bluuebunny/crossref_metadata_2025 huggingface dataset:
Environmental Cost in Indonesia Spillover Effect Between Consumption and Production
Authors: Pirmana Viktor , Alisjahbana Armida Salsiah , Yusuf Arief Anshory , Hoekstra Rutger , Tukker Arnold
Published: September 2021

Reducing environmental costs is a significant concern for Indonesia's future. This paper explores Indonesia's environmental costs from emissions and forest resources and identifies the priority sectors in terms of economic and environmental performance. We use environmentally extended input–output analysis for calculating the environmental costs and further extension with linkages analysis to identify the priority sectors. The study finds that the total environmental costs of emissions due to final demand is around 7% of the GDP. This environmental cost is significantly due to domestic products with household consumption being the largest contributor. The top 10 sectors in the Indonesian economy are responsible for about 70% of the total environmental costs of emissions. Based on pollutant source, SOx, NOx, CO2, and CH4 contribute more than half of emissions' ecological costs. We also find that forest resources' environmental cost is only 7.5% of the total environmental cost. Last, this study finds that key sectors of economic and sustainability points of view are textile manufacturing; publishing, printing, and reproduction of recorded media; chemicals n.e.c.; manufacture of other non-metallic mineral products; construction; and other land transport. Finally, this paper discusses the policy options for Indonesia to promote sustainable consumption and production in terms of reducing environmental costs while managing economic development.
Effect of Litter-Derived Dissolved Organic Carbon Addition on Forest Soil Microbial Community Composition
Authors: Wang Min , Tian Qiuxiang , Liao Chang , Zhao Rudong , Liu Feng
Published: September 2021

The input of dissolved organic carbon (DOC) into soil affects soil organic carbon mineralization and microbial community composition by changing carbon availability. However, up to now, there is little knowledge about the microbial groups that utilize the added DOC and how the incorporation process may vary over time. In this study, we added 13C-labeled litter-derived DOC (treatment) or pure water (control) to a forest soil from different layers to investigate the effects of DOC addition on soil microbial biomass and community composition in a 180-d laboratory incubation experiment. Soil microbial phospholipid fatty acid (PLFA) were measured to assess changes in the microbial community composition. The 13C incorporation into microbial biomass and PLFAs was analyzed to trace the microbial utilization of litter-derived DOC. Our results indicated that DOC addition increased the biomass of gram-negative bacteria, gram-positive bacteria, fungi, and actinomycetes, but the microbial community composition manifested a similar trend for both treatment and control soils at the end of incubation. Proportions of added DOC in different depths of soil microbial PLFAs had no significant difference. Moreover, 17:0 cy and 15:0 PLFAs which are described as the bacterial biomarkers had a greater amount of 13C incorporation than other PLFAs for the topsoil, which indicated that 13C-labeled litter-derived DOC was more easily assimilated by some specific bacterial community. Soil microbial biomass and the incorporation of 13C into PLFA reached its maximum around 30 days after DOC addition and then rapidly reduced to the level comparable to control. Overall, this study demonstrated that the incorporation of 13C-labeled litter-derived DOC into PLFA in different depth soil had no significant difference, and the incorporation of 13C by bacteria was higher than other microbial groups.
The Influence of COVID-19 Lockdown on Physical Activity, Sedentary Behavior and Social Support Specific to Physical Activity Among Belgian Adults
Authors: Van Luchene Pierre , Detemmerman Fanny , Delens Cécile
Published: September 2021

In Belgium, lockdown measures were taken to counter the spread of COVID-19. This major life-change event may disrupt a person's daily routine and influence health behaviors. Although measures were restrictive, citizens were encouraged to engage in physical activity (PA) behavior in order to maintain well-being. Social support specific to PA (SSPA) had been highlighted as an important psychosocial factor in initiating and/or maintaining active behavior. The main aims of this study were to explore the influence of COVID-19 lockdown on PA and sedentary behavior, and on SSPA from family and from friends; and investigate the potential differences in terms of professional status. An online survey was distributed during the 1st weeks of the lockdown. A total of 272 Belgian adults responded to the survey. The findings show no significant difference between prior to and during lockdown with regard to the amount of PA. The results show a significant increase in sedentary behavior among the entire sample, workers and retirees. The findings also suggest that the support of other individuals is particularly useful for certain population groups such as retirees. Given the importance of the levels of PA and sedentariness as health behaviors preceding a major life-change event such as a lockdown, there is a need to promote these health behaviors during normal life in order for the population to remain active throughout their lifespan.
Comparison of Monopolar Electrosurgical Conization and the Loop Electrosurgical Excision Procedure in the Management of High-Grade Squamous Intraepithelial Lesion
Authors: Ding Jun , Xu Haiou , Xia Lihua , Cao Shanshan , Wu Qing
Published: September 2021

Objectives: To compare the performance and outcomes of monopolar electrosurgical conization (MESC) or the loop electrosurgical excision procedure (LEEP) in the treatment of high-grade squamous intraepithelial lesion (HSIL).

Methods: This retrospective study included 554 patients diagnosed with HSIL through biopsy. The study used either LEEP or MESC for cervical conization. Additionally, the medical records of these patients, including the basic information, status of the excision margin, cone depth, cone width, fragmentation, complication, and the results of a 6-month follow-up after conization, were reviewed.

