bluuebunny/crossref_metadata_2025 huggingface dataset:
Intelligent Methods for Forest Fire Detection Using Unmanned Aerial Vehicles
Authors: Abramov Nikolay , Emelyanova Yulia , Fralenko Vitaly , Khachumov Vyacheslav , Khachumov Mikhail , Shustova Maria , Talalaev Alexander
Published: March 2024

This research addresses the problem of early detection of smoke and open fire on the observed territory by unmanned aerial vehicles. We solve the tasks of improving the quality of incoming video data by removing motion blur and stabilizing the video stream; detecting the horizon line in the frame; and identifying fires using semantic segmentation with Euclidean–Mahalanobis distance and the modified convolutional neural network YOLO. The proposed horizon line detection algorithm allows for cutting off unnecessary information such as cloud-covered areas in the frame by calculating local contrast, which is equivalent to the pixel informativeness indicator of the image. Proposed preprocessing methods give a delay of no more than 0.03 s due to the use of a pipeline method for data processing. Experimental results show that the horizon clipping algorithm improves fire and smoke detection accuracy by approximately 11%. The best results with the neural network were achieved with YOLO 5m, which yielded an F1 score of 76.75% combined with a processing speed of 45 frames per second. The obtained results differ from existing analogs by utilizing a comprehensive approach to early fire detection, which includes image enhancement and alternative real-time video processing methods.
The Classification and Evaluation of an Interlayer Shale Oil Reservoir Based on the Fractal Characteristics of Pore Systems: A Case Study in the HSN Area, China
Authors: Lu Changsheng , Wang Xixin , Ma Shuwei , Li Shaohua , Xue Ting , Li Qiangqiang
Published: March 2024

The evaluation of shale reservoir quality is of great significance for the exploration and development of shale oil. To more effectively study the distribution characteristics of shale reservoir quality, thin-section observation, scanning electron microscopy and pressure-controlled porosimetry were used to obtain the pore structure characteristics of shale in Chang 7, including pore types, pore size distribution, etc. In addition, the fractal dimensions of the shale samples were calculated based on pressure-controlled porosimetry data. The results show that residual interparticle pores, dissolution pores and clay-dominated pores were the main pore types. The overall pore size was mainly distributed between 3 nm and 50 μm. The pore system was divided into four types using fractal features, and the shale reservoir was divided into four types based on the proportion of different types of pore system. In different types of reservoirs, the production capacity of exploration wells varies significantly, as does the production capacity of horizontal wells. The classification of shale reservoirs using mercury intrusion fractal analysis proved to be suited for the efficient development of Chang 7 shale oil reservoirs.
Soil Erosion Modeling Using the Revised Universal Soil Loss Equation and a Geographic Information System in a Watershed in the Northeastern Brazilian Cerrado
Authors: Barbosa Wellynne Carla de Sousa , Guerra Antonio José Teixeira , Valladares Gustavo Souza
Published: March 2024

Soils have an important task in maintaining vegetation cover and natural resources on Earth and are indispensable to societies. However, the accelerated soil erosion has become an environmental problem related to land settlement for agricultural practices and forestry and is linked to population growth. This study aimed to evaluate soil erosion in a watershed downstream of Parnaíba river, northwest of Piauí state, in the Brazilian Cerrado using geotechnology products and tools in order to understand the soil loss and map the potential erosion and actual erosion through qualitative and quantitative results to support the management and planning of the watershed in an effective and efficient way. As a modeling tool, this research used the Revised Universal Soil Loss Equation (RUSLE). The potential erosion ranged from very low to very high. The soil loss obtained by the integration of natural physical factors with land use (anthropic action) resulted in soil loss corresponding to the category slight (0–0.01 t.ha−1.year−1) to extremely high (>100 t.ha−1.year−1). The areas with the greatest soil loss were identified in land uses linked to pasture, exposed soil, and cultivated land. It was also possible to identify erosion features in the field, indicating the need to implement soil conservation practices.
A Systematic Review on Intervention Treatment in Pathological Gambling
Authors: Moreira Diana , Dias Paulo , Azeredo Andreia , Rodrigues Anabela , Leite Ângela
Published: March 2024

Over the last century, there has been a growing interest in researching pathological gambling, particularly in industrialized nations. Historically, gambling was widely perceived as morally questionable, condemned by religious groups. However, contemporary concerns have shifted towards the health repercussions of gambling disorders and broader societal impacts like increased crime and money laundering. Governments, aiming to mitigate social harm, often regulate or directly oversee gambling activities. The global surge in legal gambling has resulted in a substantial rise in its prevalence, popularity, and accessibility in the last two decades. This paper provides a comprehensive overview of global research on interventions for pathological gambling. Through a systematic search on platforms such as EBSCO, PubMed, and Web of Science, 13 relevant records were identified. The revised findings indicate a heightened occurrence of behavioral addictions, linking them to the early onset of gambling issues and their severe consequences. The research emphasizes the active role that clients play in the process of self-directed change and therapy. Therapists recognizing clients as both catalysts for change and potential obstacles can enhance their effectiveness. A common source of resistance arises when clients and therapists are in different stages of the change process, underlining the importance of therapists aligning with clients’ readiness for change. Recognizing the urgent need for a better understanding of this problem in adolescents, this study emphasizes the necessity to tailor prevention and treatment plans based on gender and age-specific requirements.
The Work Ability Index (WAI) in the Healthcare Sector: A Cross-Sectional/Retrospective Assessment of the Questionnaire
Authors: Magnavita Nicola , Meraglia Igor , Viti Giacomo , Borghese Lorenzo
Published: March 2024

The Work Ability Index (WAI) is the most widely used questionnaire for the self-assessment of working ability. Because of its different applications, shorter versions, and widespread use in healthcare activities, assessing its characteristics is worthwhile. The WAI was distributed online among the employees of a healthcare company; the results were compared with data contained in the employees’ personal health records and with absence registers. A total of 340 out of 575 workers (59.1%) participated; 6.5% of them reported poor work ability. Exploratory factor analysis indicated that the one-factor version best described the characteristics of the WAI. The scores of the complete WAI, the shorter form without the list of diseases, and the minimal one-item version (WAS) had equal distribution and were significantly correlated. The WAI score was inversely related to age and significantly lower in women than in men, but it was higher in night workers than in their day shift counterparts due to the probable effect of selective factors. The WAI score was also correlated with absenteeism, but no differences were found between males and females in the average number of absences, suggesting that cultural or emotional factors influence the self-rating of the WAI. Workers tended to over-report illnesses in the online survey compared to data collected during occupational health checks. Musculoskeletal disorders were the most frequently reported illnesses (53%). Psychiatric illnesses affected 21% of workers and had the greatest impact on work ability. Multilevel ergonomic and human factor intervention seems to be needed to recover the working capacity of healthcare workers.
ConvTEBiLSTM: A Neural Network Fusing Local and Global Trajectory Features for Field-Road Mode Classification
Authors: Bian Cunxiang , Bai Jinqiang , Cheng Guanghe , Hao Fengqi , Zhao Xiyuan
Published: March 2024

Field-road mode classification (FRMC) that identifies “in-field” and “on-road” categories for Global Navigation Satellite System (GNSS) trajectory points of agricultural machinery containing geographic information is essential for effective crop improvement. Most previous studies utilize local trajectory features (i.e., the relationships between a point and its neighboring points), but they ignore global trajectory features (i.e., the relationships between the point and all points of the trajectory), leading to difficulty in improving the overall classification performance. The global trajectory features are useful for FRMC because they contain rich trajectory information (e.g., mode switching and motion tendency). Therefore, a ConvTEBiLSTM network-based method is proposed to improve the overall performance. Firstly, nine statistical features (e.g., speed and direction) are extracted from the original data and fed into the ConvTEBiLSTM network. Then, the ConvTEBiLSTM network combining the Bidirectional Long Short-Term Memory network, 1D Convolution network, and Transformer-Encoder network is used to extract and fuse local and global trajectory features. Finally, a linear classifier is applied to identify the “field” and “road” categories of GNSS points based on the fused features. Experimental results show that compared with the baselines, our method achieves the best accuracy and F1-score of 97.38% and 92.74% on our Harvester dataset, respectively.
Multiscale Urban Functional Zone Recognition Based on Landmark Semantic Constraints
Authors: Xie Xuejing , Xu Yongyang , Feng Bin , Wu Wenjun
Published: March 2024

The classification of urban functional areas is important for understanding the characteristics of urban areas and optimizing the utilization of urban land resources. Existing related methods have improved accuracy. However, they neglect cognitive differences amongst humans in the different scales of regional functions. Moreover, how to build the correlations of cross-scale characteristics is still unresolved when realizing the classification of multiscale urban functional zones. To resolve these problems, a transportation analysis zone involving urban buildings as research units is created and these units are described by geometric and functional characteristics using multiple data sources. Then, a hierarchical clustering model is built for the recognition of urban functional areas at varying scales with landmark semantic constraints. In the experiments, Shanghai served as the study area, and multiscale zones were created using different levels of road networks considering the constraint correlation of the significance between cross-scale maps. The experiential results show the proposed method has excellent performance and optimizes the functional zone classification at different scales. This study not only enriches the multiscale urban functional area-recognition methods but also can be used in other aspects, like cartographic generalization or spatial analysis.
MoNOT3 Subunit Has Important Roles in Infection-Related Development and Stress Responses in Magnaporthe oryzae
Authors: Kim Youngmin , Jo Miju , An Sunmin , Lee Yerim , Choi Eu Ddeum , Jeong Min-Hye , Kim Ki-Tae , Park Sook-Young
Published: March 2024

