bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Quality of Reporting to China’s National TB Surveillance Systems
Authors: Li Tao , Yang Lijia , Smith-Jeffcoat Sarah E. , Wang Alice , Guo Hui , Chen Wei , Du Xin , Zhang Hui
Published: February 2021

(1) Background: The reliability of disease surveillance may be restricted by sensitivity or ability to capture all disease. Objective: To quantify under-reporting and concordance of recording persons with tuberculosis (TB) in national TB surveillance systems: the Infectious Disease Reporting System (IDRS) and Tuberculosis Information Management System (TBIMS). (2) Methods: This retrospective review includes 4698 patients identified in 2016 in China. County staff linked TB patients identified from facility-specific health and laboratory information systems with records in IDRS and TBIMS. Under-reporting was calculated, and timeliness, concordance, accuracy, and completeness were analyzed. Multivariable logistic regression was used to examine factors associated with under-reporting. (3) Results: We found that 505 (10.7%) patients were missing within IDRS and 1451 (30.9%) patients were missing within TBIMS. Of 171 patient records reviewed in IDRS and 170 patient records in TBIMS, 12.3% and 6.5% were found to be untimely, and 10.7% and 7.1% were found to have an inconsistent home address. The risk of under-reporting to both IDRS and TBIMS was greatest at tertiary health facilities and among non-residents; the risk of under-reporting to TBIMS was greatest with patients aged 65 or older and with extrapulmonary TB (EPTB). (4) Conclusions: It is important to improve the reporting and recording of TB patients. Local TB programs that focus on training, and mentoring high-burden hospitals, facilities that cater to EPTB, and migrant patients may improve reporting and recording.
Considerations for Pediatric Retirement from Athletics Following Repetitive Concussive Traumatic Brain Injury: Incorporating the Right to an Open Future
Authors: Gibb Tyler S. , Redinger Kathryn , Fealko Casey , Parikh Sonia
Published: February 2021

Guidance regarding the decision to remove an adolescent from athletic competition immediately following an acute concussive injury and the safe return of play in the short term is widely accepted and supported by clinical evidence, local institutional policies, and state and federal laws. There is considerably less guidance regarding the decision to permanently retire an adolescent athlete for medical reasons due to concussive injuries. In this article, we discuss the clinical and non-clinical considerations that should guide clinicians in discussions regarding the adolescent athlete’s permanent retirement by emphasizing the ethical obligation to protect the child’s right to an open future as possibly determinative in otherwise ambiguous cases.
Organisational Commitment in Healthcare Systems: A Bibliometric Analysis
Authors: de las Heras-Rosas Carlos , Herrera Juan , Rodríguez-Fernández Mercedes
Published: February 2021

Business organisations are subject to high pressure to ensure their sustainability and competitiveness. In the case of healthcare institutions, moreover, there are unique characteristics where human resource management is of vital importance. The workforce in these institutions is at a critical moment where the shortages of qualified staff, burnout, or job dissatisfaction represent some of the detrimental aspects for the performance of the organisation, and more importantly, they diminish the quality of patient care. The promotion of organisational commitment is positioned as one of the tools that organisations have to face this problem. This paper aims to increase knowledge about research trends that analyse organisational commitment in healthcare institutions. To this end, using bibliometric techniques, a sample of 448 publications on this subject from journals indexed in Web of Science between 1992 and 2020 is analysed. The results obtained suggest a growing interest in this subject and a visible concern for the management of human resources in these institutions. Research has focussed mainly on organisational factors related to nursing staff. The most analysed topics have been job satisfaction, the implications of stress and high turnover, burnout syndrome, and the possibility of leaving the job. On the other hand, issues emerged such as empowerment in the workplace and others related to organisational management such as quality of service or performance. Finally, there is a lack of research that deals more deeply with other groups working in health centres, such as doctors or administrative staff. There is also a need for further development in the analysis of the implications of the ideological psychological contract in relation to normative organisational commitment in the field of healthcare organisations. The contribution of this work focusses on expanding knowledge about commitment in healthcare organisations and creating points of support for future research as well as helping healthcare managers make decisions in HR management.
Cardiovascular Autonomic Control, Sleep and Health Related Quality of Life in Systemic Sclerosis
Authors: Carandina Angelica , Bellocchi Chiara , Dias Rodrigues Gabriel , Beretta Lorenzo , Montano Nicola , Tobaldini Eleonora
Published: February 2021

Chronic pain and dysautonomic symptoms deteriorate Systemic sclerosis (SSc) patients’ health-related quality of life with serious repercussions on social life and even on sleep. Heart Rate Variability (HRV) analysis can identify cardiovascular autonomic control impairment in subclinical condition. The aim of the present observational cross-sectional study was to assess the relationship between dysautonomic symptoms, quality of life status and cardiovascular autonomic profile. ECG and respiration were recorded at rest in 20 SSc patients. HRV analysis was performed using two different approaches: Linear spectral analysis and non-linear symbolic analysis. Pain was evaluated using the Numeric Rating Scale (NRS) and 3 questionnaires were administered for the evaluation of sleep quality (PSQI), mood tone (PHQ-9) and disability (HAQ). We found that sleep impairment was related to sympathetic predominance at rest measured as low-frequency/high-frequency ratio (LF/HF) (r = 0.48 and p = 0.033); poorer sleep quality was related to higher pain values (r = 0.48 and p = 0.034) and depressive symptoms (r = 0.82 and p < 0.01); higher pain scores were related to higher cardiovascular vagal modulation and higher disability indexes (r = 0.47 and p = 0.038 & r = 0.55 and p = 0.012, respectively). In conclusion dysautonomia and chronic pain showed a severe impact on sleep quality and disability with a consequent worsening of depressive symptom in our cohort of SSc patients.
Dynamic Adjustment Model of the Water Rights Trading Price Based on Water Resource Scarcity Value Analysis
Authors: Wu Xiao-yuan , Wu Feng-ping , Li Fang , Xu Xia
Published: February 2021