Results: Compared to MESC, LEEP had a significantly higher rate of positive endocervical margin (3.77 vs. 8.65%; p = 0.018), burn injury of the margin (4.90 vs. 10.38%; p = 0.016) and a lower rate of adequate cone depth (83.40 vs. 89.62%; p = 0.034). In addition, LEEP was significantly more likely to cause fragmentation (p = 0.000). There was, however, no significant difference in the rate of abnormal cervical cytology and positive high-risk HPV (hrHPV) between these two groups, 6 months after cervical conization.

Conclusion: Both LEEP and MESC appeared to be equally effective in the clinical treatment of HSIL. Nonetheless, MESC resulted in a better pathological outcome with regard to the status of the margin, tissue fragmentation, and cone depth.
Avian Influenza Risk Environment: Live Bird Commodity Chains in Chattogram, Bangladesh
Authors: Høg Erling , Fournié Guillaume , Hoque Md. Ahasanul , Mahmud Rashed , Pfeiffer Dirk U. , Barnett Tony
Published: September 2021

In this paper, we identify behaviours in live bird commodity chains in Chattogram, Bangladesh, which may influence the risk of pathogen emergence and transmission: the nature of poultry trade, value appropriation and selling sick or infected birds. Examining the reasons why actors engage in these behaviours, we emphasise the politics of constraints within a context of real-world decisions, governed by existential and pragmatic agency. Focusing on contact zones and entanglement, analysing patron-client relationships and precarious circumstances, we argue that agency and structure specific to the Bangladeshi context produce a risk environment. Structural constraints may reinforce risky occupational practises and limit individual agency. Structural constraints need to be addressed in order to tackle animal and zoonotic disease risk along live animal commodity chains.
Zeolit és magnéziummal ioncserélt zeolit in vitro összehasonlító vizsgálata
Authors: Szilágyi Ildikó , Czibulya Zsuzsanna , Csík Attila , Braun Mihály , Hegedűs Csaba
Published: September 2021

A zeolit és magnéziummal ioncserélt zeolitrendszer vizsgálata humán őssejteken és a különböző koncentrációk hatásárabekövetkező eltérő életképesség és ALP aktivitás értékek információt nyújtanak a csontosodást, csont „turnovert”befolyásoló tényezőkről. Jelen munkánk célja a zeolit és a magnéziummal ioncserélt zeolit koncentrációk (0,605 mM,0,325 mM, 0,15 mM Mg-zeolit és zeolit) hatásának vizsgálata volt in vitro kísérleti rendszerben, tenyésztő médiumbanbölcsességfog eredetű (DPSC) sejteken, különböző mintavételi időpontokban (1., 4., 7. és 14. nap).Az életképesség és alkalikus foszfatáz aktivitás méréseink alapján mindkét vizsgált komponens, így a zeolit és a magnéziummalioncserélt zeolit több területen is ígéretes összetevője lehet a jövő mesterséges szövettenyésztést alkalmazóorvosi beavatkozásainak. Kísérleteink alapján a Mg-zeolit bizonyult hatékonyabbnak a hagyományosan használt zeolittal szemben.
An Effective Form Analysis Approach for Designing and Optimizing a Cable-Net Structure of a Giant Active Reflector
Authors: Chen Deshen , Zhang Yan , Qian Hongliang , Zhang Kai , Wang Huajie
Published: September 2021

The cable-net structure of a giant active reflector is a structure with large deformations. The effective form analysis approach can help the active reflector to achieve high surface accuracy. In this paper, a new nonlinear numerical form analysis approach is proposed for the active reflector cable-net structure. The basic principle and calculation flow of the static equilibrium are provided and the calculation program is compiled. This approach does not only achieve a uniform cable tension design based on the idea of “equal-tension replacement” but also simulates the change process from the reference state to the target working state. The obtained final form conforms to the target configuration and achieves the force balance. This, in turn, proves the adaptability of the proposed approach for the design and optimization of active reflector cable-net structure. By employing the form analysis, the length change of actuators and force distribution of all cables can also be simultaneously obtained. This provides an important basis for the actual operation and control optimization of similar active reflectors.
Tuning Potassium and Magnesium Fertilization of Potato in the South of West Siberia
Authors: Yakimenko Vladimir , Naumova Natalia
Published: September 2021

Imbalance of nutrients limits crop yields. Although K fertilization receives sufficient attention in research and practice, Mg supply is rather neglected. The effect of Mg fertilization (0, 5 and 10 g Mg/m2), combined with two K fertilization rates (10 and 15 g K/m2), on potato production and soil exchangeable K and Mg was studied in a three-season microplot field experiment in the Novosibirsk region, Russia. Tuber yield did not respond to the increased K fertilization, but increased at 5 and decreased at 10 g Mg/m2. Total Mg concentration in tubers increased at 15 g K/m2, whereas N, P and K were not affected by fertilization. The tuber yield was maximal (3.6 kg/m2) at 10 g K/m2 and 5 g Mg/m2. Soil exchangeable Mg increased by the year, resulting in preferential development of the aboveground phytomass due to apparently increased Mg availability and K/Mg imbalance. Potato production depended on the year, strongly implicating weather conditions. Therefore, the weather and the chemical nature of K and Mg fertilizers (as pertinent to their release mode from fertilizer in soil), are important for balancing their proportions and amounts while assessing interactions among nutrients in potato production and adjusting regional fertilization strategies.
Artificial-Intelligence-Based Time-Series Intervention Models to Assess the Impact of the COVID-19 Pandemic on Tomato Supply and Prices in Hyderabad, India
Authors: Chitikela Gayathri , Admala Meena , Ramalingareddy Vijaya Kumari , Bandumula Nirmala , Ondrasek Gabrijel , Sundaram Raman Meenakshi , Rathod Santosha
Published: September 2021

This study’s objective was to assess the impact of the COVID-19 pandemic on tomato supply and prices in Gudimalkapur market in Hyderabad, India. The lockdown imposed by the government of India from 25 March 2020 to 30 June 2020 particularly affected the supply chain of perishable agricultural products, including tomatoes as one of the major vegetable crops in the study area. The classical time series models such as autoregressive integrated moving average (ARIMA) intervention models and artificial intelligence (AI)-based time-series models namely support vector regression (SVR) intervention and artificial neural network (ANN) intervention models were used to predict tomato supplies and prices in the studied market. The modelling results show that the pandemic had a negative impact on supply and a positive impact on tomato prices. Moreover, the ANN intervention model outperformed the other models in both the training and test data sets. The superior performance of the ANN intervention model could be due to its ability to account for the nonlinear and complex nature of the data with exogenous intervention variable.
The Level of Selected Bacterial Phyla on the Skin Surface of Small Ruminants According to the Breed and Species
Authors: Cholewińska Paulina , Nazar Paulina , Junkuszew Andrzej , Smoliński Jakub , Czyż Katarzyna , Wyrostek Anna
Published: September 2021

For decades, skin has been assigned the main role of an insulator of the inside of the body from the external environment, but it also plays a role in maintaining homeostasis. In this study, the level of selected bacterial phyla (Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) was assessed in three sheep breeds (Świniarka sheep, Uhruska sheep and BCP line (synthetic sheep breed; n = 6) and in two breeds of goats (Boer, Saenian; n = 6) living in the same environment and fed on the same feed, where the aim was to identify differences in terms of race, species and individual differences. Significant differences were found in Firmicute, Actinobacteria and Proteobacteria phyla (p ≤ 0.05). Statistically significant and positive correlations were demonstrated between Actinobacteria and Proteobacteria, Proteobacteria and Bacteroidetes or Firmicutes and Bacteroidetes. The obtained results suggest that the species and racial differences in the level of the studied bacterial phyla may also result from the physicochemical differences of the skin surface, as they could exacerbate the variations in humidity, temperature, composition of antimicrobial peptides (AMP) and lipid content. In addition, individual differences were observed, which indicate a similar effect of an individual on the microbiological composition of its organism.
Impact of Campylobacter spp. on the Integrity of the Porcine Gut
Authors: Rath Alexandra , Rautenschlein Silke , Rzeznitzeck Janina , Breves Gerhard , Hewicker-Trautwein Marion , Waldmann Karl-Heinz , von Altrock Alexandra
Published: September 2021

Campylobacter (C.) is the most common food-borne zoonosis in humans, which mainly manifests with watery to bloody diarrhoea. While C. jejuni is responsible for most cases of infection, C. coli is less frequently encountered. The object of the study was to prove the clinical impact of mono- and co-colonisation of C. coli and C. jejuni on weaned piglets in an infection model and to investigate the impact on transepithelial transport processes in the jejunum and caecum. At an age of eight weeks, eight pigs were infected with C. coli (ST-5777), 10 pigs with C. jejuni (ST-122), eight pigs with both strains, and 11 piglets served as control. During the four-week observation period, no clinical signs were observed. During dissection, both strains could be isolated from the jejunum and the caecum, but no alteration of the tissue could be determined histopathologically. Mono-infection with C. jejuni showed an impact on transepithelial ion transport processes of the caecum. An increase in the short circuit current (Isc) was observed in the Ussing chamber resulting from carbachol- and forskolin-mediated Cl− secretion. Therefore, we speculate that caecal colonisation of C. jejuni might affect the transport mechanisms of the intestinal mucosa without detectable inflammatory reaction.
Special Issue on Wind Turbine Aerodynamics II
Authors: Shen Wen Zhong
Published: September 2021

To alleviate global warming and reduce air pollution, the world needs to rapidly shift towards renewable energy [...]
Analysis of Aerosol Optical Depth from Sun Photometer at Shouxian, China
Authors: Xun Lina , Lu Hui , Qian Congcong , Zhang Yong , Lyu Shanshan , Li Xin
Published: September 2021

We use two cloud screening methods—the clustering method and the multiplet method—to process the measurements of a sun photometer from March 2020 to April 2021 in Shouxian. The aerosol optical depth (AOD) and Angström parameters α and β are retrieved; variation characteristics and single scattering albedo are studied. The results show that: (1) The fitting coefficient of AOD retrieved by the two methods is 0.921, and the changing trend is consistent. The clustering method has fewer effective data points and days, reducing the overall average of AOD by 0.0542 (500 nm). (2) Diurnal variation of AOD can be divided into flat type, convex type, and concave type. Concave type and convex type occurred the most frequently, whereas flat type the least. (3) During observation, the overall average of AOD is 0.48, which is relatively high. Among them, AOD had a winter maximum (0.70), autumn and spring next (0.54 and 0.40), and a summer minimum (0.26). The variation trend of AOD and β is highly consistent, and the monthly mean of α is between 0.69 and 1.61, concerning mainly continental and urban aerosols. (4) Compared with others, the single scattering albedo in Shouxian is higher, reflecting strong scattering and weak aerosol absorption.
Characteristics of Potentially Toxic Elements, Risk Assessments, and Isotopic Compositions (Cu-Zn-Pb) in the PM10 Fraction of Road Dust in Busan, South Korea
Authors: Jeong Hyeryeong , Ra Kongtae
Published: September 2021

The pollution status of ten potentially toxic elements (PTEs), isotopic compositions (Cu, Zn, Pb), and the potential ecological risk posed by them were investigated in the PM10 fraction of road dust in Busan Metropolitan city, South Korea. Enrichment factors revealed extremely to strongly polluted levels of Sb, Cd, Zn, Pb, and Cu in the PM10 fraction of road dust, with Sb levels being the highest. Statistical analyses showed that the major cause for contamination with PTEs was non-exhaust traffic emissions such as tire and brake wear. Cu and Zn isotopic compositions of road dust were related to traffic-related emission sources such as brake and tires. Pb isotopic compositions were close to that of road paint, indicating that Pb was a different source from Cu and Zn in this study. No significant health risk was posed by the PTEs. Taking into account the total length of road in Busan, a high quantity of PTEs in road dust (PM10) can have serious deleterious effects on the atmospheric environment and ecosystems. The results of metal concentrations and isotopic compositions in road dust will help identify and manage atmospheric fine particle and coastal metal contamination derived from fine road dust.
PAQR6 Upregulation Is Associated with AR Signaling and Unfavorite Prognosis in Prostate Cancers
Authors: Yang Min , Li Jean Chong , Tao Chang , Wu Sa , Liu Bin , Shu Qiang , Li Benyi , Zhu Runzhi
Published: September 2021

Progesterone-induced rapid non-genomic signaling events have been confirmed through several membrane progesterone receptors (mPR). Some mPRs were reported to correlate with cancer progression and patient prognosis. In this study, we conducted a comprehensive analysis of all progesterone receptor (PGR)-related genes in prostate cancer tissues and examined the correlations of their expression levels with disease progression and patient survival outcomes. We utilized multiple RNA-seq and cDNA microarray datasets to analyze gene expression profiles and performed logistics aggression and Kaplan-Meier survival analysis after stratifying patients based on tumor stages and Gleason scores. We also used NCBI GEO datasets to examine gene expression patterns in individual cell types of the prostate gland and to determine the androgen-induced alteration of gene expression. Spearman coefficient analysis was conducted to access the correlation of target gene expression with treatment responses and disease progression status. The classic PGR was mainly expressed in stromal cells and progestin and adipoQ receptor (PAQR) genes were the predominant genes in prostate epithelial cells. Progesterone receptor membrane component-1 (PGRMC1) was significantly higher than PGRMC2 in all prostate cell types. In prostate cancer tissues, PAQR6 expression was significantly upregulated, while all other genes were largely downregulated compared to normal prostate tissues. Although both PAQR6 upregulation and PAQR5 downregulation were significantly correlated with tumor pathological stages, only PAQR6 upregulation was associated with Gleason score, free-prostate-specific antigen (fPSA)/total-PSA (tPSA) ratio, and patient overall survival outcomes. In addition, PAQR6 upregulation and PGR/PGRMC1 downregulation were significantly associated with a quick relapse. Conversely, in neuroendocrinal prostate cancer (NEPC) tissues, PAQR6 expression was significantly lower, but PAQR7/8 expression was higher than castration-resistant prostate cancer (CRPC) tissues. PAQR8 expression was positively correlated with androgen receptor (AR) score and AR-V7 expression levels but inversely correlated with NEPC score in metastatic CRPC tumors. This study provides detailed expression profiles of membrane progesterone receptor genes in primary cancer, CRPC, and NEPC tissues. PAQR6 upregulation in primary cancer tissues is a novel prognostic biomarker for disease progression, overall, and progression-free survival in prostate cancers. PAQR8 expression in CRPC tissues is a biomarker for AR activation.
Dietary Patterns Influence Target Gene Expression through Emerging Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease
Authors: Zaiou Mohamed , Amrani Rim , Rihn Bertrand , Hajri Tahar
Published: September 2021

Nonalcoholic fatty liver disease (NAFLD) refers to the pathologic buildup of extra fat in the form of triglycerides in liver cells without excessive alcohol intake. NAFLD became the most common cause of chronic liver disease that is tightly associated with key aspects of metabolic disorders, including insulin resistance, obesity, diabetes, and metabolic syndrome. It is generally accepted that multiple mechanisms and pathways are involved in the pathogenesis of NAFLD. Heredity, sedentary lifestyle, westernized high sugar saturated fat diet, metabolic derangements, and gut microbiota, all may interact on a on genetically susceptible individual to cause the disease initiation and progression. While there is an unquestionable role for gene-diet interaction in the etiopathogenesis of NAFLD, it is increasingly apparent that epigenetic processes can orchestrate many aspects of this interaction and provide additional mechanistic insight. Exciting research demonstrated that epigenetic alterations in chromatin can influence gene expression chiefly at the transcriptional level in response to unbalanced diet, and therefore predispose an individual to NAFLD. Thus, further discoveries into molecular epigenetic mechanisms underlying the link between nutrition and aberrant hepatic gene expression can yield new insights into the pathogenesis of NAFLD, and allow innovative epigenetic-based strategies for its early prevention and targeted therapies. Herein, we outline the current knowledge of the interactive role of a high-fat high-calories diet and gene expression through DNA methylation and histone modifications on the pathogenesis of NAFLD. We also provide perspectives on the advancement of the epigenomics in the field and possible shortcomings and limitations ahead.
Master Regulators of Epithelial-Mesenchymal Transition and WNT Signaling Pathways in Juvenile Nasopharyngeal Angiofibromas
Authors: Calanca Naiade , Binato Sara Martoreli Silveira , da Silva Sabrina Daniela , Brentani Helena Paula , Sennes Luiz Ubirajara , Pinto Clóvis Antonio Lopes , Domingues Maria Aparecida Custódio , Fonseca-Alves Carlos Eduardo , Rainho Claudia Aparecida , Rogatto Silvia Regina
Published: September 2021

Juvenile nasopharyngeal angiofibroma (JNA) is a rare fibrovascular benign tumor showing an invasive growth pattern and affecting mainly male adolescents. We investigated the role of epithelial–mesenchymal transition (EMT) and WNT signaling pathways in JNA. Gene expression profiles using nine JNA paired with four inferior nasal turbinate samples were interrogated using a customized 2.3K microarray platform containing genes mainly involved in EMT and WNT/PI3K pathways. The expression of selected genes (BCL2, CAV1, CD74, COL4A2, FZD7, ING1, LAMB1, and RAC2) and proteins (BCL2, CAV1, CD74, FZD7, RAF1, WNT5A, and WNT5B) was investigated by RT-qPCR (28 cases) and immunohistochemistry (40 cases), respectively. Among 104 differentially expressed genes, we found a significantly increased expression of COL4A2 and LAMB1 and a decreased expression of BCL2 and RAC2 by RT-qPCR. The immunohistochemistry analysis revealed a low expression of BCL2 and a negative to moderate expression of FZD7 in most samples, while increased CAV1 and RAF1 expression were detected. Moderate to strong CD74 protein expression was observed in endothelial and inflammatory cells. A significant number of JNAs (78%) presented reduced WNT5A and increased WNT5B expression. Overall, the transcript and protein profile indicated the involvement of EMT and WNT pathways in JNA. These candidates are promising druggable targets for treating JNA.
Yes-Associated Protein Is Required for ZO-1-Mediated Tight-Junction Integrity and Cell Migration in E-Cadherin-Restored AGS Gastric Cancer Cells
Authors: Kim Seon-Young , Park Song-Yi , Jang Hwan-Seok , Park Yong-Doo , Kee Sun-Ho
Published: September 2021

Yes-associated protein (YAP) regulates numerous cellular homeostasis processes and malignant transformation. We found that YAP influences ZO-1-mediated cell migration using E-cadherin-restored EC96 cells derived from gastric malignant AGS cells. Ectopic expression of E-cadherin enhanced straightforward migration of cells, in comparison to the meandering movement of parental AGS cells. In EC96 cells, YAP and ZO-1 expression increased but nuclear YAP levels and activity were reduced. Nuclear factor-κB (NF-κB) mediated the increase in ZO-1 expression, possibly stabilizing cytoplasmic YAP post-translationally. Downregulation of YAP expression using siYAP RNA or stable knock-down inhibited straightforward cell migration by fragmenting ZO-1 containing tight junctions (TJs) but not adherens junctions, implying involvement of YAP in ZO-1-mediated cell migration. The association of YAP with ZO-1 was mediated by angiomotin (AMOT) because downregulation of AMOT dissociated YAP from ZO-1 and reduced cell migration. E-cadherin restoration in malignant cancer cells induced NF-κB signaling to enhance ZO-1 expression and subsequently stabilize YAP. At high expression levels, YAP associates with ZO-1 via AMOT at TJs, influencing ZO-1-mediated cell migration and maintaining TJ integrity.
Stationed or Relocating: The Seesawing EMT/MET Determinants from Embryonic Development to Cancer Metastasis
Authors: Li Chien-Hsiu , Hsu Tai-I , Chang Yu-Chan , Chan Ming-Hsien , Lu Pei-Jung , Hsiao Michael
Published: September 2021

Epithelial and mesenchymal transition mechanisms continue to occur during the cell cycle and throughout human development from the embryo stage to death. In embryo development, epithelial-mesenchymal transition (EMT) can be divided into three essential steps. First, endoderm, mesoderm, and neural crest cells form, then the cells are subdivided, and finally, cardiac valve formation occurs. After the embryonic period, the human body will be subjected to ongoing mechanical stress or injury. The formation of a wound requires EMT to recruit fibroblasts to generate granulation tissues, repair the wound and re-create an intact skin barrier. However, once cells transform into a malignant tumor, the tumor cells acquire the characteristic of immortality. Local cell growth with no growth inhibition creates a solid tumor. If the tumor cannot obtain enough nutrition in situ, the tumor cells will undergo EMT and invade the basal membrane of nearby blood vessels. The tumor cells are transported through the bloodstream to secondary sites and then begin to form colonies and undergo reverse EMT, the so-called “mesenchymal-epithelial transition (MET).” This dynamic change involves cell morphology, environmental conditions, and external stimuli. Therefore, in this manuscript, the similarities and differences between EMT and MET will be dissected from embryonic development to the stage of cancer metastasis.
Timing of Psychopharmacological and Nutritional Interventions in the Inpatient Treatment of Anorexia Nervosa: An Observational Study
Authors: Pruccoli Jacopo , Pelusi Martina , Romagnoli Giorgia , Malaspina Elisabetta , Moscano Filomena , Parmeggiani Antonia
Published: September 2021

This study aims to investigate possible different outcomes in the inpatient treatment of anorexia nervosa (AN) related to different timings of psychopharmacological and nutritional interventions. A retrospective observational study was conducted, involving young patients hospitalized for AN, treated with naso-gastric tube feeding (NGT). Participants were divided into five groups according to early (0–7 days) or late (8+ days) introduction of atypical antipsychotics (AAP) and NGT: early AAP-early NGT (EE), early AAP-late NGT (EL), late AAP-early NGT (LE), late AAP-late NGT (LL) and a control group treated with NGT only (NGT). Concurrent clinical and treatment variables were analyzed. AN psychopathology was measured with the Eating Disorder Inventory-3 (EDI-3) EDRC score. Outcomes were assessed as admission-discharge body-mass index (BMI) improvement and length of hospital stay (LOS). Contributions of variables related to outcomes were assessed with multifactorial-analyses of variance (MANOVA). Seventy-nine patients were enrolled in the study. LOS was different among treatment groups (F (4, 75) = 5.993, p < 0.001), and EE patients showed lower LOS than LE (p < 0.001) and LL (p = 0.025) patients. BMI improvement was not significantly different among treatment groups but correlated negatively with age (F (1, 72) = 10.130, p = 0.002), and admission BMI (F (1, 72) = 14.681, p < 0.001). In conclusion, patients treated with early AAP and early NGT showed lower LOS than those treated with late AAP. Prognostic treatment variables should be investigated in wider samples.
Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case—Control Longitudinal Study in Human Premature Neonates
Authors: Metallinou Dimitra , Karampas Grigorios , Lazarou Eleftheria , Iacovidou Nikoletta , Pervanidou Panagiota , Lykeridou Katerina , Mastorakos George , Rizos Demetrios
Published: September 2021

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.
Tumor Microenvironment of Esophageal Cancer
Authors: Schiffmann Lars M. , Plum Patrick S. , Fuchs Hans F. , Babic Benjamin , Bruns Christiane J. , Schmidt Thomas
Published: September 2021

Esophageal cancer is among the top ten most deadly cancers worldwide with adenocarcinomas of the esophagus showing increasing incidences over the last years. The prognosis is determined by tumor stage at diagnosis and in locally advanced stages by response to (radio-)chemotherapy followed by radical surgery. Less than a third of patients with esophageal adenocarcinomas completely respond to neoadjuvant therapies which urgently asks for further strategies to improve these rates. Aiming at the tumor microenvironment with novel targeted therapies can be one strategy to achieve this goal. This review connects experimental, translational, and clinical findings on each component of the esophageal cancer tumor microenvironment involving tumor angiogenesis, tumor-infiltrating immune cells, such as macrophages, T-cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts. The review evaluates the current state of already approved concepts and depicts novel potentially targetable pathways related to esophageal cancer tumor microenvironment.
Serum Levels of the Cytokine TWEAK Are Associated with Metabolic Status in Patients with Prostate Cancer and Modulate Cancer Cell Lipid Metabolism In Vitro
Authors: Altuna-Coy Antonio , Ruiz-Plazas Xavier , Alves-Santiago Marta , Segarra-Tomás José , Chacón Matilde R.
Published: September 2021

Soluble TWEAK (sTWEAK) has been proposed as a prognostic biomarker of prostate cancer (PCa). We found that reduced serum levels of sTWEAK, together with higher levels of prostate-specific antigen and a higher HOMA-IR index, are independent predictors of PCa. We also showed that sTWEAK stimulus failed to alter the expression of glucose transporter genes (SLC2A4 and SLC2A1), but significantly reduced the expression of glucose metabolism-related genes (PFK, HK1 and PDK4) in PCa cells. The sTWEAK stimulation of PC-3 cells significantly increased the expression of the genes related to lipogenesis (ACACA and FASN), lipolysis (CPT1A and PNPLA2), lipid transport (FABP4 and CD36) and lipid regulation (SREBP-1 and PPARG) and increased the lipid uptake. Silencing the TWEAK receptor (Fn14) in PC-3 cells confirmed the observed lipid metabolic effects, as shown by the downregulation of ACACA, FASN, CPT1A, PNPLA2, FABP4, CD36, SREBP-1 and PPARG expression, which was paralleled by a reduction of FASN, CPT1A and FABP4 protein expression. Specific-signaling inhibitor assays show that ERK1/2 and AKT (ser473) phosphorylation can regulate lipid metabolism-related genes in PCa cells, pointing to the AKT locus as a possible target for PCa. Overall, our data support sTWEAK/Fn14 axis as a potential therapeutic target for PCa.
Adherence to Treatment Guidelines and Associated Survival in Older Patients with Prostate Cancer: A Prospective Multicentre Cohort Study
Authors: González Serrano Adolfo , Martínez Tapia Claudia , de la Taille Alexandre , Mongiat-Artus Pierre , Irani Jacques , Bex Axel , Paillaud Elena , Audureau Etienne , Barnay Thomas , Laurent Marie , Canouï-Poitrine Florence
Published: September 2021

The guidelines on prostate cancer treatment in older men recommend evaluating the patient’s underlying health status before treatment selection. We aimed to evaluate the frequency of a guideline–discordant treatment (GDT), identify factors associated with GDT, and assess the relationship between GDT and overall survival. We studied patients with prostate cancer aged 70 or older included in the ELCAPA cohort between 2010 and 2019. Multivariable logistic regression assessed GDT-associated factors. The restricted mean survival time (RMST) assessed the 24- and 36-month OS using stabilized inverse probability of treatment weighting of propensity scores. We included 356 patients (median age: 81 years), and 164 (46%) received a GDT (95% confidence interval (CI) = (41–51%)). Patients with metastases were less likely to receive a GDT (adjusted odds ratio (95% CI) = 0.34 (0.17–0.69); p = 0.003). After weighting, the RMST at 24 months was shorter in the GDT group (13.9 months, vs. 17 months for compliant treatments; difference (95% CI): −3.1 months (−5.3, −1.0); p = 0.004). RMST at 36 months was 18.5 months, vs. 21.8 months (difference: −3.3 months (−6.7, 0.0); p = 0.053). GDT is common in older patients with prostate cancer and especially those with non-metastatic disease. GDT was associated with worse survival, independently of health status and tumour characteristics.
Patient-Derived Explants of Colorectal Cancer: Histopathological and Molecular Analysis of Long-Term Cultures
Authors: da Mata Sara , Franchi-Mendes Teresa , Abreu Sofia , Filipe Bruno , Morgado Sónia , Mesquita Marta , Albuquerque Cristina , Fonseca Ricardo , Santo Vítor E. , Boghaert Erwin R. , Rosa Isadora , Brito Catarina
Published: September 2021

Colorectal cancer (CRC) is one of the most common cancers worldwide. Although short-term cultures of tumour sections and xenotransplants have been used to determine drug efficacy, the results frequently fail to confer clinically useful information. Biomarker discovery has changed the paradigm for advanced CRC, though the presence of a biomarker does not necessarily translate into therapeutic success. To improve clinical outcomes, translational models predictive of drug response are needed. We describe a simple method for the fast establishment of CRC patient-derived explant (CRC-PDE) cultures from different carcinogenesis pathways, employing agitation-based platforms. A total of 26 CRC-PDE were established and a subset was evaluated for viability (n = 23), morphology and genetic key alterations (n = 21). CRC-PDE retained partial tumor glandular architecture and microenvironment features were partially lost over 4 weeks of culture. Key proteins (p53 and Mismatch repair) and oncogenic driver mutations of the original tumours were sustained throughout the culture. Drug challenge (n = 5) revealed differential drug response from distinct CRC-PDE cases. These findings suggest an adequate representation of the original tumour and highlight the importance of detailed model characterisation. The preservation of key aspects of the CRC microenvironment and genetics supports CRC-PDE potential applicability in pre- and co-clinical settings, as long as temporal dynamics are considered.
Myxospermy Evolution in Brassicaceae: A Highly Complex and Diverse Trait with Arabidopsis as an Uncommon Model
Authors: Viudes Sébastien , Dunand Christophe , Burlat Vincent
Published: September 2021

The ability to extrude mucilage upon seed imbibition (myxospermy) occurs in several Angiosperm taxonomic groups, but its ancestral nature or evolutionary convergence origin remains misunderstood. We investigated seed mucilage evolution in the Brassicaceae family with comparison to the knowledge accumulated in Arabidopsis thaliana. The myxospermy occurrence was evaluated in 27 Brassicaceae species. Phenotyping included mucilage secretory cell morphology and topochemistry to highlight subtle myxospermy traits. In parallel, computational biology was driven on the one hundred genes constituting the so-called A. thaliana mucilage secretory cell toolbox to confront their sequence conservation to the observed phenotypes. Mucilage secretory cells show high morphology diversity; the three studied Arabidopsis species had a specific extrusion modality compared to the other studied Brassicaceae species. Orthologous genes from the A. thaliana mucilage secretory cell toolbox were mostly found in all studied species without correlation with the occurrence of myxospermy or even more sub-cellular traits. Seed mucilage may be an ancestral feature of the Brassicaceae family. It consists of highly diverse subtle traits, probably underlined by several genes not yet characterized in A. thaliana or by species-specific genes. Therefore, A. thaliana is probably not a sufficient reference for future myxospermy evo–devo studies.
Sustainable Effects of Human Dental Pulp Stem Cell Transplantation on Diabetic Polyneuropathy in Streptozotocine-Induced Type 1 Diabetes Model Mice
Authors: Hata Masaki , Omi Maiko , Kobayashi Yasuko , Nakamura Nobuhisa , Miyabe Megumi , Ito Mizuho , Ohno Tasuku , Imanishi Yuka , Himeno Tatsuhito , Kamiya Hideki , Nakamura Jiro , Miyachi Hitoshi , Ozawa Shogo , Miyazawa Ken , Mitani Akio , Nagao Toru , Goto Shigemi , Takebe Jun , Matsubara Tatsuaki , Naruse Keiko
Published: September 2021

Dental pulp stem cells (DPSCs) are suitable for use in regenerative medicine. Cryopreserved human DPSCs (hDPSCs) ameliorate diabetic polyneuropathy, and the effects of hDPSC transplantation are related to VEGF and NGF secretion. This study evaluated the long-term effects of a single transplantation of hDPSCs on diabetic polyneuropathy. hDPSCs were obtained from human third molars extracted for orthodontic treatment, which were then transplanted into the unilateral hindlimb skeletal muscles 8 weeks after streptozotocin injection in nude mice. The effects of hDPSC transplantation were analyzed at 16 weeks post-transplantation. DPSC transplantation significantly improved delayed nerve conduction velocity, decreased blood flow, and increased sensory perception thresholds. Furthermore, the hDPSC-conditioned medium promoted the neurite outgrowth of dorsal root ganglion neurons. In conclusion, the therapeutic effects of hDPSC transplantation with a single injection last for prolonged periods and may be beneficial in treating long-term diabetic polyneuropathy.
Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA- 34a-5p/T-Cell Intracytoplasmic Antigen-1 Pathway
Authors: Wang Hong , Ma Zhaowu , Shen Hongyuan , Wu Zijun , Liu Lian , Ren Boxu , Wong Peiyan , Sethi Gautam , Tang Fengru
Published: September 2021

Early life radiation exposure causes abnormal brain development, leading to adult depression. However, few studies have been conducted to explore pre- or post-natal irradiation-induced depression-related neuropathological changes. Relevant molecular mechanisms are also poorly understood. We induced adult depression by irradiation of mice at postnatal day 3 (P3) to reveal hippocampal neuropathological changes and investigate their molecular mechanism, focusing on MicroRNA (miR) and its target mRNA and protein. P3 mice were irradiated by γ-rays with 5Gy, and euthanized at 1, 7 and 120 days after irradiation. A behavioral test was conducted before the animals were euthanized at 120 days after irradiation. The animal brains were used for different studies including immunohistochemistry, CAP-miRSeq, Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and western blotting. The interaction of miR-34a-5p and its target T-cell intracytoplasmic antigen-1 (Tia1) was confirmed by luciferase reporter assay. Overexpression of Tia1 in a neural stem cell (NSC) model was used to further validate findings from the mouse model. Irradiation with 5 Gy at P3 induced depression in adult mice. Animal hippocampal pathological changes included hypoplasia of the infrapyramidal blade of the stratum granulosum, aberrant and impaired cell division, and neurogenesis in the dentate gyrus. At the molecular level, upregulation of miR-34a-5p and downregulation of Tia1 mRNA were observed in both animal and neural stem cell models. The luciferase reporter assay and gene transfection studies further confirmed a direct interaction between miR-43a-5p and Tia1. Our results indicate that the early life γ-radiation-activated miR-43a-5p/Tia1 pathway is involved in the pathogenesis of adult depression. This novel finding may provide a new therapeutic target by inhibiting the miR-43a-5p/Tia1 pathway to prevent radiation-induced pathogenesis of depression.
Ang II-Induced Hypertension Exacerbates the Pathogenesis of Tuberculosis
Authors: Cho Soo-Na , Choi Ji-Ae , Lee Junghwan , Son Sang-Hun , Lee Seong-Ahn , Nguyen Tam-Doan , Choi Song-Yi , Song Chang-Hwa
Published: September 2021

It has been known that infection plays a role in the development of hypertension. However, the role of hypertension in the progression of infectious diseases remain unknown. Many countries with high rates of hypertension show geographical overlaps with those showing high incidence rates of tuberculosis (TB). To explore the role of hypertension in tuberculosis, we compared the effects of hypertension during mycobacterial infection, we infected both hypertensive Angiotensin II (Ang II) and control mice with Mycobacterium tuberculosis (Mtb) strain H37Ra by intratracheal injection. Ang II-induced hypertension promotes cell death through both apoptosis and necrosis in Mtb H37Ra infected mouse lungs. Interestingly, we found that lipid accumulation in pulmonary tissues was significantly increased in the hypertension group compared to the normal controls. Ang II-induced hypertension increases the formation of foamy macrophages during Mtb infection and it leads to cell death. Moreover, the hypertension group showed more severe granuloma formation and fibrotic lesions in comparison with the control group. Finally, we observed that the total number of mycobacteria was increased in the lungs in the hypertension group compared to the normal controls. Taken together, these results suggest that hypertension increases intracellular survival of Mtb through formation of foamy macrophages, resulting in severe pathogenesis of TB.
Mitochondrial DNA Haplogroup Related to the Prevalence of Helicobacter pylori
Authors: Lee Yeonmi , Lee Sun-Mi , Choi Jiwan , Kang Seoon , So Seongjun , Kim Deokhoon , Ahn Ji-Yong , Jung Hwoon-Yong , Jeong Jin-Yong , Kang Eunju
Published: September 2021

Mitochondria are essential organelles that are not only responsible for energy production but are also involved in cell metabolism, calcium homeostasis, and apoptosis. Targeting mitochondria is a key strategy for bacteria to subvert host cells’ physiology and promote infection. Helicobacter (H.) pylori targets mitochondria directly. However, mitochondrial genome (mtDNA) polymorphism (haplogroup) is not yet considered an important factor for H. pylori infection. Here, we clarified the association of mitochondrial haplogroups with H. pylori prevalence and the ability to perform damage. Seven mtDNA haplogroups were identified among 28 H. pylori-positive subjects. Haplogroup B was present at a higher frequency and haplotype D at a lower one in the H. pylori population than in that of the H. pylori-negative one. The fibroblasts carrying high-frequency haplogroup displayed a higher apoptotic rate and diminished mitochondrial respiration following H. pylori infection. mtDNA mutations were accumulated more in the H. pylori-positive population than in that of the H. pylori-negative one in old age. Among the mutations, 57% were located in RNA genes or nonsynonymous protein-coding regions in the H. pylori-positive population, while 35% were in the H. pylori-negative one. We concluded that gastric disease caused by Helicobacter virulence could be associated with haplogroups and mtDNA mutations.