bluuebunny/crossref_metadata_2025 huggingface dataset:
The Evolution of Balanced Scorecard in Healthcare: A Systematic Review of Its Design, Implementation, Use, and Review
Authors: Betto Frida , Sardi Alberto , Garengo Patrizia , Sorano Enrico
Published: August 2022

During the last few years, the interest in performance measurement increased within the healthcare sector. Due to the COVID-19 pandemic, healthcare systems needed to boost performance measurement systems to become more resilient and improve their capability in monitoring key performance indicators. Since the 1990s, the Balanced Scorecard (BSC) model has been widely used among private and public organizations as it is the most adopted model to measure performance. The current paper aims at understanding the evolution of BSC in healthcare. The systematic literature review has been carried out by searching keywords according to PRISMA guidelines. By analyzing papers through one classification of BSC adoption phases, the results reveal that studies focused mainly on the BSC design process, rather than BSC implementation, use, or review. However, there is no agreement about the perspectives to be adopted in healthcare. Concerning BSC implementation and use, on one side especially leadership, culture and communication enable the BSC implementation. On the other side, monitoring and strategic decision-making are the most widespread objectives for using BSC. Concerning BSC review, however, the paper highlights a need for additional research. Finally, the paper provides further research opportunities concerning the phases suitable for implementing a BSC in healthcare.
Public Health Aspects of Climate Change Adaptation in Three Cities: A Qualitative Study
Authors: Macassa Gloria , Ribeiro Ana Isabel , Marttila Anneli , Stål Frida , Silva José Pedro , Rydback Michelle , Rashid Mamunur , Barros Henrique
Published: August 2022

Climate change presents an unprecedented public health challenge as it has a great impact on population health outcomes across the global population. The key to addressing these health challenges is adaptation carried out in cities through collaboration between institutions, including public health ones. Through semi-structured interviews (n = 16), this study investigated experiences and perceptions of what public health aspects are considered by urban and public health planners and researchers when planning climate change adaptation in the coastal cities of Söderhamn (Sweden), Porto (Portugal) and Navotas (the Philippines). Results of the thematic analysis indicated that participating stakeholders were aware of the main climate risks threatening their cities (rising water levels and flooding, extreme temperatures, and air pollution). In addition, the interviewees talked about collaboration with other sectors, including the public health sector, in implementing climate change adaptation plans. However, the inclusion of the public health sector as a partner in the process was identified in only two cities, Navotas and Porto. Furthermore, the study found that there were few aspects pertaining to public health (water and sanitation, prevention of heat-related and water-borne diseases, and prevention of the consequences associated with heat waves in vulnerable groups such as children and elderly persons) in the latest climate change adaptation plans posted on each city’s website. Moreover, participants pointed to different difficulties: insufficient financial resources, limited intersectoral collaboration for climate change adaptation, and lack of involvement of the public health sector in the adaptation processes, especially in one of the cities in which climate change adaptation was solely the responsibility of the urban planners. Studies using larger samples of stakeholders in larger cities are needed to better understand why the public health sector is still almost absent in efforts to adapt to climate change.
The Impacts of Nitrogen Pollution and Urbanization on the Carbon Dioxide Emission from Sewage-Draining River Networks
Authors: Hou Yongmei , Liu Xiaolong , Han Guilin , Bai Li , Li Jun , Wang Yusi
Published: August 2022

Carbon dioxide (CO2) emissions from river water have sparked worldwide concerns due to supersaturate CO2 levels in the majority of global rivers, while the knowledge on the associations among nitrogen pollution, urbanization, and CO2 emissions is still limited. In this study, the CO2 partial pressure (pCO2), carbon and nitrogen species, and water parameters in sewage-draining river networks were investigated. Extremely high pCO2 levels were observed in sewage and drainage river waters, such as Longfeng River, Beijing-drainage River, and Beitang-drainage River, which were approximately 4 times higher than the averaged pCO2 in worldwide rivers. Correlations of carbon/nitrogen species and pCO2 indicated that carbon dioxide in rural rivers and sewage waters primarily originated from soil aeration zones and biological processes of organic carbon/nitrogen input from drainage waters, while that in urban rivers and lakes was mainly dominated by organic matter degradation and biological respiration. Enhanced internal primary productivity played critical roles in absorbing CO2 by photosynthesis in some unsaturated pCO2 sampling sites. Additionally, higher pCO2 levels have been observed with higher NH4+-N and lower DO. CO2 fluxes in sewage waters exhibited extremely high levels compared with those of natural rivers. The results could provide implications for assessing CO2 emissions in diverse waters and fulfilling water management polices when considering water contamination under intense anthropogenic activities.
Analyzing the Interaction between Clinical, Neurophysiological and Psychological Outcomes Underlying Chronic Plantar Heel Pain: A Network Analysis Study
Authors: Ríos-León Marta , Valera-Calero Juan Antonio , Ortega-Santiago Ricardo , Varol Umut , Fernández-de-las-Peñas César , Plaza-Manzano Gustavo
Published: August 2022

Plantar heel pain (PHP) is one of the most common foot pain conditions in adults. Several biological and psychological factors could be involved in chronic PHP in a complex matrix. However, reciprocal interactions between these factors are unknown. The aim of the present study was to use network analysis to quantify potential multivariate relationships between pain-related, function, clinical, mechanosensitivity, psychological, and health-related variables in individuals with PHP. Demographic (age, gender), pain-related (pain intensity), function, clinical (myofascial trigger points [TrPs]), mechanosensitivity (pressure pain thresholds), psychological (Beck Depression Inventory), and health-related variables (EQ-5D-5L) were collected in 81 PHP patients. Network connectivity analysis was conducted to quantify the adjusted correlations between the modeled variables and to assess their centrality indices. The connectivity network showed local associations between pain-related variables, foot function, and mechanosensitivity. Additionally, associations between quality of life, depression, and pain-related variables were found, while TrPs was associated with quality of life and mechanosensitivity. The node with the highest strength centrality was the worst pain intensity, while mechanosensitivity and worst pain intensity showed the highest closeness and betweenness centrality. This is the first study to apply network modeling to understand the connections between pain-related, function, clinical, mechanosensitivity, psychological, and health-related variables in PHP. The role of pain severity and mechanosensitivity is highlighted and supported by the network. Thus, this study reveals potential factors that could be the target in the management of PHP, promoting a comprehensive and effective therapeutic approach.
Comparison of Secular Trends in Esophageal Cancer Mortality in China and Japan during 1990–2019: An Age-Period-Cohort Analysis
Authors: Li Ruiqing , Sun Jinyi , Wang Tong , Huang Lihong , Wang Shuwen , Sun Panglin , Yu Chuanhua
Published: August 2022

Esophageal cancer is a prevalent and often fatal malignancy all over the world, with China and Japan bearing a disproportionately high burden. Consequently, we explored and compared the long-term changes in esophageal cancer mortality in China and Japan from 1990 to 2019 to see if there were any etiological clues. From 1990 to 2019, data on mortality in China and Japan were gathered from the Global Burden of Disease Study 2019 (GBD 2019). The age-period-cohort (APC) model was utilized to evaluate the effects of age, period, and cohort. Between 1990 and 2019, the age-standardized mortality rates (ASMRs) for esophageal cancer fell in both nations, with China showing a tremendous reduction after 2005. The overall net drifts per year were more impressive in China (−5.22% [95% CI, −5.77 to −4.68] for females, −1.98% [−2.22 to −1.74] for males) than in Japan (−0.50% [−0.91 to −0.08] for females, −1.86% [−2.12 to −1.59] for males), and the local drift values in both countries were less than zero in all age groups for both sexes. The longitudinal age curves of esophageal cancer mortality increased as age advances and the sex disparity gradually exacerbates with age. The period and cohort effects were uncovered to have similar declining patterns for both sexes in both nations; however, the improvement of cohort effects for China’s younger generation has stagnated. The ASMRs, period effects, and cohort effects have decreased for both countries and sexes over the 1990–2019 period. The decline in cohort effects for China’s younger generation has plateaued, possibly due to the rising rates of smoking and obesity among Chinese youngsters. Comprehensive population-level treatments aimed at smoking cessation, obesity prevention, and gastrointestinal endoscopy screening should be carried out immediately, particularly for men and older birth cohorts at a higher risk of esophageal cancer.
Is Platinum a Real Store of Wealth?
Authors: Vochozka Marek , Bláhová Andrea , Rowland Zuzana
Published: August 2022

The research goal is to determine whether platinum can be seen as a good investment. For this purpose, content analysis of documents and deep learning neural networks with recurrent neural network were used. The results show that it pays for a koruna investor (a person holding their wealth in Czech koruna) to preserve their wealth physically in the form of a precious metal—specifically, platinum. The research confirms that platinum is a store of value but also a koruna investor’s wealth multiplier. This can be due to its rare occurrence in nature, but also to its unique use in manufacturing. A research limitation is the period for which the data were used. The finding that platinum is a store of value, as well as a wealth multiplier, can thus be concretized when using the data for a five-year period. It shall also be added that no turbulent changes are anticipated (such as interruption of platinum supply, unexpected government regulation of trade, etc.).
Role of ROX1, SKN7, and YAP6 Stress Transcription Factors in the Production of Secondary Metabolites in Xanthophyllomyces dendrorhous
Authors: Martínez-Moya Pilar , Campusano Sebastián , Sepúlveda Dionisia , Paradela Alberto , Alcaíno Jennifer , Baeza Marcelo , Cifuentes Víctor
Published: August 2022

Xanthophyllomyces dendrorhous is a natural source of astaxanthin and mycosporines. This yeast has been isolated from high and cold mountainous regions around the world, and the production of these secondary metabolites may be a survival strategy against the stress conditions present in its environment. Biosynthesis of astaxanthin is regulated by catabolic repression through the interaction between MIG1 and corepressor CYC8–TUP1. To evaluate the role of the stress-associated transcription factors SKN7, ROX1, and YAP6, we employed an omic and phenotypic approach. Null mutants were constructed and grown in two fermentable carbon sources. The yeast proteome and transcriptome were quantified by iTRAQ and RNA-seq, respectively. The total carotenoid, sterol, and mycosporine contents were determined and compared to the wild-type strain. Each mutant strain showed significant metabolic changes compared to the wild type that were correlated to its phenotype. In a metabolic context, the principal pathways affected were glycolysis/gluconeogenesis, the pentose phosphate (PP) pathway, and the citrate (TCA) cycle. Additionally, fatty acid synthesis was affected. The absence of ROX1 generated a significant decline in carotenoid production. In contrast, a rise in mycosporine and sterol synthesis was shown in the absence of the transcription factors SKN7 and YAP6, respectively.
E4orf1 Prevents Progression of Fatty Liver Disease in Mice on High Fat Diet
Authors: Afruza Rownock , Dhurandhar Nikhil V. , Hegde Vijay
Published: August 2022

Non-alcoholic fatty liver disease (NAFLD) covers a broad spectrum of liver diseases ranging from steatosis to cirrhosis. There are limited data on prevention of hepatic steatosis or its progression to liver disease. Here, we tested if either transgenic (Tg) doxycycline-induced expression in adipose tissue of E4orf1 (E4), an adenoviral protein, or dietary fat restriction attenuated hepatic steatosis or its progression in mice. Twelve to fourteen-week-old TgE4 mice (E4 group) and control mice were exposed to a 60% (Kcal) high fat diet (HFD) for 20 weeks, while another group of mice on HFD for 10 weeks were switched to a chow diet (chow group) for another 10 weeks. Glycemic control was determined at weeks 10 and 20. Tissues were collected for gene and protein analysis at sacrifice. Compared to control, diet reversal significantly reduced body weight in the chow group, whereas E4 expression attenuated weight gain, despite HFD. E4 mice evinced significantly improved glucose clearance, lower endogenous insulin secretion, reduced serum triglycerides, attenuated hepatic steatosis and inflammation. Interestingly, in spite of weight loss and lower liver fat, chow mice showed significant upregulation of hepatic genes involved in lipid metabolism. Despite HFD, E4 prevents hepatic lipid accumulation and progression of hepatic steatosis, while diet reversal maintains hepatic health, but is unable to improve molecular changes.
Microwave Radiation and the Brain: Mechanisms, Current Status, and Future Prospects
Authors: Mumtaz Sohail , Rana Juie Nahushkumar , Choi Eun Ha , Han Ihn
Published: August 2022

Modern humanity wades daily through various radiations, resulting in frequent exposure and causing potentially important biological effects. Among them, the brain is the organ most sensitive to electromagnetic radiation (EMR) exposure. Despite numerous correlated studies, critical unknowns surround the different parameters used, including operational frequency, power density (i.e., energy dose), and irradiation time that could permit reproducibility and comparability between analyses. Furthermore, the interactions of EMR with biological systems and its precise mechanisms remain poorly characterized. In this review, recent approaches examining the effects of microwave radiations on the brain, specifically learning and memory capabilities, as well as the mechanisms of brain dysfunction with exposure as reported in the literature, are analyzed and interpreted to provide prospective views for future research directed at this important and novel medical technology for developing preventive and therapeutic strategies on brain degeneration caused by microwave radiation. Additionally, the interactions of microwaves with biological systems and possible mechanisms are presented in this review. Treatment with natural products and safe techniques to reduce harm to organs have become essential components of daily life, and some promising techniques to treat cancers and their radioprotective effects are summarized as well. This review can serve as a platform for researchers to understand the mechanism and interactions of microwave radiation with biological systems, the present scenario, and prospects for future studies on the effect of microwaves on the brain.
Enhancer-Mediated Formation of Nuclear Transcription Initiation Domains
Authors: Gibbons Matthew D. , Fang Yu , Spicola Austin P. , Linzer Niko , Jones Stephen M. , Johnson Breanna R. , Li Lu , Xie Mingyi , Bungert Jörg
Published: August 2022

Enhancers in higher eukaryotes and upstream activating sequences (UASs) in yeast have been shown to recruit components of the RNA polymerase II (Pol II) transcription machinery. At least a fraction of Pol II recruited to enhancers in higher eukaryotes initiates transcription and generates enhancer RNA (eRNA). In contrast, UASs in yeast do not recruit transcription factor TFIIH, which is required for transcription initiation. For both yeast and mammalian systems, it was shown that Pol II is transferred from enhancers/UASs to promoters. We propose that there are two modes of Pol II recruitment to enhancers in higher eukaryotes. Pol II complexes that generate eRNAs are recruited via TFIID, similar to mechanisms operating at promoters. This may involve the binding of TFIID to acetylated nucleosomes flanking the enhancer. The resulting eRNA, together with enhancer-bound transcription factors and co-regulators, contributes to the second mode of Pol II recruitment through the formation of a transcription initiation domain. Transient contacts with target genes, governed by proteins and RNA, lead to the transfer of Pol II from enhancers to TFIID-bound promoters.
Deletion of Macrophage-Specific Glycogen Synthase Kinase (GSK)-3α Promotes Atherosclerotic Regression in Ldlr−/− Mice
Authors: Patel Sarvatit , Mastrogiacomo Lauren , Fulmer Madison , Shi Yuanyuan , Werstuck Geoff H.
Published: August 2022

Recent evidence from our laboratory suggests that impeding ER stress–GSK3α/β signaling attenuates the progression and development of atherosclerosis in mouse model systems. The objective of this study was to determine if the tissue-specific genetic ablation of GSK3α/β could promote the regression of established atherosclerotic plaques. Five-week-old low-density lipoprotein receptor knockout (Ldlr−/−) mice were fed a high-fat diet for 16 weeks to promote atherosclerotic lesion formation. Mice were then injected with tamoxifen to induce macrophage-specific GSK3α/β deletion, and switched to standard diet for 12 weeks. All mice were sacrificed at 33 weeks of age and atherosclerosis was quantified and characterized. Female mice with induced macrophage-specific GSK3α deficiency, but not GSK3β deficiency, had reduced plaque volume (~25%) and necrosis (~40%) in the aortic sinus, compared to baseline mice. Atherosclerosis was also significantly reduced (~60%) in the descending aorta. Macrophage-specific GSK3α-deficient mice showed indications of increased plaque stability and reduced inflammation in plaques, as well as increased CCR7 and ABCA1 expression in lesional macrophages, consistent with regressive plaques. These results suggest that GSK3α ablation promotes atherosclerotic plaque regression and identify GSK3α as a potential target for the development of new therapies to treat existing atherosclerotic lesions in patients with cardiovascular disease.
Isolation and Characterization of an LBD Transcription Factor CsLBD39 from Tea Plant (Camellia sinensis) and Its Roles in Modulating Nitrate Content by Regulating Nitrate-Metabolism-Related Genes
Authors: Teng Rui-Min , Yang Ni , Li Jing-Wen , Liu Chun-Fang , Chen Yi , Li Tong , Wang Ya-Hui , Xiong Ai-Sheng , Zhuang Jing
Published: August 2022

Nitrate nitrogen is an important nitrogen source for tea plants’ growth and development. LBD transcription factors play important roles in response to the presence of nitrate in plants. The functional study of LBD transcription factors in tea plants remains limited. In this study, the LBD family gene CsLBD39 was isolated and characterized from tea plants. Sequence analysis indicated that CsLBD39 contained a highly conserved CX2CX6CX3CX domain. The phylogenetic tree assay showed that CsLBD39 belonged to class II subfamily of the LBD family. CsLBD39 was highly expressed in flowers and root; we determined that its expression could be induced by nitrate treatment. The CsLBD39 protein was located in the nucleus and has transcriptional activation activity in yeast. Compared with the wild type, overexpression of CsLBD39 gene in Arabidopsis resulted in smaller rosettes, shorter main roots, reduced lateral roots and lower plant weights. The nitrate content and the expression levels of genes related to nitrate transport and regulation were decreased in transgenic Arabidopsis hosting CsLBD39 gene. Compared with the wild type, CsLBD39 overexpression in transgenic Arabidopsis had smaller cell structure of leaves, shorter diameter of stem cross section, and slender and compact cell of stem longitudinal section. Under KNO3 treatment, the contents of nitrate, anthocyanins, and chlorophyll in leaves, and the content of nitrate in roots of Arabidopsis overexpressing CsLBD39 were reduced, the expression levels of nitrate transport and regulation related genes were decreased. The results revealed that CsLBD39 may be involved in nitrate signal transduction in tea plants as a negative regulator and laid the groundwork for future studies into the mechanism of nitrate response.
Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice
Authors: Kim Ji-Won , Yang Young-Mo , Kwon Eun-Young , Choi Ji-Young
Published: August 2022

Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT.
Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease
Authors: Raghunathan Rekha , Turajane Kathleen , Wong Li Chin
Published: August 2022

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics is an unbiased quantitative tool capable of the high throughput quantitation of thousands of proteins from minimal sample volumes. We review recent proteomic studies in human tissues, plasma, cerebrospinal fluid (CSF), and exosomes in ALS and PD that identify proteins with potential utility as biomarkers. Further, we review disease-related post-translational modifications in key proteins TDP43 in ALS and α-synuclein in PD studies, which may serve as biomarkers. We compare relative and absolute quantitative proteomic approaches in key biomarker studies in ALS and PD and discuss recent technological advancements which may identify suitable biomarkers for the early-diagnosis treatment efficacy of these diseases.
ATP-Binding Cassette G Transporters and Their Multiple Roles Especially for Male Fertility in Arabidopsis, Rice and Maize
Authors: Wu Suowei , Fang Chaowei , Li Ziwen , Wang Yanbo , Pan Shuangshuang , Wu Yuru , An Xueli , Long Yan , Wan Xiangyuan
Published: August 2022

ATP-binding cassette subfamily G (ABCG) transporters are extensive in plants and play essential roles in various processes influencing plant fitness, but the research progress varies greatly among Arabidopsis, rice and maize. In this review, we present a consolidated nomenclature and characterization of the whole 51 ABCG transporters in maize, perform a phylogenetic analysis and classification of the ABCG subfamily members in maize, and summarize the latest research advances in ABCG transporters for these three plant species. ABCG transporters are involved in diverse processes in Arabidopsis and rice, such as anther and pollen development, vegetative and female organ development, abiotic and biotic stress response, and phytohormone transport, which provide useful clues for the functional investigation of ABCG transporters in maize. Finally, we discuss the current challenges and future perspectives for the identification and mechanism analysis of substrates for plant ABCG transporters. This review provides a basic framework for functional research and the potential application of ABCG transporters in multiple plants, including maize.
Chrono-Aerobic Exercise Optimizes Metabolic State in DB/DB Mice through CLOCK–Mitophagy–Apoptosis
Authors: Zhang Zhe , Li Xi , Zhang Jun , Du Jing , Zhang Qiang , Ge Zhe , Ding Shuzhe
Published: August 2022

Although the benefits of aerobic exercise on obesity and type 2 diabetes are well-documented, the pathogenesis of type 2 diabetes and the intervention mechanism of exercise remain ambiguous. The correlation between mitochondrial quality and metabolic diseases has been identified. Disruption of the central or peripheral molecular clock can also induce chronic metabolic diseases. In addition, the interactive effects of the molecular clock and mitochondrial quality have attracted extensive attention in recent years. Exercise and a high-fat diet have been considered external factors that may change the molecular clock and metabolic state. Therefore, we utilized a DB/DB (BSK.Cg-Dock7m +/+ Leprdb/JNju) mouse model to explore the effect of chrono-aerobic exercise on the metabolic state of type 2 diabetic mice and the effect of timing exercise as an external rhythm cue on liver molecular clock-mitochondrial quality. We found that two differently timed exercises reduced the blood glucose and serum cholesterol levels in DB/DB mice, and compared with night exercise (8:00 p.m., the active period of mice), morning exercise (8:00 a.m., the sleeping period of mice) significantly improved the insulin sensitivity in DB/DB mice. In contrast, type 2 diabetes mellitus (T2DM) increased the expression of CLOCK and impaired the mitochondrial quality (mitochondrial networks, OPA1, Fis1, and mitophagy), as well as induced apoptosis. Both morning and night exercise ameliorated impaired mitochondrial quality and apoptosis induced by diabetes. However, compared with morning exercise, night exercise not only decreased the protein expression of CLOCK but also decreased excessive apoptosis. In addition, the expression of CLOCK was negatively correlated with the expression of OPA1 and Fis1. In summary, our research suggests that morning exercise is more beneficial for increasing insulin sensitivity and promoting glucose transport in T2DM, whereas night exercise may improve lipid infiltration and mitochondrial abnormalities through CLOCK–mitophagy–apoptosis in the liver, thereby downregulating glucose and lipid disorders. In addition, CLOCK-OPA1/Fis1–mitophagy might be novel targets for T2DM treatment.
Crop Root Responses to Drought Stress: Molecular Mechanisms, Nutrient Regulations, and Interactions with Microorganisms in the Rhizosphere
Authors: Kang Jian , Peng Yunfeng , Xu Weifeng
Published: August 2022

Roots play important roles in determining crop development under drought. Under such conditions, the molecular mechanisms underlying key responses and interactions with the rhizosphere in crop roots remain limited compared with model species such as Arabidopsis. This article reviews the molecular mechanisms of the morphological, physiological, and metabolic responses to drought stress in typical crop roots, along with the regulation of soil nutrients and microorganisms to these responses. Firstly, we summarize how root growth and architecture are regulated by essential genes and metabolic processes under water-deficit conditions. Secondly, the functions of the fundamental plant hormone, abscisic acid, on regulating crop root growth under drought are highlighted. Moreover, we discuss how the responses of crop roots to altered water status are impacted by nutrients, and vice versa. Finally, this article explores current knowledge of the feedback between plant and soil microbial responses to drought and the manipulation of rhizosphere microbes for improving the resilience of crop production to water stress. Through these insights, we conclude that to gain a more comprehensive understanding of drought adaption mechanisms in crop roots, future studies should have a network view, linking key responses of roots with environmental factors.
Sex as Biological Variable in Cardiac Mitochondrial Bioenergetic Responses to Acute Stress
Authors: Scott Susan R. , Singh Kanhaiya , Yu Qing , Sen Chandan K. , Wang Meijing
Published: August 2022

Cardiac dysfunction/damage following trauma, shock, sepsis, and ischemia impacts clinical outcomes. Acute inflammation and oxidative stress triggered by these injuries impair mitochondria, which are critical to maintaining cardiac function. Despite sex dimorphisms in consequences of these injuries, it is unclear whether mitochondrial bioenergetic responses to inflammation/oxidative stress are sex-dependent. We hypothesized that sex disparity in mitochondrial bioenergetics following TNFα or H2O2 exposure is responsible for reported sex differences in cardiac damage/dysfunction. Methods and Results: Cardiomyocytes isolated from age-matched adult male and female mice were subjected to 1 h TNFα or H2O2 challenge, followed by detection of mitochondrial respiration capacity using the Seahorse XF96 Cell Mito Stress Test. Mitochondrial membrane potential (ΔΨm) was analyzed using JC-1 in TNFα-challenged cardiomyocytes. We found that cardiomyocytes isolated from female mice displayed a better mitochondrial bioenergetic response to TNFα or H2O2 than those isolated from male mice did. TNFα decreased ΔΨm in cardiomyocytes isolated from males but not from females. 17β-estradiol (E2) treatment improved mitochondrial metabolic function in cardiomyocytes from male mice subjected to TNFα or H2O2 treatment. Conclusions: Cardiomyocyte mitochondria from female mice were more resistant to acute stress than those from males. The female sex hormone E2 treatment protected cardiac mitochondria against acute inflammatory and oxidative stress.
Harmicens, Novel Harmine and Ferrocene Hybrids: Design, Synthesis and Biological Activity
Authors: Poje Goran , Marinović Marina , Pavić Kristina , Mioč Marija , Kralj Marijeta , de Carvalho Lais Pessanha , Held Jana , Perković Ivana , Rajić Zrinka
Published: August 2022

Cancer and malaria are both global health threats. Due to the increase in the resistance to the known drugs, research on new active substances is a priority. Here, we present the design, synthesis, and evaluation of the biological activity of harmicens, hybrids composed of covalently bound harmine/β-carboline and ferrocene scaffolds. Structural diversity was achieved by varying the type and length of the linker between the β-carboline ring and ferrocene, as well as its position on the β-carboline ring. Triazole-type harmicens were prepared using Cu(I)-catalyzed azide-alkyne cycloaddition, while the synthesis of amide-type harmicens was carried out by applying a standard coupling reaction. The results of in vitro biological assays showed that the harmicens exerted moderate antiplasmodial activity against the erythrocytic stage of P. falciparum (IC50 in submicromolar and low micromolar range) and significant and selective antiproliferative activity against the MCF-7 and HCT116 cell lines (IC50 in the single-digit micromolar range, SI > 5.9). Cell localization experiments showed different localizations of nonselective harmicene 36 and HCT116-selective compound 28, which clearly entered the nucleus. A cell cycle analysis revealed that selective harmicene 28 had already induced G1 cell cycle arrest after 24 h, followed by G2/M arrest with a concomitant drastic reduction in the percentage of cells in the S phase, whereas the effect of nonselective compound 36 on the cell cycle was much less pronounced, which agreed with their different localizations within the cell.
Essential Roles of the Histone Demethylase KDM4C in Renal Development and Acute Kidney Injury
Authors: Pan Heng-Chih , Chen Yau-Hung , Fang Wei-Ching , Wu Vin-Cent , Sun Chiao-Yin
Published: August 2022

Background: Lysine demethylase 4C (KDM4C) is a nuclear protein that is essential for histone modification and acts as an important regulator of several transcription factors. Previous studies have shown that KDM4C may also play a role in mediating stress responses. The purpose of this study was to examine the roles of KDM4C in kidney development and acute kidney injury (AKI). Methods: The effect of KDM4C on kidney development was assessed by comparing the kidney phenotype between 96 zebrafish embryos treated with kdm4c-morpholino oligonucleotide and 96 untreated zebrafish embryos. We further examined whether KDM4C is essential for maintaining cell survival in AKI. Cultured human renal tubular cells were used for the in vitro study. Wild-type and Kdm4c knockout mice (C57BL/6NTac-Kdm4ctm1a(KOMP)Wtsi) were divided into a sham group and model group, and then subjected to ischemic reperfusion kidney injury (IRI-AKI). Blood samples and kidneys were collected at different time points (day 3, day 7, day 14, and day 28) and were processed for in vivo studies (n = 8 in each group). Results: Kdm4c knockdown significantly decreased zebrafish embryo survival and impaired kidney development. The in vitro study showed that KDM4C inhibition by JIB04 significantly increased cellular apoptosis under oxidative stress conditions. KDM4C knockdown cells had impaired autophagy function under stress conditions. The IRI-AKI mice study showed that KDM4C protein levels dynamically changed and were significantly correlated with HIF-1α levels in AKI. Kdm4c−/− mice had significantly more severe renal impairment and increased kidney fibrosis than the wild-type mice. Cytokine array results also indicated that the kidneys of Kdm4c−/− mice had increased inflammation in AKI compared with the wild-type mice. Further RNA sequence analysis revealed that KDM4C may regulate transcription factors related to mitochondrial dynamics and function. Conclusions: Our study suggests that KDM4C may play a critical role in regulating mitochondria, which is related to a protective effect on maintaining cell survival in AKI.
Cryobanking European Mink (Mustela lutreola) Mesenchymal Stem Cells and Oocytes
Authors: Calle Alexandra , Ramírez Miguel Ángel
Published: August 2022

The European mink (Mustela lutreola) is one of Europe’s most endangered species, and it is on the brink of extinction in the Iberian Peninsula. The species’ precarious situation requires the application of new ex situ conservation methodologies that complement the existing ex situ and in situ conservation measures. Here, we report for the first time the establishment of a biobank for European mink mesenchymal stem cells (emMSC) and oocytes from specimens found dead in the Iberian Peninsula, either free or in captivity. New emMSC lines were isolated from different tissues: bone marrow (emBM-MSC), oral mucosa (emOM-MSc), dermal skin (emDS-MSC), oviduct (emO-MSc), endometrium (emE-MSC), testicular (emT-MSC), and adipose tissue from two different adipose depots: subcutaneous (emSCA-MSC) and ovarian (emOA-MSC). All eight emMSC lines showed plastic adhesion, a detectable expression of characteristic markers of MSCs, and, when cultured under osteogenic and adipogenic conditions, differentiation capacity to these lineages. Additionally, we were able to keep 227 Cumulus-oocyte complexes (COCs) in the biobank, 97 of which are grade I or II. The European mink MSC and oocyte biobank will allow for the conservation of the species’ genetic variability, the application of assisted reproduction techniques, and the development of in vitro models for studying the molecular mechanisms of infectious diseases that threaten the species’ precarious situation.
Expression of TXNRD1, HSPA4L and ATP1B1 Genes Associated with the Freezability of Boar Sperm
Authors: Mańkowska Anna , Gilun Przemysław , Zasiadczyk Łukasz , Sobiech Przemysław , Fraser Leyland
Published: August 2022

Cryopreservation is associated with increased oxidative stress, which is responsible for sperm damage. We analyzed the effect of cryopreservation on mRNA and protein expression of thioredoxin reductase 1 (TXNRD1), heat shock protein family A (HSP 70) member 4 like (HSPA4L) and sodium/potassium-transporting ATPase subunit beta-1 (ATP1B1) genes in boar sperm with different freezability. Boars were classified as having good and poor semen freezability (GSF and PSF, respectively), according to the assessment of post-thaw sperm motility. Total RNA was isolated from fresh pre-freeze (PF) and frozen-thawed (FT) sperm from five boars of the GSF and PSF groups, respectively. Quantification of TXNRD1, HSPA4L and ATP1B1 gene expression was performed by RT-qPCR analysis. Proteins extracted from sperm were subjected to Western blotting and SDS-PAGE analyses. Poor freezability ejaculates were characterized by significantly higher relative mRNA expression levels of TXNRD1 and HSPA4L in FT sperm compared with the fresh PF sperm. Furthermore, the relative mRNA expression level of ATP1B1 was significantly higher in the fresh PF sperm of the GSF group. Western blotting analysis revealed significantly higher relative expression of TXNRD1 protein in the fresh PF sperm of the GSF group, while HSPA4L protein expression was markedly increased in FT sperm of the PSF group. Electrophoretic and densitometric analyses revealed a higher number of proteins in the fresh PF and FT sperm of the PSF and GSF groups, respectively. The results of this study indicate that ATP1B1 mRNA expression in the fresh PF sperm is a promising cryotolerance marker, while the variations of TXNRD1 and HSPA4L protein expression in the fresh PF or FT sperm provide useful information that may help to elucidate their biological significance in cryo-damage.
Neural Networks Reveal the Impact of the Vibrational Dynamics in the Prediction of the Long-Time Mobility of Molecular Glassformers
Authors: Tripodo Antonio , Cordella Gianfranco , Puosi Francesco , Malvaldi Marco , Leporini Dino
Published: August 2022

Two neural networks (NN) are designed to predict the particle mobility of a molecular glassformer in a wide time window ranging from vibrational dynamics to structural relaxation. Both NNs are trained by information concerning the local structure of the environment surrounding a given particle. The only difference in the learning procedure is the inclusion (NN A) or not (NN B) of the information provided by the fast, vibrational dynamics and quantified by the local Debye–Waller factor. It is found that, for a given temperature, the prediction provided by the NN A is more accurate, a finding which is tentatively ascribed to better account of the bond reorientation. Both NNs are found to exhibit impressive and rather comparable performance to predict the four-point susceptibility χ4(t) at τα, a measure of the dynamic heterogeneity of the system.
Red Blood Cell-Derived Microparticles Exert No Cancer Promoting Effects on Colorectal Cancer Cells In Vitro
Authors: Fischer Dania , Thies Fabian , Awad Omar , Brat Camilla , Meybohm Patrick , Baer Patrick C. , Müller Markus M. , Urbschat Anja , Maier Thorsten J. , Zacharowski Kai , Roos Jessica
Published: August 2022

The biomedical consequences of allogeneic blood transfusions and the possible pathomechanisms of transfusion-related morbidity and mortality are still not entirely understood. In retrospective studies, allogeneic transfusion was associated with increased rates of cancer recurrence, metastasis and death in patients with colorectal cancer. However, correlation does not imply causation. The purpose of this study was to elucidate this empirical observation further in order to address insecurity among patients and clinicians. We focused on the in vitro effect of microparticles derived from red blood cell units (RMPs). We incubated different colon carcinoma cells with RMPs and analyzed their effects on growth, invasion, migration and tumor marker expression. Furthermore, effects on Wnt, Akt and ERK signaling were explored. Our results show RMPs do not seem to affect functional and phenotypic characteristics of different colon carcinoma cells and did not induce or inhibit Wnt, Akt or ERK signaling, albeit in cell culture models lacking tumor microenvironment. Allogeneic blood transfusions are associated with poor prognosis, but RMPs do not seem to convey tumor-enhancing effects. Most likely, the circumstances that necessitate the transfusion, such as preoperative anemia, tumor stage, perioperative blood loss and extension of surgery, take center stage.
Identification and Validation of TRIM25 as a Glucose Metabolism Regulator in Prostate Cancer
Authors: Li Chao , Dou Peng , Lu Xin , Guan Pengwei , Lin Zhikun , Zhou Yanyan , Lu Xin , Lin Xiaohui , Xu Guowang
Published: August 2022

Prostate cancer (PCa) malignant progression is accompanied with the reprogramming of glucose metabolism. However, the genes involved in the regulation of glucose metabolism in PCa are not fully understood. Here, we propose a new method, DMRG, which constructs a weighted differential network (W-K-DN) to define the important metabolism-related genes. Based on biological knowledge and prostate cancer transcriptome data, a tripartite motif-containing 25 (TRIM25) was defined using DMRG; TRIM25 was involved in the regulation of glucose metabolism, which was verified by overexpressing or knocking down TRIM25 in PCa cell lines. Differential expression analysis of TCA cycle enzymes revealed that TRIM25 regulated isocitrate dehydrogenase 1 (IDH1) and fumarate hydratase (FH) expression. Moreover, a protein–RNA interaction network of TRIM25 revealed that TRIM25 interacted with RNA-binding proteins, including DExH-box helicase 9 and DEAD-box helicase 5, to play a role in regulating the RNA processing of metabolic enzymes, including IDH1 and FH. Furthermore, TRIM25 expression level was found to be positively correlated with Gleason scores in PCa patient tissues. In conclusion, this study provides a new method to define genes influencing tumor progression, and sheds light on the role of the defined TRIM25 in regulating glucose metabolism and promoting PCa malignancy.
Statins in High Cardiovascular Risk Patients: Do Comorbidities and Characteristics Matter?
Authors: Rossini Enrica , Biscetti Federico , Rando Maria Margherita , Nardella Elisabetta , Cecchini Andrea Leonardo , Nicolazzi Maria Anna , Covino Marcello , Gasbarrini Antonio , Massetti Massimo , Flex Andrea
Published: August 2022

Atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality are decreasing in high-income countries, but ASCVD remains the leading cause of morbidity and mortality in high-income countries. Over the past few decades, major risk factors for ASCVD, including LDL cholesterol (LDL-C), have been identified. Statins are the drug of choice for patients at increased risk of ASCVD and remain one of the most commonly used and effective drugs for reducing LDL cholesterol and the risk of mortality and coronary artery disease in high-risk groups. Unfortunately, doctors tend to under-prescribe or under-dose these drugs, mostly out of fear of side effects. The latest guidelines emphasize that treatment intensity should increase with increasing cardiovascular risk and that the decision to initiate intervention remains a matter of individual consideration and shared decision-making. The purpose of this review was to analyze the indications for initiation or continuation of statin therapy in different categories of patient with high cardiovascular risk, considering their complexity and comorbidities in order to personalize treatment.
Repellent Activity of Clove Essential Oil Volatiles and Development of Nanofiber-Based Dispensers against Pear Psyllids (Hemiptera: Psyllidae)
Authors: Czarnobai De Jorge Bruna , Hummel Hans E. , Gross Jürgen
Published: August 2022

Pear psyllids are the main vectors of the pathogen ‘Candidatus Phytoplasma pyri’ causing pear decline. Based on earlier reports, we tested the behavioral activity of the major synthetic compounds of clove essential oil (eugenol, eugenyl acetate, and β-caryophyllene) against Cacopsylla pyri and C. pyricola. Of six mixtures tested in olfactometer assays, a formulation consisting of three specific compounds (M6 mixture) demonstrated a repellent effect on both psyllid species. In addition, this formulation masked the odor of the host Pyrus communis cv. Williams Christ, disturbing the host finding ability of C. pyri. Electrospun fibers were produced with biocompatible polymers poly(ε-caprolactone), cellulose acetate, and solvents formic acid and acetic acid, loaded with the repellent mixture to test their efficacy as dispensers of repellents in laboratory and field. The fibers produced were repellent to C. pyri and effectively masked the odors of pear plants in olfactometer tests. In a pear orchard, we compared the captures of pear psyllids in green-colored attractive traps treated with nanofibers loaded with M6 mixture or unloaded nanofibers (blank). The result showed no differences in the captures of C. pyri between treatments. The release rates of volatiles from the fibers were evaluated weekly over 56 days. The fibers were able to entrap the major compound of the M6 mixture, eugenol, but the release rates were significantly reduced after 21 days. Our results suggest that biodegradable dispensers could be produced with electrospinning, but further improvements are necessary to use repellents as a management tool for pear psyllids in the field.