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Cisplatin is a commonly used chemotherapeutic agent with proven efficacy in treating various malignancies, including testicular, ovarian, cervical, breast, bladder, head and neck, and lung cancer. Cisplatin is also used to treat tumors in children, such as neuroblastoma, osteosarcoma, and hepatoblastoma. However, its clinical use is limited by severe side effects, including ototoxicity, nephrotoxicity, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, and retinal toxicity. Cisplatin-induced ototoxicity manifests as irreversible, bilateral, high-frequency sensorineural hearing loss in 40–60% of adults and in up to 60% of children. Hearing loss can lead to social isolation, depression, and cognitive decline in adults, and speech and language developmental delays in children. Cisplatin causes hair cell death by forming DNA adducts, mitochondrial dysfunction, oxidative stress, and inflammation, culminating in programmed cell death by apoptosis, necroptosis, pyroptosis, or ferroptosis. Contemporary medical interventions for cisplatin ototoxicity are limited to prosthetic devices, such as hearing aids, but these have significant limitations because the cochlea remains damaged. Recently, the U.S. Food and Drug Administration (FDA) approved the first therapy, sodium thiosulfate, to prevent cisplatin-induced hearing loss in pediatric patients with localized, non-metastatic solid tumors. Other pharmacological treatments for cisplatin ototoxicity are in various stages of preclinical and clinical development. This narrative review aims to highlight the molecular mechanisms involved in cisplatin-induced ototoxicity, focusing on cochlear inflammation, and shed light on potential antioxidant and anti-inflammatory therapeutic interventions to prevent or mitigate the ototoxic effects of cisplatin. We conducted a comprehensive literature search (Google Scholar, PubMed) focusing on publications in the last five years. [ABSTRACT FROM AUTHOR]

Infopreneurship education plays a pivotal role in imparting essential entrepreneurial skills and facilitating the growth and prosperity of informationbased enterprises. China's research on infopreneurship education has continuously developed. However, there are still many shortcomings, such as insufficient teachers, not reflecting the characteristics of the specialty, and poor implementation of the practice. This paper focuses on the significance, necessity, and shortcomings of infopreneurship education for library information and archive management majors in Hebei Province, China. This paper adopts the literature analysis and other parties to cooperate in promoting the practical development and theory construction of infopreneurship education in Hebei method, extensively searches Chinese and foreign literature databases, and analyzes the closely related Chinese and English literature. Finally, the paper points out that there is a need for the government, schools, society, enterprises, scholars, China. [ABSTRACT FROM AUTHOR]

Timetable scheduling is a combinatorial optimization problem that presents formidable challenges for classical computers. This paper introduces a pioneering methodology for addressing the high-speed train timetabling problem through quantum computing. Initially, a comprehensive binary integer programming model, grounded in the space–time network, is proposed (M1). To manage the intricacy of model M1, a knapsack problem reformulation is employed to establish a simplified binary integer programming model (M2). Both M1 and M2 are subsequently converted into quadratic unconstrained binary optimization (QUBO) models to harness the potential of quantum computing. Several techniques, including the Gurobi solver, simulated annealing, and the coherent Ising machine (CIM) quantum simulator, are deployed to solve the model across four distinct scenarios of varying complexity. The findings indicate that CIM quantum simulator outperforms the simulated annealing method in terms of solution quality for medium-scale problems. [ABSTRACT FROM AUTHOR]

(1) Background: In children, SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms. However, multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here, we compare the humoral and cellular immune responses elicited in children (n = 15, aged 5–11 years) vaccinated with the RBD-based vaccines SOBERANA® 02 and SOBERANA® Plus combined in a heterologous scheme with those from children (n = 10, aged 4–11 years) who recovered from mild symptomatic COVID-19. (2) Methods: Blood samples were taken 14 days after the last dose for vaccinated children and 45–60 days after the infection diagnosis for COVID-19 recovered children. Anti-RBD IgG and ACE2-RBD inhibition were assessed by ELISA; IgA, cytokines, and cytotoxic-related proteins were determined by multiplex assays. Total B and T cell subpopulations and IFN-γ release were measured by multiparametric flow cytometry using a large panel of antibodies after in vitro stimulation with S1 peptides. (3) Results: Significant higher levels of specific anti-RBD IgG and IgA and ACE2-RBD inhibition capacity were found in vaccinated children in comparison to COVID-19 recovered children. Th1-like and Th2-like CD4+ T cells were also significantly higher in vaccinated subjects. IFN-γ secretion was higher in central memory CD4+ T cells of COVID-19 recovered children, but no differences between both groups were found in the CD4+ and CD8+ T cell effector, terminal effector, and naïve T cell subpopulations. In contrast to low levels of IL-4, high levels of IL-2, IL-6, IFN-γ, and IL-10 suggest a predominant Th1 cell polarization. Cytotoxic-related proteins granzyme A and B, perforin, and granulin were also found in the supernatant after S1 stimulation in both vaccinated and recovered children. (4) Conclusions: Vaccination with the heterologous scheme of SOBERANA® 02/SOBERANA® Plus induces a stronger antibody and cellular immune response compared to natural infections in young children. [ABSTRACT FROM AUTHOR]

This article explores the use of artificial intelligence (AI) technology in addressing the issue of rape among underage girls in Nigeria. It highlights the high prevalence of rape cases and the challenges in obtaining verifiable evidence to hold offenders accountable. The article suggests that AI tools such as surveillance devices, facial recognition, DNA matching, and video analysis can be utilized to establish evidence in these cases. It emphasizes the need for comprehensive efforts, including training security personnel and government investment in AI technology, to protect and support victims and deter potential perpetrators. The article also acknowledges the cultural and societal factors that contribute to the persistence of rape cases and calls for raising awareness and encouraging victims to come forward without fear of intimidation. [Extracted from the article]

Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment. [ABSTRACT FROM AUTHOR]

By formulating a breakfast meal from quinoa and tigernuts that is organically sweetened, this study aimed to synergistically utilize the natural bioactive compounds embedded in both foods. When compared to commercial sample, all formulations had higher protein and fat contents. The meals contained little starch, and most significantly, over 35% of this starch was non-digestible. The main minerals found in the meals were potassium (481.81—592.47 mg/100 g), phosphorus (231.75—257.20 mg/100 g), magnesium (152.34—176.29 mg/100 g), and calcium (257.45—266.61 mg/100 g, with the Na/K molar ratio < 1.0 advantageous for those with high blood pressure. Regarding overall phenol and flavonoid contents, the meals outperformed the commercial product with remarkable antioxidant capacities when tested against different assays (FRAP, ABTS, and DPPH). The meals' inhibitory capacities on both carbohydrate-hydrolyzing enzymes were noticeably higher than that of the commercial product. Regardless of the amount of quinoa or tigernuts in each blend, the inhibitory performance was satisfactory (α-amylase 26.98—60.18%; α -glucosidase 19.47—40.02%). Similarly, the chemical properties of the meals as influenced by its higher protein, fats, dietary fibre, and low sugar, modulated its functional properties in a unique way. In terms of sensory assessment, the panelists ranked the meals similar and sometimes above the commercial ones with respect to all the organoleptic parameters considered. A graphical representation of production, nutritional and functional characterization of stevia-sweetened breakfast meals from quinoa-tigernuts blends [ABSTRACT FROM AUTHOR]

The Ising model is defined by an objective function using a quadratic formula of qubit variables. The problem of an Ising model aims to determine the qubit values of the variables that minimize the objective function, and many optimization problems can be reduced to this problem. In this paper, we focus on optimization problems related to permutations, where the goal is to find the optimal permutation out of the  n !  possible permutations of n elements. To represent these problems as Ising models, a commonly employed approach is to use a kernel that applies one-hot encoding to find any one of the  n !  permutations as the optimal solution. However, this kernel contains a large number of quadratic terms and high absolute coefficient values. The main contribution of this paper is the introduction of a novel permutation encoding technique called the dual-matrix domain wall, which significantly reduces the number of quadratic terms and the maximum absolute coefficient values in the kernel. Surprisingly, our dual-matrix domain-wall encoding reduces the quadratic term count and maximum absolute coefficient values from  n 3 − n 2  and  2 n − 4  to  6 n 2 − 12 n + 4  and 2, respectively. We also demonstrate the applicability of our encoding technique to partial permutations and Quadratic Unconstrained Binary Optimization (QUBO) models. Furthermore, we discuss a family of permutation problems that can be efficiently implemented using Ising/QUBO models with our dual-matrix domain-wall encoding. [ABSTRACT FROM AUTHOR]

Biomolecular condensates are dynamic non-membrane-bound macromolecular high-order assemblies that participate in a growing list of cellular processes, such as transcription, the cell cycle, etc. Disturbed dynamics of biomolecular condensates are associated with many diseases, including cancer and neurodegeneration. Extensive efforts have been devoted to uncovering the molecular and biochemical grammar governing the dynamics of biomolecular condensates and establishing the critical roles of protein posttranslational modifications (PTMs) in this process. Here, we summarize the regulatory roles of ubiquitination (a major form of cellular PTM) in the dynamics of biomolecular condensates. We propose that these regulatory mechanisms can be harnessed to combat many diseases. [ABSTRACT FROM AUTHOR]

Liquid-liquid phase separation results in the formation of dynamic biomolecular condensates, also known as membrane-less organelles, that allow for the assembly of functional compartments and higher order structures within cells. Multivalent, reversible interactions between RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1, and/or RNA (e.g., RBP-RBP, RBP-RNA, RNA-RNA), result in the formation of ribonucleoprotein (RNP) condensates, which are critical for RNA processing, mRNA transport, stability, stress granule assembly, and translation. Stress granules, neuronal transport granules, and processing bodies are examples of cytoplasmic RNP condensates, while the nucleolus and Cajal bodies are representative nuclear RNP condensates. In neurons, RNP condensates promote long-range mRNA transport and local translation in the dendrites and axon, and are essential for spatiotemporal regulation of gene expression, axonal integrity and synaptic function. Mutations of RBPs and/or pathologic mislocalization and aggregation of RBPs are hallmarks of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease. ALS/FTD-linked mutations of RBPs alter the strength and reversibility of multivalent interactions with other RBPs and RNAs, resulting in aberrant phase transitions. These aberrant RNP condensates have detrimental functional consequences on mRNA stability, localization, and translation, and ultimately lead to compromised axonal integrity and synaptic function in disease. Pathogenic protein aggregation is dependent on various factors, and aberrant dynamically arrested RNP condensates may serve as an initial nucleation step for pathologic aggregate formation. Recent studies have focused on identifying mechanisms by which neurons resolve phase transitioned condensates to prevent the formation of pathogenic inclusions/aggregates. The present review focuses on the phase separation of neurodegenerative disease-linked RBPs, physiological functions of RNP condensates, and the pathologic role of aberrant phase transitions in neurodegenerative disease, particularly ALS/FTD. We also examine cellular mechanisms that contribute to the resolution of aberrant condensates in neurons, and potential therapeutic approaches to resolve aberrantly phase transitioned condensates at a molecular level. [ABSTRACT FROM AUTHOR]

