bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Credit Constraints from Formal Financial Institutions on Rural Residents’ Health in China
Authors: Yang Fan , Jiang Yao , Paudel Krishna P.
Published: December 2020

This is the first study in China that looks at the impact of credit constraints from formal financial institutions on Chinese rural residents’ health. We use the Chinese Household Income Project (CHIP) data collected by the Annual Household Survey Office of Integration of Urban and Rural in the National Bureau of Statistics in 2014. We measure rural residents’ health status with self-rated health assessment and the number of sick days in 2013. The results obtained from using the ordered probit model show that, in general, credit constraints from formal financial institutions significantly and negatively affect the self-rated health of Chinese rural residents. When an endogeneity issue is addressed using the instrumental variable (IV) approach, this paper’s results are still robust. The results also show that the impact of credit constraints from formal financial institutions on rural residents’ self-rated health is significant in male, female, married, and unmarried sub-groups. Further, we find that credit constraints from formal financial institutions impact rural residents’ health through income and economic vulnerability. The findings have implications for preventing rural residents from falling into a health trap due to credit constraints from formal financial institutions.
The Use of Medical and Non-Medical Services by the Elderly during the SARS-CoV-2 Pandemic Differs between General and Specialist Practice: A One-Center Study in Poland
Authors: Mazurek Justyna , Biernat Karolina , Kuciel Natalia , Hap Katarzyna , Sutkowska Edyta
Published: December 2020

In Poland, there is a lack of documented data on the use of medical and non-medical services by the elderly during the SARS-CoV-2 pandemic. The FIMA questionnaire assesses the use of medical and non-medical services by the elderly. The authors compared the demand for these services during the ongoing pandemic with similar months in 2017. It was confirmed that in the group of 61 surveyed elderly people, the number of individuals who had a medical visit decreased significantly in the three-month period. In the analyzed pandemic period, patients had significantly fewer visits to their general practitioner only. The pandemic had no significant impact on the use of other medical and non-medical services analyzed by FIMA. The limitations may include the small number of respondents, the relatively short period from the beginning of the pandemic covered by the survey, and the nature of the studied patients’ diseases. Further observation of elderly patients’ access to the abovementioned services can improve the efforts of governments and caregivers in this field, which is of particular importance in the group of chronically ill elderly patients.
The Effects of Social Networks of the Older Adults with Limited Instrumental Activities of Daily Living on Unmet Medical Needs
Authors: Jang Hye-Young , Ko Young , Han Song-Yi
Published: December 2020

This study was conducted to identify the effects of social networks on unmet medical needs among older adults with limited instrumental activities of daily living (IADL) who live in a community. This study analyzed data from 2281 older adults with limited IADL from the 2017 National Survey of Older Koreans. Data were analyzed using descriptive statistics, X2 tests, t-tests, and logistic regression analysis. About 73.0% of the subjects were female and 15.8% of the subjects had experienced unmet medical needs. The predictors of unmet medical needs according to gender are as follows: annual household income, participation in social activities, and physical support for male subjects and annual household income, number of chronic diseases, living alone in a household, living with others in a household, frequency of contacting close friends, and emotional support for female subjects. The findings of this study will be utilized as a basis for establishing relevant measures to enable older adults to receive proper medical services by heightening the understanding of the gap between medical service use and the medical needs of older adults with limited IADL.
Are There Differences in Concentric Isokinetic Strength Perfor-Mance Profiles between International and Non-International Elite Soccer Players?
Authors: Śliwowski Robert , Marynowicz Jakub , Grygorowicz Monika , Wieczorek Andrzej , Jadczak Łukasz
Published: December 2020

The purpose of this study is to evaluate the differences in concentric isokinetic strength characteristics of the knee extensor and knee flexor musculature between international (IL) and non-international level (N-IL) soccer players. The second aim is to establish strength symmetry status in knee muscles for dominant (DL) and non-dominant (NDL) legs for both within and between groups. 100 male top elite soccer players (IL: n = 36, age = 27.5 ± 3.4 years and N-IL: n = 64, age = 27.7 ± 6.4 years) underwent concentric isokinetic strength tests, using a Biodex System 3 dynamometer. Results indicate that statistically significant differences between groups were noted for peak torque of hamstrings (PT-H), hamstrings/quadriceps (H/Q) ratio, and total work of hamstrings (TW-H), where mean values for the IL were similarly higher than for the N-IL group (p = 0.006, p < 0.001, and p = 0.012, respectively). Our results also showed statistically significant differences for peak torque of quadriceps (PT-Q), PT-H, total work of quadriceps (TW-Q) and TW-H between legs, where mean values noted for the DL were higher than for the NDL for both groups (p = 0.021, p < 0.001, p = 0.006, and p = 0.004, respectively). Additional results show that IL players presented more symmetrical strength between legs than N-IL. The results of this study indicate that that the greatest differences in isokinetic strength performance across players at different soccer levels relate to the hamstring muscle. As a result, systematic strength training of these muscle groups is strongly recommended.
Knowledge and Preference Towards Mode of Delivery among Pregnant Women in the United Arab Emirates: The Mutaba’ah Study
Authors: Al-Rifai Rami H. , Elbarazi Iffat , Ali Nasloon , Loney Tom , Oulhaj Abderrahim , Ahmed Luai A.
Published: December 2020

Background: The rate of cesarean section (CS) is growing in the United Arab Emirates (UAE). Pregnant women’s knowledge on the mode of delivery, factors associated with lack of adequate knowledge, and preference towards CS delivery were investigated. Methods: Baseline cross-sectional data from 1617 pregnant women who participated in the Mutaba’ah Study between September 2018 and March 2020 were analyzed. A self-administered questionnaire inquiring about demographic and maternal characteristics, ten knowledge-based statements about mode of delivery, and one question about preference towards mode of delivery was used. Knowledge on the mode of delivery was categorized into “adequate (total score 6–10)” or “lack of adequate (total score 0–5)” knowledge. Crude and multivariable models were used to identify factors associated with “lack of adequate” knowledge on the mode of delivery and factors associated with CS preference. Results: A total of 1303 (80.6%) pregnant women (mean age 30.6 ± 5.8 years) completed the questionnaire. The majority (57.1%) were ≥30 years old, in their third trimester (54.5%), and had at least one child (76.6%). In total, 20.8% underwent CS delivery in the previous pregnancy, and 9.4% preferred CS delivery for the current pregnancy. A total of 78.4% of pregnant women lacked adequate knowledge on the mode of delivery. The level of those who lacked adequate knowledge was similar across women in different pregnancy trimesters. Young women (18–24 years) (adjusted odds ratios (aOR), 3.07, 95% confidence interval (CI), 1.07–8.86) and women who had CS delivery in the previous pregnancy (aOR, 1.90, 95% CI, 1.06–3.40) were more likely to be classified with a lack of adequate knowledge. Age (aOR, 1.08, 95% CI, 1.02–1.14), employment (aOR, 1.96, 95% CI, 1.13–3.40), or previous CS delivery (aOR, 31.10, 95% CI, 17.71–55.73) were associated with a preference towards CS delivery. Conclusion: This study showed that pregnant women may not fully appreciate the health risks associated with different modes of delivery. Therefore, antenatal care appointments should include a balanced discussion on the potential benefits and harms associated with different delivery modes.
Effect of Gestational Diabetes Mellitus History on Future Pregnancy Behaviors: The Mutaba’ah Study
Authors: Ali Nasloon , Aldhaheri Aysha S. , Alneyadi Hessa H. , Alazeezi Maha H. , Al Dhaheri Sara S. , Loney Tom , Ahmed Luai A.
Published: December 2020

Gestational diabetes mellitus (GDM) increases the risk of adverse pregnancy outcomes in any pregnancy and recurrence rates are high in future pregnancies. This study aims to investigate the effect of self-reported history of previous GDM on behaviors in a future pregnancy. This is an interim cross-sectional analysis of the pregnant women who participated in the Mutaba’ah Study between May 2017 and March 2020 in the United Arab Emirates. Participants completed a baseline self-administered questionnaire on sociodemographic and pregnancy-related information about the current pregnancy and previous pregnancies. Regression models assessed the relationships between self-reported history of GDM and pre-pregnancy and pregnancy behaviors in the current pregnancy. Out of 5738 pregnant parous women included in this analysis, nearly 30% (n = 1684) reported a history of GDM in a previous pregnancy. Women with a history of previous GDM were less likely to plan their current pregnancies (adjusted odds ratio (aOR): 0.84, 95% confidence interval (CI) 0.74–0.96) and more likely to be worried about childbirth (aOR: 1.18, 95% CI 1.03–1.36). They had shorter interpregnancy intervals between their previous child and current pregnancy (aOR: 0.88, 95% CI 0.82–0.94, per SD increase). There were no significant differences between women with and without a history of GDM in supplement use, sedentary behavior, or physical activity before and during this current pregnancy. Nearly a third of parous pregnant women in this population had a history of GDM in a previous pregnancy. Pregnant women with a previous history of GDM were similar to their counterparts with no history of GDM in the adopted pre-pregnancy and prenatal health behaviors. More intensive and long-term lifestyle counseling, possibly supported by e-health and social media materials, might be required to empower pregnant women with a history of GDM. This may assist in adopting and maintaining healthy prenatal behaviors early during the pregnancy or the preconception phase to minimize the risk of GDM recurrence and the consequential adverse maternal and infant health outcomes.
Rural Community Engagement for Health Disparities Research: The Unique Role of Historically Black Colleges and Universities (HBCUs)
Authors: Taylor Lorraine C. , Watkins Charity S. , Chesterton Hannah , Kimbro K. Sean , Gerald Ruby
Published: December 2020

