bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the Decision-Making Dilemmas in Mini-Grids: The Intricate Case of Smart Meters
Authors: Bandi Venkata , Sahrakorpi Tiia , Paatero Jukka V. , Lahdelma Risto
Published: August 2023

Mini-grids need to imitate the transition path of a traditional grid to maintain their position as a sustainable energy access alternative, while aligning with the objectives of the seventh Sustainable Development Goal. One such strategy is implementing smart-metering solutions to improve business viability and remote monitoring of distributed mini-grid assets. However, selecting smart meters presents a significant challenge for mini-grid operators, primarily due to the installation costs involved and the complexities associated with operating mini-grids in rural areas. Against this backdrop, the current case study’ demonstrates the utility of multi-criteria decision aids, such as stochastic multi-criteria acceptability analysis (SMAA), to assist mini-grid operators in making informed decisions concerning smart-meter selection. In addition, practitioners’ narratives elucidate how implementing smart metering can function as part of mini-grid operations in rural areas. Furthermore, narratives highlight the importance of considering context-specific conditions to avoid the under-utilisation of smart meters.
Analysis of Ignition Characteristics and Influencing Factors of Combustible Fly Ash in Boiler Start-Up Stage Flue Gas
Authors: He Jianle , Guo Dong , Zhang Jianli , Yu Pengfeng , Shen Mengsong , Zhang Guangxue
Published: August 2023

In order to realize the full-time denitration of a boiler, high-temperature flue gas needs to be introduced when SCR is conducted during the boiler start-up stage, and there is a fire risk due to the presence of combustible fly ash at this time. Therefore, research on reburning and the explosion risk of tail flue gas encountering high-temperature flue gas during start-up and shutdown was carried out. A small testbed was designed to record the temperature of the flue gas and the composition of the flue gas before and after the test, and the ignition characteristics of combustible fly ash in the flue gas were systematically studied. The ignition temperature of combustible fly ash in various conditions was obtained, the ignition characteristics of combustible fly ash in the airflow were analyzed, and the effects of combustible gas, high-temperature flue gas temperature, and fly ash composition on ignition were also analyzed. The results show that the flue gas temperature in the test section was about 400 °C, the low-temperature flue gas temperature increased from 650 °C to 813 °C, and the combustible fly ash did not ignite regardless of whether alcohol was added as a combustible gas component. When the volatile content of combustible fly ash was 10~26.7%, the ignition temperature was 660~760 °C. The lower the volatile content of combustible fly ash was, the higher the ignition point was. When alcohol was added as a combustible component of gas, the ignition point decreased by about 50 °C. The critical ignition temperature of combustible fly ash in this test was lower than that under actual power plant operation conditions.
Transcriptome Analysis of Populus Overexpression in SVL Transcription Factor
Authors: Wang Dongli , Cheng Renwu , Liu Yunshan , Wang Shengkun , Yang Zhende , Meng Sen
Published: August 2023

Flowering is an essential part of the productive process, and flowering time is determined by endogenous genetic components and many ambient factors. SHORT VEGETATIVE PHASE (SVP), a MADS-box transcription factor, regulates floral transition by repressing floral integrator genes and is involved in ABA-mediated drought stress. In this study, we transformed the poplar (Populus) clone “84K” with the SVP-Like gene, while stable overexpression transgenic lines were obtained. Transcriptome analysis of the leaves of the transgenic lines and WT (Wide Type) poplars revealed that a total of 477 genes showed significantly altered expression, overexpressing SVL genes, including 342 upregulated and 135 downregulated genes. Ten subclusters in DEGs were analyzed, and KEGG terms of the largest subcluster were associated with two key pathways: hormone-related genes and glutathione metabolism. Meanwhile, many transcriptional factors were involved. Our results are helpful for in-depth analysis of the MADS transcriptional factor in poplars. This work provides the basis for studying woody plant growth, and development and molecular mechanisms responded to environmental stresses.
Digital Twin Applications in Manufacturing Industry: A Case Study from a German Multi-National
Authors: Wynn Martin , Irizar Jose
Published: August 2023

This article examines how digital twins have been used in a multi-national corporation, what technologies have been used, what benefits have been delivered, and the significance of people- and process-related issues in achieving successful implementation. A qualitative, inductive research method is used, based on interviews provided by key personnel involved in three digital twin projects. The article concludes that digital twin projects are likely to involve incremental rather than disruptive change, and that successful implementation is usually underpinned by ensuring technology, people, and process change factors are progressed in a balanced and integrated fashion. Building upon existing frameworks, three “properties” are identified as being of particular value in digital twin projects—workforce adaptability, technology manageability, and process agility—and a related set of steps and actions is put forward as a template and point of reference for future digital twin implementations. The combination of assessing digital properties and following a set of key actions represents a novel approach to digital twin project planning, and overall the findings are a contribution to the developing theory around digital twins and digitalization, in general, and are also of relevance to professionals embarking on DT projects.
E-SAWM: A Semantic Analysis-Based ODF Watermarking Algorithm for Edge Cloud Scenarios
Authors: Zu Lijun , Li Hongyi , Zhang Liang , Lu Zhihui , Ye Jiawei , Zhao Xiaoxia , Hu Shijing
Published: August 2023

