bluuebunny/crossref_metadata_2025 huggingface dataset:
Intermittent Dynamic Compression Confers Anabolic Effects in Articular Cartilage
Authors: Engstrøm Amalie , Gillesberg Frederik S. , Groen Solveig S. , Frederiksen Peder , Bay-Jensen Anne-Christine , Karsdal Morten A. , Thudium Christian S.
Published: August 2021

(1) Background: Mechanical loading is an essential part of the function and maintenance of the joint. Despite the importance of intermittent mechanical loading, this factor is rarely considered in preclinical models of cartilage, limiting their translatability. The aim of this study was to investigate the effects of intermittent dynamic compression on the extracellular matrix during long-term culture of bovine cartilage explants. (2) Methods: Bovine articular cartilage explants were cultured for 21 days and subjected to 20 min of 1 Hz cyclic compressive loading five consecutive days each week. Cartilage remodeling was investigated in the presence of IGF-1 or TGF-β1, as well as a TGF-β receptor 1 (ALK5) kinase inhibitor and assessed with biomarkers for type II collagen formation (PRO-C2) and fibronectin degradation (FBN-C). (3) Results: Compression of cartilage explants increased the release of PRO-C2 and FBN-C to the conditioned media and, furthermore, IGF-1 and compression synergistically increased PRO-C2 release. Inhibition of ALK5 blocked PRO-C2 and FBN-C release in dynamically compressed explants. (4) Conclusions: Dynamic compression of cartilage explants increases both type II collagen formation and fibronectin degradation, and IGF-1 interacts synergistically with compression, increasing the overall impact on cartilage formation. These data show that mechanical loading is important to consider in translational cartilage models.
Effect of Surface Micro-Hardness Change in Multistep Machining on Friction and Wear Characteristics of Titanium Alloy
Authors: Hou Guanming , Li Anhai
Published: August 2021

The machined surface quality, especially the micro-hardness of machined surface layers, is strongly correlated to the friction and wear characteristics of titanium alloy engineering parts. Therefore, to explore relationship of the local surface micro-hardness change in multistep machining and the surface wear resistance of the machined parts is urgently necessary. The machined surfaces were acquired through two-step (roughing and finishing) and three step (roughing, semi-finishing, and finishing) cylindrical turning experiments. The dry friction and wear tests were carried out by UMT-2 friction and wear tester on the multistep final machined surface along the feed direction. The surface wear microtopography and subsurface microstructure were observed and analyzed by scanning electron microscope. The micro-hardness variation in the local area of the finishing surface will cause the extension of unstable friction time stage while withstanding the cyclic and alternating contact stresses, and the soft–hard alternating area should be the sources of friction and wear defects, for instance cracks, peeling pits, fracture striations and even the wear fracture zone to crack propagation and peeling off. This will be of great significance to accurately control the machined surface quality and adaptively improve the surface wear resistance of titanium alloy components.
Natural Radioactivity and Radon Exhalation from Building Materials in Underground Parking Lots
Authors: Jasaitis Dainius , Pečiulienė Milda
Published: August 2021

The change of natural ionizing radiation and the radon exhalation rates from typical building materials in underground parking lots are presented in the article. The activity concentration of natural radionuclides 232Th, 226Ra, and 40K in six important types of construction materials, which are mostly used in Lithuania, were analyzed using high-resolution gamma spectroscopy. The highest values were found in concrete and ferroconcrete samples: 226Ra 44 and 90 Bq kg−1; 232Th 29 and 34 Bq kg−1; 40K 581 and 603 Bq kg−1. A strong positive correlation (0.88) was observed between radium activity concentration and radon concentration. The activity indexes (Iα and Iγ) and radium equivalent activity (Req) evaluating the suitability of materials for such constructions from the view of radiation safety were determined. The average values of the calculated absorbed dose rate in samples ranged from 18.24 nGy h−1 in the sand to 87.26 nGy h−1 in ferroconcrete. The calculated annual effective dose was below the limit of 1.0 mSv y−1. The values of the external and internal hazards index (Hex and Hin) were all below unity, and the values of Iγ and Iα were below the recommended levels of 0.5 and 1. Dosimetric analysis of underground parking lots was carried out. It was determined that the external equivalent dose rate caused by the 222Rn progeny radiation in the underground car parking lots varies from 17 to 30% of the total equivalent dose rate.
Deep Feature Fusion Based Dual Branch Network for X-ray Security Inspection Image Classification
Authors: Xu Yingda , Wei Jianming
Published: August 2021

Automatic computer security inspection of X-ray scanned images has an irresistible trend in modern life. Aiming to address the inconvenience of recognizing small-sized prohibited item objects, and the potential class imbalance within multi-label object classification of X-ray scanned images, this paper proposes a deep feature fusion model-based dual branch network architecture. Firstly, deep feature fusion is a method to fuse features extracted from several model layers. Specifically, it operates these features by upsampling and dimension reduction to match identical sizes, then fuses them by element-wise sum. In addition, this paper introduces focal loss to handle class imbalance. For balancing importance on samples of minority and majority class, it assigns weights to class predictions. Additionally, for distinguishing difficult samples from easy samples, it introduces modulating factor. Dual branch network adopts the two components above and integrates them in final loss calculation through the weighted sum. Experimental results illustrate that the proposed method outperforms baseline and state-of-art by a large margin on various positive/negative ratios of datasets. These demonstrate the competitivity of the proposed method in classification performance and its potential application under actual circumstances.
Cytokine-Related Effect of Buccal-Delivered Collagen Peptide Incorporated in Mucoadhesive Films to Improve Female Skin Conditions
Authors: Kim Yeon Ho , Im Dahye , Lee Kyung-Hee , Yoon Saemi , Ham Yun Beom
Published: August 2021

