bluuebunny/crossref_metadata_2025 huggingface dataset:
Osteogenic Activities of Trifolirhizin as a Bioactive Compound for the Differentiation of Osteogenic Cells
Authors: Yun Hyung-Mun , Cho Mi Hyeon , Jeong Hoibin , Kim Soo Hyun , Jeong Yun Hee , Park Kyung-Ran
Published: December 2023

Plant extracts are widely used as traditional medicines. Sophora flavescens Aiton-derived natural compounds exert various beneficial effects, such as anti-inflammatory, anticancer, antioxidant, and antiregenerative activities, through their bioactive compounds, including flavonoids and alkaloids. In the present study, we investigated the biological effects of an S. flavescens-derived flavonoid, trifolirhizin (trifol), on the stimulation of osteogenic processes during osteoblast differentiation. Trifol (>98% purity) was successfully isolated from the root of S. flavescens and characterized. Trifol did not exhibit cellular toxicity in osteogenic cells, but promoted alkaline phosphatase (ALP) staining and activity, with enhanced expression of the osteoblast differentiation markers, including Alp, ColI, and Bsp. Trifol induced nuclear runt-related transcription factor 2 (RUNX2) expression during the differentiation of osteogenic cells, and concomitantly stimulated the major osteogenic signaling proteins, including GSK3β, β-catenin, and Smad1/5/8. Among the mitogen-activated protein kinases (MAPKs), Trifol activated JNK, but not ERK1/2 and p38. Trifol also increased the osteoblast-mediated bone-forming phenotypes, including transmigration, F-actin polymerization, and mineral apposition, during osteoblast differentiation. Overall, trifol exhibits bioactive activities related to osteogenic processes via differentiation, migration, and mineralization. Collectively, these results suggest that trifol may serve as an effective phytomedicine for bone diseases such as osteoporosis.
Socrates: A Novel N-Ethyl-N-nitrosourea-Induced Mouse Mutant with Audiogenic Epilepsy
Authors: Varlamova Elena G. , Borisova Ekaterina V. , Evstratova Yuliya A. , Newman Andrew G. , Kuldaeva Vera P. , Gavrish Maria S. , Kondakova Elena V. , Tarabykin Victor S. , Babaev Alexey A. , Turovsky Egor A.
Published: December 2023

Epilepsy is one of the common neurological diseases that affects not only adults but also infants and children. Because epilepsy has been studied for a long time, there are several pharmacologically effective anticonvulsants, which, however, are not suitable as therapy for all patients. The genesis of epilepsy has been extensively investigated in terms of its occurrence after injury and as a concomitant disease with various brain diseases, such as tumors, ischemic events, etc. However, in the last decades, there are multiple reports that both genetic and epigenetic factors play an important role in epileptogenesis. Therefore, there is a need for further identification of genes and loci that can be associated with higher susceptibility to epileptic seizures. Use of mouse knockout models of epileptogenesis is very informative, but it has its limitations. One of them is due to the fact that complete deletion of a gene is not, in many cases, similar to human epilepsy-associated syndromes. Another approach to generating mouse models of epilepsy is N-Ethyl-N-nitrosourea (ENU)-directed mutagenesis. Recently, using this approach, we generated a novel mouse strain, soc (socrates, formerly s8-3), with epileptiform activity. Using molecular biology methods, calcium neuroimaging, and immunocytochemistry, we were able to characterize the strain. Neurons isolated from soc mutant brains retain the ability to differentiate in vitro and form a network. However, soc mutant neurons are characterized by increased spontaneous excitation activity. They also demonstrate a high degree of Ca2+ activity compared to WT neurons. Additionally, they show increased expression of NMDA receptors, decreased expression of the Ca2+-conducting GluA2 subunit of AMPA receptors, suppressed expression of phosphoinositol 3-kinase, and BK channels of the cytoplasmic membrane involved in protection against epileptogenesis. During embryonic and postnatal development, the expression of several genes encoding ion channels is downregulated in vivo, as well. Our data indicate that soc mutation causes a disruption of the excitation–inhibition balance in the brain, and it can serve as a mouse model of epilepsy.
Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies
Authors: Bossio Sabrina , Perri Anna , Gallo Raffaella , De Bartolo Anna , Rago Vittoria , La Russa Daniele , Di Dio Michele , La Vignera Sandro , Calogero Aldo E. , Vitale Giovanni , Aversa Antonio
Published: December 2023

