bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights into Hemopexin-Binding to Hemin and Hemoglobin
Authors: Lechuga Guilherme C. , Napoleão-Pêgo Paloma , Morel Carlos M. , Provance David W. , De-Simone Salvatore G.
Published: March 2022

Hemopexin (Hx) is a plasma glycoprotein that scavenges heme (Fe(III) protoporphyrin IX). Hx has important implications in hemolytic disorders and hemorrhagic conditions because releasing hemoglobin increases the labile heme, which is potentially toxic, thus producing oxidative stress. Therefore, Hx has been considered for therapeutic use and diagnostics. In this work, we analyzed and mapped the interaction sequences of Hx with hemin and hemoglobin. The spot-synthesis technique was used to map human hemopexin (P02790) binding to hemin and human hemoglobin. A library of 15 amino acid peptides with a 10-amino acid overlap was designed to represent the entire coding region (aa 1-462) of hemopexin and synthesized onto cellulose membranes. An in silico approach was taken to analyze the amino acid frequency in the identified interaction regions, and molecular docking was applied to assess the protein-protein interaction. Seven linear peptide sequences in Hx were identified to bind hemin (H1–H7), and five were described for Hb (Hb1–Hb5) interaction, with just two sequences shared between hemin and Hb. The amino acid composition of the identified sequences demonstrated that histidine residues are relevant for heme binding. H105, H293, H373, H400, H429, and H462 were distributed in the H1–H7 peptide sequences, but other residues may also play an important role. Molecular docking analysis demonstrated Hx’s association with the β-chain of Hb, with several hotspot amino acids that coordinated the interaction. This study provides new insights into Hx-hemin binding motifs and protein-protein interactions with Hb. The identified binding sequences and specific peptides can be used for therapeutic purposes and diagnostics as hemopexin is under investigation to treat different diseases and there is an urgent need for diagnostics using labile heme when monitoring hemolysis.
3D Printing Soft Matters and Applications: A Review
Authors: Zhan Shuai , Guo Amy X. Y. , Cao Shan Cecilia , Liu Na
Published: March 2022

The evolution of nature created delicate structures and organisms. With the advancement of technology, especially the rise of additive manufacturing, bionics has gradually become a popular research field. Recently, researchers have concentrated on soft robotics, which can mimic the complex movements of animals by allowing continuous and often responsive local deformations. These properties give soft robots advantages in terms of integration and control with human tissue. The rise of additive manufacturing technologies and soft matters makes the fabrication of soft robots with complex functions such as bending, twisting, intricate 3D motion, grasping, and stretching possible. In this paper, the advantages and disadvantages of the additive manufacturing process, including fused deposition modeling, direct ink writing, inkjet printing, stereolithography, and selective laser sintering, are discussed. The applications of 3D printed soft matter in bionics, soft robotics, flexible electronics, and biomedical engineering are reviewed.
Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice
Authors: Tung Hsiu-Jung , Wu Ren-Chin , Lin Chiao-Yun , Lai Chyong-Huey
Published: March 2022

Endometrial cancer (EC) is one of the most common gynecologic cancers worldwide. There were 417,367 newly diagnosed cases and 97,370 deaths due to this disease worldwide in 2020. The incidence rates have increased over time, especially in countries with rapid socioeconomic transitions, and EC has been the most prevalent gynecologic malignancy in Taiwan since 2012. The new EC molecular classifications of The Cancer Genome Atlas (TCGA) Research Network include clear-cell carcinoma, serous carcinoma, and carcinosarcoma, while undifferentiated/dedifferentiated EC (UDEC) is not mentioned, and most previous clinical trials for EC have not included UDEC. UDEC is rare, has an aggressive growth pattern, tends to be diagnosed at an advanced stage, and is resistant to conventional chemotherapy. In this review, case series or case reports on the clinical features and genomic/epigenetic and expression profiles on UDEC data are summarized in order to identify potential molecular targets for current and future research.
Transdermal Delivery of Indirubin-Loaded Microemulsion Gel: Preparation, Characterization and Anti-Psoriatic Activity
Authors: He Enxue , Li Hailing , Li Xiaokun , Wu Xunxun , Lei Kun , Diao Yong
Published: March 2022

Psoriasis is an immune disease caused by rapid and incomplete differentiation of skin basal cells. Natural products such as indirubin have historically served as excellent sources for the treatments of psoriasis. However, the poor solubility and bioavailability due to its plane and rigid crystal structure, which limits its efficacy. Herein, to improve the efficacy of indirubin, a hydrogel-based microemulsion drug delivery system was developed for transdermal delivery. The mean droplet size of the optimized microemulsion was 84.37 nm, with a polydispersity index (PDI) less than 0.2 and zeta potential value of 0~−20 mV. The transdermal flux and skin retention of indirubin at 24 h were 47.34 ± 3.59 μg/cm2 and 8.77 ± 1.26 μg/cm2, respectively. The optimized microemulsion was dispersed in carbomer 934 hydrogel to increase the consistency. The indirubin-loaded microemulsion gel was tested on an imiquimod-induced psoriasis mouse model. Results showed that this preparation can improve psoriasis symptoms by down-regulating the expression of IL-17A, Ki67, and CD4+T. This experiment provides great scalability for researchers to treat psoriasis, avoid first-pass effects, and increase the concentration of targeted drugs.
Co3O4 Nanoparticles Uniformly Dispersed in Rational Porous Carbon Nano-Boxes for Significantly Enhanced Electrocatalytic Detection of H2O2 Released from Living Cells
Authors: Xiong Lulu , Zhang Yuanyuan , Wu Shiming , Chen Feng , Lei Lingli , Yu Ling , Li Changming
Published: March 2022