With the growing demand for data sharing file formats in financial applications driven by open banking, the use of the OFD (open fixed-layout document) format has become widespread. However, ensuring data security, traceability, and accountability poses significant challenges. To address these concerns, we propose E-SAWM, a dynamic watermarking service framework designed for edge cloud scenarios. This framework incorporates dynamic watermark information at the edge, allowing for precise tracking of data leakage throughout the data-sharing process. By utilizing semantic analysis, E-SAWM generates highly realistic pseudostatements that exploit the structural characteristics of documents within OFD files. These pseudostatements are strategically distributed to embed redundant bits into the structural documents, ensuring that the watermark remains resistant to removal or complete destruction. Experimental results demonstrate that our algorithm has a minimal impact on the original file size, with the watermarked text occupying less than 15%, indicating a high capacity for carrying the watermark. Additionally, compared to existing explicit watermarking schemes for OFD files based on annotation structure, our proposed watermarking scheme is suitable for the technical requirements of complex dynamic watermarking in edge cloud scenario deployment. It effectively overcomes vulnerabilities associated with easy deletion and tampering, providing high concealment and robustness.
HmbC, a Protein of the HMG Family, Participates in the Regulation of Carotenoid Biosynthesis in Fusarium fujikuroi
Authors: Franco-Losilla Marta , Nordzieke Steffen , Feldmann Ingo , Limón M. Carmen , Avalos Javier
Published: August 2023

In the fungus Fusarium fujikuroi, carotenoid production is up-regulated by light and down-regulated by the CarS RING finger protein, which modulates the mRNA levels of carotenoid pathway genes (car genes). To identify new potential regulators of car genes, we used a biotin-mediated pull-down procedure to detect proteins capable of binding to their promoters. We focused our attention on one of the proteins found in the screening, belonging to the High-Mobility Group (HMG) family that was named HmbC. The deletion of the hmbC gene resulted in increased carotenoid production due to higher mRNA levels of car biosynthetic genes. In addition, the deletion resulted in reduced carS mRNA levels, which could also explain the partial deregulation of the carotenoid pathway. The mutants exhibited other phenotypic traits, such as alterations in development under certain stress conditions, or reduced sensitivity to cell wall degrading enzymes, revealed by less efficient protoplast formation, indicating that HmbC is also involved in other cellular processes. In conclusion, we identified a protein of the HMG family that participates in the regulation of carotenoid biosynthesis. This is probably achieved through an epigenetic mechanism related to chromatin structure, as is frequent in this class of proteins.
Integrating Genomic and Chromosomal Data: A Cytogenetic Study of Transancistrus santarosensis (Loricariidae: Hypostominae) with Characterization of a ZZ/ZW Sex Chromosome System
Authors: Nirchio Tursellino Mauro , de Bello Cioffi Marcelo , de Menezes Cavalcante Sassi Francisco , Deon Geize Aparecida , Oliveira Claudio , Kuranaka Mariana , Valdiviezo-Rivera Jonathan , Gonzalez Víctor Hugo , Rossi Anna Rita
Published: August 2023

The plecos (Loricariidae) fish represent a great model for cytogenetic investigations due to their variety of karyotypes, including diploid and polyploid genomes, and different types of sex chromosomes. In this study we investigate Transancistrus santarosensis a rare loricariid endemic to Ecuador, integrating cytogenetic methods with specimens’ molecular identification by mtDNA, to describe the the species karyotype. We aim to verify whether sex chromosomes are cytologically identifiable and if they are associated with the accumulation of repetitive sequences present in other species of the family. The analysis of the karyotype (2n = 54 chromosomes) excludes recent centric fusion and pericentromeric inversion and suggests the presence of a ZZ/ZW sex chromosome system at an early stage of differentiation: the W chromosome is degenerated but is not characterized by the presence of differential sex-specific repetitive DNAs. Data indicate that although T. santarosensis has retained the ancestral diploid number of Loricariidae, it accumulated heterochromatin and shows non-syntenic ribosomal genes localization, chromosomal traits considered apomorphic in the family.
Educational Potential of Geoheritage: Textbook Localities from the Zagros and the Greater Caucasus
Authors: Habibi Tahereh , Ruban Dmitry A. , Ermolaev Vladimir A.
Published: August 2023

Geoheritage requires proper conservation and has significant importance for geoscience education at universities. Furthermore, its related potential needs to be evaluated. This study focuses on two textbook localities (these are parts of larger geosites) from the Cenozoic orogenic belts, namely the Zagros and the Greater Caucasus. The novel, tentatively proposed approach aims at general geological characteristics of the localities, identification of the principal teaching topics and teaching opportunities, and semi-quantitative evaluation of the educational potential on the basis of several objective criteria. The Abmorghan anticline (Zagros, Iran) is suitable for learning about the regional Paleogene stratigraphy, carbonate platform evolution, and karst. The locality of the Skala monocline (Greater Caucasus, Russia) allows the deposition in past tropical conditions and monocline structures to be explained. Both localities can be used for training student skills and challenging their geological thinking. The semi-quantitative evaluation shows that the geoeducational potential of the Abmorghan anticline is advanced and that of the Skala monocline is moderate. The established potential can be exploited by universities, although this requires focusing attention on the other geoheritage sites and special marketing efforts.
Neighborhood Unsafety, Discrimination, and Food Insecurity among Nigerians Aged 15–49
Authors: Ogbu Chukwuemeka E. , Oparanma Chisa O. , Ogbu Stella C. , Ujah Otobo I. , Chinenye Ndugba S. , Ogbu Chidera P. , Kirby Russell S.
Published: August 2023

