bluuebunny/crossref_metadata_2025 huggingface dataset:
Techno-Economic and Life Cycle Assessment of a Small-Scale Integrated Biorefinery for Butyric-Acid Production in Chile
Authors: Suazo Andrés , Tapia Fidel , Aroca Germán , Quintero Julián
Published: December 2023

This study evaluates the techno-economic and environmental feasibility of a small-scale biorefinery in Chile’s La Araucanía Region, which utilizes wheat straw as feedstock to produce butyric acid using Clostridium tyrobutyricum. Two scenarios were considered; the standalone wheat straw biorefinery and its integration with the anaerobic digestion of pig manure for biogas production, coupled with a cogeneration system, using the xylo-oligosaccharides and lignin obtained in the pretreatment. The simulations were carried out using Aspen Plus, while the Aspen Process Economic Analyzer was used to perform the economic evaluation. The simulation results were validated with experimental data from the literature. An economic assessment was performed considering the different processes involved. A cradle-to-gate life-cycle analysis (LCA) was also applied to evaluate the different environmental impacts. Both studied scenarios were economically feasible, with the highest butyric acid production cost being USD 2.97/kgbutyricacid; however, this value is still higher compared to corn-based biorefineries. Annexed biogas production increased the costs and was less economically attractive. Nonetheless, the integrations with biogas production had lower environmental impacts, except in the photochemical oxidant formation category, which was higher because of the combustion gases obtained by the cogeneration system. A lower carbon footprint (23.5 kg CO2-eq. per ton of wheat straw) was obtained for the scenario including biogas production.
Combined Effects of Ziziphus jujuba, Dimocarpus longan, and Lactuca sativa on Sleep-Related Behaviors through GABAergic Signaling
Authors: Bae Gi Yeon , Ko Kayoung , Yang Eunseon , Park Sung-Soo , Suh Hyung Joo , Hong Ki-Bae
Published: December 2023

We aimed to analyze the increase in the sleep-promoting effects based on the mixed ratio of botanical extracts, Ziziphus jujuba seeds, Dimocarpus longan fruits, and Lactuca sativa leaves, using animal models. Behavioral analyses, including an analysis of the total sleep time of Drosophila melanogaster, were conducted to select the optimal mixed ratio of the three botanical extracts. The effects were verified in a caffeine-induced sleepless model, specific neurotransmitter receptor antagonists, and ICR mice. In D. melanogaster exposed to 2.0% of each extract, group behavior was significantly reduced, and the mixed extracts of Z. jujuba, D. longan, and L. sativa (4:1:1 and 1:4:1) significantly increased the total sleep time with individual fruit flies. In the caffeine-induced insomnia model, mixed extracts (4:1:1 and 1:4:1) led to the highest increase in total sleep time. An analysis of locomotor ability revealed a significant reduction in the mobility percentage in the mixed extract groups (0:0:1, 1:0:1, 1:1:1, 4:1:1, and 1:4:1). The administration of Z. jujuba extract and mixed extracts (4:1:1) significantly increased the expression of GABAA-R, whereas the administration of the mixed extracts (4:1:1) and (1:4:1) significantly increased the expression of GABAB-R1 and GABAB-R2, respectively. D. longan extract and the mixed ratio (1:4:1) reduced the subjective nighttime movement and increased the total sleep time in the presence of flumazenil. An analysis of ICR mice indicated that the administration of mixed extracts (4:1:1) significantly increased sleep duration in a dose-dependent manner. These results indicated that the mixed ratio of Z. jujuba, D. longan, and L. sativa extracts, particularly the mixed ratio of 4:1:1, may have sleep-enhancing effects in fruit flies and mice. The study also identified changes in gene expression related to GABA receptors, indicating the potential mechanism for the observed sleep-promoting effects.
Eco-Innovation in the Food Industry: Exploring Consumer Motivations in an Emerging Market
Authors: Mansilla-Obando Katherine , Llanos Gonzalo , Gómez-Sotta Esteban , Buchuk Paulo , Ortiz Francisco , Aguirre Mario , Ahumada Fabian
Published: December 2023

The utilization of eco-innovative products has witnessed a surge in adoption, driven by their inherent capacity to address pressing environmental concerns. To comprehensively fathom the underlying motivations propelling consumers to embrace these products, we conducted an in-depth investigation employing “The Not Company” (Chile) as a compelling case study. We conducted qualitative interviews with a cohort of 20 Chilean consumers, guided by the Theory of Planned Behavior theoretical framework. The research methodology harnessed the principles of thematic analysis, yielding insights that underscore the significance of key determinants in shaping consumers’ choices towards eco-innovative products. Specifically, our findings highlighted that consumer choices in this domain are profoundly influenced by their attitudes, subjective norms, and perceived behavioral control. Moreover, within these overarching categories, we unearthed sub-themes illuminating the intricate influences guiding consumer choices. These sub-themes encompassed beliefs about food manufacturing and packaging, the persuasive impact of social media and advertising, and the indelible impressions left by prior encounters with eco-innovative products. This study highlights consumers’ fundamental role in the broader eco-innovation landscape, particularly within the food industry context.
Legumes and Cereals: Physicochemical Characterization, Technical Innovation and Nutritional Challenges
Authors: Abdel-Aal El-Sayed M.
Published: December 2023

Legume dry seeds (pulses) and cereal kernels or caryopses (grains) are staple foods worldwide and the primary supply of energy, protein, and fiber in our diet [...]
Characterization of a Novel Starch Isolated from the Rhizome of Colombian Turmeric (Curcuma longa L.) Cultivars
Authors: Argel-Pérez Shaydier , Gañán-Rojo Piedad , Cuartas-Marulanda Diego , Gómez-Hoyos Catalina , Velázquez-Cock Jorge , Vélez-Acosta Lina , Zuluaga Robin , Serpa-Guerra Angélica
Published: December 2023

Turmeric (Curcuma longa L.) plants are native to Southeast Asia and are part of the Zingiberaceae family. Global consumption and production of this plant are expanding. In countries such as Colombia, turmeric is a promising cultivar. Curcuminoids derived from its rhizomes are used in food, pharmaceuticals, and natural cosmetics. Curcuminoids constitute approximately 3 wt% of the rhizome. Many residues rich in cellulose and starch can thus be recovered. This study characterizes a novel starch isolated from Colombian turmeric cultivars. The morphological parameters of the starch were determined using microscopic techniques such as scanning electron microscopy (SEM). Proximate analysis and infrared spectroscopy (ATR-FTIR) were used to analyze the chemical composition, while physical analyses included thermal characterization, swelling power testing, solubility, water retention capacity, and colorimetry evaluation. The new starch granules were ellipsoidal in shape and ranged in diameter from 19.91 to 38.09. A trace amount of remaining curcumin was identified through chemical and physical characterization. The swelling power was 3.52 ± 0.30, and its water retention capacity was 3.44 ± 0.30. Based on these findings, turmeric can be useful in both food and non-food applications. Because starch was extracted from other Zingiberaceae plants, this study also includes a brief review of the related literature.
Prospective Randomized, Double-Blind, Placebo-Controlled Study of a Standardized Oral Pomegranate Extract on the Gut Microbiome and Short-Chain Fatty Acids
Authors: Sivamani Raja K. , Chakkalakal Mincy , Pan Adrianne , Nadora Dawnica , Min Mildred , Dumont Ashley , Burney Waqas A. , Chambers Cindy J.
Published: December 2023

Punica granatum L., commonly known as the pomegranate, is an abundant source of polyphenols, including hydrolyzable ellagitannins, ellagic acid, anthocyanins, and other bioactive phytochemicals shown to be effective in defending against oxidative stress, and has immunomodulatory activities. Ellagitannins, and their hydrolyzed product ellagic acid, interact with the gut microbiota to yield secondary metabolites known as urolithins that may have health benefits. The objective of this study was to determine the effects of supplementation with a standardized punicalagin-enriched pomegranate extract, Pomella® (250 mg), on the gut microbiome, circulating short-chain fatty acids, and gut microbial-derived ellagitannin metabolite urolithins. A randomized, double-blind, placebo-controlled study was conducted over 4 weeks on healthy volunteers aged 25–55 years. Subjects were randomly assigned to receive either an oral supplement containing 75 mg of punicalagin or an oral placebo. Stool sample collection and venipuncture were performed to analyze the gut microbiome, SCFAs, and urolithin. There was no significant change in the gut microbial diversity in both cohorts after 4 weeks of intervention, but there was a significantly increased relative abundance of Coprococcus eutectus, Roseburia faecis, Roseburia inullnivorans, Ruminococcus bicirculans, Ruminococcus calidus, and Faecalibacterium prausnitzii. Pomegranate extract (PE) supplementation led to the augmentation of circulating propionate levels (p = 0.02) and an increasing trend for acetate levels (p = 0.12). The pomegranate extract (PE) supplementation group had an increased level of circulating urolithins compared to the placebo group (6.6% vs. 1.1%, p = 0.13). PE supplementation correlated with shifts in the gut microbiome and with higher circulating levels of propionate and acetate. Further studies should explore the implications in larger cohorts and over a longer duration.
Updated Aims and Scope of Foundations
Authors: Bohner Martin
Published: December 2023

Foundations published its inaugural issue in 2021, establishing itself as a new international open access, peer-reviewed, multidisciplinary journal of science and techonology, covering mathematics, physics, chemistry, biology, engineering, earth sciences, materials, information sciences, and medical sciences [...]
From Hemp Waste to Bioactive Nanofiber Composites: Deep Eutectic Solvents and Electrospinning in Upcycling Endeavors
Authors: Mouro Cláudia , Gomes Ana P. , Gouveia Isabel C.
Published: December 2023

Natural fibers have attracted increasing interest as an alternative to produce environmentally friendly and sustainable materials. Particularly, hemp fibers have been widely used in various industrial applications due to their extremely unique properties. However, hemp can generate a large amount of agro-waste, and it results in an attractive source of biopolymers for the development of low-cost materials as an alternative to the raw materials and conventional petroleum-based plastics. In addition, deep eutectic solvents (DESs), a new type of truly green solvents, have been shown to remove gums, lignin, and other non-cellulosic components from hemp fibers. Reusing these components dissolved into the DESs to fabricate new materials directly by electrospinning is a very attractive but still unexplored endeavor. Thus, this innovative research to venture new upcycling pathways is focused on the fabrication of composite nanofibers by electrospinning of a gel-based blend of Poly(vinyl alcohol) (PVA) and hemp agro-waste (HW) dissolved into choline chloride (ChCl):Glycerol (1:2) and ChCl:Urea (1:2) DES mixtures. The results obtained revealed that the produced nanofibers displayed uniform appearance with diameters ranging from 257.7 ± 65.6 nm to 380.8 ± 134.0 nm. In addition, the mechanical properties of the electrospun composite nanofibers produced from the gel-based blends of HW dissolved in DESs and PVA (HW-DESs_PVA) were found to be superior, resulting in an enhanced tensile strength and Young’s modulus. Furthermore, the incorporation of HW into the nanofibers was able to provide bioactive antioxidant and antibacterial properties. Overall, this study demonstrated a promising, more sustainable, and eco-friendly way to produce electrospun composite nanofibers using HW in a circular economy perspective.
DNAJB11 Mutation in ADPKD Patients: Clinical Characteristics in a Monocentric Cohort
Authors: Aiello Valeria , Ciurli Francesca , Conti Amalia , Cristalli Carlotta Pia , Lerario Sarah , Montanari Francesca , Sciascia Nicola , Vischini Gisella , Fabbrizio Benedetta , Di Costanzo Roberta , Olivucci Giulia , Pietra Andrea , Lopez Antonia , Zambianchi Loretta , La Manna Gaetano , Capelli Irene
Published: December 2023

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a late-onset cilia-related disorder, characterized by progressive cystic enlargement of the kidneys. It is genetically heterogeneous with PKD1 and PKD2 pathogenic variants identified in approximately 78% and 15% of families, respectively. More recently, additional ADPKD genes, such as DNAJB11, have been identified and included in the diagnostic routine test for renal cystic diseases. However, despite recent progress in ADPKD molecular approach, approximately ~7% of ADPKD-affected families remain genetically unresolved. We collected a cohort of 4 families from our center, harboring heterozygous variants in the DNAJB11 gene along with clinical and imaging findings consistent with previously reported features in DNAJB11 mutated patients. Mutations were identified as likely pathogenetic (LP) in three families and as variants of uncertain significance (VUS) in the remaining one. One patient underwent to kidney biopsy and showed a prevalence of interstitial fibrosis that could be observed in ~60% of the sample. The presence in the four families from our cohort of ADPKD characteristics together with ADTKD features, such as hyperuricemia, diabetes, and chronic interstitial fibrosis, supports the definition of DNAJB11 phenotype as an overlap disease between these two entities, as originally suggested by the literature.
Electro-Acupuncture Effects Measured by Functional Magnetic Resonance Imaging—A Systematic Review of Randomized Clinical Trials
Authors: Rodrigues Jorge Magalhães , Ventura Cristina , Abreu Manuela , Santos Catarina , Monte Joana , Machado Jorge Pereira , Santos Rosa Vilares
Published: December 2023

Introduction: Electro-acupuncture, an innovative adaptation of traditional acupuncture, combines electrical stimulation with acupuncture needles to enhance therapeutic effects. While acupuncture is widely used, its biological mechanisms remain incompletely understood. Recent research has explored the neurophysiological aspects of acupuncture, particularly through functional magnetic resonance imaging (fMRI) to investigate its effects on brain activity. Methods: In this systematic review, we conducted an extensive search for randomized clinical trials examining electro-acupuncture effects measured by fMRI. We employed strict eligibility criteria, quality assessment, and data extraction. Results: Five studies met our inclusion criteria and were analyzed. The selected studies investigated electro-acupuncture in various medical conditions, including carpal tunnel syndrome, fibromyalgia, Crohn’s disease, irritable bowel syndrome, and obesity. Notably, electro-acupuncture was found to modulate brain activity and connectivity in regions associated with pain perception, emotional regulation, and cognitive processing. These findings align with the holistic approach of traditional Chinese medicine, emphasizing the interconnectedness of body and mind. Discussion: In carpal tunnel syndrome, electro-acupuncture at both local and distal sites showed neurophysiological improvements, suggesting distinct neuroplasticity mechanisms. In fibromyalgia, somatosensory electro-acupuncture correlated with reduced pain severity, enhanced brain connectivity, and increased gamma-aminobutyric acid levels. For Crohn’s disease, electro-acupuncture influenced the homeostatic afferent processing network, potentially mitigating gut inflammation. Electro-acupuncture for irritable bowel syndrome led to decreased activity in the anterior cingulate cortex, offering pain relief, while electro-acupuncture for obesity impacted brain regions associated with dietary inhibition and emotional regulation. Conclusion: This systematic review provides evidence that electro-acupuncture can positively impact a range of medical conditions, possibly by modulating brain activity and connectivity. While the quality of the reviewed studies is generally good, further research with larger sample sizes and longer-term assessments is needed to better understand the mechanisms and optimize electro-acupuncture protocols for specific health conditions. The limited number of studies in this review emphasizes the need for broader investigations in this promising field. The research protocol was registered in PROSPERO (CRD42023465866).
Structural Relationships between Socio-Cognitive Mindfulness, Everyday Creativity, and Clinical Competence in Nursing Students: Mediating Effects of Everyday Creativity
Authors: Lee Mikyoung , Jung Mijung
Published: December 2023

Background: Incorporating socio-cognitive mindfulness, which has not received much attention from nursing researchers, this study investigated the structural relationships between socio-cognitive mindfulness, everyday creativity, and clinical competence among nursing students. This study also explored the mediating effect of everyday creativity. Methods: A cross-sectional study was performed with 222 nursing students in South Korea. Students completed the questionnaire evaluating their own socio-cognitive mindfulness, everyday creativity, and clinical competence. Data were analyzed using structural equation modeling and path analysis. Results: Socio-cognitive mindfulness positively influenced everyday creativity (β = 0.791, p < 0.01), and everyday creativity also positively influenced clinical competence (β = 0.470, p < 0.01). However, the relationship between socio-cognitive mindfulness and clinical competence was not significant. Importantly, everyday creativity fully mediated the relationship between socio-cognitive mindfulness and clinical competence (a × b = 0.372, p < 0.01). Conclusions: The results indicate that socio-cognitive mindfulness effectively enhances nursing students’ clinical competence by improving their everyday creativity. The mediating result highlights the significance of everyday creativity in nursing education, underscoring the necessity for training programs aimed at cultivating creativity. This research offers a basis for developing programs that concentrate on socio-cognitive mindfulness and everyday creativity, with the goal of enhancing the clinical competence of nursing students.
Response of Microbial Recovery Rate to Straw Return after Calcium Cyanamide Soil Disinfection
Authors: Xie Xuewen , Chen Lida , Shi Yanxia , Chai Ali , Fan Tengfei , Li Baoju , Li Lei
Published: December 2023

At present, returning vegetable straw in situ is an effective measure to solve environmental pollution and improve soil properties. However, the direct return of straw to the field can reduce the release rate of soil organic matter and cause serious soilborne diseases. The combined application of calcium cyanamide (CaCN2) and straw can solve this problem. The objective of this study was to determine the effect of CaCN2 combined with pepper straw return on cucumber yield, soil physicochemical properties, and soil microbial communities during 2020 to 2021 in Shandong Province, China. The treatments were designed as follows: (1) calcium cyanamide soil disinfection, CC; (2) fresh pepper straw return, LJ; (3) fresh pepper straw return combined with calcium cyanamide disinfection, LJ+CC; and (4) natural soil without straw return treatment, CK. Compared with CK, the LJ+CC treatment significantly improved cucumber production by 20%. The cultivable microbial community in the soil was temporarily inhibited during soil fumigation treatment, and the cultivable bacterial and actinomycete communities in the soil return to their initial levels after the film was removed (harvest period). The numbers of culturable bacteria and actinomycetes in the soil in the LJ+CC treatment were 4.68 × 107 CFU/g and 5.17 × 107 CFU/g, respectively, higher than those in the soil in the CC treatment. The contents of TN and OM in the LJ+CC treatment increased by 13.1% and 13.5%, respectively, compared with that in LJ. Therefore, the LJ+CC treatment enhanced soil fertility and cucumber yields. CaCN2 can promote straw decomposition and straw can promote soil microbial recovery, and their combined application is considered a feasible and sustainable technique for utilizing vegetable residues in the greenhouse. The combination of returning pepper straw to the field and calcium cyanamide technology achieves a win-win situation of resource circulation and economic circulation by converting agricultural waste into fertilizer before being put into production. Based on this, it is recommended that the straw returning technology receives strong policy support, stimulates researchers to explore the feasibility of different vegetable straw returning to the field, promotes the implementation of this technology achievement, and leverages the environmental benefits of the application of straw returning technology.
Performance of a Drip Irrigation System under the Co-Application of Water, Fertilizer, and Air
Authors: Li Hao , Ma Zhengjun , Zhang Guangsong , Chen Jiayao , Lu Yunchao , Li Peng
Published: December 2023

The co-application of water, fertilizer, and air is a new water-saving irrigation method based on drip irrigation technology, which can effectively alleviate the phenomenon of soil rhizosphere hypoxia, improve water and fertilizer utilization efficiency, and inhibit the clogging of irrigation equipment in drip irrigation systems. The performance of drip irrigation systems is one of the important factors affecting the effectiveness of the co-application of water, fertilizer, and air. However, the impact of factors such as the aeration method, fertilization device, and working parameters on the performance of drip irrigation systems for the co-application of water, fertilizer, and air is still unclear. Therefore, based on two typical aeration methods, i.e., micro-nano and Venturi aeration, the performance of a drip irrigation system under the co-application of water, fertilizer, and air was studied by comparing and analyzing the effects of different aeration methods, working pressures of the drip irrigation system, and the pressure difference between the inlet and outlet of fertilizer irrigation on the spatial distribution uniformity of water, fertilizer, and air in the drip irrigation pipeline network. The results showed that the pressure difference between the inlet and outlet of fertilization irrigation had no significant impact on system performance, while the working pressure significantly affected system performance. Compared with the effective effect of Venturi aeration on system performance, micro-nano aeration can significantly affect drip irrigation system performance and effectively improve drip irrigation system performance. The micro-nano-aerated drip irrigation system with the co-application of water, fertilizer, and air under a working pressure of 0.1 MPa has better system performance. The research results are of great significance for revealing the mechanism underlying the impact of the co-application of water, fertilizer, and air on the performance of drip irrigation systems and constructing efficient drip irrigation technology for the co-application of water, fertilizer, and air.
ISGF3 and STAT2/IRF9 Control Basal and IFN-Induced Transcription through Genome-Wide Binding of Phosphorylated and Unphosphorylated Complexes to Common ISRE-Containing ISGs
Authors: Nowicka Hanna , Sekrecka Agata , Blaszczyk Katarzyna , Kluzek Katarzyna , Chang Chan-Yu , Wesoly Joanna , Lee Chien-Kuo , Bluyssen Hans A. R.
Published: December 2023

In addition to the canonical ISGF3 and non-canonical STAT2/IRF9 complexes, evidence is emerging of the role of their unphosphorylated counterparts in IFN-dependent and -independent ISG transcription. To better understand the relation between ISGF3 and U-ISGF3 and STAT2/IRF9 and U-STAT2/IRF9 in IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and antiviral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα-treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells, early and long-term IFNα-inducible transcription and antiviral activity relied on the DNA recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, delayed IFN responses correlated with DNA binding of phosphorylated STAT2/IRF9 but not U-STAT2/IRF9. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all the ISGF3 components (ST1-ST2-IRF9-U3C) revealed U-ISGF3 (and possibly U-STAT2/IRF9) chromatin interactions to correlate with phosphorylation-independent ISG transcription and antiviral activity. Together, our data point to the dominant role of the canonical ISGF3 and non-canonical STAT2/IRF9, without a shift to U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection. At the same time, they suggest the threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-dependent responses.
Molecular Mechanisms of Oxidative Stress in Acute Kidney Injury: Targeting the Loci by Resveratrol
Authors: Rashid Hina , Jali Abdulmajeed , Akhter Mohammad Suhail , Abdi Sayed Aliul Hasan
Published: December 2023

Reactive oxygen species are a group of cellular molecules that stand as double-edged swords, their good and bad being discriminated by a precise balance. Several metabolic reactions in the biological system generate these molecules that interact with cellular atoms to regulate functions ranging from cell homeostasis to cell death. A prooxidative state of the cell concomitant with decreased clearance of such molecules leads to oxidative stress, which contributes as a prime pathophysiological mechanism in various diseases including renal disorders, such as acute kidney injury. However, targeting the generation of oxidative stress in renal disorders by an antioxidant, resveratrol, is gaining considerable therapeutic importance and is known to improve the condition in preclinical studies. This review aims to discuss molecular mechanisms of oxidative stress in acute kidney injury and its amelioration by resveratrol. The major sources of data were PubMed and Google Scholar, with studies from the last five years primarily included, with significant earlier data also considered. Mitochondrial dysfunction, various enzymatic reactions, and protein misfolding are the major sources of reactive oxygen species in acute kidney injury, and interrupting these loci of generation or intersection with other cellular components by resveratrol can mitigate the severity of the condition.
Chronic Glaucoma Induced in Rats by a Single Injection of Fibronectin-Loaded PLGA Microspheres: IOP-Dependent and IOP-Independent Neurodegeneration
Authors: Munuera Ines , Aragon-Navas Alba , Villacampa Pilar , Gonzalez-Cela Miriam A. , Subías Manuel , Pablo Luis E. , Garcia-Feijoo Julian , Herrero-Vanrell Rocio , Garcia-Martin Elena , Bravo-Osuna Irene , Rodrigo Maria J.
Published: December 2023

To evaluate a new animal model of chronic glaucoma induced using a single injection of fibronectin-loaded biodegradable PLGA microspheres (Ms) to test prolonged therapies. 30 rats received a single injection of fibronectin-PLGA-Ms suspension (MsF) in the right eye, 10 received non-loaded PLGA-Ms suspension (Control), and 17 were non-injected (Healthy). Follow-up was performed (24 weeks), evaluating intraocular pressure (IOP), optical coherence tomography (OCT), histology and electroretinography. The right eyes underwent a progressive increase in IOP, but only induced cohorts reached hypertensive values. The three cohorts presented a progressive decrease in ganglion cell layer (GCL) thickness, corroborating physiological age-related loss of ganglion cells. Injected cohorts (MsF > Control) presented greater final GCL thickness. Histological exams explain this paradox: the MsF cohort showed lower ganglion cell counts but higher astrogliosis and immune response. A sequential trend of functional damage was recorded using scotopic electroretinography (MsF > Control > Healthy). It seems to be a function–structure correlation: in significant astrogliosis, early functional damage can be detected by electroretinography, and structural damage can be detected by histological exams but not by OCT. Males presented higher IOP and retinal and GCL thicknesses and lower electroretinography. A minimally invasive chronic glaucoma model was induced by a single injection of biodegradable Ms.
B-Cell Receptor Signaling and Beyond: The Role of Igα (CD79a)/Igβ (CD79b) in Normal and Malignant B Cells
Authors: Tkachenko Anton , Kupcova Kristyna , Havranek Ondrej
Published: December 2023