A facile and ingenious method to chemical etching-coordinating a metal-organic framework (MOF) followed by an annealing treatment was proposed to prepare Co3O4 nanoparticles uniformly dispersed in rational porous carbon nano-boxes (Co3O4@CNBs), which was further used to detect H2O2 released from living cells. The Co3O4@CNBs H2O2 sensor delivers much higher sensitivity than non-etching/coordinating Co3O4, offering a limit of detection of 2.32 nM. The wide working range covers 10 nM-359 μM H2O2, while possessing good selectivity and excellent reproducibility. Moreover, this biosensor was used to successfully real-time detect H2O2 released from living cells, including both healthy and tumor cells. The excellent performance holds great promise for Co3O4@CNBs’s applications in electrochemical biomimetic sensing, particularly real-time monitor H2O2 released from living cells.
Editorial to the Special Issue on Skin Cancer: The State of the Art
Authors: Rutkowski Piotr , Mackiewicz Andrzej
Published: March 2022

This Special Issue of the International Journal of Molecular Sciences focuses on skin cancers, specifically on the rare forms of these tumors [...]
Integrated OMICs Approach for the Group 1 Protease Mite-Allergen of House Dust Mite Dermatophagoides microceras
Authors: Hu Rei-Hsing , Cheng Chun-Wen , Wu Chia-Ta , Ko Jiunn-Liang , Lue Ko-Huang , Liu Yu-Fan
Published: March 2022

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras (Der m), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component (Der m 1). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.
Effect of Betaine and Arginine on Interaction of αB-Crystallin with Glycogen Phosphorylase b
Authors: Eronina Tatiana B. , Mikhaylova Valeriya V. , Chebotareva Natalia A. , Tugaeva Kristina V. , Kurganov Boris I.
Published: March 2022

Protein–protein interactions (PPIs) play an important role in many biological processes in a living cell. Among them chaperone–client interactions are the most important. In this work PPIs of αB-crystallin and glycogen phosphorylase b (Phb) in the presence of betaine (Bet) and arginine (Arg) at 48 °C and ionic strength of 0.15 M were studied using methods of dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation. It was shown that Bet enhanced, while Arg reduced both the stability of αB-crystallin and its adsorption capacity (AC0) to the target protein at the stage of aggregate growth. Thus, the anti-aggregation activity of αB-crystallin increased in the presence of Bet and decreased under the influence of Arg, which resulted in inhibition or acceleration of Phb aggregation, respectively. Our data show that chemical chaperones can influence the tertiary and quaternary structure of both the target protein and the protein chaperone. The presence of the substrate protein also affects the quaternary structure of αB-crystallin, causing its disassembly. This is inextricably linked to the anti-aggregation activity of αB-crystallin, which in turn affects its PPI with the target protein. Thus, our studies contribute to understanding the mechanism of interaction between chaperones and proteins.
EGFR Mutations in Head and Neck Squamous Cell Carcinoma
Authors: Nair Sindhu , Bonner James A. , Bredel Markus
Published: March 2022

EGFR is a prototypical receptor tyrosine kinase that is overexpressed in multiple cancers including head and neck squamous cell carcinoma (HNSCC). The standard of care for HNSCC remains largely unchanged despite decades of research. While EGFR blockade is an attractive target in HNSCC patients and anti-EGFR strategies including monoclonal antibodies and kinase inhibitors have shown some clinical benefit, efficacy is often due to the eventual development of resistance. In this review, we discuss how the acquisition of mutations in various domains of the EGFR gene not only alter drug binding dynamics giving rise to resistance, but also how mutations can impact radiation response and overall survival in HNSCC patients. A better understanding of the EGFR mutational landscape and its dynamic effects on treatment resistance hold the potential to better stratify patients for targeted therapies in order to maximize therapeutic benefits.
Anticoagulant Oligonucleotide–Peptide Conjugates: Identification of Thrombin Aptamer Conjugates with Improved Characteristics
Authors: Tsvetkov Vladimir B. , Varizhuk Irina V. , Kurochkin Nikolay N. , Surzhikov Sergei A. , Smirnov Igor P. , Stomakhin Andrey A. , Kolganova Natalia A. , Timofeev Edward N.
Published: March 2022

Oligonucleotide–peptide conjugates (OPCs) are a promising class of biologically active compounds with proven potential for improving nucleic acid therapeutics. OPCs are commonly recognized as an efficient instrument to enhance the cellular delivery of therapeutic nucleic acids. In addition to this application field, OPCs have an as yet unexplored potential for the post-SELEX optimization of DNA aptamers. In this paper, we report the preparation of designer thrombin aptamer OPCs with peptide side chains anchored to a particular thymidine residue of the aptamer. The current conjugation strategy utilizes unmodified short peptides and support-bound protected oligonucleotides with activated carboxyl functionality at the T3 thymine nucleobase. The respective modification of the oligonucleotide strand was implemented using N3-derivatized thymidine phosphoramidite. Aptamer OPCs retained the G-quadruplex architecture of the parent DNA structure and showed minor to moderate stabilization. In a series of five OPCs, conjugates bearing T3–Ser–Phe–Asn (SFN) or T3–Tyr–Trp–Asn (YWN) side chains exhibited considerably improved anticoagulant characteristics. Molecular dynamics studies of the aptamer OPC complexes with thrombin revealed the roles of the amino acid nature and sequence in the peptide subunit in modulating the anticoagulant activity.
Strategies for Successful Over-Expression of Human Membrane Transport Systems Using Bacterial Hosts: Future Perspectives
Authors: Galluccio Michele , Console Lara , Pochini Lorena , Scalise Mariafrancesca , Giangregorio Nicola , Indiveri Cesare
Published: March 2022

Ten percent of human genes encode for membrane transport systems, which are key components in maintaining cell homeostasis. They are involved in the transport of nutrients, catabolites, vitamins, and ions, allowing the absorption and distribution of these compounds to the various body regions. In addition, roughly 60% of FDA-approved drugs interact with membrane proteins, among which are transporters, often responsible for pharmacokinetics and side effects. Defects of membrane transport systems can cause diseases; however, knowledge of the structure/function relationships of transporters is still limited. Among the expression of hosts that produce human membrane transport systems, E. coli is one of the most favorable for its low cultivation costs, fast growth, handiness, and extensive knowledge of its genetics and molecular mechanisms. However, the expression in E. coli of human membrane proteins is often toxic due to the hydrophobicity of these proteins and the diversity in structure with respect to their bacterial counterparts. Moreover, differences in codon usage between humans and bacteria hamper translation. This review summarizes the many strategies exploited to achieve the expression of human transport systems in bacteria, providing a guide to help people who want to deal with this topic.
BECLIN1 Is Essential for Podocyte Secretory Pathways Mediating VEGF Secretion and Podocyte-Endothelial Crosstalk
Authors: Bork Tillmann , Liang Wei , Kretz Oliver , Lagies Simon , Yamahara Kosuke , Hernando-Erhard Camila , Helmstädter Martin , Schell Christoph , Kammerer Bernd , Huber Tobias B.
Published: March 2022

Vascular endothelial growth factor A (VEGFA) secretion from podocytes is crucial for maintaining endothelial integrity within the glomerular filtration barrier. However, until now, the molecular mechanisms underlying podocyte secretory function remained unclear. Through podocyte-specific deletion of BECLIN1 (ATG6 or Becn1), a key protein in autophagy initiation, we identified a major role for this molecule in anterograde Golgi trafficking. The Becn1-deficient podocytes displayed aberrant vesicle formation in the trans-Golgi network (TGN), leading to dramatic vesicle accumulation and complex disrupted patterns of intracellular vesicle trafficking and membrane dynamics. Phenotypically, podocyte-specific deletion of Becn1 resulted in early-onset glomerulosclerosis, which rapidly progressed and dramatically reduced mouse life span. Further, in vivo and in vitro studies clearly showed that VEGFA secretion, and thereby endothelial integrity, greatly depended on BECLIN1 availability and function. Being the first to demonstrate the importance of a secretory pathway for podocyte integrity and function, we identified BECLIN1 as a key component in this complex cellular process. Functionally, by promoting VEGFA secretion, a specific secretory pathway emerged as an essential component for the podocyte-endothelial crosstalk that maintains the glomerular filtration barrier.
Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review
Authors: Loizzo Davide , Pandolfo Savio Domenico , Rogers Devin , Cerrato Clara , di Meo Nicola Antonio , Autorino Riccardo , Mirone Vincenzo , Ferro Matteo , Porta Camillo , Stella Alessandro , Bizzoca Cinzia , Vincenti Leonardo , Spilotros Marco , Rutigliano Monica , Battaglia Michele , Ditonno Pasquale , Lucarelli Giuseppe
Published: March 2022

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.
Enhanced Photoluminescence and Electrical Properties of n-Al-Doped ZnO Nanorods/p-B-Doped Diamond Heterojunction
Authors: Yao Yu , Sang Dandan , Zou Liangrui , Zhang Dong , Wang Qingru , Wang Xueting , Wang Liying , Yin Jie , Fan Jianchao , Wang Qinglin
Published: March 2022

The hydrothermal approach has been used to fabricate a heterojunction of n-aluminum-doped ZnO nanorods/p-B-doped diamond (n-Al:ZnO NRs/p-BDD). It exhibits a significant increase in photoluminescence (PL) intensity and a blue shift of the UV emission peak when compared to the n-ZnO NRs/p-BDD heterojunction. The current voltage (I-V) characteristics exhibit excellent rectifying behavior with a high rectification ratio of 838 at 5 V. The n-Al:ZnO NRs/p-BDD heterojunction shows a minimum turn-on voltage (0.27 V) and reverse leakage current (0.077 μA). The forward current of the n-Al:ZnO NRs/p-BDD heterojunction is more than 1300 times than that of the n-ZnO NRs/p-BDD heterojunction at 5 V. The ideality factor and the barrier height of the Al-doped device were found to decrease. The electrical transport behavior and carrier injection process of the n-Al:ZnO NRs/p-BDD heterojunction were analyzed through the equilibrium energy band diagrams and semiconductor theoretical models.
Exploring the FGF/FGFR System in Ocular Tumors: New Insights and Perspectives
Authors: Loda Alessandra , Turati Marta , Semeraro Francesco , Rezzola Sara , Ronca Roberto
Published: March 2022

Ocular tumors are a family of rare neoplasms that develop in the eye. Depending on the type of cancer, they mainly originate from cells localized within the retina, the uvea, or the vitreous. Even though current treatments (e.g., radiotherapy, transpupillary thermotherapy, cryotherapy, chemotherapy, local resection, or enucleation) achieve the control of the local tumor in the majority of treated cases, a significant percentage of patients develop metastatic disease. In recent years, new targeting therapies and immuno-therapeutic approaches have been evaluated. Nevertheless, the search for novel targets and players is eagerly required to prevent and control tumor growth and metastasis dissemination. The fibroblast growth factor (FGF)/FGF receptor (FGFR) system consists of a family of proteins involved in a variety of physiological and pathological processes, including cancer. Indeed, tumor and stroma activation of the FGF/FGFR system plays a relevant role in tumor growth, invasion, and resistance, as well as in angiogenesis and dissemination. To date, scattered pieces of literature report that FGFs and FGFRs are expressed by a significant subset of primary eye cancers, where they play relevant and pleiotropic roles. In this review, we provide an up-to-date description of the relevant roles played by the FGF/FGFR system in ocular tumors and speculate on its possible prognostic and therapeutic exploitation.
The Microbial Mechanisms of a Novel Photosensitive Material (Treated Rape Pollen) in Anti-Biofilm Process under Marine Environment
Authors: Li Qing-Chao , Wang Bo , Zeng Yan-Hua , Cai Zhong-Hua , Zhou Jin
Published: March 2022

Marine biofouling is a worldwide problem in coastal areas and affects the maritime industry primarily by attachment of fouling organisms to solid immersed surfaces. Biofilm formation by microbes is the main cause of biofouling. Currently, application of antibacterial materials is an important strategy for preventing bacterial colonization and biofilm formation. A natural three-dimensional carbon skeleton material, TRP (treated rape pollen), attracted our attention owing to its visible-light-driven photocatalytic disinfection property. Based on this, we hypothesized that TRP, which is eco-friendly, would show antifouling performance and could be used for marine antifouling. We then assessed its physiochemical characteristics, oxidant potential, and antifouling ability. The results showed that TRP had excellent photosensitivity and oxidant ability, as well as strong anti-bacterial colonization capability under light-driven conditions. Confocal laser scanning microscopy showed that TRP could disperse pre-established biofilms on stainless steel surfaces in natural seawater. The biodiversity and taxonomic composition of biofilms were significantly altered by TRP (p < 0.05). Moreover, metagenomics analysis showed that functional classes involved in the antioxidant system, environmental stress, glucose–lipid metabolism, and membrane-associated functions were changed after TRP exposure. Co-occurrence model analysis further revealed that TRP markedly increased the complexity of the biofilm microbial network under light irradiation. Taken together, these results demonstrate that TRP with light irradiation can inhibit bacterial colonization and prevent initial biofilm formation. Thus, TRP is a potential nature-based green material for marine antifouling.
Central and Peripheral NPY Age-Related Regulation: A Comparative Analysis in Fish Translational Models
Authors: Giaquinto Daniela , De Felice Elena , Attanasio Chiara , Palladino Antonio , Schiano Valentina , Mollo Ernesto , Lucini Carla , de Girolamo Paolo , D’Angelo Livia
Published: March 2022

NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age-related regulation of NPY in the brain and foregut of the shortest- and longest-lived fish species, Nothobranchius furzeri and Danio rerio, respectively. These two research models, despite some similarities, display profound biological differences making them attractive vertebrates to elucidate the mechanisms underlying the regulation of neuropeptide synthesis and function. It is noteworthy that in both fish species only Npya has been identified, while in the other teleosts two classes of NPY (Npya and Npyb) have been annotated. Our findings document that in both species: (i) NPY is centrally regulated; (ii) NPY levels increase in the brain during aging; (iii) NPY is localized in the enteroendocrine cells as well as in the myenteric plexus and drastically decreases in old animals. According to our data, the age-related regulation in the gut resembles that described in other vertebrate species while the increased levels in the brain offer the unique possibility to explore the role of NPY in model organisms to develop future experimental and translatable approaches.
Prognostic Utility of a New Risk Stratification Protocol for Secondary Prevention in Patients Attending Cardiac Rehabilitation
Authors: Cabrera-Aguilera Ignacio , Ivern Consolació , Badosa Neus , Marco Ester , Duran Xavier , Mojón Diana , Vicente Miren , Llagostera Marc , Farré Nuria , Ruíz-Bustillo Sonia
Published: March 2022

Several risk scores have been used to predict risk after an acute coronary syndrome (ACS), but none of these risk scores include functional class. The aim was to assess the predictive value of risk stratification (RS), including functional class, and how cardiac rehabilitation (CR) changed RS. Two hundred and thirty-eight patients with ACS from an ambispective observational registry were stratified as low (L) and no-low (NL) risk and classified according to exercise compliance; low risk and exercise (L-E), low risk and control (no exercise) (L-C), no-low risk and exercise (NL-E), and no-low risk and control (NL-C). The primary endpoint was cardiac rehospitalization. Multivariable analysis was performed to identify variables independently associated with the primary endpoint. The L group included 56.7% of patients. The primary endpoint was higher in the NL group (18.4% vs. 4.4%, p < 0.001). After adjustment for age, sex, diabetes, and exercise in multivariable analysis, HR (95% CI) was 3.83 (1.51–9.68) for cardiac rehospitalization. For RS and exercise, the prognosis varied: the L-E group had a cardiac rehospitalization rate of 2.5% compared to 26.1% in the NL-C group (p < 0.001). Completing exercise training was associated with reclassification to low-risk, associated with a better outcome. This easy-to-calculate risk score offers robust prognostic information. No-exercise groups were independently associated with the worst outcomes. Exercise-based CR program changed RS, improving classification and prognosis.
Lactobacillus paracasei CNCM I 1572: A Promising Candidate for Management of Colonic Diverticular Disease
Authors: Bretto Elisabetta , D’Amico Ferdinando , Fiore Walter , Tursi Antonio , Danese Silvio
Published: March 2022

Diverticular disease (DD) is a common gastrointestinal condition. Patients with DD experience a huge variety of chronic nonspecific symptoms, including abdominal pain, bloating, and altered bowel habits. They are also at risk of complications such as acute diverticulitis, abscess formation, hemorrhage, and perforation. Intestinal dysbiosis and chronic inflammation have recently been recognized as potential key factors contributing to disease progression. Probiotics, due to their ability to modify colonic microbiota balance and to their immunomodulatory effects, could present a promising treatment option for patients with DD. Lactobacillus paracasei CNCM I 1572 (LCDG) is a probiotic strain with the capacity to rebalance gut microbiota and to decrease intestinal inflammation. This review summarizes the available clinical data on the use of LCDG in subjects with colonic DD.
Diffusion-Weighted MRI in the Genitourinary System
Authors: De Perrot Thomas , Sadjo Zoua Christine , Glessgen Carl G. , Botsikas Diomidis , Berchtold Lena , Salomir Rares , De Seigneux Sophie , Thoeny Harriet C. , Vallée Jean-Paul
Published: March 2022

Diffusion weighted imaging (DWI) constitutes a major functional parameter performed in Magnetic Resonance Imaging (MRI). The DW sequence is performed by acquiring a set of native images described by their b-values, each b-value representing the strength of the diffusion MR gradients specific to that sequence. By fitting the data with models describing the motion of water in tissue, an apparent diffusion coefficient (ADC) map is built and allows the assessment of water mobility inside the tissue. The high cellularity of tumors restricts the water diffusion and decreases the value of ADC within tumors, which makes them appear hypointense on ADC maps. The role of this sequence now largely exceeds its first clinical apparitions in neuroimaging, whereby the method helped diagnose the early phases of cerebral ischemic stroke. The applications extend to whole-body imaging for both neoplastic and non-neoplastic diseases. This review emphasizes the integration of DWI in the genitourinary system imaging by outlining the sequence’s usage in female pelvis, prostate, bladder, penis, testis and kidney MRI. In gynecologic imaging, DWI is an essential sequence for the characterization of cervix tumors and endometrial carcinomas, as well as to differentiate between leiomyosarcoma and benign leiomyoma of the uterus. In ovarian epithelial neoplasms, DWI provides key information for the characterization of solid components in heterogeneous complex ovarian masses. In prostate imaging, DWI became an essential part of multi-parametric Magnetic Resonance Imaging (mpMRI) to detect prostate cancer. The Prostate Imaging–Reporting and Data System (PI-RADS) scoring the probability of significant prostate tumors has significantly contributed to this success. Its contribution has established mpMRI as a mandatory examination for the planning of prostate biopsies and radical prostatectomy. Following a similar approach, DWI was included in multiparametric protocols for the bladder and the testis. In renal imaging, DWI is not able to robustly differentiate between malignant and benign renal tumors but may be helpful to characterize tumor subtypes, including clear-cell and non-clear-cell renal carcinomas or low-fat angiomyolipomas. One of the most promising developments of renal DWI is the estimation of renal fibrosis in chronic kidney disease (CKD) patients. In conclusion, DWI constitutes a major advancement in genitourinary imaging with a central role in decision algorithms in the female pelvis and prostate cancer, now allowing promising applications in renal imaging or in the bladder and testicular mpMRI.
Bronchoscopic Intra-Pleural Instillation of Fibrin Glue and Autologous Blood to Manage Persistent Air Leaks after Lung Resection
Authors: Ferraroli Giorgio Maria , Perroni Gianluca , Giudici Veronica Maria , Antonicelli Alberto , Fernando Hiran Chrishantha , Ambrogi Vincenzo , Alloisio Marco , Voulaz Emanuele , Bottoni Edoardo , Infante Maurizio Valentino , Testori Alberto
Published: March 2022

Background: Persistent air leak is a common complication after lung resection causing prolonged length of stay and increased healthcare costs. Surgical intervention can be an option, but other more conservative approaches should be considered first. Here, we describe the use of flexible bronchoscopy to apply fibrin glue and autologous blood sequentially to the damaged lung. We named the technique “flexible thoracoscopy”. Methods: Medical records from patients with persistent air leaks after lung resection were collected retrospectively. Depending on the type of aerostasis that was performed, two groups were created: flexible thoracoscopy and surgery (thoracotomy). Flexible thoracoscopy was introduced at our institution in 2013. We entered the pleural space with a bronchoscope following the same surgical pathway that was used for tube thoracostomy. Perioperative characteristics and outcomes were analyzed using R software (ver. 3.4.4). Results: From 1997 to 2021, a total of 23 patients required an intervention for persistent air leaks. Aerostasis was performed via flexible thoracoscopy in seventeen patients (69%) and via thoracotomy in six patients (31%). The median age was 70 years (22–82). Twenty patients were males (87%). There was no difference in age, sex distribution, BMI, comorbidities and FEV1%. An ASA score of 3 was more represented in the flexible thoracoscopy group; however, no evidence of a difference was found when compared to the thoracotomy group (p = 0.124). Length of in-hospital stay and chest tube duration was also similar between groups (p = 1 and p = 0.68, respectively). Conclusions: Aerostasis achieved either by flexible thoracoscopy or by thoracotomy showed similar results. We believe that flexible thoracoscopy could be a valid alternative to facilitate minimally invasive treatments for persistent air leaks. Further studies are needed to confirm these results.
Emphasis on Occupancy Rates in Carbon Emission Comparison for Maritime and Road Passenger Transportation Modes
Authors: Dujmović Josip , Krljan Tomislav , Lopac Nikola , Žuškin Srđan
Published: March 2022

Carbon emissions generated by the transportation sector represent a large part of total greenhouse gas emissions and are thus subject to various policies and initiatives for emission reduction and the development of sustainable transportation networks. Furthermore, passenger transportation generates a significant amount of emissions within this sector, especially in those countries with large and developed tourist sectors. Examples of such countries are Italy and Croatia, located in the Adriatic region, with a large portion of passengers between them being transported utilizing mainly maritime and/or road transportation modes. A proper analysis of the impact of these transportation mode choices on carbon emissions is essential to enable the selection of the optimal transportation mode for the particular transportation route with respect to the generated emissions. Therefore, this study determines the carbon emissions of the maritime and/or road transportation modes on the existing cross-border passenger transportation routes between Italy and Croatia. For the analysis, the Adriatic region was divided into three sections—the Northern, Middle, and Southern regions—each characterized by specific transportation routes defined by geographical features and distances. The results obtained from this research are presented as total carbon emissions for each transportation mode separately, based on each of three chosen routes in different regions. In addition, a carbon emission comparison between each transportation mode in regard to occupancy rate is performed and presented separately for each chosen route based on its specific distances, transportation means, and features. Finally, by providing an analysis of the existing state, this study can serve as a basis for Italy–Croatia cross-border passenger mobility network modernization and the introduction of new, sustainable, and multimodal transportation routes.
Lagrangian Modeling of Marine Microplastics Fate and Transport: The State of the Science
Authors: Bigdeli Mostafa , Mohammadian Abdolmajid , Pilechi Abolghasem , Taheri Mercedeh
Published: March 2022

Microplastics pollution has led to irreversible environmental consequences and has triggered global concerns. It has been shown that water resources and marine food consumers are adversely affected by microplastics due to their physico-chemical characteristics. This study attempts to comprehensively review the structure of four well-known Lagrangian particle-tracking models, i.e., Delft3D—Water Quality Particle tracking module (D-WAQ PART), Ichthyoplankton (Ichthyop), Track Marine Plastic Debris (TrackMPD), and Canadian Microplastic Simulation (CaMPSim-3D) in simulating the fate and transport of microplastics. Accordingly, the structure of each model is investigated with respect to addressing the involved physical transport processes (including advection, diffusion, windage, beaching, and washing-off) and transformation processes (particularly biofouling and degradation) that play key roles in microplastics’ behavior in the marine environment. In addition, the effects of the physical properties (mainly size, diameter, and shape) of microplastics on their fate and trajectories are reviewed. The models’ capabilities and shortcomings in the simulation of microplastics are also discussed. The present review sheds light on some aspects of microplastics’ behavior in water that were not properly addressed in particle-tracking models, such as homo- and hetero-aggregation, agglomeration, photodegradation, and chemical and biological degradation as well as additional advection due to wave-induced drift. This study can be regarded as a reliable steppingstone for the future modification of the reviewed models.
Industrial-Scale Production of Mycotoxin Binder from the Red Yeast Sporidiobolus pararoseus KM281507
Authors: Tapingkae Wanaporn , Srinual Orranee , Lumsangkul Chompunut , Doan Hien Van , Chiang Hsin-I , Manowattana Atchara , Boonchuay Pinpanit , Chaiyaso Thanongsak
Published: March 2022

Red yeast Sporidiobolus pararoseus KM281507 has been recognized as a potential feed additive. Beyond their nutritional value (carotenoids and lipids), red yeast cells (RYCs) containing high levels of β-glucan can bind mycotoxins. This study investigated the industrial feasibility of the large-scale production of RYCs, along with their ability to act as a mycotoxin binder. Under a semi-controlled pH condition in a 300 L bioreactor, 28.70-g/L biomass, 8.67-g/L lipids, and 96.10-mg/L total carotenoids were obtained, and the RYCs were found to contain 5.73% (w/w) β-glucan. The encapsulated RYC was in vitro tested for its mycotoxin adsorption capacity, including for aflatoxin B1 (AFB1), zearalenone (ZEA), ochratoxin A (OTA), T-2 toxin (T-2) and deoxynivalenol (DON). The RYCs had the highest binding capacity for OTA and T-2 at concentrations of 0.31–1.25 and 0.31–2.5 µg/mL, respectively. The mycotoxin adsorption capacity was further tested using a gastrointestinal poultry model. The adsorption capacities of the RYCs and a commercial mycotoxin binder (CMB) were comparable. The RYCs not only are rich in lipids and carotenoids but also play an important role in mycotoxin binding. Since the industrial-scale production and downstream processing of RYCs were successfully demonstrated, RYCs could be applied as possible feed additives.
Systematic Characterization of bZIP Transcription Factors Required for Development and Aflatoxin Generation by High-Throughput Gene Knockout in Aspergillus flavus
Authors: Zhao Qianqian , Pei Hao , Zhou Xiaoling , Zhao Kai , Yu Min , Han Guomin , Fan Jun , Tao Fang
Published: March 2022

The basic leucine zipper (bZIP) is an important transcription factor required for fungal development, nutrient utilization, biosynthesis of secondary metabolites, and defense against various stresses. Aspergillus flavus is a major producer of aflatoxin and an opportunistic fungus on a wide range of hosts. However, little is known about the role of most bZIP genes in A. flavus. In this study, we developed a high-throughput gene knockout method based on an Agrobacterium-mediated transformation system. Gene knockout construction by yeast recombinational cloning and screening of the null mutants by double fluorescence provides an efficient way to construct gene-deleted mutants for this multinucleate fungus. We deleted 15 bZIP genes in A. flavus. Twelve of these genes were identified and characterized in this strain for the first time. The phenotypic analysis of these mutants showed that the 15 bZIP genes play a diverse role in mycelial growth (eight genes), conidiation (13 genes), aflatoxin biosynthesis (10 genes), oxidative stress response (11 genes), cell wall stress (five genes), osmotic stress (three genes), acid and alkali stress (four genes), and virulence to kernels (nine genes). Impressively, all 15 genes were involved in the development of sclerotia, and the respective deletion mutants of five of them did not produce sclerotia. Moreover, MetR was involved in this biological process. In addition, HapX and MetR play important roles in the adaptation to excessive iron and sulfur metabolism, respectively. These studies provide comprehensive insights into the role of bZIP transcription factors in this aflatoxigenic fungus of global significance.
Second Language Assessment Issues in Refugee and Migrant Children’s Integration and Education: Assessment Tools and Practices for Young Students with Refugee and Migrant Background in Greece
Authors: Chatzina Paraskevi , Mouti Anna
Published: March 2022

European countries—Greece included—recognize the fact that the language of schooling in the host country constitutes the first step for the newcomer children’s reception and integration. Greece, as a dominant receiving country, has adopted a top-level policy for its educational system. Considering the above, this research paper presents and analyzes the assessment tests and practices that educators have access to for evaluating refugee and migrant students’ L2 Greek competence in Greece. A detailed presentation of the Assessment Tools for Refugee and Migrant children in Greece is provided, with a focus on teachers’ attitudes and beliefs toward these materials and tools. The appropriateness of the available assessment tools and practices regarding the linguistic and social needs of refugee and migrant children in the Greek context will also be discussed. Findings show that teachers’ perceptions regarding both tests and practices for refugee and migrant students during an initial and formative language assessment vary. It is important to state, though, that the vast majority of the educators feel very sure and comfortable when assessing the linguistic skills of their students.
Thermal Boost to Breast Tumor Bed—New Technique Description, Treatment Application and Example Clinical Results
Authors: Chicheł Adam , Burchardt Wojciech , Chyrek Artur J. , Bielęda Grzegorz , Zwierzchowski Grzegorz , Stefaniak Patrycja , Malicki Julian
Published: March 2022

(1) Current breast-conserving therapy for breast cancer consists of a combination of many consecutive treatment modalities. The most crucial goal of postoperative treatment is to eradicate potentially relapse-forming residual cancerous cells within the tumor bed. To achieve this, the HDR brachytherapy boost standardly added to external beam radiotherapy was enhanced with an initial thermal boost. This study presents an original thermal boost technique developed in the clinic. (2) A detailed point-by-point description of thermal boost application is presented. Data on proper patient selection, microwave thermal boost planning, and interstitial hyperthermia treatment delivery are supported by relevant figures and schemes. (3) Out of 1134 breast cancer patients who were administered HDR brachytherapy boost in the tumor bed, 262 were also pre-heated interstitially without unexpected complications. The results are supported by two example cases of hyperthermia planning and delivery. (4) Additional breast cancer interstitial thermal boost preceding HDR brachytherapy boost as a part of combined treatment in a unique postoperative setting was feasible, well-tolerated, completed in a reasonable amount of time, and reproducible. A commercially available interstitial hyperthermia system fit and worked well with standard interstitial brachytherapy equipment.
In Situ Synthesis of Silver Nanoparticles on Flame-Retardant Cotton Textiles Treated with Biological Phytic Acid and Antibacterial Activity
Authors: Zhou Qingqing , Chen Jiayi , Lu Zhenqian , Tian Qiang , Shao Jianzhong
Published: March 2022

Fabrics were flame-retardant finished using phytic acid, a cost-effective, ecologically acceptable, and easily available flame-retardant finishing chemical. Then, on the surface of the completed fabric, silver nanoparticles (Ag NPs) were grown in situ to minimize Ag NPs aggregation and heterogeneous post-finishing and to increase washing durability. Thus, flame-retardant and antibacterial qualities were added to textiles. The as-prepared textiles were evaluated for their combustion performance, thermal performance, and antibacterial capabilities. At the same time, their microstructures were studied using X-ray diffractometry (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The findings indicated that flame-retardant textiles had an excellent launderability (limiting oxygen index = 31% after 20 washing cycles). Meanwhile, Ag NPs-loaded flame-retardant textiles demonstrated self-extinguishing properties, with a limiting oxygen index (LOI) of 27%. Bacteriostatic widths of flame-retardant antibacterial textiles against Escherichia coli and Staphylococcus aureus were 5.28 and 4.32 mm, respectively, indicating that Ag NPs-loaded flame-retardant fabrics have certain flame-retardant and antibacterial capabilities. SEM and TEM analysis indicated that nanoparticles were uniformly dispersed over Ag NPs-loaded flame-retardant textiles and were around 20 nm in size. When compared to flame-retardant textiles, Ag NPs-loaded flame-retardant fabrics showed varied binding energy of P and N on the surface and Ag ion emergence. Thermogravimetric analysis at various heating rates revealed that the main pyrolysis temperature range of flame-retardant fabrics decreased, while the main pyrolysis temperature range of Ag NPs-loaded flame-retardant fabrics increased; the heating rate influenced the pyrolysis range but not the fabric mass loss. In situ reduction synthesis of Ag NPs-loaded flame-retardant textiles may successfully reduce agglomeration and heterogeneous dispersion of nano-materials during post-finishing.
Dynamic Reweighted Domain Adaption for Cross-Domain Bearing Fault Diagnosis
Authors: Meng Yu , Xuan Jianping , Xu Long , Liu Jie
Published: March 2022

Certain progress has been made in fault diagnosis under cross-domain scenarios recently. Most researchers have paid almost all their attention to promoting domain adaptation in a common space. However, several challenges that will cause negative transfer have been ignored. In this paper, a reweighting method is proposed to overcome this difficulty from two aspects. First, extracted features differ greatly from one another in promoting positive transfer, and measuring the difference is important. Measured by conditional entropy, the weight of adversarial losses for those well aligned features are reduced. Second, the balance between domain adaptation and class discrimination greatly influences the transferring task. Here, a dynamic weight strategy is adopted to compute the balance factor. Consideration is made from the perspective of maximum mean discrepancy and multiclass linear discriminant analysis. The first item is supposed to measure the degree of the domain adaptation between source and the target domain, and the second is supposed to show the classification performance of the classifier on the learned features in the current training epoch. Finally, extensive experiments on several bearing fault diagnosis datasets are conducted. The performance shows that our model has an obvious advantage compared with other common transferring algorithms.