The multifunctional carbon catabolite repression negative on TATA-box-less complex (CCR4-NOT) is a multi-subunit complex present in all eukaryotes, including fungi. This complex plays an essential role in gene expression; however, a functional study of the CCR4-NOT complex in the rice blast fungus Magnaporthe oryzae has not been conducted. Seven genes encoding the putative CCR4-NOT complex were identified in the M. oryzae genome. Among these, a homologous gene, MoNOT3, was overexpressed during appressorium development in a previous study. Deletion of MoNOT3 in M. oryzae resulted in a significant reduction in hyphal growth, conidiation, abnormal septation in conidia, conidial germination, and appressorium formation compared to the wild-type. Transcriptional analyses suggest that the MoNOT3 gene affects conidiation and conidial morphology by regulating COS1 and COM1 in M. oryzae. Furthermore, Δmonot3 exhibited a lack of pathogenicity, both with and without wounding, which is attributable to deficiencies in the development of invasive growth in planta. This result was also observed in onion epidermal cells, which are non-host plants. In addition, the MoNOT3 gene was involved in cell wall stress responses and heat shock. Taken together, these observations suggest that the MoNOT3 gene is required for fungal infection-related cell development and stress responses in M. oryzae.
GC-MS with Headspace Extraction for Non-Invasive Diagnostics of IBD Dynamics in a Model of DSS-Induced Colitis in Rats
Authors: Shagaleeva Olga Yu. , Kashatnikova Daria A. , Kardonsky Dmitry A. , Danilova Elena Yu. , Ivanov Viktor A. , Evsiev Suleiman S. , Zubkov Eugene A. , Abramova Olga V. , Zorkina Yana A. , Morozova Anna Y. , Konanov Dmitry N. , Silantiev Artemiy S. , Efimov Boris A. , Kolesnikova Irina V. , Bespyatykh Julia A. , Stimpson Joanna , Zakharzhevskaya Natalya B.
Published: March 2024

Inflammatory bowel diseases are extremely common throughout the world. However, in most cases, it is asymptomatic at the initial stage. Therefore, it is important to develop non-invasive diagnostic methods that allow identification of the IBD risks in a timely manner. It is well known that gastrointestinal microbiota secrete volatile compounds (VOCs) and their composition may change in IBD. We propose a non-invasive method to identify the dynamics of IBD development in the acute and remission stage at the level of VOCs in model of dextran sulfate sodium (DSS) with chemically induced colitis measured by headspace GC/MS (HS GC/MS). Methods: VOCs profile was identified using a headspace GC/MS (HS GC/MS). GC/MS data were processed using MetaboAnalyst 5.0 and GraphPad Prism 8.0.1 software. The disease activity index (DAI) and histological method were used to assess intestinal inflammation. The peak of intestinal inflammation activity was reached on day 7, according to the disease activity index. Histological examination data showed changes in the intestine due to different stages of inflammation. As the acute inflammation stage was reached, the metabolomic profile also underwent changes, especially at the short-fatty acids level. A higher relative amounts of acetic acid (p value < 0.025) and lower relative amounts of propanoic acid (p value < 0.0005), butanoic acid (p value < 0.005) and phenol 4-methyl- (p value = 0.053) were observed in DSS7 group on day 7 compared to the control group. In remission stage, disease activity indexes decreased, and the histological picture also improved. But metabolome changes continued despite the withdrawal of the DSS examination. A lower relative amounts of propanoic acid (p value < 0.025), butanoic acid (p value < 0.0005), pentanoic acid (p value < 0.0005), and a significant de-crease of hexanoic acid (p value < 0.0005) relative amounts were observed in the DSS14 group compared to the control group on day 14. A model of DSS-induced colitis in rats was successfully implemented for metabolomic assessment of different stages of inflammation. We demonstrated that the ratios of volatile compounds change in response to DSS before the appearance of standard signs of inflammation, determined by DAI and histological examination. Changes in the volatile metabolome persisted even after visual intestine repair and it confirms the high sensitivity of the microbiota to the damaging effects of DSS. The use of HS GC/MS may be an important addition to existing methods for assessing inflammation at early stages.
Genetic Variations in Susceptibility to Traumatic Muscle Injuries and Muscle Pain among Brazilian High-Performance Athletes
Authors: Marques Inês Soares , Tavares Valéria , Vieira Neto Beatriz , Lopes Lucas Rafael , Goes Rodrigo Araújo , Guimarães João António Matheus , Perini Jamila Alessandra , Medeiros Rui
Published: March 2024