The declining student enrollment in faculties of education is a critical issue for the development and progress of Somalia. This paper aims to investigate the major factors contributing to this decline from the perspective of graduate teacher education. Qualitative research was conducted through interviews with 20 teachers from different institutions in both higher and general education, with data saturation used as a limiting factor. The findings reveal that community perception, teacher motivation, and the implementation of policies and acts relating to the teaching profession are the primary causes of the decline. Notably, the study found that schools and scholarships did not significantly affect the decline in student enrollment. These results suggest that there is a need to restate the status of teacher education in Somalia. This can be achieved through collaborative efforts between the community, government, and universities. Specifically, there is a need to address the negative perception of teaching as a profession, improve teacher motivation, and ensure the implementation of relevant policies and acts. By addressing these issues, we can create a more conducive environment for teacher education and ensure the upcoming human capital is adequately prepared to drive development and progress in Somalia. [ABSTRACT FROM AUTHOR]

Nucleotide composition plays a crucial role in the structure, function and recognition of RNA molecules. During infection, virus RNA is exposed to multiple endogenous proteins that detect local or global compositional biases and interfere with virus replication. Recent advancements in RNA:protein mapping technologies have enabled the identification of general RNA-binding preferences in the human proteome at basal level and in the context of virus infection. In this review, we explore how cellular proteins recognise nucleotide composition in virus RNA and the impact these interactions have on virus replication. Protein-binding G-rich and C-rich sequences are common examples of how host factors detect and limit infection, and, in contrast, viruses may have evolved to purge their genomes from such motifs. We also give examples of how human RNA-binding proteins inhibit virus replication, not only by destabilising virus RNA, but also by interfering with viral protein translation and genome encapsidation. Understanding the interplay between cellular proteins and virus RNA composition can provide insights into host–virus interactions and uncover potential targets for antiviral strategies. [ABSTRACT FROM AUTHOR]

The nucleocapsid protein N of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enwraps and condenses the viral genome for packaging but is also an antagonist of the innate antiviral defense. It suppresses the integrated stress response (ISR), purportedly by interacting with stress granule (SG) assembly factors G3BP1 and 2, and inhibits type I interferon responses. To elucidate its mode of action, we systematically deleted and over-expressed distinct regions and domains. We show that N via domain N2b blocks PKR-mediated ISR activation, as measured by suppression of ISR-induced translational arrest and SG formation. N2b mutations that prevent dsRNA binding abrogate these activities also when introduced in the intact N protein. Substitutions reported to block post-translation modifications of N or its interaction with G3BP1/2 did not have a detectable additive effect. In an encephalomyocarditis virus-based infection model, N2b - but not a derivative defective in RNA binding—prevented PKR activation, inhibited β-interferon expression and promoted virus replication. Apparently, SARS-CoV-2 N inhibits innate immunity by sequestering dsRNA to prevent activation of PKR and RIG-I-like receptors. Similar observations were made for the N protein of human coronavirus 229E, suggesting that this may be a general trait conserved among members of other orthocoronavirus (sub)genera. Author summary: SARS-CoV-2 nucleocapsid protein N is an antagonist of innate immunity but how it averts virus detection by intracellular sensors remains subject to debate. We provide evidence that SARS-CoV-2 N, by sequestering dsRNA through domain N2b, prevents PKR-mediated activation of the integrated stress response as well as detection by RIG-I-like receptors and ensuing type I interferon expression. This function, conserved in human coronavirus 229E, is not affected by mutations that prevent posttranslational modifications, previously implicated in immune evasion, or that target its binding to stress granule scaffold proteins. Our findings further our understanding of how SARS-CoV-2 evades innate immunity, how this may drive viral evolution and why increased N expression may have been a selective advantage to SARS-CoV-2 variants of concern. [ABSTRACT FROM AUTHOR]

Biodiesel produced from different edible and non‐edible feedstocks is a viable alternative option for fueling a combustion engine. However, the widespread use of edible sources for biodiesel production may lead to food versus fuel controversy. Oil from non‐edible feedstock is best possible solution for problems that inhibits biodiesel production on commercial scale. This study presents the potential of different non‐edible feedstock for biodiesel production. Several aspects such as extraction technologies used for extracting oil from non‐edible sources and biodiesel production pathways from non‐edible feedstocks are discussed. The quality of biodiesel should be assured before its commercialization by different physical and chemical characterization techniques are used. In particular, the emission comparison of biodiesel derived from the different non‐edible feedstocks is discussed. Based on this study, the non‐edible feedstocks have the potential to produce biodiesel but still it has a long way to go. This is due to non‐edible feedstock is in the R&D phase and needs more research to eliminate additional treatment steps compared to edible feedstock for economic aspects. Furthermore, there has been a trade off in emission properties of biodiesels produced from non‐edible feedstocks which must be removed or evaluated for pilot scale investigations before commercialization. [ABSTRACT FROM AUTHOR]

