bluuebunny/crossref_metadata_2025 huggingface dataset:
Network-Based Pharmacology Study Reveals Protein Targets for Medical Benefits and Harms of Cannabinoids in Humans
Authors: Li Xingyu , Madhukar Kudke Amit , Joseph Nepveux V Felix , Xu Yan
Published: February 2022

This network-based pharmacology study intends to uncover the underlying mechanisms of cannabis leading to a therapeutic benefit and the pathogenesis for a wide range of diseases claimed to benefit from or be caused by the use of the cannabis plant. Cannabis contains more than 600 chemical components. Among these components, cannabinoids are well-known to have multifarious pharmacological activities. In this work, twelve cannabinoids were selected as active compounds through text mining and drug-like properties screening and used for initial protein-target prediction. The disease-associated biological functions and pathways were enriched through GO and KEGG databases. Various biological networks [i.e., protein-protein interaction, target-pathway, pathway-disease, and target-(pathway)-target interaction] were constructed, and the functional modules and essential protein targets were elucidated through the topological analyses of the networks. Our study revealed that eighteen proteins (CAT, COMT, CYP17A1, GSTA2, GSTM3, GSTP1, HMOX1, AKT1, CASP9, PLCG1, PRKCA, PRKCB, CYCS, TNF, CNR1, CNR2, CREB1, GRIN2B) are essential targets of eight cannabinoids (CBD, CBDA, Δ9-THC, CBN, CBC, CBGA, CBG, Δ8-THC), which involve in a variety of pathways resulting in beneficial and adverse effects on the human body. The molecular docking simulation confirmed that these eight cannabinoids bind to their corresponding protein targets with high binding affinities. This study generates a verifiable hypothesis of medical benefits and harms of key cannabinoids with a model which consists of multiple components, multiple targets, and multiple pathways, which provides an important foundation for further deployment of preclinical and clinical studies of cannabis.
Effects of a 6-Minute Fast-Walking Protocol on Changes in Muscle Activity in Individuals with Flatfoot
Authors: Chiang Chu-Yuan , Lin Kuang-Wei , Lee Hui-Min , Wei Shun-Hwa , Chou Li-Wei
Published: February 2022

Flatfoot causes abnormal biomechanics in the lower extremity, resulting in discomfort and excessive burden on lower extremity muscles during functional tasks, and it potentially leads to associated syndromes in the lower extremity. The aim of this study was to investigate how a demanding, repetitive task affects the muscle strength, activities, and fatigue of the lower extremities during function tasks. Nineteen individuals with flexible flatfoot (10M9F, age: 24.74 ± 2.68 years) and fifteen non-flatfoot participants (6M9F, age: 24.47 ± 3.74) took part in this study. All participants performed maximal voluntary isometric contraction and functional tasks, including walking and single-leg standing tests before and immediately after a 6-min fast-walking protocol. A surface electromyography system was used to collect muscle activation data. Our results showed that, after 6 min of fast walking, peroneus longus activity increased only in the non-flatfoot group, and gastrocnemius activity increased in the flexible flatfoot group. In the flexible flatfoot group, greater recruitment in abductor halluces and greater fatigue in the tibialis anterior was observed. Individuals with flexible flatfoot showed altered muscle activation pattern after 6-min fast walking. These findings can provide an evidence-based explanation of associated syndromes in flatfoot populations and lead to potential intervention strategies in the future.
Room-Temperature Cell Disruption and Astaxanthin Recovery from Haematococcus lacustris Cysts Using Ultrathin α-Quartz Nanoplates and Ionic Liquids
Authors: Lee Nakyeong , Narasimhan Aditya Lakshmi , Moon Gyuseop , Kim Young-Eun , Park Myeonghwa , Kim Bolam , Mahadi Rendi , Chung Sungwook , Oh You-Kwan
Published: February 2022

Ionic liquids (ILs) are new green solvents, which are widely used in lignocellulosic and microalgal biorefineries. However, high-temperature operating conditions limit their application in the extraction of heat-labile algal products, such as bioactive astaxanthin. In this study, we report the technical feasibility of room-temperature astaxanthin extraction from Haematococcus lacustris cysts with a thick and complex cell wall structure, by combining ultrathin α-quartz nanoplates (NPLs) with ethyl-3-methylimidazolium ([Emim])-based ILs. When four different [Emim]-based ILs with thiocyanate (SCN), diethylphosphate (DEP), HSO4, and Cl anions were applied to 90-day-old H. lacustris cysts at room temperature (~28 °C), the astaxanthin extraction efficiency was as low as 9.6–14.2%. Under sonication, α-quartz NPLs disrupted the cyst cell wall for a short duration (5 min). The astaxanthin extraction efficacies of a subsequent IL treatment improved significantly to 49.8% for [Emim] SCN, 60.0% for [Emim] DEP, 80.7% for [Emim] HSO4, and 74.3% for [Emim] Cl ions, which were 4.4, 6.1, 8.4, and 5.2 times higher than the extraction efficacy of only ILs, respectively. This finding suggests that α-quartz NPLs can serve as powerful cell-wall-disrupting agents for the room-temperature IL-mediated extraction of astaxanthin from robust algal cyst cells.
Spray Drying and Spout-Fluid Bed Drying Microencapsulation of Mexican Plum Fruit (Spondias purpurea L.) Extract and Its Effect on In Vitro Gastrointestinal Bioaccessibility
Authors: Aguilera-Chávez Sthefany Leticia , Gallardo-Velázquez Tzayhri , Meza-Márquez Ofelia Gabriela , Osorio-Revilla Guillermo
Published: February 2022

The Mexican plum (Spondias purpurea L.) is a source of phenolic compounds; however, these compounds are susceptible to various factors (humidity, temperature, light, oxygen), as well as the digestion process, which can modify their bioaccessibility. This study aimed to extract and microencapsulate the phenolic compounds (PC), total anthocyanins (TA), ascorbic acid (AA), dehydroascorbic acid (DHA) and total vitamin C (AA+DHA) from Mexican plum ecotype “Cuernavaqueña” by spray drying (SD) and spout-fluid bed drying (SFB) and evaluate the bioaccessibility of these compounds by in vitro digestion. Optimal extraction conditions for bioactive compounds (BC) and antioxidant capacity (AC) were: three consecutive extractions at 40 °C, for 90 min each, with 1/5 solid-solvent ratio (4 g/20 mL), and 40% v/v aqueous ethanol. The extract without the encapsulation process suffered a significant (p ≤ 0.05) decrease in bioactive compounds and antioxidant capacity after in vitro digestion. Microcapsules obtained by SFB showed better retention and encapsulation efficiencies coupled with better protection against the digestion process. Microencapsulation by SFB protects the BC of Mexican plum, and it could be used in the food industry as ingredient to develop functional foods.
Difference in Coulomb Electrostatic Energy for Localized versus Delocalized Electrons and Electron Pairs—Exact Results Based on Cubic Charge Distributions
Authors: Essén Hanno , Stén Johan C.-E.
Published: February 2022

Wigner showed that a sufficiently thin electron gas will condense into a crystal of localized electrons. Here, we show, using a model based on cubic charge distributions that gives exact results, that the Coulomb repulsion energy of localized charge distributions is lower than that of delocalized distributions in spite of the fact that the total overall charge distribution is the same. Assuming a simple cubic geometry, we obtain an explicit result for the energy reduction. This reduction results from the exclusion of self-interactions of the electrons. The corresponding results for electron pairs are also discussed.
Pizza and Poop: Using Playful Probes to Investigate Community in Semi-Public Restrooms on a University Campus
Authors: Sanders Elizabeth B.-N. , Murteza Noor Danielle , Sabatelli Madison
Published: February 2022

This exploratory paper aims to discuss how community is fostered in semi-public restrooms on a college campus. While previous research has been undertaken in similar semi-private environments, this paper differs by simultaneously offering the researchers’ reflective insights in tandem with participants’ input on the research question. We begin by unpacking the challenges around Participatory Design (PD) activities that are undertaken in sensitive and private interior environments. Gathering perceptions of these sensitive spaces required methods that allowed for both anonymity and a communal approach through the use of provocative and evocative probes such as comment boxes and graffiti wall posters. This paper not only catalogues the findings of this research but also documents the difficulties in utilizing a participant-led approach, gaining access to sites and participants, and countering our own biases throughout the study’s construction. Through researcher accounts and participatory data analysis, the researchers offer a focused reflection on a possible new frontier for advancing PD methods in sensitive environments through playful probes. The contribution of this paper offers six lessons on the efficacy of using probes in semi-private environments, with playfulness as a primary driver of engaging participants.
Assessment of the Carbon Budget of Local Governments in South Korea
Authors: Kim Gyung Soon , Kim A Reum , Lim Bong Soon , Seol Jaewon , An Ji Hong , Lim Chi Hong , Joo Seung Jin , Lee Chang Seok
Published: February 2022

This study was carried out to assess the carbon budget of local governments in South Korea. The carbon budget was obtained from the difference between net ecosystem productivity (NEP) that the natural ecosystem displays, and carbon dioxide emissions calculated from energy consumption in each local government. NEP was obtained from the difference between net primary productivity, measured by an allometric method, and soil respiration, measured with EGM-4 in natural forests and artificial plantations. Heterotrophic respiration was adjusted to 55% level of the total soil respiration based on existing research results. A field survey to obtain information for components of the carbon cycle was conducted in Cheongju (central Korea) and Yeosu (southern Korea). Pinus densiflora, Quercus acutissima, and Quercus mongolica (central Korea) and P. densiflora and Q. acutissima (southern Korea) forests were selected as the natural forests. Pinus rigida and Larix kaempferi (central Korea) and P. rigida (southern Korea) plantations were selected as the artificial plantations. Vegetation types were classified by analyzing LandSat images by applying a GIS program. CO2 emissions were the highest in Pohang, Gwangyang, and Yeosu, where the iron and the petrochemical industrial complexes are located. CO2 emissions per unit area were the highest in Seoul, followed by Pohang and Gwangyang. CO2 absorption was the highest in the Gangwon province, where the forest area ratio to the total area is the highest, and the lowest in the metropolitan areas such as Seoul, Incheon, Daegu, Daejeon, and Gwangju. The number of local governments in which the amount of absorption is more than the emission amount was highest in Gangwon-do, where 10 local governments showed a negative carbon budget. Eight, seven, five, five, three, and three local governments in Gyeongsangbuk-do, Jeollanam-do, Gyeongsangnam-do, Jeollabuk-do, Gyeonggi-do, and Chungcheongbuk-do, respectively, showed a negative carbon budget where the amount of carbon absorption was greater than the emission amount. The carbon budget showed a very close correlation with carbon emission, and the carbon emission showed a significant correlation with population size. Moreover, the amount of carbon absorption showed a negative correlation with population size, population density, and non-forest area, and a positive correlation with the total area of the forest, coniferous forest area, and broad-leaved forest area. Considering the reality that carbon emissions exceed their absorption, measures to secure absorption sources should be considered as important as measures to reduce carbon emissions to achieve carbon neutrality in the future. As a measure to secure absorption sources, it is proposed to improve the quality of existing absorption sources, secure new absorption sources such as riparian forests, and efficiently arrange absorption sources.
Clustering Analysis on Drivers of O3 Diurnal Pattern and Interactions with Nighttime NO3 and HONO
Authors: Wang Xue , Wang Shanshan , Zhang Sanbao , Gu Chuanqi , Tanvir Aimon , Zhang Ruifeng , Zhou Bin
Published: February 2022

