bluuebunny/crossref_metadata_2025 huggingface dataset:
Certain Properties and Characterizations of Multivariable Hermite-Based Appell Polynomials via Factorization Method
Authors: Zayed Mohra , Wani Shahid Ahmad , Mahnashi Ali M.
Published: August 2023

This paper introduces a new type of polynomials generated through the convolution of generalized multivariable Hermite polynomials and Appell polynomials. The paper explores several properties of these polynomials, including recurrence relations, explicit formulas using shift operators, and differential equations. Further, integrodifferential and partial differential equations for these polynomials are also derived. Additionally, the study showcases the practical applications of these findings by applying them to well-known polynomials, such as generalized multivariable Hermite-based Bernoulli and Euler polynomials. Thus, this research contributes to advancing the understanding and utilization of these hybrid polynomials in various mathematical contexts.
Tissue Reaction to Low-Density Polyacrylamide Gel as a Carrier for Microimplants in the Adipose Fin of Rainbow Trout
Authors: Borvinskaya Ekaterina , Matrosova Svetlana , Sukhovskaya Irina , Drozdova Polina , Titov Evgeniy , Anikienko Inna , Lubyaga Yulia , Gurkov Anton , Timofeyev Maxim
Published: August 2023

The implantation of optical sensors is a promising method for monitoring physiological parameters of organisms in vivo. For this, suitable hydrogels are required that can provide a biocompatible interface with the organism’s tissues. Amorphous hydrogel is advantageous for administration in animal organs due to its ease of injection compared to resilient analogs. In this study, we investigated the applicability of a semi-liquid 2.5% polyacrylamide hydrogel (PAAH) as a scaffold for fluorescent polyelectrolyte microcapsules (PMs) in rainbow trout. The hydrogel was injected subcutaneously into the adipose fin, which is a small, highly translucent fold of skin in salmonids that is convenient for implanting optical sensors. Using histological methods, we compared tissue organization and in vivo stability of the applied hydrogel at the injection site after administration of uncoated PMs or PMs coated with 2.5% PAAH (PMs-PAAH) for a period of 3 to 14 days. Our results showed that the introduction of PMs into the gel did not have a masking effect, as they were recognized, engulfed, and carried away by phagocytes from the injection site. However, both PMs and PMs-PAAH were found to provoke chronic inflammation at the injection site, although according to cytokine expression in the fish spleen, the irritating effect was local and did not affect the systemic immunity of the fish. Therefore, our study suggests low applicability of 2.5% polyacrylamide as a scaffold for injectable sensors within a timeframe of days.
Development of Blended Biopolymer-Based Photocatalytic Hydrogel Beads for Adsorption and Photodegradation of Dyes
Authors: Weon Seung Hyeon , Han Jiwoo , Choi Yong-Keun , Park Saerom , Lee Sang Hyun
Published: August 2023

Blended biopolymer-based photocatalytic hydrogel beads were synthesized by dissolving the biopolymers in 1-ethyl-3-methylimidazolium acetate ([Emim][Ac]), adding TiO2, and reconstituting the beads with ethanol. The incorporation of modifying biopolymer significantly enhanced the adsorption capacity of the cellulose/TiO2 beads. Cellulose/carrageenan/TiO2 beads exhibited a 7.0-fold increase in adsorption capacity for methylene blue (MB). In contrast, cellulose/chitosan/TiO2 beads showed a 4.8-fold increase in adsorption capacity for methyl orange (MO) compared with cellulose/TiO2 beads. In addition, cellulose/TiO2 microbeads were prepared through the sol–gel transition of the [Emim][Ac]-in-oil emulsion to enhance photodegradation activity. These microbeads displayed a 4.6-fold higher adsorption capacity and 2.8-fold higher photodegradation activity for MB than the millimeter-sized beads. Furthermore, they exhibited superior dye removal efficiencies for various dyes such as Congo red, MO, MB, crystal violet, and rhodamine B, surpassing the performance of larger beads. To expand the industrial applicability of the microbeads, biopolymer/TiO2 magnetic microbeads were developed by incorporating Fe2O3. These magnetic microbeads outperformed millimeter-sized beads regarding the efficiency and time required for MB removal from aqueous solutions. Furthermore, the physicochemical properties of magnetic microbeads can be easily controlled by adjusting the type of biopolymer modifier, the TiO2 and magnetic particle content, and the ratio of each component based on the target molecule. Therefore, biopolymer-based photocatalytic magnetic microbeads have great potential not only in environmental fields but also in biomedical fields.
Autosomal Recessive Limb-Girdle Muscular Dystrophy-3: A Case Report of a Patient with Autism Spectrum Disorder
Authors: Lewis Sivan , Woroch Amy , Hatch Mary Kate , Lozano Reymundo
Published: August 2023

Limb-girdle muscular dystrophies are a group of genetic disorders classically manifesting with progressive proximal muscle weakness. Affected individuals present with atrophy and weakness of the muscles of the shoulders and hips, and in some cases, intellectual disability or developmental delay has also been reported. Limb-girdle muscular dystrophy-3 is a recessive disorder caused by biallelic variants in the SGCA gene. Similarly, symptoms include proximal muscle weakness, elevated CPK, calf muscle pseudohypertrophy, and mobility issues. Cardiac symptoms and respiratory insufficiency are also common symptoms. This case report details a 3-year-old male with muscular weakness, elevated CK, and a neurodevelopmental disorder in whom a homozygous missense variant in c.229C>T (p.Arg77Cys) associated with limb-girdle muscular dystrophy-3 was found. This report shows the association between SGCA c.229C>T and neurodevelopmental disorders as observed in other muscular dystrophies.
Effectiveness of a Health Education Program in Hypertensive Patients with Dyslipidemia and/or Microalbuminuria: A Quasi-Experimental Study in Vinh Long Province, Vietnam
Authors: Le Minh Huu , Nguyen Trung Kien , Pham Thi Tam , Pham Trung Tin , Tran Van De
Published: August 2023

Introduction: Hypertension, a major health concern, is associated with significant mortality and disease burden worldwide, including Vietnam. Comprehensive interventions targeting medication, lifestyle modifications, dyslipidemia (DLP), and microalbuminuria (MAU) are vital for effective hypertension management and reducing the risk of cardiovascular disease complications (CDV). While medication interventions have proven efficacy, the evidence regarding the effectiveness of community-based health education interventions in managing DLP and MAU is limited. Therefore, this study aims to evaluate the effectiveness of community health education interventions in reducing hypertension risk factors and achieving hypertension management objectives, as well as managing DLP and MAU among hypertension patients. Methods: A quasi-experimental study was conducted on 330 hypertensive patients with dyslipidemia (DLP) and/or microalbuminuria (MAU) who were divided into a control group (n = 164) and an intervention group (n = 166). The control group received standard national hypertension management, while the intervention group received additional intensive health education provided by trained volunteers. The effectiveness of the intervention was assessed by comparing outcomes such as lifestyle factors, BMI control, treatment adherence, hypertension control, and DLP and MAU status between the two groups before and after a two-year intervention period. Results: The health education intervention resulted in significant reductions in dietary risk factors, specifically in fruit and vegetable consumption (p < 0.001). There was a lower prevalence of high salt intake in the intervention group compared to the control group (p = 0.002), while no significant differences were observed in other dietary factors. Smoking habits and low physical activity significantly decreased in the intervention group, with a notable disparity in physical activity proportions (p < 0.001). Both groups showed significant improvements in achieving hypertension management targets, with the intervention group demonstrating superior outcomes. The intervention was effective in reducing the prevalence of risk factors, particularly treatment non-adherence, blood pressure control, and low physical activity. Additionally, the intervention group had a higher likelihood of achieving DLP and MAU control compared to the control group. Conclusions: This study underscored the additional positive impact of incorporating health education by non-professional educators in achieving favorable outcomes, including better control of BMI, blood pressure, medication adherence, and management of dyslipidemia (DLP) and microalbuminuria (MAU). Further research is warranted to fully explore the potential of health education in primary healthcare settings and maximize its effectiveness.
Factor Structure of the GHQ-12 and Their Applicability to Epilepsy Patients for Screening Mental Health Problems
Authors: Kang Weixi
Published: August 2023

Epilepsy, a severe neurological disorder impacting approximately 50 million individuals worldwide, is associated with a high prevalence of mental health issues. However, existing research has predominantly examined the relationship between epilepsy and depression or anxiety, neglecting other dimensions of mental health as assessed by factor scores from the general health survey (GHQ), such as the GHQ-12. This study aimed to explore how epilepsy affects both general mental health and specific dimensions of mental health. By employing a factor analysis and a predictive normative modeling approach, the study examined 426 epilepsy patients and 39,171 individuals without epilepsy. The findings revealed that epilepsy patients experienced poorer general mental health and specific aspects of mental health. Consequently, this study highlights the validity of GHQ-12 as a measure of mental health problems in epilepsy patients and emphasizes the importance of considering the impact of epilepsy on various dimensions of mental health, rather than focusing solely on depression or anxiety. Clinicians should incorporate these study results into the development of interventions aimed at enhancing mental well-being in epilepsy patients, ultimately leading to improved outcomes.
Removing English Walnut (Juglans Regia) Ready-to-Use Shelled Walnuts Consumption Barriers
Authors: Crisosto Carlos H. , Donis-Gonzalez Irwin R. , Wang Selina C. , Lampinen Bruce D.
Published: August 2023

Because of the vast information on health benefits and the urbanization impact changes in eating habits, the demand for ready-to-use shelled walnuts as a convenient, healthy, and nutritious snack food is increasing all over the world. However, shelled nuts sold as halves or pieces in ‘ready-to-use’ small packages are more susceptible to pellicle darkening and rancidity than their in-shell equivalents. Currently, about two-thirds of the USA crop is exported, and ~66% of these exports are sold as shelled ‘ready to use’, and its demand is increasing. Yet, this package style is generating quality challenges due to the darkening and rancidification of the kernel pellicle. Protection against kernel color quality loss and rancidity during postharvest handling, even at warm temperatures, can be accomplished at 6 kPa (%) oxygen or less for ‘Chandler’ and 3 kPa or less for ‘Howard’ and ‘Tulare’. The application of the ‘cold chain’ principle and/or low oxygen technology is unpractical for large cropping systems. Thus, a useful quality control system to rank the lots based on their potential visual and sensory quality is important. Then, the lots can be selected based on their potential quality, match market destinations, and are subjected to proper postharvest technologies.
Effect of Ti-Based Additives on the Hydrogen Storage Properties of MgH2: A Review
Authors: Jangir Mukesh , Jain Indra Prabh , Mirabile Gattia Daniele
Published: August 2023

For the few past decades, study of new hydrogen storage materials has been captivating scientists worldwide. Magnesium hydride, MgH2, is considered one of the most promising materials due to its low cost, high hydrogen capacity, reversibility and the abundance of Mg. However, it requires further research to improve its hydrogen storage performance as it has some drawbacks such as poor dehydrogenation kinetic, high operational temperature, which limit its practical application. In this study, we introduce an overview of recent progress in improving the hydrogen storage performance of MgH2 by the addition of titanium-based additives, which are one of the important groups of additives. The role of Ti-based additive hydrides, oxides, halides, carbides and carbonitrides are overviewed. In addition, the existing challenges and future perspectives of Mg-based hydrides are also discussed.
The Status of Sanitation in Malawi: Is SDG6.2 Achievable?
Authors: Hinton Rebekah G. K. , Macleod Christopher J. A. , Troldborg Mads , Kanjaye Modesta B. , Kalin Robert M.
Published: August 2023

Ensuring access to adequate and equitable sanitation and ending open defecation by 2030 is the focus of Sustainable Development Goal 6.2 (SDG6.2). We evaluated Malawi’s progress towards SDG 6.2 (specifically the goal to end open defecation), presenting the results of a national survey of over 200,000 sanitary facilities and evaluating their management. Based on non-linear population dynamics, we used a linear model to evaluate the reduction in open defecation between 1992–2018, and to project whether Malawi can meet the SDG target to end open defecation by 2030 under multiple scenarios of population growth. Whilst Malawi has made considerable progress in providing sanitary provision for the population, we estimate that, at the current rate of the provision of sanitary facilities, Malawi will not reach SDG 6.2 by 2030 under any of the modelled socioeconomic scenarios. Furthermore, we compare the estimates of the extent of sanitary provision classed as improved from multiple surveys, including the USAID Demographic and Health (DHS) Surveys and Government of Malawi Census data. We conclude that some of the surveys (particularly the 2015/16 DHS) may be overestimating the level of improved sanitary provision, and we hypothesize that this is due to how pit-latrines with earth/sand slabs are classed. Furthermore, we examine the long-term sustainability of pit-latrine use, investigating the challenge of pit-latrine abandonment and identifying pit-latrine filling as a cause of the abandonment in 30.2% of cases. We estimate that between 2020–2070, 31.8 (range 2.8 to 3320) million pit-latrines will be filled and abandoned, representing a major challenge for the safe management of abandoned latrines, a potential for long-term impacts on the groundwater quality, and a significant loss of investment in sanitary infrastructure. For Malawi to reach SDG 6.2, improvements are needed in both the quantity and quality of its sanitary facilities.
Behavioral Self-Blame in PTSD—Etiology, Risk Factors, and Proposed Interventions
Authors: Raz Aviad , Rubinstein Ravit , Shadach Eran , Chaikin Gal , Ben Yehuda Ariel , Tatsa-Laur Lucian , Kedem Ron , Shelef Leah
Published: August 2023

Background: Feeling out of control during a traumatic event may evoke behavioral self-blame (BSB) to avoid feeling helpless following trauma by restoring one’s sense of control. BSB is a common, persistent, and treatment-resistant post-traumatic stress symptom. The present study investigates the etiology and risk factors of BSB following a traumatic event and the reasons for its persistence over time. Method: Subjects were a group of 546 Israeli ex-combat soldiers (M age = 24.93 ± 5.657) registered in an Israel Defense Forces (IDF) combat reaction clinic. All completed the Peritraumatic Dissociative Experiences Questionnaire (PDEQ), the Brief Symptom Inventory (BSI), and the PTSD Checklist for the DSM-5 (PCL-5). Item 10 of the PCL-5 served to measure BSB. The PDEQ and BSI measured distress and feeling out of control during the event. We used descriptive analyses of the data, t-test, and linear regression analysis to reveal the relationship between the research variables. Results: Feeling out of control during a traumatic event often increases BSB and post-traumatic stress symptoms. A significant correlation emerged between continuing distress characterizing individuals who experience a persistent lack of control and BSB. Female combat soldiers were at a higher risk of BSB than their male counterparts. Conclusion: Loss of control experienced during a traumatic event may result in persistent long-term feelings of lack of control over one’s behavior.
Broad Scale Spatial Modelling of Wet Bulb Globe Temperature to Investigate Impact of Shade and Airflow on Heat Injury Risk and Labour Capacity in Warm to Hot Climates
Authors: Hall Andrew , Horta Ana
Published: August 2023

While shade and air flow are recognised factors that reduce outdoor heat exposure, the level of reduction in terms of labour capacity at varying air temperature and humidity levels is poorly understood. This study investigated cooling effects on the commonly used heat index, wet bulb globe temperature (WBGT), and subsequent impact on labour capacity, for a range of air flow and shade conditions in warm to hot climates. We modelled heat exposure using a physics-based method to map WBGT for a case study region which experiences a range of heat categories with varying levels of health risks for outdoor workers. Continent-scale modelling confirmed significant spatial variability in the effect of various shade and wind speed scenarios across a range of real-world mid-summer daytime conditions. At high WBGTs, increasing shade or air flow for outdoor workers lowered heat exposure and increases labour capacity, with shade giving the greatest benefit, but cooling varied considerably depending upon underlying air temperature and humidity. Shade had the greater cooling effect; reducing incident radiation by 90% decreased WBGT by 2–6 °C depending on location. Wind had a lower cooling effect in the hottest regions, with a decreasing exponential relationship between wind speed and WBGT observed.
Comparison of Soft Indicator and Poisson Kriging for the Noise-Filtering and Downscaling of Areal Data: Application to Daily COVID-19 Incidence Rates
Authors: Goovaerts Pierre , Hermans Thomas , Goossens Peter F. , Van De Vijver Ellen
Published: August 2023

This paper addresses two common challenges in analyzing spatial epidemiological data, specifically disease incidence rates recorded over small areas: filtering noise caused by small local population sizes and deriving estimates at different spatial scales. Geostatistical techniques, including Poisson kriging (PK), have been used to address these issues by accounting for spatial correlation patterns and neighboring observations in smoothing and changing spatial support. However, PK has a limitation in that it can generate unrealistic rates that are either negative or greater than 100%. To overcome this limitation, an alternative method that relies on soft indicator kriging (IK) is presented. The performance of this method is compared to PK using daily COVID-19 incidence rates recorded in 2020–2021 for each of the 581 municipalities in Belgium. Both approaches are used to derive noise-filtered incidence rates for four different dates of the pandemic at the municipality level and at the nodes of a 1 km spacing grid covering the country. The IK approach has several attractive features: (1) the lack of negative kriging estimates, (2) the smaller smoothing effect, and (3) the better agreement with observed municipality-level rates after aggregation, in particular when the original rate was zero.
LRG1 Promotes ECM Integrity by Activating the TGF-β Signaling Pathway in Fibroblasts
Authors: Park Han Na , Song Min Ji , Choi Young Eun , Lee Dong Hun , Chung Jin Ho , Lee Seung-Taek
Published: August 2023

Leucine-rich alpha-2-glycoprotein 1 (LRG1) mediates skin repair and fibrosis by stimulating the transforming growth factor-beta (TGF-β) signaling pathway. In the present study, we investigated the effect of LRG1 on extracellular matrix (ECM) integrity in fibroblasts, as well as on skin aging. The treatment of dermal fibroblasts with purified recombinant human LRG1 increased type I collagen secretion and decreased matrix metalloproteinase-1 secretion. Additionally, LRG1 promoted SMAD2/SMAD3 phosphorylation in a pattern similar to that of TGF-β1 treatment. An inhibitor of TGF-β receptor 1 abolished LRG1-induced SMAD2 phosphorylation. RNA sequencing identified “extracellular region”, “extracellular space”, and “extracellular matrix” as the main Gene Ontology terms in the differentially expressed genes of fibroblasts treated with or without LRG1. LRG1 increased TGF-β1 mRNA levels, suggesting that LRG1 partially transactivates the expression of TGF-β1. Furthermore, an increased expression of type I collagen was also observed in fibroblasts grown in three-dimensional cultures on a collagen gel mimicking the dermis. LRG1 mRNA and protein levels were significantly reduced in elderly human skin tissues with weakened ECM integrity compared to in young human skin tissues. Taken together, our results suggest that LRG1 could retard skin aging by activating the TGF-β signaling pathway, increasing ECM deposition while decreasing its degradation.
A Comprehensive Self-Resistance Gene Database for Natural-Product Discovery with an Application to Marine Bacterial Genome Mining
Authors: Dong Hua , Ming Dengming
Published: August 2023

In the world of microorganisms, the biosynthesis of natural products in secondary metabolism and the self-resistance of the host always occur together and complement each other. Identifying resistance genes from biosynthetic gene clusters (BGCs) helps us understand the self-defense mechanism and predict the biological activity of natural products synthesized by microorganisms. However, a comprehensive database of resistance genes is still lacking, which hinders natural product annotation studies in large-scale genome mining. In this study, we compiled a resistance gene database (RGDB) by scanning the four available databases: CARD, MIBiG, NCBIAMR, and UniProt. Every resistance gene in the database was annotated with resistance mechanisms and possibly involved chemical compounds, using manual annotation and transformation from the resource databases. The RGDB was applied to analyze resistance genes in 7432 BGCs in 1390 genomes from a marine microbiome project. Our calculation showed that the RGDB successfully identified resistance genes for more than half of the BGCs, suggesting that the database helps prioritize BGCs that produce biologically active natural products.
Genome-Wide Identification and Expression Analysis under Abiotic Stress of BrAHL Genes in Brassica rapa
Authors: Zhang Xiaoyu , Li Jiali , Cao Yunyun , Huang Jiabao , Duan Qiaohong
Published: August 2023

The AT-hook motif nuclear localized (AHL) gene family is a highly conserved transcription factor critical for the growth, development, and stress tolerance of plants. However, the function of the AHL gene family in Brassica rapa (B. rapa) remains unclear. In this study, 42 AHL family members were identified from the B. rapa genome and mapped to nine B. rapa chromosomes. Two clades have formed in the evolution of the AHL gene family. The results showed that most products encoded by AHL family genes are located in the nucleus. Gene duplication was common and expanded the BrAHL gene family. According to the analysis of cis-regulatory elements, the genes interact with stress responses (osmotic, cold, and heavy metal stress), major hormones (abscisic acid), and light responses. In addition, the expression profiles revealed that BrAHL genes are widely expressed in different tissues. BrAHL16 was upregulated at 4 h under drought stress, highly expressed under cadmium conditions, and downregulated in response to cold conditions. BrAHL02 and BrAHL24 were upregulated at the initial time point and peaked at 12 h under cold and cadmium stress, respectively. Notably, the interactions between AHL genes and proteins under drought, cold, and heavy metal stresses were observed when predicting the protein-protein interaction network.
Innovative Approaches for Food: Using Natural Phenolic-Rich Extracts to Produce Value-Added Fresh Pasta
Authors: Gomes Sandra M. , Albuquerque Daniela , Santos Lúcia
Published: August 2023

Cereal-based products, which are rich in carbohydrates, are widely consumed worldwide; however, this type of food lacks other nutrients. Phenolic compounds from natural sources, such as Moringa oleifera, can be incorporated into these products to increase their nutritional and biological value. In this study, a phenolic-rich extract was obtained from M. oleifera leaf powder using a Soxhlet extractor. The extract obtained presented a total phenolic content of 79.0 mg of gallic acid equivalents/g and the ABTS and DPPH assays showed that the extract can act as an anti-oxidant agent, with IC50 values of 205.2 mg/L and 636.0 mg/L, respectively. Afterwards, fresh pasta was produced and the extract was incorporated into the pasta to improve its biological properties and extend its shelf-life. The results demonstrated that the addition of M. oleifera to the fresh pasta increased its anti-oxidant capacity and did not interfere with the cooking properties of the product. Moreover, the fortified pasta presented an increased shelf-life, since the extract conferred protection against microbial contamination for longer periods of time. Therefore, these findings showed that the incorporation of phenolic-rich extracts from natural sources (such as M. oleifera) is a feasible sustainable biotechnological approach to produce value-added cereal-based products.
Changes in the Mitochondria in the Aging Process—Can α-Tocopherol Affect Them?
Authors: Napolitano Gaetana , Fasciolo Gianluca , Muscari Tomajoli Maria Teresa , Venditti Paola
Published: August 2023

Aerobic organisms use molecular oxygen in several reactions, including those in which the oxidation of substrate molecules is coupled to oxygen reduction to produce large amounts of metabolic energy. The utilization of oxygen is associated with the production of ROS, which can damage biological macromolecules but also act as signaling molecules, regulating numerous cellular processes. Mitochondria are the cellular sites where most of the metabolic energy is produced and perform numerous physiological functions by acting as regulatory hubs of cellular metabolism. They retain the remnants of their bacterial ancestors, including an independent genome that encodes part of their protein equipment; they have an accurate quality control system; and control of cellular functions also depends on communication with the nucleus. During aging, mitochondria can undergo dysfunctions, some of which are mediated by ROS. In this review, after a description of how aging affects the mitochondrial quality and quality control system and the involvement of mitochondria in inflammation, we report information on how vitamin E, the main fat-soluble antioxidant, can protect mitochondria from age-related changes. The information in this regard is scarce and limited to some tissues and some aspects of mitochondrial alterations in aging. Improving knowledge of the effects of vitamin E on aging is essential to defining an optimal strategy for healthy aging.
The Complex Proteolipidic Behavior of the SARS-CoV-2 Envelope Protein Channel: Weak Selectivity and Heterogeneous Oligomerization
Authors: Surya Wahyu , Tavares-Neto Ernesto , Sanchis Andrea , Queralt-Martín María , Alcaraz Antonio , Torres Jaume , Aguilella Vicente M.
Published: August 2023

The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum–Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of “cation-selective channels”. However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms bona fide specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca2+ ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures.
Amniotic Membrane-Derived Stromal Cells Release Extracellular Vesicles That Favor Regeneration of Dystrophic Skeletal Muscles
Authors: Sandonà Martina , Esposito Federica , Cargnoni Anna , Silini Antonietta , Romele Pietro , Parolini Ornella , Saccone Valentina
Published: August 2023

Duchenne muscular dystrophy (DMD) is a muscle disease caused by mutations in the dystrophin gene characterized by myofiber fragility and progressive muscle degeneration. The genetic defect results in a reduced number of self-renewing muscle stem cells (MuSCs) and an impairment of their activation and differentiation, which lead to the exhaustion of skeletal muscle regeneration potential and muscle replacement by fibrotic and fatty tissue. In this study, we focused on an unexplored strategy to improve MuSC function and to preserve their niche based on the regenerative properties of mesenchymal stromal cells from the amniotic membrane (hAMSCs), that are multipotent cells recognized to have a role in tissue repair in different disease models. We demonstrate that the hAMSC secretome (CM hAMSC) and extracellular vesicles (EVs) isolated thereof directly stimulate the in vitro proliferation and differentiation of human myoblasts and mouse MuSC from dystrophic muscles. Furthermore, we demonstrate that hAMSC secreted factors modulate the muscle stem cell niche in dystrophic–mdx-mice. Interestingly, local injection of EV hAMSC in mdx muscles correlated with an increase in the number of activated Pax7+/Ki67+ MuSCs and in new fiber formation. EV hAMSCs also significantly reduced muscle collagen deposition, thus counteracting fibrosis and MuSCs exhaustion, two hallmarks of DMD. Herein for the first time we demonstrate that CM hAMSC and EVs derived thereof promote muscle regeneration by supporting proliferation and differentiation of resident muscle stem cells. These results pave the way for the development of a novel treatment to counteract DMD progression by reducing fibrosis and enhancing myogenesis in dystrophic muscles.
Amino Acid Profiling of Follicular Fluid in Assisted Reproduction Reveals Important Roles of Several Amino Acids in Patients with Insulin Resistance
Authors: Kurdi Csilla , Lelovics Vanessza , Hesszenberger Dávid , Lajtai Anikó , Lakatos Ágnes , Herczeg Róbert , Gödöny Krisztina , Mauchart Péter , Várnagy Ákos , Kovács Gábor L. , Kőszegi Tamás
Published: August 2023

The global prevalence of insulin resistance (IR) is increasing continuously, influencing metabolic parameters and fertility. The metabolic changes due to IR can alter the molecular composition of plasma and other body fluids. Follicular fluid (FF) is derived mainly from plasma, and it is a critical microenvironment for the developing oocytes. It contains various metabolites and amino acids, and the quality of the oocytes is linked at least partially to amino acid metabolism. Our goal was to quantitatively determine the amino acid (AA) profile of FF in IVF patients and to compare IR and non-insulin resistance (NIR) groups to investigate the AA changes in their FF. Using UHPLC-based methods, we quantified the main 20 amino acids from human FF samples in the IR and NIR groups. Several amino acids (aspartate, glycine, glutamate, and cysteine) differed significantly (p < 0.05 or less) between the two groups. The most significant alterations between the IR and NIR groups were related to the glutathione metabolic pathway involving glycine, serine, and threonine. Since insulin resistance alters the amino acid composition of the FF, the oocytes may undergo metabolism-induced changes resulting in poor oocyte quality and less fertility in the insulin resistance groups.
BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study
Authors: Bertol Bruna C. , Massaro Juliana D. , Debortoli Guilherme , Santos André L. P. , de Araújo Jéssica N. G. , Giorgenon Tatiana M. V. , Costa e Silva Matheus , de Figueiredo-Feitosa Nathalie L. , Collares Cristhianna V. A. , de Freitas Luiz Carlos C. , Soares Edson G. , Neder Luciano , Silbiger Vivian N. , Calado Rodrigo T. , Maciel Léa M. Z. , Donadi Eduardo A.
Published: August 2023

As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAFV600E and TERT promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAFV600E (52.9%) and TERTC228T (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The TERT rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the BRAF, TERT, and/or HLA-G genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAFV600E and TERTC228T; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the BRAF and/or HLA-G genes may explain their increased expression in the tumor milieu.
Enzymatic Redox Properties and Cytotoxicity of Irreversible Nitroaromatic Thioredoxin Reductase Inhibitors in Mammalian Cells
Authors: Nemeikaitė-Čėnienė Aušra , Misevičienė Lina , Marozienė Audronė , Jonušienė Violeta , Čėnas Narimantas
Published: August 2023

NADPH:thioredoxin reductase (TrxR) is considered a potential target for anticancer agents. Several nitroheterocyclic sulfones, such as Stattic and Tri-1, irreversibly inhibit TrxR, which presumably accounts for their antitumor activity. However, it is necessary to distinguish the roles of enzymatic redox cycling, an inherent property of nitroaromatics (ArNO2), and the inhibition of TrxR in their cytotoxicity. In this study, we calculated the previously unavailable values of single-electron reduction potentials of known inhibitors of TrxR (Stattic, Tri-1, and 1-chloro-2,4-dinitrobenzene (CDNB)) and inhibitors identified (nitrofuran NSC697923 and nitrobenzene BTB06584). These calculations were according to the rates of their enzymatic single-electron reduction (PMID: 34098820). This enabled us to compare their cytotoxicity with that of model redox cycling ArNO2. In MH22a and HCT-116 cells, Tri-1, Stattic, CDNB, and NSC697023 possessed at least 10-fold greater cytotoxicity than can be expected from their redox cycling activity. This may be related to TrxR inhibition. The absence of enhanced cytotoxicity in BTB06548 may be attributed to its instability. Another known inhibitor of TrxR, tetryl, also did not possess enhanced cytotoxicity, probably because of its detoxification by DT-diaphorase (NQO1). Apart from the reactions with NQO1, the additional mechanisms influencing the cytotoxicity of the examined inhibitors of TrxR are their reactions with cytochromes P-450. Furthermore, some inhibitors, such as Stattic and NSC697923, may also inhibit glutathione reductase. We suggest that these data may be instrumental in the search for TrxR inhibitors with enhanced cytotoxic/anticancer activity.
Potential Harm of IQOS Smoke to Rat Liver
Authors: Granata Silvia , Canistro Donatella , Vivarelli Fabio , Morosini Camilla , Rullo Laura , Mercatante Dario , Rodriguez-Estrada Maria Teresa , Baracca Alessandra , Sgarbi Gianluca , Solaini Giancarlo , Ghini Severino , Fagiolino Ivan , Sangiorgi Stefano , Paolini Moreno
Published: August 2023

The Food and Drug Administration has recently classified the IQOS electronic cigarette as a modified-risk tobacco product. However, IQOS cigarettes still release various harmful constituents typical of conventional cigarettes (CCs), although the concentrations are markedly lower. Here, we investigated the damaging effects of IQOS smoking on the liver. Male Sprague Dawley rats were exposed, whole body, 5 days/week for 4 weeks to IQOS smoke (4 sticks/day), and hepatic xenobiotic metabolism, redox homeostasis and lipidomic profile were investigated. IQOS boosted reactive radicals and generated oxidative stress. Exposure decreased cellular reserves of total glutathione (GSH) but not GSH-dependent antioxidant enzymes. Catalase and xanthine oxidase were greater in the exposed group, as were various hepatic CYP-dependent monooxygenases (CYP2B1/2, CYP1A1, CYP2A1, CYP2E1-linked). Respiratory chain activity was unaltered, while the number of liver mitochondria was increased. IQOS exposure had an impact on the hepatic lipid profile. With regard to the expression of some MAP kinases commonly activated by CC smoking, IQOS increased the p-p38/p38 ratio, while erythroid nuclear transcription factor 2 (Nrf2) was negatively affected. Our data suggest that IQOS significantly impairs liver function, supporting the precautionary stance taken by the WHO toward the use of these devices, especially by young people and pregnant women.
An Update on Toll-like Receptor 2, Its Function and Dimerization in Pro- and Anti-Inflammatory Processes
Authors: Colleselli Katrin , Stierschneider Anna , Wiesner Christoph
Published: August 2023

While a certain level of inflammation is critical for humans to survive infection and injury, a prolonged inflammatory response can have fatal consequences. Pattern recognition Toll-like receptors (TLRs) are key players in the initiation of an inflammatory process. TLR2 is one of the most studied pattern recognition receptors (PRRs) and is known to form heterodimers with either TLR1, TLR4, TLR6, and TLR10, allowing it to recognize a wide range of pathogens. Although a large number of studies have been conducted over the past decades, there are still many unanswered questions regarding TLR2 mechanisms in health and disease. In this review, we provide an up-to-date overview of TLR2, including its homo- and heterodimers. Furthermore, we will discuss the pro- and anti-inflammatory properties of TLR2 and recent findings in prominent TLR2-associated infectious and neurodegenerative diseases.
Involvement of Innate Immune System in the Pathogenesis of Sepsis-Associated Acute Kidney Injury
Authors: Uchida Takahiro , Yamada Muneharu , Inoue Dan , Kojima Tadasu , Yoshikawa Noriko , Suda Shingo , Kamohara Hidenobu , Oda Takashi
Published: August 2023

Although experimental models have shown that the innate immune system is a main contributor to acute kidney injury (AKI), its involvement in human sepsis-associated AKI (SA-AKI) remains unclear. We retrospectively evaluated 19 patients with SA-AKI who were treated with continuous renal replacement therapy (CRRT). Serum cytokine, complement components, and the proportion and functions of innate immune cells, such as CD56+ T cells, CD56+ natural killer (NK) cells, and monocytes, were analyzed. There were no differences in the proportions of CD56+ T and NK cells between patients with SA-AKI and healthy controls. In patients with SA-AKI, fas ligand (FasL) expression in CD56+ T cells was significantly upregulated, and the proportion of perforin-positive CD56+ T cells tended to be higher than that in healthy controls. The positive rate of both FasL and perforin of CD56+ T cells was significantly higher than that of CD56- T cells, which include cytotoxic T cells. Antigen-presenting capacity and phagocytic activity of monocytes in patients with SA-AKI were significantly decreased compared to those of healthy controls and did not recover soon after the initiation of CRRT. CD56+ T cells are involved in the disease processes of human SA-AKI through effector molecules such as FasL or perforin.
The Transcription Factor MbWRKY46 in Malus baccata (L.) Borkh Mediate Cold and Drought Stress Responses
Authors: Liu Wanda , Wang Tianhe , Wang Yu , Liang Xiaoqi , Han Jilong , Hou Ruining , Han Deguo
Published: August 2023

The living environment of plants is not static; as such, they will inevitably be threatened by various external factors for their growth and development. In order to ensure the healthy growth of plants, in addition to artificial interference, the most important and effective method is to rely on the role of transcription factors in the regulatory network of plant responses to abiotic stress. This study conducted bioinformatics analysis on the MbWRKY46 gene, which was obtained through gene cloning technology from Malus baccata (L.) Borkh, and found that the MbWRKY46 gene had a total length of 1068 bp and encodes 355 amino acids. The theoretical molecular weight (MW) of the MbWRKY46 protein was 39.76 kDa, the theoretical isoelectric point (pI) was 5.55, and the average hydrophilicity coefficient was −0.824. The subcellular localization results showed that it was located in the nucleus. After conducting stress resistance studies on it, it was found that the expression of MbWRKY46 was tissue specific, with the highest expression level in roots and old leaves. Low temperature and drought had a stronger induction effect on the expression of this gene. Under low temperature and drought treatment, the expression levels of several downstream genes related to low temperature and drought stress (AtKIN1, AtRD29A, AtCOR47A, AtDREB2A, AtERD10, AtRD29B) increased more significantly in transgenic Arabidopsis. This indicated that MbWRKY46 gene can be induced to upregulate expression in Arabidopsis under cold and water deficient environments. The results of this study have a certain reference value for the application of M. baccata MbWRKY46 in low-temperature and drought response, and provide a theoretical basis for further research on its function in the future.
A Systematic Review on the Continuous Cropping Obstacles and Control Strategies in Medicinal Plants
Authors: Zeeshan Ul Haq Muhammad , Yu Jing , Yao Guanglong , Yang Huageng , Iqbal Hafiza Amina , Tahir Hassam , Cui Hongguang , Liu Ya , Wu Yougen
Published: August 2023

Continuous cropping (CC) is a common practice in agriculture, and usually causes serious economic losses due to soil degeneration, decreased crop yield and quality, and increased disease incidence, especially in medicinal plants. Continuous cropping obstacles (CCOs) are mainly due to changes in soil microbial communities, nutrient availability, and allelopathic effects. Recently, progressive studies have illustrated the molecular mechanisms of CCOs, and valid strategies to overcome them. Transcriptomic and metabolomics analyses revealed that identified DEGs (differently expressed genes) and metabolites involved in the response to CCOs are involved in various biological processes, including photosynthesis, carbon metabolism, secondary metabolite biosynthesis, and bioactive compounds. Soil improvement is an effective strategy to overcome this problem. Soil amendments can improve the microbial community by increasing the abundance of beneficial microorganisms, soil fertility, and nutrient availability. In this review, we sum up the recent status of the research on CCOs in medicinal plants, the combination of transcriptomic and metabolomics studies, and related control strategies, including uses of soil amendments, crop rotation, and intercropping. Finally, we propose future research trends for understanding CCOs, and strategies to overcome these obstacles and promote sustainable agriculture practices in medicinal plants.
Comparative Phylogenetic Analysis for Aerides (Aeridinae, Orchidaceae) Based on Six Complete Plastid Genomes
Authors: Chen Jinliao , Wang Fei , Zhou Chengyuan , Ahmad Sagheer , Zhou Yuzhen , Li Minghe , Liu Zhongjian , Peng Donghui
Published: August 2023

Aerides Lour. (Orchidaceae, Aeridinae) is a group of epiphytic orchids with high ornamental value, mainly distributed in tropical and subtropical forests, that comprises approximately 20 species. The species are of great value in floriculture and garden designing because of their beautiful flower shapes and colors. Although the morphological boundaries of Aerides are clearly defined, the relationship between Aerides and other closely related genera is still ambiguous in terms of phylogeny. To better understand their phylogenetic relationships, this study used next-generation sequencing technology to investigate the phylogeny and DNA barcoding of this taxonomic unit using genetic information from six Aerides plastid genomes. The quadripartite-structure plastomes ranged from 147,244 bp to 148,391 bp and included 120 genes. Among them, 74 were protein coding genes, 38 were tRNA genes and 8 were rRNA genes, while the ndh genes were pseudogenized or lost. Four non-coding mutational hotspots (rpl20–rpl33, psbM, petB, rpoB–trnCGCA, Pi > 0.06) were identified. A total of 71–77 SSRs and 19–46 long repeats (>30 bp) were recognized in Aerides plastomes, which were mostly located in the large single-copy region. Phylogenetic analysis indicated that Aerides was monophylic and sister to Renanthera. Moreover, our results confirmed that six Aerides species can be divided into three major clades. These findings provide assistance for species identification and DNA barcoding investigation in Aerides, as well as contributes to future research on the phylogenomics of Orchidaceae.
Harnessing the Power of Enteric Glial Cells’ Plasticity and Multipotency for Advancing Regenerative Medicine
Authors: Lefèvre Marie A. , Soret Rodolphe , Pilon Nicolas
Published: August 2023

The enteric nervous system (ENS), known as the intrinsic nervous system of the gastrointestinal tract, is composed of a diverse array of neuronal and glial cell subtypes. Fascinating questions surrounding the generation of cellular diversity in the ENS have captivated ENS biologists for a considerable time, particularly with recent advancements in cell type-specific transcriptomics at both population and single-cell levels. However, the current focus of research in this field is predominantly restricted to the study of enteric neuron subtypes, while the investigation of enteric glia subtypes significantly lags behind. Despite this, enteric glial cells (EGCs) are increasingly recognized as equally important regulators of numerous bowel functions. Moreover, a subset of postnatal EGCs exhibits remarkable plasticity and multipotency, distinguishing them as critical entities in the context of advancing regenerative medicine. In this review, we aim to provide an updated overview of the current knowledge on this subject, while also identifying key questions that necessitate future exploration.