We investigated the association between discrimination, neighborhood unsafety, and household food insecurity (FI) among Nigerian adults, as well as the gender-specific differences in these associations. Our analysis utilized data from the 2021 Multiple Indicator Cluster Survey (MICS), comprising 56,146 Nigerian adults aged 15–49 (17,346 males and 38,800 females). For bivariate analysis, we employed the Rao–Scott chi-square test to examine the relationship between predictors (discrimination, neighborhood unsafety, and a composite variable of both) and the outcome variable (FI). Food insecurity was assessed using both a dichotomous measure (food insecure vs. food secure) and a multinomial variable (food secure, mild FI, moderate FI, and severe FI). To model the association between predictors and FI while controlling for potential confounding factors, we utilized weighted binary and multinomial logistic regression. Among Nigerian adults, the prevalence of having ever experienced FI was 86.1%, with the prevalence of mild FI, moderate FI, and severe FI being 11.5%, 30.1%, and 44.5%, respectively. In the binary model, experiencing discrimination (OR = 1.36, 95% CI = 1.19–1.55), living in an unsafe neighborhood (OR = 1.33, 95% CI = 1.14–1.54), and facing both discrimination and unsafe neighborhood conditions (OR = 1.97, 95% CI = 1.57–2.48) were significantly associated with FI. In the multinomial model, discrimination, neighborhood unsafety, and experiencing both remained associated with moderate and severe FI. In the gender-specific models, discrimination and neighborhood unsafety were found to be significantly associated with FI in women but not in men. This study underscores the importance of implementing policies and programs that address the underlying causes of food insecurity, with specific attention to discrimination and neighborhood safety concerns, particularly for Nigerian women.
Coping Mechanisms of Psychiatric Nurses in Child Mental Health Environments in North West Province, South Africa: A Qualitative Call for Urgency
Authors: Machailo Rorisang Mary , Matsipane Molekodi Jacob , Koen Daleen
Published: August 2023

There is currently a growing understanding of child mental health. However, with little attention and investment from decision-makers, the prevalence of child mental health challenges shows no signs of diminishing. Psychiatric nursing is a process in which the major knowledge and skills dealing with the interpersonal and intrapersonal dynamics of human beings are practised. These nurses have to cope with this demand in a scant clinical child psychiatric environment. An exploratory, descriptive, and contextual research design was used to postulate the coping mechanism of these nurses in a clinical child psychiatric environment. This study comprised psychiatric nurses, and data were collected through focused group interviews. The findings emphasised the importance of clinical support to enhance quality nursing care and adjustment related to the demands on psychiatric nurses to participate fully in the service. Conclusion: Child and mental health services ought to enable nurses to better deal with the service demands and quality of psychiatric health care. An increased understanding of child mental health challenges is needed so that nurses’ roles and functions in child psychiatric practice can be defined. Effective management and support ought to enable psychiatric nurses and health care teams to make decisions that support international development targets.
Age-Friendly Approach Is Necessary to Prevent Depopulation: Resident Architectural Designers and Constructors’ Evaluation of the Age-Friendliness of Japanese Municipalities
Authors: Yamada Kazumasa , Murotani Kenta , Mano Makiko , Lim Youngmi , Yoshimatsu Jun
Published: August 2023

Japan has the world’s largest old population ratio; thus, aging is an urgent societal issue. As global trends seem to be following Japan’s social changes, there is an emphasis on municipalities becoming more age-friendly. Hence, we examine the age-friendliness of 135 Japanese municipalities, selecting 240 resident architectural designers and constructors to assess their municipalities using the Age-Friendly Cities and Communities Questionnaire (AFCCQ). The findings indicate that Japan lacks “outdoor spaces and buildings”. Additionally, the evaluation of “housing”, “community support and health services”, and “transportation” in populated municipalities in the past five years was found to be significantly higher than that in depopulated ones. Age-friendliness is significantly affected by the AFCCQ total score (hereafter, Score) based on “housing”, “social participation”, “community support and health services”, “transportation”, and “financial situation” evaluations. High specificity (0.939) was found when the score was treated as a marker of depopulation; an age-friendly approach is a necessary condition for preventing depopulation. Furthermore, a lack of “communication and information” was observed in municipalities with a higher rate of single-person households aged 65 years and older. Therefore, resident architectural designers’ and constructors’ assessments, combined with the AFCCQ, will be a powerful tool for evaluating the age-friendliness of municipalities.
A Review on Inflammasomes and Immune Checkpoints in Pre-Eclampsia Complicated with Tuberculosis and Human Immune Deficiency Virus
Authors: Phoswa Wendy N. , Khaliq Olive P. , Eche Simeon
Published: August 2023