The formation of the water rights trading price is an important part of the water rights trading system. In order to continuously and dynamically reflect the social–economic development changes and water resource scarcity, herein, we discuss the dynamic adjustment of the water rights trading price from the perspective of water resource scarcity value analysis. First, we constructed the water resource scarcity evaluation index system from the four dimensions of the water resource natural endowment, the water resource supply, the water resource demand, and the water environment, and then we constructed the water resource scarcity index calculation model of the transferor, the transferee, and the comprehensive water resource scarcity index calculation model of both parties of the trading. Second, by analyzing the 30 comparable water rights trading cases in China since 2016, we established the response function of the water rights trading price to the water resource scarcity index, and then we analyzed the impact mechanism of the water resource scarcity index on the water rights trading price. Third, based on the two factors of “the water resource scarcity value” and “the capital time value,” we constructed a dynamic price adjustment model of water rights trading for different adjustment factors, so as to adjust the water rights trading price scientifically. Finally, we took the water rights trading in Helan County (Helan) of Ningxia Hui Autonomous Region (Ningxia) as an example. The research shows that: (1) During the trading period of water rights in Helan, the water resource scarcity index rises, and the water rights trading price should be increased year-by-year. Additionally, there are certain differences in the water rights trading price changes with the adjustment of different elements. Among them, considering the adjustment of “the water resource scarcity value” element, the water rights trading price of Helan should be increased from 1.0940 to 2.8574 CNY/m³ during the water rights trading period; (2) there are differences in the water rights trading cost under different payment modes, among which the annual payment mode increased the most, i.e., from 2.7350 × 108 to 7.4500 × 108 CNY. This study suggests exerting a regulating effect of the water scarcity value on the water rights trading price, so as to promote the construction of a more equitable and long-term water rights trading market.
Comparative Assessment of Female Sexual Function Following Transobturator Midurethral Sling for Stress Urinary Incontinence
Authors: Zalewski Maciej , Kołodyńska Gabriela , Zalewska Agata , Andrzejewski Waldemar
Published: February 2021

Urinary incontinence (UI) is a significant social problem. According to the World Health Organization, UI affects as much as 30% of premenopausal women and 60% of postmenopausal women. Urinary incontinence can lead to certain problems that negatively affect a woman’s sex life. They result from the fact that certain processes take place in the body during intercourse. As a result of orgasm, the intra-abdominal pressure increases, which in women with urinary incontinence can cause an uncontrolled leakage of urine. The discomfort that this causes, in turn, lowers sexual attractiveness, as well as causes embarrassment. The study involved 50 patients hospitalized in the period from February to May 2019 at the Gynecology Department of the Independent Public Healthcare Center of the Ministry of the Interior and Administration in Wrocław. All patients underwent surgical treatment of stress urinary incontinence using the transobturator tape (TOT) method. To assess sexuality, the international standardized Female Sexual Function Index (FSFI) questionnaire. Analysis of the results obtained from the FSFI questionnaire shows that the operation significantly affects the reduction in pain sensation during intercourse, a reduction in the sensation of sexual arousal, and a worsening vaginal wetness. Stress urinary incontinence significantly affects women’s sex life.
COVID-19 Pandemic Lockdown and Religious Mediatization of Social Sustainability. A Case Study of Romania
Authors: Tudor Mihaela Alexandra , Filimon Benea Anamaria , Bratosin Stefan
Published: February 2021

This article presents an empirical study on the institutional audiovisual mediatization of social sustainability made by the eighteen religious denominations officially recognized in Romania during the period of the COVID-19 pandemic onset. Research is undertaken based on the mediatization theories. Specifically, it highlights and discusses the conditions for producing the meaning of social sustainability as a result of religious mediatization during the months of March, April and May 2020, a period with strong religious connotations since it involved the dates of the major annual feasts celebrated by the three majority monotheistic religions, i.e., the Christian Easter, the Muslim Ramadan and the Jewish Passover. As a result, we noticed that the production of meaning in terms of social sustainability was simultaneously anchored in the accumulation of four contextual “social worlds”: (a) that of social transformation induced by mediatization, (b) that of the COVID-19 pandemic, a crisis that is neither social, economic, or environmental, but with consequences on the three levels of reality mentioned above, (c) that of spirituality during the time of the great monotheistic religious feasts and (d) that of the national culture of Romania, statistically the most religious country of the European Union.
Moral Reasoning about Aggressive Behavior in Relation to Type of Aggression, Age and Gender in South Korean Pupils
Authors: Lee Seung-Ha , Smith Peter K. , Monks Claire P.
Published: February 2021

Studies of moral reasoning in relation to aggressive behaviors have paid limited attention to different types of aggression, and have mainly been conducted in Western societies. We describe findings from a study of 157 children, aged 6 or 11 years, from two schools in South Korea. Using a cartoon scenario methodology, we assessed moral reasoning about eight types of aggression: verbal, physical individual, physical group, social exclusion, rumor spreading, breaking one’s belongings, sending a nasty text via mobile phone, and sending a nasty message/email via computer. Four aspects of moral reasoning were assessed: moral judgment, harmfulness, reason for judgment, and causal responsibility. Many significant differences by type of aggression were found, especially for social exclusion (seen as less wrong and harmful, and more the victim’s responsibility), physical group aggression (seen as more wrong or harmful, and a matter of fairness, especially in older children and boys), and cyber aggression (seen more as the aggressor’s responsibility). Older children gave more reasons based on welfare, and fewer “don’t know” responses for reasons and attributions. Gender differences were relatively few, but girls did make more use of welfare in the moral reasoning domain. Findings are discussed in relation to previous research and the cultural context in South Korea.
Relations between Air Quality and Covid-19 Lockdown Measures in Valencia, Spain
Authors: Donzelli Gabriele , Cioni Lorenzo , Cancellieri Mariagrazia , Llopis-Morales Agustin , Morales-Suárez-Varela María
Published: February 2021

The set of measures to contain the diffusion of COVID-19 instituted by the European governments gave an unparalleled opportunity to improve our understanding of the transport and industrial sectors’ contribution to urban air pollution. The purpose of this study was to assess the impacts of the lockdown measures on air quality and pollutant emissions in Valencia, Spain. For this reason, we determined if there was a significant difference in the concentration levels of different particulate matter (PM) sizes, PM10, PM2.5, and NOx, NO2, NO, and O3, between the period of restrictions in 2020 and the same period in 2019. Our findings indicated that PM pollutant levels during the lockdown period were significantly different from the same period of the previous year, even if there is variability in the different local areas. The highest variations reduction in the PM10 and PM2.5 levels were observed for the València Centre, València Avd Francia, and València Pista de Silla (all of the urban traffic type) in which there was a reduction of 58%–42%, 56%–53%, and 60%–41% respectively. Moreover, consistent with recent studies, we observed a significant reduction in nitric oxide levels in all the air monitoring stations. In all seven monitoring stations, it was observed, in 2020, NOx, NO2, and NO concentrations decreased by 48.5%–49.8%–46.2%, 62.1%–67.4%–45.7%, 37.4%–35.7%–35.3%, 60.7%–67.7%–47.1%, 65.5%–65.8%–63.5%, 60.0%–64.5%–41.3%, and 60.4%–61.6%–52.5%, respectively. Lastly, overall O3 levels decreased during the lockdown period, although this phenomenon was more closely related to weather conditions. Overall, no significant differences were observed between the meteorological conditions in 2019 and 2020. Our findings suggest that further studies on the effect of human activities on air quality are needed and encourage the adoption of a holistic approach to improve urban air quality.
Moderating Roles of Social Support in the Association between Hope and Life Satisfaction among Ethnic Minority College Students in China
Authors: Chen Xin , Ma Yonghong , Wu Ruilin , Liu Xia
Published: February 2021

Ethnic minority college students in China are Chinese students who migrate from ethnic minority-dominant areas to Han-dominant areas to attend college. Acculturative stress would lead to maladjustments for ethnic minority college students in China, such as low levels of life satisfaction. To help improve the life satisfaction of these students, this study adopted resilience theory to explore the beneficial effects of hope and social support and their influencing mechanisms. The participants included 362 ethnic minority college students in Beijing, China, and a questionnaire method was used. The results indicated that Han social support had a promotive effect on life satisfaction, while hope did not have a promotive effect on life satisfaction. Moreover, Han social support moderated the relationship between hope and life satisfaction. Specifically, the effect of hope on life satisfaction was stronger under the condition of a higher level of Han social support compared with those under a lower level of Han social support. In conclusion, Han social support can play a promotive effect individually, while hope only affected life satisfaction when a high level of Han social support existed. Han social support should be strengthened to improve the life satisfaction among ethnic minority college students in China.
Population Preparedness for Disasters and Extreme Weather Events as a Predictor of Building a Resilient Society: The Slovak Republic
Authors: Titko Michal , Ristvej Jozef , Zamiar Zenon
Published: February 2021

