel Trine Engelbrecht , Madsen Charlotte , Lauridsen Kristina Lystlund , Honoré Bent , Plesner Trine Lindhardt , Hamilton-Dutoit Stephen , d’Amore Francesco , Ludvigsen Maja
Published: March 2022

Histological transformation (HT) remains the leading cause of mortality in follicular lymphoma (FL), underlining the need to identify reliable transformation predictors. The hyaluronic acid receptors CD44 and the receptor for hyaluronan mediated motility (RHAMM, also known as HMMR and CD168), have been shown to be involved in the pathogeneses of both solid tumors and hematological malignancies. In an attempt to improve risk stratification, expression of RHAMM and CD44 were evaluated by immunohistochemistry and digital image analysis in pre-therapeutic tumor-tissue biopsies from FL patients, either without (nt-FL, n = 34), or with (st-FL, n = 31) subsequent transformation, and in paired biopsies from the transformed lymphomas (tFL, n = 31). At the time of initial diagnosis, samples from st-FL patients had a higher expression of RHAMM compared with samples from nt-FL patients (p < 0.001). RHAMM expression further increased in tFL samples following transformation (p < 0.001). Evaluation of CD44 expression showed no differences in expression comparing nt-FL, st-FL, and tFL samples. Shorter transformation-free survival was associated with high tumoral and intrafollicular RHAMM expression, as well as with low intrafollicular CD44 expression (p = 0.002, p < 0.001, and p = 0.034, respectively). Our data suggest that high tumor-tissue RHAMM expression predicts the risk of shorter transformation-free survival in FL patients already at initial diagnosis.
Association between Antibiotic Exposure and Systemic Immune Parameters in Cancer Patients Receiving Checkpoint Inhibitor Therapy
Authors: von Itzstein Mitchell S. , Gonugunta Amrit S. , Sheffield Thomas , Homsi Jade , Dowell Jonathan E. , Koh Andrew Y. , Raj Prithvi , Fattah Farjana , Wang Yiqing , Basava Vijay S. , Khan Shaheen , Park Jason Y. , Popat Vinita , Saltarski Jessica M. , Gloria-McCutchen Yvonne , Hsiehchen David , Ostmeyer Jared , Xie Yang , Li Quan-Zhen , Wakeland Edward K. , Gerber David E.
Published: March 2022

Antibiotic administration is associated with worse clinical outcomes and changes to the gut microbiome in cancer patients receiving immune checkpoint inhibitors (ICI). However, the effects of antibiotics on systemic immune function are unknown. We, therefore, evaluated antibiotic exposure, therapeutic responses, and multiplex panels of 40 serum cytokines and 124 antibodies at baseline and six weeks after ICI initiation, with p < 0.05 and false discovery rate (FDR) < 0.2 considered significant. A total of 251 patients were included, of whom the 135 (54%) who received antibiotics had lower response rates and shorter survival. Patients who received antibiotics prior to ICI initiation had modestly but significantly lower baseline levels of nucleolin, MDA5, c-reactive protein, and liver cytosol antigen type 1 (LC1) antibodies, as well as higher levels of heparin sulfate and Matrigel antibodies. After ICI initiation, antibiotic-treated patients had significantly lower levels of MDA5, CENP.B, and nucleolin antibodies. Although there were no clear differences in cytokines in the overall cohort, in the lung cancer subset (53% of the study population), we observed differences in IFN-γ, IL-8, and macrophage inflammatory proteins. In ICI-treated patients, antibiotic exposure is associated with changes in certain antibodies and cytokines. Understanding the relationship between these factors may improve the clinical management of patients receiving ICI.
Metformin Intervention—A Panacea for Cancer Treatment?
Authors: Buczyńska Angelika , Sidorkiewicz Iwona , Krętowski Adam Jacek , Zbucka-Krętowska Monika , Adamska Agnieszka
Published: March 2022