Alpha-lipoic acid (ALA) is a natural antioxidant dithiol compound, exerting antiproliferative and antimetastatic effects in various cancer cell lines. In our study, we demonstrated that ALA reduces the cell growth of prostate cancer cells LNCaP and DU-145. Western blot results revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3. Concomitantly, MTT assays showed that chloroquine (CQ) exposure, a well-known autophagy inhibitor, reduced cells’ viability. This was more evident for treatment using the combination ALA + CQ, suggesting that ALA can reduce cells’ viability by inhibiting autophagy. In addition, in DU-145 cells we observed that ALA affected the oxidative/redox balance system by deregulating the KEAP1/Nrf2/p62 signaling pathway. ALA decreased ROS production, SOD1 and GSTP1 protein expression, and significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2, concomitantly downregulating p62, suggesting that ALA disrupted p62-Nrf2 feedback loop. Conversely, in LNCaP cells, ALA exposure upregulated both SOD1 and p62 protein expression, but did not affect the KEAP1/Nrf2/p62 signaling pathway. In addition, wound-healing, Western blot, and immunofluorescence assays evidenced that ALA significantly reduced the motility of LNCaP and DU-145 cells and downregulated the protein expression of TGFβ1 and vimentin and the deposition of fibronectin. Finally, a soft agar assay revealed that ALA decreased the colony formation of both the prostate cancer cells by affecting the anchorage independent growth. Collectively, our in vitro evidence demonstrated that in prostate cancer cells, ALA reduces cell growth and counteracts both migration and invasion. Further studies are needed in order to achieve a better understanding of the underlined molecular mechanisms.
New Insights into the TIFY Gene Family of Brassica napus and Its Involvement in the Regulation of Shoot Branching
Authors: Li Yarong , Zhang Qian , Wang Luman , Wang Xinfa , Qiao Jiangwei , Wang Hanzhong
Published: December 2023

As plant-specific transcription factors, the TIFY family genes are involved in the responses to a series of biotic and abiotic stresses and the regulation of the development of multiple organs. To explore the potential roles of the TIFY gene family in shoot branching, which can shape plant architecture and finally determine seed yield, we conducted comprehensive genome-wide analyses of the TIFY gene family in Brassica napus. Here, HMMER search and BLASTp were used to identify the TIFY members. A total of 70 TIFY members were identified and divided into four subfamilies based on the conserved domains and motifs. These TIFY genes were distributed across 19 chromosomes. The predicted subcellular localizations revealed that most TIFY proteins were located in the nucleus. The tissue expression profile analyses indicated that TIFY genes were highly expressed in the stem, flower bud, and silique at the transcriptional level. High-proportioned activation of the dormant axillary buds on stems determined the branch numbers of rapeseed plants. Here, transcriptome analyses were conducted on axillary buds in four sequential developing stages, that is, dormant, temporarily dormant, being activated, and elongating (already activated). Surprisingly, the transcription of the majority of TIFY genes (65 of the 70) significantly decreased on the activation of buds. GO enrichment analysis and hormone treatments indicated that the transcription of TIFY family genes can be strongly induced by jasmonic acid, implying that the TIFY family genes may be involved in the regulation of jasmonic acid-mediated branch development. These results shed light on the roles of TIFY family genes in plant architecture.
Influence of N1-Methylpseudouridine in Guide RNAs on CRISPR/Cas9 Activity
Authors: Prokhorova Daria , Matveeva Anastasiya , Zakabunin Alexander , Ryabchenko Alexander , Stepanov Grigory
Published: December 2023

At present, there are many strategies to improve the activity of CRISPR/Cas9. A well-known and effective approach is guide RNA modification. Many chemical guide RNA modifications have been studied, whereas naturally occurring RNA modifications are largely unexplored. N1-methylpseudouridine (m1Ψ) is an RNA base modification widely used in mRNA therapy, and it holds great promise for application in genome editing systems. The present study focuses on investigating the effect of N1-methylpseudouridine on the functioning of CRISPR/Cas9. In vitro cleavage assays helped determine the level of m1Ψ guide RNA modification that is sufficient to cleave the target substrate. By analyzing FAM-labeled dsDNA substrate cleavage, we calculated the kinetic parameters and the specificity scores of modified guide RNAs. Neon transfection and digital PCR enabled us to assess the activity of modified guide RNAs in mammalian cells. Our study shows that the presence of m1Ψ in guide RNAs can help preserve on-target genome editing while significantly reducing the off-target effects of CRISPR/Cas9 in vitro. We also demonstrate that Cas9 complexes with guide RNAs containing m1Ψ allow for genome editing in human cells. Thus, the incorporation of m1Ψ into guide RNAs supports CRISPR/Cas9 activity both in vitro and in cells.
Regulation of Peptidase Activity beyond the Active Site in Human Health and Disease
Authors: Obaha Ana , Novinec Marko
Published: December 2023

