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Aging is associated with the accumulation of damaged and misfolded proteins through a decline in the protein homeostasis (proteostasis) machinery, leading to various age-associated protein misfolding diseases such as Huntington's or Parkinson's. The efficiency of cellular stress response pathways also weakens with age, further contributing to the failure to maintain proteostasis. MicroRNAs (miRNAs or miRs) are a class of small, non-coding RNAs (ncRNAs) that bind target messenger RNAs at their 3′UTR, resulting in the post-transcriptional repression of gene expression. From the discovery of aging roles for lin-4 in C. elegans, the role of numerous miRNAs in controlling the aging process has been uncovered in different organisms. Recent studies have also shown that miRNAs regulate different components of proteostasis machinery as well as cellular response pathways to proteotoxic stress, some of which are very important during aging or in age-related pathologies. Here, we present a review of these findings, highlighting the role of individual miRNAs in age-associated protein folding and degradation across different organisms. We also broadly summarize the relationships between miRNAs and organelle-specific stress response pathways during aging and in various age-associated diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cell carcinomas (RCCs) can build a so-called tumor thrombus and grow into the renal vein and the vena cava, thereby representing a high-risk situation for affected patients. Nevertheless, there are substantial differences in the clinical courses of RCC patients with a tumor thrombus. Currently, there is no established biomarker which helps identifying patients with a substantial risk of tumor relapse or even cancer-related death. