bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Occupational Health and Safety Management of Listed Companies in China’s Energy Industry Based on the Combined Weight-Cloud Model: From the Perspective of FPE Information Disclosure
Authors: Wang Yujie , Chen Hong , Long Ruyin , Jiang Shiyan , Liu Bei
Published: July 2022

Protecting labor safety and health and actively carrying out occupational safety and health management (OSHM) is a common need worldwide, and it is also one of the important efforts of Chinese enterprises under the background of promoting the implementation of the Healthy China strategy. Based on in-depth thinking on the current stage of OHSM, this study incorporated “management framework, management process, management effectiveness” (FPE) into an integrated framework and constructed an FPE evaluation system for enterprise OHSM. This study innovatively collected and refined FPE information from the perspective of information disclosure and used the combined weight cloud model to evaluate the occupational health and safety management level (OHSML) of 69 listed companies in China’s energy industry from 2009–2019. The results showed the following. (1) The OHSML of most listed companies in China’s energy industry was still at a low-end level. Among the companies that have issued relevant information reports, only 5.58% (S = 30) of the sample companies’ OHSML were at an acceptable level (Level IV) or declarable level (Level V). The OHSML comprehensive evaluation level of 92.56% (S = 498) of the sample companies was between the transitional level (Level III) and the improved level (Level II). (2) During 2009–2019, although the annual OHSML of listed companies in China’s energy industry showed an upward trend, the growth rate was low, and even the OHSML of some listed companies in the energy industry showed the characteristics of reduced fluctuations. (3) From the perspective of the PFT three-dimensional subsystem level of OHSM, the evaluation level of the governance framework subsystem was the highest, whereas the evaluation level of the management process subsystem and the management effectiveness subsystem were relatively low. Finally, according to the relevant results, some suggestions were proposed to improve the OHSML of listed companies in China’s energy industry. These findings can provide guidance for companies to improve their OSHM performance.
Psychological Stress Perceived by Pregnant Women in the Last Trimester of Pregnancy
Authors: Răchită Anca , Strete Gabriela Elena , Suciu Laura Mihaela , Ghiga Dana Valentina , Sălcudean Andreea , Mărginean Claudiu
Published: July 2022

Pregnancy is characterized by changes in neuroendocrine, cardiovascular, and immune function. For this reason, pregnancy itself is perceived as a psychological “stress test”. Research to date has focused on stress exposure. The aim of the study was to evaluate the influence of associated factors on the level of stress experienced by pregnant patients. We conducted a prospective study that included 215 pregnant women in the third trimester of pregnancy, hospitalized in the Obstetrics and Gynecology Clinic II in Târgu-Mureș, between December 2019 and December 2021, who were evaluated by the ABS II scale. All patients included in the study filled in a questionnaire that included 76 questions/items, in which all the data necessary for the study were recorded. The results obtained from the study showed that pregnant women in urban areas (53.49%) are more vulnerable than those in rural areas (46.51%), being influenced by social and professional stressors, social determinants playing a critical role in pregnancy and in the newborn. Patients who have had an imminent abortion in their current pregnancy have a significantly higher score of irrationality than those with normal pregnancy, which shows that their emotional state can negatively influence the phenomenon of irrationality. There is a statistically significant association between pregnancy type I (normal pregnancy or imminent pregnancy) and irrationality class (p = 0.0001; RR: 2.150, CI (95%): 1.154–4.007). In the case of women with desired pregnancies, the risk of developing irrationality class IV–V is 4.739 times higher, with the association being statistically significant (p < 0.0001; RR 4.739; CI (95%): 2.144–10.476). The analysis of the obtained results demonstrates the importance of contributing factors and identifies the possibility of stress disorders, occurring in the last trimester of pregnancy, disorders that can have direct effects on maternal and fetal health. We consider it extremely important to carry out evaluations throughout the pregnancy. At the same time, it is necessary to introduce a screening program to provide psychological counseling in the prenatal care of expectant mothers.
Risk Factors for Back Pain among Southern Brazilian School Children: A 6-Year Prospective Cohort Study
Authors: Rosa Bruna Nichele da , Noll Matias , Candotti Cláudia Tarragô , Loss Jefferson Fagundes
Published: July 2022

Risk factors associated with back pain vary in different countries. Given the lack of studies in Latin America, our study aimed to assess back pain and its associated factors for six years in Southern Brazilian school children. All children attending the fifth grade of Teutônia, Brazil, were invited to participate in the study. Only schoolchildren who did not report back pain were included in the first assessment. The schoolchildren completed the Back Pain and Body Posture Evaluation Instrument (BackPEI) during three assessments (2011, 2014, and 2017). BackPEI assesses the presence of back pain and possible associated risk factors (postural, behavioral, and sociodemographic). Generalized estimated equations (GEE) were used to perform a Poisson regression model with robust variance for longitudinal analysis. After six years of follow-up, 75 schoolchildren completed all the assessments. The risk factors associated with back pain were spending more than six hours daily watching television, lifting objects from the ground adopting an inadequate posture, using another backpack type different from those with two straps, and carrying a backpack in an asymmetric way. These results are important in guiding the planning of public policies to minimize this public health problem.
The Relationship between Intimate Partner Violence and Online Help-Seeking: A Moderated Mediation Model of Emotion Dysregulation and Perceived Anonymity
Authors: Xu Heng , Zeng Jun , Cao Zheng , Hao Huihui
Published: July 2022

During the COVID-19 pandemic, lockdowns and isolation have limited the availability of face-to-face support services for victims of intimate partner violence (IPV). Despite the growing need for online help in supporting IPV victims, far less is known about the underlying mechanisms between IPV and online help-seeking. We studied the mediating role of emotion dysregulation (ED) and the moderating role of perceived anonymity (PA) on the internet to explain IPV victims’ willingness of online help-seeking (WOHS). Through a PROCESS analysis of the questionnaire data (n = 510, 318 female, 192 male, Mage = 22.41 years), the results demonstrate that: (1) ED has been linked with the experience of IPV, and IPV significantly induces ED. (2) When IPV victims realize the symptoms of ED, they have a strong willingness to seek external intervention to support themselves. ED mediates the relationship between IPV and online help-seeking. (3) For youth growing up in the era of social networking sites (SNS), personal privacy protection is an important factor when seeking online help. The anonymity of the internet has a positive effect on victims who experience IPV and ED, and it increases WOHS. This study introduces a new perspective on the psychological mechanism behind IPV victims’ help-seeking behaviors, and it suggests that the improvement of anonymity in online support can be an effective strategy for assisting IPV victims.
Wind Dynamic Characteristics and Wind Tunnel Simulation of Subgrade Sand Hazard in the Shannan Wide Valley of the Sichuan–Tibet Railway
Authors: Xie Shengbo , Zhang Xian , Pang Yingjun
Published: July 2022

The Shannan wide valley section of the Sichuan–Tibet Railway is located in the middle reaches of the Yarlung Zangbo River, where sand hazard is severe. A wind tunnel simulation experiment was conducted by establishing a subgrade model and performing field observation to carry out research on the dynamic environment of blown sand and the sand hazard formation mechanism of subgrade in the Shannan wide valley. Observation results showed that the sand-moving wind of the Shannan wide valley was chiefly derived from the ENE direction, and the resultant sand transport direction was WSW. Wind speed, the frequency of sand-moving wind, the sand drift potential, and the maximum possible sand transport quantity were relatively high in the spring. Meanwhile, the dynamic of the wind-blown sand flow was further enhanced in the spring, particularly influenced by the flow action of the Yarlung Zangbo River. Thus, sand hazard mainly occurred in the spring. The Sichuan–Tibet Railway subgrade evidently changed the wind speed, the wind-blown sand flow field, and conditions of transport and accumulation. Within the distance of 5 times the model height in the windward direction and at the subgrade top center to 20 times the model height of the leeward direction was the wind speed deceleration zone, resulting in sand particle sediments. A wind speed acceleration zone appeared on the subgrade windward slope shoulder, resulting in wind-blown sand flow erosion. This study provides a scientific basis for sand hazard prevention and control in the Sichuan–Tibet Railway.
Participating in Different Activities and Their Association with Mental Health Problems in the Working Disabled Population in Korea
Authors: Chon Doukyoung , Moon Jong Youn , Kim Jae-Hyun
Published: July 2022

Background: There are a large number of people suffering from disabilities and this number is rapidly rising. People with disabilities experience various hardships and are more vulnerable to mental health problems. Participating in different types of activities (e.g., leisure, social, etc.) has been shown to ameliorate people’s mental health problems such as stress and depression. The aim of this study was to assess the effects of leisure and social activities on the mental well-being of the working disabled population in Korea. Methods: A total of 1521 disabled people aged between 15 and 64 were included in the study. The degree of participation in leisure (i.e., weekends or weekdays) and social activities, as well as stress and depressive symptoms, were measured using single-item questions. The association between participation in different activities (i.e., leisure and social) and mental health (i.e., stress and depression) was analyzed using a generalized estimating equation (GEE) model. Results: In the fully adjusted model, participation in leisure activities was associated with the level of stress, and less leisure participation was significantly associated with higher odds of stress. For example, in the “2 or fewer hours” group (odds ratio [OR] = 1.461, 95% confidence interval [CI] = 1.193–1.789) with the “5 h or more” group used as the reference for weekdays and the “5–9 h” group (OR = 1.223, 95% CI = 1.007–1.486) with the “10 h or more” group used as the reference for weekends. In terms of participation in social activities, increased participation was associated with lower levels of depression. For example, in the “Very much” group (OR = 0.314, 95% CI = 0.156–0.633) compared to the “Not at all” group. Conclusions: Participation in different activities was associated with better mental health outcomes in the working disabled population in Korea.
Exposure to Public Open Spaces and Leisure-Time Physical Activity: An Analysis of Adults in Primary Health Care in Brazil
Authors: Mello Rafael Luciano de , Lopes Adalberto Aparecido dos Santos , Fermino Rogério César
Published: July 2022

Public open spaces (POS) enable many leisure activities. However, few studies have evaluated how different exposures to POS with structured physical activities (PA) could affect the leisure-time PA (LTPA) of adults with chronic diseases. This study aimed to analyze the associations between different exposures to POS and LTPA in adults in primary health care in Brazil. In 2019, a cross-sectional study was conducted with a representative sample of 615 users of 15 Basic Health Units in São José dos Pinhais. The POS exposure was measured by the presence and distance (GIS), and the usage and frequency of usage were self-reported. The IPAQ identified walking and moderate-to-vigorous PA (MVPA). Data were analyzed with multilevel Poisson regression adjusted for the possible confounders (sex, age, economic level, chronic diseases). The prevalence of walking and MVPA ≥150 min/week was 12% and 14%, respectively. The usage of POS increased by 52% the likelihood of walking ≥10 min/week (PR: 1.52; 95%CI: 1.02–2.21), while usage ≥2 times/week increased by 2 times the likelihood of this outcome (PR: 2.01; 95%CI: 1.28–3.05). The usage of POS increased by 2.7 times the likelihood of MVPA ≥10 min/week (PR: 2.73; 95%CI: 1.86–3.97), and usage ≥2 times/week increased by 3.5 times the likelihood of this outcome (PR: 3.45; 95%CI: 2.14–5.42). Finally, the usage of POS increased by 3 times the likelihood of MVPA ≥150 min/week (PR: 3.03; 95%CI: 1.92–4.74), while usage ≥2 times/week increased by 3.8 times the likelihood of this outcome (PR: 3.81; 95%CI: 2.19–6.38). In conclusion, only the usage of POS is positively associated with walking and MVPA in the leisure time of adult primary health care users.
Horizontal Integration and Financing Reform of Rural Primary Care in China: A Model for Low-Resource and Remote Settings
Authors: Zeng Zhi , Tao Wenjuan , Ding Shanlong , Fang Jianlong , Wen Jin , Yao Jianhong , Zhang Wei
Published: July 2022

Primary health care (PHC) systems are compromised by under-resourcing and inadequate governance, and fail to provide high-quality health care services in most low- and middle-income countries (LMICs). As a response to solve the problems of underfunding and understaffing, Pengshui County, an impoverished area in rural Chongqing, China, implemented a profound reform of its PHC delivery system in 2009, focusing on horizontal integration and financing mechanisms. This paper aims to present new evidence from the Pengshui model, and to assess the relevant changes over the past 10 years (2009–2018). An inductive approach was adopted, based on analysis of national and local policy documents and administrative data. From 2009 to 2018, the proportion of outpatients who sought first-contact care in rural community or township health centers increased from 29% (522,700 of 1,817,600) in 2009, to 40% (849,900 of 2,147,800) in 2018 (the national average in 2018 was 23%). Our findings suggest that many positive results have been achieved through the reform, and that innovations in financial governance and incentive mechanisms are the main driving forces behind the improvement. Pengshui County’s experience has proven to be a successful experiment, particularly in rural and low-income areas.
Mental Health Disturbance after a Major Earthquake in Northern Peru: A Preliminary, Cross-Sectional Study
Authors: Valladares-Garrido Mario J. , Zapata-Castro Luis E. , Domínguez-Troncos Helena , García-Vicente Abigaíl , León-Figueroa Darwin A. , Zila-Velasque J. Pierre , Grados-Espinoza Pamela , Astudillo-Rueda David , Peralta C. Ichiro , Díaz-Vélez Cristian
Published: July 2022

Little has been studied in Peru on the mental health repercussions after a major earthquake. We aimed to explore the factors associated with depressive and anxiety symptoms in people who experienced a 6.1 magnitude earthquake in Piura, Peru, on 30 July 2021. A preliminary cross-sectional study was conducted in the general population between August–September 2021. An online questionnaire was provided using PHQ-9, GAD-7, and other relevant measures. Generalized linear models were applied. Of the 177 participants, the median age was 22 years, the majority were female (56%), and many experienced depressive (52%) or anxiety symptoms (52%). Presence of depressive symptoms was associated with a personal history of mental disorder, moderate housing damage, social/material support from politicians, moderate food insecurity, and insomnia. Presence of anxiety symptoms was associated with physical injury caused by the earthquake, mild food insecurity, and insomnia. The development of depressive and anxiety symptoms following the 2021 earthquake experienced in Piura depended on multiple individual and socioeconomic factors. Additional studies should reinforce the factors identified here given the methodological limitations, such as the study design, sampling method, and sample size. This would lead to effective intervention measures to mitigate the impact of earthquakes on mental health.
Gender Equity in Initial Teacher Training: Descriptive and Factorial Study of Students’ Conceptions in a Spanish Educational Context
Authors: Lucas-Palacios Laura , García-Luque Antonia , Delgado-Algarra Emilio José
Published: July 2022

In recent years, progress has been made to integrate the gender perspective into university curricula. Despite this, the lack in university degrees for initial teacher training is especially remarkable. This is because, together with families, teachers have the co-responsibility of educating new generations for the future. Issues such as the low presence of concepts related to gender in teaching guides or the lack of interest of teachers regarding their inclusion in classes lead to defining research to know and understand the conceptions of a sample of 162 teachers in the initial teacher training of a Bachelor’s degree on Early Childhood and Primary Education and a Master degree of Secondary Education on the incorporation of feminist thought in education. This research is a part of a broader doctoral dissertation and a research and development project. In general terms, from a quantitative, non-experimental approach, a questionnaire is designed and sent. The analysis includes a descriptive phase and a factorial phase that allows researchers to discover latent relationships between variables. Among the main conclusions, despite showing a relatively high knowledge of feminist theory, they confuse equity and equality. Students recognize the importance of having female references with whom to identify and they consider that feminist thought is a transversal content in education.
Cryptocurrencies Intraday High-Frequency Volatility Spillover Effects Using Univariate and Multivariate GARCH Models
Authors: Ampountolas Apostolos
Published: July 2022

Over the past years, cryptocurrencies have drawn substantial attention from the media while attracting many investors. Since then, cryptocurrency prices have experienced high fluctuations. In this paper, we forecast the high-frequency 1 min volatility of four widely traded cryptocurrencies, i.e., Bitcoin, Ethereum, Litecoin, and Ripple, by modeling volatility to select the best model. We propose various generalized autoregressive conditional heteroscedasticity (GARCH) family models, including an sGARCH(1,1), GJR-GARCH(1,1), TGARCH(1,1), EGARCH(1,1), which we compare to a multivariate DCC-GARCH(1,1) model to forecast the intraday price volatility. We evaluate the results under the MSE and MAE loss functions. Statistical analyses demonstrate that the univariate GJR-GARCH model (1,1) shows a superior predictive accuracy at all horizons, followed closely by the TGARCH(1,1), which are the best models for modeling the volatility process on out-of-sample data and have more accurately indicated the asymmetric incidence of shocks in the cryptocurrency market. The study determines evidence of bidirectional shock transmission effects between the cryptocurrency pairs. Hence, the multivariate DCC-GARCH model can identify the cryptocurrency market’s cross-market volatility shocks and volatility transmissions. In addition, we introduce a comparison of the models using the improvement rate (IR) metric for comparing models. As a result, we compare the different forecasting models to the chosen benchmarking model to confirm the improvement trends for the model’s predictions.
A Spatial Decision Support Approach for Flood Vulnerability Analysis in Urban Areas: A Case Study of Tehran
Authors: Afsari Rasoul , Nadizadeh Shorabeh Saman , Kouhnavard Mostafa , Homaee Mehdi , Arsanjani Jamal Jokar
Published: July 2022

Preparedness against floods in a hazard management perspective plays a major role in the pre-event phase. Hence, assessing urban vulnerability and resilience towards floods for different risk scenarios is a prerequisite for urban planners and decision makers. Therefore, the main objective of this study is to propose the design and implementation of a spatial decision support tool for mapping flood vulnerability in the metropolis of Tehran under different risk scenarios. Several factors reflecting topographical and hydrological characteristics, demographics, vegetation, land use, and urban features were considered, and their weights were determined using expert opinions and the fuzzy analytic hierarchy process (FAHP) method. Thereafter, a vulnerability map for different risk scenarios was prepared using the ordered weighted averaging (OWA) method. Based on our findings from the vulnerability analysis of the case study, it was concluded that in the optimistic scenario (ORness = 1), more than 36% of Tehran’s metropolis area was marked with very high vulnerability, and in the pessimistic scenario (ORness = 0), it was less than 1%was marked with very high vulnerability. The sensitivity analysis of our results confirmed that the validity of the model’s outcomes in different scenarios, i.e., high reliability of the model’s outcomes. The methodical approach, choice of data, and the presented results and discussions can be exploited by a wide range of stakeholders, e.g., urban planners, decision makers, and hydrologists, to better plan and build resilience against floods.
Increase in Anticancer Drug-Induced Toxicity by Fisetin in Lung Adenocarcinoma A549 Spheroid Cells Mediated by the Reduction of Claudin-2 Expression
Authors: Eguchi Hiroaki , Kimura Riho , Matsunaga Haruka , Matsunaga Toshiyuki , Yoshino Yuta , Endo Satoshi , Ikari Akira
Published: July 2022

Claudin-2 (CLDN2), a component of tight junction, is involved in the reduction of anticancer drug-induced toxicity in spheroids of A549 cells derived from human lung adenocarcinoma. Fisetin, a dietary flavonoid, inhibits cancer cell growth, but its effect on chemosensitivity in spheroids is unknown. Here, we found that fisetin (20 μM) decreases the protein level of CLDN2 to 22.3%. Therefore, the expression mechanisms were investigated by real-time polymerase chain reaction and Western blotting. Spheroids were formed in round-bottom plates, and anticancer drug-induced toxicity was measured by ATP content. Fisetin decreased the phosphorylated-Akt level, and CLDN2 expression was decreased by a phosphatidylinositol 3-kinase (PI3K) inhibitor, suggesting the inhibition of PI3K/Akt signal is involved in the reduction of CLDN2 expression. Hypoxia level, one of the hallmarks of tumor microenvironment, was reduced by fisetin. Although fisetin did not change hypoxia inducible factor-1α level, it decreased the protein level of nuclear factor erythroid 2-related factor 2, a stress response factor, by 25.4% in the spheroids. The toxicity of doxorubicin (20 μM) was enhanced by fisetin from 62.8% to 40.9%, which was rescued by CLDN2 overexpression (51.7%). These results suggest that fisetin can enhance anticancer drug toxicity in A549 spheroids mediated by the reduction of CLDN2 expression.
Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production
Authors: Baldassarri Samantha , Benati Daniela , D’Alessio Federica , Patrizi Clarissa , Cattin Eleonora , Gentile Michela , Raggioli Angelo , Recchia Alessandra
Published: July 2022

Sleeping Beauty (SB) is the first DNA transposon employed for efficient transposition in vertebrate cells, opening new applications for genetic engineering and gene therapies. A transposon-based gene delivery system holds the favourable features of non-viral vectors and an attractive safety profile. Here, we employed SB to engineer HEK293 cells for optimizing the production of a chimpanzee Adenovector (chAd) belonging to the Human Mastadenovirus C species. To date, chAd vectors are employed in several clinical settings for infectious diseases, last but not least COVID-19. A robust, efficient and quick viral vector production could advance the clinical application of chAd vectors. To this aim, we firstly swapped the hAd5 E1 with chAd-C E1 gene by using the CRISPR/Cas9 system. We demonstrated that in the absence of human Ad5 E1, chimp Ad-C E1 gene did not support HEK293 survival. To improve chAd-C vector production, we engineered HEK293 cells to stably express the chAd-C precursor terminal protein (ch.pTP), which plays a crucial role in chimpanzee Adenoviral DNA replication. The results indicate that exogenous ch.pTP expression significantly ameliorate the packaging and amplification of recombinant chAd-C vectors thus, the engineered HEK293ch.pTP cells could represent a superior packaging cell line for the production of these vectors.
Isothermal Nucleic Acid Amplification to Detect Infection Caused by Parasites of the Trypanosomatidae Family: A Literature Review and Opinion on the Laboratory to Field Applicability
Authors: Sereno Denis , Oury Bruno , Geiger Anne , Vela Andrea , Karmaoui Ahmed , Desquesnes Marc
Published: July 2022

Isothermal amplification of nucleic acids has the potential to be applied in resource-limited areas for the detection of infectious agents, as it does not require complex nucleic purification steps or specific and expensive equipment and reagents to perform the reaction and read the result. Since human and animal infections by pathogens of the Tryponasomatidae family occur mainly in resource-limited areas with scant health infrastructures and personnel, detecting infections by these methodologies would hold great promise. Here, we conduct a narrative review of the literature on the application of isothermal nucleic acid amplification for Trypanosoma and Leishmania infections, which are a scourge for human health and food security. We highlight gaps and propose ways to improve them to translate these powerful technologies into real-world field applications for neglected human and animal diseases caused by Trypanosomatidae.
Can a Scaffold Enriched with Mesenchymal Stem Cells Be a Good Treatment for Spinal Cord Injury?
Authors: Blando Santino , Anchesi Ivan , Mazzon Emanuela , Gugliandolo Agnese
Published: July 2022

Spinal cord injury (SCI) is a worldwide highly crippling disease that can lead to the loss of motor and sensory neurons. Among the most promising therapies, there are new techniques of tissue engineering based on stem cells that promote neuronal regeneration. Among the different types of stem cells, mesenchymal stem cells (MSCs) seem the most promising. Indeed, MSCs are able to release trophic factors and to differentiate into the cell types that can be found in the spinal cord. Currently, the most common procedure to insert cells in the lesion site is infusion. However, this causes a low rate of survival and engraftment in the lesion site. For these reasons, tissue engineering is focusing on bioresorbable scaffolds to help the cells to stay in situ. Scaffolds do not only have a passive role but become fundamental for the trophic support of cells and the promotion of neuroregeneration. More and more types of materials are being studied as scaffolds to decrease inflammation and increase the engraftment as well as the survival of the cells. Our review aims to highlight how the use of scaffolds made from biomaterials enriched with MSCs gives positive results in in vivo SCI models as well as the first evidence obtained in clinical trials.
Synergistic Antibacterial Activity with Conventional Antibiotics and Mechanism of Action of Shikonin against Methicillin-Resistant Staphylococcus aureus
Authors: Li Qian-Qian , Chae Hee-Sung , Kang Ok-Hwa , Kwon Dong-Yeul
Published: July 2022

Methicillin-resistant Staphylococcus aureus (MRSA) is a troublesome pathogen that poses a global threat to public health. Shikonin (SKN) isolated from Lithospermum erythrorhizon (L. erythrorhizon) possesses a variety of biological activities. This study aims to explore the effect of the combined application of SKN and traditional antibiotics on the vitality of MRSA and the inherent antibacterial mechanism of SKN. The synergies between SKN and antibiotics against MRSA and its clinical strain have been demonstrated by the checkerboard assay and the time-kill assay. The effect of SKN on disrupting the integrity and permeability of bacterial cell membranes was verified by a nucleotide and protein leakage assay and a bacteriolysis assay. As determined by crystal violet staining, SKN inhibited the biofilm formation of clinical MRSA strains. The results of Western blot and qRT-PCR showed that SKN could inhibit the expression of proteins and genes related to drug resistance and S. aureus exotoxins. SKN inhibited the ability of RAW264.7 cells to release the pro-inflammatory cytokines TNF-α and IL-6, as measured by ELISA. Our findings suggest that SKN has the potential to be developed as a promising alternative for the treatment of MRSA infections.
Extracellular Vesicles—Oral Therapeutics of the Future
Authors: Cieślik Martyna , Nazimek Katarzyna , Bryniarski Krzysztof
Published: July 2022

Considered an artifact just after discovery, the possibility of oral delivery of extracellular vesicles (EVs) and their functional cargos has recently gained much research attention. EVs from various sources, including edible plants, milk, bacteria and mammalian cells, have emerged as a platform for miRNA and drug delivery that seem to induce the expected immune effects locally and in distant tissues after oral administration. Such a possibility greatly expands the clinical applicability of EVs. The present review summarizes research findings that either support or deny the biological/therapeutical activity of orally administered EVs and their role in cross-species and cross-kingdom signaling.
Transcriptional Profiling of the Candida albicans Response to the DNA Damage Agent Methyl Methanesulfonate
Authors: Feng Yuting , Zhang Yan , Li Jie , Omran Raha Parvizi , Whiteway Malcolm , Feng Jinrong
Published: July 2022

The infection of a mammalian host by the pathogenic fungus Candida albicans involves fungal resistance to reactive oxygen species (ROS)—induced DNA damage stress generated by the defending macrophages or neutrophils. Thus, the DNA damage response in C. albicans may contribute to its pathogenicity. Uncovering the transcriptional changes triggered by the DNA damage—inducing agent MMS in many model organisms has enhanced the understanding of their DNA damage response processes. However, the transcriptional regulation triggered by MMS remains unclear in C. albicans. Here, we explored the global transcription profile in response to MMS in C. albicans and identified 306 defined genes whose transcription was significantly affected by MMS. Only a few MMS-responsive genes, such as MGT1, DDR48, MAG1, and RAD7, showed potential roles in DNA repair. GO term analysis revealed that a large number of induced genes were involved in antioxidation responses, and some downregulated genes were involved in nucleosome packing and IMP biosynthesis. Nevertheless, phenotypic assays revealed that MMS-induced antioxidation gene CAP1 and glutathione metabolism genes GST2 and GST3 showed no direct roles in MMS resistance. Furthermore, the altered transcription of several MMS—responsive genes exhibited RAD53—related regulation. Intriguingly, the transcription profile in response to MMS in C. albicans shared a limited similarity with the pattern in S. cerevisiae, including COX17, PRI2, and MGT1. Overall, C. albicans cells exhibit global transcriptional changes to the DNA damage agent MMS; these findings improve our understanding of this pathogen’s DNA damage response pathways.
Integration of eQTL Analysis and GWAS Highlights Regulation Networks in Cotton under Stress Condition
Authors: Han Xiao , Gao Chenxu , Liu Lisen , Zhang Yihao , Jin Yuying , Yan Qingdi , Yang Lan , Li Fuguang , Yang Zhaoen
Published: July 2022

The genus Gossypium is one of the most economically important crops in the world. Here, we used RNA-seq to quantify gene expression in a collection of G. arboreum seedlings and performed eGWAS on 28,382 expressed genes. We identified a total of 30,089 eQTLs in 10,485 genes, of which >90% were trans-regulate target genes. Using luciferase assays, we confirmed that different cis-eQTL haplotypes could affect promoter activity. We found ~6600 genes associated with ~1300 eQTL hotspots. Moreover, hotspot 309 regulates the expression of 325 genes with roles in stem length, fresh weight, seed germination rate, and genes related to cell wall biosynthesis and salt stress. Transcriptome-wide association study (TWAS) identified 19 candidate genes associated with the cotton growth and salt stress response. The variation in gene expression across the population played an essential role in population differentiation. Only a small number of the differentially expressed genes between South China, the Yangtze River region, and the Yellow River region sites were located in different chromosomal regions. The eQTLs found across the duplicated gene pairs showed conservative cis- or trans- regulation and that the expression levels of gene pairs were correlated. This study provides new insights into the evolution of gene expression regulation in cotton, and identifies eQTLs in stress-related genes for use in breeding improved cotton varieties.
Discovery of New 3,3-Diethylazetidine-2,4-dione Based Thiazoles as Nanomolar Human Neutrophil Elastase Inhibitors with Broad-Spectrum Antiproliferative Activity
Authors: Donarska Beata , Świtalska Marta , Wietrzyk Joanna , Płaziński Wojciech , Mizerska-Kowalska Magdalena , Zdzisińska Barbara , Łączkowski Krzysztof Z.
Published: July 2022

A series of 3,3-diethylazetidine-2,4-dione based thiazoles 3a–3j were designed and synthesized as new human neutrophil elastase (HNE) inhibitors in nanomolar range. The representative compounds 3c, 3e, and 3h exhibit high HNE inhibitory activity with IC50 values of 35.02–44.59 nM, with mixed mechanism of action. Additionally, the most active compounds 3c and 3e demonstrate high stability under physiological conditions. The molecular docking study showed good correlation of the binding energies with the IC50 values, suggesting that the inhibition properties are largely dependent on the stage of ligand alignment in the binding cavity. The inhibition properties are correlated with the energy level of substrates of the reaction of ligand with Ser195. Moreover, most compounds showed high and broad-spectrum antiproliferative activity against human leukemia (MV4-11), human lung carcinoma (A549), human breast adenocarcinoma (MDA-MB-231), and urinary bladder carcinoma (UMUC-3), with IC50 values of 4.59–9.86 μM. Additionally, compounds 3c and 3e can induce cell cycle arrest at the G2/M phase and apoptosis via caspase-3 activation, leading to inhibition of A549 cell proliferation. These findings suggest that these new types of drugs could be used to treat cancer and other diseases in which immunoreactive HNE is produced.
The Exploring Functional Role of Ammonium Transporters of Aspergillus oryzae in Nitrogen Metabolism: Challenges towards Cell Biomass Production
Authors: Chutrakul Chanikul , Panchanawaporn Sarocha , Vorapreeda Tayvich , Jeennor Sukanya , Anantayanon Jutamas , Laoteng Kobkul
Published: July 2022

Ammonium is a source of fermentable inorganic nitrogen essential for the growth and development of filamentous fungi. It is involved in several cellular metabolic pathways underlying nitrogen transport and assimilation. Ammonium can be transferred into the cell by an ammonium transporter. This study explored the role of ammonium transporters in nitrogen metabolism and cell biomass production in Aspergillus oryzae strain BCC 7051. Specific sequences encoding ammonium transporters (Amts) in A. oryzae were identified using genomic analysis. Four of the identified ammonium transporter genes, aoamt1-aoamt4, showed similarity in deduced amino acid sequences to the proteins in the ammonium transporter/methylammonium permease (AMT/MEP) family. Transcriptional analysis showed that the expression of aoamt2 and aoamt3 was ammonium-dependent, and was highly upregulated under ammonium-limited conditions. Their functional roles are characterized by genetic perturbations. The gene disruption and overexpression of aoamt3 indicated that the protein encoded by it was a crucial ammonium transporter associated with nitrogen metabolism and was required for filamentous growth. Compared with the wild type, the aoamt3-overexpressing strain showed superior growth performance, high biomass yield, and low glucose consumption. These results shed light on further improvements in the production of potent bioproducts by A. oryzae by manipulating the ammonium uptake capacity and nitrogen metabolism.
Sigma-1 Receptor in Retina: Neuroprotective Effects and Potential Mechanisms
Authors: Xu Zifen , Lei Yushuang , Qin Huan , Zhang Shiyao , Li Ping , Yao Kai
Published: July 2022

Retinal degenerative diseases are the major factors leading to severe visual impairment and even irreversible blindness worldwide. The therapeutic approach for retinal degenerative diseases is one extremely urgent and hot spot in science research. The sigma-1 receptor is a novel, multifunctional ligand-mediated molecular chaperone residing in endoplasmic reticulum (ER) membranes and the ER-associated mitochondrial membrane (ER-MAM); it is widely distributed in numerous organs and tissues of various species, providing protective effects on a variety of degenerative diseases. Over three decades, considerable research has manifested the neuroprotective function of sigma-1 receptor in the retina and has attempted to explore the molecular mechanism of action. In the present review, we will discuss neuroprotective effects of the sigma-1 receptor in retinal degenerative diseases, mainly in aspects of the following: the localization in different types of retinal neurons, the interactions of sigma-1 receptors with other molecules, the correlated signaling pathways, the influence of sigma-1 receptors to cellular functions, and the potential therapeutic effects on retinal degenerative diseases.
GsRSS3L, a Candidate Gene Underlying Soybean Resistance to Seedcoat Mottling Derived from Wild Soybean (Glycine soja Sieb. and Zucc)
Authors: Song Shuang , Wang Jing , Yang Xingqi , Zhang Xuan , Xin Xiuli , Liu Chunyan , Zou Jianan , Cheng Xiaofei , Zhang Ning , Hu Yuxi , Wang Jinhui , Chen Qingshan , Xin Dawei
Published: July 2022

Soybeans are a major crop that produce the best vegetable oil and protein for use in food and beverage products worldwide. However, one of the most well-known viral infections affecting soybeans is the Soybean Mosaic Virus (SMV), a member of the Potyviridae family. A crucial method for preventing SMV damage is the breeding of resistant soybean cultivars. Adult resistance and resistance of seedcoat mottling are two types of resistance to SMV. Most studies have focused on adult-plant resistance but not on the resistance to seedcoat mottling. In this study, chromosome segment-substituted lines derived from a cross between Suinong14 (cultivated soybean) and ZYD00006 (wild soybean) were used to identify the chromosome region and candidate genes underlying soybean resistance to seed coat mottling. Herein, two quantitative trait loci (QTLs) were found on chromosome 17, and eighteen genes were found in the QTL region. RNA-seq was used to evaluate the differentially expressed genes (DEGs) among the eighteen genes located in the QTLs. According to the obtained data, variations were observed in the expression of five genes following SMV infection. Furthermore, Nicotiana benthamiana was subjected to an Agrobacterium-mediated transient expression assay to investigate the role of the five candidate genes in SMV resistance. It has also been revealed that Glyma.17g238900 encoding a RICE SALT SENSITIVE 3-like protein (RSS3L) can inhibit the multiplication of SMV in N.benthamiana. Moreover, two nonsynonymous single-nucleotide polymorphisms (SNPs) were found in the coding sequence of Glyma.17g238900 derived from the wild soybean ZYD00006 (GsRSS3L), and the two amino acid mutants may be associated with SMV resistance. Hence, it has been suggested that GsRSS3L confers seedcoat mottling resistance, shedding light on the mechanism of soybean resistance to SMV.
Sphingosine Phosphate Lyase Is Upregulated in Duchenne Muscular Dystrophy, and Its Inhibition Early in Life Attenuates Inflammation and Dystrophy in Mdx Mice
Authors: De la Garza-Rodea Anabel S. , Moore Steven A. , Zamora-Pineda Jesus , Hoffman Eric P. , Mistry Karishma , Kumar Ashok , Strober Jonathan B. , Zhao Piming , Suh Jung H. , Saba Julie D.
Published: July 2022

Duchenne muscular dystrophy (DMD) is a congenital myopathy caused by mutations in the dystrophin gene. DMD pathology is marked by myositis, muscle fiber degeneration, and eventual muscle replacement by fibrosis and adipose tissue. Satellite cells (SC) are muscle stem cells critical for muscle regeneration. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes SC proliferation, regulates lymphocyte trafficking, and is irreversibly degraded by sphingosine phosphate lyase (SPL). Here, we show that SPL is virtually absent in normal human and murine skeletal muscle but highly expressed in inflammatory infiltrates and degenerating fibers of dystrophic DMD muscle. In mdx mice that model DMD, high SPL expression is correlated with dysregulated S1P metabolism. Perinatal delivery of the SPL inhibitor LX2931 to mdx mice augmented muscle S1P and SC numbers, reduced leukocytes in peripheral blood and skeletal muscle, and attenuated muscle inflammation and degeneration. The effect on SC was also observed in SCID/mdx mice that lack mature T and B lymphocytes. Transcriptional profiling in the skeletal muscles of LX2931-treated vs. control mdx mice demonstrated changes in innate and adaptive immune functions, plasma membrane interactions with the extracellular matrix (ECM), and axon guidance, a known function of SC. Our cumulative findings suggest that by raising muscle S1P and simultaneously disrupting the chemotactic gradient required for lymphocyte egress, SPL inhibition exerts a combination of muscle-intrinsic and systemic effects that are beneficial in the context of muscular dystrophy.
Retinal Ciliopathy in the Patient with Transplanted Kidney: Case Report
Authors: Bućan Ivona , Bjeloš Mirjana , Marković Irena , Bućan Diana
Published: July 2022

A review of a rare case of a proven mutation in the RP1 gene (RP1c.2029C>T, p. (ARG677*) in a kidney transplant patient was presented herein. According to his medical history, he had tonsillectomy performed at the age of 20 due to erythrocyturia, and at the age of 32 he was treated for malignant hypertension. The patient had been diagnosed with chronic renal failure at age 56 years. During an eye examination in 2016, retinitis pigmentosa was suspected and the patient was advised to run further tests. After an ophthalmological examination and tests, genetic testing was performed and a mutation in the RP1 gene encoding a family of proteins which are components of microtubules in photoreceptor primary cilia was proven. The literature search found that mutations in the RP1 gene have so far been exclusively associated with a non-syndromic form of retinal degeneration. However, the RP1 protein is expressed in the kidneys, and it remains unclear why the mutation of this gene so far was only specifically related to retinal photoreceptor function and not to arterial hypertension and renal disease. Primary cilia are thought to act as potential mechanosensory fluid-flow receptors in the vascular endothelium and kidney and their dysfunction results in atherosclerotic changes, hypertension, and chronic renal failure.
A Panel of Eight miRNAs Is Deregulated in HTLV-2 Infected PBMCs and BJABGu Cell Line
Authors: Pilotti Elisabetta , Cannata Attilio , Magnani Giacomo , Bignami Fabio , Corsi Andrea , Valenti Maria Teresa , Shallak Mariam , Forlani Greta , Romanelli Maria Grazia
Published: July 2022

Despite human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 being retroviruses closely related at a genomic level, HTLV-2 differs from HTLV-1 in terms of pathogenicity in both single infection and coinfection contexts. Moreover, the HTLV-2 association with clinical outcomes is still debated and several mechanisms underlying HTLV-2 infection remain unexplored as well. Cellular miRNAs are key factors in the post-transcriptional regulation of gene expression and they are known to be potential targets for several pathogens to control the host microenvironment and, in particular, escape immune responses. Here, we identified a HTLV-2-related signature of eight miRNAs (miR-125a-3p, miR-381-3p, miR-502-5p, miR-708-5p, miR-548d-5p, miR-548c-5p, miR-1-3p, and miR-511-5p) in both HTLV-2 infected PBMC and BJABGu cell lines. Altered miRNA expression patterns were correlated with the impairment of Th cell differentiation and signaling pathways driven by cytokines and transcriptional factors such as the Runt-related transcription factor (RUNX) family members. Specifically, we demonstrated that the RUNX2 protein was significantly more expressed in the presence of Tax-2 compared with Tax-1 in an in vitro cell model. To the best of our knowledge, these data represent the first contribution to elucidating the HTLV-2 mediated alteration of host cell miRNA profiles that may impact on HTLV-2 replication and persistent infection.
Molecular and Circulating Biomarkers of Gastric Cancer
Authors: Jelski Wojciech , Mroczko Barbara
Published: July 2022

Gastric cancer (GC)—a common tumor that affects humans worldwide—is highly malignant with a poor prognosis. GC is frequently not diagnosed until a relatively advanced stage. Early detection and efficient monitoring of tumor dynamics are prerequisites for reducing disease burden and mortality. Minimally invasive methods are needed to establish a diagnosis or monitoring the response to treatment of gastric cancer. Blood-based biomarker assays for the detection of early-stage GC could be of great relevance both for the risk group or for population-wide based screening programs, The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identified and tested for their clinical relevance in the management of gastric cancer. Here we review the available literature on plasma classical tumor markers, circulating free microRNAs (cfmiRNAs), circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs), autoantibodies against tumor associated antigens (TAAs), and circulating extracellular vesicles (EVs) for diagnosis and monitoring of gastric cancer. This review summarizes the present status and approaches for these biomarkers, which could be potentially used for early diagnosis and accurate prediction of therapeutic approaches. We also discuss the future perspective and challenges in the search for new biomarkers of gastric cancer.