bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose-Dependent Effect of Melatonin on BAT Thermogenesis in Zücker Diabetic Fatty Rat: Future Clinical Implications for Obesity
Authors: Aouichat Samira , Raya Enrique , Molina-Carballo Antonio , Munoz-Hoyos Antonio , Aloweidi Abdelkarim Saleh , Elmahallawy Ehab Kotb , Agil Ahmad
Published: August 2022

Experimental data have revealed that melatonin at high doses reduced obesity and improved metabolic outcomes in experimental models of obesity, mainly by enhancing brown adipose tissue (BAT) thermogenesis. A potential dose-response relationship has yet to be performed to translate these promising findings into potential clinical therapy. This study aimed to assess the effects of different doses of melatonin on interscapular BAT (iBAT) thermogenic capacity in Zücker diabetic fatty (ZDF) rats. At 6 wk of age, male ZDF rats were divided into four groups (n = 4 per group): control and those treated with different doses of melatonin (0.1, 1, and 10 mg/kg of body weight) in their drinking water for 6 wk. Body weight (BW) was significantly decreased at doses of 1 and 10 mg/kg of melatonin, but not at 0.1 mg/kg compared with the control, with a similar rate of BW decrease being reached at the dose of 1 mg/kg (by ~11%) and 10 mg/kg (by ~12%). This effect was associated with a dose-dependent increase in the thermal response to the baseline condition or acute cold challenge in the interscapular area measurable by infrared thermography, with the highest thermal response being recorded at the 10 mg/kg dose. Upon histology, melatonin treatment markedly restored the typical brownish appearance of the tissue and promoted a shift in size distribution toward smaller adipocytes in a dose-dependent fashion, with the most pronounced brownish phenotype being observed at 10 mg/kg of melatonin. As a hallmark of thermogenesis, the protein level of uncoupled protein 1 (UCP1) from immunofluorescence and Western blot analysis increased significantly and dose-dependently at all three doses of melatonin, reaching the highest level at the dose of 10 mg/kg. Likewise, all three doses of melatonin modulated iBAT mitochondrial dynamics by increasing protein expression of the optic atrophy protein type 1 (OPA1) fusion marker and decreasing that of the dynamin-related protein1 (DRP1) fission marker, again dose-dependently, with the highest and lowest expression levels, respectively, being reached at the 10 mg/kg dose. These findings highlight for the first time the relevance of the dose-dependency of melatonin toward BW control and BAT thermogenic activation, which may have potential therapeutic implications for the treatment of obesity. To clinically apply the potential therapeutic of melatonin for obesity, we consider that the effective animal doses that should be extrapolated to obese individuals may be within the dose range of 1 to 10 mg/kg.
Potential Antioxidative and Anti-Hyperuricemic Components Targeting Superoxide Dismutase and Xanthine Oxidase Explored from Polygonatum Sibiricum Red.
Authors: Li Jing , Wang Zhi , Fan Minxia , Hu Guangwan , Guo Mingquan
Published: August 2022

Polygonatum sibiricum Red. (P. sibiricum) has been used as a traditional Chinese medicine with a wide range of pharmacology effects. However, the responsible bioactive compounds and their mechanisms of action concerning its antioxidative and anti-hyperuricemic activities remain unexplored. In this work, the antioxidant capacity of P. sibiricum was firstly evaluated with the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azinobis-(3ethylbenzthiazoline)-6-sulfonic acid (ABTS) and ferric-reducing antioxidant power (FRAP) assays, from which the ethyl acetate (EA) fraction exhibited the highest DPPH, ABTS radical scavenging, and ferric-reducing capacities. Meanwhile, the EA fraction displayed the highest total phenolic and flavonoid contents among the four fractions. Next, the potential ligands from the EA fraction were screened out by bio-affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC-MS) with superoxide dismutase (SOD) and xanthine oxidase (XOD). As a result, N-trans-p-coumaroyloctopamine, N-trans-feruloyloctopamine, N-trans-feruloyltyramine were identified as potential SOD ligands, while N-cis-p-coumaroyltyramine was determined as potential XOD ligand. Additionally, these four ligands effectively interact with SOD and XOD in the molecular docking analysis, with binding energies (BEs) ranging from –6.83 to –6.51 kcal/mol, and the inhibition constants (Ki) from 9.83 to 16.83 μM, which were better than the positive controls. In conclusion, our results indicated that P. sibiricum has good antioxidative and anti-hyperuricemic activities, and its corresponding active ligands targeting SOD and XOD could be explored by the UF-LC-MS method.
Optimal DL-Methionyl-DL-Methionine Supplementation Improved Intestinal Physical Barrier Function by Changing Antioxidant Capacity, Apoptosis and Tight Junction Proteins in the Intestine of Juvenile Grass Carp (Ctenopharyngodon idella)
Authors: Wu Pei , Su Yuening , Feng Lin , Jiang Weidan , Kuang Shengyao , Tang Ling , Jiang Jun , Liu Yang , Zhou Xiaoqiu
Published: August 2022

