bluuebunny/crossref_metadata_2025 huggingface dataset:
Green and Gold Buildings? Detecting Real Estate Market Premium for Green Buildings through Evolutionary Polynomial Regression
Authors: Massimo Domenico Enrico , De Paola Pierfrancesco , Musolino Mariangela , Malerba Alessandro , Del Giudice Francesco Paolo
Published: May 2022

This study concerns the determination of empirical evidence of a real estate market premium for Green Buildings and of an aware role of the private real estate market as driver to foster-up urban and architectural sustainability and energy efficiency. In real estate markets, there is growing relevance of Green Buildings, especially in cities where the greater part of residential buildings is built before the first regulations on energy performance. Through policies oriented towards sustainable practices, a twofold goal can be achieved: energy consumption mitigation respecting the historical value for existing buildings, direct economic impacts on real estate values. In some metropolitan or urban contexts, the “green premium” for buildings can be understood as a real “gold premium”. This result has been highlighted and quantified with a real estate market analysis developed for a central area of an Italian mid-size city, pursued through the innovative tool of Evolutionary Polynomial Regression (EPR). The study highlighted a higher sale price for properties characterized by the best ecological characteristics and energy efficiency (+41.52%).
Three-Dimensional Printing Materials for Cultural Innovation Products of Historical Buildings
Authors: Hu Hao , Cao Xiaoxiao , Zhang Tao , Chen Zhenfu , Xie Jinliang
Published: May 2022

Innovation products from historical cultural architectural have widely adopted 3D printing technology in recent years. To study the applicability of existing 3D printing materials, it is necessary to analyze the performance indicators of 3D printing materials and carry out material science experiments. Step 1: the material performance index composition of cultural innovation products was derived by integrating the literature of cultural heritage, product design, quality system, and material science. Step 2: The columns of Chengs’ Miyake in Huizhou were taken as the creative source. Its geometric shape model was obtained through 3D scanning, and the design of the cultural innovation products was completed. Step 3: Photosensitive resin, nylon, and stainless steel, three commonly used 3D printing materials, were used to make samples, with one sample of each material. Finally, we carried out material science tests according to the material performance index. The experimental data of three materials were obtained and compared. The properties of the three 3D printing materials, photosensitive resin, nylon, and stainless steel, have advantages and disadvantages. Still, they all struggle to meet the needs of cultural and creative products in historical buildings. It is necessary to integrate the three materials’ properties to develop new 3D printing materials.
Bearing Capacity of Annular Foundations on Rock Mass with Heterogeneous Disturbance by Finite Element Limit Analysis
Authors: Kim Bo Sung , Kwon O-il , Choi Yong Hyuk , Lee Joon Kyu
Published: May 2022

Estimating the performance of foundations on rock mass is essential in designing buildings. Stability assessment of weathered rocks under foundation load is a complicated task if there is an internal opening within the foundation. This study applies finite element limit analysis to evaluate the bearing capacity of annular foundations resting on medium to highly weathered rocks following the modified Hoek–Brown rock mass. Special attention is focused on the effect of rock mass disturbance. The level and heterogeneity of rock mass disturbance are considered as constant or linearly varying disturbance factors with depth, which capture the damage level and zones due to construction and blasting. The results obtained from the analysis compare well with the existing solutions. The numerical results are presented in the familiar form of bearing capacity factors as a function of the dimensionless parameters related to foundation perforation and rock mass properties as well as the foundation-rock interface. The failure patterns of annular foundations are also investigated for a few cases with different levels of disturbance and foundation roughness.
Chemical Production of Graphene Oxide with High Surface Energy for Supercapacitor Applications
Authors: Karbak Mehdi , Boujibar Ouassim , Lahmar Sanaa , Autret-Lambert Cecile , Chafik Tarik , Ghamouss Fouad
Published: May 2022

The chemical exfoliation of graphite to produce graphene and its oxide is undoubtedly an economical method for scalable production. Carbon researchers have dedicated significant resources to developing new exfoliation methods leads to graphene oxides with high quality. However, only a few studies have been dedicated to the effect of the starting graphite material on the resulting GO. Herein, we have prepared two different GOs through chemical exfoliation of graphite materials having different textural and structural characteristics. All samples have been subjected to structural investigations and comprehensive characterizations using Raman, X-ray diffraction, scanning electron microscopy, TGA, N2 physisorption, and FTIR spectroscopy. Our results provide direct evidence of how the crystallite size of the raw graphite affects the oxidation degree, surface functionality, and sheet size of the resulting GO. Building on these significant understandings, the optimized GO achieves a highly specific capacitance of 191 F·g−1 at the specific current of 0.25 A·g−1 in an aqueous electrolyte. This superior electrochemical performance was attributed to several factors, among which the specific surface area was accessible to the electrolyte ions and oxygenated functional groups on the surface, which can significantly modify the electronic structure of graphene and further enhance the surface energy.
Cancer Therapy-Related Cardiac Dysfunction in Patients Treated with a Combination of an Immune Checkpoint Inhibitor and Doxorubicin
Authors: Lee Seon-Hwa , Cho Iksung , You Seng-Chan , Cha Min-Jae , Chang Jee-Suk , Kim William D. , Go Kyu-yong , Kim Dae-Young , Seo Jiwon , Shim Chi-Young , Hong Geu-Ru , Kang Seok-Min , Ha Jong-Won , Rha Sun-Young , Kim Hyo-Song
Published: May 2022

