bluuebunny/crossref_metadata_2025 huggingface dataset:
Valuation of Ecosystem Services Based on EU Carbon Allowances—Optimal Recovery for a Coal Mining Area
Authors: Krzemień Alicja , Álvarez Fernández Juan José , Riesgo Fernández Pedro , Fidalgo Valverde Gregorio , Garcia-Cortes Silverio
Published: December 2022

This paper presents a new way of valuing ecosystem services based on the price of EU carbon dioxide emission allowances. Its main advantage is that it facilitates the monetisation of non-provisioning ecosystem services, which is the Achilles heel of current frameworks. The research approach is built on the notion that land rehabilitation and ecological restoration involve trade-offs between ecosystem services. A quantitative assessment (valuation) of these trade-offs is necessary to make sound decisions. However, using different valuation methods to estimate monetary values creates a non-comparability in the valuation process that is difficult to correct. To address this problem, in the first place, the propagation of imprecise preference statements in hierarchical weighting is proposed, avoiding the non-comparability caused by the different current approaches while reducing the effort of preference elicitation. In the second place, to achieve consistency, monetisation of all non-provisioning ecosystem services was carried on the above comparison and the monetary valuation of the attribute with the most direct and market-related valuation possible: carbon sequestration, using the EU Emissions Trading System. A former coal mining area exemplifies the valuation of ecosystem services provided by alternative ecological restoration scenarios. The aim is to estimate their contribution to human well-being, understand the incentives faced by decision makers to manage ecosystems in different ways and assess the values of alternative solutions. An exercise is then carried out to show that the price of EU carbon permits (as of December 2021) after the price escalation that coincides with phase 4 of the allocation of allowances under the EU Emissions Trading System can be estimated by prioritising biodiversity over other ecosystem services.
Photosynthesis Responses of Tibetan Freshwater Algae Chlorella vulgaris to Herbicide Glyphosate
Authors: Zhang Yixiao , Chen Zixu , Li Xiaoyan , Wu Xinguo , Chen Lanzhou , Wang Gaohong
Published: December 2022

With the development of agriculture and the widespread application of agrichemicals in Tibet, herbicide residues have become a threat to the ecological safety of Tibetan water bodies. Algae, as the producers in the food chain in water bodies, play an important role in aquatic ecosystems. Therefore, the impact of herbicides on Tibetan algae is of great significance for evaluating ecological health and the protection of Tibetan water ecosystems. In this study, we investigated the inhibitory effect of glyphosate, a herbicide, on the photosynthetic system of Chlorella vulgaris, Tibetan algae, by determining chlorophyll fluorescence and the activity of an antioxidant system. The results revealed that glyphosate at low concentration did not affect the photosynthetic activity of C. vulgaris; however, glyphosate at a high concentration significantly inhibited photosynthetic activity and reduced pigment content. Moreover, high levels of glyphosate also decreased photochemical efficiency and electron transport rate and resulted in ROS accumulation, high SOD activity, and lipid peroxidation. These results suggested that glyphosate could decrease the primary production of aquatic ecosystems and influence their performance. Therefore, reducing the herbicide levels could protect the Tibetan aquatic environment and maintain the health of ecosystems.
Sexual Dysfunction and Quality of Life in Patients with Hidradenitis Suppurativa and Their Partners
Authors: Cuenca-Barrales Carlos , Montero-Vilchez Trinidad , Krajewski Piotr K , Szepietowski Jacek C , Matusiak Lukasz , Arias-Santiago Salvador , Molina-Leyva Alejandro
Published: December 2022

Hidradenitis suppurativa (HS) is a chronic skin disease that profoundly affects patients’ quality of life (QoL) and sexuality. Few data are available on the impact of HS on patients’ partners. We aimed to explore the QoL and sexual function of patients’ partners and the factors associated with their impairment and to compare the QoL and sexual function of single patients and those in a stable relationship. We conducted a cross-sectional study at Hospital Universitario Virgen de las Nieves (Granada, Spain) and at the Wroclaw Medical University (Wroclaw, Poland). Patients over the age of 16 years attending their scheduled follow-up and their partners, if any, were included. The Dermatology Life Quality Index (DLQI) and the Family Dermatology Life Quality Index (FDLQI) were used to estimate the QoL of patients and partners, respectively. The FSFI-6 was used to determine sexual dysfunction in women and the IIEF-5 for erectile dysfunction in men. Thirty-four single patients and twenty-eight patients in a stable relationship and their partners were included. Patients had a very large impact (DLQI 12.5 ± 7.5) and their partners a moderate impact (FDLQI 10.3 ± 7.1) in their QoL due to HS. Women with HS had a high prevalence of sexual dysfunction (13/32, 40.6%) and men of erectile dysfunction (19/30, 63.3%). Male partners also had a high prevalence of erectile dysfunction (10/17, 58.8%), while only one female partner had sexual dysfunction (1/11, 9.1%). Factors related to disease severity, intensity of symptoms and body mass index were associated with poorer QoL in partners and time of disease evolution with greater erectile dysfunction in male partners. In conclusion, HS not only profoundly affects the QoL and sexuality of patients but also of their partners. Several risk factors have been identified, which should be taken into account in the holistic approach of the disease.
Health Care on Rare Diseases
Authors: Cortés-Martín Jonathan , Sánchez-García Juan Carlos , Rodríguez-Blanque Raquel
Published: December 2022

Rare diseases are a subject of great scientific and health interest that has been on the rise in recent years [...]
Out-of-School Learning in the Wadden Sea: The Influence of a Mudflat Hiking Tour on the Environmental Attitudes and Environmental Knowledge of Secondary School Students
Authors: Schmäing Till , Grotjohann Norbert
Published: December 2022

In this study, the Wadden Sea, as an out-of-school learning site, is considered from an empirical-research perspective of environmental education. The Wadden Sea in Germany is part of the largest contiguous mudflat area in the world. Although much evidence is already available on different teaching and learning processes at various out-of-school learning sites, this is not yet the case for the Wadden Sea. This research gap was taken up. In this paper, 427 students (mean age: 11.74 years) participated in a mudflat hiking tour. A pre–post-test design followed by a retention test was used to determine the impact of this on participants’ environmental attitudes and environmental knowledge. The single factor analyses of variance with repeated measures demonstrated that the mudflat hiking tour had both a positive short-term and a positive long-term impact on environmental attitudes, as well as on environmental knowledge. All three constructs could, therefore, be positively influenced by the intervention. Correlation analyses revealed a positive relationship between environmental attitudes and environmental knowledge at three measurement time points. These results empirically confirm the potential of the Wadden Sea as an out-of-school learning site for environmental education with students from secondary schools. The effectiveness of non-formal education in this ecological environment can be proven.
The Relationship between Psychological Safety and Management Team Effectiveness: The Mediating Role of Behavioral Integration
Authors: Mogård Emil Viduranga , Rørstad Ole Bendik , Bang Henning
Published: December 2022

This study explores whether there is an indirect effect of psychological safety on team effectiveness in management teams, operating through the mediating variable of behavioral integration. Whilst there exists a fair amount of research on the relationship between psychological safety and team effectiveness, few have looked at potential mechanisms that can explain this association in management teams. We propose behavioral integration to be a potential mediator. Data are collected from 1150 leaders in 160 Norwegian management teams, answering a questionnaire measuring team functioning and effectiveness. Team size ranged from 3 to 19 members. Our results show a significant indirect effect of psychological safety on management team effectiveness, mediated by behavioral integration. Thus, the more team members perceive the climate as safe in terms of speaking their mind without the fear of repercussions, the more they partake in mutual collaboration, information sharing and experience ownership in the decisions being made. This is associated with management teams performing better. We also found a positive relationship between psychological safety and behavioral integration, and—in line with previous studies—that psychological safety and behavioral integration both were positively related to team effectiveness. This study adds to the existing team research literature by expanding our knowledge about the importance of psychological safety and the way it influences management team performance at all levels throughout the organizational hierarchy.
What Are the Recipes of an Entrepreneur’s Subjective Well-Being? A Fuzzy-Set Approach for China
Authors: Yang Zihan , Cai Xu , Jiang Yujia , Li Guobiao , Zhao Guojing , Wang Peng , Huang Zhaoxin
Published: December 2022

Entrepreneurs face more pressure and challenges than ordinary workers, which has a serious impact on their physical and mental health. Therefore, the research focus has gradually shifted from objective indicators of entrepreneurial performance to exploration of entrepreneurs’ subjective well-being. However, previous studies were often limited to a net effect analysis of a single dimension under symmetric thinking in quantitative research. Therefore, this study uses fuzzy-set qualitative comparative analysis (fsQCA) to analyze the configuration path of entrepreneurs’ physical and mental health at the individual level, social capital at the collective level, and subjective well-being from the perspective of configuration. The sample was of 279 effective entrepreneurs from the 2017 China General Social Survey (CGSS). Four types of entrepreneurs were found to improve their high well-being profiles: optimistic efficiency-driven, trust efficiency-driven, strong psychology-driven, and weak relationship-driven. Research shows that the interaction between physical and mental health and social capital jointly affects the subjective well-being of entrepreneurs. The research findings reinforce the need for attention to the physical and mental health of entrepreneurs, which are conducive to their active participation in social life. Additionally, establishing weak relationship-oriented interpersonal networks and accumulating social resources to further achieve higher subjective well-being is required.
Do Financial Crises Matter for Nonlinear Exchange Rate and Stock Market Cointegration? A Heterogeneous Nonlinear Panel Data Model with PMG Approach
Authors: Tabash Mosab I. , Sheikh Umaid A. , Matar Ali , Ahmed Adel , Tran Dang Khoa
Published: December 2022

The existing literature has explained the causality flow from the exchange rates toward the stock market without explaining the role of the economic crisis in effecting this nexus. This study examines the role of the financial crisis in affecting the nonlinear causality flowing from the exchange rates toward the stock market indexes of the ASEAN-5 region. The precrisis, postcrisis, and overall sample duration comprised 365, 650, and 1085 observations over the periods from January 2002 to January 2008, January 2010 to January 2020, and January 2002 to January 2020, respectively. The results showed that the conventional symmetrical panel ARDL (PARDL) model was not able to formulate long-run cointegration between currency value fluctuations and stock market indexes for both regimes, i.e., the post recessionary and pre recessionary periods. However, asymmetrical cointegration was established between the currency values and stock market indexes for the pre recessionary period and the overall sampling time frame by utilizing the panel-based NARDL framework (PNARDL). The study suggests practical implications for the exporters and importers to consider the regime as well as both the negative and positive shocks in the international dollar values while making forward contractual agreements.
Characterizing Intercity Mobility Patterns for the Greater Bay Area in China
Authors: Yin Yanzhong , Wu Qunyong , Li Mengmeng
Published: December 2022

Understanding intercity mobility patterns is important for future urban planning, in which the intensity of intercity mobility indicates the degree of urban integration development. This study investigates the intercity mobility patterns of the Greater Bay Area (GBA) in China. The proposed workflow starts by analyzing intercity mobility characteristics, proceeds to model the spatial-temporal heterogeneity of intercity mobility structures, and then identifies the intercity mobility patterns. We first conduct a complex network analysis, based on weighted degrees and the PageRank algorithm, to measure intercity mobility characteristics. Next, we calculate the Normalized Levenshtein Distance for Population Mobility Structure (NLPMS) to quantify the differences in intercity mobility structures, and we use the Non-negative Matrix Factorization (NMF) to identify intercity mobility patterns. Our results showed an evident ‘Core-Periphery’ differentiation characterized by intercity mobility, with Guangzhou and Shenzhen as the two core cities. An obvious daily intercity commuting pattern was found between Guangzhou and Foshan, and between Shenzhen and Dongguan cities at working time. This pattern, however, changes during the holidays. This is because people move from the core cities to peripheral cities at the beginning of holidays and return at the end of holidays. This study concludes that Guangzhou and Foshan have formed a relatively stable intercity mobility pattern, and the Shenzhen–Dongguan–Huizhou metropolitan area has been gradually formed.
Transcriptomic Evidence Reveals Low Gelatinous Layer Biosynthesis in Neolamarckia cadamba after Gravistimulation
Authors: Qaseem Mirza Faisal , Wang Kaili , Yang Haoqiang , Zhao Shuai , Li Huiling , Wu Ai-Min
Published: December 2022

Trees can control their shape and resist gravity by producing tension wood (TW), which is a special wood that results from trees being put under stress. TW is characterized by the presence of a gelatinous layer (G layer) and the differential distribution of cell wall polymers. In this study, we investigated whether or not gravistimulation in N. cadamba resulted in TW with an obvious G layer. The results revealed an absence of an obvious G layer in samples of the upper side of a leaning stem (UW), as well as an accumulation of cellulose and a decrease in lignin content. A negligible change in the content of these polymers was recorded and compared to untreated plant (NW) samples, revealing the presence of a G layer either in much lower concentrations or in a lignified form. A transcriptomic investigation demonstrated a higher expression of cell wall esterase- and hydrolase-related genes in the UW, suggesting an accumulation of noncellulosic sugars in the UW, similar to the spectroscopy results. Furthermore, several G-layer-specific genes were also downregulated, including fasciclin-like arabinogalactan proteins (FLA), beta-galactosidase (BGAL) and chitinase-like proteins (CTL). The gene coexpression network revealed a strong correlation between cell-wall-synthesis-related genes and G-layer-synthesis-specific genes, suggesting their probable antagonistic role during G layer formation. In brief, the G layer in N. cadamba was either synthesized in a very low amount or was lignified during an early stage of growth; further experimental validation is required to understand the exact mechanism and stage of G layer formation in N. cadamba during gravistimulation.
E as in Enigma: The Mysterious Role of the Voltage-Dependent Anion Channel Glutamate E73
Authors: Rister Alexander Bernhard , Gudermann Thomas , Schredelseker Johann
Published: December 2022

The voltage-dependent anion channel (VDAC) is the main passageway for ions and metabolites over the outer mitochondrial membrane. It was associated with many physiological processes, including apoptosis and modulation of intracellular Ca2+ signaling. The protein is formed by a barrel of 19 beta-sheets with an N-terminal helix lining the inner pore. Despite its large diameter, the channel can change its selectivity for ions and metabolites based on its open state to regulate transport into and out of mitochondria. VDAC was shown to be regulated by a variety of cellular factors and molecular partners including proteins, lipids and ions. Although the physiological importance of many of these modulatory effects are well described, the binding sites for molecular partners are still largely unknown. The highly symmetrical and sleek structure of the channel makes predictions of functional moieties difficult. However, one residue repeatedly sticks out when reviewing VDAC literature. A glutamate at position 73 (E73) located on the outside of the channel facing the hydrophobic membrane environment was repeatedly proposed to be involved in channel regulation on multiple levels. Here, we review the distinct hypothesized roles of E73 and summarize the open questions around this mysterious residue.
A Lignin-Based Carbon Anode with Long-Cycle Stability for Li-Ion Batteries
Authors: Li Shiyue , Luo Wenbin , He Qi , Lu Jie , Du Jian , Tao Yehan , Cheng Yi , Wang Haisong
Published: December 2022

Due to its wide source and low cost, biomass-based hard carbon is considered a valuable anode for lithium-ion batteries (LIBs). Lignins, as the second most abundant source in nature, are being intensively studied as candidate anode materials for next generation LIBs. However, direct carbonization of pure lignin usually leads to low specific surface area and porosity. In this paper, we design a porous carbon material from natural lignin assisted by sacrificing a metal–organic framework (MOF) as the template. The MOF nanoparticles can disperse the lignin particles uniformly and form abundant mesopores in the composites to offer fast transfer channels for Li+. The as-prepared carbon anode shows a high specific capacity of 420 mAh g−1 with the capacity retention of 99% after 300 cycles at 0.2 A g−1. Additionally, it keeps the capacity retention of 85% after long cycle of 1000 cycles, indicating the good application value of the designed anode in LIBs. The work provides a renewable and low-cost candidate anode and a feasible design strategy of the anode materials for LIBs.
COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients
Authors: Tyagi Suresh C. , Pushpakumar Sathnur , Sen Utpal , Mokshagundam Sri Prakash L. , Kalra Dinesh K. , Saad Mohamed A. , Singh Mahavir
Published: December 2022

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.
Effects of Ascorbic Acid on Physiological Characteristics during Somatic Embryogenesis of Fraxinus mandshurica
Authors: Cheng Xue , Xie Tianyi , Yang Ling , Shen Hailong
Published: December 2022

Fraxinus mandshurica is one of the precious tree species in northeast China and has important economic and ecological value. Ascorbic acid (ASA) is a strong antioxidant that can significantly improve plant photosynthetic efficiency and stress resistance and participate widely in plant growth and development. In this study, we investigated the development process of mature zygotic embryos of F. mandshurica under different concentrations of ASA and found that 100 mg·L−1 exogenous ASA was the optimal concentration and that the induction rate of somatic embryos (SEs) was the highest at 72.89%, which was 7.13 times higher than that of the control group. The polyphenol content, peroxidase (POD) activity, nitric oxide (NO) content, nitrate reductase (NR) activity, total ascorbic acid (T-ASA) content, ASA content, ASA/Dehydroascorbic acid (DHA) ratio, GSH/GSSG ratio, and ascorbate peroxidase (APX) activity were significantly increased under the application of exogenous ASA in explants, whereas the polyphenol oxidase (PPO) activity, phenylalanine ammonia-lyase (PAL) activity, superoxide dismutase (SOD) activity, and catalase (CAT) activity, malondialdehyde (MDA) content and nitric oxide synthase (NOS) activity were decreased. At the same time, the content of T-ASA and ASA, T-GSH and GSSG, and PAL and SOD had the same change pattern in the control group and the treatment group. These results suggested that high or low concentrations of ASA could not promote the somatic embryogenesis of F. mandshurica and that exogenous ASA had significant effects on the physiology of F. mandshurica explants. ASA was also highly related to somatic embryogenesis and the explant browning of F. mandshurica. Our results could provide a reference for further study on the browning mechanism of F. mandshurica explants and lay the foundation for optimizing the condition of somatic embryogenesis in F. mandshurica.
Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins
Authors: Malfeld Kathrin , Armbrecht Nina , Pich Andreas , Volk Holger A. , Lenarz Thomas , Scheper Verena
Published: December 2022

As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.
Tumor Microenvironment and Metabolism: Role of the Mitochondrial Melatonergic Pathway in Determining Intercellular Interactions in a New Dynamic Homeostasis
Authors: Anderson George
Published: December 2022

There is a growing interest in the role of alterations in mitochondrial metabolism in the pathoetiology and pathophysiology of cancers, including within the array of diverse cells that can form a given tumor microenvironment. The ‘exhaustion’ in natural killer cells and CD8+ t cells as well as the tolerogenic nature of dendritic cells in the tumor microenvironment seems determined by variations in mitochondrial function. Recent work has highlighted the important role played by the melatonergic pathway in optimizing mitochondrial function, limiting ROS production, endogenous antioxidants upregulation and consequent impacts of mitochondrial ROS on ROS-dependent microRNAs, thereby impacting on patterned gene expression. Within the tumor microenvironment, the tumor, in a quest for survival, seeks to ‘dominate’ the dynamic intercellular interactions by limiting the capacity of cells to optimally function, via the regulation of their mitochondrial melatonergic pathway. One aspect of this is the tumor’s upregulation of kynurenine and the activation of the aryl hydrocarbon receptor, which acts to metabolize melatonin and increase the N-acetylserotonin/melatonin ratio, with effluxed N-acetylserotonin acting as a brain-derived neurotrophic factor (BDNF) mimic via its activation of the BDNF receptor, TrkB, thereby increasing the survival and proliferation of tumors and cancer stem-like cells. This article highlights how many of the known regulators of cells in the tumor microenvironment can be downstream of the mitochondrial melatonergic pathway regulation. Future research and treatment implications are indicated.
Phage Therapy for Crops: Concepts, Experimental and Bioinformatics Approaches to Direct Its Application
Authors: Villalpando-Aguilar José Luis , Matos-Pech Gilberto , López-Rosas Itzel , Castelán-Sánchez Hugo Gildardo , Alatorre-Cobos Fulgencio
Published: December 2022

Phage therapy consists of applying bacteriophages, whose natural function is to kill specific bacteria. Bacteriophages are safe, evolve together with their host, and are environmentally friendly. At present, the indiscriminate use of antibiotics and salt minerals (Zn2+ or Cu2+) has caused the emergence of resistant strains that infect crops, causing difficulties and loss of food production. Phage therapy is an alternative that has shown positive results and can improve the treatments available for agriculture. However, the success of phage therapy depends on finding effective bacteriophages. This review focused on describing the potential, up to now, of applying phage therapy as an alternative treatment against bacterial diseases, with sustainable improvement in food production. We described the current isolation techniques, characterization, detection, and selection of lytic phages, highlighting the importance of complementary studies using genome analysis of the phage and its host. Finally, among these studies, we concentrated on the most relevant bacteriophages used for biocontrol of Pseudomonas spp., Xanthomonas spp., Pectobacterium spp., Ralstonia spp., Burkholderia spp., Dickeya spp., Clavibacter michiganensis, and Agrobacterium tumefaciens as agents that cause damage to crops, and affect food production around the world.
Natural Killer Cell Receptors and Endometriosis: A Systematic Review
Authors: Reis José Lourenço , Rosa Natacha Nurdine , Ângelo-Dias Miguel , Martins Catarina , Borrego Luís Miguel , Lima Jorge
Published: December 2022

Endometriosis is a chronic inflammatory disorder, characterized by the presence of endometrial cells outside the uterine cavity. An increasing number of studies correlate the immune system with endometriosis, particularly NK receptors (NKR), which have been suggested to play an essential role in the pathogenesis of the disease. This systematic review aims to enlighten the role of NKR in endometriosis. A literature search was performed independently by two reviewers, to identify studies assessing the role of NKR in endometriosis. In total, 18 studies were included. Endometriosis pathogenesis seems to be marked by the overexpression of NK inhibitor receptors (KIRS), namely, CD158a+, KIR2DL1, CD94/NKG2A, PD-1, NKB1, and EB6, and inhibiting ligands such as PD-L1, HLA-E, HLA-G, and HLA-I. Concurrently, there is a decrease in NK-activating receptors and natural cytotoxicity receptors (NCRs), such as NKp46, NKp30, and NKG2D. The immune shift from NK surveillance to NK suppression is also apparent in the greater relative number of ITIM domains compared with ITAM domains in NKRs. In conclusion, NK receptor activity seems to dictate the immunocompetency of women to clear endometriotic cells from the peritoneal cavity. Future research could explore NKRs as therapeutic targets, such as that which is now well established in cancer therapy through immunotherapy.
Relative Contribution of Blood Pressure and Renal Sympathetic Nerve Activity to Proximal Tubular Sodium Reabsorption via NHE3 Activity
Authors: Pontes Roberto B. , Nishi Erika E. , Crajoinas Renato O. , Milanez Maycon I. O. , Girardi Adriana C. C. , Campos Ruy R , Bergamaschi Cassia T
Published: December 2022

We examined the effects of an acute increase in blood pressure (BP) and renal sympathetic nerve activity (rSNA) induced by bicuculline (Bic) injection in the paraventricular nucleus of hypothalamus (PVN) or the effects of a selective increase in rSNA induced by renal nerve stimulation (RNS) on the renal excretion of sodium and water and its effect on sodium-hydrogen exchanger 3 (NHE3) activity. Uninephrectomized anesthetized male Wistar rats were divided into three groups: (1) Sham; (2) Bic PVN: (3) RNS + Bic injection into the PVN. BP and rSNA were recorded, and urine was collected prior and after the interventions in all groups. RNS decreased sodium (58%) and water excretion (53%) independently of BP changes (p < 0.05). However, after Bic injection in the PVN during RNS stimulation, the BP and rSNA increased by 30% and 60% (p < 0.05), respectively, diuresis (5-fold) and natriuresis (2.3-fold) were increased (p < 0.05), and NHE3 activity was significantly reduced, independently of glomerular filtration rate changes. Thus, an acute increase in the BP overcomes RNS, leading to diuresis, natriuresis, and NHE3 activity inhibition.
Molecular Dynamics Investigation of MFS Efflux Pump MdfA Reveals an Intermediate State between Its Inward and Outward Conformations
Authors: Li Ying , Ge Xizhen
Published: December 2022

Multidrug resistance poses a major challenge to antibiotic therapy. A principal cause of antibiotic resistance is through active export by efflux pumps embedded in the bacterial membrane. Major facilitator superfamily (MFS) efflux pumps constitute a major group of transporters, which are often related to quinolone resistance in clinical settings. Although a rocker-switch model is proposed for description of their conformational transitions, detailed changes in this process remain poorly understood. Here we used MdfA from E. coli as a representative MFS efflux pump to investigate factors that can affect its conformational transition in silico. Molecular dynamics (MD) simulations of MdfA’s inward and outward conformations revealed an intermediate state between these two conformations. By comparison of the subtle differences between the intermediate state and the average state, we indicated that conformational transition from outward to inward was initiated by protonation of the periplasmic side. Subsequently, hydrophilic interaction of the periplasmic side with water was promoted and the regional structure of helix 1 was altered to favor this process. As the hydrophobic interaction between MdfA and membrane was also increased, energy was concentrated and stored for the opposite transition. In parallel, salt bridges at the cytoplasmic side were altered to lower probabilities to facilitate the entrance of substrate. In summary, we described the total and local changes during MdfA’s conformational transition, providing insights for the development of potential inhibitors.
Genetic Code Expansion: Another Solution to Codon Assignments
Authors: Sakamoto Kensaku
Published: December 2022

This Special Issue is intended to highlight recent advances in genetic code expansion, particularly the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins [...]
Mechanisms of Myofibre Death in Muscular Dystrophies: The Emergence of the Regulated Forms of Necrosis in Myology
Authors: Bencze Maximilien
Published: December 2022

Myofibre necrosis is a central pathogenic process in muscular dystrophies (MD). As post-lesional regeneration cannot fully compensate for chronic myofibre loss, interstitial tissue accumulates and impairs muscle function. Muscle regeneration has been extensively studied over the last decades, however, the pathway(s) controlling muscle necrosis remains largely unknown. The recent discovery of several regulated cell death (RCD) pathways with necrotic morphology challenged the dogma of necrosis as an uncontrolled process, opening interesting perspectives for many degenerative disorders. In this review, we focus on how cell death affects myofibres in MDs, integrating the latest research in the cell death field, with specific emphasis on Duchenne muscular dystrophy, the best-known and most common hereditary MD. The role of regulated forms of necrosis in myology is still in its infancy but there is increasing evidence that necroptosis, a genetically programmed form of necrosis, is involved in muscle degenerating disorders. The existence of apoptosis in myofibre demise will be questioned, while other forms of non-apoptotic RCDs may also have a role in myonecrosis, illustrating the complexity and possibly the heterogeneity of the cell death pathways in muscle degenerating conditions.
The Endothelial Glycocalyx and Neonatal Sepsis
Authors: Fatmi Ahlam , Saadi Wiam , Beltrán-García Jesús , García-Giménez José Luis , Pallardó Federico V.
Published: December 2022

Sepsis carries a substantial risk of morbidity and mortality in newborns, especially preterm-born neonates. Endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the vascular endothelium, with important vascular barrier function and cell adhesion properties, serving also as a mechano-sensor for blood flow. eGC shedding is recognized as a fundamental pathophysiological process generating microvascular dysfunction, which in turn contributes to multiple organ failure and death in sepsis. Although the disruption of eGC and its consequences have been investigated intensively in the adult population, its composition, development, and potential mechanisms of action are still poorly studied during the neonatal period, and more specifically, in neonatal sepsis. Further knowledge on this topic may provide a better understanding of the molecular mechanisms that guide the sepsis pathology during the neonatal period, and would increase the usefulness of endothelial glycocalyx dysfunction as a diagnostic and prognostic biomarker. We reviewed several components of the eGC that help to deeply understand the mechanisms involved in the eGC disruption during the neonatal period. In addition, we evaluated the potential of eGC components as biomarkers and future targets to develop therapeutic strategies for neonatal sepsis.
Application of Extracellular Vesicles in Allergic Rhinitis: A Systematic Review
Authors: Czerwaty Katarzyna , Dżaman Karolina , Miechowski Wiktor
Published: December 2022

The pathophysiology of allergic rhinitis (AR), one of the most common diseases in the world, is still not sufficiently understood. Extracellular vesicles (EVs), which are secreted by host and bacteria cells and take part in near and distant intracellular communication, can provide information about AR. Recently, attention has been drawn to the potential use of EVs as biomarkers, vaccines, or transporters for drug delivery. In this review, we present an up-to-date literature overview on EVs in AR to reveal their potential clinical significance in this condition. A comprehensive and systematic literature search was conducted following PRISMA statement guidelines for original, completed articles, available in English concerning EVs and AR. For this purpose, PubMed/MEDLINE, Scopus, Web of Science, and Cochrane, were searched up until 10 Novenmber 2022. From 275 records, 18 articles were included for analysis. The risk of bias was assessed for all studies as low or moderate risk of overall bias using the Office and Health Assessment and Translation Risk of Bias Rating Tool for Human and Animal Studies. We presented the role of exosomes in the pathophysiology of AR and highlighted the possibility of using exosomes as biomarkers and treatment in this disease.
Effects of Oleuropein and Hydroxytyrosol on Inflammatory Mediators: Consequences on Inflammaging
Authors: Pojero Fanny , Aiello Anna , Gervasi Francesco , Caruso Calogero , Ligotti Mattia Emanuela , Calabrò Anna , Procopio Antonio , Candore Giuseppina , Accardi Giulia , Allegra Mario
Published: December 2022

Aging is associated with a low-grade, systemic inflammatory state defined as “inflammaging”, ruled by the loss of proper regulation of the immune system leading to the accumulation of pro-inflammatory mediators. Such a condition is closely connected to an increased risk of developing chronic diseases. A number of studies demonstrate that olive oil phenolic compound oleuropein and its derivative hydroxytyrosol contribute to modulating tissue inflammation and oxidative stress, thus becoming attractive potential candidates to be used in the context of nutraceutical interventions, in order to ameliorate systemic inflammation in aging subjects. In this review, we aim to summarize the available data about the anti-inflammatory properties of oleuropein and hydroxytyrosol, discussing them in the light of molecular pathways involved in the synthesis and release of inflammatory mediators in inflammaging.
Self-Assembled Daunorubicin/Epigallocatechin Gallate Nanocomplex for Synergistic Reversal of Chemoresistance in Leukemia
Authors: Bae Ki Hyun , Lai Fritz , Oruc Betul , Osato Motomi , Chen Qingfeng , Kurisawa Motoichi
Published: December 2022

Chemoresistance is one of the major challenges for the treatment of acute myeloid leukemia. Epigallocatechin gallate (EGCG), a bioactive polyphenol from green tea, has attracted immense interest as a potential chemosensitizer, but its application is limited due to the need for effective formulations capable of co-delivering EGCG and anti-leukemic drugs. Herein, we describe the formation and characterization of a micellar nanocomplex self-assembled from EGCG and daunorubicin, an anthracycline drug for the first-line treatment of acute myeloid leukemia. This nanocomplex was highly stable at pH 7.4 but stimulated to release the incorporated daunorubicin at pH 5.5, mimicking an acidic endosomal environment. More importantly, the nanocomplex exhibited superior cytotoxic efficacy against multidrug-resistant human leukemia cells over free daunorubicin by achieving a strong synergism, as supported by median-effect plot analysis. The observed chemosensitizing effect was in association with enhanced nucleus accumulation of daunorubicin, elevation of intracellular reactive oxygen species and caspase-mediated apoptosis induction. Our study presents a promising strategy for circumventing chemoresistance for more effective leukemia therapy.
Structural Factors That Determine the Activity of the Xenobiotic Reductase B Enzyme from Pseudomonas putida on Nitroaromatic Compounds
Authors: Osorio Manuel I. , Bruna Nicolás , García Víctor , González-Rodríguez Lisdelys , Leal Matías S. , Salgado Francisco , Vargas-Reyes Matías , González-Nilo Fernando , Pérez-Donoso José M. , Yáñez Osvaldo
Published: December 2022

Xenobiotic reductase B (XenB) catalyzes the reduction of the aromatic ring or nitro groups of nitroaromatic compounds with methyl, amino or hydroxyl radicals. This reaction is of biotechnological interest for bioremediation, the reuse of industrial waste or the activation of prodrugs. However, the structural factors that explain the binding of XenB to different substrates are unknown. Molecular dynamics simulations and quantum mechanical calculations were performed to identify the residues involved in the formation and stabilization of the enzyme/substrate complex and to explain the use of different substrates by this enzyme. Our results show that Tyr65 and Tyr335 residues stabilize the ligands through hydrophobic interactions mediated by the aromatic rings of these aminoacids. The higher XenB activity determined with the substrates 1,3,5-trinitrobenzene and 2,4,6-trinitrotoluene is consistent with the lower energy of the highest occupied molecular orbital (LUMO) orbitals and a lower energy of the homo orbital (LUMO), which favors electrophile and nucleophilic activity, respectively. The electrostatic potential maps of these compounds suggest that the bonding requires a large hydrophobic region in the aromatic ring, which is promoted by substituents in ortho and para positions. These results are consistent with experimental data and could be used to propose point mutations that allow this enzyme to process new molecules of biotechnological interest.
Protective Effect of Pioglitazone on Retinal Ganglion Cells in an Experimental Mouse Model of Ischemic Optic Neuropathy
Authors: Sun Ming-Hui , Chen Kuan-Jen , Sun Chi-Chin , Tsai Rong-Kung
Published: December 2022

The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL/6 mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-γ inhibitor) (1 mg/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 ± 4.9 cells/field) than in group 2 (24.0 ± 11.5 cells/field) and 3 (25.0 ± 7.7 cells/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 ± 2.6 cells/field; group 2: 15.6 ± 3.5 cells/field; and group 3: 14.8 ± 7.5 cells/field) and retinal thinning (group 1: 6.7 ± 5.7 μm; group 2: 12.8 ± 6.1 μm; and group 3: 15.8 ± 5.8 μm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A+ cells were significantly greater in group 2 (2382 ± 140 Brn3A+ cells/mm2, n = 7) than in group 1 (1920 ± 228 Brn3A+ cells/mm2; p = 0.03, n = 4), group 3 (1938 ± 213 Brn3A+ cells/mm2; p = 0.002, n = 4), and group 4 (2138 ± 126 Brn3A+ cells/mm2; p = 0.03, n = 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.
Coronavirus-Specific Antibody and T Cell Responses Developed after Sputnik V Vaccination in Patients with Chronic Lymphocytic Leukemia
Authors: Komissarov Alexey A. , Kislova Maria , Molodtsov Ivan A. , Petrenko Andrei A. , Dmitrieva Elena , Okuneva Maria , Peshkova Iuliia O. , Shakirova Naina T. , Potashnikova Daria M. , Tvorogova Anna V. , Ptushkin Vadim V. , Efimov Grigory A. , Nikitin Eugene A. , Vasilieva Elena
Published: December 2022

The clinical course of the new coronavirus disease 2019 (COVID-19) has shown that patients with chronic lymphocytic leukemia (CLL) are characterized by a high mortality rate, poor response to standard treatment, and low virus-specific antibody response after recovery and/or vaccination. To date, there are no data on the safety and efficacy of the combined vector vaccine Sputnik V in patients with CLL. Here, we analyzed and compared the magnitudes of the antibody and T cell responses after vaccination with the Sputnik V vaccine among healthy donors and individuals with CLL with different statuses of preexposure to coronavirus. We found that vaccination of the COVID-19–recovered individuals resulted in the boosting of pre-existing immune responses in both healthy donors and CLL patients. However, the COVID-19–naïve CLL patients demonstrated a considerably lower antibody response than the healthy donors, although they developed a robust T cell response. Regardless of the previous infection, the individuals over 70 years old demonstrated a decreased response to vaccination, as did those receiving anti-CD20 therapy. In summary, we showed that Sputnik V, like other vaccines, did not induce a robust antibody response in individuals with CLL; however, it provided for the development of a significant anti-COVID-19 T cell response.