The current increase and severity of the natural disasters whose effects on the public health are likely to be even more extreme and complex, requires enhancing and developing the disaster preparedness on the population level. In order to be able to do so, it is inevitable and determinative to know the factors that affect people’s preparedness on the population level. Therefore, the objective of this article is to present the results from assessing the factors related to the population preparedness for the disasters on a sample of citizens living from the Slovak Republic. Our research is based on the exploration of the questionnaire survey’ results aimed at investigating the preparedness and preventive proactive behaviour of the population against the disasters. The search for the initiators of such a behaviour and assessment of the influence of various aspects (e.g., the respondents’ experience with disasters, their vulnerability to disasters, the risk awareness, the perception of the disaster risks in the changing environment, etc.) on the respondents’ behaviour against disasters is the main part of the article and is supported by the statistical analysis. The results of the survey suggest that the disaster risk awareness and overall disaster preparedness level is rather poor and the population is inactive. The proactive behaviour of the respondents against the disasters is partially affected by some of their personality and socio-economic characteristics, especially the younger respondents currently incline more to adopting the protective measures. In addition, other aspects, e.g., the negative experience with the disasters in the past influence the preparedness. However, the impacts must have been relatively serious for the proactive behaviour to be influenced. The influences of other aspects as well as the possible methods for improving the disaster preparedness and the possibilities of increasing the resilience of the population as a whole are also discussed in this article.
A Note on Universal Bilinear Portfolios
Authors: Garivaltis Alex
Published: February 2021

This note provides a neat and enjoyable expansion and application of the magnificent Ordentlich-Cover theory of “universal portfolios”. I generalize Cover’s benchmark of the best constant-rebalanced portfolio (or 1-linear trading strategy) in hindsight by considering the best bilinear trading strategy determined in hindsight for the realized sequence of asset prices. A bilinear trading strategy is a mini two-period active strategy whose final capital growth factor is linear separately in each period’s gross return vector for the asset market. I apply Thomas Cover’s ingenious performance-weighted averaging technique to construct a universal bilinear portfolio that is guaranteed (uniformly for all possible market behavior) to compound its money at the same asymptotic rate as the best bilinear trading strategy in hindsight. Thus, the universal bilinear portfolio asymptotically dominates the original (1-linear) universal portfolio in the same technical sense that Cover’s universal portfolios asymptotically dominate all constant-rebalanced portfolios and all buy-and-hold strategies. In fact, like so many Russian dolls, one can get carried away and use these ideas to construct an endless hierarchy of ever more dominant H-linear universal portfolios.
LONP1 Regulates Mitochondrial Accumulations of HMGB1 and Caspase-3 in CA1 and PV Neurons Following Status Epilepticus
Authors: Kim Ji-Eun , Park Hana , Kim Tae-Hyun , Kang Tae-Cheon
Published: February 2021

Lon protease 1 (LONP1) is a highly conserved serine peptidase that plays an important role in the protein quality control system in mammalian mitochondria. LONP1 catalyzes the degradation of oxidized, dysfunctional, and misfolded matrix proteins inside mitochondria and regulates mitochondrial gene expression and genome integrity. Therefore, LONP1 is up-regulated and suppresses cell death in response to oxidative stress, heat shock, and nutrient starvation. On the other hand, translocation of high mobility group box 1 (HMGB1) and active caspase-3 into mitochondria is involved in apoptosis of parvalbumin (PV) cells (one of the GABAergic interneurons) and necrosis of CA1 neurons in the rat hippocampus, respectively, following status epilepticus (SE). In the present study, we investigated whether LONP1 may improve neuronal viability to prevent or ameliorate translocation of active caspase-3 and HMGB1 in mitochondria within PV and CA1 neurons. Following SE, LONP1 expression was up-regulated in mitochondria of PV and CA1 neurons. LONP1 knockdown deteriorated SE-induced neuronal death with mitochondrial accumulation of active caspase-3 and HMGB1 in PV cells and CA1 neurons, respectively. LONP1 knockdown did not affect the aberrant mitochondrial machinery induced by SE. Therefore, our findings suggest, for the first time, that LONP1 may contribute to the alleviation of mitochondrial overloads of active caspase-3 and HMGB1, and the maintenance of neuronal viability against SE.
Contribution of Particle-Induced Lysosomal Membrane Hyperpolarization to Lysosomal Membrane Permeabilization
Authors: Ziglari Tahereh , Wang Zifan , Holian Andrij
Published: February 2021

Lysosomal membrane permeabilization (LMP) has been proposed to precede nanoparticle-induced macrophage injury and NLRP3 inflammasome activation; however, the underlying mechanism(s) of LMP is unknown. We propose that nanoparticle-induced lysosomal hyperpolarization triggers LMP. In this study, a rapid non-invasive method was used to measure changes in lysosomal membrane potential of murine alveolar macrophages (AM) in response to a series of nanoparticles (ZnO, TiO2, and CeO2). Crystalline SiO2 (micron-sized) was used as a positive control. Changes in cytosolic potassium were measured using Asante potassium green 2. The results demonstrated that ZnO or SiO2 hyperpolarized the lysosomal membrane and decreased cytosolic potassium, suggesting increased lysosome permeability to potassium. Time-course experiments revealed that lysosomal hyperpolarization was an early event leading to LMP, NLRP3 activation, and cell death. In contrast, TiO2- or valinomycin-treated AM did not cause LMP unless high doses led to lysosomal hyperpolarization. Neither lysosomal hyperpolarization nor LMP was observed in CeO2-treated AM. These results suggested that a threshold of lysosomal membrane potential must be exceeded to cause LMP. Furthermore, inhibition of lysosomal hyperpolarization with Bafilomycin A1 blocked LMP and NLRP3 activation, suggesting a causal relation between lysosomal hyperpolarization and LMP.
Involvement of Cholinergic, Adrenergic, and Glutamatergic Network Modulation with Cognitive Dysfunction in Alzheimer’s Disease
Authors: Cheng Yu-Jung , Lin Chieh-Hsin , Lane Hsien-Yuan
Published: February 2021

Alzheimer’s disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. The number of AD cases has been rapidly growing worldwide. Several the related etiological hypotheses include atypical amyloid β (Aβ) deposition, neurofibrillary tangles of tau proteins inside neurons, disturbed neurotransmission, inflammation, and oxidative stress. During AD progression, aberrations in neurotransmission cause cognitive decline—the main symptom of AD. Here, we review the aberrant neurotransmission systems, including cholinergic, adrenergic, and glutamatergic network, and the interactions among these systems as they pertain to AD. We also discuss the key role of N-methyl-d-aspartate receptor (NMDAR) dysfunction in AD-associated cognitive impairment. Furthermore, we summarize the results of recent studies indicating that increasing glutamatergic neurotransmission through the alteration of NMDARs shows potential for treating cognitive decline in mild cognitive impairment or early stage AD. Future studies on the long-term efficiency of NMDA-enhancing strategies in the treatment of AD are warranted.
Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis
Authors: Wei Hao , Wang Ji-Yang
Published: February 2021

Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.
Vascular Inflammation and Dysfunction in Lupus-Prone Mice-IL-6 as Mediator of Disease Initiation
Authors: Marczynski Paul , Meineck Myriam , Xia Ning , Li Huige , Kraus Daniel , Roth Wilfried , Möckel Tamara , Boedecker Simone , Schwarting Andreas , Weinmann-Menke Julia
Published: February 2021

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease and patients are under an increased risk for cardiovascular (CV) events and mortality. The increased CV risk for patients with SLE seems to be caused by a premature and accelerated atherosclerosis, attributable to lupus-specific risk factors (i.e., increased systemic inflammation, altered immune status), apart from traditional CV risk factors. To date, there is no established experimental model to explore the pathogenesis of this increased CV risk in SLE patients. Methods: Here we investigated whether MRL-Faslpr mice, which develop an SLE-like phenotype, may serve as a model to study lupus-mediated vascular disease. Therefore, MRL-Faslpr, MRL-++, and previously generated Il6−/− MRL-Faslpr mice were used to evaluate vascular changes and possible mechanisms of vascular dysfunction and damage. Results: Contrary to MRL-++ control mice, lupus-prone MRL-Faslpr mice exhibited a pronounced vascular and perivascular leukocytic infiltration in various organs; expression of pro-inflammatory cytokines in the aorta and kidney was augmented; and intima-media thickness of the aorta was increased. IL-6 deficiency reversed these changes and restored aortic relaxation. Conclusion: Our findings demonstrate that the MRL-Faslpr mouse model is an excellent tool to investigate vascular damage in SLE mice. Moreover, IL-6 promotes vascular inflammation and damage and could potentially be a therapeutic target for the treatment of accelerated arteriosclerosis in SLE.
The Effects of Naringenin on miRNA-mRNA Profiles in HepaRG Cells
Authors: Fan Weiyang , Shi Rui , Guan Minyi , Chen Pan , Wu Hao , Su Weiwei , Wang Yonggang , Li Peibo
Published: February 2021

Naringenin, a natural flavonoid widely found in citrus fruits, has been reported to possess anti-oxidant, anti-inflammatory, and hepatoprotective properties as a natural dietary supplement. However, the regulatory mechanism of naringenin in human liver remains unclear. In the present study, messenger RNA sequencing (mRNA-seq), microRNA sequencing (miRNA-seq), and real-time qPCR were used to distinguish the expression differences between control and naringenin-treated HepaRG cells. We obtained 1037 differentially expressed mRNAs and 234 miRNAs. According to the target prediction and integration analysis in silico, we found 20 potential miRNA-mRNA pairs involved in liver metabolism. This study is the first to provide a perspective of miRNA–mRNA interactions in the regulation of naringenin via an integrated analysis of mRNA-seq and miRNA-seq in HepaRG cells, which further characterizes the nutraceutical value of naringenin as a food additive.
Dictyostelium Differentiation-Inducing Factor-1 Promotes Glucose Uptake, at Least in Part, via an AMPK-Dependent Pathway in Mouse 3T3-L1 Cells
Authors: Kubohara Yuzuru , Homma Yoshimi , Shibata Hiroshi , Oshima Yoshiteru , Kikuchi Haruhisa
Published: February 2021

Differentiation-inducing factor-1 (DIF-1) is a chlorinated alkylphenone (a polyketide) found in the cellular slime mold Dictyostelium discoideum. DIF-1 and its derivative, DIF-1(3M) promote glucose consumption in vitro in mammalian cells and in vivo in diabetic rats; they are expected to be the leading antiobesity and antidiabetes compounds. In this study, we investigated the mechanisms underlying the actions of DIF-1 and DIF-1(3M). In isolated mouse liver mitochondria, these compounds at 2–20 μM promoted oxygen consumption in a dose-dependent manner, suggesting that they act as mitochondrial uncouplers, whereas CP-DIF-1 (another derivative of DIF-1) at 10–20 μM had no effect. In confluent mouse 3T3-L1 fibroblasts, DIF-1 and DIF-1(3M) but not CP-DIF-1 induced phosphorylation (and therefore activation) of AMP kinase (AMPK) and promoted glucose consumption and metabolism. The DIF-induced glucose consumption was reduced by compound C (an AMPK inhibitor) or AMPK knock down. These data suggest that DIF-1 and DIF-1(3M) promote glucose uptake, at least in part, via an AMPK-dependent pathway in 3T3-L1 cells, whereas cellular metabolome analysis revealed that DIF-1 and DIF-1(3M) may act differently at least in part.
Diagnostic Significance of Selected Serum Inflammatory Markers in Women with Advanced Endometriosis
Authors: Kokot Izabela , Piwowar Agnieszka , Jędryka Marcin , Sołkiewicz Katarzyna , Kratz Ewa Maria
Published: February 2021

Endometriosis is a gynecological disease, the pathogenesis of which seems to be directly associated with inflammatory processes. Serum concentrations of IL-1β, IL-6, hs-CRP, IgG, YKL 40 and PRL, in comparison to the well-known CA 125 levels, were studied with the aim of identifying an additional noninvasive inflammatory marker or set of markers characteristic for endometriosis. The study group included 43 women with endometriosis (E), 35 women with benign gynecological disorders but without endometriosis (NE, non-endometriosis) as a comparative group, and a control group consisting of 18 healthy subjects (C). The serum concentrations of IL-1β, IL-6, hs-CRP, YKL-40, PRL and CA 125 were significantly higher in the E group (median values: 0.41 pg/mL, 2.42 pg/mL, 2.33 mg/L, 79.30 ng/mL, 21.88 ng/mL and 68.00 U/mL, respectively) than in the control group (median values: 0.21 pg/mL, 0.98 pg/mL, 0.52 mg/L, 49.77 ng/mL, 12.08 ng/mL and 12.20 U/mL respectively), with the significance of p = 0.011, p < 0.001, p = 0.028, p = 0.005, p < 0.001 and p < 0.001, respectively. The IgG concentrations were significantly lower in the endometriosis group (median value: 1061.21 mg/dL) as compared to healthy women (median value: 1210.50 mg/dL; p = 0.025). Significant differences in concentrations of IL-6 (p = 0.040), hs-CRP (p = 0.007) and CA 125 (p < 0.001) were observed in stage III vs. stage IV of endometriosis. Significantly higher concentrations of IL-6 (p = 0.010), hs-CRP (p = 0.037) and PRL (p < 0.001) were observed in the NE group vs. the control group. Only CA 125 concentrations were significantly higher in endometriosis patients as compared to the non-endometriosis group (p < 0.001). The proposed panel of inflammatory markers, especially IL-6, PRL and CA 125, may become a useful tool to identify women with advanced endometriosis who could qualify for treatment.
Kalkitoxin Reduces Osteoclast Formation and Resorption and Protects against Inflammatory Bone Loss
Authors: Li Liang , Yang Ming , Shrestha Saroj Kumar , Kim Hyoungsu , Gerwick William H. , Soh Yunjo
Published: February 2021

Osteoclasts, bone-specified multinucleated cells produced by monocyte/macrophage, are involved in numerous bone destructive diseases such as arthritis, osteoporosis, and inflammation-induced bone loss. The osteoclast differentiation mechanism suggests a possible strategy to treat bone diseases. In this regard, we recently examined the in vivo impact of kalkitoxin (KT), a marine product obtained from the marine cyanobacterium Moorena producens (previously Lyngbya majuscula), on the macrophage colony-stimulating factor (M-CSF) and on the receptor activator of nuclear factor κB ligand (RANKL)-stimulated in vitro osteoclastogenesis and inflammation-mediated bone loss. We have now examined the molecular mechanism of KT in greater detail. KT decreased RANKL-induced bone marrow-derived macrophages (BMMs) tartrate-resistant acid phosphatase (TRAP)-multinucleated cells at a late stage. Likewise, KT suppressed RANKL-induced pit area and actin ring formation in BMM cells. Additionally, KT inhibited several RANKL-induced genes such as cathepsin K, matrix metalloproteinase (MMP-9), TRAP, and dendritic cell-specific transmembrane protein (DC-STAMP). In line with these results, RANKL stimulated both genes and protein expression of c-Fos and nuclear factor of activated T cells (NFATc1), and this was also suppressed by KT. Moreover, KT markedly decreased RANKL-induced p-ERK1/2 and p-JNK pathways at different time points. As a result, KT prevented inflammatory bone loss in mice, such as bone mineral density (BMD) and osteoclast differentiation markers. These experiments demonstrated that KT markedly inhibited osteoclast formation and inflammatory bone loss through NFATc1 and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, KT may have potential as a treatment for destructive bone diseases.
Opportunities and Challenges in Tunneling Nanotubes Research: How Far from Clinical Application?
Authors: Han Xiaoning , Wang Xiang
Published: February 2021

Tunneling nanotubes (TNTs) are recognized long membrane nanotubes connecting distance cells. In the last decade, growing evidence has shown that these subcellular structures mediate the specific transfer of cellular materials, pathogens, and electrical signals between cells. As intercellular bridges, they play a unique role in embryonic development, collective cell migration, injured cell recovery, cancer treatment resistance, and pathogen propagation. Although TNTs have been considered as potential drug targets for treatment, there is still a long way to go to translate the research findings into clinical practice. Herein, we emphasize the heterogeneous nature of TNTs by systemically summarizing the current knowledge on their morphology, structure, and biogenesis in different types of cells. Furthermore, we address the communication efficiency and biological outcomes of TNT-dependent transport related to diseases. Finally, we discuss the opportunities and challenges of TNTs as an exciting therapeutic approach by focusing on the development of efficient and safe drugs targeting TNTs.
Renal Tubular Epithelial TRPA1 Acts as An Oxidative Stress Sensor to Mediate Ischemia-Reperfusion-Induced Kidney Injury through MAPKs/NF-κB Signaling
Authors: Wu Chung-Kuan , Wu Chia-Lin , Lee Tzong-Shyuan , Kou Yu Ru , Tarng Der-Cherng
Published: February 2021

Oxidative stress and inflammation play important roles in the pathophysiology of acute kidney injury (AKI). Transient receptor potential ankyrin 1 (TRPA1) is a Ca2+-permeable ion channel that is sensitive to reactive oxygen species (ROS). The role of TRPA1 in AKI remains unclear. In this study, we used human and animal studies to assess the role of renal TRPA1 in AKI and to explore the regulatory mechanism of renal TRPA1 in inflammation via in vitro experiments. TRPA1 expression increased in the renal tubular epithelia of patients with AKI. The severity of tubular injury correlated well with tubular TRPA1 or 8-hydroxy-2′-deoxyguanosine expression. In an animal model, renal ischemia-reperfusion injury (IR) increased tubular TRPA1 expression in wild-type (WT) mice. Trpa1−/− mice displayed less IR-induced tubular injury, oxidative stress, inflammation, and dysfunction in kidneys compared with WT mice. In the in vitro model, TRPA1 expression increased in renal tubular cells under hypoxia-reoxygenation injury (H/R) conditions. We demonstrated that H/R evoked a ROS-dependent TRPA1 activation, which elevated intracellular Ca2+ level, increased NADPH oxidase activity, activated MAPK/NF-κB signaling, and increased IL-8. Renal tubular TRPA1 may serve as an oxidative stress sensor and a crucial regulator in the activation of signaling pathways and promote the subsequent transcriptional regulation of IL-8. These actions might be evident in mice with IR or patients with AKI.
Some New Methodological and Conceptual Aspects of the “Acid Growth Theory” for the Auxin Action in Maize (Zea mays L.) Coleoptile Segments: Do Acid- and Auxin-Induced Rapid Growth Differ in Their Mechanisms?
Authors: Polak Małgorzata , Karcz Waldemar
Published: February 2021

Two arguments against the “acid growth theory” of auxin-induced growth were re-examined. First, the lack of a correlation between the IAA-induced growth and medium acidification, which is mainly due to the cuticle, which is a barrier for proton diffusion. Second, acid- and the IAA-induced growth are additive processes, which means that acid and the IAA act via different mechanisms. Here, growth, medium pH, and membrane potential (in some experiments) were simultaneously measured using non-abraded and non-peeled segments but with the incubation medium having access to their lumen. Using such an approach significantly enhances both the IAA-induced growth and proton extrusion (similar to that of abraded segments). Staining the cuticle on the outer and inner epidermis of the coleoptile segments showed that the cuticle architecture differs on both sides of the segments. The dose-response curves for the IAA-induced growth and proton extrusion were bell-shaped with the maximum at 10−4 M over 10 h. The kinetics of the IAA-induced hyperpolarisation was similar to that of the rapid phase of the IAA-induced growth. It is also proposed that the K+/H+ co-transporters are involved in acid-induced growth and that the combined effect of the K+ channels and K+/ H+ co-transporters is responsible for the IAA-induced growth. These findings support the “acid growth theory” of auxin action.
SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking
Authors: Amatya Bibhas , Lee Hewang , Asico Laureano D. , Konkalmatt Prasad , Armando Ines , Felder Robin A. , Jose Pedro A.
Published: February 2021

The SNX-PXA-RGS-PXC subfamily of sorting nexins (SNXs) belongs to the superfamily of SNX proteins. SNXs are characterized by the presence of a common phox-homology (PX) domain, along with other functional domains that play versatile roles in cellular signaling and membrane trafficking. In addition to the PX domain, the SNX-PXA-RGS-PXC subfamily, except for SNX19, contains a unique RGS (regulators of G protein signaling) domain that serves as GTPase activating proteins (GAPs), which accelerates GTP hydrolysis on the G protein α subunit, resulting in termination of G protein-coupled receptor (GPCR) signaling. Moreover, the PX domain selectively interacts with phosphatidylinositol-3-phosphate and other phosphoinositides found in endosomal membranes, while also associating with various intracellular proteins. Although SNX19 lacks an RGS domain, all members of the SNX-PXA-RGS-PXC subfamily serve as dual regulators of receptor cargo signaling and endosomal trafficking. This review discusses the known and proposed functions of the SNX-PXA-RGS-PXC subfamily and how it participates in receptor signaling (both GPCR and non-GPCR) and endosomal-based membrane trafficking. Furthermore, we discuss the difference of this subfamily of SNXs from other subfamilies, such as SNX-BAR nexins (Bin-Amphiphysin-Rvs) that are associated with retromer or other retrieval complexes for the regulation of receptor signaling and membrane trafficking. Emerging evidence has shown that the dysregulation and malfunction of this subfamily of sorting nexins lead to various pathophysiological processes and disorders, including hypertension.
Teneurins: Role in Cancer and Potential Role as Diagnostic Biomarkers and Targets for Therapy
Authors: Peppino Giulia , Ruiu Roberto , Arigoni Maddalena , Riccardo Federica , Iacoviello Antonella , Barutello Giuseppina , Quaglino Elena
Published: February 2021

Teneurins have been identified in vertebrates as four different genes (TENM1-4), coding for membrane proteins that are mainly involved in embryonic and neuronal development. Genetic studies have correlated them with various diseases, including developmental problems, neurological disorders and congenital general anosmia. There is some evidence to suggest their possible involvement in cancer initiation and progression, and drug resistance. Indeed, mutations, chromosomal alterations and the deregulation of teneurins expression have been associated with several tumor types and patient survival. However, the role of teneurins in cancer-related regulatory networks is not fully understood, as both a tumor-suppressor role and pro-tumoral functions have been proposed, depending on tumor histotype. Here, we summarize and discuss the literature data on teneurins expression and their potential role in different tumor types, while highlighting the possibility of using teneurins as novel molecular diagnostic and prognostic biomarkers and as targets for cancer treatments, such as immunotherapy, in some tumors.
Acute Tubulointerstitial Nephritis in Clinical Oncology: A Comprehensive Review
Authors: Martínez-Valenzuela Laura , Draibe Juliana , Fulladosa Xavier , Gomà Montserrat , Gómez Francisco , Antón Paula , Cruzado Josep María , Torras Joan
Published: February 2021

Acute kidney injury in patients who suffer a malignancy is a common complication. Due to its high prevalence and effective treatment, one of the most frequent causes that both oncologists and nephrologists must be aware of is acute tubulointerstitial nephritis (ATIN). ATIN is an immunomediated condition and the hallmark of the disease, with the presence of a tubulointerstitial inflammatory infiltrate in the renal parenchyma. This infiltrate is composed mainly of T lymphocytes that can be accompanied by macrophages, neutrophils, or eosinophils among other cells. One of the major causes is drug-related ATIN, and some antineoplastic treatments have been related to this condition. Worthy of note are the novel immunotherapy treatments aimed at enhancing natural immunity in order to defeat cancer cells. In the context of the immunosuppression status affecting ATIN patients, some pathogen antigens can trigger the development of the disease. Finally, hematological malignancies can also manifest in the kidney leading to ATIN, even at the debut of the disease. In this review, we aim to comprehensively examine differential diagnosis of ATIN in the setting of a neoplastic patient.
Structural Insights into Carboxylic Polyester-Degrading Enzymes and Their Functional Depolymerizing Neighbors
Authors: Leitão Ana Lúcia , Enguita Francisco J.
Published: February 2021

Esters are organic compounds widely represented in cellular structures and metabolism, originated by the condensation of organic acids and alcohols. Esterification reactions are also used by chemical industries for the production of synthetic plastic polymers. Polyester plastics are an increasing source of environmental pollution due to their intrinsic stability and limited recycling efforts. Bioremediation of polyesters based on the use of specific microbial enzymes is an interesting alternative to the current methods for the valorization of used plastics. Microbial esterases are promising catalysts for the biodegradation of polyesters that can be engineered to improve their biochemical properties. In this work, we analyzed the structure-activity relationships in microbial esterases, with special focus on the recently described plastic-degrading enzymes isolated from marine microorganisms and their structural homologs. Our analysis, based on structure-alignment, molecular docking, coevolution of amino acids and surface electrostatics determined the specific characteristics of some polyester hydrolases that could be related with their efficiency in the degradation of aromatic polyesters, such as phthalates.
Targeting Microglia-Synapse Interactions in Alzheimer’s Disease
Authors: Piccioni Gaia , Mango Dalila , Saidi Amira , Corbo Massimo , Nisticò Robert
Published: February 2021

In this review, we focus on the emerging roles of microglia in the brain, with particular attention to synaptic plasticity in health and disease. We present evidence that ramified microglia, classically believed to be “resting” (i.e., inactive), are instead strongly implicated in dynamic and plastic processes. Indeed, there is an intimate relationship between microglia and neurons at synapses which modulates activity-dependent functional and structural plasticity through the release of cytokines and growth factors. These roles are indispensable to brain development and cognitive function. Therefore, approaches aimed at maintaining the ramified state of microglia might be critical to ensure normal synaptic plasticity and cognition. On the other hand, inflammatory signals associated with Alzheimer’s disease are able to modify the ramified morphology of microglia, thus leading to synapse loss and dysfunction, as well as cognitive impairment. In this context, we highlight microglial TREM2 and CSF1R as emerging targets for disease-modifying therapy in Alzheimer’s disease (AD) and other neurodegenerative disorders.