Backgrounds: There are scarce data on whether immune checkpoint inhibitors (ICIs) increase the risk of cardiac dysfunction when used with cardiotoxic agents. Thus, we evaluated cardiac dysfunction in patients with sarcoma receiving doxorubicin with or without ICI using echocardiography and left ventricular global longitudinal strain (LVGLS). Methods: A total of 95 patients were included in this study. Echocardiography and LVGLS were evaluated at baseline and follow-up (at 3 and 6 months of chemotherapy) and compared with the doxorubicin (Dox; n = 73) and concomitant ICI with doxorubicin (Dox-ICI; n = 22) groups. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a left ventricular ejection fraction (LVEF) drop of >10% and LVEF of <50% (definite CTRCD), LVEF drop of >10%, LVEF of ≥50%, and LVGLS relative reduction of >15% (probable CTRCD) at six months. Results: There were no significant differences in age, cumulative dose of doxorubicin, and cardiovascular risk factors between the two groups. At baseline, the LVEF was similar in the Dox and Dox-ICI groups (p = 0.493). In the Dox group, LVEF decreased to 59 ± 6% (Δ −7 ± 1.3%, p < 0.001) and LVGLS decreased from −17.3 ± 3.2% to −15.4 ± 3.2% (Δ −10.1 ± −1.9%, p < 0.001) at six months. In the Dox-ICI group, LVEF decreased to 55 ± 9% (Δ −9 ± 2.1%, p < 0.001), along with a significant decrease in LVGLS (from −18.6 ± 1.9% to −15.3 ± 3.6%, Δ −12.4 ± −2.4%, p < 0.001). Over a median follow-up of 192 days, there were no cases with clinical manifestations of fulminant myocarditis. In the Dox group, definite and probable CTRCD were observed in seven (10.1%) and five (7.4%) patients, respectively. In the Dox-ICI group, definite and probable CTRCD were observed in four (19%) and four (19%) patients, respectively. The total number of patients who developed CTRCD was significantly higher in the Dox-ICI group than in the Dox group (38.1% vs. 17.4%, p = 0.042). Serum troponin-T level was significantly higher in the Dox-ICI group than in the Dox group (53.3 vs. 27.5 pg/mL, p = 0.023). Conclusions: ICIs may increase the risk of CTRCD when used with cardiotoxic agents. CTRCD should be monitored in patients treated with ICIs by cardiac biomarkers and echocardiography, including LV-GLS.
Current Pathology Model of Pancreatic Cancer
Authors: Szymoński Krzysztof , Milian-Ciesielska Katarzyna , Lipiec Ewelina , Adamek Dariusz
Published: May 2022

Pancreatic cancer (PC) is one of the most aggressive and lethal malignant neoplasms, ranking in seventh place in the world in terms of the incidence of death, with overall 5-year survival rates still below 10%. The knowledge about PC pathomechanisms is rapidly expanding. Daily reports reveal new aspects of tumor biology, including its molecular and morphological heterogeneity, explain complicated “cross-talk” that happens between the cancer cells and tumor stroma, or the nature of the PC-associated neural remodeling (PANR). Staying up-to-date is hard and crucial at the same time. In this review, we are focusing on a comprehensive summary of PC aspects that are important in pathologic reporting, impact patients’ outcomes, and bring meaningful information for clinicians. Finally, we show promising new trends in diagnostic technologies that might bring a difference in PC early diagnosis.
Muscarinic Receptors Associated with Cancer
Authors: Calaf Gloria M. , Crispin Leodan A. , Muñoz Juan P. , Aguayo Francisco , Bleak Tammy C.
Published: May 2022

Cancer has been considered the pathology of the century and factors such as the environment may play an important etiological role. The ability of muscarinic agonists to stimulate growth and muscarinic receptor antagonists to inhibit tumor growth has been demonstrated for breast, melanoma, lung, gastric, colon, pancreatic, ovarian, prostate, and brain cancer. This work aimed to study the correlation between epidermal growth factor receptors and cholinergic muscarinic receptors, the survival differences adjusted by the stage clinical factor, and the association between gene expression and immune infiltration level in breast, lung, stomach, colon, liver, prostate, and glioblastoma human cancers. Thus, targeting cholinergic muscarinic receptors appears to be an attractive therapeutic alternative due to the complex signaling pathways involved.
Recurrence of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Systematic Review of the Literature
Authors: Di Giuseppe Jacopo , Grelloni Camilla , Giuliani Lucia , Delli Carpini Giovanni , Giannella Luca , Ciavattini Andrea
Published: May 2022

Background: This study aimed to systematically review the existing literature on uterine smooth muscle tumor of uncertain malignant potential (STUMP) to provide information about characteristics and outcomes of patients and the risk factors for recurrence over a period of 60 years (1960–2021). Methods: According to PRISMA guidelines, we searched for "uterine smooth muscle tumor of uncertain malignant potential" in PubMed (all fields) and Scopus (Title/Abstract/Keywords) databases (accessed on 1 January 2022). Relevant articles were obtained in full-text format and screened for additional references. The only filter used was the English language. Studies including full case description of patients with histopathological diagnosis of STUMP in accordance with Stanford criteria were included. Results: Thirty-four studies, including 189 cases, were included. The median age was 43 years, and in 21.5% of cases there was a recurrence of the disease. Bivariate analysis showed a significant association between use of morcellation without bag and risk of recurrence (p = 0.001). Unprotected morcellation during demolitive or conservative surgery was independently associated with a higher risk of disease recurrence with a relative risk of 2.94 (p < 0.001). A significant progressive decrease in the recurrence rate was observed over time (r = −0.671, p = 0.008). The percentage of patients who underwent surgery followed by in-bag protected morcellation significantly increased after the publication of the U.S. Food and Drug Administration alert about the risk linked to this procedure (p = 0.01). Conclusions: Unprotected morcellation of the lesion is associated with the relapse of the disease. However, this clinical condition showed a drastic decrease over time. This could likely be due to the increased awareness by surgeons of the importance of customizing surgical treatment.
Sinonasal Side Effects of Chemotherapy and/or Radiation Therapy for Head and Neck Cancer: A Literature Review
Authors: Riva Giuseppe , Cravero Ester , Pizzo Claudia , Briguglio Marco , Iorio Giuseppe Carlo , Cavallin Chiara , Ostellino Oliviero , Airoldi Mario , Ricardi Umberto , Pecorari Giancarlo
Published: May 2022

