bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of pH and Optical Properties of Dual Rinse HEDP Irrigating Solution
Authors: Simic Andjelka , Papic Mirjana V. , Nikitovic Ana , Kocovic Aleksandar , Petrovic Renata , Melih Irena , Zivanovic Suzana , Papic Milos , Popovic Milica
Published: February 2024

This study investigates the pH values and optical characteristics of Dual Rinse HEDP, either independently or combined with sodium hypochlorite (NaOCl), and compares them to other irrigants used in endodontics. The solutions used in this study were commercially acquired and prepared, followed by pH measurements using a pH meter and spectral analysis using UV/Vis spectrophotometry in specified wavelengths of the ultraviolet (UV) C (190–280 nm), UVB (281–315 nm), UVA (316–400 nm), visible light (VL) (401–780 nm), and near-infrared (NIR) spectra (781–1100 nm). The pH analysis revealed alkaline values for NaOCl, EDTA, Dual Rinse HEDP, and the HEDP + NaOCl combination, an acidic value for citric acid, and nearly neutral values for chlorhexidine and distilled water. Spectral analysis revealed the notable absorption characteristics of endodontic irrigants. In the UV range, all solutions exhibited higher absorption values to water (p < 0.05), with Dual Rinse HEDP resembling EDTA and citric acid, and HEDP + NaOCl resembling NaOCl. The NIR region highlights absorption peaks around 975 nm for all solutions, including NaOCl and Dual Rinse HEDP + NaOCl, suggesting potential applications in laser-activated irrigation. This study provides comprehensive insights into the pH and optical features of endodontic irrigants, emphasizing their potential roles in enhancing disinfection strategies and optimizing laser-activated irrigation protocols.
Enhanced Enzymatic Degradability of Livestock Blood Pretreated with Ultrasonic Technique
Authors: Jeon Mi-Jin , Jeon Yong-Woo
Published: February 2024

Livestock blood, a major organic waste generated by the livestock industry, poses a risk of pollution due to its rapid decomposition. However, it is a potential protein source for agricultural purposes due to its protein-rich organic matter. In this study, we conducted studies on an eco-friendly, scalable, and effective protein degradation process using livestock blood to reduce waste and produce an amino acid liquid fertilizer that can be recycled for agricultural use. Ultrasonic technology was applied as a pretreatment method to improve the enzymatic hydrolysis efficiency of proteins in livestock blood, and the optimal conditions that led to 95.91% solubilization rate of hemoglobin were ultrasound duration for 30 min at an ultrasound density of 0.5 W/mL. As a result of hydrolyzing ultrasonically pretreated blood by mixing exo- and endo-type proteolytic enzymes, the optimal combination was a mixture of Savinase® 1% and Flavourzyme® 1%. After 4 h of reaction, the protein concentration was 27.8 mg/mL and the amino acid concentration was confirmed to be 54.6 mg/mL. This is about 4.2 times higher than the amino acid concentration of blood without ultrasound pretreatment, 13.1 mg/mL, and it was confirmed that sonication has a significant effect on improving protein degradation efficiency. As protein degradation increased, the viscosity of blood gradually decreased, suggesting that the physical force applied to the agitator torque diminished during the enzyme reaction; a significant correlation between protein and amino acid concentrations (biological factors) and torque (mechanical factor) was observed. Measuring torque during an enzyme reaction can confirm the extent of the enzyme reaction, so it can be used as an indicator of reaction progress when scaling up the process in the future.
A Distinct Form of Socio-Political and Economic Organization in the Pazyryk Culture
Authors: Rubinson Karen S. , Linduff Katheryn M.
Published: February 2024

The Pazyryk Culture, situated in the Altai Mountains of Russia, Kazakhstan, Mongolia, and China, flourished for a relatively short period: 5th–3rd centuries BCE. A series of burial grounds from the later phase, 4th–mid-3rd centuries BCE, to be studied here reveal the remains of three groups of individuals of high, mid, and lower status. Within the limiting topographical and environmental confines of the local region, in contrast to the vast grasslands of the steppe and the deserts and oases of Central Asia, it is possible via the analysis of material culture and with reference to ethnographic studies to see nuances of interaction among these three groups and the regions immediately adjacent during this short period. Aided by modern scientific techniques, including DNA and isotopic analysis, together with analysis of excavated and often frozen remains, it is also possible to map out a heterarchical set of relationships within the hierarchical framework. The model developed in this unique landscape might be tested elsewhere in Eurasia as it extends the application of the notion of nonuniform socio-political organization among pastoralists noted for Bronze Age societies in the Eurasian steppe to the late Iron Age.
Viewpoints/Points of View: Building a Transdisciplinary Data Theatre Collaboration in Six Scenes
Authors: Snyder-Young Dani , Arnold Mages Michael , Bhargava Rahul , Carr Jonathan , Perovich Laura , Talmadge Victor , Wason Oliver , Zellner Moira , C-Dina Angelique , Birnholz Ren , Brockett Halle , D’Ascoli Ezekiel , Holt Donovan , Love Sydney , Belliveau George
Published: February 2024