Traumatic muscle injuries (TMIs) and muscle pain (MP) negatively impact athletes’ performance and quality of life. Both conditions have a complex pathophysiology involving the interplay between genetic and environmental factors. Yet, the existing data are scarce and controversial. To provide more insights, this study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) previously linked to athletic status with TMI and MP after exercise among Brazilian high-performance athletes from different sports modalities (N = 345). The impact of important environmental determinants was also assessed. From the six evaluated SNPs (ACTN3 rs1815739, FAAH rs324420, PPARGC1A rs8192678, ADRB2 rs1042713, NOS3 rs1799983, and VDR rs731236), none was significantly associated with TMI. Regarding MP after exercise, ACTN3 rs1815739 (CC/CT vs. TT; adjusted odds ratio (aOR) = 1.90; 95% confidence interval (95%Cl), 1.01–3.57) and FAAH rs324420 (AA vs. AC/CC; aOR = 2.30; 95%Cl, 1.08–4.91) were independent predictors according to multivariate binomial analyses adjusted for age (≥23 vs. <23 years), sex (male vs. female), and tobacco consumption (yes vs. no). External validation is warranted to assess the predictive value of ACTN3 rs1815739 and FAAH rs324420. This could have implications for prophylactic interventions to improve athletes’ quality of life.
Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia–Reperfusion Injury through NR4A2-Mediated Mitophagy
Authors: Yu Yifan , Li Zhiliang , Cai Yuqing , Guo Jiahui , Lin Yushuang , Zhao Jing
Published: March 2024

Cardiomyocyte survival is a critical contributing process of host adaptive responses to cardiovascular diseases (CVD). Cells of the cardiovascular endothelium have recently been reported to promote cardiomyocyte survival through exosome-loading cargos. Sphingosylphosphorylcholine (SPC), an intermediate metabolite of sphingolipids, mediates protection against myocardial infarction (MI). Nevertheless, the mechanism of SPC delivery by vascular endothelial cell (VEC)-derived exosomes (VEC-Exos) remains uncharacterized at the time of this writing. The present study utilized a mice model of ischemia/reperfusion (I/R) to demonstrate that the administration of exosomes via tail vein injection significantly diminished the severity of I/R-induced cardiac damage and prevented apoptosis of cardiomyocytes. Moreover, SPC was here identified as the primary mediator of the observed protective effects of VEC-Exos. In addition, within this investigation, in vitro experiments using cardiomyocytes showed that SPC counteracted myocardial I/R injury by activating the Parkin and nuclear receptor subfamily group A member 2/optineurin (NR4A2/OPTN) pathways, in turn resulting in increased levels of mitophagy within I/R-affected myocardium. The present study highlights the potential therapeutic effects of SPC-rich exosomes secreted by VECs on alleviating I/R-induced apoptosis in cardiomyocytes, thereby providing strong experimental evidence to support the application of SPC as a potential therapeutic target in the prevention and treatment of myocardial infarction.
Labdane-Type Diterpenoids from Streptomyces griseorubens and Their Antimicrobial and Cytotoxic Activities
Authors: Heo Chang-Su , Kang Jong Soon , Yang Jeong-Wook , Lee Min Ah , Lee Hwa-Sun , Shin Hee Jae
Published: March 2024

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1–3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC50) values ranging from 1.2 to 22.5 µM.
TRIM21 Promotes Oxidative Stress and Ferroptosis through the SQSTM1-NRF2-KEAP1 Axis to Increase the Titers of H5N1 Highly Pathogenic Avian Influenza Virus
Authors: Wei Yifan , Gu Yongxia , Zhou Ziwei , Wu Changrong , Liu Yanwei , Sun Hailiang
Published: March 2024

Tripartite motif-containing protein 21 (TRIM21) is involved in signal transduction and antiviral responses through the ubiquitination of protein targets. TRIM21 was reported to be related to the imbalance of host cell homeostasis caused by viral infection. Our studies indicated that H5N1 highly pathogenic avian influenza virus (HPAIV) infection up-regulated TRIM21 expression in A549 cells. Western blot and qPCR results showed that knockdown of TRIM21 alleviated oxidative stress and ferroptosis induced by H5N1 HPAIV and promoted the activation of antioxidant pathways. Co-IP results showed that TRIM21 promoted oxidative stress and ferroptosis by regulating the SQSTM1-NRF2-KEAP1 axis by increasing SQSTM1 K63-linked polyubiquitination under the condition of HPAIV infection. In addition, TRIM21 attenuated the inhibitory effect of antioxidant NAC on HPAIV titers and enhanced the promoting effect of ferroptosis agonist Erastin on HPAIV titers. Our findings provide new insight into the role of TRIM21 in oxidative stress and ferroptosis induced by viral infection.
Unveiling Prognostic RNA Biomarkers through a Multi-Cohort Study in Colorectal Cancer
Authors: Kim Zehwan , Lee Jaebon , Yoon Ye Eun , Yun Jae Won
Published: March 2024