Radiotherapy and chemotherapy represent important treatment modalities for head and neck cancer. Rhinosinusitis and smell alterations are common side effects in the sinonasal region. This review will summarize and analyze our current knowledge of the sinonasal side effects of chemotherapy and/or radiation therapy for head and neck cancer (HNC), with a specific focus on mucosal and olfactory disorders. A review of the English literature was performed using several databases (PubMed, Embase, Cochrane, Scopus). Fifty-six articles were included in qualitative synthesis: 28 assessed mucosal disorders (rhinitis or rhinosinusitis), 26 evaluated olfactory alterations, and 2 articles addressed both topics. The incidence and severity of olfactory dysfunction and chronic rhinosinusitis were highest at the end of radiotherapy and at three months after treatment and decreased gradually over time. Smell acuity deterioration and chronic rhinosinusitis seemed to be related to radiation dose on olfactory area and nasal cavities, but different degrees of recovery were observed. In conclusion, it is important to establish the severity of chronic rhinosinusitis and olfactory dysfunction in order to find strategies to support patients and improve their quality of life.
Upregulation of the Mevalonate Pathway through EWSR1-FLI1/EGR2 Regulatory Axis Confers Ewing Cells Exquisite Sensitivity to Statins
Authors: Buchou Charlie , Laud-Duval Karine , van der Ent Wietske , Grossetête Sandrine , Zaidi Sakina , Gentric Géraldine , Corbé Maxime , Müller Kévin , Del Nery Elaine , Surdez Didier , Delattre Olivier
Published: May 2022

Ewing sarcoma (EwS) is an aggressive primary bone cancer in children and young adults characterized by oncogenic fusions between genes encoding FET-RNA-binding proteins and ETS transcription factors, the most frequent fusion being EWSR1-FLI1. We show that EGR2, an Ewing-susceptibility gene and an essential direct target of EWSR1-FLI1, directly regulates the transcription of genes encoding key enzymes of the mevalonate (MVA) pathway. Consequently, Ewing sarcoma is one of the tumors that expresses the highest levels of mevalonate pathway genes. Moreover, genome-wide screens indicate that MVA pathway genes constitute major dependencies of Ewing cells. Accordingly, the statin inhibitors of HMG-CoA-reductase, a rate-limiting enzyme of the MVA pathway, demonstrate cytotoxicity in EwS. Statins induce increased ROS and lipid peroxidation levels, as well as decreased membrane localization of prenylated proteins, such as small GTP proteins. These metabolic effects lead to an alteration in the dynamics of S-phase progression and to apoptosis. Statin-induced effects can be rescued by downstream products of the MVA pathway. Finally, we further show that statins impair tumor growth in different Ewing PDX models. Altogether, the data show that statins, which are off-patent, well-tolerated, and inexpensive compounds, should be strongly considered in the therapeutic arsenal against this deadly childhood disease.
Correlation between Colon Perfusion and Postoperative Fecal Output through a Transanal Drainage Tube during Laparoscopic Low Anterior Resection
Authors: Kawada Kenji , Wada Toshiaki , Yamamoto Takehito , Itatani Yoshiro , Hida Koya , Obama Kazutaka
Published: May 2022

In order to prevent anastomotic leakage (AL) following rectal surgery, various solutions—such as intraoperative indocyanine green (ICG) angiography and transanal drainage tubes (TDT)—have been proposed. This study investigated the relationship between intestinal perfusion and fecal volume through TDT in laparoscopic low anterior resection (LAR). A total of 59 rectal cancer patients who underwent laparoscopic LAR with both intraoperative ICG angiography and postoperative TDT placement were retrospectively analyzed. The relationship between intestinal perfusion and fecal volume through TDT was examined. Based on the ICG fluorescence, the transection site was shifted more proximally in 20 cases (33.9%). Symptomatic AL occurred in seven patients (11.8%). The AL rate of the patients whose daily fecal volume exceeded 100 mL/day in 2 or more days was significantly higher than that of those whose daily fecal volume exceeded it in 0 or 1 day (44.4% vs. 6.0%; p < 0.01). Univariate and multivariate analyses showed that the need for a proximal shift of the transection site was significantly associated with a high fecal volume. The quantitative analysis of ICG fluorescence indicated that Fmax (the fluorescence difference between the baseline and maximum) was significantly associated with fecal volume through TDT.
Return to Work, Fatigue and Cancer Rehabilitation after Curative Radiotherapy and Radiochemotherapy for Pelvic Gynecologic Cancer
Authors: Meixner Eva , Sandrini Elisabetta , Hoeltgen Line , Eichkorn Tanja , Hoegen Philipp , König Laila , Arians Nathalie , Lischalk Jonathan W. , Wallwiener Markus , Weis Ilse , Roob Daniela , Debus Jürgen , Hörner-Rieber Juliane
Published: May 2022

Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the use of in-house social services and post-treatment inpatient rehabilitation, and RTW were assessed for 424 women, diagnosed with cervical, uterine, or vaginal/vulvar cancer, receiving curative radio(chemo)therapy. Progression-free RTW rate at 3 months was 32.3%, and increased to 58.1% and 63.2% at 12 and 18 months, respectively. Patients with advanced FIGO stages and intensified treatments significantly suffered more from acute pain and fatigue. A higher Charlson-Comorbidity-Index reliably predicted patients associated with a higher risk of acute fatigue during RT. Aside from the presence of children, no other household or lifestyle factor was correlated with increased fatigue rates. Women aged ≤ 45 years had a significantly higher risk of developing depression requiring treatment during follow-up. Post-treatment inpatient cancer rehabilitation, including exercise and nutrition counseling, significantly relieved fatigue symptoms. The burdens for recovery from cancer therapy remain multi-factorial. Special focus needs to be placed on identifying high-risk groups experiencing fatigue or pain. Specialized post-treatment inpatient cancer rehabilitation can improve RTW rates.
Exploration of the Interactions between Maltase–Glucoamylase and Its Potential Peptide Inhibitors by Molecular Dynamics Simulation
Authors: Guan Shanshan , Han Xu , Li Zhan , Xu Xifei , Cui Yongran , Chen Zhiwen , Zhang Shuming , Chen Shi , Shan Yaming , Wang Song , Li Hao
Published: May 2022

Diabetes mellitus, a chronic metabolic disorder, represents a serious threat to human health. The gut enzyme maltase–glucoamylase (MGAM) has attracted considerable attention as a potential therapeutic target for the treatment of type 2 diabetes. Thus, developing novel inhibitors of MGAM holds the promise of improving clinical management. The dipeptides, Thr-Trp (TW) and Trp-Ala (WA), are known inhibitors of MGAM; however, studies on how they interact with MGAM are lacking. The work presented here explored these interactions by utilizing molecular docking and molecular dynamics simulations. Results indicate that the active center of the MGAM could easily accommodate the flexible peptides. Interactions involving hydrogen bonds, cation-π, and hydrophobic interactions are predicted between TW/WA and residues including Tyr1251, Trp1355, Asp1420, Met1421, Glu1423, and Arg1510 within MGAM. The electrostatic energy was recognized as playing a dominant role in both TW-MGAM and WA-MGAM systems. The binding locations of TW/WA are close to the possible acid-base catalytic residue Asp1526 and might be the reason for MGAM inhibition. These findings provide a theoretical structural model for the development of future inhibitors.
Research Progress in ZIF-8 Derived Single Atomic Catalysts for Oxygen Reduction Reaction
Authors: Shen Siqi , Sun Yuanyuan , Sun Hao , Pang Yuepeng , Xia Shuixin , Chen Taiqiang , Zheng Shiyou , Yuan Tao
Published: May 2022

Transition metal (TM) single atomic catalysts (MSAC-N-C) derived from doped zeolite imidazolate frameworks (ZIF-8) are considered attractive oxygen reduction reaction (ORR) catalysts for fuel cells and metal-air batteries due to their advantages of high specific surface area, more active catalytic sites, adjustable pore size, and coordination topology features. This review provides an updated overview of the latest advances of MSAC-N-C catalysts derived from ZIF-8 precursors in ORR electrocatalysis. Particularly, some key challenges, including coordination environments regulation of catalysis center in MSAC-N-C, the active sites loading optimization and synergistic effects between TM nanoclusters/nanoparticles and the single atoms on MSAC-N-C catalysis activity, as well as their adaptability in various devices, are summarized for improving future development and application of MSAC-N-C catalysts. In addition, this review puts forward future research directions, making it play a better role in ORR catalysis for fuel cells and metal air batteries.
Copper Catalyzed Inverse Electron Demand [4+2] Cycloaddition for the Synthesis of Oxazines
Authors: Yang Weiguang , Zhou Zitong , Zhao Yu , Luo Danyang , Luo Xiai , Luo Hui , Cui Liao , Li Li
Published: May 2022

A copper catalyzed tandem CuAAC/ring cleavage/[4+2] annulation reaction of terminal ynones, sulfonyl azides, and imines has been developed to synthesize the functionalized oxazines under mild conditions. Particularly, the intermediate N-sulfonyl acylketenimines undergo cycloaddition of an inverse electron demand Diels–Alder reaction with imines and a series of 1,3-oxazine derivatives were obtained successfully in good yields.
Flower-like Co3O4 Catalysts for Efficient Catalytic Oxidation of Multi-Pollutants from Diesel Exhaust
Authors: Li Zihao , Chen Xianhuai , Chen Jinghuan , Chang Huazhen , Ma Lei , Yan Naiqiang
Published: May 2022