The molecular mechanism of action and the individual influence of various metabolic pathways related to metformin intervention are under current investigation. The available data suggest that metformin provides many advantages, exhibiting anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, otoprotective, radioprotective, and radio-sensitizing properties depending on cellular context. This literature review was undertaken to provide novel evidence concerning metformin intervention, with a particular emphasis on cancer treatment and prevention. Undoubtedly, the pleiotropic actions associated with metformin include inhibiting inflammatory processes, increasing antioxidant capacity, and improving glycemic and lipid metabolism. Consequently, these characteristics make metformin an attractive medicament to translate to human trials, the promising results of which were also summarized in this review.
Blood Circulating CD133+ Extracellular Vesicles Predict Clinical Outcomes in Patients with Metastatic Colorectal Cancer
Authors: Brocco Davide , Simeone Pasquale , Buca Davide , Marino Pietro Di , De Tursi Michele , Grassadonia Antonino , De Lellis Laura , Martino Maria Teresa , Veschi Serena , Iezzi Manuela , De Fabritiis Simone , Marchisio Marco , Miscia Sebastiano , Cama Alessandro , Lanuti Paola , Tinari Nicola
Published: March 2022

Colorectal cancer (CRC) is one of the most incident and lethal malignancies worldwide. Recent treatment advances prolonged survival in patients with metastatic colorectal cancer (mCRC). However, there are still few biomarkers to guide clinical management and treatment selection in mCRC. In this study, we applied an optimized flow cytometry protocol for EV identification, enumeration, and subtyping in blood samples of 54 patients with mCRC and 48 age and sex-matched healthy controls (HCs). The overall survival (OS) and overall response rate (ORR) were evaluated in mCRC patients enrolled and treated with a first line fluoropyrimidine-based regimen. Our findings show that patients with mCRC presented considerably higher blood concentrations of total EVs, as well as CD133+ and EPCAM+ EVs compared to HCs. Overall survival analysis revealed that increased blood concentrations of total EVs and CD133+ EVs before treatment were significantly associated with shorter OS in mCRC patients (p = 0.001; and p = 0.0001, respectively). In addition, we observed a correlation between high blood levels of CD133+ EVs at baseline and reduced ORR to first-line systemic therapy (p = 0.045). These findings may open exciting perspectives into the application of novel blood-based EV biomarkers for improved risk stratification and optimized treatment strategies in mCRC.
Neutrophil Extracellular Traps in Cancer Therapy Resistance
Authors: Shahzad Muhammad H. , Feng Lixuan , Su Xin , Brassard Ariane , Dhoparee-Doomah Iqraa , Ferri Lorenzo E. , Spicer Jonathan D. , Cools-Lartigue Jonathan J.
Published: March 2022

Neutrophils and their products are increasingly recognized to have a key influence on cancer progression and response to therapy. Their involvement has been shown in nearly every aspect of cancer pathophysiology with growing evidence now supporting their role in resistance to a variety of cancer therapies. Recently, the role of neutrophils in cancer progression and therapy resistance has been further complicated with the discovery of neutrophil extracellular traps (NETs). NETs are web-like structures of chromatin decorated with a variety of microbicidal proteins. They are released by neutrophils in a process called NETosis. NET-dependent mechanisms of cancer pathology are beginning to be appreciated, particularly with respect to tumor response to chemo-, immuno-, and radiation therapy. Several studies support the functional role of NETs in cancer therapy resistance, involving T-cell exhaustion, drug detoxification, angiogenesis, the epithelial-to-mesenchymal transition, and extracellular matrix remodeling mechanisms, among others. Given this, new and promising data suggests NETs provide a microenvironment conducive to limited therapeutic response across a variety of neoplasms. As such, this paper aims to give a comprehensive overview of evidence on NETs in cancer therapy resistance with a focus on clinical applicability.
β-Arsenene Monolayer: A Promising Electrocatalyst for Anodic Chlorine Evolution Reaction
Authors: Liu Junxian , Hinsch Jack Jon , Yin Huajie , Liu Porun , Zhao Huijun , Wang Yun
Published: March 2022

Materials innovation plays an essential role to address the increasing demands of gaseous chlorine from anodic chlorine evolution reaction (CER) in chlor-alkali electrolysis. In this study, two-dimensional (2D) semiconducting group-VA monolayers were theoretically screened for the electrochemical CER by means of the density functional theory (DFT) method. Our results reveal the monolayered β-arsenene has the ultralow thermodynamic overpotential of 0.068 V for CER, which is close to that of the commercial Ru/Ir-based dimensionally stable anode (DSA) of 0.08 V @ 10 mA cm−2 and 0.13 V from experiments and theory, respectively. The change of CER pathways via Cl* intermediate on 2D β-arsenene also efficiently suppresses the parasitical oxygen gas production because of a high theoretical oxygen evolution reaction (OER) overpotential of 1.95 V. Our findings may therefore expand the scope of the electrocatalysts design for CER by using emerging 2D materials.
Structural and Biochemical Characterization of Endo-β-1,4-glucanase from Dictyoglomus thermophilum, a Hyperthermostable and Halotolerant Cellulase
Authors: Berisio Rita , Barra Giovanni , Romano Maria , Squeglia Flavia , Ruggiero Alessia
Published: March 2022

Enzymatic conversion of polysaccharides in the lignocellulosic biomass is currently the subject of intensive research and will be a key technology in future biorefineries. Using a bioinformatics approach, we previously identified a putative endo-β-1,4-glucanase (DtCel5A) from Dictyoglomus thermophilum, a chemoorganotrophic and thermophilic bacterium. Here, we structurally and functionally characterize DtCel5A and show that it is endowed with remarkable thermal and chemical stability. The structural features of DtCel5A and of its complex with cellobiose have been investigated by combining X-ray crystallography and other biophysical studies. Importantly, biochemical assays show that DtCel5A retains its activity on cellulose at high temperatures and at elevated salt concentrations. These features make DtCel5A an enzyme with interesting biotechnological applications for biomass degradation.
Nebivolol Increases Nitric Oxide Synthase via β3 Adrenergic Receptor in Endothelial Cells Following Exposure to Plasma from Preeclamptic Patients
Authors: Bueno-Pereira Thaina Omia , Nunes Priscila Rezeck , Matheus Mariana Bertozzi , Vieira da Rocha Ananda Lini , Sandrim Valeria Cristina
Published: March 2022

Background: Low bioavailability of nitric oxide (NO) is related to the pathophysiology of preeclampsia (PE). In the present study, we investigated the effect of nebivolol (NEB), a β3-receptor agonist with vasodilator properties, on the NO synthesis in endothelial cells incubated with plasma from preeclamptic patients. Methods and results: Human umbilical vein endothelial cells (HUVECs) were incubated with plasma from healthy pregnant (HP) and PE women; NO quantification was assessed by a fluorescence compound. We found that endothelial cells incubated with plasma from women with PE show lower NO levels compared with the HP group (p < 0.0001). However, NEB treatment increases NO levels, partially, mediated by β3 adrenergic receptors (p < 0.0001) and through eNOS activation (p < 0.0001). Conclusions: Our results suggest that NEB acts in NO synthesis through eNOS activation and β3 adrenergic receptors in the endothelium. However, further studies will be needed to understand this molecule.
Bile Acids: Key Players in Inflammatory Bowel Diseases?
Authors: Kriaa Aicha , Mariaule Vincent , Jablaoui Amin , Rhimi Soufien , Mkaouar Hela , Hernandez Juan , Korkmaz Brice , Lesner Adam , Maguin Emmanuelle , Aghdassi Ali , Rhimi Moez
Published: March 2022

Inflammatory bowel diseases (IBDs) have emerged as a public health problem worldwide with a limited number of efficient therapeutic options despite advances in medical therapy. Although changes in the gut microbiota composition are recognized as key drivers of dysregulated intestinal immunity, alterations in bile acids (BAs) have been shown to influence gut homeostasis and contribute to the pathogenesis of the disease. In this review, we explore the interactions involving BAs and gut microbiota in IBDs, and discuss how the gut microbiota–BA–host axis may influence digestive inflammation.
EZH2 and Endometrial Cancer Development: Insights from a Mouse Model
Authors: Fang Xin , Ni Nan , Wang Xiaofang , Tian Yanan , Ivanov Ivan , Rijnkels Monique , Bayless Kayla J. , Lydon John P. , Li Qinglei
Published: March 2022

Enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, plays an important role in cancer development. As both oncogenic and tumor suppressive functions of EZH2 have been documented in the literature, the objective of this study is to determine the impact of Ezh2 deletion on the development and progression of endometrial cancer induced by inactivation of phosphatase and tensin homolog (PTEN), a tumor suppressor gene frequently dysregulated in endometrial cancer patients. To this end, we created mice harboring uterine deletion of both Ezh2 and Pten using Cre recombinase driven by the progesterone receptor (Pgr) promoter. Our results showed reduced tumor burden in Ptend/d; Ezh2d/d mice compared with that of Ptend/d mice during early carcinogenesis. The decreased Ki67 index in EZH2 and PTEN-depleted uteri versus that in PTEN-depleted uteri indicated an oncogenic role of EZH2 during early tumor development. However, mice harboring uterine deletion of both Ezh2 and Pten developed unfavorable disease outcome, accompanied by exacerbated epithelial stratification and heightened inflammatory response. The observed effect was non-cell autonomous and mediated by altered immune response evidenced by massive accumulation of intraluminal neutrophils, a hallmark of endometrial carcinoma in Ptend/d; Ezh2d/d mice during disease progression. Hence, these results reveal dual roles of EZH2 in endometrial cancer development.
Targeting the Pulmonary Microbiota to Fight against Respiratory Diseases
Authors: Li Zongjie , Li Yuhao , Sun Qing , Wei Jianchao , Li Beibei , Qiu Yafeng , Liu Ke , Shao Donghua , Ma Zhiyong
Published: March 2022

The mucosal immune system of the respiratory tract possesses an effective “defense barrier” against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.
Thermogravimetric Kinetic Analysis of Non-Recyclable Waste CO2 Gasification with Catalysts Using Coats–Redfern Method
Authors: Al-Moftah Ahmad Mohamed S. H. , Marsh Richard , Steer Julian
Published: March 2022

In the present study, the effect of dolomite and olivine as catalysts on the carbon dioxide (CO2) gasification of a candidate renewable solid recovered fuel, known as Subcoal™ was determined. Thermogravimetric analysis (TGA) was used to produce the TGA curves and derivative thermogravimetry (DTG) for the gasification reaction at different loadings of the catalyst (5, 10, 15 wt.%). The XRD results showed that the crystallinity proportion in Subcoal™ powder and ash was 42% and 38%, respectively. The Arrhenius constants of the gasification reaction were estimated using the model-fitting Coats–Redfern (CR) method. The results showed that the mass loss reaction time and thermal degradation decreased with the increase in catalyst content. The degradation reaction for complete conversion mainly consists of three sequences: dehydration, devolatilisation, and char/ash formation. The complete amount of thermal degradation of the Subcoal™ sample obtained with dolomite was lower than with olivine. In terms of kinetic analysis, 19 mechanism models of heterogeneous solid-state reaction were compared by the CR method to identify the most applicable model to the case in consideration. Among all models, G14 provided excellent linearity for dolomite and G15 for olivine at 15 wt.% of catalyst. Both catalysts reduced the activation energy (Ea) as the concentration increased. However, dolomite displayed higher CO2 gasification efficiency of catalysis and reduction in Ea. At 15 wt.% loading, the Ea was 41.1 and 77.5 kJ/mol for dolomite and olivine, respectively. Calcination of the mineral catalyst is substantial in improving the activity through enlarging the active surface area and number of pores. In light of the study findings, dolomite is a suitable mineral catalyst for the industrial-scale of non-recyclable waste such as Subcoal™ gasification.
A Label-Free Colorimetric Assay Based on Gold Nanoparticles for the Detection of H2O2 and Glucose
Authors: Zheng Cong , Wu Da , Wang Tao , Xiao Jianhong , Yu Li
Published: March 2022

The significance of sensing hydrogen peroxide (H2O2) is due to its ubiquity, being a potential biomarker as well as an end-product of several oxidation reactions. Herein, based on gold nanoparticles (AuNPs) and coupled with single-stranded DNA (ssDNA) and ceria nanoparticles (CeO2), we developed a novel colorimetric method to detect H2O2 and glucose in NaCl solutions. In the presence of H2O2, ssDNA adsorbed on the surface of CeO2 could be released and subsequently decorated AuNPs, resulting in a distinct color change of the aqueous solution from purple to red, which could be observed by the naked eye. Since H2O2 can be produced in the process of glucose oxidation by glucose oxidase (GOx), this approach can also be employed to detect glucose. By employing this sensing system, the detection limits for H2O2 and glucose are about 0.21 μM and 3.01 µM, respectively. Additionally, monitoring the content of glucose in blood serum samples was successfully achieved by the proposed strategy. This work opens a potential avenue for the quantitative detection of H2O2 and glucose in clinical diagnostics.
Implications of the COVID-19 Pandemic on Children and Adolescents: Cognitive and Emotional Representations
Authors: Maftei Alexandra , Merlici Ioan-Alex , Roca Iulia-Cristina
Published: March 2022

The present research investigated children and adolescents’ explicit and spontaneous representation of the COVID-19 pandemic and their related emotions, cognitions, and coping strategies. We explored the self-reported protective factors and coping mechanisms, in addition to similar attributional emotional experiences, i.e., the ways participants evaluated others’ pandemic experiences. Our sample consisted of 155 children and adolescents aged 10 to 13 (M = 10.70, SD = 0.85, 56.1% females). We designed a 12-item survey and analyzed our data using both qualitative and quantitative methods. Our findings suggested that most children and adolescents associated masks with the thought of the novel coronavirus, and the most frequently associated emotion was sadness (45.2%), followed by fear (17.4%). Generally, participants reported a medium level of perceived adverse effects of the pandemic, mainly because their regular physical school classes moved to the online setting. We also found a significant association between children’s self-reported levels of harmful effects of the pandemic and perceived adverse effects on their families. Most participants expressed their dissatisfaction concerning online school classes, primarily due to poor online interaction. In our sample, the children and adolescents reported positive thoughts and family relationships as their primary coping mechanisms during the pandemic, suggesting similar perceived coping mechanisms in the others around them. Finally, more than half of the participants considered that the COVID-19 pandemic had no positive effects, while 40% considered the increased time spent with their families the primary positive consequences following the COVID-19 health crisis. Results are discussed regarding their implications concerning healthcare, social, and educational policies.
Impact of the First COVID Lockdown on Accident- and Injury-Related Pediatric Intensive Care Admissions in Germany—A Multicenter Study
Authors: Bruns Nora , Willemsen Lea Y. , Holtkamp Katharina , Kamp Oliver , Dudda Marcel , Kowall Bernd , Stang Andreas , Hey Florian , Blankenburg Judith , Sabir Hemmen , Eifinger Frank , Fuchs Hans , Haase Roland , Andrée Clemens , Heldmann Michael , Potratz Jenny , Kurz Daniel , Schumann Anja , Müller-Knapp Merle , Mand Nadine , Doerfel Claus , Dahlem Peter , Rothoeft Tobias , Ohlert Manuel , Silkenbäumer Katrin , Dohle Frank , Indraswari Fithri , Niemann Frank , Jahn Peter , Merker Michael , Braun Nicole , Brevis Nunez Francisco , Engler Matthias , Heimann Konrad , Wolf Gerhard K. , Wulf Dominik , Hankel Saskia , Freymann Holger , Allgaier Nicolas , Knirsch Felix , Dercks Martin , Reinhard Julia , Hoppenz Marc , Felderhoff-Müser Ursula , Dohna-Schwake Christian
Published: March 2022

Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.
Orthorexia Nervosa in Adolescents and Young Adults: A Literature Review
Authors: Gkiouleka Maria , Stavraki Christina , Sergentanis Theodoros N. , Vassilakou Tonia
Published: March 2022

Adolescents are a nutritionally vulnerable population; eating disorders are more common among adolescents and young adults. Orthorexia nervosa (ON) is a non-formally recognized condition characterized by an obsessive preoccupation with eating healthy and “pure” foods; the quality and not the quantity of food is pivotal in ON. ON is a complex entity which can be associated with severe diet restrictions, a negative impact on social relationships, and with physical and mental health conditions, including obsessive–compulsive disorder. In light of this, a literature review regarding the background, diagnosis, features, risk factors, interplay with the social media, and management of ON is presented in this article, with a focus on adolescents and young adults.
Prospective Study on Prophylactic Micafungin Sodium against Invasive Fungal Disease during Neutropenia in Pediatric & Adolescent Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Authors: Kim Bo-Kyung , Choi Jung-Yoon , Hong Kyung-Taek , An Hong-Yul , Shin Hee-Young , Kang Hyoung-Jin
Published: March 2022

Background: Invasive fungal diseases (IFDs) increase the mortality rate of patients with neutropenia who receive chemotherapy or have previously undergone hematopoietic stem cell transplantation (HSCT). Micafungin is a broad-spectrum echinocandin with minimal toxicity and low drug interactions. We therefore investigated the efficacy and safety of prophylactic micafungin in pediatric and adolescent patients who underwent autologous HSCT. Methods: This was a phase II, prospective, single-center, open-label, and single-arm study. From November 2011 to February 2017, 125 patients were screened from Seoul National University Children’s Hospital, Korea, and 112 were enrolled. Micafungin was administered intravenously at a dose of 1 mg/kg/day (maximum 50 mg/day) from day 8 of autologous HSCT until neutrophil engraftment. Treatment success was defined as the absence of proven, probable, or possible IFD up to 4 weeks after therapy. Results: The study protocol was achieved without premature interruption in 110 patients (98.2%). The reasons interrupting micafungin treatment included early death (n = 1) and patient refusal (n = 1). Treatment success was achieved in 109 patients (99.1%). Only one patient was diagnosed with probable IFD. No patients were diagnosed with possible or proven IFD. In the full analysis set, 21 patients (18.8%) experienced 22 adverse events (AEs); however, all AEs were classified as “unlikely” related to micafungin. No patient experienced grade IV AEs nor discontinued treatment, and none of the deaths were related to micafungin. Conclusions: Our study demonstrated that micafungin is a safe and effective option for antifungal prophylaxis in pediatric patients who underwent autologous HSCT, with promising efficacy without significant AEs.
Electrochemical Deposition of Fe–Co–Ni Samples with Different Co Contents and Characterization of Their Microstructural and Magnetic Properties
Authors: Cao Long Van , Saraç Umut , Baykul Mevlana Celalettin , Trong Luong Duong , Ţălu Ştefan , Nguyen Trong Dung
Published: March 2022