Data now plays a central role in civic life and community practices. This has created a pressing need for new forms of translation and sense-making that can engage diverse publics. Research-based Theatre (RbT) has proven to be an effective approach to delivering qualitative data to community stakeholders. We extend this tradition by proposing “community-engaged data theatre”. This approach translates quantitative data into theatrical language to engage communities in deliberative conversations on relevant issues. Community-engaged data theatre requires bridging multiple disciplines and involves creating new definitions and shared vocabularies in discourses that formerly have had little overlap in meaning. In this article, we share key insights from our initial experiments in which we adapted quantitative and qualitative data to devise a pilot piece in collaboration with a local community partner. In this essay, we communicate our collaborative process in polyvocal, artistic form. We edit and adapt materials from our conversations and creative practices into scenes illustrating how we taught and learned from each other about data science, participatory modeling, material deliberation and Composition to pilot our lab’s first community-engaged data theatre prototype.
The Discursive Power of Digital Popular Art during the Russo-Ukrainian War: Re/Shaping Visual Narratives
Authors: Kot Svitlana , Mozolevska Alina , Polishchuk Olha , Stodolinska Yuliya
Published: February 2024

Twenty-first century digital technologies and popular visual art have transformed the ways military conflicts are experienced, narrated, and shared. It demonstrates that digital platforms have become arenas for constructing visual narratives that influence public perception and engagement with the conflict. Through a multimodal and visual analysis of over 950 digital artworks shared on Instagram during the first three months of the Russian full-scale invasion of Ukraine, this study investigates how these artworks form specific visual narratives which contribute to portraying the new wartime reality while also constructing images of the self and the other through heroization, victimization, dehumanization, and other strategies. All these visual narratives jointly represent the complexity of the war reality and form an epistemic understanding of the conflict. This study highlights the important function that popular visual art on digital platforms such as Instagram plays in shaping perceptions of the Russo-Ukrainian War, particularly in expressing emotions, conveying traumas, and influencing public opinions.
FeC4H22+ Encompassing Planar Tetracoordinate Iron: Structure and Bonding Patterns
Authors: Shajan Shilpa , Thirunavukkarsu Kandasamy , Chandrasekaran Vijayanand , Thimmakondu Venkatesan S. , Thirumoorthy Krishnan
Published: February 2024

The singlet, triplet, and quintet electronic states of the FeC4H22+ system are theoretically explored using quantum chemical methods, and 39 isomers are identified in the singlet electronic state and 4 isomers in both triplet and quintet electronic states. A molecule with a planar tetracoordinate iron (ptFe) is found on the potential energy surface of singlet and triplet electronic states. The bonding features of ptFe in the singlet electronic state are analyzed with natural bond orbital (NBO) analysis, adaptive natural density partitioning (AdNDP), and molecular orbital analysis. The resultant data delineate that the ptFe is stabilized through electron delocalization in the ptFe system.
On Equivalence Operators Derived from Overlap and Grouping Functions
Authors: Du Lei , Xu Yingying , Song Haifeng , Dai Songsong
Published: February 2024

This paper introduces the concept of equivalence operators based on overlap and grouping functions where the associativity property is not strongly required. Overlap functions and grouping functions are weaker than positive and continuous t-norms and t-conorms, respectively. Therefore, these equivalence operators do not necessarily satisfy certain properties, such as associativity and the neutrality principle. In this paper, two models of fuzzy equivalence operators are obtained by the composition of overlap functions, grouping functions and fuzzy negations. Their main properties are also studied.
Existence and Properties of the Solution of Nonlinear Differential Equations with Impulses at Variable Times
Authors: Xia Huifu , Peng Yunfei , Zhang Peng
Published: February 2024

In this paper, a class of nonlinear ordinary differential equations with impulses at variable times is considered. The existence and uniqueness of the solution are given. At the same time, modifying the classical definitions of continuous dependence and Gâteaux differentiability, some results on the continuous dependence and Gâteaux differentiable of the solution relative to the initial value are also presented in a new topology sense. For the autonomous impulsive system, the periodicity of the solution is given. As an application, the properties of the solution for a type of controlled nonlinear ordinary differential equation with impulses at variable times is obtained. These results are a foundation to study optimal control problems of systems governed by differential equations with impulses at variable times.
Entropy of Difference: A New Tool for Measuring Complexity
Authors: Nardone Pasquale , Sonnino Giorgio
Published: February 2024

We propose a new tool for estimating the complexity of a time series: the entropy of difference (ED). The method is based solely on the sign of the difference between neighboring values in a time series. This makes it possible to describe the signal as efficiently as prior proposed parameters, such as permutation entropy (PE) or modified permutation entropy (mPE). Firstly, this method reduces the size of the sample that is necessary to estimate the parameter value, and secondly it enables the use of the Kullback–Leibler divergence to estimate the “distance” between the time series data and random signals.
The Fourier–Legendre Series of Bessel Functions of the First Kind and the Summed Series Involving 1F2 Hypergeometric Functions That Arise from Them
Authors: Straton Jack C.
Published: February 2024

The Bessel function of the first kind JNkx is expanded in a Fourier–Legendre series, as is the modified Bessel function of the first kind INkx. The purpose of these expansions in Legendre polynomials was not an attempt to rival established numerical methods for calculating Bessel functions but to provide a form for JNkx useful for analytical work in the area of strong laser fields, where analytical integration over scattering angles is essential. Despite their primary purpose, one can easily truncate the series at 21 terms to provide 33-digit accuracy that matches the IEEE extended precision in some compilers. The analytical theme is furthered by showing that infinite series of like-powered contributors (involving  1F2 hypergeometric functions) extracted from the Fourier–Legendre series may be summed, having values that are inverse powers of the eight primes 1/2i3j5k7l11m13n17o19p multiplying powers of the coefficient k.
Risk Factors for Early Implant Failure and Selection of Bone Grafting Materials for Various Bone Augmentation Procedures: A Narrative Review
Authors: Munakata Motohiro , Kataoka Yu , Yamaguchi Kikue , Sanda Minoru
Published: February 2024

Implant therapy is now an established treatment with high long-term success and survival rates. However, early implant failure, which occurs within one year of superstructure placement, occurs at a higher rate than late failure, which is represented by peri-implantitis caused by bacterial infection. Furthermore, various risk factors for early failure have been reported, including patient-related factors, such as systemic diseases, smoking, and bone quality and quantity, as well as surgery-related factors, such as surgeons’ skill, osteogenesis technique, and selection of graft material, and implant-related factors, such as initial implant fixation and implant length diameter. Due to the wide variety of relevant factors reported, it is difficult to identify the cause of the problem. The purpose of this review is to discuss the risk factors associated with various types of bone augmentation which have a close causal relationship with early implant failure, and to determine the optimal bone grafting material for bone augmentation procedures to avoid early implant failure.
3D Printed Piezoelectric BaTiO3/Polyhydroxybutyrate Nanocomposite Scaffolds for Bone Tissue Engineering
Authors: Strangis Giovanna , Labardi Massimiliano , Gallone Giuseppe , Milazzo Mario , Capaccioli Simone , Forli Francesca , Cinelli Patrizia , Berrettini Stefano , Seggiani Maurizia , Danti Serena , Parchi Paolo
Published: February 2024

Bone defects are a significant health problem worldwide. Novel treatment approaches in the tissue engineering field rely on the use of biomaterial scaffolds to stimulate and guide the regeneration of damaged tissue that cannot repair or regrow spontaneously. This work aimed at developing and characterizing new piezoelectric scaffolds to provide electric bio-signals naturally present in bone and vascular tissues. Mixing and extrusion were used to obtain nanocomposites made of polyhydroxybutyrate (PHB) as a matrix and barium titanate (BaTiO3) nanoparticles as a filler, at BaTiO3/PHB compositions of 5/95, 10/90, 15/85 and 20/80 (w/w%). The morphological, thermal, mechanical and piezoelectric properties of the nanocomposites were studied. Scanning electron microscopy analysis showed good nanoparticle dispersion within the polymer matrix. Considerable increases in the Young’s modulus, compressive strength and the piezoelectric coefficient d31 were observed with increasing BaTiO3 content, with d31 = 37 pm/V in 20/80 (w/w%) BaTiO3/PHB. 3D printing was used to produce porous cubic-shaped scaffolds using a 90° lay-down pattern, with pore size ranging in 0.60–0.77 mm and good mechanical stability. Biodegradation tests conducted for 8 weeks in saline solution at 37 °C showed low mass loss (∼4%) for 3D printed scaffolds. The results obtained in terms of piezoelectric, mechanical and chemical properties of the nanocomposite provide a new promising strategy for vascularized bone tissue engineering.
Surgical Medical Education via 3D Bioprinting: Modular System for Endovascular Training
Authors: Foresti Ruben , Fornasari Anna , Bianchini Massoni Claudio , Mersanne Arianna , Martini Chiara , Cabrini Elisa , Freyrie Antonio , Perini Paolo
Published: February 2024

There is currently a shift in surgical training from traditional methods to simulation-based approaches, recognizing the necessity of more effective and controlled learning environments. This study introduces a completely new 3D-printed modular system for endovascular surgery training (M-SET), developed to allow various difficulty levels. Its design was based on computed tomography angiographies from real patient data with femoro-popliteal lesions. The study aimed to explore the integration of simulation training via a 3D model into the surgical training curriculum and its effect on their performance. Our preliminary study included 12 volunteer trainees randomized 1:1 into the standard simulation (SS) group (3 stepwise difficulty training sessions) and the random simulation (RS) group (random difficulty of the M-SET). A senior surgeon evaluated and timed the final training session. Feedback reports were assessed through the Student Satisfaction and Self-Confidence in Learning Scale. The SS group completed the training sessions in about half time (23.13 ± 9.2 min vs. 44.6 ± 12.8 min). Trainees expressed high satisfaction with the training program supported by the M-SET. Our 3D-printed modular training model meets the current need for new endovascular training approaches, offering a customizable, accessible, and effective simulation-based educational program with the aim of reducing the time required to reach a high level of practical skills.
Differences of Pine Wood Nematode (Bursaphelenchus xylophilus) Developmental Stages under High-Osmotic-Pressure Stress
Authors: Wang Shuting , Chen Qiaoli , Wang Feng
Published: February 2024

Under ion imbalance, water deficiency, and salt stress, the osmotic pressure of the tree sap increases, and pine wood nematodes (Bursaphelenchus xylophilus, PWN) parasitizing in the trees may be subjected to high-osmotic-pressure stress. KCl, L-malic acid, sucrose, and glycerol solutions were used as osmolytes to explore the highest osmotic concentration that PWN can tolerate. Survival analysis showed that when the treatment concentration exceeded 90%, only a few nematodes in the glycerol group survived under 6 h treatment, and most of the survivors were third-stage dispersal juveniles (DJ3). Further examination revealed that under different concentrations of glycerol-induced high osmotic pressure, the survival rate and body length change rate were the highest in the DJ3 and the lowest in the second-stage propagative juveniles. In order to explore the molecular mechanism of resistance of DJ3 to high osmotic stress, transcriptome sequencing was performed at each developmental stage of PWN and differentially expressed genes that were up-regulated or down-regulated only in DJ3 were screened. The expression of genes related to CoA in DJ3, a key enzyme in metabolism, was significantly higher than the other developmental stages. In addition, the expression of the anti-reversal signal pathway-related gene AKT-1 in DJ3 was significantly lower than in the other development stages. Therefore, the specific expression of genes in DJ3 under high osmotic pressure may help them rapidly produce and accumulate energy-related compounds and activate the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) pathway to respond to damage caused by high-osmotic-pressure stress in time, thus promoting survival.
PoxiPred: An Artificial-Intelligence-Based Method for the Prediction of Potential Antigens and Epitopes to Accelerate Vaccine Development Efforts against Poxviruses
Authors: Martinez Gustavo Sganzerla , Dutt Mansi , Kelvin David J. , Kumar Anuj
Published: February 2024

Poxviridae is a family of large, complex, enveloped, and double-stranded DNA viruses. The members of this family are ubiquitous and well known to cause contagious diseases in humans and other types of animals as well. Taxonomically, the poxviridae family is classified into two subfamilies, namely Chordopoxvirinae (affecting vertebrates) and Entomopoxvirinae (affecting insects). The members of the Chordopoxvirinae subfamily are further divided into 18 genera based on the genome architecture and evolutionary relationship. Of these 18 genera, four genera, namely Molluscipoxvirus, Orthopoxvirus, Parapoxvirus, and Yatapoxvirus, are known for infecting humans. Some of the popular members of poxviridae are variola virus, vaccine virus, Mpox (formerly known as monkeypox), cowpox, etc. There is still a pressing demand for the development of effective vaccines against poxviruses. Integrated immunoinformatics and artificial-intelligence (AI)-based methods have emerged as important approaches to design multi-epitope vaccines against contagious emerging infectious diseases. Despite significant progress in immunoinformatics and AI-based techniques, limited methods are available to predict the epitopes. In this study, we have proposed a unique method to predict the potential antigens and T-cell epitopes for multiple poxviruses. With PoxiPred, we developed an AI-based tool that was trained and tested with the antigens and epitopes of poxviruses. Our tool was able to locate 3191 antigen proteins from 25 distinct poxviruses. From these antigenic proteins, PoxiPred redundantly located up to five epitopes per protein, resulting in 16,817 potential T-cell epitopes which were mostly (i.e., 92%) predicted as being reactive to CD8+ T-cells. PoxiPred is able to, on a single run, identify antigens and T-cell epitopes for poxviruses with one single input, i.e., the proteome file of any poxvirus.
Depletion of PHLDB2 Suppresses Epithelial–Mesenchymal Transition and Enhances Anti-Tumor Immunity in Head and Neck Squamous Cell Carcinoma
Authors: Li Hongyu , Wang Ziyi , Liang Huiting , Liu Xiaoyong , Liu Haichao , Zhuang Zehang , Hou Jinsong
Published: February 2024

The role of Pleckstrin homology-like domain family B member 2 (PHLDB2) in the regulation of cell migration has been extensively studied. However, the exploration of PHLDB2 in head and neck squamous cell carcinoma (HNSCC) is still limited in terms of expression, function, and therapeutic potential. In this study, we discovered an upregulation of PHLDB2 expression in HNSCC tissues which was correlated with a negative prognosis in patients with HNSCC. Additionally, we determined that a high level of expression of PHLDB2 is crucial for maintaining cell migration through the regulation of the epithelial–mesenchymal transition (EMT). Furthermore, we demonstrated that the ablation of PHLDB2 in tumor cells inhibited tumorigenicity in a C3H syngeneic tumor-bearing mouse model. Mechanistically, PHLDB2 was found to be involved in the regulation of T cell anti-tumor immunity, primarily by enhancing the activation and infiltration of CD8+ T cells. In light of these findings, PHLDB2 emerges as a promising biomarker and therapeutic target for interventions in HNSCC.
Steroid Metabolomic Signature in Term and Preterm Infants
Authors: Heckmann Matthias , Runkel Anna S. , Sunny Donna E. , Hartmann Michaela F. , Ittermann Till , Wudy Stefan A.
Published: February 2024

Adrenal function is essential for survival and well-being of preterm babies. In addition to glucocorticoids, it has been hypothesized that C19-steroids (DHEA-metabolites) from the fetal zone of the adrenal gland may play a role as endogenous neuroprotective steroids. In 39 term-born (≥37 weeks gestational age), 42 preterm (30–36 weeks) and 51 early preterm (<30 weeks) infants 38 steroid metabolites were quantified by GC-MS in 24-h urinary samples. In each gestational age group, three distinctive cluster were identified by pattern analysis (k-means clustering). Individual steroidal fingerprints and clinical phenotype were analyzed at the 3rd day of life. Overall, the excretion rates of C21-steroids (glucocorticoid precursors, cortisol, and cortisone metabolites) were low (<99 μg/kg body weight/d) whereas the excretion rates of C19-steroids were up to 10 times higher. There was a shift to higher excretion rates of C19-steroids in both preterm groups compared to term infants but only minor differences in the distribution of C21-steroids. Comparable metabolic patterns were found between gestational age groups: Cluster 1 showed mild elevation of C21- and C19-steroids with the highest incidence of neonatal morbidities in term and severe intraventricular hemorrhage in early preterm infants. In cluster 2 lowest excretion in general was noted but no clinically unique phenotype. Cluster 3 showed highest elevation of C21-steroids and C19-steroids but no clinically unique phenotype. Significant differences in steroid metabolism between clusters are only partly reflected by gestational age and disease severity. In early preterm infants, higher excretion rates of glucocorticoids and their precursors were associated with severe cerebral hemorrhage. High excretion rates of C19-steroids in preterm infants may indicate a biological significance.
Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models
Authors: Stoppa Ian , Dianzani Chiara , Clemente Nausicaa , Bozza Annalisa , Bordano Valentina , Garelli Sara , Cangemi Luigi , Dianzani Umberto , Battaglia Luigi
Published: February 2024

Bone is a site of distant metastases, which are a common cause of morbidity and mortality with a high socio-economic impact, for many malignant tumours. In order to engineer pharmacological therapies that are suitable for this debilitating disease, this experimental work presents injectable lipid nanoemulsions, which are endowed with a long history of safe clinical usage in parenteral nutrition, their loading with vincristine and their grafting with alendronate, with a dual purpose: merging the anticancer activity of bisphosphonates and vincristine, and enhancing bone-targeted delivery. In cell studies, alendronate synergised with the anti-migration activity of vincristine, which is important as migration plays a key role in the metastatisation process. In preliminary animal studies, carried out thanks to IVIS technology, alendronate conjugation enhanced the bone targeting of fluorescently labelled nanoemulsions. These encouraging results will drive further studies on suitable animal models of the disease.
Lactobacillus crispatus CCFM1339 Inhibits Vaginal Epithelial Barrier Injury Induced by Gardnerella vaginalis in Mice
Authors: Huang Xiaoyan , Lin Rumeng , Mao Bingyong , Tang Xin , Zhao Jianxin , Zhang Qiuxiang , Cui Shumao
Published: February 2024

The vaginal epithelial barrier, which integrates mechanical, immune, chemical, and microbial defenses, is pivotal in safeguarding against external pathogens and upholding the vaginal microecological equilibrium. Although the widely used metronidazole effectively curtails Gardnerella vaginalis, a key pathogen in bacterial vaginosis, it falls short in restoring the vaginal barrier or reducing recurrence rates. Our prior research highlighted Lactobacillus crispatus CCFM1339, a vaginally derived Lactobacillus strain, for its capacity to modulate the vaginal epithelial barrier. In cellular models, L. crispatus CCFM1339 fortified the integrity of the cellular monolayer, augmented cellular migration, and facilitated repair. Remarkably, in animal models, L. crispatus CCFM1339 substantially abated the secretion of the barrier disruption biomarker E-cadherin (from 101.45 to 82.90 pg/mL) and increased the anti-inflammatory cytokine IL-10 (35.18% vs. the model), consequently mitigating vaginal inflammation in mice. Immunological assays in vaginal tissues elucidated increased secretory IgA levels (from 405.56 to 740.62 ng/mL) and curtailed IL-17 gene expression. Moreover, L. crispatus CCFM1339 enhanced Lactobacilli abundance and attenuated Enterobacterium and Enterococcus within the vaginal microbiome, underscoring its potential in probiotic applications for vaginal barrier regulation.
CLPP-Null Eukaryotes with Excess Heme Biosynthesis Show Reduced L-arginine Levels, Probably via CLPX-Mediated OAT Activation
Authors: Key Jana , Gispert Suzana , Kandi Arvind Reddy , Heinz Daniela , Hamann Andrea , Osiewacz Heinz D. , Meierhofer David , Auburger Georg
Published: February 2024