The current review evaluates how inflammasomes and immune checkpoints are regulated in pre-eclampsia (PE) associated with tuberculosis (TB) and Human Immune Deficiency Virus (HIV). Studies indicate that inflammasomes such as (NRLP3, NEK7, and AIM2) and immune checkpoints such as (CLT4, PD-1, TIM3, and LAG-3) are dysregulated in TB- and HIV-infected individuals, and also in pre-eclamptic pregnancies, which explains why pregnant women who are either infected with TB or HIV have an increased risk of developing PE. Evidence suggests that inhibition of inflammasomes and immune checkpoints may assist in the development of novel anti-inflammatory drugs for the prevention and management of PE in patients with or without TB and HIV infection.
Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles
Authors: Murillo Carrasco Alexis Germán , Otake Andreia Hanada , Macedo-da-Silva Janaina , Feijoli Santiago Veronica , Palmisano Giuseppe , Andrade Luciana Nogueira de Sousa , Chammas Roger
Published: August 2023

Breast cancer (BC) accounts for the highest incidence of tumor-related mortality among women worldwide, justifying the growing search for molecular tools for the early diagnosis and follow-up of BC patients under treatment. Circulating extracellular vesicles (EVs) are membranous nanocompartments produced by all human cells, including tumor cells. Since minimally invasive methods collect EVs, which represent reservoirs of signals for cell communication, these particles have attracted the interest of many researchers aiming to improve BC screening and treatment. Here, we analyzed the cargoes of BC-derived EVs, both proteins and nucleic acids, which yielded a comprehensive list of potential markers divided into four distinct categories, namely, (i) modulation of aggressiveness and growth; (ii) preparation of the pre-metastatic niche; (iii) epithelial-to-mesenchymal transition; and (iv) drug resistance phenotype, further classified according to their specificity and sensitivity as vesicular BC biomarkers. We discuss the therapeutic potential of and barriers to the clinical implementation of EV-based tests, including the heterogeneity of EVs and the available technologies for analyzing their content, to present a consistent, reproducible, and affordable set of markers for further evaluation.
PON-Fold: Prediction of Substitutions Affecting Protein Folding Rate
Authors: Yang Yang , Chong Zhang , Vihinen Mauno
Published: August 2023

Most proteins fold into characteristic three-dimensional structures. The rate of folding and unfolding varies widely and can be affected by variations in proteins. We developed a novel machine-learning-based method for the prediction of the folding rate effects of amino acid substitutions in two-state folding proteins. We collected a data set of experimentally defined folding rates for variants and used them to train a gradient boosting algorithm starting with 1161 features. Two predictors were designed. The three-class classifier had, in blind tests, specificity and sensitivity ranging from 0.324 to 0.419 and from 0.256 to 0.451, respectively. The other tool was a regression predictor that showed a Pearson correlation coefficient of 0.525. The error measures, mean absolute error and mean squared error, were 0.581 and 0.603, respectively. One of the previously presented tools could be used for comparison with the blind test data set, our method called PON-Fold showed superior performance on all used measures. The applicability of the tool was tested by predicting all possible substitutions in a protein domain. Predictions for different conformations of proteins, open and closed forms of a protein kinase, and apo and holo forms of an enzyme indicated that the choice of the structure had a large impact on the outcome. PON-Fold is freely available.
Cyclosporine A Decreases Dryness-Induced Hyperexcitability of Corneal Cold-Sensitive Nerve Terminals
Authors: Gyenes Andrea , Tapasztó Zsófia , Quirce Susana , Luna Carolina , Frutos-Rincón Laura , Gallar Juana , Acosta M. Carmen , Kovács Illés
Published: August 2023

Cyclosporine A (CsA) is used for the treatment of dry eye (DE) with good clinical results, improving tear secretion and decreasing subjective symptoms. These effects are attributed to the improved tear film dynamics, but there are no data on the effect of CsA on the abnormal sensory nerve activity characteristic in DE. Our purpose was to evaluate the CsA effect on the enhanced activity of corneal cold thermoreceptors in a tear-deficient DE animal model using in vitro extracellular recording of cold thermoreceptors nerve terminal impulses (NTIs) before and in the presence of CsA. NTI shape was also analyzed. Blinking frequency and tearing rate were also measured in awake animals before and after topical CsA. CsA increased the tearing and blinking of treated animals. CsA significantly decreased the peak response to cold of cold thermoreceptors. Neither their spontaneous NTIs discharge rate nor their cooling threshold were modified. CsA also seemed to reverse some of the changes in NTI shape induced by tear deficiency. These data suggest that, at least in part, the beneficial clinical effects of CsA in DE can be attributed to a direct effect on sensory nerve endings, although the precise mechanisms underlying this effect need further studies to be fully clarified.
Placental, Foetal, and Maternal Serum Metabolomic Profiles in Pregnancy-Associated Cancer: Walker-256 Tumour Model in a Time-Course Analysis
Authors: De Moraes Salgado Carla , Viana Laís Rosa , Gomes-Marcondes Maria Cristina Cintra
Published: August 2023