One way of solving 3sat instances on a quantum computer is to transform the 3sat instances into instances of Quadratic Unconstrained Binary Optimizations (QUBOs), which can be used as an input for the QAOA algorithm on quantum gate systems or as an input for quantum annealers. This mapping is performed by a 3sat-to-QUBO transformation. Recently, it has been shown that the choice of the 3sat-to-QUBO transformation can significantly impact the solution quality of quantum annealing. It has been shown that the solution quality can vary up to an order of magnitude difference in the number of correct solutions received, depending solely on the 3sat-to-QUBO transformation. An open question is: what causes these differences in the solution quality when solving 3sat-instances with different 3sat-to-QUBO transformations? To be able to conduct meaningful studies that assess the reasons for the differences in the performance, a larger number of different 3sat-to-QUBO transformations would be needed. However, currently, there are only a few known 3sat-to-QUBO transformations, and all of them were created manually by experts, who used time and clever reasoning to create these transformations. In this paper, we will solve this problem by proposing an algorithmic method that is able to create thousands of new and different 3sat-to-QUBO transformations, and thus enables researchers to systematically study the reasons for the significant difference in the performance of different 3sat-to-QUBO transformations. Our algorithmic method is an exhaustive search procedure that exploits properties of 4 × 4 dimensional pattern QUBOs, a concept which has been used implicitly in the creation of 3sat-to-QUBO transformations before, but was never described explicitly. We will thus also formally and explicitly introduce the concept of pattern QUBOs in this paper. [ABSTRACT FROM AUTHOR]

An artificial neural network (ANN) model was developed for the photocatalytic degradation of rhodamine B by TiO2 nanoparticles synthesized by the electrochemical method, under direct sunlight irradiation. The four inputs are: irradiation time, initial dye concentration, pH of the initial solution, and catalyst loading. The ANN model with 20 hidden neurons and with R2 of 0.999 shows minimum values of the performance metrics of 0.169, 2.020, 1.531, and 0.215 for the mean square error, the root mean square error, the mean absolute error, and the mean absolute percentage error, respectively. The optimized ANN configuration of 4‐20‐1 shows a good fit with the experimental data. The result shows that the sunlight irradiation time has the main impact on rhodamine B degradation at ∼55 %. [ABSTRACT FROM AUTHOR]

Estimation of distribution algorithms (EDAs) is a subset of evolutionary algorithms widely used in various optimization problems, known for their favorable results. Each generation of EDAs builds a probabilistic model to represent the most promising individuals, and the next generation is created by sampling from this model. The primary challenge in designing such algorithms lies in effectively constructing the probabilistic model. The mutual exclusivity constraint imposes an additional challenge for EDAs to approach permutation-based problems. In this study, we propose a new EDA called Position-Guided Sampling Estimation of Distribution Algorithm (PGS-EDA) specifically designed for permutation-based problems. Unlike conventional approaches, our algorithm focuses on the positions rather than the elements during the sampling phase. We evaluate the performance of our algorithm on the Permutation Flow-shop Scheduling Problem (PFSP). The experiments conducted on various sizes of Taillard instances provide evidence of the effectiveness of our algorithm in addressing the PFSP, particularly for small and medium-sized problems. The comparison results with other EDAs designed to handle permutation problems demonstrate that our PSG-EDA algorithm consistently achieves the lowest Average Relative Percentage Deviation (ARPD) values in 19 out of the 30 instances of sizes 20 and 50 used in the study. These findings validate the superior performance of our algorithm in terms of minimizing the makespan criterion of the PFSP. [ABSTRACT FROM AUTHOR]

Cells trigger the assembly of stress granules (SGs) under various stress conditions. Among the many proteins recruited to SGs are RNA-binding proteins and transcription regulators. Here, we report the translocation of human (h)Cdc73, a component of the PAF1 transcription complex, to cytosolic SGs in response to arsenic stress. The hCdc73 protein possesses a long intrinsically disordered region (IDR) from amino acids 256-416, the presence of which is required for the translocation of hCdc73 to cytosolic SGs. The purified hCdc73 IDR formed droplets in vitro, and the light-activated assembly of hCdc73-IDR-mCherry-CRY2 was verified. For translocation of hCdc73 to SGs, physical interactions with SG carrier proteins, such as FMR1, are also needed. Previously, we reported that the cytosolic hCdc73-eEF1Bγ complex controls the stability of p53 mRNA. Under arsenic stress, selective sequestration of cytosolic hCdc73, but not eEF1Bγ (EEF1G) or p53 (TP53) mRNA, was detected. As a result, a transient increase in p53 mRNA at the post-transcriptional level was observed. In conclusion, we propose that the availability of mRNAs for stress-responsive genes can be controlled by restraining their negative regulators within SGs. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective platinum-based chemotherapeutic with several side effects, including ototoxicity. Cochlear cells have low rates of proliferation yet are highly susceptible to cisplatin. We hypothesised that cisplatin ototoxicity might be caused by cisplatin-protein interactions rather than cisplatin-DNA interactions. Two known cisplatin-binding proteins are involved in the stress granule (SG) response. SGs are a pro-survival mechanism involving formation of transient ribonucleoprotein complexes during stress. We examined the effects of cisplatin on SG dynamics and composition in cell lines derived from the cochlea and retinal pigment epithelium. Cisplatin-induced SGs are significantly diminished in size and quantity compared to arsenite-induced SGs and are persistent after 24 h recovery. Additionally, cisplatin pretreated cells were unable to form a typical SG response to subsequent arsenite stress. Cisplatin-induced SGs had significant reductions in the sequestration of eIF4G and the proteins RACK1 and DDX3X. Live-cell imaging of Texas Red-conjugated cisplatin revealed its localisation to SGs and retention for at least 24 h. We show cisplatin-induced SGs have impaired assembly, altered composition and are persistent, providing evidence of an alternate mechanism for cisplatin-induced ototoxicity via an impaired SG response. [ABSTRACT FROM AUTHOR]

CeO2 nanooxide has been synthesized from cerium(III) nitrate using powdered cellulose (PC) and its mixture with sucrose as templates. The removal of templates from composites (PC–Ce(NO3)3 and PC–sucrose–Ce(NO3)3) has been carried out in two ways: via direct burning-out of PC (PC–sucrose) in an air flow and via burning-out of the carbonizate after template pyrolysis. Using UV and IR spectroscopy, X-ray powder diffraction (XRD), and electron microscopy, the influence of the template composition and the method of its removal on the physicochemical characteristics of CeO2 nanoparticles has been studied. A carbon–oxide material CeO2/C has been synthesized by pyrolysis of PC–Ce(NO3)3 and PC–sucrose–Ce(NO3)3 composites. It has been established that the pyrolysis of PC–Ce(NO3)3 and PC–sucrose–Ce(NO3)3 leads to the formation, in the carbonizate, of CeO2 (cerianite) nanoparticles with sizes of 3–4 and 1–2.5 nm, respectively. The average diameter of nanoparticles (according to XRD data) is 3.8 and 2.3 nm. CeO2/C synthesized from the PC–sucrose–Ce(NO3)3 composite contains cerium(III) oxide. All CeO2 nanoparticles in the carbon matrix have a hydroxyl–hydrate cover. The burning of the organic or carbon matrix of the composites leads, regardless of the template used and synthesis conditions, to the formation of CeO2 (cerianite) nanoparticles with the same average diameter of 25 ± 1 nm (according to XRD data), containing an admixture of the Ce(III) phase and having a hydroxyl–hydrate cover. Carbon is present in the material in trace amounts (≤0.15 wt %). The size scatter of CeO2 nanoparticles produced by burning out PC from the PC–Ce(NO3)3 composite is 15–30 nm. In those cases when the organic component from PC–sucrose–Ce(NO3)3 is subjected to burning or the pyrolysis stage of both composites is included in the synthesis process, the appearance of a fraction of larger CeO2 particles (50–60 nm) is observed. The correctness of the obtained data has been confirmed in the course of the model process of hydrogen peroxide decomposition. [ABSTRACT FROM AUTHOR]

The problem of finding the maximum weighted cycle in a directed graph map to solve optimization problems is NP -hard, implying that approaches in classical computing are inefficient. Here, Quantum computing might be a promising alternative. Many current approaches to the quantum computer are based on a Quadratic Unconstrained Binary Optimization (QUBO) problem formulation. This paper develops four different QUBO approaches to this problem. The first two take the starting vertex and the number of vertices used in the cycle as given, while the latter two loosen the second assumption of knowing the size of the cycle. A QUBO formulation is derived for each approach. Further, the number of binary variables required to encode the maximum weighted cycle problem with one or both assumptions for the respective approach is made explicit. The problem is motivated by finding the maximum weighted debt cycle in a debt graph. This paper compares classical computing versus currently available (hybrid) quantum computing approaches for various debt graphs. For the classical part, it investigated the Depth-First-Search (DFS) method and Simulated Annealing. For the (hybrid) quantum approaches, a direct embedding on the quantum annealer and two types of quantum hybrid solvers were utilized. Simulated Annealing and the usage of the hybrid CQM (Constrained Quadratic Model) had promising functionality. The DFS method, direct QPU, and hybrid BQM (Binary Quadratic Model), on the other hand, performed less due to memory issues, surpassing the limit of decision variables and finding the right penalty values, respectively. [ABSTRACT FROM AUTHOR]

Transposable elements (TE) are mobile DNA sequences whose excessive proliferation endangers the host. Although animals have evolved robust TE-targeting defenses, including Piwi-interacting (pi)RNAs, retrotransposon LINE-1 (L1) still thrives in humans and mice. To gain insights into L1 endurance, we characterized L1 Bodies (LBs) and ORF1p complexes in germ cells of piRNA-deficient Maelstrom null mice. We report that ORF1p interacts with TE RNAs, genic mRNAs, and stress granule proteins, consistent with earlier studies. We also show that ORF1p associates with the CCR4-NOT deadenylation complex and PRKRA, a Protein Kinase R factor. Despite ORF1p interactions with these negative regulators of RNA expression, the stability and translation of LB-localized mRNAs remain unchanged. To scrutinize these findings, we studied the effects of PRKRA on L1 in cultured cells and showed that it elevates ORF1p levels and L1 retrotransposition. These results suggest that ORF1p-driven condensates promote L1 propagation, without affecting the metabolism of endogenous RNAs. Author summary: Transposable elements (TEs) are mobile DNA sequences whose proliferation endangers the integrity of the host cell and its genome. Although cells have acquired sophisticated TE-targeting defenses, TEs continue to thrive in all life forms. To address this fascinating question, this study focused on a particular type of TE known as retrotransposon LINE-1. This work shows that LINE-1-expressing germ cells of mice develop cytoplasmic aggregates (LINE-1 bodies or LBs) enriched in LINE-1, RNAs, and proteins implicated in the negative regulation of RNA expression. Despite the overwhelming repressive nature of LBs, the integrity and translation of LB-localized RNAs are not affected. RNA expression appears to stay intact because LINE-1 has adapted to interact with the PRKRA protein that relays stress signals to downstream proteins, triggering general translational inhibition. Indeed, the simultaneous expression of LINE-1 and PRKRA in cultured cells elevates LINE-1 protein expression and mobilization. Our data suggest that LINE-1 has evolved a mechanism to counteract the translational shut-off, thus increasing its chances of propagation without compromising the host cell. [ABSTRACT FROM AUTHOR]