Nowadays, the oxidation activity at the low-temperature regime for Co3O4 catalysts needs to be improved to meet the stringent regulation of multi-pollutant diesel exhaust. Herein, nanoflower-like Co3O4 diesel oxide catalysts (DOCs) were fabricated with the addition of a low-content Pt to trigger better catalytic activities for oxidizing multi-pollutants (CO, C3H6, and NO) emissions by taking advantage of the strong-metal supporting interaction. Compared to the conventional DOCs based on Pt/Al2O3, the as-synthesized Pt/Co3O4 catalysts not only exhibited better multi-pollutants oxidation activities at the low temperature but also obtained better resistance toward NO inhibition. Moreover, Pt/Co3O4 catalysts showed exceptional hydrothermal durability throughout long-term tests in the presence of water vapor. According to the XPS and H2-TPR results, Pt promoted low-temperature catalytic activity by increasing the active surface oxygen species and reducibility due to the robust synergistic interaction between metallic Pt and supporting Co3O4. Meanwhile, TGA curves confirmed the Pt atoms that facilitated the desorption of surface-active oxygen and hydroxyl radicals in a low-temperature regime. Furthermore, instead of probing the intermediates during CO and C3H6 oxidation for Pt/Co3O4 catalysts, which included carbonates, formate, and acetate species, in situ DRIFTs experiments also revealed C3H6 oxidation mainly took place over metallic Pt sites.
Pt–Pd Bimetallic Aerogel as High-Performance Electrocatalyst for Nonenzymatic Detection of Hydrogen Peroxide
Authors: Pan Chuxuan , Zheng Yuanyuan , Yang Jing , Lou Dongyang , Li Jian , Sun Yujing , Liu Wei
Published: May 2022

Hydrogen peroxide (H2O2) plays an indispensable role in the biological, medical, and chemical fields. The development of an effective H2O2 detecting method is of great importance. In the present work, a series of PtxPdy bimetallic aerogels and Pt, Pd monometallic aerogels were controllably synthesized by one-step gelation method. Their morphologies and compositions were characterized by transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy, and so forth. These aerogels were used as nonenzyme electrocatalysts for the detection of H2O2. The cyclic voltammetric and amperometric results demonstrated that the performance of the metal aerogels showed volcano-type behavior, with the Pt50Pd50 aerogel sitting on top. The Pt50Pd50 aerogel-based electrochemical sensor exhibited excellent comprehensive performance, with a low overpotential of −0.023 V vs. Ag/AgCl, a broad linear range from 5.1 to 3190 μM (R2 = 0.9980), and a high sensitivity of 0.19 mA mM−1 cm−2, in combination with good anti-interference ability and stability. A comprehensive study indicated that the superior sensing performance of the Pt50Pd50 aerogel is closely related to its optimized d-band center and larger cumulative pore volume. This work first applied Pt–Pd bimetallic aerogels into the detection of H2O2 and shows the promising application of noble metal aerogels in the electrochemical sensing area.
Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential
Authors: Guindolet Damien , Woodward Ashley M. , Gabison Eric E. , Argüeso Pablo
Published: May 2022

Glycans function as valuable markers of stem cells but also regulate the ability of these cells to self-renew and differentiate. Approximately 2% of the human genome encodes for proteins that are involved in the biosynthesis and recognition of glycans. In the present study, we evaluated the expression of a small subset of glycogenes in human limbal epithelial cells with distinct clonogenic potential. Individual clones were classified as abortive or clonogenic, based on the fraction of the terminal colonies produced; clones leading exclusively to terminal colonies were referred to as abortive while those with half or fewer terminal colonies were referred to as clonogenic. An analysis of glycogene expression in clonogenic cultures revealed a high content of transcripts regulating the galactose and mannose metabolic pathways. Abortive clones were characterized by increased levels of GCNT4 and FUCA2, genes that are responsible for the branching of mucin-type O-glycans and the hydrolysis of fucose residues on N-glycans, respectively. The expansion of primary cultures of human limbal epithelial cells for 10 days resulted in stratification and a concomitant increase in MUC16, GCNT4 and FUCA2 expression. These data indicate that the clonogenic potential of human limbal epithelial cells is associated with specific glycosylation pathways. Mucin-type O-glycan branching and increased fucose metabolism are linked to limbal epithelial cell differentiation.
Biodegradable Poly(D-L-lactide-co-glycolide) (PLGA)-Infiltrated Bioactive Glass (CAR12N) Scaffolds Maintain Mesenchymal Stem Cell Chondrogenesis for Cartilage Tissue Engineering
Authors: Gögele Clemens , Müller Silvana , Belov Svetlana , Pradel Andreas , Wiltzsch Sven , Lenhart Armin , Hornfeck Markus , Kerling Vera , Rübling Achim , Kühl Hannes , Schäfer-Eckart Kerstin , Minnich Bernd , Weiger Thomas Martin , Schulze-Tanzil Gundula
Published: May 2022

Regeneration of articular cartilage remains challenging. The aim of this study was to increase the stability of pure bioactive glass (BG) scaffolds by means of solvent phase polymer infiltration and to maintain cell adherence on the glass struts. Therefore, BG scaffolds either pure or enhanced with three different amounts of poly(D-L-lactide-co-glycolide) (PLGA) were characterized in detail. Scaffolds were seeded with primary porcine articular chondrocytes (pACs) and human mesenchymal stem cells (hMSCs) in a dynamic long-term culture (35 days). Light microscopy evaluations showed that PLGA was detectable in every region of the scaffold. Porosity was greater than 70%. The biomechanical stability was increased by polymer infiltration. PLGA infiltration did not result in a decrease in viability of both cell types, but increased DNA and sulfated glycosaminoglycan (sGAG) contents of hMSCs-colonized scaffolds. Successful chondrogenesis of hMSC-colonized scaffolds was demonstrated by immunocytochemical staining of collagen type II, cartilage proteoglycans and the transcription factor SOX9. PLGA-infiltrated scaffolds showed a higher relative expression of cartilage related genes not only of pAC-, but also of hMSC-colonized scaffolds in comparison to the pure BG. Based on the novel data, our recommendation is BG scaffolds with single infiltrated PLGA for cartilage tissue engineering.
Glatiramer Acetate Immunomodulation: Evidence of Neuroprotection and Cognitive Preservation
Authors: Kasindi Arielle , Fuchs Dieu-Trang , Koronyo Yosef , Rentsendorj Altan , Black Keith , Koronyo-Hamaoui Maya
Published: May 2022