The present study was a part of a larger research project that aimed to investigate the effects of Met-Met supplementation on fish growth and intestinal health. This study mainly focused on the relationship between dietary Met-Met and intestinal physical barrier function in fish. Seven iso-nitrogenous diets supplemented with 2.50 g/kg DL-methionine (DL-Met) and six graded levels of Met-Met (0.00, 0.79, 1.44, 1.84, 2.22, and 2.85 g/kg) were used to feed juvenile grass carp for 10 weeks, after which a 14-day Aeromonas hydrophila challenge test was performed. The results indicated that optimum levels of Met-Met decreased intestinal oxidative damage, probably by increasing total antioxidant capacity, and the activity and gene expression levels of several antioxidant enzymes, which were closely related to the changed Nrf2/Keap1 signaling. Meanwhile, optimum levels of Met-Met decreased intestinal apoptosis and improved the intestinal tight junction, as evident by the downregulated mRNA levels of initiator and executioner caspases; the pro-apoptotic-related proteins FasL, Apaf-1, and Bax; and upregulated mRNA levels of the anti-apoptotic proteins Bcl-2, Mcl-1b, and IAP and the TJ proteins claudins, occludin, and ZOs. Furthermore, the positive effects of Met-Met on improving intestinal physical barrier function were superior to those of DL-Met in fish. These findings showed that optimal Met-Met supplementation improved intestinal physical barrier function, probably by changing antioxidant capacity, apoptosis, and tight junction proteins in fish.
Effects of Number of Atoms and Doping Concentration on the Structure, Phase Transition, and Crystallization Process of Fe1-x-yNixCoy Alloy: A Molecular Dynamic Study
Authors: Trong Dung , Long Van , Ţălu Ştefan
Published: August 2022

In this study, molecular dynamics simulations are employed to study the influencing factors such as doping concentration, number of atoms, and temperature on the structural characteristics, phase transition, and crystallization of Fe1-x-yNixCoy alloy. The results show that Fe1-x-yNixCoy alloy always exists with three metals, Fe, Ni, and Cu, which are distributed quite evenly according to the ratio of tap phase concentration. In Fe1-x-yNixCoy alloy, there are always six types of links, Fe–Fe, Fe–Ni, Fe–Co, Ni–Ni, Ni–Co, and Co–Co. Calculated results showed with the increases in the doping concentration, the length of links (r) has a constant value and the height g(r) of the Radial Distribution Function (RDF) has a modified value. The process of increasing the concentration of Fe doping, and reducing the concentration of Co doping leads to an increase in crystallization, a decrease in the size (l) of the alloy, and the total energy of the system (Etot) increases and then decreases. Similarly, increasing the number of atoms leads to an increase in crystallization, but with an increase in temperature, the crystallization process decreases (that corresponds to the change in the number of structural units for the Face-centered cubic (FCC), Hexagonal Close-Packed (HCP), Body-centered cubic (BCC), and Amorphous (Amor)). The obtained results serve as a basis for experimental research in developing new magnetic materials in the future.
WUAD (Wheelchair User Assisted Design): A VR-Based Strategy to Make Buildings More Accessible
Authors: Pérez Emiliano , Espacio Alejandro , Salamanca Santiago , Merchán Pilar
Published: August 2022

Accessibility regulations towards building design and public places are more restrictive than in past years. Along with energy efficiency, accessibility is one of the pillars of an optimal building design. However, even buildings adapted for actual regulations are not always optimal, and there is still much to do to avoid adding more difficulties for people with disabilities. We proposed a wheelchair-user-assisted design methodology based on iterative bidirectional communication between a wheelchair simulator user and the building designer to reach the optimum specifications for an accessibility-friendly design. First-hand experience may be crucial to detect obstacles hardly noticeable to people with no impairments. To this end, VR technology was employed along with the mentioned wheelchair simulator to show the advantages of this kind of device when working on real-life experiences.
Simulated Annealing-Based Wavelength Selection for Robust Tissue Oxygenation Estimation Powered by the Extended Modified Lambert–Beer Law
Authors: Chauvin John , Akhbardeh Alireza , Brunnemer Robert , Vasefi Fartash , Bearman Gregory , Huong Audrey , Tavakolian Kouhyar
Published: August 2022

In this paper, we present a set of algorithms to enable the development of inexpensive hyperspectral sensors capable of estimating tissue oxygenation for wound monitoring. Estimation is conducted using the extended modified Lambert–Beer law, which has previously been proven robust to differences in melanin concentration. We introduce a novel wavelength selection algorithm that enables the estimation to be performed with high accuracy using only a small number (5–10) of wavelengths. Validation performed with Monte Carlo simulation data resulted in prediction errors <1%, with no significant differences among various skin types, for as few as five wavelengths under conditions representing both high precision instrumentation and more cost-effective sensors designed with inexpensive LEDs and/or filters. Validation with in vivo data collected from an occlusion study with 13 Asian volunteers showed statistically significant separation between the estimates for the at-rest and arterial occlusion states. Additional stability testing proved the proposed algorithms to be robust to small changes in the selected wavelengths as may occur in a real LED due to manufacturing tolerances and temperature fluctuations. This work concluded that the development of an inexpensive hyperspectral device for wound monitoring in all skin types is feasible using just a small number of wavelengths.
Specific Relation Attention-Guided Graph Neural Networks for Joint Entity and Relation Extraction in Chinese EMR
Authors: Pang Yali , Qin Xiaohui , Zhang Zhichang
Published: August 2022