Stress granules (SGs), hallmarks of the cellular adaptation to stress, promote survival, conserve cellular energy, and are fully dissolved upon the cessation of stress treatment. Different stresses can initiate the assembly of SGs, but arsenite and heat are the best studied of these stresses. The composition of SGs and posttranslational modifications of SG proteins differ depending on the type and severity of the stress insult, methodology used, cell line, and presence of overexpressed and tagged proteins. A group of 18 proteins showing differential localization to SGs in heat- and arsenite-stressed mammalian cell lines is described. Upon severe and prolonged stress, physiological SGs transform into more solid protein aggregates that are no longer reversible and do not contain mRNA. Similar pathological inclusions are hallmarks of neurodegenerative diseases. SGs induced by heat stress are less dynamic than SGs induced by arsenite and contain a set of unique proteins and linkage-specific polyubiquitinated proteins. The same types of ubiquitin linkages have been found to contribute to the development of neurodegenerative disorders such as Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis (ALS). We propose heat stress-induced SGs as a possible model of an intermediate stage along the transition from dynamic, fully reversible arsenite stress-induced SGs toward aberrant SGs, the hallmark of neurodegenerative diseases. Stress- and methodology-specific differences in the compositions of SGs and the transition of SGs to aberrant protein aggregates are discussed. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA Export and Localization > RNA Localization., (© 2020 Wiley Periodicals, Inc.)

Essential oils are among the most well-known phyto-compounds, and since ancient times, they have been utilized in medicine. Over 100 essential oils have been identified and utilized as therapies for various skin infections and related ailments. While numerous commercial medicines are available in different dosage forms to treat skin diseases, the persisting issues include their side effects, toxicity, and low efficacy. As a result, researchers are seeking novel classes of compounds as substitutes for synthetic drugs, aiming for minimal side effects, no toxicity, and high efficacy. Essential oils have shown promising antimicrobial activity against skin-associated pathogens. This review presents essential knowledge and scientific information regarding essential oil's antimicrobial capabilities against microorganisms that cause skin infections. Essential oils mechanisms against different pathogens have also been explored. Many essential oils exhibit promising activity against various microbes, which has been qualitatively assessed using the agar disc diffusion experiment, followed by determining the minimum inhibitory concentration for quantitative evaluation. It has been observed that Staphylococcus aureus and Candida albicans have been extensively researched in the context of skin-related infections and their antimicrobial activity, including established modes of action. In contrast, other skin pathogens such as Staphylococcus epidermidis, Streptococcus pyogens, Propionibacterium acnes, and Malassezia furfur have received less attention or neglected. This review report provides an updated understanding of the mechanisms of action of various essential oils with antimicrobial properties. This review explores the anti-infectious activity and mode of action of essential against distinct skin pathogens. Such knowledge can be valuable in treating skin infections and related ailments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Energy stress, characterized by the reduction of intracellular ATP, has been implicated in various diseases, including cancer. Here, we show that energy stress promotes the formation of P-bodies in a ubiquitin-dependent manner. Upon ATP depletion, the E3 ubiquitin ligase TRIM23 catalyzes lysine-63 (K63)-linked polyubiquitination of HCLS1-associated protein X-1 (HAX1). HAX1 ubiquitination triggers its liquid‒liquid phase separation (LLPS) and contributes to P-bodies assembly induced by energy stress. Ubiquitinated HAX1 also interacts with the essential P-body proteins, DDX6 and LSM14A, promoting their condensation. Moreover, we find that this TRIM23/HAX1 pathway is critical for the inhibition of global protein synthesis under energy stress conditions. Furthermore, high HAX1 ubiquitination, and increased cytoplasmic localization of TRIM23 along with elevated HAX1 levels, promotes colorectal cancer (CRC)-cell proliferation and correlates with poor prognosis in CRC patients. Our data not only elucidate a ubiquitination-dependent LLPS mechanism in RNP granules induced by energy stress but also propose a promising target for CRC therapy., (© 2024. The Author(s).)

Polyethylene (PE), a highly prevalent non-biodegradable polymer in the field of plastics, presents a waste management issue. To alleviate this issue, bio-based PE (bio-PE), derived from renewable resources like corn and sugarcane, offers an environmentally friendly alternative. This review discusses various production methods of bio-PE, including fermentation, gasification, and catalytic conversion of biomass. Interestingly, the bio-PE production volumes and market are expanding due to the growing environmental concerns and regulatory pressures. Additionally, the production of PE and bio-PE biocomposites using agricultural waste as filler materials, highlights the growing demand for sustainable alternatives to conventional plastics. According to previous studies, addition of ≈50% defibrillated corn and abaca fibers into bio-PE matrix and a compatibilizer, results in the highest Young's modulus of 4.61 and 5.81 GPa, respectively. These biocomposites have potential applications in automotive, building construction, and furniture industries. Moreover, the advancement made in abiotic and biotic degradation of PE and PE biocomposites is elucidated to address their environmental impacts. Finally, the paper concludes with insights into the opportunities, challenges, and future perspectives in the sustainable production and utilization of PE and bio-PE biocomposites. In summary, production of PE and bio-PE biocomposites can contribute to a cleaner and sustainable future., (© 2024 Wiley‐VCH GmbH.)