This comprehensive review addresses the intricate and multifaceted regulation of peptidase activity in human health and disease, providing a comprehensive investigation that extends well beyond the boundaries of the active site. Our review focuses on multiple mechanisms and highlights the important role of exosites, allosteric sites, and processes involved in zymogen activation. These mechanisms play a central role in shaping the complex world of peptidase function and are promising potential targets for the development of innovative drugs and therapeutic interventions. The review also briefly discusses the influence of glycosaminoglycans and non-inhibitory binding proteins on enzyme activities. Understanding their role may be a crucial factor in the development of therapeutic strategies. By elucidating the intricate web of regulatory mechanisms that control peptidase activity, this review deepens our understanding in this field and provides a roadmap for various strategies to influence and modulate peptidase activity.
Expression and Functional Analysis of the Compact Thermophilic Anoxybacillus flavithermus Cas9 Nuclease
Authors: Matveeva Anastasiya , Ryabchenko Alexander , Petrova Viktoria , Prokhorova Daria , Zhuravlev Evgenii , Zakabunin Alexander , Tikunov Artem , Stepanov Grigory
Published: December 2023

Research on Cas9 nucleases from different organisms holds great promise for advancing genome engineering and gene therapy tools, as it could provide novel structural insights into CRISPR editing mechanisms, expanding its application area in biology and medicine. The subclass of thermophilic Cas9 nucleases is actively expanding due to the advances in genome sequencing allowing for the meticulous examination of various microorganisms’ genomes in search of the novel CRISPR systems. The most prominent thermophilic Cas9 effectors known to date are GeoCas9, ThermoCas9, IgnaviCas9, AceCas9, and others. These nucleases are characterized by a varying temperature range of the activity and stringent PAM preferences; thus, further diversification of the naturally occurring thermophilic Cas9 subclass presents an intriguing task. This study focuses on generating a construct to express a compact Cas9 nuclease (AnoCas9) from the thermophilic microorganism Anoxybacillus flavithermus displaying the nuclease activity in the 37–60 °C range and the PAM preference of 5′-NNNNCDAA-3′ in vitro. Here, we highlight the close relation of AnoCas9 to the GeoCas9 family of compact thermophilic Cas9 effectors. AnoCas9, beyond broadening the repertoire of Cas9 nucleases, suggests application in areas requiring the presence of thermostable CRISPR/Cas systems in vitro, such as sequencing libraries’ enrichment, allele-specific isothermal PCR, and others.
miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review
Authors: Occhipinti Carla , La Russa Raffaele , Iacoponi Naomi , Lazzari Julia , Costantino Andrea , Di Fazio Nicola , Del Duca Fabio , Maiese Aniello , Fineschi Vittorio
Published: December 2023

Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.
Role of Mitochondria in Inflammatory Bowel Diseases: A Systematic Review
Authors: Sánchez-Quintero María José , Rodríguez-Díaz Cristina , Rodríguez-González Francisco J. , Fernández-Castañer Alejandra , García-Fuentes Eduardo , López-Gómez Carlos
Published: December 2023

Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from H2S and NH3. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn’s disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota– and brain–gut axes and the development of colitis-associated colorectal cancer.
Hexafluoroisopropylboranes and -Borates
Authors: Zapf Ludwig , Finze Maik
Published: December 2023

Novel hexafluoroisopropylboranes (CF3)(CF2H)CFBH2·L and -borate anions [(CF3)(CF2H)CFBH2X]− with Lewis basic heterocyclic ligands L and the anionic substituents X = F− and CN− were obtained. The syntheses were accomplished by substitution reactions of the dimethyl sulfide adduct (CF3)(CF2H)CFBH2·SMe2, which was synthesized on a large scale. The hexafluoroisopropylboranes and -borates were characterized by NMR and vibrational spectroscopy, elemental analysis, and single-crystal X-ray diffraction. In addition, the thermal and electrochemical stabilities were investigated by DSC measurements and cyclic voltammetry and selected experimental data and trends are compared with theoretical ones.
Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity
Authors: Zinser Emily , Tan Ky-Lyn , Kim Da-In , O’Brien Rachael , Winstanley Alison , Yong Patrick
Published: December 2023

Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence.
Updates on Potential Therapeutic Approaches for Vitiligo: Janus Kinase Inhibitors and Biologics
Authors: Pala Valentina , Ribero Simone , Quaglino Pietro , Mastorino Luca
Published: December 2023