Recently, interest in collagen products has increased in the industries However, collagen products that are taken orally have the problem of being degraded by digestive enzymes. Therefore, a collagen peptide buccal delivery film (C-BDF) was developed to enhance the absorption without destruction and a clinical trial was conducted. A C-BDF was developed as a double layer and the permeation of collagen peptide (CP) through swine mucosa was investigated. This clinical study was performed on 43 healthy women, who were divided into either a control (n = 21) or test group (n = 22), over the course of 4 weeks. Skin assessments analyzed the hydration, elasticity, and roughness. In addition, the production of peroxynitrite and IL-1α in RAW 264.7 cells in supernatant media was conducted. A total of 1 kDa of CP in BDF showed significantly stronger permeation through swine mucosa compared to 3 kDa of CP in BDF. The C-BDF significantly enhanced skin hydration, elasticity, and roughness, and it removed wrinkles with no side effects after 2 weeks of intake. In addition, the production of peroxynitrite and IL-1α after the treatment with CP was significantly increased. Therefore, this study showed that collagen peptides could be completely absorbed into mucosa via a buccal delivery system and homeopathic effects might occur.
Predictive Modelling for Blasting-Induced Vibrations from Open-Pit Excavations
Authors: Choi Yo-Hyun , Lee Sean Seungwon
Published: August 2021

Reliable estimates of peak particle velocity (PPV) from blasting-induced vibrations at a construction site play a crucial role in minimizing damage to nearby structures and maximizing blasting efficiency. However, reliably estimating PPV can be challenging due to complex connections between PPV and influential factors such as ground conditions. While many efforts have been made to estimate PPV reliably, discrepancies remain between measured and predicted PPVs. Here, we analyzed various methods for assessing PPV with several key relevant factors and 1191 monitored field blasting records at 50 different open-pit sites across South Korea to minimize the discrepancies. Eight prediction models are used based on artificial neural network, conventional empirical formulas, and multivariable regression analyses. Seven influential factors were selected to develop the prediction models, including three newly included and four already formulated in empirical formulas. The three newly included factors were identified to have a significant influence on PPV, as well as the four existing factors, through a sensitivity analysis. The measured and predicted PPVs were compared to evaluate the performances of prediction models. The assessment of PPVs by an artificial neural network yielded the lowest errors, and site factors, K and m were proposed for preliminary open-pit blasting designs.
Effects of Sinusoidal Model on Non-Parallel Voice Conversion with Adversarial Learning
Authors: Al-Radhi Mohammed Salah , Csapó Tamás Gábor , Németh Géza
Published: August 2021

Voice conversion (VC) transforms the speaking style of a source speaker to the speaking style of a target speaker by keeping linguistic information unchanged. Traditional VC techniques rely on parallel recordings of multiple speakers uttering the same sentences. Earlier approaches mainly find a mapping between the given source–target speakers, which contain pairs of similar utterances spoken by different speakers. However, parallel data are computationally expensive and difficult to collect. Non-parallel VC remains an interesting but challenging speech processing task. To address this limitation, we propose a method that allows a non-parallel many-to-many voice conversion by using a generative adversarial network. To the best of the authors’ knowledge, our study is the first one that employs a sinusoidal model with continuous parameters to generate converted speech signals. Our method involves only several minutes of training examples without parallel utterances or time alignment procedures, where the source–target speakers are entirely unseen by the training dataset. Moreover, empirical study is carried out on the publicly available CSTR VCTK corpus. Our conclusions indicate that the proposed method reached the state-of-the-art results in speaker similarity to the utterance produced by the target speaker, while suggesting important structural ones to be further analyzed by experts.
A 2.4 GHz 20 W 8-Channel RF Source Module with Improved Channel Output Balance
Authors: Nam Hyosung , Kim Taewan , Sim Taejoo , Bae Sooji , Kim Junghyun
Published: August 2021

This paper presents a 2.4 GHz 20 W 8-channel radio frequency (RF) source module with improved channel output balance. The proposed RF source module is composed of an RF source generation/DC control part, a power amplification part, and a power dividing part. A 2-stage power amplifier (PA) is combined with gallium nitride high-electron-mobility transistors, including a 25 W transistor and 2-way combined 120 W transistors as the drive and main PA, respectively. In addition, a structure was applied to improve the channel output balance compared to that of the previous module, and the differences of the phase and magnitude of the output power between channels are alleviated within 0.35° and 0.18 dB, respectively. A water jacket was implemented under the drive and main PAs for liquid cooling; however, unlike in the previous work, it was designed by optimizing the size of the water jacket and reducing unnecessary materials using a brazing process. The output power at each channel was 43 dBm, and the drain efficiency was more than 50% at 2.4 GHz. The total module size was 244 mm × 247.4 mm × 30 mm, and its volume was reduced by approximately 58.4% compared to that of the previous module.
Fundamental Numerical Analysis of a Porous Micro-Combustor Filled with Alumina Spheres: Pore-Scale vs. Volume-Averaged Models
Authors: Li Qingqing , Wang Jiansheng , Li Jun , Shi Junrui
Published: August 2021

Inserting porous media into the micro-scale combustor space could enhance heat recirculation from the flame zone, and could thus extend the flammability limits and improve flame stability. In the context of porous micro-combustors, the pore size is comparable to the combustor characteristic length. It is insufficient to treat the porous medium as a continuum with the volume-averaged model (VAM). Therefore, a pore-scale model (PSM) is developed to consider the detailed structure of the porous media to better understand the coupling among the gas mixture, the porous media and the combustor wall. The results are systematically compared to investigate the difference in combustion characteristics and flame stability limits. A quantified study is undertaken to examine heat recirculation, including preheating and heat loss, in the porous micro-combustor using the VAM and PSM, which are beneficial for understanding the modeled differences in temperature distribution. The numerical results indicate that PSM predicts a scattered flame zone in the pore areas and gives a larger flame stability range, a lower flame temperature and peak solid matrix temperature, a higher peak wall temperature and a larger Rp-hl than a VAM counterpart. A parametric study is subsequently carried out to examine the effects of solid matrix thermal conductivity (ks) on the PSM and VAM, and then the results are analyzed briefly. It is found that for the specific configurations of porous micro-combustor considered in the present study, the PSM porous micro-combustor is more suitable for simplifying to a VAM with a larger Φ and a smaller ks, and the methods can be applied to other configurations of porous micro-combustors.
Comparing the Air Turbulence above Smooth and Rough Surfaces in the Amazon Region
Authors: Santana Raoni A. S. , Dias-Júnior Cléo Q. , do Vale Roseilson S. , Tóta Júlio , da Silva Rodrigo , Tapajós Raphael , Manzi Antônio O. , Beldini Troy P.
Published: August 2021

The goal of this work is to compare the main air turbulence characteristics of two common areas in the Amazonian landscape: a dense forest (rough surface) and a water surface (smooth surface). Using wind components data collected at high frequency by sonic anemometers located just above these surfaces, turbulence intensity and power spectra, temporal and length scales of the eddies, as well as the main terms of the TKE budget (TKE = turbulent kinetic energy) were evaluated for each surface type. The results showed that in general, the air turbulence intensity above the forest was higher than above the lake during the daytime, due to the high efficiency of the forest in absorbing the momentum of the turbulent flow. During the nighttime, the situation was reversed, with greater air turbulence intensity above the lake, except in some periods in which intermittent turbulence bursts occured above the forest.
Predicting the Nonlinear Response of PM2.5 and Ozone to Precursor Emission Changes with a Response Surface Model
Authors: Kelly James T. , Jang Carey , Zhu Yun , Long Shicheng , Xing Jia , Wang Shuxiao , Murphy Benjamin N. , Pye Havala O. T.
Published: August 2021

Reducing PM2.5 and ozone concentrations is important to protect human health and the environment. Chemical transport models, such as the Community Multiscale Air Quality (CMAQ) model, are valuable tools for exploring policy options for improving air quality but are computationally expensive. Here, we statistically fit an efficient polynomial function in a response surface model (pf-RSM) to CMAQ simulations over the eastern U.S. for January and July 2016. The pf-RSM predictions were evaluated using out-of-sample CMAQ simulations and used to examine the nonlinear response of air quality to emission changes. Predictions of the pf-RSM are in good agreement with the out-of-sample CMAQ simulations, with some exceptions for cases with anthropogenic emission reductions approaching 100%. NOx emission reductions were more effective for reducing PM2.5 and ozone concentrations than SO2, NH3, or traditional VOC emission reductions. NH3 emission reductions effectively reduced nitrate concentrations in January but increased secondary organic aerosol (SOA) concentrations in July. More work is needed on SOA formation under conditions of low NH3 emissions to verify the responses of SOA to NH3 emission changes predicted here. Overall, the pf-RSM performs well in the eastern U.S., but next-generation RSMs based on deep learning may be needed to meet the computational requirements of typical regulatory applications.
On the Problem of Critical Electric Field of Atmospheric Air
Authors: Syssoev Artem , Iudin Dmitry , Iudin Fedor , Klimashov Vitaly , Emelyanov Alexey
Published: August 2021

It is traditionally accepted to define the dielectric strength of air as an electric field corresponding to the balance between the rates of impact ionization and electrons’ attachment to neutrals. Its reduced value is known to be about 110 Td regardless of the altitude above the mean sea level. In this study, the altitude profile of the critical electric field of atmospheric air in the 0–40 km altitude range is specified. Unlike the conventional approach, a wide range of additional plasma-chemical processes occurring in atmospheric air, such as electron detachment from negative ions and ion-ion conversion is taken into account. Atmospheric air is considered to be a mixture of N2:O2 = 4:1 containing a small amount of chemically active small gas components, such as water vapor, atomic oxygen, ozone, and several types of nitrogen oxides. It is shown that the dielectric strength of air falls noticeably compared to its conventional value. The results of the study can be important to solve the problems of initiation and propagation of lightning discharges, blue starters, and blue jets.
Office Indoor PM and BC Level in Lithuania: The Role of a Long-Range Smoke Transport Event
Authors: Pauraite Julija , Mainelis Gediminas , Kecorius Simonas , Minderytė Agnė , Dudoitis Vadimas , Garbarienė Inga , Plauškaitė Kristina , Ovadnevaite Jurgita , Byčenkienė Steigvilė
Published: August 2021

While the impacts of climate change on wildfires and resulting air pollution levels have been observed, little is known about how indoor air filtering systems are performing under intensive smoke conditions. For this aim, particle number size distribution and concentration in a size range 0.5–18 µm and equivalent black carbon (eBC) mass concentration were measured in a modern office with a mechanical ventilation system. Measurements took place from 30 September to 6 October 2020 in the Center for Physical Sciences and Technology (FTMC) campus located in the urban background environment in Lithuania. During the measurement campaign, an intensive pollution episode, related to long-range transport wildfire smoke, was observed. The results indicated that the smoke event increased both indoor and outdoor eBC mass concentrations twice. Filters were non-selective for different eBC sources (biomass burning versus traffic) or chemical composition of carbonaceous aerosol particles (eBC versus brown carbon (BrC)). Air filtering efficiency was found to be highly dependent on particle size. During the smoke event the highest particle number concentration was observed at 2.1 µm and 1.0 µm size particles in outdoor and indoor air, respectively. Differences of indoor to outdoor ratio between event and non-event days were not significant. Because of lower removal rate for small particles, eBC had higher contribution to total PM2.5 mass concentration in indoor air than in outdoor air. The results gained are crucial for decision-making bodies in order to implement higher-quality air-filtering systems in office buildings and, as a result, minimize potential health impacts.
Radon Spatial Variations in University’s Buildings Located in an Italian Karst Region
Authors: Leonardi Federica , Botti Teresa , Buresti Giuliana , Caricato Anna Paola , Chezzi Alberto , Pepe Carlo , Spagnolo Sabina , Tonnarini Sabrina , Veschetti Miriam , Trevisi Rosabianca
Published: August 2021

In the framework of a collaboration between INAIL and University of Salento, an indoor radon survey in 54 buildings belonging to the UniSalento University (Southeast Italy) was carried out. The monitored buildings differ by type, construction period, materials, etc., and are located in an area with a morphology characterized mainly by marls, calcareous marls, and calcarenites (karst area). The sample of the survey includes 963 rooms at different floors: it consists in rooms mainly located at ground floor (67%), first floor (12%), and below ground (12%). SSNTD passive dosimeters measured the average radon activity concentration for two consecutive semesters (spring/summer and autumn/winter) from which annual radon averages were estimated for each room. The spatial variability within buildings was investigated in terms of variation between floors and among rooms at the same floor. Data analysis provides evidence that the distributions (in terms of arithmetic mean, standard deviation, median, and geometric mean) of indoor radon annual averages at ground floor and at first floor within building are very similar. This highlights that the karstic characteristics of soil and building materials affect radon levels not only below ground and at ground floor, but also at first floor. Moreover, to evaluate the spatial variability of radon among buildings or floors, the analysis of the distribution of coefficient of variation (CV) was carried out: the results show a low spatial variability with median and average values of CVs ≤ 30% both for the whole building and at different floor levels.
Deterministic and Probabilistic Evaluation of Sub-Seasonal Precipitation Forecasts at Various Spatiotemporal Scales over China during the Boreal Summer Monsoon
Authors: Li Yuan , Wu Zhiyong , He Hai , Lu Guihua
Published: August 2021

Skillful sub-seasonal precipitation forecasts can provide valuable information for both flood and drought disaster mitigations. This study evaluates both deterministic and probabilistic sub-seasonal precipitation forecasts of ECMWF, ECCC, and UKMO models derived from the Sub-seasonal to Seasonal (S2S) Database at various spatiotemporal scales over China during the boreal summer monsoon. The Multi-Source Weighted-Ensemble Precipitation, version 2 (MSWEP V2), is used as the reference dataset to evaluate the forecast skills of the models. The results suggest that skillful deterministic sub-seasonal precipitation forecasts are found when the lead time is within 2 weeks. The deterministic forecast skills reduce quickly when the lead time is beyond 2 weeks. Positive ranked probability skill scores (RPSS) are only found when the lead time is within 2 weeks for probabilistic forecasts as well. Multimodel ensembling helps to improve forecast skills by removing large negative skill scores in northwestern China. The forecast skills are also improved at larger spatial scales or longer temporal scales. However, the improvement is only observed for certain regions where the predictable low frequency signals remain at longer lead times. The composite analysis suggests that both the El Niño–Southern Oscillation (ENSO) and Madden–Julian Oscillation (MJO) have an impact on weekly precipitation variability over China. The forecast skills are found to be enhanced during active ENSO and MJO phases. In particular, the forecast skills are found to be enhanced during active MJO phases.
Influence of Krakow Winter and Summer Dusts on the Redox Cycling of Vitamin B12a in the Presence of Ascorbic Acid
Authors: Polaczek Justyna , Jodłowska Angelika , Stochel Grażyna , van Eldik Rudi
Published: August 2021

Air pollution remains a serious problem in Krakow, Poland. According to the European Environmental Agency, annual mean levels of both PM2.5 and PM10 recorded in Krakow are much higher than EU limit values. Thus, the influence of particulate matter (PM) on the function of living organisms, as well as different physiological processes, is an urgent subject to be studied. The reported research forms part of the multi-disciplinary project ‘Air Pollution versus Autoimmunity: Role of multiphase aqueous Inorganic Chemistry,’ which aims to demonstrate the PM effect on the immune system. The present studies focused on the role of dust collected in Krakow on the redox cycling of vitamin B12a in the presence of ascorbic acid. Dust samples collected during the winter 2019/2020 and summer 2020 months in the city center of Krakow were characterized using various analytical techniques. The influence of Krakow dusts on the kinetics of the reaction between nitrocobalamin and ascorbic acid was confirmed and discussed in terms of the composition of the samples. Possible reasons for the reported findings are provided.
Biosurfactants: Properties and Applications in Drug Delivery, Biotechnology and Ecotoxicology
Authors: Bjerk Thiago R. , Severino Patricia , Jain Sona , Marques Conrado , Silva Amélia M. , Pashirova Tatiana , Souto Eliana B.
Published: August 2021

Surfactants are amphiphilic compounds having hydrophilic and hydrophobic moieties in their structure. They can be of synthetic or of microbial origin, obtained respectively from chemical synthesis or from microorganisms’ activity. A new generation of ecofriendly surfactant molecules or biobased surfactants is increasingly growing, attributed to their versatility of applications. Surfactants can be used as drug delivery systems for a range of molecules given their capacity to create micelles which can promote the encapsulation of bioactives of pharmaceutical interest; besides, these assemblies can also show antimicrobial properties. The advantages of biosurfactants include their high biodegradability profile, low risk of toxicity, production from renewable sources, functionality under extreme pH and temperature conditions, and long-term physicochemical stability. The application potential of these types of polymers is related to their properties enabling them to be processed by emulsification, separation, solubilization, surface (interfacial) tension, and adsorption for the production of a range of drug delivery systems. Biosurfactants have been employed as a drug delivery system to improve the bioavailability of a good number of drugs that exhibit low aqueous solubility. The great potential of these molecules is related to their auto assembly and emulsification capacity. Biosurfactants produced from bacteria are of particular interest due to their antibacterial, antifungal, and antiviral properties with therapeutic and biomedical potential. In this review, we discuss recent advances and perspectives of biosurfactants with antimicrobial properties and how they can be used as structures to develop semisolid hydrogels for drug delivery, in environmental bioremediation, in biotechnology for the reduction of production costs and also their ecotoxicological impact as pesticide alternative.
Peri-Implantitis Regenerative Therapy: A Review
Authors: Mordini Lorenzo , Sun Ningyuan , Chang Naiwen , De Guzman John-Paul , Generali Luigi , Consolo Ugo
Published: August 2021

The surgical techniques available to clinicians to treat peri-implant diseases can be divided into resective and regenerative. Peri-implant diseases are inflammatory conditions affecting the soft and hard tissues around dental implants. Despite the large number of investigations aimed at identifying the best approach to treat these conditions, there is still no universally recognized protocol to solve these complications successfully and predictably. This review will focus on the regenerative treatment of peri-implant osseous defects in order to provide some evidence that can aid clinicians in the approach to peri-implant disease treatment.
New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma
Authors: Wadowska Katarzyna , Błasiak Piotr , Rzechonek Adam , Bil-Lula Iwona , Śliwińska-Mossoń Mariola
Published: August 2021

Background: Lung cancer is a multifactorial disease with a heterogeneous tumor group that hampers diagnostic and therapeutic approaches, as well as understanding of the processes that underlie its pathogenesis. Current research efforts are focused on examining alterations in the tumor microenvironment, which may affect the pathogenesis and further malignant progression in lung cancer. The aim of this study was to investigate changes in the levels of biomarkers involved in the lung tumor microenvironment and their diagnostic utility in differentiating lung cancer subtypes and stages. Methods: This study comprised 112 lung cancer patients, 50 with adenocarcinoma, 35 with squamous cell carcinoma, 13 with other non-small cell lung carcinoma subtypes, and 14 with other lung neoplasms than non-small cell lung carcinoma. Tumor markers (CEA, CYFRA 21-1, and NSE) were measured in the patients’ sera and plasmas, along with IL-6, TNF-α, SAA1, CRP, MMP-2, MMP-9, glucose, lactate, and LDH, utilizing enzyme-linked immunosorbent assays, enzyme immunoassays, and automated clinical chemistry and turbidimetry systems. The results were statistically analyzed across patient groups based on the subtype and stage of lung cancer. Results: Glucose concentrations showed statistically significant (p < 0.05) differences both between lung cancer subtypes and stages, with the highest levels in patients with other lung neoplasms (me = 130.5 mg/dL) and in patients with stage IIB lung cancer (me = 132.0 mg/dL). In patients with advanced lung cancer, IL-6 and LDH had considerably higher concentration and activity. There was also a significant positive correlation between IL-6 and MMP-9 in adenocarcinoma and SqCC, with correlation coefficients of 0.53 and 0.49, respectively. The ROC analyses showed that the best single biomarkers for distinguishing adenocarcinoma from squamous cell carcinoma are glucose, CRP, and CYFRA 21-1; however, their combination did not significantly improve sensitivity, specificity, and the AUC value. The combinations of IL-6, glucose, LDH and CEA, IL-6, SAA1, MMP-9, and lactate can distinguish patients with stage IIB lung cancer from those with stage IIA with 100% sensitivity, 100% specificity, and with an AUC value of 0.8333 and 1.0000, respectively, whereas the combination of CEA, IL-6, and LDH can identify patients with stage IIIA lung cancer from those with stage IIB with 72.73% sensitivity, 94.44% specificity, and an AUC value of 0.8686. Conclusion: There is a link between biomarkers of tumor microenvironment changes and tumor markers, and combinations of these markers may be clinically useful in the differential diagnosis of adenocarcinoma and squamous cell carcinoma, as well as lung cancer stages IIB and IIA, and IIIA and IIB.
Histatin 5 Metallopeptides and Their Potential against Candida albicans Pathogenicity and Drug Resistance
Authors: Zolin Gabriela Vieira Silva , Fonseca Fauller Henrique da , Zambom Carolina Reis , Garrido Saulo Santesso
Published: August 2021

Usually caused by Candida albicans, buccal candidiasis begins with the morphological transition between yeast and hyphal cells. Over time and without the correct treatment, it can be disseminated through the bloodstream becoming a systemic infection with high mortality rates. C. albicans already shows resistance against antifungals commonly used in treatments. Therefore, the search for new drugs capable of overcoming antifungal resistance is essential. Histatin 5 (Hst5) is an antimicrobial peptide of the Histatin family, that can be found naturally in human saliva. This peptide presents high antifungal activity against C. albicans. However, Hst5 action can be decreased for interaction with enzymes and metal ions present in the oral cavity. The current work aims to bring a brief review of relevant aspects of the pathogenesis and resistance mechanisms already reported for C. albicans. In addition, are also reported here the main immune responses of the human body and the most common antifungal drugs. Finally, the most important aspects regarding Histatin 5 and the benefits of its interaction with metals are highlighted. The intention of this review is to show the promising use of Hst5 metallopeptides in the development of effective drugs.
A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals
Authors: Kawamura Yusuke , Nakayama Akiyoshi , Shimizu Seiko , Toyoda Yu , Nishida Yuichiro , Hishida Asahi , Katsuura-Kamano Sakurako , Shibuya Kenichi , Tamura Takashi , Kawaguchi Makoto , Suzuki Satoko , Iwasawa Satoko , Nakashima Hiroshi , Ibusuki Rie , Uemura Hirokazu , Hara Megumi , Takeuchi Kenji , Takada Tappei , Tsunoda Masashi , Arisawa Kokichi , Takezaki Toshiro , Tanaka Keitaro , Ichida Kimiyoshi , Wakai Kenji , Shinomiya Nariyoshi , Matsuo Hirotaka
Published: August 2021

Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.
Regulation of the HTRA2 Protease Activity by an Inhibitory Antibody-Derived Peptide Ligand and the Influence on HTRA2-Specific Protein Interaction Networks in Retinal Tissues
Authors: Schmelter Carsten , Fomo Kristian Nzogang , Perumal Natarajan , Pfeiffer Norbert , Grus Franz H.
Published: August 2021

The mitochondrial serine protease HTRA2 has many versatile biological functions ranging from being an important regulator of apoptosis to being an essential component for neuronal cell survival and mitochondrial homeostasis. Loss of HTRA2 protease function is known to cause neurodegeneration, whereas overactivation of its proteolytic function is associated with cell death and inflammation. In accordance with this, our group verified in a recent study that the synthetic peptide ASGYTFTNYGLSWVR, encoding the hypervariable sequence part of an antibody, showed a high affinity for the target protein HTRA2 and triggered neuroprotection in an in vitro organ culture model for glaucoma. To unravel this neuroprotective mechanism, the present study showed for the first time that the synthetic CDR1 peptide significantly (p < 0.01) inhibited the proteolytic activity of HTRA2 up to 50% using a specific protease function assay. Furthermore, using state-of-the-art co-immunoprecipitation technologies in combination with high-resolution MS, we identified 50 significant protein interaction partners of HTRA2 in the retina of house swine (p < 0.01; log2 fold change > 1.5). Interestingly, 72% of the HTRA2-specific interactions (23 of 31 binders) were inhibited by additional treatment with UCF-101 (HTRA2 protease inhibitor) or the synthetic CDR peptide. On the other hand, the remaining 19 binders of HTRA2 were exclusively identified in the UCF101 and/or CDR group. However, many of the interactors were involved in the ER to Golgi anterograde transport (e.g., AP3D1), aggrephagy (e.g., PSMC1), and the pyruvate metabolism/citric acid cycle (e.g., SHMT2), and illustrated the complex protein interaction networks of HTRA2 in neurological tissues. In conclusion, the present study provides, for the first time, a comprehensive protein catalogue of HTRA2-specific interaction partners in the retina, and will serve as reference map in the future for studies focusing on HTRA2-mediated neurodegeneration.
Treatment of Critical-Size Femoral Bone Defects with Chitosan Scaffolds Produced by a Novel Process from Textile Engineering
Authors: Zwingenberger Bruno , Vater Corina , Bell Roland L. , Bolte Julia , Mehnert Elisabeth , Brünler Ronny , Aibibu Dilbar , Zwingenberger Stefan
Published: August 2021

The purpose of this study was to investigate, in vitro and in vivo, the suitability of chitosan (CHS) scaffolds produced by the net-shape-nonwoven (NSN) technology, for use as bone graft substitutes in a critical-size femoral bone defect in rats. For in vitro investigations, scaffolds made of CHS, mineralized collagen (MCM), or human cancellous bone allograft (CBA) were seeded with human telomerase-immortalized mesenchymal stromal cells (hTERT-MSC), incubated for 14 days, and thereafter evaluated for proliferation and osteogenic differentiation. In vivo, CHS, MCM and CBA scaffolds were implanted into 5 mm critical-size femoral bone defects in rats. After 12 weeks, the volume of newly formed bone was determined by microcomputed tomography (µCT), while the degree of defect healing, as well as vascularization and the number of osteoblasts and osteoclasts, was evaluated histologically. In vitro, CHS scaffolds showed significantly higher osteogenic properties, whereas treatment with CHS, in vivo, led to a lower grade of bone-healing compared to CBA and MCM. While chitosan offers a completely new field of scaffold production by fibers, these scaffolds will have to be improved in the future, regarding mechanical stability and osteoconductivity.
Targeting STAT3 Signaling Pathway in Colorectal Cancer
Authors: Gargalionis Antonios N. , Papavassiliou Kostas A. , Papavassiliou Athanasios G.
Published: August 2021

Signal transducer and activator of transcription 3 (STAT3) is a critical transcription factor that has been firmly associated with colorectal cancer (CRC) initiation and development. STAT3 mediates key inflammatory mechanisms in colitis-associated cancer, becomes excessively activated in CRC, and enhances cancer cell proliferation, tumor growth, angiogenesis, invasion, and migration. STAT3 hyperactivation in malignant cells, surrounding immune cells and cancer-associated fibroblasts, mediates inhibition of the innate and adaptive immunity of the tumor microenvironment, and, therefore, tumor evasion from the immune system. These features highlight STAT3 as a promising therapeutic target; however, the mechanisms underlying these features have not been fully elucidated yet and STAT3 inhibitors have not reached the clinic in everyday practice. In the present article, we review the STAT3 signaling network in CRC and highlight the current notion for the design of STAT3-focused treatment approaches. We also discuss recent breakthroughs in combination immunotherapy regimens containing STAT3 inhibitors, therefore providing a new perception for the clinical application of STAT3 in CRC.
Disease-Modifying Potential of Metformin and Alendronate in an Experimental Mouse Model of Osteoarthritis
Authors: Belenska-Todorova Lyudmila , Lambova Sevdalina Nikolova , Stoyanova Stela , Georgieva Elenka , Batsalova Tsvetelina , Moten Dzhemal , Kolchakova Desislava , Dzhambazov Balik
Published: August 2021

Osteoarthritis (OA) is the most common degenerative joint disease causing progressive damages of the cartilage and subchondral bone, synovial inflammation, and severe pain. Despite the complex pathomorphological changes that occur in OA, the approach to different forms of OA is standardized. The global results from pharmacological treatment are not satisfactory. Hence, this study aimed to explore the effects of metformin, alendronate, and their combination on OA development and progression in mice with collagenase-induced osteoarthritis (CIOA). Female ICR (CD-2) mice were randomized to five groups: control group, CIOA untreated, CIOA + metformin, CIOA + alendronate, and CIOA + metformin + alendronate. OA was induced by the intra-articular (i.a.) injection of collagenase. OA phenotype was analyzed by flow cytometry (bone marrow cell differentiation), ELISA (serum levels of the adipokines leptin and resistin), and histology (pathological changes of the knee joint). Treatment with metformin, alendronate, or their combination inhibited the expression of RANK and RANKL on osteoblasts and osteoclasts obtained by ex vivo cultivation of bone marrow cells in mineralization or osteoclastogenic media. In addition, metformin treatment was effective for the attenuation of fibroblast differentiation, but not of mesenchymal stem cells (MSCs), while alendronate had an opposite effect. The combination of metformin and alendronate had a suppressive effect on both MSCs and fibroblasts differentiation. Treatment with metformin, alendronate, and their combination decreased serum concentrations of leptin and resistin in the chronic phase of arthritis. The histopathological examination showed that compared with the untreated CIOA group (OA score 9), the groups treated with metformin (OA score 4) or alendronate (OA score 6) had lower scores for cartilage changes. Metformin combined with alendronate significantly decreased the degree of cartilage degeneration (OA score 2), suggesting that this combination might be a useful approach for the treatment of OA patients.
Clinical Implication of Metformin in Relation to Diabetes Mellitus and Ovarian Cancer
Authors: Singh Santosh Kumar , Apata Tejumola , Singh Shriti , McFadden Melayshia , Singh Rajesh
Published: August 2021

Since multiple reports established an association between diabetes mellitus and various cancers, emerging studies have surfaced to understand the effects of metformin as an anti-cancer agent. Although there was previous, but conflicting evidence, of a relationship between diabetes and ovarian cancer (OvCa), recent studies have supported this association. The mechanism of cancer development in patients with diabetes is likely to involve hyperglycemia, hyperinsulinemia, chronic inflammation, reactive oxygen species, regulation of cellular homeostasis, and activation of various pathways that lead to tumor cell proliferation. Preclinical evidence indicating that metformin, a medication commonly used to treat type 2 diabetes mellitus, may protect against OvCa. Metformin exerts anti-cancer properties by activating the MAPK pathway, inhibiting the PI3K/AKT/mTOR pathway, increasing tumor suppressor genes, inducing G2/M cycle arrest, and various other processes. Several studies have shown the efficacy of metformin as an adjunct with standard chemotherapeutic agents due to its synergistic effects on OvCa cells. This review highlights the epidemiologic evidence supporting a link between diabetes and OvCa, the fundamental molecular mechanism underlying carcinogenesis in patients with diabetes, the anti-cancer effects of metformin, and the need for further clinical investigations on combination therapies with metformin and standard chemotherapeutic agents for OvCa.
Sequence-Independent DNA Adsorption on Few-Layered Oxygen-Functionalized Graphene Electrodes: An Electrochemical Study for Biosensing Application
Authors: Asefifeyzabadi Narges , Holland Torrey E. , Sivakumar Poopalasingam , Talapatra Saikat , Senanayake Ishani M. , Goodson Boyd M. , Shamsi Mohtashim H.
Published: August 2021

DNA is strongly adsorbed on oxidized graphene surfaces in the presence of divalent cations. Here, we studied the effect of DNA adsorption on electrochemical charge transfer at few-layered, oxygen-functionalized graphene (GOx) electrodes. DNA adsorption on the inkjet-printed GOx electrodes caused amplified current response from ferro/ferricyanide redox probe at concentration range 1 aM–10 nM in differential pulse voltammetry. We studied a number of variables that may affect the current response of the interface: sequence type, conformation, concentration, length, and ionic strength. Later, we showed a proof-of-concept DNA biosensing application, which is free from chemical immobilization of the probe and sensitive at attomolar concentration regime. We propose that GOx electrodes promise a low-cost solution to fabricate a highly sensitive platform for label-free and chemisorption-free DNA biosensing.
Ratiometric G-Quadruplex Assay for Robust Lead Detection in Food Samples
Authors: Liu Yumei , Yang Hao , Wan Rui , Khan Mohammad Rizwan , Wang Nan , Busquets Rosa , Deng Ruijie , He Qiang , Zhao Zhifeng
Published: August 2021

Lead (Pb2+) pollution is a serious food safety issue, rapid detection of Pb2+ residual in food is vital to guarantee food quality and safety. Here we proposed ratiometric aptamer probes, allowing robust Pb2+ supervision in food samples. Pb2+ specific aptamer can bolster a transition of G-quadruplex structural response to Pb2+; this process can be monitored by N-methyl mesoporphyrin IX (NMM), which is highly specific to G-quadruplex. Particularly, the utilization of G-quadruplex specific dye and terminal-labeled fluorophore allowed to endue ratiometric signal outputs towards Pb2+, dramatically increase the robustness for lead detection. The ratiometric G-quadruplex assay allowed a facile and one-pot Pb2+ detection at room temperature using a single-stranded DNA aptamer. We demonstrated its feasibility for detecting lead pollution in fresh eggs and tap water samples. The ratiometric G-quadruplex design is expected to be used for on-site Pb2+ testing associated with food safety.
Building Embodied Spaces for Spatial Memory Neurorehabilitation with Virtual Reality in Normal and Pathological Aging
Authors: Tuena Cosimo , Serino Silvia , Pedroli Elisa , Stramba-Badiale Marco , Riva Giuseppe , Repetto Claudia
Published: August 2021

Along with deficits in spatial cognition, a decline in body-related information is observed in aging and is thought to contribute to impairments in navigation, memory, and space perception. According to the embodied cognition theories, bodily and environmental information play a crucial role in defining cognitive representations. Thanks to the possibility to involve body-related information, manipulate environmental stimuli, and add multisensory cues, virtual reality is one of the best candidates for spatial memory rehabilitation in aging for its embodied potential. However, current virtual neurorehabilitation solutions for aging and neurodegenerative diseases are in their infancy. Here, we discuss three concepts that could be used to improve embodied representations of the space with virtual reality. The virtual bodily representation is the combination of idiothetic information involved during virtual navigation thanks to input/output devices; the spatial affordances are environmental or symbolic elements used by the individual to act in the virtual environment; finally, the virtual enactment effect is the enhancement on spatial memory provided by actively (cognitively and/or bodily) interacting with the virtual space and its elements. Theoretical and empirical findings will be presented to propose innovative rehabilitative solutions in aging for spatial memory and navigation.