Reducing health disparities in rural communities of color remains a national concern. Efforts to reduce health disparities often center on community engagement, which is historically the strategy used to provide rural minority populations with support to access and utilize health information and services. Historically Black Colleges and Universities (HBCUs), with their origins derived from social injustices and discrimination, are uniquely positioned to conduct this type of engagement. We present the “Research with Care” project, a long-standing positive working relationship between North Carolina Central University (NCCU) and rural Halifax County, North Carolina, demonstrating an effective campus–community partnership. The importance of readiness to implement Community-based Participatory Research (CBPR) principles is underscored. As demonstrated by the NCCU–Halifax partnership, we recommend leveraging the positive associations of the HBCU brand identity as a method of building and sustaining meaningful relationships with rural Black communities. This underscores the role and value of HBCUs in the health disparities research arena and should be communicated and embraced.
Ancient Sturgeons Possess Effective DNA Repair Mechanisms: Influence of Model Genotoxicants on Embryo Development of Sterlet, Acipenser ruthenus
Authors: Gazo Ievgeniia , Franěk Roman , Šindelka Radek , Lebeda Ievgen , Shivaramu Sahana , Pšenička Martin , Steinbach Christoph
Published: December 2020

DNA damage caused by exogenous or endogenous factors is a common challenge for developing fish embryos. DNA damage repair (DDR) pathways help organisms minimize adverse effects of DNA alterations. In terms of DNA repair mechanisms, sturgeons represent a particularly interesting model due to their exceptional genome plasticity. Sterlet (Acipenser ruthenus) is a relatively small species of sturgeon. The goal of this study was to assess the sensitivity of sterlet embryos to model genotoxicants (camptothecin, etoposide, and benzo[a]pyrene), and to assess DDR responses. We assessed the effects of genotoxicants on embryo survival, hatching rate, DNA fragmentation, gene expression, and phosphorylation of H2AX and ATM kinase. Exposure of sterlet embryos to 1 µM benzo[a]pyrene induced low levels of DNA damage accompanied by ATM phosphorylation and xpc gene expression. Conversely, 20 µM etoposide exposure induced DNA damage without activation of known DDR pathways. Effects of 10 nM camptothecin on embryo development were stage-specific, with early stages, before gastrulation, being most sensitive. Overall, this study provides foundational information for future investigation of sterlet DDR pathways.
Extracellular Amyloid Deposits in Alzheimer’s and Creutzfeldt–Jakob Disease: Similar Behavior of Different Proteins?
Authors: Jankovska Nikol , Olejar Tomas , Matej Radoslav
Published: December 2020

Neurodegenerative diseases are characterized by the deposition of specific protein aggregates, both intracellularly and/or extracellularly, depending on the type of disease. The extracellular occurrence of tridimensional structures formed by amyloidogenic proteins defines Alzheimer’s disease, in which plaques are composed of amyloid β-protein, while in prionoses, the same term “amyloid” refers to the amyloid prion protein. In this review, we focused on providing a detailed didactic description and differentiation of diffuse, neuritic, and burnt-out plaques found in Alzheimer’s disease and kuru-like, florid, multicentric, and neuritic plaques in human transmissible spongiform encephalopathies, followed by a systematic classification of the morphological similarities and differences between the extracellular amyloid deposits in these disorders. Both conditions are accompanied by the extracellular deposits that share certain signs, including neuritic degeneration, suggesting a particular role for amyloid protein toxicity.
Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability
Authors: Gokulan Kuppan , Williams Katherine , Orr Sarah , Khare Sangeeta
Published: December 2020

Consumer products manufactured with antimicrobial silver nanoparticles (AgNPs) may affect the gastrointestinal (GI) system. The human GI-tract is complex and there are physiological and anatomical differences between human and animal models that limit comparisons between species. Thus, assessment of AgNP toxicity on the human GI-tract may require tools that allow for the examination of subtle changes in inflammatory markers and indicators of epithelial perturbation. Fresh tissues were excised from the GI-tract of human male and female subjects to evaluate the effects of AgNPs on the GI-system. The purpose of this study was to perform an assessment on the ability of the ex vivo model to evaluate changes in levels of pro-/anti-inflammatory cytokines/chemokines and mRNA expression of intestinal permeability related genes induced by AgNPs in ileal tissues. The ex vivo model preserved the structural and biological functions of the in-situ organ. Analysis of cytokine expression data indicated that intestinal tissue of male and female subjects responded differently to AgNP treatment, with male samples showing significantly elevated Granulocyte-macrophage colony-stimulating factor (GM-CSF) after treatment with 10 nm and 20 nm AgNPs for 2 h and significantly elevated RANTES after treatment with 20 nm AgNPs for 24 h. In contrast, tissues of female showed no significant effects of AgNP treatment at 2 h and significantly decreased RANTES (20 nm), TNF-α (10 nm), and IFN-γ (10 nm) at 24 h. Smaller size AgNPs (10 nm) perturbed more permeability-related genes in samples of male subjects, than in samples from female subjects. In contrast, exposure to 20 nm AgNPs resulted in upregulation of a greater number of genes in female-derived samples (36 genes) than in male-derived samples (8 genes). The ex vivo tissue model can distinguish sex dependent effects of AgNP and could serve as a translational non-animal model to assess the impacts of xenobiotics on human intestinal mucosa.
Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families
Authors: Gorecki Matthias , Müller Simon F. , Leidolf Regina , Geyer Joachim
Published: December 2020

Background: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion. In humans, the organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion MATE1 and MATE2-K carriers showed TCl transport. However, their individual role for distribution and excretion of TCl is unclear. Knockout mouse models lacking mOct1/mOct2 or mMate1 might help to clarify their role for the overall pharmacokinetics of TCl. Method: In preparation of such experiments, TCl transport was analyzed in HEK293 cells stably transfected with the mouse carriers mOct1, mOct2, mMate1, and mMate2, respectively. Results: Mouse mOct1, mOct2, and mMate1 showed significant TCl transport with Km values of 58.7, 78.5, and 29.3 µM, respectively. In contrast, mMate2 did not transport TCl but showed MPP+ transport with Km of 60.0 µM that was inhibited by the drugs topotecan, acyclovir, and levofloxacin. Conclusion: TCl transport behavior as well as expression pattern were quite similar for the mouse carriers mOct1, mOct2, and mMate1 compared to their human counterparts.
ANP and BNP Exert Anti-Inflammatory Action via NPR-1/cGMP Axis by Interfering with Canonical, Non-Canonical, and Alternative Routes of Inflammasome Activation in Human THP1 Cells
Authors: Mezzasoma Letizia , Talesa Vincenzo Nicola , Romani Rita , Bellezza Ilaria
Published: December 2020

Dysregulated inflammasome activation and interleukin (IL)-1β production are associated with several inflammatory disorders. Three different routes can lead to inflammasome activation: a canonical two-step, a non-canonical Caspase-4/5- and Gasdermin D-dependent, and an alternative Caspase-8-mediated pathway. Natriuretic Peptides (NPs), Atrial Natriuretic Peptide (ANP) and B-type Natriuretic Peptide (BNP), binding to Natriuretic Peptide Receptor-1 (NPR-1), signal by increasing cGMP (cyclic guanosine monophosphate) levels that, in turn, stimulate cGMP-dependent protein kinase-I (PKG-I). We previously demonstrated that, by counteracting inflammasome activation, NPs inhibit IL-1β secretion. Here we aimed to decipher the molecular mechanism underlying NPs effects on THP-1 cells stimulated with lipopolysaccharide (LPS) + ATP. Involvement of cGMP and PKG-I were assessed pre-treating THP-1 cells with the membrane-permeable analogue, 8-Br-cGMP, and the specific inhibitor KT-5823, respectively. We found that NPs, by activating NPR-1/cGMP/PKG-I axis, lead to phosphorylation of NLRP3 at Ser295 and to inflammasome platform disassembly. Moreover, by increasing intracellular cGMP levels and activating phosphodiesterases, NPs interfere with both Gasdermin D and Caspase-8 cleavage, indicating that they disturb non-canonical and alternative routes of inflammasome activation. These results showed that ANP and BNP anti-inflammatory and immunomodulatory actions may involve the inhibition of all the known routes of inflammasome activation. Thus, NPs might be proposed for the treatment of the plethora of diseases caused by a dysregulated inflammasome activation.
Disclosing the Interaction of Gold Nanoparticles with Aβ(1–40) Monomers through Replica Exchange Molecular Dynamics Simulations
Authors: Tavanti Francesco , Pedone Alfonso , Menziani Maria Cristina
Published: December 2020

Amyloid-β aggregation is one of the principal causes of amyloidogenic diseases that lead to the loss of neuronal cells and to cognitive impairments. The use of gold nanoparticles treating amyloidogenic diseases is a promising approach, because the chemistry of the gold surface can be tuned in order to have a specific binding, obtaining effective tools to control the aggregation. In this paper, we show, by means of Replica Exchange Solute Tempering Molecular Simulations, how electrostatic interactions drive the absorption of Amyloid-β monomers onto citrates-capped gold nanoparticles. Importantly, upon binding, amyloid monomers show a reduced propensity in forming β-sheets secondary structures that are characteristics of mature amyloid fibrils.
miR-205 in Breast Cancer: State of the Art
Authors: Plantamura Ilaria , Cataldo Alessandra , Cosentino Giulia , Iorio Marilena V.
Published: December 2020

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.
New Insights in Molecular Mechanisms and Pathophysiology of Ischemia-Reperfusion Injury 2.0: An Updated Overview
Authors: Panisello-Roselló Arnau , Roselló-Catafau Joan , Adam René
Published: December 2020

Ischemia reperfusion injury (IRI) is related to different surgical interventions such as organ resection and transplantation, and therefore its prevention is of great interest [...]
Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro
Authors: Gatti Martina , Beretti Francesca , Zavatti Manuela , Bertucci Emma , Ribeiro Luz Soraia , Palumbo Carla , Maraldi Tullia
Published: December 2020

Background—Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods—human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological assays. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results—AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexamethasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion—these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.
Role of Cobalt(III) Cationic Complexes in the Self-Assembling Process of a Water Soluble Porphyrin
Authors: Manganaro Nadia , Zagami Roberto , Trapani Mariachiara , Castriciano Maria Angela , Romeo Andrea , Scolaro Luigi Monsù
Published: December 2020

Under moderate acidic conditions, the cationic (+3) complexes ions tris(1,10-phenanthroline)cobalt(III), [Co(phen)3]3+, and hexamminecobalt(III), [Co(NH3)6]3+, efficiently promote the self-assembling process of the diacid 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (H2TPPS4) into J-aggregates. The growth kinetics have been analyzed according to a well-established autocatalytic model, in which the rate determining step is the initial formation of a nucleus containing m porphyrin units (in the range 2–3), followed by a stage whose rate constant kc evolves as a power of time. The observed catalytic rate constants and the extent of J-aggregation increase on increasing the metal complex concentration, with the phen complex being the less active. The UV/Vis extinction spectra display quite broad envelops at the J-band, especially for the amino-complex, suggesting that electronic dipolar coupling between chromophores is operative in these species. The occurrence of spontaneous symmetry breaking has been revealed by circular dichroism and the measured dissymmetry g-factor decreases on increasing the aggregation rates. The role of these metal complexes on the growth and stabilization of porphyrin nano-assemblies is discussed in terms of the different degree of hydrophilicity and hydrogen bonding ability of the ligands present in the coordination sphere around the metal center.
Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein as a Screening Tool for Significant Liver Fibrosis in Health Checkup
Authors: Tamaki Nobuharu , Kurosaki Masayuki , Takahashi Yuka , Itakura Yoshie , Kirino Sakura , Inada Kento , Yamashita Koji , Sekiguchi Shuhei , Hayakawa Yuka , Osawa Leona , Higuchi Mayu , Takaura Kenta , Maeyashiki Chiaki , Kaneko Shun , Yasui Yutaka , Tsuchiya Kaoru , Nakanishi Hiroyuki , Itakura Jun , Loomba Rohit , Izumi Namiki
Published: December 2020

Chronic liver disease is generally widespread, and a test for screening fibrotic subjects in a large population is needed. The ability of Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA+-M2BP) to detect significant fibrosis was investigated in health checkup subjects in this research. Of 2021 health checkup subjects enrolled in this prospective cross-sectional study, those with WFA+-M2BP ≥ 1.0 were defined as high risk. Liver fibrosis was evaluated using magnetic resonance elastography (MRE) in subjects with high risk. The primary outcome was the positive predictive value (PPV) of WFA+-M2BP for significant fibrosis (liver stiffness ≥ 2.97 kPa by MRE). This trial was registered with the UMIN clinical trial registry, UMIN000036175. WFA+-M2BP ≥ 1.0 was observed in 5.3% of the 2021 subjects. The PPV for significant fibrosis with the threshold of WFA+-M2BP at ≥1.0, ≥1.1, ≥1.2, ≥1.3, ≥1.4, and ≥1.5 was 29.2%, 36.4%, 43.5%, 42.9%, 62.5%, and 71.4%, respectively. A WFA+-M2BP of 1.2 was selected as the optimal threshold for significant fibrosis among high-risk subjects, and the PPV, negative predictive value, sensitivity, and specificity for significant fibrosis were 43.5%, 84.0%, 71.4%, and 61.8%, respectively. WFA+-M2BP ≥ 1.2 was significantly associated with significant fibrosis, with an odds ratio (OR) of 4.04 (95% confidence interval (CI): 1.1–16, p = 0.04), but not FIB-4 ≥ 2.67 (OR: 2.40, 95%CI: 0.7–8.6, p-value = 0.2). In conclusion, WFA+-M2BP is associated with significant fibrosis and could narrow down potential subjects with liver fibrosis. The strategy of narrowing down fibrosis subjects using WFA+-M2BP may be used to screen for fibrotic subjects in a large population.
Rapid Hormetic Responses of Photosystem II Photochemistry of Clary Sage to Cadmium Exposure
Authors: Adamakis Ioannis-Dimosthenis S. , Sperdouli Ilektra , Hanć Anetta , Dobrikova Anelia , Apostolova Emilia , Moustakas Michael
Published: December 2020

Five-day exposure of clary sage (Salvia sclarea L.) to 100 μM cadmium (Cd) in hydroponics was sufficient to increase Cd concentrations significantly in roots and aboveground parts and affect negatively whole plant levels of calcium (Ca) and magnesium (Mg), since Cd competes for Ca channels, while reduced Mg concentrations are associated with increased Cd tolerance. Total zinc (Zn), copper (Cu), and iron (Fe) uptake increased but their translocation to the aboveground parts decreased. Despite the substantial levels of Cd in leaves, without any observed defects on chloroplast ultrastructure, an enhanced photosystem II (PSII) efficiency was observed, with a higher fraction of absorbed light energy to be directed to photochemistry (ΦPSΙΙ). The concomitant increase in the photoprotective mechanism of non-photochemical quenching of photosynthesis (NPQ) resulted in an important decrease in the dissipated non-regulated energy (ΦNO), modifying the homeostasis of reactive oxygen species (ROS), through a decreased singlet oxygen (1O2) formation. A basal ROS level was detected in control plant leaves for optimal growth, while a low increased level of ROS under 5 days Cd exposure seemed to be beneficial for triggering defense responses, and a high level of ROS out of the boundaries (8 days Cd exposure), was harmful to plants. Thus, when clary sage was exposed to Cd for a short period, tolerance mechanisms were triggered. However, exposure to a combination of Cd and high light or to Cd alone (8 days) resulted in an inhibition of PSII functionality, indicating Cd toxicity. Thus, the rapid activation of PSII functionality at short time exposure and the inhibition at longer duration suggests a hormetic response and describes these effects in terms of “adaptive response” and “toxicity”, respectively.
Infections and Immunotherapy in Lung Cancer: A Bad Relationship?
Authors: Belluomini Lorenzo , Caldart Alberto , Avancini Alice , Dodi Alessandra , Trestini Ilaria , Kadrija Dzenete , Sposito Marco , Tregnago Daniela , Casali Miriam , Riva Silvia Teresa , Sartori Giulia , Menis Jessica , Milella Michele , Pilotto Sara
Published: December 2020

Infectious diseases represent a relevant issue in lung cancer patients. Bacterial and viral infections might influence the patients’ prognosis, both directly affecting the immune system and indirectly impairing the outcome of anticancer treatments, mainly immunotherapy. In this analysis, we aimed to review the current evidence in order to clarify the complex correlation between infections and lung cancer. In detail, we mainly explored the potential impact on immunotherapy outcome/safety of (1) bacterial infections, with a detailed focus on antibiotics; and (2) viral infections, discriminating among (a) human immune-deficiency virus (HIV), (b) hepatitis B/C virus (HBV-HCV), and (c) Sars-Cov-2. A series of studies suggested the prognostic impact of antibiotic therapy administration, timing, and exposure ratio in patients treated with immune checkpoint inhibitors, probably through an antibiotic-related microbiota dysbiosis. Although cancer patients with HIV, HBV, and HCV were usually excluded from clinical trials evaluating immunotherapy, some retrospective and prospective trials performed in these patient subgroups reported similar results compared to those described in not-infected patients, with a favorable safety profile. Moreover, patients with thoracic cancers are particularly at risk of COVID-19 severe outcomes and mortality. Few reports speculated about the prognostic implications of anticancer therapy, including immunotherapy, in lung cancer patients with concomitant Sars-Cov-2 infection, showing, to date, inconsistent results. The correlation between infectious diseases and immunotherapy remains to be further explored and clarified in the context of dedicated trials. In clinical practice, the accurate and prompt multidisciplinary management of lung cancer patients with infections should be encouraged in order to select the best treatment options for these patients, avoiding unexpected toxicities, while maintaining the anticancer effect.
Effects of Gut Metabolites and Microbiota in Healthy and Marginal Livers Submitted to Surgery
Authors: Micó-Carnero Marc , Rojano-Alfonso Carlos , Álvarez-Mercado Ana Isabel , Gracia-Sancho Jordi , Casillas-Ramírez Araní , Peralta Carmen
Published: December 2020

Microbiota is defined as the collection of microorganisms within the gastrointestinal ecosystem. These microbes are strongly implicated in the stimulation of immune responses. An unbalanced microbiota, termed dysbiosis, is related to the development of several liver diseases. The bidirectional relationship between the gut, its microbiota and the liver is referred to as the gut–liver axis. The translocation of bacterial products from the intestine to the liver induces inflammation in different cell types such as Kupffer cells, and a fibrotic response in hepatic stellate cells, resulting in deleterious effects on hepatocytes. Moreover, ischemia-reperfusion injury, a consequence of liver surgery, alters the microbiota profile, affecting inflammation, the immune response and even liver regeneration. Microbiota also seems to play an important role in post-operative outcomes (i.e., liver transplantation or liver resection). Nonetheless, studies to determine changes in the gut microbial populations produced during and after surgery, and affecting liver function and regeneration are scarce. In the present review we analyze and discuss the preclinical and clinical studies reported in the literature focused on the evaluation of alterations in microbiota and its products as well as their effects on post-operative outcomes in hepatic surgery.
Human Nitric Oxide Synthase—Its Functions, Polymorphisms, and Inhibitors in the Context of Inflammation, Diabetes and Cardiovascular Diseases
Authors: Król Magdalena , Kepinska Marta
Published: December 2020

In various diseases, there is an increased production of the free radicals needed to carry out certain physiological processes but their excessive amounts can cause oxidative stress and cell damage. Enzymes play a major role in the transformations associated with free radicals. One of them is nitric oxide synthase (NOS), which catalyzes the formation of nitric oxide (NO). This enzyme exists in three forms (NOS1, NOS2, NOS3), each encoded by a different gene. The following work presents the most important information on the NOS isoforms and their role in the human body, including NO synthesis in various tissues and cells, intercellular signaling and activities supporting the immune system and regulating blood vessel functions. The role of NOS in pathological conditions such as obesity, diabetes and heart disease is considered. Attention is also paid to the influence of the polymorphisms of these genes, encoding particular isoforms, on the development of these pathologies and the role of NOS inhibitors in the treatment of patients.
Glutamatergic Dysfunction and Synaptic Ultrastructural Alterations in Schizophrenia and Autism Spectrum Disorder: Evidence from Human and Rodent Studies
Authors: Eltokhi Ahmed , Santuy Andrea , Merchan-Perez Angel , Sprengel Rolf
Published: December 2020

The correlation between dysfunction in the glutamatergic system and neuropsychiatric disorders, including schizophrenia and autism spectrum disorder, is undisputed. Both disorders are associated with molecular and ultrastructural alterations that affect synaptic plasticity and thus the molecular and physiological basis of learning and memory. Altered synaptic plasticity, accompanied by changes in protein synthesis and trafficking of postsynaptic proteins, as well as structural modifications of excitatory synapses, are critically involved in the postnatal development of the mammalian nervous system. In this review, we summarize glutamatergic alterations and ultrastructural changes in synapses in schizophrenia and autism spectrum disorder of genetic or drug-related origin, and briefly comment on the possible reversibility of these neuropsychiatric disorders in the light of findings in regular synaptic physiology.
MD-TSPC4: Computational Method for Predicting the Thermal Stability of I-Motif
Authors: Shamim Amen , Razzaq Maria , Kim Kyeong Kyu
Published: December 2020

I-Motif is a tetrameric cytosine-rich DNA structure with hemi-protonated cytosine: cytosine base pairs. Recent evidence showed that i-motif structures in human cells play regulatory roles in the genome. Therefore, characterization of novel i-motifs and investigation of their functional implication are urgently needed for comprehensive understanding of their roles in gene regulation. However, considering the complications of experimental investigation of i-motifs and the large number of putative i-motifs in the genome, development of an in silico tool for the characterization of i-motifs in the high throughput scale is necessary. We developed a novel computation method, MD-TSPC4, to predict the thermal stability of i-motifs based on molecular modeling and molecular dynamic simulation. By assuming that the flexibility of loops in i-motifs correlated with thermal stability within certain temperature ranges, we evaluated the correlation between the root mean square deviations (RMSDs) of model structures and the thermal stability as the experimentally obtained melting temperature (Tm). Based on this correlation, we propose an equation for Tm prediction from RMSD. We expect this method can be useful for estimating the overall structure and stability of putative i-motifs in the genome, which can be a starting point of further structural and functional studies of i-motifs.
Lignin for Bioeconomy: The Present and Future Role of Technical Lignin
Authors: Ekielski Adam , Mishra Pawan Kumar
Published: December 2020

Lignin, the term commonly used in literature, represents a group of heterogeneous aromatic compounds of plant origin. Protolignin or lignin in the cell wall is entirely different from the commercially available technical lignin due to changes during the delignification process. In this paper, we assess the status of lignin valorization in terms of commercial products. We start with existing knowledge of the lignin/protolignin structure in its native form and move to the technical lignin from various sources. Special attention is given to the patents and lignin-based commercial products. We observed that the technical lignin-based commercial products utilize coarse properties of the technical lignin in marketed formulations. Additionally, the general principles of polymers chemistry and self-assembly are difficult to apply in lignin-based nanotechnology, and lignin-centric investigations must be carried out. The alternate upcoming approach is to develop lignin-centric or lignin first bio-refineries for high-value applications; however, that brings its own technological challenges. The assessment of the gap between lab-scale applications and lignin-based commercial products delineates the challenges lignin nanoparticles-based technologies must meet to be a commercially viable alternative.
TCR Recognition of Peptide–MHC-I: Rule Makers and Breakers
Authors: Szeto Christopher , Lobos Christian A. , Nguyen Andrea T. , Gras Stephanie
Published: December 2020

T cells are a critical part of the adaptive immune system that are able to distinguish between healthy and unhealthy cells. Upon recognition of protein fragments (peptides), activated T cells will contribute to the immune response and help clear infection. The major histocompatibility complex (MHC) molecules, or human leukocyte antigens (HLA) in humans, bind these peptides to present them to T cells that recognise them with their surface T cell receptors (TCR). This recognition event is the first step that leads to T cell activation, and in turn can dictate disease outcomes. The visualisation of TCR interaction with pMHC using structural biology has been crucial in understanding this key event, unravelling the parameters that drive this interaction and their impact on the immune response. The last five years has been the most productive within the field, wherein half of current unique TCR–pMHC-I structures to date were determined within this time. Here, we review the new insights learned from these recent TCR–pMHC-I structures and their impact on T cell activation.
NAC Transcription Factors as Positive or Negative Regulators during Ongoing Battle between Pathogens and Our Food Crops
Authors: Bian Zhiyuan , Gao Huanhuan , Wang Chongying
Published: December 2020

The NAC (NAM, ATAF1/2, and CUC2) family of proteins is one of the largest plant-specific transcription factor (TF) families and its members play varied roles in plant growth, development, and stress responses. In recent years, NAC TFs have been demonstrated to participate in crop-pathogen interactions, as positive or negative regulators of the downstream defense-related genes. NAC TFs link signaling pathways between plant hormones, including salicylic acid (SA), jasmonic acid (JA), ethylene (ET), and abscisic acid (ABA), or other signals, such as reactive oxygen species (ROS), to regulate the resistance against pathogens. Remarkably, NAC TFs can also contribute to hypersensitive response and stomatal immunity or can be hijacked as virulence targets of pathogen effectors. Here, we review recent progress in understanding the structure, biological functions and signaling networks of NAC TFs in response to pathogens in several main food crops, such as rice, wheat, barley, and tomato, and explore the directions needed to further elucidate the function and mechanisms of these key signaling molecules.
Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity
Authors: Andersen Phillip Alexander Keller , Petrenko Volodymyr , Rose Peter Horskjær , Koomen Melissa , Fischer Nico , Ghiasi Seyed Mojtaba , Dahlby Tina , Dibner Charna , Mandrup-Poulsen Thomas
Published: December 2020

Pancreatic β-cell-specific clock knockout mice develop β-cell oxidative-stress and failure, as well as glucose-intolerance. How inflammatory stress affects the cellular clock is under-investigated. Real-time recording of Per2:luciferase reporter activity in murine and human pancreatic islets demonstrated that the proinflammatory cytokine interleukin-1β (IL-1β) lengthened the circadian period. qPCR-profiling of core clock gene expression in insulin-producing cells suggested that the combination of the proinflammatory cytokines IL-1β and interferon-γ (IFN-γ) caused pronounced but uncoordinated increases in mRNA levels of multiple core clock genes, in particular of reverse-erythroblastosis virus α (Rev-erbα), in a dose- and time-dependent manner. The REV-ERBα/β agonist SR9009, used to mimic cytokine-mediated Rev-erbα induction, reduced constitutive and cytokine-induced brain and muscle arnt-like 1 (Bmal1) mRNA levels in INS-1 cells as expected. SR9009 induced reactive oxygen species (ROS), reduced insulin-1/2 (Ins-1/2) mRNA and accumulated- and glucose-stimulated insulin secretion, reduced cell viability, and increased apoptosis levels, reminiscent of cytokine toxicity. In contrast, low (<5,0 μM) concentrations of SR9009 increased Ins-1 mRNA and accumulated insulin-secretion without affecting INS-1 cell viability, mirroring low-concentration IL-1β mediated β-cell stimulation. Inhibiting nitric oxide (NO) synthesis, the lysine deacetylase HDAC3 and the immunoproteasome reduced cytokine-mediated increases in clock gene expression. In conclusion, the cytokine-combination perturbed the intrinsic clocks operative in mouse and human pancreatic islets and induced uncoordinated clock gene expression in INS-1 cells, the latter effect associated with NO, HDAC3, and immunoproteasome activity.
Ovule Development and in Planta Transformation of Paphiopedilum Maudiae by Agrobacterium-Mediated Ovary-Injection
Authors: Luo Bai-Xue , Zhang Li , Zheng Feng , Wu Kun-Lin , Li Lin , Zhang Xin-Hua , Ma Guo-Hua , Teixeira da Silva Jaime A. , Fang Lin , Zeng Song-Jun
Published: December 2020

In this paper, the development of the Paphiopedilum Maudiae embryo sac at different developmental stages after pollination was assessed by confocal laser scanning microscopy. The mature seeds of P. Maudiae consisted of an exopleura and a spherical embryo, but without an endosperm, while the inner integument cells were absorbed by the developing embryo. The P. Maudiae embryo sac exhibited an Allium type of development. The time taken for the embryo to develop to a mature sac was 45-50 days after pollination (DAP) and most mature embryo sacs had completed fertilization and formed zygotes by about 50–54 DAP. In planta transformation was achieved by injection of the ovaries by Agrobacterium, resulting in 38 protocorms or seedlings after several rounds of hygromycin selection, corresponding to 2, 7, 5, 1, 3, 4, 9, and 7 plantlets from Agrobacterium-mediated ovary-injection at 30, 35, 42, 43, 45, 48, 50, and 53 DAP, respectively. Transformation efficiency was highest at 50 DAP (2.54%), followed by 2.48% at 53 DAP and 2.45% at 48 DAP. Four randomly selected hygromycin-resistant plants were GUS-positive after PCR analysis. Semi-quantitative PCR and quantitative real-time PCR analysis revealed the expression of the hpt gene in the leaves of eight hygromycin-resistant seedlings following Agrobacterium-mediated ovary-injection at 30, 35, 42, 43, 45, 48, 50, and 53 DAP, while hpt expression was not detected in the control. The best time to inject P. Maudiae ovaries in planta with Agrobacterium is 48-53 DAP, which corresponds to the period of fertilization. This protocol represents the first genetic transformation protocol for any Paphiopedilum species and will allow for expanded molecular breeding programs to introduce useful and interesting genes that can expand its ornamental and horticulturally important characteristics.
Long Non-Coding RNAs, the Dark Matter: An Emerging Regulatory Component in Plants
Authors: Waseem Muhammad , Liu Yuanlong , Xia Rui
Published: December 2020

Long non-coding RNAs (lncRNAs) are pervasive transcripts of longer than 200 nucleotides and indiscernible coding potential. lncRNAs are implicated as key regulatory molecules in various fundamental biological processes at transcriptional, post-transcriptional, and epigenetic levels. Advances in computational and experimental approaches have identified numerous lncRNAs in plants. lncRNAs have been found to act as prime mediators in plant growth, development, and tolerance to stresses. This review summarizes the current research status of lncRNAs in planta, their classification based on genomic context, their mechanism of action, and specific bioinformatics tools and resources for their identification and characterization. Our overarching goal is to summarize recent progress on understanding the regulatory role of lncRNAs in plant developmental processes such as flowering time, reproductive growth, and abiotic stresses. We also review the role of lncRNA in nutrient stress and the ability to improve biotic stress tolerance in plants. Given the pivotal role of lncRNAs in various biological processes, their functional characterization in agriculturally essential crop plants is crucial for bridging the gap between phenotype and genotype.