Vitiligo, the most prevalent skin depigmenting disease, is characterized by the selective loss of melanocytes, impacting patients’ quality of life significantly. This autoimmune disorder progresses through a complex interplay of genetic and non-genetic factors, posing challenges in comprehending its pathogenesis and devising effective treatment strategies for achieving remission. Existing conventional therapeutic approaches, such as topical and oral corticosteroids, calcineurin inhibitors, and phototherapy, lack specificity, offer modest efficacy, and may entail potential adverse effects. Consequently, there is a pressing need for a more nuanced understanding of vitiligo’s pathogenesis to pave the way for targeted therapeutic innovations. This review aims to provide a comprehensive overview of recent developments and findings concerning Januse Kinase (JAK) inhibitors and biologics tested in vitiligo patients. JAK inhibitors have exhibited promising results, showcasing both efficacy and tolerability. In contrast, the outcomes of biologics treatment have been more varied. However, to establish a clearer understanding of which specific pathways to target for a more effective approach to vitiligo, additional in vitro studies and extensive clinical research involving a larger population are imperative.
Diamine Oxidase Interactions with Anti-Inflammatory and Anti-Migraine Medicines in the Treatment of Migraine
Authors: Tobajas Yaiza , Alemany-Fornés Marc , Samarra Iris , Romero-Giménez Jordi , Tintoré Maria , del Pino Antoni , Canela Núria , del Bas Josep M. , Ortega-Olivé Nàdia , de Lecea Carlos , Escoté Xavier
Published: December 2023

Histamine intolerance arises when there is a disparity between the production of histamine and the body’s ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice.
Effects of Gamma Irradiation on the AC Electrical Properties of Cross-Linked Epoxy Resin/Bisphenol A-Based Polycarbonate Composites
Authors: Alqudah Ziad , Juwhari Hassan K. , Elimat Ziad
Published: December 2023

The effects of gamma radiation on the AC electrical properties of highly cross-linked epoxy resin/bisphenol A-based polycarbonate samples have been investigated as a function of concentrations of bisphenol A-based polycarbonate, frequency, and temperature. The composite samples contained different bisphenol A-based polycarbonate concentrations of 0, 4, 8, 10, and 15 by wt%. The gamma irradiation process was performed at different gamma doses of 0, 100, 300, and 500 Gy. The AC electrical properties of the tested samples were studied before and after gamma irradiation within a frequency range of 200 kHz to 1 MHz. The results show that after irradiation, a consistent decrease in complex impedance values (Z∗) was observed, indicating an increase in conductivity due to radiation-induced scission of the composite structure. Dielectric properties, including the dielectric constant (εr) and dielectric loss (εi), exhibited an increase with higher doses and higher polycarbonate concentrations, signifying the formation of defect sites and charge carrier trapping. AC electrical conductivity (σac) displayed a notable rise post irradiation, with temperatures ranging from 30 °C to 110 °C, and higher radiation doses and higher temperatures led to increased conductivity. The activation energy ( Ea) decreased as the radiation dose increased, reflecting structural modifications induced by radiation.
The Influence of High-Temperature Tests on the Resistance to Degradation and Reduction in Strength Properties of Lithium-Containing Ceramics Used as Blanket Materials for Tritium Breeding
Authors: Kozlovskiy Artem L. , Moldabayeva Gulnaz Zh. , Shlimas Dmitriy I. , Borgekov Daryn B. , Rusakov Vyacheslav S.
Published: December 2023

Conducting high-temperature tests on ceramics-containing lithium, which are employed as tritium breeding materials, plays a crucial role in comprehending their ability to withstand degradation and maintain their strength properties throughout operation. From the standpoint of fusion research, it is imperative to grasp these phenomena in order to guarantee the safety and effectiveness of reactors. Additionally, these factors could impact the choice of particular materials and designs for blanket materials. The primary objective of this research is to evaluate alterations in the strength characteristics of ceramics-containing lithium when subjected to high-temperature thermal stability tests, while also preserving the hardness stability and resistance to cracking in ceramics subjected to cyclic tests. Lithium-containing ceramics based on lithium titanate (Li2TiO3), lithium orthosilicate (Li4SiO4), and lithium methacyrconate (Li2ZrO3), having a high structural ordering degree and good strength properties, were chosen as objects for assessing resistance to high-temperature degradation. During the studies, it was discovered that the presence of interphase boundaries in the composition of ceramics linked to the development of impurity phases results in crack resistance growth during long-term high-temperature tests simulating the stress effect on the material. At the same time, an assessment of high-temperature aging as a result of modeling destruction processes showed that ceramics based on lithium metazirconate are the most resistant to degradation of strength properties. By simulating high-temperature aging processes, it became feasible to establish connections between structural alterations resulting from the thermal expansion of the crystal lattice and oxygen migration phenomena occurring at elevated temperatures. These factors collectively contribute to a detrimental reduction in the strength properties of ceramics-containing lithium.
A Geographic Information System (GIS)-Based Investigation of Spatiotemporal Characteristics of Pirate Attacks in the Maritime Industry
Authors: Chen Qiong , Zhang Hongyu , Lau Yui-yip , Liu Kaiyuan , Ng Adolf K. Y. , Chen Weijie , Liao Qingmei , Dulebenets Maxim A.
Published: December 2023

Maritime transportation is vital for the movement of cargo between different continents and distant locations but can be disrupted by the frequent occurrence of pirate attacks. Based on the pirate attacks from July 1994 to December 2019, a spatial analysis of pirate attacks using a Geographic Information System (GIS) was conducted in the present study using the data available for tankers, dry bulk carriers, container vessels, general cargo vessels, and tugs. The adoption of the kernel density analysis was intended to identify the spatial pattern of global pirate attacks. The research results demonstrated that the pirate attacks showed a clustering pattern and were mostly associated with areas experiencing economic depression, a high unemployment rate, and social unrest. Accordingly, spatiotemporal hot spot analysis was carried out to recognize the changing directions of cold spots and hot spots over a period of time. The waters off Somalia, the Strait of Malacca, the Philippines, the Bay of Bengal, the Gulf of Guinea, and the northwest of South America were found to be the common locations of pirate attacks. The cold and hot spots of pirate attacks on the three key vessel types, including tankers, dry bulk carriers, and container vessels, were found to be similar. When considering the same area, the trends of cold and hot spots of different vessel types being attacked were substantially different. This study can provide a useful guideline for the International Maritime Organization and other relevant organizations in the world to design and implement targeted strategies to combat and mitigate pirate attacks. Additionally, the introduction of a GIS may help to envision the spatial and temporal distribution of pirate attacks and to explore the characteristics of pirate behaviors at sea and the patterns of piracy.
Risk Assessment and Traffic Behaviour Evaluation of Ships
Authors: Huang Juan-Chen , Ung Shuen-Tai
Published: December 2023

Recent advancements in information technology and ship equipment have led to massive data collection on maritime traffic, particularly through automatic identification systems (AIS) [...]
Dark Pigments in Entomopathogenic Fungal Microsclerotia: Preliminary Evidence of a 1,8-Dihydroxynaphthalene-melanin-like Compound in Metarhizium robertsii
Authors: Espín-Sánchez Daysi , Preisegger Lautaro , Mazzolenis Romina , Santana Marianela , Saparrat Mario C. N. , Pedrini Nicolás , Huarte-Bonnet Carla
Published: December 2023

Metarhizium robertsii microsclerotia are fungal aggregates composed of compacted, pigmented hyphae. As they are highly tolerant to desiccation and produce infective conidia, they are promising candidates to be formulated as bioinsecticides. Despite this potential, the nature of the pigments within these structures remains unclear. In this study, routine culture media used for the differentiation of M. robertsii microsclerotia were supplemented with four melanin inhibitors, and the resulting propagules were characterized. Inhibitors of the 1,8-dihydroxynaphthalene (DHN)-melanin biosynthetic pathway such as tricyclazole and guaiacol induced significant phenotypic and molecular modifications in the obtained M. robertsii propagules, which exhibited a more spherical shape, reduced size, and increased susceptibility to desiccation, heat, and oxidative stress than microsclerotia obtained without inhibitors. Additionally, genes encoding for a polyketide synthase (Mrpks2) and a putative 1,3,6,8-tetrahydroxynaphthalene reductase (Mrthnr), potentially involved in the DHN-melanin biosynthetic pathway, were upregulated in fungi grown in the inhibitor-added media. In conclusion, M. robertsii microsclerotia contain melanins of type DHN that might play a role in both microsclerotia differentiation and environmental stress tolerance.
Kazachstania pintolopesii in Blood and Intestinal Wall of Macrophage-Depleted Mice with Cecal Ligation and Puncture, the Control of Fungi by Macrophages during Sepsis
Authors: Hiengrach Pratsanee , Chindamporn Ariya , Leelahavanichkul Asada
Published: December 2023

Although macrophage depletion is a possible emerging therapeutic strategy for osteoporosis and melanoma, the lack of macrophage functions can lead to inappropriate microbial control, especially the regulation of intestinal microbiota. Cecal ligation and puncture (CLP) sepsis was performed in regular mice and in mice with clodronate-induced macrophage depletion. Macrophage depletion significantly increased the mortality and severity of sepsis-CLP mice, partly through the increased fecal Ascomycota, especially Kazachstania pintolopesii, with polymicrobialbacteremia (Klebsiella pneumoniae, Enterococcus faecalis, and Acinetobacter radioresistens). Indeed, macrophage depletion with sepsis facilitated gut dysbiosis that directly affected gut permeability as yeast cells were located and hidden in the colon crypts. To determine the interactions of fungal molecules on bacterial abundance, the heat-kill lysate of fungi (K. pintolopesii and C. albicans) and purified (1→3)-β-d-glucan (BG; a major component of the fungal cell wall) were incubated with bacteria that were isolated from the blood of macrophage-depleted mice. There was enhanced cytokine production of enterocytes (Caco-2) after the incubation of the lysate of K. pintolopesii (isolated from sepsis mice), the lysate of C. albicans (extracted from sepsis patients), and BG, together with bacterial lysate. These data support a possible influence of fungi in worsening sepsis severity. In conclusion, macrophage depletion enhanced K. pintolopesii in feces, causing the overgrowth of fecal pathogenic bacteria and inducing a gut permeability defect that additively worsened sepsis severity. Hence, the fecal fungus could be spontaneously elevated and altered in response to macrophage-depleted therapy, which might be associated with sepsis severity.
The Identity, Virulence, and Antifungal Effects of the Didymellacesous Fungi Associated with the Rapeseed Blackleg Pathogen Leptosphaeria biglobosa
Authors: Cheng Junyu , Luo Tao , Wu Mingde , Yang Long , Chen Weidong , Li Guoqing , Zhang Jing
Published: December 2023

Eight fungal strains (P1 to P8) were isolated from rapeseed stems (Brassica napus) infected with the blackleg pathogen Leptosphaeria biglobosa (Lb). They formed pycnidia with similar morphology to those of Lb, and thus were considered as Lb relatives (LbRs). The species-level identification of these strains was performed. Their virulence on rapeseed and efficacy in the suppression of Lb infection were determined, and the biocontrol potential and biocontrol mechanisms of strain P2 were investigated. The results showed that the LbRs belong to two teleomorphic genera in the family Didymellaceae, Didymella for P1 to P7 and Boeremia for P8. Pathogenicity tests on rapeseed cotyledons and stems indicated the LbRs were weakly virulent compared to L. biglobosa. Co-inoculation assays on rapeseed cotyledons demonstrated that P1 to P7 (especially P1 to P4) had a suppressive effect on Lb infection, whereas P8 had a marginal effect on infection by L. biglobosa. Moreover, D. macrostoma P2 displayed a more aggressive behavior than L. biglobosa in the endophytic colonization of healthy rapeseed cotyledons. Cultures of P2 in potato dextrose broth (PDB) and pycnidiospore mucilages exuded from P2 pycnidia showed antifungal activity to L. biglobosa. Further leaf assays revealed that antifungal metabolites (AM) of strain P2 from PDB cultures effectively suppressed infection by L. biglobosa, Botrytis cinerea (gray mold), and Sclerotinia sclerotiorum (white mold). An antifungal metabolite, namely penicillither, was purified and identified from PDB cultures and detected in pycnidiospore mucilages of strain P2. This study suggests that the LbRs are a repertoire for screening biocontrol agents (BCAs) against rapeseed diseases, and D. macrostoma P2 is a multi-functional BCA, a penicillither producer, and an endophyte.
Moral Judgment and Social Critique in Journalistic News Satire
Authors: Ödmark Sara
Published: December 2023

Journalistic news satire is a satire subgenre that is gaining legitimacy in academic research as well as in the journalistic field as an opinion news format and arena for public debate. News satirists claim journalistic roles and operate under the mandate of exposing moral wrongs and auditing power. The development of a more substantial news satire coincides with an observed repoliticization of humor and comedy and intensified moral negotiation around comedic content, particularly on social media. Based on the Moral Foundation Theory, this study identifies moral judgments in journalistic news satire, using a content analysis of TV news satire material from Sweden and the U.S. The results show an overwhelming majority of moral judgments related to the individualizing foundations of Harm and Fairness, while the binding foundations of Ingroup, Authority, and Purity were less frequent. In addition, the results show strong similarities between the two countries in the material, indicating moral common ground and displaying how moral judgment is connected to the inherent nature of satire in general and the genre conventions of journalistic news satire in particular.
Role of FGF21 and Leptin for the Diagnosis of Metabolic Health in Children with and without Obesity
Authors: Domouzoglou Eleni M. , Vlahos Antonios P. , Papafaklis Michail I. , Cholevas Vasileios K. , Chaliasos Nikolaos , Siomou Ekaterini , Michalis Lampros K. , Tsatsoulis Agathocles , Naka Katerina K.
Published: December 2023

Obesity and unfavorable metabolic profiles increase the risk for cardiovascular complications in adults. Although it is important to distinguish different metabolic health states at an early stage, there are limited data on the related value of biomarkers in childhood. We aimed to identify biomarkers for the detection of different metabolic health states in children with and without obesity. The serum levels of metabolic regulators (fibroblast growth factor 21 [FGF21], leptin, adiponectin and insulin-like growth factor binding protein 1) and vascular indices (flow-mediated dilation [FMD] and carotid intima-media thickness) were assessed in 78 children. Differences between the metabolically healthy and unhealthy state within children with normal weight (MHN vs. MUN), and within children with overweight/obesity (MHO vs. MUO) were investigated; the discriminatory power of the biomarkers was studied. Both MUN and MUO groups expressed altered lipid and glucose homeostasis compared to their healthy counterparts. The metabolic unhealthy state in children with normal weight was linked to higher FGF21 levels which had good discriminatory ability (area under the curve [AUC]: 0.71, 95% CI: 0.54–0.88; p = 0.044). In overweight/obese children, leptin was increased in the metabolically unhealthy subgroup (AUC: 0.81, 95% CI: 0.68–0.95; p = 0.01). There was a decrease in FMD indicating worse endothelial function in overweight/obese children versus those with normal weight. Distinct states of metabolic health exist in both children with normal weight and overweight/obese children. FGF21 and leptin may help to identify the metabolic unhealthy state in children with normal weight and in overweight/obese children, respectively, early in life.
Oral Health and Behavior Patterns of Women with Eating Disorders—A Clinical Pilot Study
Authors: Dehghan Mojdeh , Tantbirojn Daranee , Harrison Janet , Stewart Colette W. , Johnson Nancy , Tolley Elizabeth A. , Zhang Yanhui H.
Published: December 2023

Background: Chronic stomach regurgitation associated with eating disorders (EDs) poses a high risk for tooth erosion. This study investigated oral health conditions, behavioral patterns, and tooth erosion in women with EDs. Methods: 16 ED and 13 healthy women were enrolled; 14 ED and 10 healthy control subjects completed the study. Subjects completed demographic, medical, oral, and behavioral health history questionnaires. Dental caries status was recorded as Decayed, Missing and Filled Teeth (DMFT)index and the severity of tooth erosion as Basic Erosive Wear Examination (BEWE) scores. Saliva was collected for flow rate, pH, and buffering capacity analysis. Results: The ED group had a lower stimulated saliva flow rate and higher DMFT index but no significant difference in BEWE scores compared to the controls (t-test, significance level 0.05). Five of the fourteen ED subjects exhibited extensive tooth erosion, which may have been exacerbated by their tooth-brushing behavior. Conclusions: Although some ED subjects showed extensive tooth erosion in this pilot study, the average BEWE score of the ED group was not significantly different from the controls. Extensive tooth erosion in ED may relate to the low stimulated salivary flow. A larger-scale clinical study is necessary to validate these results.
Implants Placed with a Ring Technique Using Inlay and Onlay Block Xenografts in the Mandible of Rabbits
Authors: Kaneko Naoki , Xavier Samuel Porfirio , Morinaga Kenzo , Botticelli Daniele , Silva Erick Ricardo , Nakajima Yasushi , Baba Shunsuke
Published: December 2023

Background: Xenogenous bone has been proposed as an alternative to overcome the disadvantages of autogenous grafting. The aim of the present study was to study bone dynamics at inlay and onlay xenografts used for bone augmentation applying a ring technique. Methods: The bone at the lateral surface of the mandibular angle of 12 adult male New Zealand White rabbits was exposed bilaterally. The cortical layer received multiple perforations on one side of the mandible, and a xenograft block of collagenated cancellous equine bone, 7 mm in diameter and 3 mm in width, was fixed on the prepared surface using an implant (onlay group). On the opposite side, a defect 7 mm in diameter and 3 mm in depth was prepared, and the xenograft block was adapted to the defect and fixed with an implant (inlay group). Results: After ten weeks of healing, in the onlay grafts, new bone was mainly formed on the trabeculae surface, reaching in some specimens the most coronal regions of the block. In the inlay grafts, new bone was found arranged on the trabecular surfaces but also occupying the spaces among the trabeculae. The entrance of the defect was often found close to the top of the block by newly formed bone. A higher percentage of new bone was found in the inlay (19.0 ± 9.3%) compared to the onlay (10.4 ± 7.4%) groups (p = 0.031). The mean gain in osseointegration at the implant in relation to the base of the original 3 mm deep defect was 0.95 ± 1.05% in the onlay group and 0.78 ± 0.71% in the inlay group (p = 0.603). Conclusion: The inlay grafts exhibited a higher new bone percentage than the onlay block grafts possibly due to the defect conformation that presented more sources for bone growth. The trabecular conformation and the composition of the grafts made possible the expression of the osteoconductive properties of the material used. This resulted, in several specimens, in the growth of bone on the graft trabeculae toward the most superior regions in both groups and in the closure of the coronal entrance of the defects in the inlay group. The clinical relevance of this experiment is that the ring technique applied as an inlay method could be suitable for bone augmentation.
Effective Macroscopic Thermomechanical Characterization of Multilayer Circuit Laminates for Advanced Electronic Packaging
Authors: Cheng Hsien-Chie , Jhu Wen-You
Published: December 2023

Laminate substrates in advanced IC packages serve as not only the principal heat dissipation pathway but also the critical component governing the thermomechanical performance of advanced packaging technologies. A solid and profound grasp of their thermomechanical properties is of crucial importance to better understand IC packages’ thermomechanical behavior. This study attempts to introduce a subregion homogenization modeling framework for effectively and efficiently modeling and characterizing the equivalent thermomechanical behavior of large-scale and high-density laminate substrates comprising the non-uniform distribution and non-unidirectional orientation of tiny metal traces. This framework incorporates subregion modeling, trace mapping and modeling, and finite element analysis (FEA)-based effective modeling. In addition, the laminates are macroscopically described as elastic orthotropic or elastic anisotropic material. This framework is first validated with simple uniaxial tensile and thermomechanical test simulations, and the calculation results associated with these two effective material models are compared with each other, as well as with those of two existing mixture models, and direct the detailed FEA. This framework is further tested on the prediction of the process-induced warpage of a flip chip chip-scale package, and the results are compared against the measurement data and the results of the whole-domain modeling-based effective approach and two existing mixture models.
Pervious Concrete Made with Recycled Coarse Aggregate and Reinforced with Date Palm Leaves Fibers
Authors: Tamimi Adil , Tabsh Sami W. , El-Emam Magdi
Published: December 2023

This study considers 12 pervious concrete mixes incorporating 100% recycled coarse aggregate from old concrete demolition waste and containing various amounts of natural fine aggregate and date palm leaves fibers. First, the properties of the recycled aggregate in terms of their particle size distribution, abrasion resistance, crushing values, specific gravity and water absorption are obtained. Next, the pervious concrete density, compressive strength, tensile strength, permeability and porosity are determined by experimental testing following the relevant standards. The results are analyzed and compared to determine the influence of using recycled coarse aggregate in the mixtures and the impact of the amount of natural sand and volume fraction of the fibers on the mechanical properties, permeability and porosity of the concrete. Findings of the study showed that the use of recycled coarse aggregate in pervious concrete without fine aggregate reduced the compressive strength by 36% and tensile strength by 57%. Replacing 11.7% of the recycled coarse aggregate with natural sand and adding date palm leaves fibers in an amount equivalent to 0.64% volumetric content to such concrete helped increase the compressive strength by 16.2% and tensile strength by 3.2% above the corresponding strengths of the control mix. There is a clear relationship between permeability and porosity due to their correlation with the density of pervious concrete, and the effect of porosity on tensile strength is more influential than it is on the compressive strength. An equation that can predict the tensile strength of pervious concrete from the compressive strength is proposed, as a function of the natural fine aggregate fraction of the coarse aggregate and volumetric content of natural fibers. Results of the research confirm the feasibility of using recycled aggregate in pervious concrete mixes and the positive impact of natural fibers on the mechanical properties.
Luminescent Metal–Organic Frameworks for Electrochemiluminescent Detection of Water Pollutants
Authors: Sentic Milica , Trajkovic Ivana , Manojlovic Dragan , Stankovic Dalibor , Nikolic Maria Vesna , Sojic Neso , Vidic Jasmina
Published: December 2023

The modern lifestyle has increased our utilization of pollutants such as heavy metals, aromatic compounds, and contaminants that are of rising concern, involving pharmaceutical and personal products and other materials that may have an important environmental impact. In particular, the ultimate results of the intense use of highly stable materials, such as heavy metals and chemical restudies, are that they turn into waste materials, which, when discharged, accumulate in environmental water bodies. In this context, the present review presents the application of metal–organic frameworks (MOFs) in electrochemiluminescent (ECL) sensing for water pollutant detection. MOF composites applied as innovative luminophore or luminophore carriers, materials for electrode modification, and the enhancement of co-reaction in ECL sensors have enabled the sensitive monitoring of some of the most common contaminants of emerging concern such as heavy metals, volatile organic compounds, pharmaceuticals, industrial chemicals, and cyanotoxins. Moreover, we provide future trends and prospects associated with ECL MOF composites for environmental sensing.