T-cell intracellular antigen-1 (TIA-1) is a key RNA-binding protein that participates in translation regulation and RNA splicing. TIA-1 undergoes liquid-liquid phase separation as a fundamental mechanism that enables the condensation of RNA and proteins into membraneless organelles called stress granules (SGs). However, this dynamic behavior can lead to aberrant fibril formation, implicated in neurodegenerative disorders, and must be tightly regulated. In this study, we investigated the role in the cell of histidine residues His94 and His96, responsible for Zn 2+ binding. Using fluorescence microscopy, we found that the specific binding site formed by these residues is critical for SG assembly. Furthermore, it also plays a role maintaining the dynamic behavior of SG-assembled TIA-1. Collectively, our findings confirm the physiological relevance of TIA-1 His94 and His96 in the Zn 2+ -mediated regulatory mechanism for protection against fibril formation in SGs., (© 2024 International Union of Biochemistry and Molecular Biology.)

The mechanics of how proteins are generated from mRNA is increasingly well understood. However, much less is known about how protein production is coordinated and orchestrated within the crowded intracellular environment, especially in eukaryotic cells. Recent studies suggest that localized sites exist for the coordinated production of specific proteins. These sites have been termed "translation factories" and roles in protein complex formation, protein localization, inheritance, and translation regulation have been postulated. In this article, we review the evidence supporting the translation of mRNA at these sites, the details of their mechanism of formation, and their likely functional significance. Finally, we consider the key uncertainties regarding these elusive structures in cells. This article is categorized under: Translation Translation > Mechanisms RNA Export and Localization > RNA Localization Translation > Regulation., (© 2024 The Author(s). WIREs RNA published by Wiley Periodicals LLC.)

Eukaryotic cells are stimulated by external pressure such as that derived from heat shock, oxidative stress, nutrient deficiencies, or infections, which induce the formation of stress granules (SGs) that facilitates cellular adaptation to environmental pressures. As aggregated products of the translation initiation complex in the cytoplasm, SGs play important roles in cell gene expression and homeostasis. Infection induces SGs formation. Specifically, a pathogen that invades a host cell leverages the host cell translation machinery to complete the pathogen life cycle. In response, the host cell suspends translation, which leads to SGs formation, to resist pathogen invasion. This article reviews the production and function of SGs, the interaction between SGs and pathogens, and the relationship between SGs and pathogen-induced innate immunity to provide directions for further research into anti-infection and anti-inflammatory disease strategies. [ABSTRACT FROM AUTHOR]

Focusing on the dynamic improvement of the underlying service network configuration, this paper aims to address a specific challenge of redesigning a multi-echelon city logistics distribution network. By considering the intra-echelon connection of facilities within the same layer of echelon, we propose a new distribution network design model by reformulating the classical quadratic assignment problem (QAP). To minimize the overall transportation costs, the proposed model jointly optimizes two types of decisions to enable agile distribution with dynamic "shortcuts": (i) the allocation of warehouses to supply the corresponding distribution centers (DCs), and (ii) the demand coverage decision from distribution centers to delivery stations. Furthermore, a customized branch-and-bound algorithm is developed, where the lower bound is obtained by adopting Gilmore and Lawler lower Bound (GLB) for QAP. We conduct extensive computational experiments, highlighting the significant contribution of GLB-oriented lower bound, to obtain practical solutions; this type of efficient mathematical lower bounds offers a powerful tool for balancing theoretical research ideas with practical and industrial applicability. [ABSTRACT FROM AUTHOR]

Liquid–liquid phase separation is a multicomponent system separated into phases with different compositions and structures. It has been identified and explored in organisms after being introduced from the thermodynamic field. Condensate, the product of phase separation, exists in different scales of cellular structures, such as nucleolus, stress granules, and other organelles in nuclei or cytoplasm. And also play critical roles in different cellular behaviors. Here, we review the concept, thermodynamical and biochemical principles of phase separation. We summarized the main functions including the adjustment of biochemical reaction rates, the regulation of macromolecule folding state, subcellular structural support, the mediation of subcellular location, and intimately linked to different kinds of diseases, such as cancer and neurodegeneration. Advanced detection methods to investigate phase separation are collected and analyzed. We conclude with the discussion of anxiety of phase separation, and thought about how progress can be made to develop precise detection methods and disclose the potential application of condensates. [ABSTRACT FROM AUTHOR]

Stress granules are the RNA/protein condensates assembled in the cells under stress. They play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, how stress granule assembly is regulated and related to ALS/FTD pathomechanism is incompletely understood. Mutation in the C9orf72 gene is the most common cause of familial ALS and FTD. C9orf72 mutation causes the formation of toxic dipeptide repeats. Here we show that the two most toxic dipeptide repeats [i.e., poly(GR) and poly(PR)] activate c-Jun N-terminal kinase (JNK) via the ERstress response protein IRE1 using fly and cellular models. Further, we show that activated JNK promotes stress granule assembly in cells by promoting the transcription of one of the key stress granule proteins (i.e., G3BP1) by inducing histone 3 phosphorylation. Consistent with these findings, JNK or IRE1 inhibition reduced stress granule formation, histone 3 phosphorylation, G3BP1 mRNA and protein levels, and neurotoxicity in cells overexpressing poly(GR) and poly(PR) or neurons derived from male and female C9ALS/FTD patient-induced pluripotent stem cells. Our findings connect ER stress, JNK activation, and stress granule assembly in a unified pathway contributing to C9ALS/FTD neurodegeneration. [ABSTRACT FROM AUTHOR]