In this study, to explore the effect of Co contents on the electroplated Fe–Co–Ni samples, three different Fe–Co33–Ni62, Fe–Co43–Ni53, and Fe–Co61–Ni36 samples were electrochemically grown from Plating Solutions (PSs) containing different amounts of Co ions on indium tin oxide substrates. Compositional analysis showed that an increase in the Co ion concentration in the PS gives rise to an increment in the weight fraction of Co in the sample. In all samples, the co–deposition characteristic was described as anomalous. The samples exhibited a predominant reflection from the (111) plane of the face–centered cubic structure. However, the Fe–Co61–Ni36 sample also had a weak reflection from the (100) plane of the hexagonal close–packed structure of Co. An enhancement in the Co contents caused a strong decrement in the crystallinity, resulting in a decrease in the size of the crystallites. The Fe–Co33–Ni62 sample exhibited a more compact surface structure comprising only cauliflower–like agglomerates, while the Fe–Co43–Ni53 and Fe–Co61–Ni36 samples had a surface structure consisting of both pyramidal particles and cauliflower–like agglomerates. The results also revealed that different Co contents play an important role in the surface roughness parameters. From the magnetic analysis of the samples, it was understood that the Fe–Co61–Ni36 sample has a higher coercive field and magnetic squareness ratio than the Fe–Co43–Ni53 and Fe–Co33–Ni62 samples. The differences observed in the magnetic characteristics of the samples were attributed to the changes revealed in their phase structure and surface roughness parameters. The obtained results are the basis for the fabrication of future magnetic devices.
Solution and Double Aging Treatments of Cold Sprayed Inconel 718 Coatings
Authors: Sun Wen , Chu Xin , Huang Jibo , Lan Haiming , Tan Adrian Wei-Yee , Huang Renzhong , Liu Erjia
Published: March 2022

In this study, Inconel 718 coatings were deposited by the high-pressure cold spray technique, and post-process solution and double aging treatments were conducted. The microstructures of the as-deposited and heat-treated IN718 were analyzed, and their mechanical properties were tested. It was found that the micro-dendritic structures in the original powder were severely elongated in the as-deposited IN718 coating due to plastic deformation during the cold spray process. After solution heat treatment, Nb, Mo, and Ti-rich segregations could be dissolved, transforming to MC carbide and a needle-like δ phase. It was found that the needle-like δ phase at the grain boundary had a pinning effect to slow down the grain growth. In addition, strengthening phases could be formed by aging treatments. The mechanical properties of the cold sprayed Inconel 718 could be improved by proper solution and aging heat treatments.
SiGeSn Quantum Dots in HfO2 for Floating Gate Memory Capacitors
Authors: Palade Catalin , Slav Adrian , Cojocaru Ovidiu , Teodorescu Valentin Serban , Stoica Toma , Ciurea Magdalena Lidia , Lepadatu Ana-Maria
Published: March 2022

Group IV quantum dots (QDs) in HfO2 are attractive for non-volatile memories (NVMs) due to complementary metal-oxide semiconductor (CMOS) compatibility. Besides the role of charge storage centers, SiGeSn QDs have the advantage of a low thermal budget for formation, because Sn presence decreases crystallization temperature, while Si ensures higher thermal stability. In this paper, we prepare MOS capacitors based on 3-layer stacks of gate HfO2/floating gate of SiGeSn QDs in HfO2/tunnel HfO2/p-Si obtained by magnetron sputtering deposition followed by rapid thermal annealing (RTA) for nanocrystallization. Crystalline structure, morphology, and composition studies by cross-section transmission electron microscopy and X-ray diffraction correlated with Raman spectroscopy and C–V measurements are carried out for understanding RTA temperature effects on charge storage behavior. 3-layer morphology and Sn content trends with RTA temperature are explained by the strongly temperature-dependent Sn segregation and diffusion processes. We show that the memory properties measured on Al/3-layer stack/p-Si/Al capacitors are controlled by SiGeSn-related trapping states (deep electronic levels) and low-ordering clusters for RTA at 325–450 °C, and by crystalline SiGeSn QDs for 520 and 530 °C RTA. Specific to the structures annealed at 520 and 530 °C is the formation of two kinds of crystalline SiGeSn QDs, i.e., QDs with low Sn content (2 at.%) that are positioned inside the floating gate, and QDs with high Sn content (up to 12.5 at.%) located at the interface of floating gate with adjacent HfO2 layers. The presence of Sn in the SiGe intermediate layer decreases the SiGe crystallization temperature and induces the easier crystallization of the diamond structure in comparison with 3-layer stacks with Ge-HfO2 intermediate layer. High frequency-independent memory windows of 3–4 V and stored electron densities of 1–2 × 1013 electrons/cm2 are achieved.