Search Results (6,756)

Recent studies have uncovered intriguing connections between Parkinson’s disease (PD) and cancer, two seemingly distinct disease categories. Disulfidptosis has garnered attention as a novel form of regulated cell death that is implicated in various pathological conditions, including neurodegenerative disorders and cancer. Disulfidptosis involves the dysregulation of intracellular redox homeostasis, leading to the accumulation of disulfide bonds and subsequent cell demise. This has sparked our interest in exploring common molecular mechanisms and genetic factors that may be involved in the relationship between neurodegenerative diseases and tumorigenesis. The Gene4PD database was used to retrieve PD differentially expressed genes (DEGs), the biological functions of differential expression disulfidptosis-related genes (DEDRGs) were analyzed, the ROCs of DEDRGs were analyzed using the GEO database, and the expression of DEDRGs was verified by an MPTP-induced PD mouse model in vivo. Then, the DEDRGs in more than 9000 samples of more than 30 cancers were comprehensively and systematically characterized by using multi-omics analysis data. In PD, we obtained a total of four DEDRGs, including ACTB, ACTN4, INF2, and MYL6. The enriched biological functions include the regulation of the NF-κB signaling pathway, mitochondrial function, apoptosis, and tumor necrosis factor, and these genes are rich in different brain regions. In the MPTP-induced PD mouse model, the expression of ACTB was decreased, while the expression of ACTN4, INF2, and MYL6 was increased. In pan-cancer, the high expression of ACTB, ACTN4, and MYL6 in GBMLGG, LGG, MESO, and LAML had a poor prognosis, and the high expression of INF2 in LIHC, LUAD, UVM, HNSC, GBM, LAML, and KIPAN had a poor prognosis. Our study showed that these genes were more highly infiltrated in Macrophages, NK cells, Neutrophils, Eosinophils, CD8 T cells, T cells, T helper cells, B cells, dendritic cells, and mast cells in pan-cancer patients. Most substitution mutations were G-to-A transitions and C-to-T transitions. We also found that miR-4298, miR-296-3p, miR-150-3p, miR-493-5p, and miR-6742-5p play important roles in cancer and PD. Cyclophosphamide and ethinyl estradiol may be potential drugs affected by DEDRGs for future research. This study found that ACTB, ACTN4, INF2, and MYL6 are closely related to PD and pan-cancer and can be used as candidate genes for the diagnosis, prognosis, and therapeutic biomarkers of neurodegenerative diseases and cancers. Full article

New smartphones provide real-time access to GNSS pseudorange, Doppler, or carrier-phase measurement data at 1 Hz. Simultaneously, they can receive corrections broadcast by GNSS reference stations to perform real-time kinematic (RTK) positioning. This study aims at the real-time positioning capabilities of smartphones using raw GNSS measurements as a conventional method and proposes an improvement to the positioning through the integration of Inertial Navigation System (INS) measurements. A U-Blox GNSS receiver, model ZED-F9R, was used as a benchmark for comparison. We propose an enhanced ambiguity resolution algorithm that integrates the traditional LAMBDA method with an adaptive thresholding mechanism based on real-time quality metrics. The RTK/INS fusion method integrates RTK and INS measurements using an extended Kalman filter (EKF), where the state vector x includes the position, velocity, orientation, and their respective biases. The innovation here is the inclusion of a real-time weighting scheme that adjusts the contribution of the RTK and INS measurements based on their current estimated accuracy. Also, we use the tightly coupled (TC) RTK/INS fusion framework. By leveraging INS data, the system can maintain accurate positioning even when the GNSS data are unreliable, allowing for the detection and exclusion of abnormal GNSS measurements. However, in complex urban areas such as Qazvin City in Iran, the fusion method achieved positioning accuracies of approximately 0.380 m and 0.415 m for the Xiaomi Mi 8 and Samsung Galaxy S21 Ultra smartphones, respectively. The subsequent detailed analysis across different urban streets emphasized the significance of choosing the right positioning method based on the environmental conditions. In most cases, RTK positioning outperformed Single-Point Positioning (SPP), offering decimeter-level precision, while the fusion method bridged the gap between the two, showcasing improved stability accuracy. The comparative performance between the Samsung Galaxy S21 Ultra and Xiaomi Mi 8 revealed minor differences, likely attributed to variations in the hardware design and software algorithms. The fusion method emerged as a valuable alternative when the RTK signals were unavailable or impractical. This demonstrates the potential of integrating RTK and INS measurements for enhanced real-time smartphone positioning, particularly in challenging urban environments. Full article

We analyzed the whole genome sequences (WGS) and antibiograms of 35 Enterobacter isolates, including E. hormaechei and E. asburiae, and the recently described E. bugandensis, E. kobei, E. ludwigii, and E. roggenkampii species. Isolates were obtained from human blood and urinary tract infections in patients in the United States. Our goal was to understand the genetic diversity of antimicrobial resistance genes and virulence factors among the various species. Thirty-four of 35 isolates contained an AmpC class bla_ACT allele; however, the E. roggenkampii isolate contained bla_MIR-5. Of the six Enterobacter isolates resistant to ertapenem, imipenem, and meropenem, four harbored a carbapenemase gene, including bla_KPC or bla_NDM. All four isolates were mCIM-positive. The remaining two isolates had alterations in ompC genes that may have contributed to the resistance phenotype. Interpretations of cefepime test results were variable when disk diffusion and automated broth microdilution results were compared due to the Clinical Laboratory and Standards Institute use of the “susceptible dose-dependent” classification. The diversity of the bla_ACT alleles paralleled species identifications, as did the presence of various virulence genes. The classification of recently described Enterobacter species is consistent with their resistance gene and virulence gene profiles. Full article

Crop monitoring with unmanned aerial vehicles (UAVs) has the potential to reduce field monitoring costs while increasing monitoring frequency and improving efficiency. However, the utilization of RGB-based UAV imagery for crop-specific monitoring, especially for sugarcane, remains limited. This work proposes a UAV platform with an RGB camera as a low-cost solution to monitor sugarcane fields, complementing the commonly used multi-spectral methods. This new approach optimizes the RGB vegetation indices for accurate prediction of sugarcane growth, providing many improvements in scalable crop-management methods. The images were captured by a DJI Mavic Pro drone. Four RGB vegetation indices (VIs) (GLI, VARI, GRVI, and MGRVI) and the crop surface model plant height (CSM_PH) were derived from the images. The fractional vegetation cover (FVC) values were compared by image classification. Sugarcane plant height predictions were generated using two machine learning (ML) algorithms—multiple linear regression (MLR) and random forest (RF)—which were compared across five predictor combinations (CSM_PH and four VIs). At the early stage, all VIs showed significantly lower values than later stages (p < 0.05), indicating an initial slow progression of crop growth. MGRVI achieved a classification accuracy of over 94% across all growth phases, outperforming traditional indices. Based on the feature rankings, VARI was the least sensitive parameter, showing the lowest correlation (r < 0.5) and mutual information (MI < 0.4). The results showed that the RF and MLR models provided better predictions for plant height. The best estimation results were observed withthe combination of CSM_PH and GLI utilizing RF model (R² = 0.90, RMSE = 0.37 m, MAE = 0.27 m, and AIC = 21.93). This study revealed that VIs and the CSM_PH derived from RGB images captured by UAVs could be useful in monitoring sugarcane growth to boost crop productivity. Full article

Sepsis is an insidious and frequent condition of severe inflammation due to infections. Several biomarkers have been established for initial screening, but the non-specific nature of the existing biomarkers has led to the investigation of more sensitive and specific tools, such as microRNAs (miRs). These non-coding RNAs are involved in several diseases, including sepsis, due to their roles in cellular homeostasis. Herein, a literature overview was attempted to distinguish the most prominent miRs identified in septic conditions and their usefulness in diagnosis, prognosis and even classification of sepsis. miRs implicated in the regulation of pro and anti-inflammatory mechanisms, such as MIR-146a, MIR-155, MIR-181b, MIR-223-5p, MIR-494-3p, MIR-2055b, MIR-150 and MIR-143 have been pinpointed as acceptable testing tools. Furthermore, the use of miRs as screening panels, specific for septic parameters, such as type of causal infection, inflammation immune pathways affected (NF-kB, STAT/JACK), organs inflicted, as well as parallel screening of certain miRs alongside other long non-coding RNAs (LNCs), as co-regulators of sepsis progression. Overall, miRs exhibit benefits in terms of specificity and sensitivity, as well as practical ease of use and test stability. Furthermore, miRs could offer valuable insights into the molecular basis of disease causality and provide valuable therapeutic information. Full article

We present a comprehensive investigation of mid-infrared (MIR) flux variability at 3.4 μm (W1 band) for a large sample of 3816 blazars, using Wide-field Infrared Survey Explorer (WISE) data through December 2022. The sample consists of 1740 flat-spectrum radio quasars (FSRQs), 1281 BL Lac objects (BL Lacs), and 795 blazars of uncertain type (BCUs). Considering Fermi Large Area Telescope detection, we classify 2331 as Fermi blazars and 1485 as non-Fermi blazars. Additionally, based on synchrotron peak frequency, the sample includes 2264 low-synchrotron peaked (LSP), 512 intermediate-synchrotron peaked (ISP), and 655 high-synchrotron peaked (HSP) sources. We conduct a comparative analysis of short- and long-term intrinsic variability amplitude (σm), duty cycle (DC), and ensemble structure function (ESF) across blazar subclasses. The median short-term σm values were 0.181−0.106+0.153, 0.104−0.054+0.101, 0.135−0.076+0.154, 0.173−0.097+0.158, 0.177−0.100+0.156, 0.096−0.050+0.109, and 0.106−0.058+0.100 mag for FSRQs, BL Lacs, Fermi blazars, non-Fermi blazars, LSPs, ISPs, and HSPs, respectively. The median DC values were 71.03−22.48+14.17, 64.02−22.86+16.97, 68.96−25.52+15.66, 69.40−22.17+14.42, 71.24−21.36+14.25, 63.03−33.19+16.93, and 64.63−24.26+15.88 percent for the same subclasses. The median long-term σm values were 0.137−0.105+0.408, 0.171−0.132+0.206, 0.282−0.184+0.332, 0.071−0.062+0.143, 0.218−0.174+0.386, 0.173−0.132+0.208, and 0.101−0.077+0.161 mag for the same subclasses, respectively. Our results reveal significant differences in 3.4 μm flux variability among these subclasses. FSRQs (LSPs) exhibit larger σm and DC values compared to BL Lacs (ISPs and HSPs). Fermi blazars display higher long-term σm but lower short-term σm relative to non-Fermi blazars, while DC distributions between the two groups are similar. ESF analysis further confirms the greater variability of FSRQs, LSPs, and Fermi blazars across a wide range of time scales compared to BL Lacs, ISPs/HSPs, and non-Fermi blazars. These findings highlight a close correlation between MIR variability and blazar properties, providing valuable insights into the underlying physical mechanisms responsible for their emission. Full article

MicroRNA-27a-5p (miR-27a-5p) was significantly upregulated in dental pulp inflammation, yet its underlying mechanisms remain unclear. This study investigated the effect of miR-27a-5p on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS). LPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-κB inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated the expression of proinflammatory cytokines, NF-κB activity, and the expression of NF-κB signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3’-UTR of TAB1. siTAB1 downregulated NF-κB activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-κB activity, and NF-κB signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimic ex vivo. MiR-27a-5p, whose expression was induced by NF-κB signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-κB signaling. In particular, TAB1, a potent NF-κB activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-κB signaling pathway, on pulp inflammation. Full article

MiR-155 is a multifunctional microRNA involved in many biological processes. Since miR-155 is overexpressed in several pathologies, its detection deserves high interest in clinical diagnostics. Biosensing approaches often exploit the hybridization of miR-155 with its complementary strand. Molecular Dynamics (MD) simulations were applied to investigate the complex formed by miR-155 and its complementary strand in aqueous solution with Na+ and Cl− ions at ionic strengths in the 100–400 mM range, conditions commonly used in biosensing experiments. We found that the main structural properties of the duplex are preserved at all the investigated ionic strengths. The radial distribution functions of both Na+ and Cl− ions around the duplex show deviation from those of bulk with peaks whose relative intensity depends on the ionic strength. The number of ions monitored as a function of the distance from the duplex reveals a behavior reminiscent of the counterion condensation near the duplex surface. The occurrence of such a phenomenon could affect the Debye length with possible effects on the sensitivity in biosensing experiments. Full article

Low fertility is the main cause of the low productivity in beef cattle and is mainly associated with a lack of conception after fertilization. The establishment of early pregnancy in cattle is a complex physiological process, and embryo implantation is crucial for the successful establishment of pregnancy. Exosomal miRNAs play an important role in regulating mammalian embryo implantation and development. This study used synchronous estrus technology to extract exosomes from bovine serum at 0, 14, and 21 days of early pregnancy and analyzed the expression profile of exosomal miRNAs through RNA-seq technology. We identified 472 miRNA precursor sequences and 367 mature miRNA sequences in the three sample groups, with the majority of the miRNAs having high abundance. Differentially expressed miRNAs (DEmiRNAs) were screened, and 20 DEmiRNAs were obtained. The differential expression analysis results show that compared to day 0, there were 15 DEmiRNAs in the serum on day 14 and 5 on day 21 of pregnancy. Compared to the 14th day of pregnancy, there were eight DEmiRNAs in the serum on the 21st day of pregnancy. Bioinformatics analysis shows that the target genes of DEmiRNAs regulated the signaling pathways closely related to early pregnancy, including the VEGF, NF-κB, and MAPK signaling pathways. In addition, the newly discovered miRNAs were bta-miR-3604, bta-miR-2889, bta-miR-3432a, and bta-miR-409b. These results provide a theoretical reference for screening the molecular markers for early pregnancy establishment and maternal recognition of pregnancy (MRP) in cattle and new ideas for shortening the calving interval in cows. Full article

Myocarditis is an inflammatory disease that may lead to dilated cardiomyopathy. Viral infection of the myocardium triggers immune responses, which involve, among others, macrophage infiltration, oxidative stress, expression of pro-inflammatory cytokines, and microRNAs (miRNAs). The cardioprotective role of estrogen in myocarditis is well documented; however, sex differences in the miRNA expression in chronic myocarditis are still poorly understood, and studying them further was the aim of the present study. Male and female ABY/SnJ mice were infected with CVB3. Twenty-eight days later, cardiac tissue from both infected and control mice was used for real-time PCR and Western blot analysis. NFκB, IL-6, iNOS, TNF-α, IL-1β, MCP-1, c-fos, and osteopontin (OPN) were used to examine the inflammatory state in the heart. Furthermore, the expression of several inflammation- and remodeling-related miRNAs was analyzed. NFκB, IL-6, TNF-α, IL-1β, iNOS, and MCP-1 were significantly upregulated in male mice with CVB3-induced chronic myocarditis, whereas OPN mRNA expression was increased only in females. Further analysis revealed downregulation of some anti-inflammatory miRNA in male hearts (let7a), with upregulation in female hearts (let7b). In addition, dysregulation of remodeling-related miRNAs (miR27b and mir199a) in a sex-dependent manner was observed. Taken together, the results of the present study suggest a sex-specific expression of pro-inflammatory markers as well as inflammation- and remodeling-related miRNAs, with a higher pro-inflammatory response in male CVB3 myocarditis mice. Full article

Multiple sclerosis (MS) is a chronic autoimmune disease with an unknown etiology. The purpose of this research was to assess miR-223, miR-146a, and miR-193a in acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) mice to consider the possible role of these genes in the pathogenesis of MS. EAE induction was given by myelin oligodendrocyte glycoprotein peptide on female C57BL/6 mice. Clinical scores and other criteria were followed daily until day 21 for the acute group and day 77 for the chronic group. At the end of the course, inflammation and demyelination of the central nervous system (CNS) were assessed by histological analysis. MicroRNA expression levels were assessed by real-time PCR. EAE development attenuated in the chronic group, and histological analysis showed less infiltration and demyelination in the chronic group compared to the acute group. The upper expression of miR-223 is demonstrated in the acute phase of EAE. Moreover, the expression levels of miR-146a and miR-193a decreased in the chronic phase of EAE. MiR-223 showed a highly coordinated elevation in the acute phase both in vivo and in vitro. MiR-146a shares a pathway with miR-223 through effecting IL-6 expression. Further studies are needed to reveal their impact on EAE and possible applications as drug targets and biomarkers. Full article

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets. Full article

Krüppel-like factors (KLFs) are a class of fundamental transcription factors that are widely present in various eukaryotes from nematodes to humans, named after their DNA binding domain which is highly homologous to the Krüppel factor in fruit flies. To investigate the composition, organization, and evolutionary trajectory of KLF gene family members in chickens, in our study, we leveraged conserved sequences of KLF genes from representative classes across fish, amphibians, birds, and mammals as foundational sequences. Bioinformatic tools were employed to perform homology alignment on the chicken genome database, ultimately identifying the KLF family members present in chickens. The gene structure, phylogenetic analysis, conserved base sequences, physicochemical properties, collinearity analysis, and protein structure were then analyzed using bioinformatic tools. Additionally, the impact of miRNA-22, related to poultry lipid metabolism, on the expression of the KLF gene family in the liver, heart, and muscle of Qingyuan partridge chickens was explored. The results showed that: (1) compared to fish, the KLF family in birds is more closely related to mammals and amphibians; (2) KLFs within the same subgroups are likely to be derived from a common ancestral gene duplication; (3) KLF3/8/12 in the same subgroup may have some similar or overlapping functions; (4) the motif 4 of KLF5 was most likely lost during evolution; (5) KLF9 may perform a similar function in chickens and pigs; (6) there are collinear relationships between certain KLF genes, indicating that there are related biomolecular functions between these KLF genes; (7) all members of the KLF family in chickens are non-transmembrane proteins; and (8) interference and overexpression of miRNA-22 in Qingyuan partridge chickens can affect the expression levels of KLF genes in liver, heart, and muscle. Full article

Cow milk possesses high nutritional value due to its rich array of beneficial fatty acids. It is important to understand the mechanisms involved in lipid metabolism in dairy cows. These mechanisms are driven by a complex molecular regulatory network. In addition, there are many regulatory factors involved in the process of fatty acid metabolism, including transcription factors and non-coding RNAs, amongst others. MicroRNAs (miRNAs) can regulate the expression of target genes and modulate various biological processes, including lipid metabolism. Specifically, miR-206 has been reported to impair lipid accumulation in nonruminant hepatocytes. However, the effects and regulatory mechanisms of miR-206 on lipid metabolism in bovine mammary cells remain unclear. In the present study, we investigated the effects of miR-206 on lipid-related genes and TAG accumulation. The direct downstream gene of miR-206 was subsequently determined via a dual-luciferase assay. Finally, the fatty acid content of bovine mammary epithelial cells (BMECs) upon ELOVL6 inhibition was examined. The results revealed that miR-206 overexpression significantly decreased triacylglycerol (TAG) concentration and abundances of the following: acetyl-coenzyme A carboxylase alpha (ACACA); fatty acid synthase (FASN); sterol regulatory element binding transcription factor 1 (SREBF1); diacylglycerol acyltransferase 1 (DGAT1); 1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT6); lipin 1 (LPIN1); and fatty acid elongase 6 (ELOVL6). Overexpression of miR-206 was also associated with an increase in patatin-like phospholipase domain-containing 2 (PNPLA2), while inhibition of miR-206 promoted milk fat metabolism in vitro. In addition, we found that ELOVL6 is a direct target gene of miR-206 through mutation of the binding site. Furthermore, ELOVL6 intervention significantly decreased the TAG levels and elongation indexes of C16:0 and C16:1n-7 in BMECs. Finally, ELOVL6 siRNA partially alleviated the increased TAG accumulation caused by miR-206 inhibition. In summary, we found that miR-206 inhibits milk fatty acid synthesis and lipid accumulation by targeting ELOVL6 in BMECs. The results presented in this paper may contribute to the development of strategies for enhancing the quality of cow milk and its beneficial fatty acids, from the perspective of miRNA–mRNA networks. Full article

RaTG13 is phylogenomically the closest related coronavirus to SARS-CoV-2; consequently, understanding the provenance of this high-value genome sequence is important in understanding the origin of SARS-CoV-2. While RaTG13 was described as being generated from a Rhinolophus affinis fecal swab obtained from a mine in Mojiang, Yunnan, numerous investigators have pointed out that this is inconsistent with the low proportion of bacterial reads in the sequencing dataset. Metagenomic analysis confirms that only 10.3% of small-subunit (SSU) rRNA sequences in the dataset are bacterial, which is inconsistent with a fecal sample. In addition, the bacterial taxa present in the sample are shown to be inconsistent with fecal material. The assembly of mitochondrial SSU rRNA sequences in the dataset produces a sequence 98.7% identical to R. affinis mitochondrial SSU rRNA, indicating that the sample was generated from R. affinis or a closely related species. In addition, 87.5% of the reads in the dataset map to the Rhinolophus ferrumequinum genome, and 62.2% of these map to protein-coding genes, indicating that the dataset represents a Rhinolophus sp. transcriptome rather than a fecal swab sample. Differential gene expression analysis reveals that the pattern of expressed genes in the RaTG13 dataset is similar to that of RaTG15, which was also collected from the Mojiang mine. GO enrichment analysis reveals the overexpression of spermatogenesis- and olfaction-related genes in both datasets. This observation is consistent with a mating plug found in female Rhinolophid bats and suggests that RaTG13 was mis-sampled from such a plug. A validated natural provenance of the RaTG13 dataset throws into relief the unusual features of the SARS-CoV-2 genome. Full article