The serine peptidase CLPP is conserved among bacteria, chloroplasts, and mitochondria. In humans and mice, its loss causes Perrault syndrome, which presents with growth deficits, infertility, deafness, and ataxia. In the filamentous fungus Podospora anserina, CLPP loss leads to longevity. CLPP substrates are selected by CLPX, an AAA+ unfoldase. CLPX is known to target delta-aminolevulinic acid synthase (ALAS) to promote pyridoxal phosphate (PLP) binding. CLPX may also influence cofactor association with other enzymes. Here, the evaluation of P. anserina metabolomics highlighted a reduction in arginine/histidine levels. In Mus musculus cerebellum, reductions in arginine/histidine and citrulline occurred with a concomitant accumulation of the heme precursor protoporphyrin IX. This suggests that the increased biosynthesis of 5-carbon (C5) chain deltaALA consumes not only C4 succinyl-CoA and C1 glycine but also specific C5 delta amino acids. As enzymes responsible for these effects, the elevated abundance of CLPX and ALAS is paralleled by increased OAT (PLP-dependent, ornithine delta-aminotransferase) levels. Possibly as a consequence of altered C1 metabolism, the proteome profiles of P. anserina CLPP-null cells showed strong accumulation of a methyltransferase and two mitoribosomal large subunit factors. The reduced histidine levels may explain the previously observed metal interaction problems. As the main nitrogen-storing metabolite, a deficiency in arginine would affect the urea cycle and polyamine synthesis. Supplementation of arginine and histidine might rescue the growth deficits of CLPP-mutant patients.
Current Status and Future Prospects of Stem Cell Therapy for Infertile Patients with Premature Ovarian Insufficiency
Authors: Kim Hye Kyeong , Kim Tae Jin
Published: February 2024

Premature ovarian insufficiency (POI), also known as premature menopause or premature ovarian failure, signifies the partial or complete loss of ovarian endocrine function and fertility before 40 years of age. This condition affects approximately 1% of women of childbearing age. Although 5–10% of patients may conceive naturally, conventional infertility treatments, including assisted reproductive technology, often prove ineffective for the majority. For infertile patients with POI, oocyte donation or adoption exist, although a prevalent desire persists among them to have biological children. Stem cells, which are characterized by their undifferentiated nature, self-renewal capability, and potential to differentiate into various cell types, have emerged as promising avenues for treating POI. Stem cell therapy can potentially reverse the diminished ovarian endocrine function and restore fertility. Beyond direct POI therapy, stem cells show promise in supplementary applications such as ovarian tissue cryopreservation and tissue engineering. However, technological and ethical challenges hinder the widespread clinical application of stem cells. This review examines the current landscape of stem cell therapy for POI, underscoring the importance of comprehensive assessments that acknowledge the diversity of cell types and functions. Additionally, this review scrutinizes the limitations and prospects associated with the clinical implementation of stem cell treatments for POI.
The Role of the Dysregulated JNK Signaling Pathway in the Pathogenesis of Human Diseases and Its Potential Therapeutic Strategies: A Comprehensive Review
Authors: Yan Huaying , He Lanfang , Lv De , Yang Jun , Yuan Zhu
Published: February 2024

JNK is named after c-Jun N-terminal kinase, as it is responsible for phosphorylating c-Jun. As a member of the mitogen-activated protein kinase (MAPK) family, JNK is also known as stress-activated kinase (SAPK) because it can be activated by extracellular stresses including growth factor, UV irradiation, and virus infection. Functionally, JNK regulates various cell behaviors such as cell differentiation, proliferation, survival, and metabolic reprogramming. Dysregulated JNK signaling contributes to several types of human diseases. Although the role of the JNK pathway in a single disease has been summarized in several previous publications, a comprehensive review of its role in multiple kinds of human diseases is missing. In this review, we begin by introducing the landmark discoveries, structures, tissue expression, and activation mechanisms of the JNK pathway. Next, we come to the focus of this work: a comprehensive summary of the role of the deregulated JNK pathway in multiple kinds of diseases. Beyond that, we also discuss the current strategies for targeting the JNK pathway for therapeutic intervention and summarize the application of JNK inhibitors as well as several challenges now faced. We expect that this review can provide a more comprehensive insight into the critical role of the JNK pathway in the pathogenesis of human diseases and hope that it also provides important clues for ameliorating disease conditions.
Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions
Authors: Wang Jianqiu , Kunze Markus , Villoria-González Andrea , Weinhofer Isabelle , Berger Johannes
Published: February 2024

3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, HMGCR) is one of the rate-limiting enzymes in the mevalonate pathway required for cholesterol biosynthesis. It is an integral membrane protein of the endoplasmic reticulum (ER) but has occasionally been described in peroxisomes. By co-immunofluorescence microscopy using different HMGCR antibodies, we present evidence for a dual localization of HMGCR in the ER and peroxisomes in differentiated human monocytic THP-1 cells, primary human monocyte-derived macrophages and human primary skin fibroblasts under conditions of low cholesterol and statin treatment. Using density gradient centrifugation and Western blot analysis, we observed a truncated HMGCR variant of 76 kDa in the peroxisomal fractions, while a full-length HMGCR of 96 kDa was contained in fractions of the ER. In contrast to primary human control fibroblasts, peroxisomal HMGCR was not found in fibroblasts from patients suffering from type-1 rhizomelic chondrodysplasia punctata, who lack functional PEX7 and, thus, cannot import peroxisomal matrix proteins harboring a type-2 peroxisomal targeting signal (PTS2). Moreover, in the N–terminal region of the soluble 76 kDa C-terminal catalytic domain, we identified a PTS2-like motif, which was functional in a reporter context. We propose that under sterol-depleted conditions, part of the soluble HMGCR domain, which is released from the ER by proteolytic processing for further turnover, remains sufficiently long in the cytosol for peroxisomal import via a PTS2/PEX7-dependent mechanism. Altogether, our findings describe a dual localization of HMGCR under combined lipid depletion and statin treatment, adding another puzzle piece to the complex regulation of HMGCR.
Lateral Flow Biosensor for On-Site Multiplex Detection of Viruses Based on One-Step Reverse Transcription and Strand Displacement Amplification
Authors: Lu Xuewen , Ding Kangning , Fang Zhiyuan , Liu Yilei , Ji Tianxing , Sun Jian , Zeng Zhenling , He Limin
Published: February 2024

Respiratory pathogens pose a huge threat to public health, especially the highly mutant RNA viruses. Therefore, reliable, on-site, rapid diagnosis of such pathogens is an urgent need. Traditional assays such as nucleic acid amplification tests (NAATs) have good sensitivity and specificity, but these assays require complex sample pre-treatment and a long test time. Herein, we present an on-site biosensor for rapid and multiplex detection of RNA pathogens. Samples with viruses are first lysed in a lysis buffer containing carrier RNA to release the target RNAs. Then, the lysate is used for amplification by one-step reverse transcription and single-direction isothermal strand displacement amplification (SDA). The yield single-strand DNAs (ssDNAs) are visually detected by a lateral flow biosensor. With a secondary signal amplification system, as low as 20 copies/μL of virus can be detected in this study. This assay avoids the process of nucleic acid purification, making it equipment-independent and easier to operate, so it is more suitable for on-site molecular diagnostic applications.
Magnetic Metallic Nanoparticles Coated with Carbon for the Catalytic Removal of Bromate from Water
Authors: Ramalho Patrícia S. F. , Soares Olívia Salomé G. P. , Órfão José J. M. , Pereira Manuel Fernando R.
Published: February 2024

Bromate, often detected in drinking water, is associated with a significant risk of cancer. Catalytic reduction has been recognized as an effective treatment technique to remove ions by reducing them over metal catalysts in the presence of a reducing agent, usually hydrogen. This work aims to synthesize metallic magnetic nanoparticles of iron oxide (FeO) and mixed iron oxides with manganese (MnFeO), cobalt (CoFeO), and copper (CuFeO) coated with carbon via chemical vapor deposition (C-MNP) to be applied as catalysts to the reduction of bromate in water. The use of magnetic nanoparticles coated with carbon enables catalyst recovery via magnetic separation and takes advantage of the catalytic properties of the carbon materials. The iron particles proved to be the most promising catalysts for the reduction of bromate into bromide, the highest removal being obtained with the CFeO@CVD750 sample, resulting in a 99% conversion after 120 min of reaction under the conditions tested. Due to its magnetic nature, the catalytic material was easily removed after the reaction and applied in four consecutive cycles without losing its catalytic properties. These results highlight the great potential of carbon-coated magnetic nanoparticles for reducing bromate in water.
Platinum-Modified Mixed Metal Oxide Electrodes for Efficient Chloralkaline-Based Energy Storage
Authors: Ribeiro Jamylle Y. C. , Santos Gessica O. S. , Dória Aline R. , Requena Iñaki , Lanza Marcos R. V. , Eguiluz Katlin I. B. , Salazar-Banda Giancarlo R. , Lobato Justo , Rodrigo Manuel A.
Published: February 2024

In this work, a series of novel mixed metal oxide (MMO) electrodes with the composition Ti/RuO2Sb2O4Ptx (0 ≤ x ≤ 10.0) were developed, envisaging their application in a reversible electrochemical cell based on the chloralkaline process as an energy storage system. These electrodes were synthesized via the ionic liquid method. Comprehensive physical, chemical, and electrochemical characterizations were conducted to evaluate their performance. The feasibility of employing these electrodes within reversible processes was explored, using the products generated during the electrolytic operation of the system for fuel cell operation. During the electrolyzer operation, higher current densities resulted in enhanced current efficiencies for the production of oxidized chlorine species. Notably, the presence of platinum in the catalyst exhibited a negligible impact on the coulombic efficiency at low current densities where water oxidation predominates. However, at higher current densities, the presence of platinum significantly improved coulombic efficiency, approaching values of approximately 60%. Transitioning to a fuel cell operation, despite the improved kinetic performance associated with a higher platinum content, the process efficiency was predominantly governed by ohmic losses. Curiously, the MMO electrode made without platinum (Ti/(RuO2)70-(Sb2O4)30) displayed the lowest ohmic losses. This study establishes optimal conditions for future investigations into this promising possibility, which holds great potential for energy storage via chloralkaline-based reversible reactions.
Recent Advances in Electrocatalytic Oxidation of 5-Hydroxymethylfurfural to 2,5-Furandicarboxylic Acid by Heterogeneous Catalysts
Authors: Ma Zhiming , Wang Lei , Li Guangyu , Song Tao
Published: February 2024

The utilization and development of biomass resources is an efficient solution to mitigate the fossil energy crisis. Based on the advantages of mild reaction conditions, rapid reaction, and high conversion, the synthesis of 2,5-furandicarboxylic acid (FDCA) by the electrocatalytic oxidation of 5-hydroxymethylfurfural (HMFOR) has attracted considerable attention. This review will summarize the recent advances of HMFOR to FDCA, including the reaction pathway and mechanism, as well as the catalytic performance of various heterogeneous electrocatalysts. The challenges and prospects for HMFOR are also focused on. Finally, it is expected that this work may provide guidance for the design of high-efficiency electrocatalysts and thereby accelerate the industrialization process of biomass utilization.
Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease
Authors: Camacho-Encina Maria , Booth Laura K. , Redgrave Rachael E. , Folaranmi Omowumi , Spyridopoulos Ioakim , Richardson Gavin D.
Published: February 2024

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disability. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, an increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to an even greater health and economic burden as the global average life expectancy increases and consequently the world’s population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction including energy starvation and oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility.
Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line
Authors: Scordino Miriana , Urone Giulia , Frinchi Monica , Valenza Chiara , Bonura Angela , Cipollina Chiara , Ciriminna Rosaria , Meneguzzo Francesco , Pagliaro Mario , Mudò Giuseppa , Di Liberto Valentina
Published: February 2024

In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin’s therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation.
Signaling Pathways of AXL Receptor Tyrosine Kinase Contribute to the Pathogenetic Mechanisms of Glioblastoma
Authors: Repici Alberto , Ardizzone Alessio , De Luca Fabiola , Colarossi Lorenzo , Prestifilippo Angela , Pizzino Gabriele , Paterniti Irene , Esposito Emanuela , Capra Anna Paola
Published: February 2024

Brain tumors are a diverse collection of neoplasms affecting the brain with a high prevalence rate in people of all ages around the globe. In this pathological context, glioblastoma, a form of glioma that belongs to the IV-grade astrocytoma group, is the most common and most aggressive form of the primary brain tumors. Indeed, despite the best treatments available including surgery, radiotherapy or a pharmacological approach with Temozolomide, glioblastoma patients’ mortality is still high, within a few months of diagnosis. Therefore, to increase the chances of these patients surviving, it is critical to keep finding novel treatment opportunities. In the past, efforts to treat glioblastoma have mostly concentrated on customized treatment plans that target specific mutations such as epidermal growth factor receptor (EGFR) mutations, Neurotrophic Tyrosine Receptor Kinase (NTRK) fusions, or multiple receptors using multi-kinase inhibitors like Sunitinib and Regorafenib, with varying degrees of success. Here, we focused on the receptor tyrosine kinase AXL that has been identified as a mediator for tumor progression and therapy resistance in various cancer types, including squamous cell tumors, small cell lung cancer, and breast cancer. Activated AXL leads to a significant increase in tumor proliferation, tumor cell migration, and angiogenesis in different in vitro and in vivo models of cancer since this receptor regulates interplay with apoptotic, angiogenic and inflammatory pathways. Based on these premises, in this review we mainly focused on the role of AXL in the course of glioblastoma, considering its primary biological mechanisms and as a possible target for the application of the most recent treatments.
Al2O3 Thin Layer Formed inside Porous Membrane Using Spray Synthesis Method and Its Application
Authors: Imai Masato , Kubota Tadahiko , Miyazawa Atsushi , Aoki Masahiro , Mori Haruna , Komaki Yuta , Yoshino Kenji
Published: February 2024

Aluminum oxide (Al2O3) films have been investigated for use in various applications, and numerous deposition techniques have been reported. The spray synthesis method has the advantage of forming a thin layer of crystal at low temperatures using the appropriate precursors. A precursor prepared by diluting Methylaluminoxane with N-methyl pyrrolidone was sprayed onto a porous membrane while varying conditions such as the substrate temperature, feeding speed, and spray amount. The solution penetrated the film during spray application, and the ultra-thin layers deposited on the side wall of the internal pores were observed using a cross-sectional transmission electron microscope (XTEM). The lattice image obtained using the TEM and the composition analysis conducted using a scanning TEM and an energy-dispersive X-ray spectroscope suggest that this thin layer is a layer of Al2O3. The formation of Al2O3 occurred at lower temperatures than in previous reports. This is a major advantage for applications with low-melting-point materials. The most suitable spraying conditions were determined based on the state of deposition on the surface and inside the membrane. These conditions were applied to a three-layer separator for lithium-ion batteries and their effect on thermal stability was investigated. Through heating experiments and XRD analysis, it was confirmed that the shrinkage and melting of the separator are suppressed by spraying. This process can be expected to have wide applications in low-melting-point materials such as polyolefin.
Probability Turns Material: The Boltzmann Equation
Authors: Rondoni Lamberto , Di Florio Vincenzo
Published: February 2024

We review, under a modern light, the conditions that render the Boltzmann equation applicable. These are conditions that permit probability to behave like mass, thereby possessing clear and concrete content, whereas generally, this is not the case. Because science and technology are increasingly interested in small systems that violate the conditions of the Boltzmann equation, probability appears to be the only mathematical tool suitable for treating them. Therefore, Boltzmann’s teachings remain relevant, and the present analysis provides a critical perspective useful for accurately interpreting the results of current applications of statistical mechanics.