The long-path differential optical absorption spectroscopy (LP-DOAS) technique was deployed in Shanghai to continuously monitor ozone (O3), formaldehyde (HCHO), nitrogen dioxide (NO2), nitrous acid (HONO), and nitrate radical (NO3) mixing ratios from September 2019 to August 2020. Through a clustering method, four typical clusters of the O3 diurnal pattern were identified: high during both the daytime and nighttime (cluster 1), high during the nighttime but low during the daytime (cluster 2), low during both the daytime and nighttime (cluster 3), and low during the nighttime but high during the daytime (cluster 4). The drivers of O3 variation for the four clusters were investigated for the day- and nighttime. Ambient NO caused the O3 gap after midnight between clusters 1 and 2 and clusters 3 and 4. During the daytime, vigorous O3 generation (clusters 1 and 4) was found to accompany higher temperature, lower humidity, lower wind speed, and higher radiation. Moreover, O3 concentration correlated with HCHO for all clusters except for the low O3 cluster 3, while O3 correlated with HCHO/NOx, but anti-correlated with NOx for all clusters. The lower boundary layer height before midnight hindered O3 diffusion and accordingly determined the final O3 accumulation over the daily cycle for clusters 1 and 4. The interactions between the O3 diel profile and other atmospheric reactive components established that higher HONO before sunrise significantly promoted daytime O3 generation, while higher daytime O3 led to a higher nighttime NO3 level. This paper summarizes the interplays between day- and nighttime oxidants and oxidation products, particularly the cause and effect for daytime O3 generation from the perspective of nighttime atmospheric components.
Monitoring and Analysis of Outdoor Carbon Dioxide Concentration by Autonomous Sensors
Authors: Soares Paulo Henrique , Monteiro Johny Paulo , de Freitas Hanniel Ferreira Sarmento , Ogiboski Luciano , Vieira Felipe Silva , Andrade Cid Marcos G.
Published: February 2022

Countless problems have been caused by the excessive emission of polluting gases, such as carbon dioxide (CO2), into the atmosphere. Therefore, more effective monitoring of CO2 is essential, especially in central or industrial regions. Thus, this work shows the development of a platform for monitoring the CO2 concentration, which is composed of autonomous and independent sensors that have their own energy source, storage capacity, and data replication for the central server. To validate the platform, CO2 measurements were taken at three strategic points in an outdoor environment in a Brazilian urban center. This platform proved to be an evolution over another system previously proposed by the group that was based on the use of a wireless network of sensors to monitor CO2. This new project managed to overcome limitations that compromised the efficiency of the first platform, which were mainly related to the interference in the communication signals between the network sensors due to the existence of physical barriers in the monitoring environment. With that, this new platform showed greater security in the maintenance of collected data and allowed for the expansion of the physical complexity of the environments that can be monitored.
Automated Cell Foreground–Background Segmentation with Phase-Contrast Microscopy Images: An Alternative to Machine Learning Segmentation Methods with Small-Scale Data
Authors: Ye Guochang , Kaya Mehmet
Published: February 2022

Cell segmentation is a critical step for image-based experimental analysis. Existing cell segmentation methods are neither entirely automated nor perform well under basic laboratory microscopy. This study proposes an efficient and automated cell segmentation method involving morphological operations to automatically achieve cell segmentation for phase-contrast microscopes. Manual/visual counting of cell segmentation serves as the control group (156 images as ground truth) to evaluate the proposed method’s performance. The proposed technology’s adaptive performance is assessed at varying conditions, including artificial blurriness, illumination, and image size. Compared to the Trainable Weka Segmentation method, the Empirical Gradient Threshold method, and the ilastik segmentation software, the proposed method achieved better segmentation accuracy (dice coefficient: 90.07, IoU: 82.16%, and 6.51% as the average relative error on measuring cell area). The proposed method also has good reliability, even under unfavored imaging conditions at which manual labeling or human intervention is inefficient. Additionally, similar degrees of segmentation accuracy were confirmed when the ground truth data and the generated data from the proposed method were applied individually to train modified U-Net models (16848 images). These results demonstrated good accuracy and high practicality of the proposed cell segmentation method with phase-contrast microscopy image data.
Large-Scale Distribution of the European Seahorses (Hippocampus Rafinesque, 1810): A Systematic Review
Authors: Pierri Cataldo , Lazic Tamara , Gristina Michele , Corriero Giuseppe , Sinopoli Mauro
Published: February 2022

Human pressures on marine ecosystems have caused extensive degradation of marine habitats and several local extinctions. Overexploitation and destructive fishing practices are responsible for biodiversity loss in many coastal ecosystems. The definition of conservation programs in marine fish requires comprehensive knowledge on large-scale geographical distribution, while considering distribution/abundance patterns in relation to key environmental variables. Due to their life-cycle traits, the two European seahorses (Hippocampus guttulatus and H. hippocampus), as with other congeneric species, are particularly sensitive to the effects of anthropogenic activities and habitat changes. However, information on the ecological distribution of these two species is scattered, patchy, and mainly focused on small-scale studies. In this paper, we followed an international standard protocol for systematic reviews (the PRISMA protocol) to provide a detailed assessment of the two species’ geographical distribution in relation to the environmental characteristics. According to the 134 analyzed studies, Hippocampus guttulatus is more common in confined areas, while H. hippocampus is found in marine shelf waters. With several interspecific differences, seagrasses were the most used holdfasts of both species. The EUNIS codes (European nature information system) referring to a specific and unique habitat were discussed as a potential tool for defining the ecological distribution of the two species. The obtained results and their future implementation could help plan conservation actions.
Feeding Habits and the Occurrence of Anthropogenic Debris in the Stomach Content of Marine Fish from Pattani Bay, Gulf of Thailand
Authors: Soe Kay Khine , Hajisamae Sukree , Sompongchaiyakul Penjai , Towatana Prawit , Pradit Siriporn
Published: February 2022

This study assessed the feeding habits and ingestion of anthropogenic debris in 34 marine fish species from the southern Gulf of Thailand. A total of 5478 fish samples of 12 families were categorised into seven groups: planktivore, Lucifer feeder, fish feeder, Acetes feeder, shrimp feeder, piscivore, and zoobenthivore fish. A total of 2477 anthropogenic debris items were extracted from 12 fish species by visual inspection. Their ingestion of anthropogenic debris was influenced by season (p < 0.0001), with the highest ingestion during the northeast monsoon season. Furthermore, planktivorous fish displayed more ingested anthropogenic debris than the other investigated species (p = 0.022). Blue-coloured anthropogenic debris was commonly detected in the stomachs of fish and significantly differed between species (p > 0.001). Water depth and season significantly influenced the availability of food types (AF) for fish (p < 0.001). These findings provide evidence of the ingestion of anthropogenic debris by fish inhabiting a natural bay and signal the future anthropogenic pollution of marine fish.
The Acute Immune Responses of the Common Carp Cyprinus carpio to PLGA Microparticles—The Interactions of a Teleost Fish with a Foreign Material
Authors: Montero Ruth , Chan Justin Tze Ho , Köllner Bernd , Kuchta Roman , Vysloužil Jakub , Podhorec Peter , Holzer Astrid Sibylle , Korytář Tomáš
Published: February 2022

Poly lactic-co-glycolic acid (PLGA) particles safely and effectively deliver pharmaceutical ingredients, with many applications approved for clinical use in humans. In fishes, PLGA particles are being considered as carriers of therapeutic drugs and vaccine antigens. However, existing studies focus mainly on vaccine antigens, the endpoint immune responses to these (e.g., improved antibody titres), without deeper understanding of whether fishes react to the carrier. To test whether or not PLGA are recognized by or interact at all with the immune system of a teleost fish, we prepared, characterized and injected PLGA microparticles intraperitoneally into common carp. The influx, phenotype of inflammatory leukocytes, and their capacity to produce reactive oxygen species and phagocytose PLGA microparticles were tested by flow cytometry, qPCR, and microscopy. PLGA microparticles were indeed recognized. However, they induced only transient recruitment of inflammatory leukocytes that was resolved 4 days later whereas only the smallest µm-sized particles were phagocytosed. The overall response resembled that described in mammals against foreign materials. Given the similarities between our findings and those described in mammals, PLGA particles can be adapted to play a dual role as both antigen and drug carriers in fishes, depending on the administered dose and their design.
Optimization of an Inclusion Body-Based Production of the Influenza Virus Neuraminidase in Escherichia coli
Authors: Lipničanová Sabina , Legerská Barbora , Chmelová Daniela , Ondrejovič Miroslav , Miertuš Stanislav
Published: February 2022

Neuraminidase (NA), as an important protein of influenza virus, represents a promising target for the development of new antiviral agents for the treatment and prevention of influenza A and B. Bacterial host strain Escherichia coli BL21 (DE3)pLysS containing the NA gene of the H1N1 influenza virus produced this overexpressed enzyme in the insoluble fraction of cells in the form of inclusion bodies. The aim of this work was to investigate the effect of independent variables (propagation time, isopropyl β-d-1-thiogalactopyranoside (IPTG) concentration and expression time) on NA accumulation in inclusion bodies and to optimize these conditions by response surface methodology (RSM). The maximum yield of NA (112.97 ± 2.82 U/g) was achieved under optimal conditions, namely, a propagation time of 7.72 h, IPTG concentration of 1.82 mM and gene expression time of 7.35 h. This study demonstrated that bacterially expressed NA was enzymatically active.
Levels of Coenzyme Q10 and Several COQ Proteins in Human Astrocytoma Tissues Are Inversely Correlated with Malignancy
Authors: Yen Hsiu-Chuan , Chen Bing-Shian , Yang Si-Ling , Wu Shin-Yu , Chang Chun-Wei , Wei Kuo-Chen , Hsu Jee-Ching , Hsu Yung-Hsing , Yen Tzung-Hai , Lin Chih-Lung
Published: February 2022

In a previous study, we reported the alterations of primary antioxidant enzymes and decreased citrate synthase (CS) activities in different grades of human astrocytoma tissues. Here, we further investigated coenzyme Q10 (CoQ10) levels and protein levels of polyprenyl diphosphate synthase subunit (PDSS2) and several COQ proteins required for CoQ10 biosynthesis in these tissues. We found that the level of endogenous CoQ10, but not of exogenous α-tocopherol, was higher in nontumor controls than in all grades of astrocytoma tissues. The levels of COQ3, COQ5, COQ6, COQ7, COQ8A, and COQ9, but not of COQ4, were lower in Grade IV astrocytoma tissues than in controls or low-grade (Grades I and II) astrocytomas, but PDSS2 levels were higher in astrocytoma tissues than in controls. Correlation analysis revealed that the levels of CoQ10 and COQ proteins were negatively correlated with malignancy degree and positively correlated with CS activity, whereas PDSS2 level was positively correlated with malignancy. Moreover, lower level of mitochondrial DNA-encoded cytochrome c oxidase subunit 2 was not only associated with a higher malignancy degree but also with lower level of all COQ proteins detected. The results revealed that mitochondrial abnormalities are associated with impaired CoQ10 maintenance in human astrocytoma progression.
Characterization of Systemic and Regional Hemodynamics and Vascular Dysfunction in Mice with Fecal Induced Peritonitis
Authors: Jahandideh Forough , Panahi Sareh , Noble Ronan M. N. , Gragasin Ferrante S. , Khadaroo Rachel G. , Macala Kimberly F. , Bourque Stephane L.
Published: February 2022

Sepsis is associated with circulatory dysfunction contributing to disturbed blood flow and organ injury. Decreased organ perfusion in sepsis is attributed, in part, to the loss of vasoregulatory mechanisms. Identifying which vascular beds are most susceptible to dysfunction is important for monitoring the recovery of organ function and guiding interventions. This study aimed to investigate the development of vascular dysfunction as sepsis progressed to septic shock. Anesthetized C57Bl/6 mice were instrumented with a fiberoptic pressure sensor in the carotid artery for blood pressure measurements. In subgroups of mice, regional blood flow measurements were taken by positioning a perivascular flow probe around either the left carotid, left renal, or superior mesenteric arteries. Hemodynamic parameters and their responsiveness to bolus doses of vasoactive drugs were recorded prior to and continuously after injection of fecal slurry (1.3 mg/g body weight) for 4 h. Fecal slurry-induced peritonitis reduced mean arterial pressure (62.7 ± 2.4 mmHg vs. 37.5 ± 3.2 mmHg in vehicle and septic mice, respectively), impaired cardiac function, and eventually reduced organ blood flow (71.9%, 66.8%, and 65.1% in the superior mesenteric, renal, and carotid arteries, respectively). The mesenteric vasculature exhibited dysregulation before the renal and carotid arteries, and this underlying dysfunction preceded the blood pressure decline and impaired organ blood flow.
Effect of Clostridium butyricum on Gastrointestinal Infections
Authors: Ariyoshi Tadashi , Hagihara Mao , Takahashi Motomichi , Mikamo Hiroshige
Published: February 2022

Clostridium butyricum is a human commensal bacterium with beneficial effects including butyrate production, spore formation, increasing levels of beneficial bacteria, and inhibition of pathogenic bacteria. Owing to its preventive and ameliorative effects on gastrointestinal infections, C. butyricum MIYAIRI 588 (CBM 588) has been used as a probiotic in clinical and veterinary medicine for decades. This review summarizes the effects of C. butyricum, including CBM 588, on bacterial gastrointestinal infections. Further, the characteristics of the causative bacteria, examples of clinical and veterinary use, and mechanisms exploited in basic research are presented. C. butyricum is widely effective against Clostoridioides difficile, the causative pathogen of nosocomial infections; Helicobacter pylori, the causative pathogen of gastric cancer; and antibiotic-resistant Escherichia coli. Accordingly, its mechanism is gradually being elucidated. As C. butyricum is effective against gastrointestinal infections caused by antibiotics-induced dysbiosis, it can inhibit the transmission of antibiotic-resistant genes and maintain homeostasis of the gut microbiome. Altogether, C. butyricum is expected to be one of the antimicrobial-resistance (AMR) countermeasures for the One-health approach.
Testicular Macrophages Produce Progesterone De Novo Promoted by cAMP and Inhibited by M1 Polarization Inducers
Authors: Yamauchi Sawako , Yamamoto Kousuke , Ogawa Kazushige
Published: February 2022

Tissue-resident macrophages (Mø) originating from fetal precursors are maintained via self-renewal under tissue-/organ-specific microenvironments. Herein, we developed a propagation method of testicular tissue-resident Mø in mixed primary culture with interstitial cells composed of Leydig cells from the mouse testis. We examined Mø/monocyte marker expression in propagated testicular Mø using flow cytometry; gene expression involved in testosterone production as well as spermatogenesis in testicular Mø and interstitial cells propagated by mixed culture via RT-PCR; and progesterone (P4) de novo production in propagated testicular Mø treated with cyclic adenosine monophosphate, isoproterenol, and M1 polarization inducers using ELISA. Mø marker expression patterns in the propagated Mø were identical to those in testicular interstitial Mø with a CD206-positive/major histocompatibility complex (MHC) II-negative M2 phenotype. We identified the genes involved in P4 production, transcription factors essential for steroidogenesis, and androgen receptors, and showed that P4 production de novo was upregulated by cyclic adenosine monophosphate and β2-adrenergic stimulation and was downregulated by M1 polarization stimulation in Mø. We also demonstrated the formation of gap junctions between Leydig cells and interstitial Mø. This is the first study to demonstrate de novo P4 production in tissue-resident Mø. Based on previous studies revealing inhibition of testosterone production by P4, we propose that local feedback machinery between Leydig cells and adjacent interstitial Mø regulates testosterone production. The results presented in this study can facilitate future studies on immune-endocrine interactions in gonads that are related to infertility and hormonal disorders.
The Inflammatory Pattern of Chronic Limb-Threatening Ischemia in Muscles: The TNF-α Hypothesis
Authors: Caicedo Diego , Alvarez Clara V. , Perez-Romero Sihara , Devesa Jesús
Published: February 2022

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analysis was performed by using univariate (Spearman, t-Student, and X2) and multivariate (multiple logistic regression) tests. Results: A total of 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age: 71.4 ± 12.4 years (79.4% male); TNF-α: 10.7 ± 4.9 pg/mL; hsCRP:1.6 ± 2.2 mg/dL; and neutrophil-to-lymphocyte ratio (NLR): 3.5 ± 2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hsCRP (≥0.5) was found in 60.5%. Diabetic patients with a high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p = 0.0346). Plasma TNF-α had a negative correlation with NOS3 (eNOS) expression (−0.5, p = 0.015) and plasma hsCRP with VEGFA (−0.63, p = 0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p = 0.037), especially in DM. Cumulative mortality at 12 months was related to NLR ≥ 3 (p = 0.019) and TNF-α ≥ 8.1 (p = 0.048). The best cutoff point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hsCRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suitable markers of mortality in CLTI. These results are novel because they connect muscle gene expression and plasma information in patients with advanced PAD, deepening the search for new and accurate targets for this condition.
Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymeric Micelles for Improved Gene Delivery of VGF to the Brain through Intranasal Route
Authors: Lamptey Richard Nii Lante , Gothwal Avinash , Trivedi Riddhi , Arora Sanjay , Singh Jagdish
Published: February 2022

Multifunctional fatty acid grafted polymeric micelles are an effective and promising approach for drug and gene delivery to the brain. An alternative approach to bypass the blood–brain barrier is administration through intranasal route. Multifunctional fatty acid grafted polymeric micelles were prepared and characterized for pVGF delivery to the brain. In vitro pVGF expression was analyzed in bEnd.3 cells, primary astrocytes, and neurons. Comparative in-vivo pVGF expression was analyzed to evaluate the effective route of administration between intranasal and intravenous. Biocompatible, multifunctional polymeric micelles were prepared, having an average size of 200 nm, and cationic zeta potential. Modified polymers were found to be hemo- and cyto-compatible. When transfected with the different modified chitosan formulations, significantly (p < 0.05) higher VGF expression was observed in primary astrocytes and neurons using the mannose, Tat peptide, and oleic acid grafted chitosan polymer. Compared to intravenous administration, intranasal administration of pVGF in polyplex formulation led to significantly (p < 0.05) higher pVGF expression. Developed multifunctional polymeric micelles were an effective pVGF delivery platform to the brain. Mannose and Tat ligand tagging improved the pVGF delivery to the brain.
FCGR2A-HH Gene Variants Encoding the Fc Gamma Receptor for the C-Reactive Protein Are Associated with Enhanced Monocyte CD32 Expression and Cardiovascular Events’ Recurrence after Primary Acute Coronary Syndrome
Authors: Paul Pascale , Picard Christophe , Lyonnet Luc , Resseguier Noémie , Hubert Lucas , Arnaud Laurent , Di Cristofaro Julie , Laine Marc , Paganelli Franck , Dignat-George Françoise , Frère Corinne , Sabatier Florence , Guieu Regis , Bonello Laurent
Published: February 2022