The green synthesis of silver nanoparticles has been proposed as an eco-friendly and cost-effective substitute for chemical and physical methods. The aim of this study was to synthesize and characterize silver nanoparticles using the peel extract of Citrus aurantifolia fruit, and to determine the possible phytochemical constituents' presence in the plant extracts that might be responsible for the synthesis. Citrus aurantifolia fruit peel extraction was followed by phytochemical studies of secondary metabolites, FTIR analysis confirmation of functional groups, and GC–MS analysis. Silver nanoparticles were synthesized through bio-reduction of silver ions (Ag+) to silver nanoparticles using CAFPE and characterized using UV-Vis spectroscopy, HR–TEM, FESEM, EDX, XRD, DLS, and FTIR. The presence of plant secondary metabolites such as alkaloids, flavonoids, tannins, saponins, phenols, terpenoids, and steroids was detected. The FTIR analysis of the extract revealed the presence of functional groups like hydroxyl, carboxyl, carbonyl, amine, and phenyl, whereas the GC–MS analysis indicated presence of chemical compounds such as 1,2,4-Benzenetricarboxylic acid, Fumaric acid, nonyl pentadecyl, and 4-Methyl-2-trimethylsilyloxy-acetophenone, etc., with similar functional groups. The synthesized silver nanoparticle (AgNP) has displayed the characteristics of a surface plasmon resonance (SPR) band peak from 360–405 nm. High resolution transmission electron microscope (HR-TEM) and field emission scan electron microscope (FESEM) confirm polydisperse, spherical shaped, and smooth surface nanoparticles with an average size of 24.023 nm. Energy dispersive X-ray (EDX) analysis further revealed that silver is the most abundant element found in the micrograph of the nanoparticles, and FTIR analysis further confirmed the presence of different functional groups in the surface of the nanoparticle. The XRD analysis also confirmed that the nanoparticles synthesized are crystalline in nature. Based on the findings of this study, it is understood that the variety of natural compounds that are present in plant extracts of Citrus aurantifolia fruit peel can act as both reducing and stabilizing agents for the synthesis of silver nanoparticles. It is, therefore, concluded that Citrus aurantifolia peel extract can be potentially used for the large production of silver nanoparticles for several applications. [ABSTRACT FROM AUTHOR]

Mycotoxins are naturally occurring toxins that contaminate different crops and foodstuffs under certain circumstances during harvesting, handling, storage, and processing. Neither the dietary intake of mycotoxins in Cameroon is well characterized, nor its health effects on the consumers. This review is intended to be the first milestone towards national risk management of mycotoxins. It is noteworthy that mycotoxins contaminate the main staple foods of Cameroonian communities, which are also often used as complementary foods for infants, young children, and people with compromised immune systems (e.g., HIV/AIDS), thus calling for urgent intervention in primary and secondary prevention. Very few data exist on mycotoxin contamination in Cameroonian agricultural commodities and food items. Only 25 studies from 14 different authors have been published in the last decade. On the basis of available data in Cameroon, the Estimated Daily Intake (EDI) of major mycotoxins in foods for Aflatoxins was 0.0018–14.2 µg/kgbw/day in maize, 0.027–2.36 µg/kgbw/day in cassava, and 0.023–0.1 µg/kgbw/day in groundnuts. The estimated daily intake of fumonisins was 0.12–60.6 µg/kgbw/day in maize and 0.056–0.82 µg/kgbw/day in beans. Based on the estimated distribution of human exposure levels by food, maize and cassava are the major sources of exposure and should be prioritized, followed by beans and spices. This estimate will be updated along with improvements on the national database on mycotoxin contamination of Cameroonian foods. [ABSTRACT FROM AUTHOR]

The presence of foreign nucleic acids in the cytosol is a marker of infection. Cells have sensors, also known as pattern recognition receptors (PRRs), in the cytosol that detect foreign nucleic acid and initiate an innate immune response. Recent studies have reported the condensation of multiple PRRs including PKR, NLRP6, and cGAS, with their nucleic acid activators into discrete nucleoprotein assemblies. Nucleic acid–protein condensates form due to multivalent interactions and can create high local concentrations of components. The formation of PRR‐containing condensates may alter the magnitude or timing of PRR activation. In addition, unique condensates form following RNase L activation or during paracrine signaling from virally infected cells that may play roles in antiviral defense. These observations suggest that condensate formation may be a conserved mechanism that cells use to regulate activation of the innate immune response and open an avenue for further investigation into the composition and function of these condensates. Here we review the nucleic acid–protein granules that are implicated in the innate immune response, discuss general consequences of condensate formation and signal transduction, as well as what outstanding questions remain. [ABSTRACT FROM AUTHOR]

Nondeterministic measurements are common in real-world scenarios: the performance of a stochastic optimization algorithm or the total reward of a reinforcement learning agent in a chaotic environment are just two examples in which unpredictable outcomes are common. These measures can be modeled as random variables and compared among each other via their expected values or more sophisticated tools such as null hypothesis statistical tests. In this article, we propose an alternative framework to visually compare two samples according to their estimated cumulative distribution functions. First, we introduce a dominance measure for two random variables that quantifies the proportion in which the cumulative distribution function of one of the random variables stochastically dominates the other one. Then, we present a graphical method that decomposes in quantiles (i) the proposed dominance measure and (ii) the probability that one of the random variables takes lower values than the other. With illustrative purposes, we reevaluate the experimentation of an already published work with the proposed methodology and we show that additional conclusions—missed by the rest of the methods—can be inferred. Additionally, the software package RVCompare was created as a convenient way of applying and experimenting with the proposed framework. [ABSTRACT FROM AUTHOR]