Novel, neuroprotective uses of Copaxone (generic name: glatiramer acetate—GA) are being examined, primarily in neurological conditions involving cognitive decline. GA is a well-studied synthetic copolymer that is FDA-approved for immune-based treatment of relapsing remitting multiple sclerosis (RRMS). Clinical studies have explored the potential mechanism of action (MOA) and outcomes of GA immunization in patients. Furthermore, results from these and animal studies suggest that GA has a direct immunomodulatory effect on adaptive and innate immune cell phenotypes and responses. These MOAs have been postulated to have a common neuroprotective impact in several neuroinflammatory and neurodegenerative diseases. Notably, several clinical studies report that the use of GA mitigated MS-associated cognitive decline. Its propensity to ameliorate neuro-proinflammatory and degenerative processes ignites increased interest in potential alternate uses such as in age-related macular degeneration (AMD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). Preclinical studies are exploring less frequent subcutaneous administration of GA, such as once weekly or monthly or a single dosing regimen. Indeed, cognitive functions were found to be either preserved, reversed, or improved after the less frequent treatment regimens with GA in animal models of AD. In this systematic review, we examine the potential novel uses of GA across clinical and pre-clinical studies, with evidence for its beneficial impact on cognition. Future investigation in large-size, double-blind clinical trials is warranted to establish the impact of GA immunomodulation on neuroprotection and cognitive preservation in various neurological conditions.
Proteomic, Biochemical, and Morphological Analyses of the Effect of Silver Nanoparticles Mixed with Organic and Inorganic Chemicals on Wheat Growth
Authors: Komatsu Setsuko , Yamaguchi Hisateru , Hitachi Keisuke , Tsuchida Kunihiro
Published: May 2022

Wheat is vulnerable to numerous diseases; on the other hand, silver nanoparticles (AgNPs) exhibit a sterilizing action. To understand the combined effects of AgNPs with nicotinate and potassium nitrate (KNO3) for plant growth and sterilization, a gel- and label-free proteomics was performed. Root weight was promoted by the treatment of AgNPs mixed with nicotinate and KNO3. From a total of 5557 detected proteins, 90 proteins were changed by the mixture of AgNPs, nicotinate, and KNO3; among them, 25 and 65 proteins increased and decreased, respectively. The changed proteins were mainly associated with redox and biotic stress in the functional categorization. By immunoblot analysis, the abundance of glutathione reductase/peroxiredoxin and pathogen-related protein three significantly decreased with the mixture. Furthermore, from the changed proteins, the abundance of starch synthase and lipoxygenase significantly increased and decreased, respectively. Through biochemical analysis, the starch contents increased with the mixture. The application of esculetin, which is a lipoxygenase inhibitor, increased the weight and length of the root. These results suggest that the AgNPs mixed with nicotinate and KNO3 cause positive effects on wheat seedlings by regulating pathogen-related protein and reactive-oxygen species scavenging. Furthermore, increasing starch and decreasing lipoxygenase might improve wheat growth.
The Molecular Mechanisms Governing the Assembly of the Immuno- and Thymoproteasomes in the Presence of Constitutive Proteasomes
Authors: Watanabe Ayaka , Yashiroda Hideki , Ishihara Satoshi , Lo Megan , Murata Shigeo
Published: May 2022

The proteasome is a large protein complex responsible for proteolysis in cells. Though the proteasome is widely conserved in all eukaryotes, vertebrates additionally possess tissue-specific proteasomes, termed immunoproteasomes and thymoproteasomes. These specialized proteasomes diverge from constitutive proteasomes in the makeup of their catalytic 20S core particle (CP), whereby the constitutive β1, β2, and β5 catalytic subunits are replaced by β1i, β2i, and β5i in immunoproteasomes, or β1i, β2i, and β5t in thymoproteasomes. However, as constitutive β1, β2, and β5 are also present in tissues and cells expressing immuno- and thymoproteasomes, the specialized proteasomes must be able to selectively incorporate their specific subunits. Here, we review the mechanisms governing the assembly of constitutive and specialized proteasomes elucidated thus far. Studies have revealed that β1i and β2i are added onto the α-ring of the CP prior to the other β subunits. Furthermore, β5i and β5t can be incorporated independent of β4, whereas constitutive β5 incorporation is dependent on β4. These mechanisms allow the immuno- and thymoproteasomes to integrate tissue-specific β-subunits without contamination from constitutive β1, β2, and β5. We end the review with a brief discussion on the diseases caused by mutations to the immunoproteasome and the proteins involved with its assembly.
Multifaceted and Intricate Oncogenic Mechanisms of NDRG1 in Head and Neck Cancer Depend on Its C-Terminal 3R-Motif
Authors: You Guo-Rung , Chang Joseph T. , Li Hsiao-Fan , Cheng Ann-Joy
Published: May 2022

N-Myc downstream-regulated 1 (NDRG1) has inconsistent oncogenic functions in various cancers. We surveyed and characterized the role of NDRG1 in head and neck cancer (HNC). Cellular methods included spheroid cell formation, clonogenic survival, cell viability, and Matrigel invasion assays. Molecular techniques included transcriptomic profiling, RT-qPCR, immunoblotting, in vitro phosphorylation, immunofluorescent staining, and confocal microscopy. Prognostic significance was assessed by Kaplan–Meier analysis. NDRG1 participated in diverse oncogenic functions in HNC cells, mainly stress response and cell motility. Notably, NDRG1 contributed to spheroid cell growth, radio-chemoresistance, and upregulation of stemness-related markers (CD44 and Twist1). NDRG1 facilitated cell migration and invasion, and was associated with modulation of the extracellular matrix molecules (fibronectin, vimentin). Characterizing the 3R-motif in NDRG1 revealed its mechanism in the differential regulation of the phenotypes. The 3R-motif displayed minimal effect on cancer stemness but was crucial for cell motility. Phosphorylating the motif by GSK3b at serine residues led to its nuclear translocation to promote motility. Clinical analyses supported the oncogenic function of NDRG1, which was overexpressed in HNC and associated with poor prognosis. The data elucidate the multifaceted and intricate mechanisms of NDRG1 in HNC. NDRG1 may be a prognostic indicator or therapeutic target for refractory HNC.
Electrospun Membrane Surface Modification by Sonocoating with HA and ZnO:Ag Nanoparticles—Characterization and Evaluation of Osteoblasts and Bacterial Cell Behavior In Vitro
Authors: Higuchi Julia , Klimek Katarzyna , Wojnarowicz Jacek , Opalińska Agnieszka , Chodara Agnieszka , Szałaj Urszula , Dąbrowska Sylwia , Fudala Damian , Ginalska Grazyna
Published: May 2022

Guided tissue regeneration and guided bone regeneration membranes are some of the most common products used for bone regeneration in periodontal dentistry. The main disadvantage of commercially available membranes is their lack of bone cell stimulation and easy bacterial colonization. The aim of this work was to design and fabricate a new membrane construct composed of electrospun poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) fibers sonocoated with layers of nanoparticles with specific properties, i.e., hydroxyapatite and bimetallic nanocomposite of zinc oxide–silver. Thus, within this study, four different variants of biomaterials were evaluated, namely: poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) biomaterial, poly(D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite biomaterial, poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano zinc oxide–silver biomaterial, and poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite/nano zinc oxide–silver biomaterial. First, it was demonstrated that the wettability of biomaterials—a prerequisite property important for ensuring desired biological response—was highly increased after the sonocoating process. Moreover, it was indicated that biomaterials composed of poly (D,L-lactic acid)/poly (lactic-co-glycolic acid) with or without a nano hydroxyapatite layer allowed proper osteoblast growth and proliferation, but did not have antibacterial properties. Addition of a nano zinc oxide–silver layer to the biomaterial inhibited growth of bacterial cells around the membrane, but at the same time induced very high cytotoxicity towards osteoblasts. Most importantly, enrichment of this biomaterial with a supplementary underlayer of nano hydroxyapatite allowed for the preservation of antibacterial properties and also a decrease in the cytotoxicity towards bone cells, associated with the presence of a nano zinc oxide–silver layer. Thus, the final structure of the composite poly (D,L-lactic acid)/poly (lactic-co-glycolic acid)/nano hydroxyapatite/nano zinc oxide–silver seems to be a promising construct for tissue engineering products, especially guided tissue regeneration/guided bone regeneration membranes. Nevertheless, additional research is needed in order to improve the developed construct, which will simultaneously protect the biomaterial from bacterial colonization and enhance the bone regeneration properties.
An Ex Vivo 3D Tumor Microenvironment-Mimicry Culture to Study TAM Modulation of Cancer Immunotherapy
Authors: Li Yan-Ruide , Yu Yanqi , Kramer Adam , Hon Ryan , Wilson Matthew , Brown James , Yang Lili
Published: May 2022

Tumor-associated macrophages (TAMs) accumulate in the solid tumor microenvironment (TME) and have been shown to promote tumor growth and dampen antitumor immune responses. TAM-mediated suppression of T-cell antitumor reactivity is considered to be a major obstacle for many immunotherapies, including immune checkpoint blockade and adoptive T/CAR-T-cell therapies. An ex vivo culture system closely mimicking the TME can greatly facilitate the study of cancer immunotherapies. Here, we report the development of a 3D TME-mimicry culture that is comprised of the three major components of a human TME, including human tumor cells, TAMs, and tumor antigen-specific T cells. This TME-mimicry culture can readout the TAM-mediated suppression of T-cell antitumor reactivity, and therefore can be used to study TAM modulation of T-cell-based cancer immunotherapy. As a proof-of-principle, the studies of a PD-1/PD-L1 blockade therapy and a MAO-A blockade therapy were performed and validated.
Characterization of Peripheral Blood TCR in Patients with Type 1 Diabetes Mellitus by BD RhapsodyTM VDJ CDR3 Assay
Authors: Okamura Takuro , Hamaguchi Masahide , Tominaga Hiroyuki , Kitagawa Noriyuki , Hashimoto Yoshitaka , Majima Saori , Senmaru Takafumi , Okada Hiroshi , Ushigome Emi , Nakanishi Naoko , Shichino Shigeyuki , Fukui Michiaki
Published: May 2022

The sequence of complementarity-determining region 3 of the T-cell receptor (TCR) varies widely due to the insertion of random bases during V-(D)-J recombination. In this study, we used single-cell VDJ sequencing using the latest technology, BD Rhapsody, to identify the TCR sequences of autoreactive T-cells characteristic of Japanese type 1 diabetes mellitus (T1DM) and to clarify the pairing of TCR of peripheral blood mononuclear cells from four patients with T1DM at the single-cell level. The expression levels of the TCR alpha variable (TRAV) 17 and TRAV21 in T1DM patients were higher than those in healthy Japanese subjects. Furthermore, the Shannon index of CD8+ T cells and FOXP3+ cells in T1DM patients was lower than that of healthy subjects. The gene expression of PRF1, GZMH, ITGB2, NKG7, CTSW, and CST7 was increased, while the expression of CD4, CD7, CD5, HLA-A, CD27, and IL-32 was decreased in the CD8+ T cells of T1DM patients. The upregulated gene expression was IL4R and TNFRSF4 in FOXP3+ cells of T1DM patients. Overall, these findings demonstrate that TCR diversity and gene expression of CD8+ and FOXP3+ cells are different in patients with T1DM and healthy subjects.
The Impact of Escherichia coli Probiotic Strain O83:K24:H31 on the Maturation of Dendritic Cells and Immunoregulatory Functions In Vitro and In Vivo
Authors: Súkeníková Lenka , Černý Viktor , Věcek Jan , Petrásková Petra , Novotná Olga , Vobruba Šimon , Michalčíková Tereza , Procházka Jan , Kolářová Libuše , Prokešová Ludmila , Hrdý Jiří
Published: May 2022

Early postnatal events are important for the development of the neonatal immune system. Harboring the pioneering microorganisms forming the microbiota of the neonatal gastrointestinal tract is important for priming the immune system, as well as inducing appropriate tolerance to the relatively innocuous environmental antigens and compounds of normal healthy microbiota. Early postnatal supplementation of suitable, safe probiotics could accelerate this process. In the current study, the immunomodulatory capacity of the probiotic strain of Escherichia coli O83:K24:H31 (EcO83) was characterized in vitro and in vivo. We compared the capacity of EcO83 with and without hemolytic activity on selected immune characteristics in vitro as determined by flow cytometry and quantitative real-time PCR. Both strains with and without hemolytic activity exerted comparable capacity on the maturation of dendritic cells while preserving the induction of interleukin 10 (Il10) expression in dendritic cells and T cells cocultured with EcO83 primed dendritic cells. Early postnatal supplementation with EcO83 led to massive but transient colonization of the neonatal gastrointestinal tract, as detected by in vivo bioimaging. Early postnatal EcO83 administration promoted gut barrier function by increasing the expression of claudin and occludin and the expression of Il10. Early postnatal EcO83 application promotes maturation of the neonatal immune system and promotes immunoregulatory and gut barrier functions.
Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study
Authors: Pellegrin Maria Chiara , Penco Arturo , Amadio Leonardo , Naviglio Samuele , De Leo Luigina , Radillo Oriano , Biolo Gianni , Fiotti Nicola , Mearelli Filippo , Rabusin Marco , Barbi Egidio , Monasta Lorenzo
Published: May 2022

Serious bacterial infections (SBI) in children are associated with considerable morbidity and mortality, and their early identification remains challenging. The role of laboratory tests in this setting is still debated, and new biomarkers are needed. This prospective, observational, single-center study aims to evaluate the diagnostic role of blood biomarkers in detecting SBI in children presenting with signs of systemic inflammatory response syndrome (SIRS). A panel of biomarkers was performed, including C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), absolute neutrophil count (ANC), interleukin (IL)-6, IL-8, IL-10, human terminal complement complex (C5b-9), Plasmalemma-Vesicle-associated protein 1 (PV-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Phospholipase A2 (PLA2). Among 103 patients (median age 2.9 years, 60% males), 39 had a diagnosis of SBI (38%). Significant predictors of SBI were CRP (p = 0.001) and ICAM-1 (p = 0.043). WBC (p = 0.035), ANC (p = 0.012) and ANC/WBC ratio (p = 0.015) were also significantly associated with SBI in children without pre-existing neutropenia. ROC curves, however, revealed suboptimal performance for all variables. Nevertheless, a model that combined CRP and ANC/WBC ratio had more in-depth diagnostic accuracy than either of the two variables. Overall, this study confirms the limited usefulness of blood biomarkers for the early diagnosis of SBI. WBC, ANC, ANC/WBC ratio, CRP, and ICAM-1 showed the best, albeit moderate, diagnostic accuracy.
Orthopedic and Nonsurgical Orthodontic Treatment of Adolescent Skeletal Class III Malocclusion Using Bone-Anchored Maxillary Protraction and Temporary Anchorage Devices: A Case Report
Authors: Alnefaie Mohammed , Han Woo-Jin , Ahn Yoon-Soo , Baik Won-Kyeong , Choi Sung-Hwan
Published: May 2022

This report describes the case of a 12-year-old female patient with a long mandible experiencing difficulty chewing with the right molar. Considering the age of the patient, bone-anchored maxillary protraction using four miniplates placed below the maxillary zygomatic arch and anterior symphysis of the mandible and Class III intermaxillary elastics were planned. After 12 months, orthodontic treatment was initiated. After extraction of the impacted maxillary right second premolar and mandibular right second primary molar, protraction of the mandibular right molars was performed using a miniplate placed on the anterior part of the mandible as an anchor. Miniscrews were placed in the left posterior part of the mandible to improve the molar relationship and correct the dental midline through distalization of the mandibular left posterior teeth. We reported successful sequential comprehensive nonsurgical treatment in an adolescent with skeletal Class III malocclusion.