B-cell receptor (BCR) is a B cell hallmark surface complex regulating multiple cellular processes in normal as well as malignant B cells. Igα (CD79a)/Igβ (CD79b) are essential components of BCR that are indispensable for its functionality, signal initiation, and signal transduction. CD79a/CD79b-mediated BCR signaling is required for the survival of normal as well as malignant B cells via a wide signaling network. Recent studies identified the great complexity of this signaling network and revealed the emerging role of CD79a/CD79b in signal integration. In this review, we have focused on functional features of CD79a/CD79b, summarized signaling consequences of CD79a/CD79b post-translational modifications, and highlighted specifics of CD79a/CD79b interactions within BCR and related signaling cascades. We have reviewed the complex role of CD79a/CD79b in multiple aspects of normal B cell biology and how is the normal BCR signaling affected by lymphoid neoplasms associated CD79A/CD79B mutations. We have also summarized important unresolved questions and highlighted issues that remain to be explored for better understanding of CD79a/CD79b-mediated signal transduction and the eventual identification of additional therapeutically targetable BCR signaling vulnerabilities.
Molecular Research on Heart Protection
Authors: Abdelwahid Eltyeb , de Carvalho Katherine Athayde Teixeira
Published: December 2023

Recently, various molecular bases of heart protection have been discovered and used in many experimental and clinical investigations [...]
Polystyrene Microplastics Exacerbate Candida albicans Infection Ability In Vitro and In Vivo
Authors: Maione Angela , Norcia Mariangela , Sinoca Marica , Galdiero Marilena , Maselli Valeria , Feola Antonia , Carotenuto Rosa , Cuomo Paola , Capparelli Rosanna , Guida Marco , Galdiero Emilia
Published: December 2023

Plastic pollution is an important environmental problem, and microplastics have been shown to have harmful effects on human and animal health, affecting immune and metabolic physiological functions. Further, microplastics can interfere with commensal microorganisms and exert deleterious effects on exposure to pathogens. Here, we compared the effects of 1 µm diameter polystyrene microplastic (PSMPs) on Candida albicans infection in both in vitro and in vivo models by using HT29 cells and Galleria mellonella larvae, respectively. The results demonstrated that PSMPs could promote Candida infection in HT29 cells and larvae of G. mellonella, which show immune responses similar to vertebrates. In this study, we provide new experimental evidence for the risk to human health posed by PSMPs in conjunction with Candida infections.
Polycondensed Peptide-Based Polymers for Targeted Delivery of Anti-Angiogenic siRNA to Treat Endometriosis
Authors: Egorova Anna , Maretina Marianna , Krylova Iuliia , Kiselev Anton
Published: December 2023

Endometriosis (EM) is a prevalent gynecological disease characterized by the abnormal growth of tissue similar to the endometrium outside of the uterus. This condition is accompanied by the development of new blood vessels in endometriotic lesions. While surgical intervention is effective in removing endometriotic lesions, some patients require multiple surgeries. Therefore, finding non-surgical treatments for EM is of great interest. One of the promising approaches is anti-angiogenic therapy using siRNA-therapeutics to target the expression of the VEGFA gene. Peptide-based polymers have shown promise as siRNA delivery systems due to their biocompatibility and ease of modification. We conducted a study to evaluate the effectiveness of the R6p-cRGD peptide carrier as a non-viral vehicle for delivering siRNA to endothelial cells in vitro and endometrial implants in vivo. We investigated the physicochemical properties of the siRNA-complexes, assessed cellular toxicity, and examined the efficiency of GFP and VEGFA genes silencing. Furthermore, we tested the anti-angiogenic effects of these complexes in cellular and animal models. The transfection with siRNA complexes led to a significant increase in VEGFA gene knockdown efficiency and a decrease in the migration of endothelial cells. For the animal model, we induced endometriosis in rats by transplanting endometrial tissue subcutaneously. We evaluated the efficiency of anti-angiogenic therapy for EM in vivo using anti-VEGF siRNA/R6p-RGD complexes. During this assessment, we measured the volume of the implants, analyzed VEGFA gene expression, and conducted CD34 immunohistochemical staining. The results showed a significant decrease in the growth of endometriotic implants and in VEGFA gene expression. Overall, our findings demonstrate the potential of the R6p-cRGD peptide carrier as a delivery system for anti-angiogenic therapy of EM.
Challenges to Cannabis sativa Production from Pathogens and Microbes—The Role of Molecular Diagnostics and Bioinformatics
Authors: Punja Zamir K. , Kahl Dieter , Reade Ron , Xiang Yu , Munz Jack , Nachappa Punya
Published: December 2023

The increased cultivation of Cannabis sativa L. in North America, represented by high Δ9-tetrahydrocannabinol-containing (high-THC) cannabis genotypes and low-THC-containing hemp genotypes, has been impacted by an increasing number of plant pathogens. These include fungi which destroy roots, stems, and leaves, in some cases causing a build-up of populations and mycotoxins in the inflorescences that can negatively impact quality. Viroids and viruses have also increased in prevalence and severity and can reduce plant growth and product quality. Rapid diagnosis of the occurrence and spread of these pathogens is critical. Techniques in the area of molecular diagnostics have been applied to study these pathogens in both cannabis and hemp. These include polymerase chain reaction (PCR)-based technologies, including RT-PCR, multiplex RT-PCR, RT-qPCR, and ddPCR, as well as whole-genome sequencing (NGS) and bioinformatics. In this study, examples of how these technologies have enhanced the rapidity and sensitivity of pathogen diagnosis on cannabis and hemp will be illustrated. These molecular tools have also enabled studies on the diversity and origins of specific pathogens, specifically viruses and viroids, and these will be illustrated. Comparative studies on the genomics and metabolomics of healthy and diseased plants are urgently needed to provide insight into their impact on the quality and composition of cannabis and hemp-derived products. Management of these pathogens will require monitoring of their spread and survival using the appropriate technologies to allow accurate detection, followed by appropriate implementation of disease control measures.
Comparative Insight into Microglia/Macrophages-Associated Pathways in Glioblastoma and Alzheimer’s Disease
Authors: Shi Jian , Huang Shiwei
Published: December 2023

Microglia and macrophages are pivotal to the brain’s innate immune response and have garnered considerable attention in the context of glioblastoma (GBM) and Alzheimer’s disease (AD) research. This review delineates the complex roles of these cells within the neuropathological landscape, focusing on a range of signaling pathways—namely, NF-κB, microRNAs (miRNAs), and TREM2—that regulate the behavior of tumor-associated macrophages (TAMs) in GBM and disease-associated microglia (DAMs) in AD. These pathways are critical to the processes of neuroinflammation, angiogenesis, and apoptosis, which are hallmarks of GBM and AD. We concentrate on the multifaceted regulation of TAMs by NF-κB signaling in GBM, the influence of TREM2 on DAMs’ responses to amyloid-beta deposition, and the modulation of both TAMs and DAMs by GBM- and AD-related miRNAs. Incorporating recent advancements in molecular biology, immunology, and AI techniques, through a detailed exploration of these molecular mechanisms, we aim to shed light on their distinct and overlapping regulatory functions in GBM and AD. The review culminates with a discussion on how insights into NF-κB, miRNAs, and TREM2 signaling may inform novel therapeutic approaches targeting microglia and macrophages in these neurodegenerative and neoplastic conditions. This comparative analysis underscores the potential for new, targeted treatments, offering a roadmap for future research aimed at mitigating the progression of these complex diseases.
Everolimus Acts in Synergy with Vinorelbine to Suppress the Growth of Hepatocellular Carcinoma
Authors: Huynh Hung , Ng Wai Har , Soo Khee Chee
Published: December 2023

Hepatocellular carcinoma (HCC) is a challenging cancer to treat, as traditional chemotherapies have shown limited effectiveness. The mammalian target of rapamycin/sirolimus (mTOR) and microtubules are prominent druggable targets for HCC. In this study, we demonstrated that co-targeting mTOR using mTOR inhibitors (everolimus and sirolimus) along with the microtubule inhibitor vinorelbine yielded results superior to those of the monotherapies in HCC PDX models. Our research showed that the vinorelbine arrests cells at the mitotic phase, induces apoptosis, and normalizes tumor blood vessels but upregulates survivin and activates the mTOR/p70S6K/4EBP1 pathway. The addition of the everolimus significantly improved the tumor response to the vinorelbine, leading to improved overall survival (OS) in most tested orthotopic HCC PDX models. The mechanistic investigation revealed that this marked antitumor effect was accompanied by the downregulations of mTOR targets (p-p70S6K, p-4EBP1, and p-S6K); several key cell-cycle regulators; and the antiapoptotic protein survivin. These effects did not compromise the normalization of the blood vessels observed in response to the vinorelbine in the vinorelbine-sensitive PDX models or to the everolimus in the everolimus-sensitive PDX models. The combination of the everolimus and vinorelbine (everolimus/vinorelbine) also promoted apoptosis with minimal toxicity. Given the cost-effectiveness and established effectiveness of everolimus, and especially sirolimus, this strategy warrants further investigation in early-phase clinical trials.
MDSPACE and MDTOMO Software for Extracting Continuous Conformational Landscapes from Datasets of Single Particle Images and Subtomograms Based on Molecular Dynamics Simulations: Latest Developments in ContinuousFlex Software Package
Authors: Vuillemot Rémi , Harastani Mohamad , Hamitouche Ilyes , Jonic Slavica
Published: December 2023

Cryo electron microscopy (cryo-EM) instrumentation allows obtaining 3D reconstruction of the structure of biomolecular complexes in vitro (purified complexes studied by single particle analysis) and in situ (complexes studied in cells by cryo electron tomography). Standard cryo-EM approaches allow high-resolution reconstruction of only a few conformational states of a molecular complex, as they rely on data classification into a given number of classes to increase the resolution of the reconstruction from the most populated classes while discarding all other classes. Such discrete classification approaches result in a partial picture of the full conformational variability of the complex, due to continuous conformational transitions with many, uncountable intermediate states. In this article, we present the software with a user-friendly graphical interface for running two recently introduced methods, namely, MDSPACE and MDTOMO, to obtain continuous conformational landscapes of biomolecules by analyzing in vitro and in situ cryo-EM data (single particle images and subtomograms) based on molecular dynamics simulations of an available atomic model of one of the conformations. The MDSPACE and MDTOMO software is part of the open-source ContinuousFlex software package (starting from version 3.4.2 of ContinuousFlex), which can be run as a plugin of the Scipion software package (version 3.1 and later), broadly used in the cryo-EM field.
Anti-Aging Potential of a Novel Ingredient Derived from Sugarcane Straw Extract (SSE)
Authors: Carvalho Maria João , Pedrosa Sílvia Santos , Mendes Adélia , Azevedo-Silva João , Fernandes João , Pintado Manuela , Oliveira Ana L. S. , Madureira Ana Raquel
Published: December 2023

Natural and sustainable anti-aging ingredients have gained attention from the cosmetic industry. This study evaluated the anti-aging potential of a sugarcane straw extract-based (SSE) cosmetic ingredient. First, cytotoxicity tests were assessed in keratinocytes and fibroblast cell lines, and sensitization was carried out through the direct peptide reactivity assay. Subsequently, various anti-aging properties were investigated, including inhibiting skin aging-related enzymes, promoting elastin and hyaluronic acid synthesis, and anti-pollution activity. Finally, a permeability assay using a synthetic membrane resembling skin was conducted. The results demonstrated that the SSE ingredient effectively inhibited elastase (55%), collagenase (25%), and tyrosinase (47%) while promoting hyaluronic acid production at non-cytotoxic and low-sensitizer concentrations. Moreover, it reduced the inflammatory response provoked by urban pollution, as evidenced by decreased levels of IL1-α and IL-6. However, it was observed that the phenolic compounds predominantly reached the skin’s surface, indicating a limited ability to penetrate deeper layers of the skin. Therefore, it can be concluded that the SSE ingredient holds anti-aging properties, albeit with limited penetration into deeper skin layers. Further research and formulation advancements are needed to optimize the ingredient’s ability to reach and exert its effects in deeper skin layers.
High-Throughput Measure of Mitochondrial Superoxide Levels as a Marker of Coronary Artery Disease to Accelerate Drug Translation in Patient-Derived Endothelial Cells Using Opera Phenix® Technology
Authors: Lee Weiqian E. , Besnier Marie , Genetzakis Elijah , Tang Owen , Kott Katharine A. , Vernon Stephen T. , Gray Michael P. , Grieve Stuart M. , Kassiou Michael , Figtree Gemma A.
Published: December 2023

Improved human-relevant preclinical models of coronary artery disease (CAD) are needed to improve translational research and drug discovery. Mitochondrial dysfunction and associated oxidative stress contribute to endothelial dysfunction and are a significant factor in the development and progression of CAD. Endothelial colony-forming cells (ECFCs) can be derived from peripheral blood mononuclear cells (PBMCs) and offer a unique potentially personalised means for investigating new potential therapies targeting important components of vascular function. We describe the application of the high-throughput and confocal Opera Phenix® High-Content Screening System to examine mitochondrial superoxide (mROS) levels, mitochondrial membrane potential, and mitochondrial area in both established cell lines and patient-derived ECFCs simultaneously. Unlike traditional plate readers, the Opera Phenix® is an imaging system that integrates automated confocal microscopy, precise fluorescent detection, and multi-parameter algorithms to visualize and precisely quantify targeted biological processes at a cellular level. In this study, we measured mROS production in human umbilical vein endothelial cells (HUVECs) and patient-derived ECFCs using the mROS production probe, MitoSOXTM Red. HUVECs exposed to oxidized low-density lipoprotein (oxLDL) increased mROS levels by 47.7% (p < 0.0001). A pooled group of patient-derived ECFCs from participants with CAD (n = 14) exhibited 30.9% higher mROS levels compared to patients with no CAD when stimulated with oxLDL (n = 14; p < 0.05). When tested against a small group of candidate compounds, this signal was attenuated by PKT-100 (36.22% reduction, p = 0.03), a novel P2X7 receptor antagonist. This suggests the P2X7 receptor as a valid target against excess mROS levels. As such, these findings highlight the potential of the MitoSOX-Opera Phenix technique to be used for drug discovery efforts in CAD.
Role of Thyroid Hormone in Dynamic Variation of gdf6a Gene during Metamorphosis of Paralichthys olivaceus
Authors: Shi Yaxin , Qiu Junqiang , Li Xike , Lin Yue , Li Wenjuan , Hou Jilun , Fu Yuanshuai
Published: December 2023

The Japanese flounder (Paralichthys olivaceus) is a marine fish that undergoes a dramatic postembryonic metamorphosis, with the right eye shifting to the left and its lifestyle transitioning from planktonic to benthic. As the light environment of the habitat changes from bright to dim, its photoreceptor system also undergoes adaptive change. Growth differentiation factor 6a (Gdf6a) is a member of the BMP family, which plays a key role in regulating the dorsal–ventral pattern of the retina and photoreceptor fate, and the differentiation of different photoreceptors is also modulated by a thyroid hormone (TH) binding its receptor (TR). However, the relationship between gdf6a and TH and its role in the regulation of photoreceptors during flounder metamorphosis is still poorly understood. In this study, bioinformatics analysis showed that Gdf6a had a conserved TGFB structural domain and clusters with fishes. The expression analysis showed that the expression of gdf6a was highest in the eye tissue of adult flounder and tended to increase and then decrease during metamorphosis, reaching its highest levels at the peak of metamorphosis. Moreover, the expression of gdf6a increased in the early stages of metamorphosis after exogenous TH treatment, while it was inhibited after exogenous thiourea (a TH inhibitor, TU) treatment. To further investigate the targeting role of TH and gdf6a in the metamorphosis of flounder, the results of the Dual-Luciferase revealed that triiodothyronine (T3) may regulate the expression of gdf6a through TRβ. In conclusion, we speculate that TH influences the development of cone photoreceptors during the metamorphosis of the flounder by regulating the expression of gdf6a.