Cancer during pregnancy presents a delicate coexistence, imposing ethical and professional challenges on both the patient and medical team. In this study, we aimed to explore in a pre-clinical model the impact of tumour evolution in serum, placental and foetal metabolomics profiles during pregnancy in a time-course manner. Pregnant Wistar rats were distributed into two experimental groups: Control (C) and Walker-256 tumour-bearing (W). The rats were euthanised on three different gestational periods: at 12 days post-conception (dpc), at 16 dpc, and at 19 dpc. Serum, placenta and foetal metabolomic profiles were performed by 1H-NMR spectra following the analyses using Chenomx NMR Analysis Software V8.3. The tumour evolution was exponential, affecting the placental metabolomic profile during all the pregnancy stages. The placental tissue in tumour-bearing dams developed at a lower speed, decreasing the foetus’s weight. Associated with the serum metabolomic changes related to tumour growth, the placental metabolomic alterations impacted many metabolic pathways related to energy provision, protein synthesis and signalling, which directly harmed the foetus’s development. The development of the foetus is clearly affected by the damage induced by the tumour evolution, which alters the metabolic profile of both the serum and the placenta, impairing early embryonic development.
Apoptosis Regulation in Osteoarthritis and the Influence of Lipid Interactions
Authors: Werry Frederike , Mazur Emilia , Theyse Lars F. H. , Edlich Frank
Published: August 2023

Osteoarthritis (OA) is one of the most common chronic diseases in human and animal joints. The joints undergo several morphological and histological changes during the development of radiographically visible osteoarthritis. The most discussed changes include synovial inflammation, the massive destruction of articular cartilage and ongoing joint destruction accompanied by massive joint pain in the later stadium. Either the increased apoptosis of chondrocytes or the insufficient apoptosis of inflammatory macrophages and synovial fibroblasts are likely to underly this process. In this review, we discuss the current state of research on the pathogenesis of OA with special regard to the involvement of apoptosis.
Anisotropic and Highly Sensitive Flexible Strain Sensors Based on Carbon Nanotubes and Iron Nanowires for Human–Computer Interaction Systems
Authors: Wu Decheng , Su Yinlei , Li Rui , Zhao Jingyuan , Yang Li , Yang Pingan
Published: August 2023

Flexible strain sensors for multi-directional strain detection are crucial in complicated hman–computer interaction (HCI) applications. However, enhancing the anisotropy and sensitivity of the sensors for multi-directional detection in a simple and effective method remains a significant issue. Therefore, this study proposes a flexible strain sensor with anisotropy and high sensitivity based on a high-aspect-ratio V-groove array and a hybrid conductive network of iron nanowires and carbon nanotubes (Fe NWs/CNTs). The sensor exhibits significant anisotropy, with a difference in strain detection sensitivity of up to 35.92 times between two mutually perpendicular directions. Furthermore, the dynamic performance of the sensor shows a good response rate, ranging from 223 ms to 333 ms. The sensor maintains stability and consistent performance even after undergoing 1000 testing cycles. Additionally, the constructed flexible strain sensor is tested using the remote control application of a trolley, demonstrating its high potential for usage in practical HCI systems. This research offers a significant competitive advantage in the development of flexible strain sensors in the field of HCI.
The Functional Role of Myogenin in Cardiomyoblast H9c2 Cells Treated with High Glucose and Palmitic Acid: Insights into No-Rejection Heart Transplantation
Authors: Hsu Po-Shun , Liu Shu-Ting , Chiu Yi-Lin , Tsai Chien-Sung
Published: August 2023

Various pathological alterations, including lipid-deposition-induced comparative cardiac lipotoxicity, contribute to cardiac aging in the failing heart. A decline in endogenous myogenin proteins can lead to the reversal of muscle cell differentiation and the creation of mononucleated muscle cells. Myogenin may be a specific regulator of adaptive responses to avoid pathological hypertrophy in the heart. Hence, it is important to understand the regulation of myogenin expression and functions in response to exposure to varied stresses. In this study, we first examined and verified the cytotoxic effect of palmitic acid on H9c2 cells. The reduction in myogenin mRNA and protein expression by palmitic acid was independent of the effect of glucose. Meanwhile, the induction of cyclooxygenase 2 and activating transcription factor 3 mRNAs and proteins by palmitic acid was dependent on the presence of glucose. In addition, palmitic acid failed to disrupt cell cycle progression when H9c2 cells were treated with no glucose. Next, we examined the functional role of myogenin in palmitic-acid-treated H9c2 cells and found that myogenin may be involved in palmitic-acid-induced mitochondrial and cytosolic ROS generation, cellular senescence, and mitochondrial membrane potential. Finally, the GSE150059 dataset was deposited in the Gene Expression Omnibus website and the dataset was further analyzed via the molecular microscope diagnostic system (MMDx), demonstrating that many heart transplant biopsies currently diagnosed as no rejection have mild molecular-antibody-mediated rejection-related changes. Our data show that the expression levels of myogenin were lower than the average level in the studied population. Combining these results, we uncover part of the functional role of myogenin in lipid- and glucose-induced cardiac cell stresses. This finding provides valuable insight into the differential role of fatty-acid-associated gene expression in cardiovascular tissues. Additionally, the question of whether this gene expression is regulated by myogenin also highlights the usefulness of a platform such as MMDx-Heart and can help elucidate the functional role of myogenin in heart transplantation.
Evaluating the Cysteine-Rich and Catalytic Subdomains of Human Tyrosinase and OCA1-Related Mutants Using 1 μs Molecular Dynamics Simulation
Authors: Woods Taariq , Sergeev Yuri V.
Published: August 2023

The inherited disorder oculocutaneous albinism type 1 (OCA1) is caused by mutations in the TYR gene encoding tyrosinase (Tyr), an enzyme essential to producing pigments throughout the human body. The intramelanosomal domain of Tyr consists of the cysteine-rich and tyrosinase catalytic subdomains, which are essential for enzymatic activity. In protein unfolding, the roles of these subdomains are not well established. Here, we performed six molecular dynamics simulations at room temperature for Tyr and OCA1-related mutant variants P406L and R402Q intramelanosomal domains. The proteins were simulated for 1 μs in water and urea to induce unfolding. In urea, we observed increases in surface area, decreases in intramolecular hydrogen bonding, and decreases in hydrophobic interactions, suggesting a ‘molten globule’ state for each protein. Between all conditions, the cysteine-rich subdomain remains stable, whereas the catalytic subdomain shows increased flexibility. This flexibility is intensified by the P406L mutation, while R402Q increases the catalytic domain’s rigidity. The cysteine-rich subdomain is rigid, preventing the protein from unfolding, whereas the flexibility of the catalytic subdomain accommodates mutational changes that could inhibit activity. These findings match the conclusions from our experimental work suggesting the function alteration by the P406L mutation, and the potential role of R402Q as a polymorphism.
UPR-Induced miR-616 Inhibits Human Breast Cancer Cell Growth and Migration by Targeting c-MYC
Authors: Arabkari Vahid , Sultana Afrin , Barua David , Webber Mark , Smith Terry , Gupta Ananya , Gupta Sanjeev
Published: August 2023

C/EBP homologous protein (CHOP), also known as growth arrest and DNA damage-inducible protein 153 (GADD153), belongs to the CCAAT/enhancer-binding protein (C/EBP) family. CHOP expression is induced by unfolded protein response (UPR), and sustained CHOP activation acts as a pivotal trigger for ER stress-induced apoptosis. MicroRNA-616 is located within an intron of the CHOP gene. However, the regulation of miR-616 expression during UPR and its function in breast cancer is not clearly understood. Here we show that the expression of miR-616 and CHOP (host gene of miR-616) is downregulated in human breast cancer. Both miR-5p/-3p arms of miR-616 are expressed with levels of the 5p arm higher than the 3p arm. During conditions of ER stress, the expression of miR-616-5p and miR-616-3p arms was concordantly increased primarily through the PERK pathway. Our results show that ectopic expression of miR-616 significantly suppressed cell proliferation and colony formation, whereas knockout of miR-616 increased it. We found that miR-616 represses c-MYC expression via binding sites located in its protein coding region. Furthermore, we show that miR-616 exerted growth inhibitory effects on cells by suppressing c-MYC expression. Our results establish a new role for the CHOP locus by providing evidence that miR-616 can inhibit cell proliferation by targeting c-MYC. In summary, our results suggest a dual function for the CHOP locus, where CHOP protein and miR-616 can cooperate to inhibit cancer progression.
On the Importance of Halogen and Chalcogen Bonds in the Solid State of Nucleic Acids: A Combined Crystallographic and Theoretical Perspective
Authors: Piña María de las Nieves , Bauzá Antonio
Published: August 2023

In this work, intra- and intermolecular halogen and chalcogen bonds (HlgBs and ChBs, respectively) present in the solid state of nucleic acids (NAs) have been studied at the RI-MP2/def2-TZVP level of theory. To achieve this, a Protein Data Bank (PDB) survey was carried out, revealing a series of structures in which Br/I or S/Se/Te atoms belonging to nucleobases or pentose rings were involved in noncovalent interactions (NCIs) with electron-rich species. The energetics and directionality of these NCIs were rationalized through a computational study, which included the use of Molecular Electrostatic Potential (MEP) surfaces, the Quantum Theory of Atoms in Molecules (QTAIM), and Non Covalent Interaction plot (NCIplot) and Natural Bonding Orbital (NBO) techniques.
Tiliroside Combined with Anti-MUC1 Monoclonal Antibody as Promising Anti-Cancer Strategy in AGS Cancer Cells
Authors: Radziejewska Iwona , Supruniuk Katarzyna , Jakimiuk Katarzyna , Tomczyk Michał , Bielawska Anna , Galicka Anna
Published: August 2023

Specific changes in mucin-type O-glycosylation are common for many cancers, including gastric ones. The most typical alterations include incomplete synthesis of glycan structures, enhanced expression of truncated O-glycans (Tn, T antigens and their sialylated forms), and overexpression of fucosylation. Such altered glycans influence many cellular activities promoting cancer development. Tiliroside is a glycosidic dietary flavonoid with pharmacological properties, including anti-cancer. In this study, we aim to assess the effect of the combined action of anti-MUC1 and tiliroside on some cancer-related factors in AGS gastric cancer cells. Cancer cells were treated with 40, 80, and 160 µM tiliroside, 5 µg/mL anti-MUC1, and flavonoid together with mAb. Real-Time PCR, ELISA, and Western blotting were applied to examine MUC1 expression, specific, tumor-associated antigens, enzymes taking part in their formation, Gal-3, Akt, and NF-κB. MUC1 expression was significantly reduced by mAb action. The combined action of anti-MUC1 and tiliroside was more effective in comparison with monotherapy in the case of C1GalT1, ST3GalT1, FUT4, Gal-3, NF-κB, Akt mRNAs, and Tn antigen, as well as sialyl T antigen expression. The results of our study indicate that applied combined therapy may be a promising anti-gastric cancer strategy.
Exosomal miR-17-5p, miR-146a-3p, and miR-223-3p Correlate with Radiologic Sequelae in Survivors of COVID-19-Related Acute Respiratory Distress Syndrome
Authors: Curcio Rosa , Poli Giulia , Fabi Consuelo , Sugoni Chiara , Pasticci Maria Bruna , Ferranti Roberto , Rossi Monica , Folletti Ilenia , Sanesi Leandro , Santoni Edoardo , Dominioni Irene , Cavallo Massimiliano , Morgana Giovanni , Mordeglia Lorenzo , Luca Giovanni , Pucci Giacomo , Brancorsini Stefano , Vaudo Gaetano
Published: August 2023

We investigated the association between circulating microRNAs (miRNAs) potentially involved in the lung inflammatory process and fibrosis development among COVID-19-related acute respiratory distress syndrome (ARDS) survivors. At 4 ± 2 months from clinical recovery, COVID-19-related ARDS survivors matched for age, sex, and clinical characteristics underwent chest high-resolution computerized tomography (HRCT) and were selected based on imaging pattern evolution into fully recovered (N = normal), pulmonary opacities (PO) and fibrosis-like lesions (FL). Based on the previous literature, we performed plasma miRNA profiling of exosomal miRNAs belonging to the NLRP3-inflammasome platform with validated (miR-17-5p, miR-223-3p) and putative targets (miR-146a-5p), miRNAs involved in the post-transcriptional regulation of acute phase cytokines (miR128-3p, miR3168, miR125b-2-3p, miR106a-5p), miRNAs belonging to the NLRP4-inflammasome platform (miR-141-3p) and miRNAs related to post-transcriptional regulation of the fibrosis process (miR-21-5p). miR-17-5p, miR-223-3p, and miR-146a-5p were significantly down-regulated in patients with FL when compared to patients with PO. miR-146a-5p was also down-regulated in patients with FL than in N. The expression of the remaining miRNAs did not differ by group. In patients with long-term pulmonary radiological sequelae following COVID-19-related ARDS, a down-regulation of miR-17-5p, miR-146a-3p, and miR-223-3p correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. Our results support the hypothesis that NLRP3-Inflammasome could be implicated in the process of fibrotic evolution of COVID-19-associated ARDS.
Repeated Methamphetamine Administration Results in Axon Loss Prior to Somatic Loss of Substantia Nigra Pars Compacta and Locus Coeruleus Neurons in Male but Not Female Mice
Authors: Pilski Alexander , Graves Steven M.
Published: August 2023

Methamphetamine (meth) is a neurotoxic psychostimulant that increases monoamine oxidase (MAO)-dependent mitochondrial oxidant stress in axonal but not somatic compartments of substantia nigra pars compacta (SNc) and locus coeruleus (LC) neurons. Chronic meth administration results in the degeneration of SNc and LC neurons in male mice, and MAO inhibition is neuroprotective, suggesting that the deleterious effects of chronic meth begin in axons before advancing to the soma of SNc and LC neurons. To test this hypothesis, mice were administered meth (5 mg/kg) for 14, 21, or 28 days, and SNc and LC axonal lengths and numbers of neurons were quantified. In male mice, the SNc and LC axon lengths decreased with 14, 21, and 28 days of meth, whereas somatic loss was only observed after 28 days of meth; MAO inhibition (phenelzine; 20 mg/kg) prevented axonal and somatic loss of SNc and LC neurons. In contrast, chronic (28-day) meth had no effect on the axon length or numbers of SNc or LC neurons in female mice. The results demonstrate that repeated exposure to meth produces SNc and LC axonal deficits prior to somatic loss in male subjects, consistent with a dying-back pattern of degeneration, whereas female mice are resistant to chronic meth-induced degeneration.
The Rationale of Complement Blockade of the MCPggaac Haplotype following Atypical Hemolytic Uremic Syndrome of Three Southeastern European Countries with a Literature Review
Authors: Turudic Daniel , Pokrajac Danka , Tasic Velibor , Kasumovic Dino , Prohaszka Zoltan , Milosevic Danko
Published: August 2023

We present eight cases of the homozygous MCPggaac haplotype, which is considered to increase the likelihood and severity of atypical hemolytic uremic syndrome (aHUS), especially in combination with additional risk aHUS mutations. Complement blockade (CBT) was applied at a median age of 92 months (IQR 36–252 months). The median number of relapses before CBT initiation (Eculizumab) was two. Relapses occurred within an average of 22.16 months (median 17.5, minimum 8 months, and maximum 48 months) from the first subsequent onset of the disease (6/8 patients). All cases were treated with PI/PEX, and rarely with renal replacement therapy (RRT). When complement blockade was applied, children had no further disease relapses. Children with MCPggaac haplotype with/without additional gene mutations can achieve remission through renal replacement therapy without an immediate need for complement blockade. If relapse of aHUS occurs soon after disease onset or relapses are repeated frequently, a permanent complement blockade is required. However, the duration of such a blockade remains uncertain. If complement inhibition is not applied within 4–5 relapses, proteinuria and chronic renal failure will eventually occur.
Double Network Physical Crosslinked Hydrogel for Healing Skin Wounds: New Formulation Based on Polysaccharides and Zn2+
Authors: Cui Shenghao , Yang Faming , Yu Dingyi , Shi Chao , Zhao Di , Chen Liqi , Chen Jingdi
Published: August 2023

Developing convenient, efficient, and natural wound dressings remain the foremost strategy for treating skin wounds. Thus, we innovatively combined the semi-dissolved acidified sol-gel conversion method with the internal gelation method to fabricate SA (sodium alginate)/CS (chitosan)/Zn2+ physically cross-linked double network hydrogel and named it SA/CS/Zn2+ PDH. The characterization results demonstrated that increased Zn2+ content led to hydrogels with improved physical and chemical properties, such as rheology, water retention, and swelling capacity. Moreover, the hydrogels exhibited favorable antibacterial properties and biocompatibility. Notably, the establishment of an in vitro pro-healing wound model further confirmed that the hydrogel had a superior ability to repair wounds and promote skin regeneration. In future, as a natural biomaterial with antimicrobial properties, it has the potential to promote wound healing.
Advances in Platelet Rich Plasma-Derived Extracellular Vesicles for Regenerative Medicine: A Systematic-Narrative Review
Authors: Anitua Eduardo , Troya María , Falcon-Pérez Juan Manuel , López-Sarrio Silvia , González Esperanza , Alkhraisat Mohammad H.
Published: August 2023

The use of platelet-rich plasma (PRP) has gained increasing interest in recent decades. The platelet secretome contains a multitude of growth factors, cytokines, chemokines, and other biological biomolecules. In recent years, developments in the field of platelets have led to new insights, and attention has been focused on the platelets’ released extracellular vesicles (EVs) and their role in intercellular communication. In this context, the aim of this review was to compile the current evidence on PRP-derived extracellular vesicles to identify the advantages and limitations fortheir use in the upcoming clinical applications. A total of 172 articles were identified during the systematic literature search through two databases (PubMed and Web of Science). Twenty publications met the inclusion criteria and were included in this review. According to the results, the use of PRP-EVs in the clinic is an emerging field of great interest that represents a promising therapeutic option, as their efficacy has been demonstrated in the majority of fields of applications included in this review. However, the lack of standardization along the procedures in both the field of PRP and the EVs makes it extremely challenging to compare results among studies. Establishing standardized conditions to ensure optimized and detailed protocols and define parameters such as the dose or the EV origin is therefore urgent. Further studies to elucidate the real contribution of EVs to PRP in terms of composition and functionality should also be performed. Nevertheless, research on the field provides promising results and a novel basis to deal with the regenerative medicine and drug delivery fields in the future.
Reticular Chemistry for Optical Sensing of Anions
Authors: Helal Aasif , Khan Mohd Yusuf , Khan Abuzar , Usman Muhammad , Zahir Md. Hasan
Published: August 2023

In the last few decades, reticular chemistry has grown significantly as a field of porous crystalline molecular materials. Scientists have attempted to create the ideal platform for analyzing distinct anions based on optical sensing techniques (chromogenic and fluorogenic) by assembling different metal-containing units with suitable organic linking molecules and different organic molecules to produce crystalline porous materials. This study presents novel platforms for anion recognition based on reticular chemistry with high selectivity, sensitivity, electronic tunability, structural recognition, strong emission, and thermal and chemical stability. The key materials for reticular chemistry, Metal-Organic Frameworks (MOFs), Zeolitic Imidazolate Frameworks (ZIFs), and Covalent-Organic Frameworks (COFs), and the pre- and post-synthetic modification of the linkers and the metal oxide clusters for the selective detection of the anions, have been discussed. The mechanisms involved in sensing are also discussed.
Deregulated miRNA Expression in Triple-Negative Breast Cancer of Ancestral Genomic-Characterized Latina Patients
Authors: Almohaywi Maram , Sugita Bruna M. , Centa Ariana , Fonseca Aline S. , Antunes Valquiria C. , Fadda Paolo , Mannion Ciaran M. , Abijo Tomilowo , Goldberg Stuart L. , Campbell Michael C. , Copeland Robert L. , Kanaan Yasmine , Cavalli Luciane R.
Published: August 2023

Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease.