bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Policy-Relevant Indicators for Injury Prevention in British Columbia by the Key Decision-Makers
Authors: Oakey Megan , Evans David C. , Copley Tobin T. , Karbakhsh Mojgan , Samarakkody Diana , Brubacher Jeff R. , Pawer Samantha , Zheng Alex , Rajabali Fahra , Fyfe Murray , Pike Ian
Published: November 2021

Indicators can help decision-makers evaluate interventions in a complex, multi-sectoral injury system. We aimed to create indicators for road safety, seniors falls, and ‘all-injuries’ to inform and evaluate injury prevention initiatives in British Columbia, Canada. The indicator development process involved a five-stage mixed methodology approach, including an environmental scan of existing indicators, generating expert consensus, selection of decision-makers and conducting a survey, selection of final indicators, and specification of indicators. An Indicator Reference Group (IRG) reviewed the list of indicators retrieved in the environmental scan and selected candidate indicators through expert consensus based on importance, modifiability, acceptance, and practicality. Key decision-makers (n = 561) were invited to rank each indicator in terms of importance and actionability (online survey). The IRG applied inclusion criteria and thresholds to survey responses from decision-makers, which resulted in the selection of 47 road safety, 18 seniors falls, and 33 all-injury indicators. After grouping “like” indicators, a final list of 23 road safety, 8 seniors falls, and 13 all-injury indicators were specified. By considering both decision-maker ranking and expert opinion, we anticipate improved injury system performance through advocacy, accountability, and evidence-based resource allocation in priority areas. Our indicators will inform a data management framework for whole-system reporting to drive policy and funding for provincial injury prevention improvement.
Community Nurses’ Preparations for and Challenges in Providing Palliative Home Care: A Qualitative Study
Authors: Wu Chien-Yi , Wu Yu-Hsuan , Chang Yi-Hui , Tsay Min-Shiow , Chen Hung-Cheng , Hsieh Hui-Ya
Published: November 2021

Hospitals have played a leading role in providing palliative care in Taiwan as its care model has developed over the past few decades. However, earlier local studies in Taiwan showed that terminal patients prefer to die at home, highlighting the need to promote community-based palliative care instead of hospital-based care. Along with this shift, how community nurses provide palliative home care merits further exploration. This qualitative descriptive study aims to understand (1) how community nurses implement community-based palliative care, (2) what preparations are needed, and (3) what challenges they may face. Purposive sampling was used for recruiting nurses. We conducted one-on-one, in-depth, semi-structured interviews. Interview recordings were transcribed verbatim and analyzed using thematic analysis. Eight community nurses with a range of experience in palliative home care were interviewed. Four major themes emerged: (1) Opportunities, (2) Qualifications, (3) Support, and (4) Commitments. Psychological preparedness, well-developed professional capabilities, external assistance, and peer support motivate community nurses to offer community-based palliative care. As the requests for palliative home care services increase, community nurses play a critical role in palliative home care. Although the sample size is small and the findings retrieved from a small number of experiences might not be generalized to every region, the study results could inform future experience-sharing and workshop sessions to train more nurses for community-based care, expanding service coverage, and providing optimal palliative care.
Environmental Substances Associated with Alzheimer’s Disease—A Scoping Review
Authors: Elonheimo Hanna Maria , Andersen Helle Raun , Katsonouri Andromachi , Tolonen Hanna
Published: November 2021

Alzheimer’s disease (AD) is the most common form of dementia, prevalent in approximately 50–70% of the dementia cases. AD affects memory, and it is a progressive disease interfering with cognitive abilities, behaviour and functioning of the person affected. In 2015, there were 47 million people affected by dementia worldwide, and the figure was estimated to increase to 75 million in 2030 and to 132 million by 2050. In the framework of European Human Biomonitoring Initiative (HBM4EU), 18 substances or substance groups were prioritized for investigation. For each of the priority substances, a scoping document was prepared. Based on these scoping documents and complementary review of the recent literature, a scoping review of HBM4EU-priority substances which might be associated with AD was conducted. A possible association between risk of AD and pesticides was detected. For mercury (Hg), association is possible but inconsistent. Regarding cadmium (Cd) and arsenic (As), the results are inconsistent but inclined towards possible associations between the substances and the risk of disease. The evidence regarding lead (Pb) was weaker than for the other substances; however, possible associations exist. Although there is evidence of adverse neurological effects of environmental substances, more research is needed. Environmental chemical exposure and the related hazards are essential concerns for public health, and they could be preventable.
Analysis of the Spatial and Temporal Changes of NDVI and Its Driving Factors in the Wei and Jing River Basins
Authors: Huang Chenlu , Yang Qinke , Huang Weidong
Published: November 2021

This study aimed to explore the long-term vegetation cover change and its driving factors in the typical watershed of the Yellow River Basin. This research was based on the Google Earth Engine (GEE), a remote sensing cloud platform, and used the Landsat surface reflectance datasets and the Pearson correlation method to analyze the vegetation conditions in the areas above Xianyang on the Wei River and above Zhangjiashan on the Jing River. Random forest and decision tree models were used to analyze the effects of various climatic factors (precipitation, temperature, soil moisture, evapotranspiration, and drought index) on NDVI (normalized difference vegetation index). Then, based on the residual analysis method, the effects of human activities on NDVI were explored. The results showed that: (1) From 1987 to 2018, the NDVI of the two watersheds showed an increasing trend; in particular, after 2008, the average increase rate of NDVI in the growing season (April to September) increased from 0.0032/a and 0.003/a in the base period (1987–2008) to 0.0172/a and 0.01/a in the measurement period (2008–2018), for the Wei and Jing basins, respectively. In addition, the NDVI significantly increased from 21.78% and 31.32% in the baseline period (1987–2008) to 83.76% and 92.40% in the measurement period (2008–2018), respectively. (2) The random forest and classification and regression tree model (CART) can assess the contribution and sensitivity of various climate factors to NDVI. Precipitation, soil moisture, and temperature were found to be the three main factors that affect the NDVI of the study area, and their contributions were 37.05%, 26.42%, and 15.72%, respectively. The changes in precipitation and soil moisture in the entire Jing River Basin and the upper and middle reaches of the Wei River above Xianyang caused significant changes in NDVI. Furthermore, changes in precipitation and temperature led to significant changes in NDVI in the lower reaches of the Wei River. (3) The impact of human activities in the Wei and Jing basins on NDVI has gradually changed from negative to positive, which is mainly due to the implementation of soil and water conservation measures. The proportions of areas with positive effects of human activities were 80.88% and 81.95%, of which the proportions of areas with significant positive effects were 11.63% and 7.76%, respectively. These are mainly distributed in the upper reaches of the Wei River and the western and eastern regions of the Jing River. These areas are the key areas where soil and water conservation measures have been implemented in recent years, and the corresponding land use has transformed from cultivated land to forest and grassland. The negative effects accounted for 1.66% and 0.10% of the area, respectively, and were mainly caused by urban expansion and coal mining.
Considering Autonomous Exploration in Healthy Environments: Reflections from an Urban Wildscape
Authors: Little Sarah , Rice Art
Published: November 2021

Autonomous exploration should be considered in the creation of healthy environments since autonomy is an important developmental experience for children. For a group of boys in Raleigh, N.C., U.S. during the period 2002–2006, autonomous exploration was a meaningful experience. Results of a qualitative research project (n = 5) which highlight the importance of autonomous exploration are organized within a proposed framework for thick description. The framework creates verisimilitude by reporting on the context, social action and cultural context, and behavior and intentionality. The context of Raleigh and urban wildscapes furnished areas ripe for exploration. The social action and cultural context of attachment supported the autonomous exploration through scaffolded experiences of autonomy. The intentionality of the behavior was a desire to distinct themselves through a focus on individual development and the pursuit of extraordinary experiences. The ultimate outcomes of autonomous exploration for the boys were the development of long-term, intimate friendships and confidence in their decision-making ability. As cities become more health-focused, attention should be paid to preserve the rough edges of a city for children to explore.
Economic Impacts on Human Health Resulting from the Use of Mercury in the Illegal Gold Mining in the Brazilian Amazon: A Methodological Assessment
Authors: de Bakker Leonardo Barcellos , Gasparinetti Pedro , de Queiroz Júlia Mello , de Vasconcellos Ana Claudia Santiago
Published: November 2021

Artisanal small-scale gold mining (ASGM) in the Amazon results in the dumping of tons of mercury into the environment annually. Despite consensus on the impacts of mercury on human health, there are still unknowns regarding: (i) the extent to which mercury from ASGM can be dispersed in the environment until it becomes toxic to humans; and (ii) the economic value of losses caused by contamination becomes evident. The main objective of this study is to propose a methodology to evaluate the impacts of ASGM on human health in different contexts in the Brazilian Amazon. We connect several points in the literature based on hypotheses regarding mercury dispersion in water, its transformation into methylmercury, and absorption by fish and humans. This methodology can be used as a tool to estimate the extent of environmental damage caused by artisanal gold mining, the severity of damage to the health of individuals contaminated by mercury and, consequently, can contribute to the application of fines to environmental violators. The consequences of contamination are evaluated by dose-response functions relating to mercury concentrations in hair and the development of the following health outcomes: (i) mild mental retardation, (ii) acute myocardial infarction, and (iii) hypertension. From disability-adjusted life years and statistical life value, we found that the economic losses range from 100,000 to 400,000 USD per kilogram of gold extracted. A case study of the Yanomami indigenous land shows that the impacts of mercury from illegal gold mining in 2020 totaled 69 million USD, which could be used by local authorities to compensate the Yanomami people.
Predictors of Problematic Social Media Use in a Nationally Representative Sample of Adolescents in Luxembourg
Authors: van Duin Claire , Heinz Andreas , Willems Helmut
Published: November 2021

Social media use has increased substantially over the past decades, especially among adolescents. A proportion of adolescents develop a pattern of problematic social media use (PSMU). Predictors of PSMU are insufficiently understood and researched. This study aims to investigate predictors of PSMU in a nationally representative sample of adolescents in Luxembourg. Data from the Health Behavior in School-aged Children (HBSC) study in Luxembourg were used, in which 8687 students aged 11–18 years old participated. The data were analyzed using hierarchical multiple regression. A range of sociodemographic, social support, well-being and media use predictors were added to the model in four blocks. The predictors in the final model explained 22.3% of the variance in PSMU. The block of sociodemographic predictors explained the lowest proportion of variance in PSMU compared with the other blocks. Age negatively predicted PSMU. Of the predictors related to social support, cyberbullying perpetration was the strongest predictor of PSMU. Perceived stress and psychosomatic complaints positively predicted PSMU. The intensity of electronic media communication and preference for online social interaction were stronger predictors of PSMU than the other predictors in the model. The results indicate that prevention efforts need to consider the diverse range of predictors related to PSMU.
Ecological Civilization Demonstration Zone, Air Pollution Reduction, and Political Promotion Tournament in China: Empirical Evidence from a Quasi-Natural Experiment
Authors: Wang Haijie , Geng Yong , Zhang Jingxue , Xia Xiqiang , Feng Yanchao
Published: November 2021

Using the ecological civilization demonstration zone as a quasi-natural experiment, this study has explored the effect of it on air pollution in China by employing the difference-in-differences model and the spatial difference-in-differences model, and further tested the political promotion tournament in China by employing the binary logit model. The results show that the ecological civilization demonstration zone has basically and effectively reduced air pollution, except for carbon monoxide and ozone. In addition, the spatial spillover effects of the ecological civilization demonstration zone on air pollution are not only basically supported among the treated cities, but also extremely established in the untreated cities neighboring the treated cities. Furthermore, no clear evidence supports the establishment of the political promotion tournament in China, while local cadres tend to cope with the assessment of higher officials passively rather than actively. Overall, this study sheds light on the coordination of economic development and ecological civilization from the perspective of the career concerns of local cadres.
Impact of Working from Home on Cardiovascular Health: An Emerging Issue with the COVID-19 Pandemic
Authors: Di Fusco Stefania Angela , Spinelli Antonella , Castello Lorenzo , Mocini Edoardo , Gulizia Michele Massimo , Oliva Fabrizio , Gabrielli Domenico , Imperoli Giuseppe , Colivicchi Furio
Published: November 2021

Mandatory working from home is one of the consequences of the COVID-19 pandemic for a large number of workers. Transition to working from home may significantly impact lifestyle, psychosocial status, and the overall health of workers. This review summarizes available data about the effects of lockdown measures, particularly working from home, on cardiovascular risk factors including sedentary lifestyle, unhealthy diet pattern, psychological distress, smoking, alcohol misuse, and cardiometabolic parameters. Finally, we suggest countermeasures that can attenuate the negative health impact of working from home. Indeed, timely and tailored interventions implemented by companies in cooperation with the health care system could allow workers to benefit more from some of the advantages associated with working from home.
Overparenting, Parent-Child Conflict and Anxiety among Chinese Adolescents: A Cross-Lagged Panel Study
Authors: Leung Janet Tsin-Yee
Published: November 2021

Background: Overparenting is an emerging parenting style in which parents over-protect their children from difficulties and challenges by intruding into their lives and providing extensive assistance to them. Unfortunately, longitudinal studies related to overparenting were severely lacking, particularly on its impacts on early adolescents. Moreover, studies examining the mediational pathways through which overparenting is associated with adolescent anxiety are scant. This study examined the mediating role of parent-child conflict (father-child and mother-child) in the relationship between overparenting (paternal and maternal) and adolescent anxiety over time. Method: Based on a three-wave longitudinal data of 1074 Chinese early adolescents in Hong Kong, the relationships among paternal and maternal overparenting, father- and mother-child conflict, and adolescent anxiety were assessed. Results: Mother-child conflict mediated the relationship between maternal overparenting and adolescent anxiety over time. Besides, a reverse association of prior adolescent anxiety with subsequent maternal overparenting via mother-child conflict was also identified. In addition, adolescent gender and family intactness did not moderate the relationships among overparenting, parent-child conflict, and adolescent anxiety. Discussion: This present study identified that the bidirectional relationship between maternal overparenting and adolescent anxiety via mother-child conflict over time, which sheds new light on the study of overparenting on adolescent well-being in the Chinese communities.
Development of a New Application-Based Chewing Efficiency Test (Mini Dental Assessment) and Its Evaluation by Nursing Staff in Geriatric Care: A Pilot Study
Authors: Schmidt Alexander , Schlenz Maximiliane Amelie , Gäbler Clara Sophie , Schlee Steffen , Wöstmann Bernd
Published: November 2021

The increasing average life expectancy worldwide results in an elderly population with significant health care needs. However, dental care is often not a focus of care. It is well known that oral and overall health are directly related. Therefore, the Mini Dental Assessment (MDA) was developed to provide a simple analysis of oral health status, although it is currently only available in paper form, with all associated drawbacks, from illegible writing to the inability to quickly search the collected forms. This study aimed to develop a digital application (app) for mobile devices that can overcome the problems associated with paper forms. After the digital MDA was developed, its usability was evaluated by nurses, a questionnaire was answered, and it was compared to the analog MDA with patients in a pilot study. The usability of the app (System Usability Scale) was 95.18 ± 4.26, representing a very high usability. Furthermore, this app showed good clinical applicability. The results also showed that the digital MDA was accepted by nurses in their daily routine and was preferred to the analog MDA. A follow-up study with a higher number of subjects is highly recommended.
Evaluation of a Fast Test Based on Biometric Signals to Assess Mental Fatigue at the Workplace—A Pilot Study
Authors: Ramírez-Moreno Mauricio A. , Carrillo-Tijerina Patricio , Candela-Leal Milton Osiel , Alanis-Espinosa Myriam , Tudón-Martínez Juan Carlos , Roman-Flores Armando , Ramírez-Mendoza Ricardo A. , Lozoya-Santos Jorge de J.
Published: November 2021

Non-pathological mental fatigue is a recurring, but undesirable condition among people in the fields of office work, industry, and education. This type of mental fatigue can often lead to negative outcomes, such as performance reduction and cognitive impairment in education; loss of focus and burnout syndrome in office work; and accidents leading to injuries or death in the transportation and manufacturing industries. Reliable mental fatigue assessment tools are promising in the improvement of performance, mental health and safety of students and workers, and at the same time, in the reduction of risks, accidents and the associated economic loss (e.g., medical fees and equipment reparations). The analysis of biometric (brain, cardiac, skin conductance) signals has proven to be effective in discerning different stages of mental fatigue; however, many of the reported studies in the literature involve the use of long fatigue-inducing tests and subject-specific models in their methodologies. Recent trends in the modeling of mental fatigue suggest the usage of non subject-specific (general) classifiers and a time reduction of calibration procedures and experimental setups. In this study, the evaluation of a fast and short-calibration mental fatigue assessment tool based on biometric signals and inter-subject modeling, using multiple linear regression, is presented. The proposed tool does not require fatigue-inducing tests, which allows fast setup and implementation. Electroencephalography, photopletismography, electrodermal activity, and skin temperature from 17 subjects were recorded, using an OpenBCI helmet and an Empatica E4 wristband. Correlations to self-reported mental fatigue levels (using the fatigue assessment scale) were calculated to find the best mental fatigue predictors. Three-class mental fatigue models were evaluated, and the best model obtained an accuracy of 88% using three features, β/θ (C3), and the α/θ (O2 and C3) ratios, from one minute of electroencephalography measurements. The results from this pilot study show the feasibility and potential of short-calibration procedures and inter-subject classifiers in mental fatigue modeling, and will contribute to the use of wearable devices for the development of tools oriented to the well-being of workers and students, and also in daily living activities.
The Proteoglycan Biglycan Modulates Platelet Adhesion and Thrombus Formation in a GPVI-Dependent Manner
Authors: Hoermann Henrike , Krueger Irena , Maurus Nadine , Reusswig Friedrich , Sun Yi , Kohlmorgen Christina , Grandoch Maria , Fischer Jens W. , Elvers Margitta
Published: November 2021

Background: Vascular injury induces the exposure of subendothelial extracellular matrix (ECM) important to serve as substrate for platelets to adhere to the injured vessel wall to avoid massive blood loss. Different ECM proteins are known to initiate platelet adhesion and activation. In atherosclerotic mice, the small, leucine-rich proteoglycan biglycan is important for the regulation of thrombin activity via heparin cofactor II. However, nothing is known about the role of biglycan for hemostasis and thrombosis under nonatherosclerotic conditions. Methods: The role of biglycan for platelet adhesion and thrombus formation was investigated using a recombinant protein and biglycan knockout mice. Results: The present study identified biglycan as important ECM protein for the adhesion and activation of platelets, and the formation of three-dimensional thrombi under flow conditions. Platelet adhesion to immobilized biglycan induces the reorganization of the platelet cytoskeleton. Mechanistically, biglycan binds and activates the major collagen receptor glycoprotein (GP)VI, because reduced platelet adhesion to recombinant biglycan was observed when GPVI was blocked and enhanced tyrosine phosphorylation in a GPVI-dependent manner was observed when platelets were stimulated with biglycan. In vivo, the deficiency of biglycan resulted in reduced platelet adhesion to the injured carotid artery and prolonged bleeding times. Conclusions: Loss of biglycan in the vessel wall of mice but not in platelets led to reduced platelet adhesion at the injured carotid artery and prolonged bleeding times, suggesting a crucial role for biglycan as ECM protein that binds and activates platelets via GPVI upon vessel injury.
IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells
Authors: de Pedro María Ángeles , Gómez-Serrano María , Marinaro Federica , López Esther , Pulido María , Preußer Christian , Pogge von Strandmann Elke , Sánchez-Margallo Francisco Miguel , Álvarez Verónica , Casado Javier G.
Published: November 2021

Mesenchymal stromal cells isolated from menstrual blood (MenSCs) exhibit a potent pro-angiogenic and immunomodulatory capacity. Their therapeutic effect is mediated by paracrine mediators released by their secretomes. In this work, we aimed to evaluate the effect of a specific priming condition on the phenotype and secretome content of MenSCs. Our results revealed that the optimal condition for priming MenSCs was the combination of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) that produced a synergistic and additive effect on IDO1 release and immune-related molecule expression. The analyses of MenSC-derived secretomes after IFNγ and TNFα priming also revealed an increase in EV release and in the differentially expressed miRNAs involved in the immune response and inflammation. Proliferation assays on lymphocyte subsets demonstrated a decrease in CD4+ T cells and CD8+ T cells co-cultured with secretomes, especially in the lymphocytes co-cultured with secretomes from primed cells. Additionally, the expression of immune checkpoints (PD-1 and CTLA-4) was increased in the CD4+ T cells co-cultured with MenSC-derived secretomes. These findings demonstrate that the combination of IFNγ and TNFα represents an excellent priming strategy to enhance the immunomodulatory capacity of MenSCs. Moreover, the secretome derived from primed MenSCs may be postulated as a therapeutic option for the regulation of adverse inflammatory reactions.
Patient-Specific iPSC-Derived Neural Differentiated and Hepatocyte-like Cells, Carrying the Compound Heterozygous Mutation p.V1023Sfs*15/p.G992R, Present the “Variant” Biochemical Phenotype of Niemann-Pick Type C1 Disease
Authors: Völkner Christin , Liedtke Maik , Untucht Robert , Hermann Andreas , Frech Moritz J.
Published: November 2021

Niemann–Pick disease type C1 (NP-C1) is a rare lysosomal storage disorder caused by autosomal recessive mutations in the NPC1 gene. Patients display a wide spectrum on the clinical as well as on the molecular level, wherein a so-called “variant” biochemical phenotype can be observed. Here, we report an in vitro analysis of fibroblasts obtained from an NP-C1 patient carrying the undescribed compound heterozygous mutation p.V1023Sfs*15/p.G992R. Since NP-C1 is a neurovisceral disease and the patient suffers from severe neurological as well as hepatic symptoms, we extended our study to neural differentiated and hepatocyte-like cells derived from patient-specific induced pluripotent stem cells. We detected slightly increased intracellular cholesterol levels compared to the control cell line in fibroblasts, neural differentiated and hepatocyte-like cells, suggesting a “variant” biochemical phenotype. Furthermore, the total NPC1 protein, as well as post-ER glycoforms of the NPC1 protein, tended to be reduced. In addition, colocalization analysis revealed a mild reduction of the NPC1 protein in the lysosomes. The patient was diagnosed with NP-C1 at the age of 34 years, after an initial misdiagnosis of schizophrenia. After years of mild and unspecific symptoms, such as difficulties in coordination and concentration, symptoms progressed and the patient finally presented with ataxia, dysarthria, dysphagia, vertical supranuclear gaze palsy, and hepatosplenomegaly. Genetic testing finally pointed towards an NP-C1 diagnosis, revealing the so-far undescribed compound heterozygous mutation p.V1023Sfs*15/p.G992R in the NPC1 gene. In light of these findings, this case provides support for the p.G992R mutation being causative for a “variant” biochemical phenotype leading to an adult-onset type of NP-C1 disease.
Chromosome Folding Promotes Intrachromosomal Aberrations under Radiation- and Nuclease-Induced DNA Breakage
Authors: Eidelman Yuri , Salnikov Ilya , Slanina Svetlana , Andreev Sergey
Published: November 2021

The long-standing question in radiation and cancer biology is how principles of chromosome organization impact the formation of chromosomal aberrations (CAs). To address this issue, we developed a physical modeling approach and analyzed high-throughput genomic data from chromosome conformation capture (Hi-C) and translocation sequencing (HTGTS) methods. Combining modeling of chromosome structure and of chromosomal aberrations induced by ionizing radiation (IR) and nuclease we made predictions which quantitatively correlated with key experimental findings in mouse chromosomes: chromosome contact maps, high frequency of cis-translocation breakpoints far outside of the site of nuclease-induced DNA double-strand breaks (DSBs), the distinct shape of breakpoint distribution in chromosomes with different 3D organizations. These correlations support the heteropolymer globule principle of chromosome organization in G1-arrested pro-B mouse cells. The joint analysis of Hi-C, HTGTS and physical modeling data offers mechanistic insight into how chromosome structure heterogeneity, globular folding and lesion dynamics drive IR-recurrent CAs. The results provide the biophysical and computational basis for the analysis of chromosome aberration landscape under IR and nuclease-induced DSBs.
Cordyceps militaris Immunomodulatory Protein Promotes the Phagocytic Ability of Macrophages through the TLR4-NF-κB Pathway
Authors: Fan Hong-Bo , Zou Yuan , Han Qing , Zheng Qian-Wang , Liu Ying-Li , Guo Li-Qiong , Lin Jun-Fang
Published: November 2021

Enhancing the phagocytosis of immune cells with medicines provides benefits to the physiological balance by removing foreign pathogens and apoptotic cells. The fungal immunomodulatory protein (FIP) possessing various immunopotentiation functions may be a good candidate for such drugs. However, the effect and mechanism of FIP on the phagocytic activity is limitedly investigated. Therefore, the present study determined effects of Cordyceps militaris immunomodulatory protein (CMIMP), a novel FIP reported to induce cytokines secretion, on the phagocytosis using three different types of models, including microsphere, Escherichia Coli and Candida albicans. CMIMP not only significantly improved the phagocytic ability (p < 0.05), but also enhanced the bactericidal activity (p < 0.05). Meanwhile, the cell size, especially the cytoplasm size, was markedly increased by CMIMP (p < 0.01), accompanied by an increase in the F-actin expression (p < 0.001). Further experiments displayed that CMIMP-induced phagocytosis, cell size and F-actin expression were alleviated by the specific inhibitor of TLR4 (p < 0.05). Similar results were observed in the treatment with the inhibitor of the NF-κB pathway (p < 0.05). In conclusion, it could be speculated that CMIMP promoted the phagocytic ability of macrophages through increasing F-actin expression and cell size in a TLR4-NF-κB pathway dependent way.
Plasmonic Core–Shell–Satellites with Abundant Electromagnetic Hotspots for Highly Sensitive and Reproducible SERS Detection
Authors: Pandey Puran , Kunwar Sundar , Shin Ki-Hoon , Seo Min-Kyu , Yoon Jongwon , Hong Woong-Ki , Sohn Jung-Inn
Published: November 2021

In this work, we develop a Ag@Al2O3@Ag plasmonic core–shell–satellite (PCSS) to achieve highly sensitive and reproducible surface-enhanced Raman spectroscopy (SERS) detection of probe molecules. To fabricate PCSS nanostructures, we employ a simple hierarchical dewetting process of Ag films coupled with an atomic layer deposition (ALD) method for the Al2O3 shell. Compared to bare Ag nanoparticles, several advantages of fabricating PCSS nanostructures are discovered, including high surface roughness, high density of nanogaps between Ag core and Ag satellites, and nanogaps between adjacent Ag satellites. Finite-difference time-domain (FDTD) simulations of the PCSS nanostructure confirm an enhancement in the electromagnetic field intensity (hotspots) in the nanogap between the Ag core and the satellite generated by the Al2O3 shell, due to the strong core–satellite plasmonic coupling. The as-prepared PCSS-based SERS substrate demonstrates an enhancement factor (EF) of 1.7 × 107 and relative standard deviation (RSD) of ~7%, endowing our SERS platform with highly sensitive and reproducible detection of R6G molecules. We think that this method provides a simple approach for the fabrication of PCSS by a solid-state technique and a basis for developing a highly SERS-active substrate for practical applications.
Genome-Wide Identification, Characterization and Expression Analysis of Soybean CHYR Gene Family
Authors: Jia Bowei , Wang Yan , Zhang Dajian , Li Wanhong , Cui Hongli , Jin Jun , Cai Xiaoxi , Shen Yang , Wu Shengyang , Guo Yongxia , Sun Mingzhe , Sun Xiaoli
Published: November 2021

The CHYR (CHY ZINC-FINGER AND RING FINGER PROTEIN) proteins have been functionally characterized in iron regulation and stress response in Arabidopsis, rice and Populus. However, their roles in soybean have not yet been systematically investigated. Here, in this study, 16 GmCHYR genes with conserved Zinc_ribbon, CHY zinc finger and Ring finger domains were obtained and divided into three groups. Moreover, additional 2–3 hemerythrin domains could be found in the N terminus of Group III. Phylogenetic and homology analysis of CHYRs in green plants indicated that three groups might originate from different ancestors. Expectedly, GmCHYR genes shared similar conserved domains/motifs distribution within the same group. Gene expression analysis uncovered their special expression patterns in different soybean tissues/organs and under various abiotic stresses. Group I and II members were mainly involved in salt and alkaline stresses. The expression of Group III members was induced/repressed by dehydration, salt and alkaline stresses, indicating their diverse roles in response to abiotic stress. In conclusion, our work will benefit for further revealing the biological roles of GmCHYRs.
The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor
Authors: Cho Jin Hyoung , Ju Won Seok , Seo Sang Young , Kim Bo Hyun , Kim Ji-Su , Kim Jong-Geol , Park Soon Ju , Choo Young-Kug
Published: November 2021

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.
Insulin-like Growth Factor Binding Protein-2 (IGFBP2) Is a Key Molecule in the MACC1-Mediated Platelet Communication and Metastasis of Colorectal Cancer Cells
Authors: Haschemi Reza , Kobelt Dennis , Steinwarz Elisabeth , Schlesinger Martin , Stein Ulrike , Bendas Gerd
Published: November 2021

Tumor cell crosstalk with platelets and, subsequently, their activation are key steps in hematogenous tumor metastasis. MACC1 is an oncogene involved in molecular pathogenesis of colorectal cancer (CRC) and other solid tumor entities, mediating motility and metastasis, making MACC1 an accepted prognostic biomarker. However, the impact of MACC1 on platelet activation has not yet been addressed. Here, we investigated the activation of platelets by human CRC cells upon MACC1 modulation, indicated by platelet aggregation and granule release. These approaches led to the identification of insulin-like growth factor binding protein-2 (IGFBP2) as a functional downstream molecule of MACC1, affecting communication with platelets. This was confirmed by an shRNA-mediated IGFBP2 knockdown, while maintaining MACC1 activity. Although IGFBP2 displayed an attenuated platelet activation potential, obviously by scavenging IGF-I as a platelet costimulatory mediator, the MACC1/IGFBP2 axis did not affect the thrombin formation potential of the cells. Furthermore, the IGFBP2/MACC1-driven cell migration and invasiveness was further accelerated by platelets. The key role of IGFBP2 for the metastatic spread in vivo was confirmed in a xenograft mouse model. Data provide evidence for IGFBP2 as a downstream functional component of MACC1-driven metastasis, linking these two accepted oncogenic biomarkers for the first time in a platelet context.
A Possible Role for HMG-CoA Reductase Inhibitors and Its Association with HMGCR Genetic Variation in Parkinson’s Disease
Authors: Pierzchlińska Anna , Droździk Marek , Białecka Monika
Published: November 2021

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterised by both motor- and non-motor symptoms, including cognitive impairment. The aetiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. Neuroprotective effects of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors—statins—via both cholesterol-dependent and independent mechanisms have been shown in animal and cell culture models. However, the available data provide conflicting results on the role of statin treatment in PD patients. Moreover, cholesterol is a vital component for brain functions and may be considered as protective against PD. We present possible statin effects on PD under the hypothesis that they may depend on the HMG-CoA reductase gene (HMGCR) variability, such as haplotype 7, which was shown to affect cholesterol synthesis and statin treatment outcome, diminishing possible neuroprotection associated with HMG-CoA reductase inhibitors administration. Statins are among the most prescribed groups of drugs. Thus, it seems important to review the available data in the context of their possible neuroprotective effects in PD, and the HMG-CoA reductase gene’s genetic variability.
Synthesis, Properties and Bioimaging Applications of Silver-Based Quantum Dots
Authors: Borovaya Mariya , Horiunova Inna , Plokhovska Svitlana , Pushkarova Nadia , Blume Yaroslav , Yemets Alla
Published: November 2021

Ag-based quantum dots (QDs) are semiconductor nanomaterials with exclusive electrooptical properties ideally adaptable for various biotechnological, chemical, and medical applications. Silver-based semiconductor nanocrystals have developed rapidly over the past decades. They have become a promising luminescent functional material for in vivo and in vitro fluorescent studies due to their ability to emit at the near-infrared (NIR) wavelength. In this review, we discuss the basic features of Ag-based QDs, the current status of classic (chemical) and novel methods (“green” synthesis) used to produce these QDs. Additionally, the advantages of using such organisms as bacteria, actinomycetes, fungi, algae, and plants for silver-based QDs biosynthesis have been discussed. The application of silver-based QDs as fluorophores for bioimaging application due to their fluorescence intensity, high quantum yield, fluorescent stability, and resistance to photobleaching has also been reviewed.
Identification of Molecular Markers of Clozapine Action in Ketamine-Induced Cognitive Impairment: A GPCR Signaling PathwayFinder Study
Authors: Korlatowicz Agata , Kuśmider Maciej , Szlachta Marta , Pabian Paulina , Solich Joanna , Dziedzicka-Wasylewska Marta , Faron-Górecka Agata
Published: November 2021

Background: Cognitive disorders associated with schizophrenia are closely linked to prefrontal cortex (PFC) dysfunction. Administration of the non-competitive NMDA receptor antagonist ketamine (KET) induces cognitive impairment in animals, producing effects similar to those observed in schizophrenic patients. In a previous study, we showed that KET (20 mg/kg) induces cognitive deficits in mice and that administration of clozapine (CLZ) reverses this effect. To identify biochemical mechanisms related to CLZ actions in the context of KET-induced impairment, we performed a biochemical analysis using the same experimental paradigm—acute and sub-chronic administration of these drugs (0.3 and 1 mg/kg). Methods: Since the effect of CLZ mainly depends on G-protein-related receptors, we used the Signaling PathwayFinder Kit to identify 84 genes involved in GPCR-related signal transduction and then verified the genes that were statistically significantly different on a larger group of mice using RT-PCR and Western blot analyses after the administration of acute and sub-chronic drugs. Results: Of the 84 genes involved in GPCR-related signal transduction, the expression of six, βarrestin1, βarrestin2, galanin receptor 2 (GalR2), dopamine receptor 2 (DRD2), metabotropic glutamate receptor 1 (mGluR1), and metabotropic glutamate receptor 5 (mGluR5), was significantly altered. Since these genes affect the levels of other signaling proteins, e.g., extracellular signal-regulated kinase 1/2 (ERK1/2), G protein-coupled receptor kinase 2 (Grk2), and G protein-gated inwardly rectifying potassium 3 (Girk3), we determined their levels in PFC using Western blot. Most of the observed changes occurred after acute treatment with 0.3 mg/kg CLZ. We showed that acute treatment with CLZ at a lower dose significantly increased βarrestin1 and ERK1/2. KET treatment induced the upregulation of βarrestin1. Joint administration of these drugs had no effect on the βarrestin1 level. Conclusion: The screening kit we used to study the expression of GPCR-related signal transduction allowed us to select several important genes affected by CLZ. However, the obtained data do not explain the mechanism of action of CLZ that is responsible for reversing KET-induced cognitive impairment.
Dissection of the Regulatory Elements of the Complex Expression Pattern of Puckered, a Dual-Specificity JNK Phosphatase
Authors: Karkali Katerina , Martin-Blanco Enrique
Published: November 2021

For developmental processes, we know most of the gene networks controlling specific cell responses. We still have to determine how these networks cooperate and how signals become integrated. The JNK pathway is one of the key elements modulating cellular responses during development. Yet, we still know little about how the core components of the pathway interact with additional regulators or how this network modulates cellular responses in the whole organism in homeostasis or during tissue morphogenesis. We have performed a promoter analysis, searching for potential regulatory sequences of puckered (puc) and identified different specific enhancers directing gene expression in different tissues and at different developmental times. Remarkably, some of these domains respond to the JNK activity, but not all. Altogether, these analyses show that puc expression regulation is very complex and that JNK activities participate in non-previously known processes during the development of Drosophila.
Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice
Authors: Shuster Benjamin , Casserly Ryan , Lipford Erika , Olszewski Rafal , Milon Béatrice , Viechweg Shaun , Davidson Kanisa , Enoch Jennifer , McMurray Mark , Rutherford Mark A. , Ohlemiller Kevin K. , Hoa Michael , Depireux Didier A. , Mong Jessica A. , Hertzano Ronna
Published: November 2021

Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17β-estradiol (E2), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E2-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E2-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E2-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E2-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.
Role of Salivary MicroRNA and Cytokines in the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma
Authors: Manzano-Moreno Francisco Javier , Costela-Ruiz Victor J. , García-Recio Enrique , Olmedo-Gaya Maria Victoria , Ruiz Concepción , Reyes-Botella Candelaria
Published: November 2021

Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignant tumor worldwide. An early diagnosis can have a major positive impact on its prognosis. Human saliva contains cytokines, DNA and RNA molecules, circulating cells, and derivatives of tissues and extracellular vesicles, among other factors that can serve as biomarkers. Hence, the analysis of saliva may provide useful information for the early diagnosis of OSCC for its prognosis. The objective of this review was to determine the potential usefulness of salivary biomarkers (cytokines and microRNA) to diagnose OSCC and improve its prognosis. A combination of salivary miRNA and proteomic data could allow a definitive and early diagnosis to be obtained. However, there remains a need to optimize and standardize the protocols used to quantify miRNAs.
The Evolution of Fluoroquinolone Resistance in Salmonella under Exposure to Sub-Inhibitory Concentration of Enrofloxacin
Authors: Gu Yufeng , Huang Lulu , Wu Cuirong , Huang Junhong , Hao Haihong , Yuan Zonghui , Cheng Guyue
Published: November 2021

The evolution of resistance in Salmonella to fluoroquinolones (FQs) under a broad range of sub-inhibitory concentrations (sub-MICs) has not been systematically studied. This study investigated the mechanism of resistance development in Salmonella enterica serovar Enteritidis (S. Enteritidis) under sub-MICs of 1/128×MIC to 1/2×MIC of enrofloxacin (ENR), a widely used veterinary FQ. It was shown that the resistance rate and resistance level of S. Enteritidis varied with the increase in ENR concentration and duration of selection. qRT-PCR results demonstrated that the expression of outer membrane porin (OMP) genes, ompC, ompD and ompF, were down-regulated first to rapidly adapt and develop the resistance of 4×MIC, and as the resistance level increased (≥8×MIC), the up-regulated expression of efflux pump genes, acrB, emrB amd mdfA, along with mutations in quinolone resistance-determining region (QRDR) gradually played a decisive role. Cytohubba analysis based on transcriptomic profiles demonstrated that purB, purC, purD, purF, purH, purK, purL, purM, purN and purT were the hub genes for the FQs resistance. The ‘de novo’ IMP biosynthetic process, purine ribonucleoside monophosphate biosynthetic process and purine ribonucleotide biosynthetic process were the top three biological processes screened by MCODE. This study first described the dynamics of FQ resistance evolution in Salmonella under a long-term selection of sub-MICs of ENR in vitro. In addition, this work offers greater insight into the transcriptome changes of S. Enteritidis under the selection of ENR and provides a framework for FQs resistance of Salmonella for further studies.