Because cancer is a leading cause of death and is thought to be caused by genetic errors or genomic instability in many circumstances, there have been studies exploring cancer’s genetic basis using microarray and RNA-seq methods, linking gene expression data to patient survival. This research introduces a methodological framework, combining heterogeneous gene expression data, random forest selection, and pathway analysis, alongside clinical information and Cox regression analysis, to discover prognostic biomarkers. Heterogeneous gene expression data for colorectal cancer were collected from TCGA-COAD (RNA-seq), and GSE17536 and GSE39582 (microarray), and were integrated with Entrez Gene IDs. Using Cox regression analysis and random forest, genes with consistent hazard ratios and significantly affecting patient survivability were chosen. Predictive accuracy was evaluated using ROC curves. Pathway analysis identified potential RNA biomarkers. The authors identified 28 RNA biomarkers. Pathway analysis revealed enrichment in cancer-related pathways, notably EGFR downstream signaling and IGF1R signaling. Three RNA biomarkers (ZEB1-AS1, PI4K2A, and ITGB8-AS1) and two clinical biomarkers (stage and age) were chosen for a prognostic model, improving predictive performance compared to using clinical biomarkers alone. Despite biomarker identification challenges, this study underscores integration of heterogenous gene expression data for discovery.
Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients
Authors: Belo Luís , Valente Maria João , Rocha Susana , Coimbra Susana , Catarino Cristina , Lousa Irina , Bronze-da-Rocha Elsa , Rocha-Pereira Petronila , Sameiro-Faria Maria do , Oliveira José Gerardo , Madureira José , Fernandes João Carlos , Miranda Vasco , Nunes José Pedro L. , Santos-Silva Alice
Published: March 2024

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: −0.407, 0.272, −0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.
Candidate Gene Identification and Transcriptome Analysis of Tomato male sterile-30 and Functional Marker Development for ms-30 and Its Alleles, ms-33, 7B-1, and stamenless-2
Authors: Wei Kai , Li Xin , Cao Xue , Li Shanshan , Zhang Li , Lu Feifei , Liu Chang , Guo Yanmei , Liu Lei , Zhu Can , Du Yongchen , Li Junming , Yang Wencai , Huang Zejun , Wang Xiaoxuan
Published: March 2024

Male sterility is a valuable trait for hybrid seed production in tomato (Solanum lycopersicum). The mutants male sterile-30 (ms-30) and ms-33 of tomato exhibit twisted stamens, exposed stigmas, and complete male sterility, thus holding potential for application in hybrid seed production. In this study, the ms-30 and ms-33 loci were fine-mapped to 53.3 kb and 111.2 kb intervals, respectively. Tomato PISTILLATA (TPI, syn. SlGLO2), a B-class MADS-box transcription factor gene, was identified as the most likely candidate gene for both loci. TPI is also the candidate gene of tomato male sterile mutant 7B-1 and sl-2. Allelism tests revealed that ms-30, ms-33, 7B-1, and sl-2 were allelic. Sequencing analysis showed sequence alterations in the TPI gene in all these mutants, with ms-30 exhibiting a transversion (G to T) that resulted in a missense mutation (S to I); ms-33 showing a transition (A to T) that led to alternative splicing, resulting in a loss of 46 amino acids in protein; and 7B-1 and sl-2 mutants showing the insertion of an approximately 4.8 kb retrotransposon. On the basis of these sequence alterations, a Kompetitive Allele Specific PCR marker, a sequencing marker, and an Insertion/Deletion marker were developed. Phenotypic analysis of the TPI gene-edited mutants and allelism tests indicated that the gene TPI is responsible for ms-30 and its alleles. Transcriptome analysis of ms-30 and quantitative RT-PCR revealed some differentially expressed genes associated with stamen and carpel development. These findings will aid in the marker-assisted selection for ms-30 and its alleles in tomato breeding and support the functional analysis of the TPI gene.
Overexpression of REST Represses the Epithelial–Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells
Authors: Indo Sebastián , Orellana-Serradell Octavio , Torres María José , Castellón Enrique A. , Contreras Héctor R.
Published: March 2024

The RE-1 silencing transcription factor (REST) is a repressor factor related to neuroendocrine prostate cancer (PCa) (NEPC), a poor prognostic stage mainly associated with castration-resistant PCa (CRPC). NEPC is associated with cell transdifferentiation and the epithelial–mesenchymal transition (EMT) in cells undergoing androgen deprivation therapy (ADT) and enzalutamide (ENZ). The effect of REST overexpression in the 22rv1 cell line (xenograft-derived prostate cancer) on EMT, migration, invasion, and the viability for ENZ was evaluated. EMT genes, Twist and Zeb1, and the androgen receptor (AR) were evaluated through an RT-qPCR and Western blot in nuclear and cytosolic fractions of REST-overexpressing 22rv1 cells (22rv1-REST). The migratory and invasive capacities of 22rv1-REST cells were evaluated via Transwell® assays with and without Matrigel, respectively, and their viability for enzalutamide via MTT assays. The 22rv1-REST cells showed decreased nuclear levels of Twist, Zeb1, and AR, and a decreased migration and invasion and a lower viability for ENZ compared to the control. Results were expressed as the mean + SD of three independent experiments (Mann–Whitney U test, Kruskal–Wallis, Tukey test). REST behaves like a tumor suppressor, decreasing the aggressiveness of 22rv1 cells, probably through the repression of EMT and the neuroendocrine phenotype. Furthermore, REST could represent a response marker to ENZ in PCa patients.
HFE Mutations in Neurodegenerative Disease as a Model of Hormesis
Authors: Marshall Moscon Savannah L. , Connor James R.
Published: March 2024

Common variants in the iron regulatory protein HFE contribute to systematically increased iron levels, yet the effects in the brain are not fully characterized. It is commonly believed that iron dysregulation is a key contributor to neurodegenerative disease due to iron’s ability to catalyze reactive oxygen species production. However, whether HFE variants exacerbate or protect against neurodegeneration has been heavily debated. Some claim that mutated HFE exacerbates oxidative stress and neuroinflammation, thus predisposing carriers to neurodegeneration-linked pathologies. However, H63D HFE has also been shown to slow the progression of multiple neurodegenerative diseases and to protect against environmental toxins that cause neurodegeneration. These conflicting results showcase the need to further understand the contribution of HFE variants to neurodegenerative disease heterogeneity. Data from mouse models consistently demonstrate robust neuroprotection against toxins known to increase the risk of neurodegenerative disease. This may represent an adaptive, or hormetic, response to increased iron, which leaves cells better protected against future stressors. This review describes the current research regarding the contribution of HFE variants to neurodegenerative disease prognosis in the context of a hormetic model. To our knowledge, this is the first time that a hormetic model for neurodegenerative disease has been presented.
A Novel Model of Staphylococcus aureus-Induced Lymphoplasmacytic Rhinosinusitis in Rats
Authors: Murphy William , Liu Sha , Hon Karen , Finnie John , Bouras George Spyro , Feizi Sholeh , Houtak Ghais , Shaghayegh Gohar , Vyskocil Erich , Wormald Peter-John , Vreugde Sarah , Psaltis Alkis J.
Published: March 2024

Chronic rhinosinusitis (CRS) is characterized by sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe CRS phenotypes. Different animal models have been proposed to study the association of CRS and S. aureus. However, current animal models are expensive due to the use of large animals, have high barriers to ethics approval, or require invasive surgical intervention, necessitating a need for a model that can overcome these limitations. This study aimed at establishing a reliable and efficient rat lymphoplasmacytic inflammatory model for rhinosinusitis. Sprague Dawley rats received a daily intranasal application of 20 μL of saline, S. aureus CI-182 exoprotein (250 μg/mL), or exoprotein CI-182 in combination with S. aureus clinical isolate (CI-908 or CI-913) 108 colony-forming unit (CFU)/mL. The rats’ sinuses were harvested at 1 and 2 weeks post-intervention. The CFU and histopathologic examination of inflammation were evaluated. S. aureus clinical isolates CI-908 or CI-913 in combination with the exoprotein (CI-182) had higher CFUs and caused persistently higher inflammation at both the 1 and 2-week post-intervention compared to the exoprotein and saline group. The observed inflammatory cell type was lymphoplasmacytic. This study provided evidence that the combination of a S. aureus exoprotein with S. aureus induces inflammation that persists for a minimum of two weeks post-intervention. This model is the first known animal model to create the lymphoplasmacytic inflammation subtype seen in CRS patients. This offers a cost-effective, accessible, non-invasive, and easy-to-replicate model to study the causes and treatment of such inflammation.
The Chronic Effects of a Single Low-Intensity Blast Exposure on Phosphoproteome Networks and Cognitive Function Influenced by Mutant Tau Overexpression
Authors: Jackson Marcus , Chen Shanyan , Nguyen Thao Thi , Siedhoff Heather R. , Balderrama Ashley , Zuckerman Amitai , Li Runting , Greenlief C. Michael , Cole Gregory , Frautschy Sally A. , Cui Jiankun , Gu Zezong
Published: March 2024

Blast-induced neurotrauma (BINT) is a pressing concern for veterans and civilians exposed to explosive devices. Affected personnel may have increased risk for long-term cognitive decline and developing tauopathies including Alzheimer’s disease-related disorders (ADRD) or frontal-temporal dementia (FTD). The goal of this study was to identify the effect of BINT on molecular networks and their modulation by mutant tau in transgenic (Tg) mice overexpressing the human tau P301L mutation (rTg4510) linked to FTD or non-carriers. The primary focus was on the phosphoproteome because of the prominent role of hyperphosphorylation in neurological disorders. Discrimination learning was assessed following injury in the subsequent 6 weeks, using the automated home-cage monitoring CognitionWall platform. At 40 days post injury, label-free phosphoproteomics was used to evaluate molecular networks in the frontal cortex of mice. Utilizing a weighted peptide co-expression network analysis (WpCNA) approach, we identified phosphopeptide networks tied to associative learning and mossy-fiber pathways and those which predicted learning outcomes. Phosphorylation levels in these networks were inversely related to learning and linked to synaptic dysfunction, cognitive decline, and dementia including Atp6v1a and Itsn1. Low-intensity blast (LIB) selectively increased pSer262tau in rTg4510, a site implicated in initiating tauopathy. Additionally, individual and group level analyses identified the Arhgap33 phosphopeptide as an indicator of BINT-induced cognitive impairment predominantly in rTg4510 mice. This study unveils novel interactions between ADRD genetic susceptibility, BINT, and cognitive decline, thus identifying dysregulated pathways as targets in potential precision-medicine focused therapeutics to alleviate the disease burden among those affected by BINT.
TRIM2 Selectively Regulates Inflammation-Driven Pathological Angiogenesis without Affecting Physiological Hypoxia-Mediated Angiogenesis
Authors: Wong Nathan K. P. , Solly Emma L. , Le Richard , Nankivell Victoria A. , Mulangala Jocelyne , Psaltis Peter J. , Nicholls Stephen J. , Ng Martin K. C. , Bursill Christina A. , Tan Joanne T. M.
Published: March 2024

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2−/− mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2−/− and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.
Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review
Authors: Pereira Francisca , Domingues M. Rosário , Vitorino Rui , Guerra Inês M. S. , Santos Lúcio Lara , Ferreira José Alexandre , Ferreira Rita
Published: March 2024

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.
Arsenic Methyltransferase and Apolipoprotein E Polymorphism in Pregnant Women Exposed to Inorganic Arsenic in Drinking Water in Western Romania
Authors: Pop Laura Ancuta , Berindan-Neagoe Ioana , Bloom Michael S. , Neamtiu Iulia Adina , Bica Cecilia , Gurzau Eugen S.
Published: March 2024

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure.
Low-Dose Sorafenib Promotes Cancer Stem Cell Expansion and Accelerated Tumor Progression in Soft Tissue Sarcomas
Authors: Cruz Sylvia M. , Iranpur Khurshid R. , Judge Sean J. , Ames Erik , Sturgill Ian R. , Farley Lauren E. , Darrow Morgan A. , Crowley Jiwon Sarah , Monjazeb Arta M. , Murphy William J. , Canter Robert J.
Published: March 2024

The cancer stem cell (CSC) hypothesis postulates that heterogeneous human cancers harbor a population of stem-like cells which are resistant to cytotoxic therapies, thus providing a reservoir of relapse following conventional therapies like chemotherapy and radiation (RT). CSCs have been observed in multiple human cancers, and their presence has been correlated with worse clinical outcomes. Here, we sought to evaluate the impact of drug dosing of the multi-tyrosine kinase inhibitor, sorafenib, on CSC and non-CSCs in soft tissue sarcoma (STS) models, hypothesizing differential effects of sorafenib based on dose and target cell population. In vitro, human cancer cell lines and primary STS from surgical specimens were exposed to escalating doses of sorafenib to determine cell viability and expression of CSC marker aldehyde dehydrogenase (ALDH). In vivo, ALDHbright CSCs were isolated, exposed to sorafenib, and xenograft growth and survival analyses were performed. We observed that sarcoma CSCs appear to paradoxically respond to the tyrosine kinase inhibitor sorafenib at low doses with increased proliferation and stem-like function of CSCs, whereas anti-viability effects dominated at higher doses. Importantly, STS patients receiving neoadjuvant sorafenib and RT on a clinical trial (NCT00864032) showed increased CSCs post therapy, and higher ALDH scores post therapy were associated with worse metastasis-free survival. These data suggest that low-dose sorafenib may promote the CSC phenotype in STS with clinically significant effects, including increased tumor growth and higher rates of metastasis formation in sarcoma patients.
Deciphering “Immaturity-Stemness” in Human Epidermal Stem Cells at the Levels of Protein-Coding and Non-Coding Genomes: A Prospective Computational Approach
Authors: Vinasco-Sandoval Tatiana , Lemaître Gilles , Soularue Pascal , Martin Michèle T. , Fortunel Nicolas O.
Published: March 2024

The epidermis hosts populations of epithelial stem cells endowed with well-documented renewal and regenerative functions. This tissue thus constitutes a model for exploring the molecular characteristics of stem cells, which remain to date partially characterized at the molecular level in human skin. Our group has investigated the regulatory functions of the KLF4/TGFB1 and the MAD4/MAX/MYC signaling pathways in the control of the immaturity-stemness versus differentiation fate of keratinocyte stem and precursor cells from human interfollicular epidermis. We described that down-modulation of either KLF4 or MXD4/MAD4 using RNA interference tools promoted an augmented stemness cellular status; an effect which was associated with significant transcriptional changes, as assessed by RNA-sequencing. Here, we have implemented a computational approach aimed at integrating the level of the coding genome, comprising the transcripts encoding conventional proteins, and the non-coding genome, with a focus on long non-coding RNAs (lncRNAs). In addition, datasets of micro-RNAs (miRNAs) with validated functions were interrogated in view of identifying miRNAs that could make the link between protein-coding and non-coding transcripts. Putative regulons comprising both coding and long non-coding transcripts were built, which are expected to contain original pro-stemness candidate effectors available for functional validation approaches. In summary, interpretation of our basic functional data together with in silico biomodeling gave rise to a prospective picture of the complex constellation of transcripts regulating the keratinocyte stemness status.
Gene and lncRNA Profiling of ω3/ω6 Polyunsaturated Fatty Acid-Exposed Human Visceral Adipocytes Uncovers Different Responses in Healthy Lean, Obese and Colorectal Cancer-Affected Individuals
Authors: Tait Sabrina , Calura Enrica , Baldassarre Antonella , Masotti Andrea , Varano Barbara , Gessani Sandra , Conti Lucia , Del Cornò Manuela
Published: March 2024

Colorectal cancer (CRC) is a major life-threatening disease, being the third most common cancer and a leading cause of death worldwide. Enhanced adiposity, particularly visceral fat, is a major risk factor for CRC, and obesity-associated alterations in metabolic, inflammatory and immune profiles in visceral adipose tissue (VAT) strongly contribute to promoting or sustaining intestinal carcinogenesis. The role of diet and nutrition in obesity and CRC has been extensively demonstrated, and AT represents the main place where diet-induced signals are integrated. Among the factors introduced with diet and processed or enriched in AT, ω3/ω6 polyunsaturated fatty acids (PUFAs) are endowed with pro- or anti-inflammatory properties and have been shown to exert either promoting or protective roles in CRC. In this study, we investigated the impact of ex vivo exposure to the ω3 and ω6 PUFAs docosahexaenoic and arachidonic acids on VAT adipocyte whole transcription in healthy lean, obese and CRC-affected individuals. High-throughput sequencing of protein-coding and long non-coding RNAs allowed us to identify specific pathways and regulatory circuits controlled by PUFAs and highlighted an impaired responsiveness of obese and CRC-affected individuals as compared to the strong response observed in healthy lean subjects. This further supports the role of healthy diets and balanced ω3/ω6 PUFA intake in the primary prevention of obesity and cancer.
Oxidative Stress and Bio-Regulation
Authors: Yoshikawa Toshikazu , You Fukka
Published: March 2024

Reactive oxygen species (ROS) and free radicals work to maintain homeostasis in the body, but their excessive production causes damage to the organism. The human body is composed of a variety of cells totaling over 60 trillion cells. Each cell performs different functions and has a unique lifespan. The lifespan of cells is preprogrammed in their genes, and the death of cells that have reached the end of their lifespan is called apoptosis. This is contrary to necrosis, which is the premature death of cells brought about by physical or scientific forces. Each species has its own unique lifespan, which in humans is estimated to be up to 120 years. Elucidating the mechanism of the death of a single cell will lead to a better understanding of human death, and, conversely, the death of a single cell will lead to exploring the mechanisms of life. In this sense, research on active oxygen and free radicals, which are implicated in biological disorders and homeostasis, requires an understanding of both the physicochemical as well as the biochemical aspects. Based on the discussion above, it is clear to see that active oxygen and free radicals have dual functions of both injuring and facilitating homeostasis in living organisms.