Fcγ receptors (FcγRs) interact with the C-reactive protein (CRP) and mediate activation of inflammation-related pathogenic mechanisms affecting cardiovascular health. Our study evaluated whether FcγRIIA and FcγRIIIA profiles are associated with the recurrence of adverse cardiovascular events during the first year after a primary acute coronary syndrome (ACS). The primary endpoint was the recurrence of cardiovascular events (RCE), identified as a composite outcome comprising acute heart failure (AHF) and major adverse cardiovascular events (MACE). We obtained blood samples of 145 ACS patients to measure hsCRP circulating levels, to identify FcγRIIA-131RH rs1801274 and FcγRIIIA-158FV rs396991 polymorphisms, to analyze circulating monocytes and NK cell subsets expressing CD16 and CD32, and to detect serum-mediated FCGR2A-HH activation by luciferase reporter assays. The hsCRP, CD32-expression, and Fc-R mediated activation levels were similar in all patients regardless of their MACE risk. In contrast, the hsCRP levels and the proportion of CD14+ circulating monocytes expressing the CD32 receptor for CRP were significantly higher in the patients who developed AHF. The FCGR2A rs1801274 HH genotype was significantly more common in patients who developed RCE and MACE than in RCE-free patients and associated with an enhanced percentage of circulating CD32+CD14+ monocytes. The FCGR2A-HH genotype was identified as an independent predictor of subsequent RCE (OR, 2.7; p = 0.048; CI, 1.01–7.44) by multivariate analysis. These findings bring preliminary evidence that host FCGR2A genetic variants can influence monocyte CD32 receptor expression and may contribute to the fine-tuning of CD32-driven chronic activating signals that affect the risk of developing RCEs following primary ACS events.
Visual Neglect after PICA Stroke—A Case Study
Authors: Geiser Nora , Kaufmann Brigitte Charlotte , Rühe Henrik , Maaijwee Noortje , Nef Tobias , Cazzoli Dario , Nyffeler Thomas
Published: February 2022

After cerebellar stroke, cognition can be impaired, as described within the framework of the so-called Cerebellar Cognitive Affective Syndrome (CCAS). However, it remains unclear whether visual neglect can also be part of CCAS. We describe the case of a patient with a subacute cerebellar stroke after thrombosis of the left posterior inferior cerebellar artery (PICA), who showed a left-sided visual neglect, indicating that the cerebellum also has a modulatory function on visual attention. The neglect, however, was mild and only detectable when using the sensitive neuro-psychological Five-Point Test as well as video-oculography assessment, yet remained unnoticed when evaluated with common neglect-specific paper-pencil tests. Three weeks later, follow-up assessments revealed an amelioration of neglect symptoms. Therefore, these findings suggest that visual neglect may be a part of CCAS, but that the choice of neglect assessments and the time delay since stroke onset may be crucial. Although the exact underlying pathophysiological mechanisms remain unclear, we propose cerebellar–cerebral diaschisis as a possible explanation of why neglect can occur on the ipsilateral side. Further research applying sensitive assessment tools at different post-stroke stages is needed to investigate the incidence, lesion correlates, and pathophysiology of neglect after cerebellar lesions.
Development of an Ecologically Valid Assessment for Social Cognition Based on Real Interaction: Preliminary Results
Authors: Benito-Ruiz Guillermo , Luzón-Collado Cristina , Arrillaga-González Javier , Lahera Guillermo
Published: February 2022

Many social cognitive assessment measures that are appropriate for clinical use are currently available, but there is a general concern about their ecological validity. This study aimed to develop an applicable real interaction-based test to assess social cognition. A sample of 50 subjects (mean age 22 ± 5.8, 56% women) took the Social Interaction Test as well as two instruments for assessing social cognition: (1) the Movie for Assessment of Social Cognition (MASC) and (2) branch 4 from the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). The test showed no incidence on its application. The reliability of the 18-item final version of the test was a medium-high level (Cronbach’s alpha = 0.701). To assess the internal structure of the test, a multidimensional scaling procedure was used. The common space of coordinates for the two-dimensional solution showed a normalized raw stress of 0.076 and Tucker’s congruence coefficient of 0.965. The social interaction test showed stronger association with MASC (more realistic, video-based format) than with MSCEIT (less realistic, paper-based format). The Social Interaction Test is applicable and feasible to use it to assess social cognition in the general population.
Insights into Metal Sheet Novelty Detection via Simulated Electromagnetic Ultrasonic Surface Wave
Authors: Zhou Yunlai , He Longlong , Yang Fei , Xu Jingmang
Published: February 2022

Metal sheets have good performance and have been widely used. Different kinds of defects can be generated during the preparation and service of metal plates, which will cause the structural performance of the metal plates to decline, thus requiring structural health monitoring (SHM). This study proposes an electromagnetic ultrasonic (EMUS) surface wave detection technique for metal sheet defects via simulation. The numerical results show that after the excitation parameters of the EMUS transducer are optimized through orthogonal experimental design, the amplitude of the EMUS signal generated is increased by about 80%. The power spectrum density (PSD) of the EMUS response signal is used to detect defects. Compared with the peak-to-peak detection, the accuracy is higher, and the reliability is better. The accuracy of the proposed “central zero-point” method for measuring the time delay of the EMUS signal wave packet is higher than that of the “peak-to-peak amplitude” method and the “vibration starting point” method and is close to the accuracy of the “cross-correlation” method.
Ontology-Based Approach Supporting Multi-Objective Holistic Decision Making for Energy Pile System
Authors: Meng Kun , Cui Chunyi , Li Haijiang , Liu Hailong
Published: February 2022

The traditional way of designing energy pile system is mostly single domain/objective oriented, which lacks of means to coherently consider different while relevant factors across domains. The cost for life cycle design, construction and maintenance, return of investment, CO2 emission related sustainable requirements, and so on also need to be considered, in a systematic manner, along with the main functional design objective for loading capacity and robustness. This paper presents a novel multi-objective holistic approach for energy pile system design using ontology based multi-domain knowledge orchestration, which can holistically provide the designers with across domain factors regarding financial, safety, and environmental impact, for smart and holistic consideration during the early design stage. A prototypical ontology-based decision tool has been developed, aiming at the holistic optimization for energy pile system by combining ontology and Semantic Web Rule Language rules. A case study was performed to illustrate the details on how to apply knowledge query to provide a series of design alternatives autonomously by taking different design parameters into account. The method has demonstrated its practicability and scientific feasibility, it also shows the potential to be adopted and extended for other domains when dealing with multi-objective holistic design making.
The Mechanism of Influencing Green Technology Innovation Behavior: Evidence from Chinese Construction Enterprises
Authors: Li Xingwei , Huang Yicheng , Li Jingru , Liu Xiang , He Jinrong , Dai Jiachi
Published: February 2022

The Green Technology Innovation Behavior (GTIB) of construction enterprises is crucial for promoting green development in the construction industry. In order to clarify the mechanism of action affecting the GTIB of construction enterprises, this paper considers the context of green development in the construction industry based on the vector autoregressive model and constructs a theoretical model of GTIB in construction enterprises. Time series data collected by the Chinese government (2000–2018) were used to analyze the mechanism of action of the factors influencing the GTIB of construction enterprises by EViews 10.0. The results of the paper showed the following: (1) direct government investment has the greatest impact on the GTIB of construction enterprises and has made a positive contribution; (2) the added value of Gross Domestic Product (GDP) of the construction industry has a relatively small impact on the GTIB of construction enterprises; (3) the role of environmental regulation on the GTIB of construction enterprises is non-linear. This paper further broadens the research to the factors influencing the GTIB of construction enterprises. Meanwhile, this paper provides a reference basis for local governments to formulate policies related to the GTIB of construction enterprises.
Association between Prior Malignancy Exclusion Criteria and Age Disparities in Cancer Clinical Trials
Authors: Patel Roshal R. , Parisi Rose , Verma Vivek , Kouzy Ramez , Abi Jaoude Joseph , Lin Timothy A. , Fuller Clifton David , VanderWalde Noam A. , Jagsi Reshma , Smith Benjamin D. , Guadagnolo Beverly Ashleigh , Thomas Charles R. , Ludmir Ethan B.
Published: February 2022

Prior malignancy exclusion criteria (PMEC) are often utilized in cancer clinical trials; however, the incidence of PMEC and the association of PMEC with trial participant age disparities remain poorly understood. This study aimed to identify age disparities in oncologic randomized clinical trials as a result of PMEC. Using a comprehensive collection of modern phase III cancer clinical trials obtained via ClinicalTrials.gov, we assessed the incidence and covariates associated with trials excluding patients with prior cancers within 5+ years from registration (PMEC-5). Using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we further sought to determine the correlation between PMEC-5 and age disparities. PMEC-5 were used in 41% of all trials, with higher PMEC-5 utilization among industry-supported trials as well as trials evaluating a targeted therapy. Comparing trial patient median ages with population-matched median ages by disease site and time-period, we assessed the association between PMEC-5 and age disparities among trial participants. PMEC-5 were independently associated with heightened age disparities, which further worsened with longer exclusionary timeframes. Together, PMEC likely contribute to age disparities, suggesting that eligibility criteria modernization through narrower PMEC timeframes may work toward reducing such disparities in cancer clinical trial enrollment.
Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors
Authors: Ishihara Seiichiro , Haga Hisashi
Published: February 2022

Matrix stiffness is critical for the progression of various types of cancers. In solid cancers such as mammary and pancreatic cancers, tumors often contain abnormally stiff tissues, mainly caused by stiff extracellular matrices due to accumulation, contraction, and crosslinking. Stiff extracellular matrices trigger mechanotransduction, the conversion of mechanical cues such as stiffness of the matrix to biochemical signaling in the cells, and as a result determine the cellular phenotypes of cancer and stromal cells in tumors. Transcription factors are key molecules for these processes, as they respond to matrix stiffness and are crucial for cellular behaviors. The Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) is one of the most studied transcription factors that is regulated by matrix stiffness. The YAP/TAZ are activated by a stiff matrix and promotes malignant phenotypes in cancer and stromal cells, including cancer-associated fibroblasts. In addition, other transcription factors such as β-catenin and nuclear factor kappa B (NF-κB) also play key roles in mechanotransduction in cancer tissues. In this review, the mechanisms of stiffening cancer tissues are introduced, and the transcription factors regulated by matrix stiffness in cancer and stromal cells and their roles in cancer progression are shown.