Electronic medical records (EMRs) contain a variety of valuable medical entities and their relations. The extraction of medical entities and their relations has important application value in the structuring of EMR and the development of various types of intelligent assistant medical systems, and hence is a hot issue in intelligent medicine research. In recent years, most research aims to firstly identify entities and then to recognize the relations between the entities, and often suffers from many redundant operations. Furthermore, the challenge remains of identifying overlapping relation triplets along with the entire medical entity boundary and detecting multi-type relations. In this work, we propose a Specific Relation Attention-guided Graph Neural Networks (SRAGNNs) model to jointly extract entities and their relations in Chinese EMR, which uses sentence information and attention-guided graph neural networks to perceive the features of every relation in a sentence and then to extract those relations. In addition, a specific sentence representation is constructed for every relation, and sequence labeling is performed to extract its corresponding head and tail entities. Experiments on a medical evaluation dataset and a manually labeled Chinese EMR dataset show that our model improves the performance of Chinese medical entities and relation extraction.
Stator Design Method in Rotor–Stator Interference Flow Fields in Order to Suppress the Vibration of Bladed Disks
Authors: Ma Haoran , Zhou Zhou , Li Lin
Published: August 2022

Based on the computation and analysis of three-dimensional unsteady flow induced by rotor/stator interactions, the characteristics of flow excitation towards bladed disks were studied, including frequency components and circumferential wave components. By combining the resonant condition of bladed disks, a design principle was derived for determining the stator structural period from the view of averting resonance. The influences of different topologies on mistuned stators are also studied, for which the sectional non-uniform mistuned stator showed a clear effect in lowering the amplitude of formal excitation characteristics compared to tuned cases. A formula was developed to predict frequency components and circumferential wave components in the wake of both tuned and mistuned stators, making it easier to determine stator structural topologies in the design phase without performing three-dimensional unsteady CFD.
Evaluation and Recognition of Handwritten Chinese Characters Based on Similarities
Authors: Zhao Yuliang , Zhang Xinyue , Fu Boya , Zhan Zhikun , Sun Hui , Li Lianjiang , Zhang Guanglie
Published: August 2022

To accurately recognize ordinary handwritten Chinese characters, it is necessary to recognize the normative level of these characters. This study proposes methods to quantitatively evaluate and recognize these characters based on their similarities. Three different types of similarities, including correlation coefficient, pixel coincidence degree, and cosine similarity, are calculated between handwritten and printed Song typeface Chinese characters. Eight features are derived from the similarities and used to verify the evaluation performance and an artificial neural network is used to recognize the character content. The results demonstrate that our proposed methods deliver satisfactory evaluation effectiveness and recognition accuracy (up to 98%~100%). This indicates that it is possible to improve the accuracy in recognition of ordinary handwritten Chinese characters by evaluating the normative level of these characters and standardizing writing actions in advance. Our study can offer some enlightenment for developing methods for the identification of handwritten Chinese characters used in transaction processing activities.
A Review on the Current Status of Numerical Weather Prediction in Portugal 2021: Surface–Atmosphere Interactions
Authors: Monteiro Maria José , Couto Flavio T. , Bernardino Mariana , Cardoso Rita M. , Carvalho David , Martins João P. A. , Santos João A. , Argain José Luís , Salgado Rui
Published: August 2022

Earth system modelling is currently playing an increasing role in weather forecasting and understanding climate change, however, the operation, deployment and development of numerical Earth system models are extremely demanding in terms of computational resources and human effort. Merging synergies has become a natural process by which national meteorological services assess and contribute to the development of such systems. With the advent of joining synergies at the national level, the second edition of the workshop on Numerical Weather Prediction in Portugal was promoted by the Portuguese Institute for the Sea and Atmosphere, I.P. (IPMA), in cooperation with several Portuguese Universities. The event was hosted by the University of Évora, during the period of 11–12 of November 2021. It was dedicated to surface–atmosphere interactions and allowed the exchange of experiences between experts, students and newcomers. The workshop provided a refreshed overview of ongoing research and development topics in Portugal on surface–atmosphere interaction modelling and its applications and an opportunity to revisit some of the concepts associated with this area of atmospheric sciences. This article reports on the main aspects discussed and offers guidance on the many technical and scientific modelling platforms currently under study.
On Special Fuzzy Differential Subordinations Obtained for Riemann–Liouville Fractional Integral of Ruscheweyh and Sălăgean Operators
Authors: Alb Lupaş Alina
Published: August 2022

New results concerning fuzzy differential subordination theory are obtained in this paper using the operator denoted by Dz−λLαn, previously introduced by applying the Riemann–Liouville fractional integral to the convex combination of well-known Ruscheweyh and Sălăgean differential operators. A new fuzzy subclass DLnFδ,α,λ is defined and studied involving the operator Dz−λLαn. Fuzzy differential subordinations are obtained considering functions from class DLnFδ,α,λ and the fuzzy best dominants are also given. Using particular functions interesting corollaries are obtained and an example shows how the obtained results can be applied.
Scale-Up of Capsular Polysaccharide Production Process by Haemophilus influenzae Type b Using kLa Criterion
Authors: Pillaca-Pullo Omar , Vieira Lucas Dias , Takagi Mickie
Published: August 2022

Polyribosyl-ribitol-phosphate (PRP) from Haemophilus influenzae type b (Hib) is an active immunizing molecule used in the production of the vaccine against H. influenzae, and industrial production could contribute to satisfying a world demand especially in developing countries. In this sense, the aim of this study was to establish a scale-up process using the constant oxygen mass transfer coefficient (kLa) such as the criterion for production of PRP in three different sizes of bioreactor systems. Three different kLa values (24, 52 and 80 h−1) were evaluated in which the biological influence in a 1.5 L bioreactor and 52 h−1 was selected to scale-up the production process until a 75 L pilot-scale bioreactor was achieved. Finally, the fed-batch phase was started under a dissolved oxygen concentration (pO2) at 30% of the saturation in the 75 L bioreactor to avoid oxygen limitation; the performance of production presented high efficiency (9.0 g/L DCW-dry cell weight and 1.4 g/L PRP) in comparison with previous scale-up studies. The yields, productivity and kinetic behavior were similar in the three-size bioreactor systems in the batch mode indicating that kLa is possible to use for PRP production at large scales. This process operated under two stages and successfully produced DCW and PRP in the pilot scale and could be beneficial for future bioprocess operations that may lead to higher production and less operative cost.
Recent Advances in Analytical Methods for the Detection of Olive Oil Oxidation Status during Storage along with Chemometrics, Authenticity and Fraud Studies
Authors: Tarapoulouzi Maria , Agriopoulou Sofia , Koidis Anastasios , Proestos Charalampos , Enshasy Hesham Ali El , Varzakas Theodoros
Published: August 2022

Olive oil is considered to be a food of utmost importance, especially in the Mediterranean countries. The quality of olive oil must remain stable regarding authenticity and storage. This review paper emphasizes the detection of olive oil oxidation status or rancidity, the analytical techniques that are usually used, as well as the application and significance of chemometrics in the research of olive oil. The first part presents the effect of the oxidation of olive oil during storage. Then, lipid stability measurements are described in parallel with instrumentation and different analytical techniques that are used for this particular purpose. The next part presents some research publications that combine chemometrics and the study of lipid changes due to storage published in 2005–2021. Parameters such as exposure to light, air and various temperatures as well as different packaging materials were investigated to test olive oil stability during storage. The benefits of each chemometric method are provided as well as the overall significance of combining analytical techniques and chemometrics. Furthermore, the last part reflects on fraud in olive oil, and the most popular analytical techniques in the authenticity field are stated to highlight the importance of the authenticity of olive oil.
The Pro-Fibrotic Response to Lens Injury Is Signaled in a PI3K Isoform-Specific Manner
Authors: Menko A. Sue , Walker Janice L.
Published: August 2022

The signaling inputs that function to integrate biochemical and mechanical cues from the extracellular environment to alter the wound-repair outcome to a fibrotic response remain poorly understood. Here, using a clinically relevant post-cataract surgery wound healing/fibrosis model, we investigated the role of Phosphoinositide-3-kinase (PI3K) class I isoforms as potential signaling integrators to promote the proliferation, emergence and persistence of collagen I-producing alpha smooth muscle actin (αSMA+) myofibroblasts that cause organ fibrosis. Using PI3K isoform specific small molecule inhibitors, our studies revealed a requisite role for PI3K p110α in signaling the CD44+ mesenchymal leader cell population that we previously identified as resident immune cells to produce and organize a fibronectin-EDA rich provisional matrix and transition to collagen I-producing αSMA+ myofibroblasts. While the PI3K effector Akt was alone insufficient to regulate myofibroblast differentiation, our studies revealed a role for Rac, another potential PI3K effector, in this process. Our studies further uncovered a critical role for PI3K p110α in signaling the proliferation of CD44+ leader cells, which is important to the emergence and expansion of myofibroblasts. Thus, these studies identify activation of PI3K p110α as a critical signaling input following wounding to the development and progression of fibrotic disease.
Trafficking of Xylan to Plant Cell Walls
Authors: Avci Utku
Published: August 2022

Plant cell walls are classified as primary and secondary walls. The primary wall is necessary for plant morphogenesis and supports cell growth and expansion. Once the growth and expansion ceases, specialized cells form secondary walls in order to give strength and rigidity to the plant. Secondary cell walls are the main constituent of woody biomass. This biomass is raw material for industrial products, food, and biomaterials. Recently, there are an increasing number of studies using biomass for biofuel production and this area has gained importance. However, there are still many unknowns regarding the synthesis and structure of complex polysaccharides forming biomass. Cellulose, being one of the main components of the cell wall, is synthesized at the plasma membrane by cellulose synthase complexes and does not require transportation. On the other hand, pectin and hemicelluloses are synthesized by enzymes located in the Golgi apparatus. Therefore, they need to be transported to the plasma membrane. Even though this transport mechanism is very important, it is one of the least understood parts of the endomembrane system. Xylan is the major hemicellulose in many biomasses and is important for renewable material production. There is limited knowledge about the cellular trafficking of xylan. In this review, we cover the current information and what we know about the vesicular transport of xylan to the cell wall.
Physicochemical Characterization of the Catalytic Unit of Hammerhead Ribozyme and Its Relationship with the Catalytic Activity
Authors: Tanaka Yoshiyuki , Yamanaka Daichi , Morioka Saori , Yamaguchi Taishi , Morikawa Masayuki , Kodama Takashi S. , Sychrovský Vladimír , Kojima Chojiro , Hattori Yoshikazu
Published: August 2022

The catalytic mechanism of hammerhead ribozymes (HHRzs) attracted great attention in relation to the chemical origin of life. However, the basicity (pKa) of the catalytic sites of HHRzs has not been studied so far. As a result, the investigation of the currently assumed mechanism from an experimentally derived pKa value has been impossible. In HHRzs, there exists a highly functionalized structural unit (A9-G10.1 site) with a catalytic residue (G12) for the nucleophile activation and metal ion-binding residue (G10.1). As inferred from this fact, there might be a possibility that HHRzs may utilize specific functions of the A9-G10.1 motif for the catalytic reaction. Therefore, here we studied the basicity of G12/G10.1-corresponding residues using RNA duplexes including the A9-G10.1 motif without other conserved residues of HHRzs. From the pH-titration experiments with NMR spectra, we have obtained the intrinsic basicity of the G12/G10.1-corresponding residues in the motif, with pKa > 11.5 (N1 of G12) and pKa 4.5 (N7 of G10.1) for the first time. Based on the derived irregular basicity, their correlation with a catalytic activity and a metal affinity were investigated. In total, the derived thermodynamic properties are an intrinsic nature of the exclusive catalytic unit of HHRzs, which will be an outstanding pivot point for the mechanistic analyses.
Diversity of Endophytic Yeasts from Agricultural Fruits Positive for Phytohormone IAA Production
Authors: Kachalkin Aleksey , Glushakova Anna , Streletskii Rostislav
Published: August 2022

This study reports the diversity of cultivable endophytic yeasts from agricultural fruits that respond positively to the plant-promoting property of indole-3-acetic acid (IAA) production. The IAA synthesis by the strains was quantified with an Agilent 1100 series liquid chromatography system. IAA was present in the culture liquid of 72% of all 97 strains examined after three days of cultivation. The most active endophytic yeast strains in this study belonged to the species Aureobasidium pullulans, Candida zeylanoides, Hanseniaspora uvarum, Metschnikowia pulcherrima, Meyerozyma caribbica, Rhodotorula mucilaginosa, and Yarrowia galli. The highest IAA production was observed in the endophytic strain of A. pullulans (9109.19 ± 146.02 μg/g). No significant differences were found between IAA production in strains from agricultural products of different countries. However, the level of IAA production was strictly strain-specific. Our results suggest that the internal tissues of fruits may be a promising source for the isolation of plant-beneficial yeasts that can be used to promote plant growth.
Is Cortical Theta-Gamma Phase-Amplitude Coupling Memory-Specific?
Authors: Papaioannou Orestis , Crespo Laura P. , Clark Kailey , Ogbuagu Nicole N. , Alliende Luz Maria , Silverstein Steven M. , Erickson Molly A.
Published: August 2022

One of the proposed neural mechanisms involved in working memory is coupling between the theta phase and gamma amplitude. For example, evidence from intracranial recordings shows that coupling between hippocampal theta and cortical gamma oscillations increases selectively during working memory tasks. Theta-gamma phase-amplitude coupling can also be measured non-invasively through scalp EEG; however, EEG can only assess coupling within cortical areas, and it is not yet clear if this cortical-only coupling is truly memory-specific, or a more general phenomenon. We tested this directly by measuring cortical coupling during three different conditions: a working memory task, an attention task, and a passive perception condition. We find similar levels of theta-gamma coupling in all three conditions, suggesting that cortical theta-gamma phase-amplitude coupling is not a memory-specific signal, but instead reflects some other attentional or perceptual processes. Implications for understanding the brain dynamics of visual working memory are discussed.
Hilbert-Huang Transform-Based Seismic Intensity Parameters for Performance-Based Design of RC-Framed Structures
Authors: Tyrtaiou Magdalini , Elenas Anaxagoras , Andreadis Ioannis , Vasiliadis Lazaros
Published: August 2022

This study aims to develop the optimal artificial neural networks (ANNs) capable of estimating the seismic damage of reinforced concrete (RC)-framed structures by considering several seismic intensity parameters based on the Hilbert–Huang Transform (HHT) analysis. The selected architecture of ANN is the multi-layer feedforward perceptron (MFP) network. The values of the HHT-based parameters were calculated for a set of seismic excitations, and a combination of five to twenty parameters was performed to develop input datasets. The output data were the structural damage expressed by the Park and Ang overall damage index (DIPA,global). The potential contribution of nine training algorithms to developing the most effective MFP was also investigated. The results confirm that the evolved MFP networks, utilizing the employed parameters, provide an accurate estimation of the target output of DIPA,global. As a result, the developed MFPs can constitute a reliable computational intelligence approach for determining the seismic damage induced on structures and, thus, a powerful tool for the scientific community for the performance-based design of buildings.
Masonry Elements Strengthened with TRM: A Review of Experimental, Design and Numerical Methods
Authors: Boem Ingrid
Published: August 2022

Textile-Reinforced Mortar (TRM) is a modern and compatible strengthening strategy for existing masonry, which consists in plastering the walls by means of mortar layers with embedded grids or textiles made of long fibers. TRM can be very useful for the reduction of the seismic vulnerability of masonry buildings, since the fiber-based reinforcement, carrying high tensile stresses, opposes the widening of cracks and provides “pseudo-ductility” to the masonry. The increasing number of available studies on the subject testifies to its relevance but also the lack of a standardized or well-establish approach to quantify the benefits of these systems on the performance of masonry. The present review is aimed at providing a broad overview of how the study of TRM-strengthened masonry elements has been addressed in the literature. In particular, the main features of the different experimental tests are compared, dealing with both in-plane and out-of-plane behavior. Moreover, the different design methods and numerical modeling strategies are presented and discussed.
Treatment of Recurrent Nasopharyngeal Carcinoma: A Sequential Challenge
Authors: Peng Zhouying , Wang Yumin , Fan Ruohao , Gao Kelei , Xie Shumin , Wang Fengjun , Zhang Junyi , Zhang Hua , He Yuxiang , Xie Zhihai , Jiang Weihong
Published: August 2022

Recurrent nasopharyngeal carcinoma (NPC), which occurs in 10–20% of patients with primary NPC after the initial treatment modality of intensity-modulated radiation therapy (IMRT), is one of the major causes of death among NPC patients. Patients with recurrent disease without distant metastases still have a chance to be saved, but re-treatment often carries more serious toxicities or higher risks. For this group of patients, both otolaryngologists and oncologists are committed to developing more appropriate treatment regimens that can prolong patient survival and improve survival therapy. Currently, there are no international guidelines for the treatment of patients with recurrent NPC. In this article, we summarize past publications on clinical research and mechanistic studies related to recurrent NPC, combined with the experience and lessons learned by our institutional multidisciplinary team in the treatment of recurrent NPC. We propose an objective protocol for the treatment of recurrent NPC.
Identification of Gender- and Subtype-Specific Gene Expression Associated with Patient Survival in Low-Grade and Anaplastic Glioma in Connection with Steroid Signaling
Authors: Hirtz Alex , Lebourdais Nolwenn , Thomassin Magalie , Rech Fabien , Dumond Hélène , Dubois-Pot-Schneider Hélène
Published: August 2022

Low-grade gliomas are rare primary brain tumors, which fatally evolve to anaplastic gliomas. The current treatment combines surgery, chemotherapy, and radiotherapy. If gender differences in the natural history of the disease were widely described, their underlying mechanisms remain to be determined for the identification of reliable markers of disease progression. We mined the transcriptomic and clinical data from the TCGA-LGG and CGGA databases to identify male-over-female differentially expressed genes and selected those associated with patient survival using univariate analysis, depending on molecular characteristics (IDH wild-type/mutated; 1p/19q codeleted/not) and grade. Then, the link between the expression levels (low or high) of the steroid biosynthesis enzyme or receptors of interest and survival was studied using the log-rank test. Finally, a functional analysis of gender-specific correlated genes was performed. HOX-related genes appeared to be differentially expressed between males and females in both grades, suggesting that a glioma could originate in perturbation of developmental signals. Moreover, aromatase, androgen, and estrogen receptor expressions were associated with patient survival and were mainly related to angiogenesis or immune response. Therefore, consideration of the tight control of steroid hormone production and signaling seems crucial for the understanding of glioma pathogenesis and emergence of future targeted therapies.
Phototherapeutic Induction of Immunogenic Cell Death and CD8+ T Cell-Granzyme B Mediated Cytolysis in Human Lung Cancer Cells and Organoids
Authors: Valančiūtė Asta , Mathieson Layla , O’Connor Richard A. , Scott Jamie I. , Vendrell Marc , Dorward David A. , Akram Ahsan R. , Dhaliwal Kevin
Published: August 2022

Augmenting T cell mediated tumor killing via immunogenic cancer cell death (ICD) is the cornerstone of emerging immunotherapeutic approaches. We investigated the potential of methylene blue photodynamic therapy (MB-PDT) to induce ICD in human lung cancer. Non-Small Cell Lung Cancer (NSCLC) cell lines and primary human lung cancer organoids were evaluated in co-culture killing assays with MB-PDT and light emitting diodes (LEDs). ICD was characterised using immunoblotting, immunofluorescence, flow cytometry and confocal microscopy. Phototherapy with MB treatment and low energy LEDs decreased the proliferation of NSCLC cell lines inducing early necrosis associated with reduced expression of the anti-apoptotic protein, Bcl2 and increased expression of ICD markers, calreticulin (CRT), intercellular cell-adhesion molecule-1 (ICAM-1) and major histocompatibility complex I (MHC-I) in NSCLC cells. MB-PDT also potentiated CD8+ T cell-mediated cytolysis of lung cancer via granzyme B in lung cancer cells and primary human lung cancer organoids.
Interface Engineering-Induced 1T-MoS2/NiS Heterostructure for Efficient Hydrogen Evolution Reaction
Authors: Wei Helei , Tan Aidong , Liu Wenbo , Piao Jinhua , Wan Kai , Liang Zhenxing , Xiang Zhipeng , Fu Zhiyong
Published: August 2022

Metal phase molybdenum disulfide (1T-MoS2) is considered a promising electrocatalyst for the hydrogen evolution reaction (HER). In this work, an interface engineering-induced strategy is reported to prepare a 1T-MoS2/NiS heterostructure. The 1T-MoS2/NiS heterostructure exhibits an enhanced HER activity compared with that of the 1T-MoS2 in 1.0 M KOH. It achieves an overpotential of 0.12 V at a current density of 10 mA cm−2 with a Tafel slope of 69 mV dec−1. The density functional theory (DFT) calculations reveal that the interface engineering-induced 1T-MoS2/NiS heterostructure exhibits regulated electronic states of the S sites in 1T-MoS2, thus promoting the HER activity. This work demonstrates that tuning the electronic structure through interface engineering to enhance the intrinsic activity of electrocatalysts is a feasible strategy.
The ADP-Ribosylation Factor 4d Restricts Regulatory T-Cell Induction via Control of IL-2 Availability
Authors: Geers Bernd , Hagenstein Julia , Endig Jessica , Ulrich Hanna , Fleig Laura , Sprezyna Paulina , Mikulec Julita , Heukamp Lukas , Tiegs Gisa , Diehl Linda
Published: August 2022

Interleukin-2 is central to the induction and maintenance of both natural (nTreg) and induced Foxp3-expressing regulatory T cells (iTreg). Thus, signals that modulate IL-2 availability may, in turn, also influence Treg homeostasis. Using global knockout and cell-specific knockout mouse models, we evaluated the role of the small GTPase ADP-ribosylation factor 4d (Arl4d) in regulatory T-cell biology. We show that the expression of Arl4d in T cells restricts both IL-2 production and responsiveness to IL-2, as measured by the phosphorylation of STAT5. Arl4d-deficient CD4 T cells converted more efficiently into Foxp3+ iTreg in vitro in the presence of αCD3ε and TGFβ, which was associated with their enhanced IL-2 secretion. As such, Arl4d−/− CD4 T cells induced significantly less colonic inflammation and lymphocytic infiltration in a model of transfer colitis. Thus, our data reveal a negative regulatory role for Arl4d in CD4 T-cell biology, limiting iTreg conversion via the restriction of IL-2 production, leading to reduced induction of Treg from conventional CD4 T cells.
Noradrenaline and Movement Initiation Disorders in Parkinson’s Disease: A Pharmacological Functional MRI Study with Clonidine
Authors: Criaud Marion , Laurencin Chloé , Poisson Alice , Metereau Elise , Redouté Jérôme , Thobois Stéphane , Boulinguez Philippe , Ballanger Bénédicte
Published: August 2022

Slowness of movement initiation is a cardinal motor feature of Parkinson’s disease (PD) and is not fully reverted by current dopaminergic treatments. This trouble could be due to the dysfunction of executive processes and, in particular, of inhibitory control of response initiation, a function possibly associated with the noradrenergic (NA) system. The implication of NA in the network supporting proactive inhibition remains to be elucidated using pharmacological protocols. For that purpose, we administered 150 μg of clonidine to 15 healthy subjects and 12 parkinsonian patients in a double-blind, randomized, placebo-controlled design. Proactive inhibition was assessed by means of a Go/noGo task, while pre-stimulus brain activity was measured by event-related functional MRI. Acute reduction in noradrenergic transmission induced by clonidine enhanced difficulties initiating movements reflected by an increase in omission errors and modulated the activity of the anterior node of the proactive inhibitory network (dorsomedial prefrontal and anterior cingulate cortices) in PD patients. We conclude that NA contributes to movement initiation by acting on proactive inhibitory control via the α2-adrenoceptor. We suggest that targeting noradrenergic dysfunction may represent a new treatment approach in some of the movement initiation disorders seen in Parkinson’s disease.
Modelling Neurological Diseases in Large Animals: Criteria for Model Selection and Clinical Assessment
Authors: Eaton Samantha L. , Murdoch Fraser , Rzechorzek Nina M. , Thompson Gerard , Hartley Claudia , Blacklock Benjamin Thomas , Proudfoot Chris , Lillico Simon G. , Tennant Peter , Ritchie Adrian , Nixon James , Brennan Paul M. , Guido Stefano , Mitchell Nadia L. , Palmer David N. , Whitelaw C. Bruce A. , Cooper Jonathan D. , Wishart Thomas M.
Published: August 2022

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models.
Distinct and Dynamic Transcriptome Adaptations of iPSC-Generated Astrocytes after Cytokine Stimulation
Authors: Spreng Anna-Sophie , Brüll Markus , Leisner Heidrun , Suciu Ilinca , Leist Marcel
Published: August 2022

Astrocytes (ACs) do not only play a role in normal neurogenesis and brain homeostasis, but also in inflammatory and neurodevelopmental disorders. We studied here the different patterns of inflammatory activation triggered by cytokines in human induced pluripotent stem cell (iPSC)-derived ACs. An optimized differentiation protocol provided non-inflamed ACs. These cells reacted to TNFα with a rapid translocation of NFκB, while AC precursors showed little response. Transcriptome changes were quantified at seven time points (2–72 h) after stimulation with TNFα, IFNγ or TNFα plus IFNγ. TNFα triggered a strong response within 2 h. It peaked from 12–24 h and reverted towards the ground state after 72 h. Activation by IFNγ was also rapid, but the response pattern differed from that of TNFα. For instance, several chemokines up-regulated by TNFα were not affected by IFNγ. Instead, MHC-II-related antigen presentation was drastically enhanced. The combination of the two cytokines led to a stronger and more persistent response. For instance, TRIB3 up-regulation by the combination of TNFα plus IFNγ may have slowed NFκB inactivation. Additionally, highly synergistic regulation was observed for inflammation modifiers, such as CASP4, and for STAT1-controlled genes. The combination of the cytokines also increased oxidative stress markers (e.g., CHAC1), led to phenotypic changes in ACs and triggered markers related to cell death. In summary, these data demonstrate that there is a large bandwidth of pro-inflammatory AC states, and that single markers are not suitable to describe AC activation or their modulation in disease, development and therapy.
Hydrogen Sulfide Improves Angiogenesis by Regulating the Transcription of pri-miR-126 in Diabetic Endothelial Cells
Authors: Xue Wenlong , Zhang Qingqing , Chen Ying , Zhu Yichun
Published: August 2022

Introduction: Diabetes mellitus results in high rates of cardiovascular disease, such as microcirculation disorder of the lower limbs, with angiogenesis impairment being the main factor. The endothelium functions as a barrier between blood and the vessel wall. Vascular endothelial cell dysfunction caused by hyperglycemia is the main factor leading to angiogenesis impairment. Hydrogen sulfide (H2S) and miR-126-3p are known for their pro-angiogenesis effects; however, little is known about how H2S regulates miR-126-3p to promote angiogenesis under high-glucose conditions. Objectives: The main objective of this research was to explore how H2S regulates the miR-126-3p levels under high-glucose conditions. Methods: We evaluated the pro-angiogenesis effects of H2S in the diabetic hindlimb of an ischemia mice model and in vivo Matrigel plugs. Two microRNA datasets were used to screen microRNAs regulated by both diabetes and H2S. The mRNA and protein levels were detected through real-time PCR and Western blot, respectively. Immunofluorescent staining was also used to assess the capillary density and to evaluate the protein levels in vascular endothelial cells. Human umbilical vein endothelial cells (HUVECs) were used in in vitro experiments. A scratch wound-healing assay was applied to detect the migration ability of endothelial cells. Methylated DNA immunoprecipitation combined with real-time PCR was chosen to identify the DNA methylation level in the HUVECs. Results: Exogenous H2S improved angiogenesis in diabetic mice. miR-126-3p was regulated by both diabetes and H2S. Exogenous H2S up-regulated the miR-126-3p level and recovered the migration rate of endothelial cells via down-regulating the DNMT1 protein level, which was increased by high glucose. Furthermore, DNMT1 upregulation in the HUVECs increased the methylation levels of the gene sequences upstream of miR-126-3p and then inhibited the transcription of primary-miR-126, thus decreasing the miR-126-3p level. CSE overexpression in the HUVECs rescued the miR-126-3p level, by decreasing the methylation level to improve migration. Conclusion: H2S increases the miR-126-3p level through down-regulating the methylation level, by decreasing the DNMT1 protein level induced by high glucose, thus improving the angiogenesis originally impaired by high glucose.
Can Physical Exercise Promote the Development of Teenagers’ Non-Cognitive Ability?—Evidence from China Education Panel Survey (2014–2015)
Authors: Yuan Shiwei , Gu Qian , Lei Yuanyuan , Shen Jinbo , Niu Qian
Published: August 2022

Background: With the development of educational philosophy, physical exercise is considered to be an important factor in the development of individual cognitive abilities in adolescents. However, the effects of physical exercise on non-cognitive abilities in adolescents remain inadequate. Objective: This study examined the effect of physical exercise on non-cognitive ability and further examined the differences in this effect in different groups. Methods: Survey data on non-cognitive ability, physical exercise and covariates were collected in the China Education Panel Survey (2014–2015) from a nationally representative sample of adolescents (n = 7904) in the eighth (follow-up) grade. Results: The results show that, after controlling for the influence of other factors, physical exercise has a promoting effect on six non-cognitive abilities—social behavior (p < 0.001), communication ability (p < 0.01), perseverance (p < 0.05), school adaptation (p < 0.001), educational expectation (p < 0.01) and creative thinking (p < 0.01)—and there is no significant effect on emotional control (p > 0.05). Furthermore, the development of non-cognitive ability in physical exercise shows certain group differences. Conclusions: There are gender differences in the performance of non-cognitive ability. Girls perform better than boys in non-cognitive ability. Physical exercise is an important means to develop non-cognitive ability, which indicates that non-cognitive ability has plasticity in adolescence. Future intervention may improve the non-cognitive ability of Chinese adolescents by increasing physical exercise.
(–)-Xanthatin as a Killer of Human Breast Cancer MCF-7 Mammosphere Cells: A Comparative Study with Salinomycin
Authors: Takeda Shuso , Hirao-Suzuki Masayo , Shindo Mitsuru , Aramaki Hironori
Published: August 2022

Experimental evidence accumulated by our research group and others strongly suggests that (–)-xanthatin, a xanthanolide sesquiterpene lactone, exhibits anti-proliferative effects on human breast cancer cells (in vitro) as well as anti-tumor effects in experimental animals (in vivo). In cancer biology, it is now critically important for anti-cancer agents to selectively target cancer stem cells (CSCs) in order to overcome cancer therapeutic resistance and recurrence. However, it has not yet been established whether (–)-xanthatin abrogates the formation of breast CSCs. In the present study, we utilized chemically synthesized pure (–)-xanthatin and a culture system to obtain mammospheres from human breast cancer MCF-7 cells, which are a CSC-enriched population. We herein demonstrated for the first time that (–)-xanthatin exhibited the ability to kill mammospheres, similar to salinomycin, an established selective killer of CSCs. A possible anti-proliferative mechanism toward mammospheres by (–)-xanthatin is discussed.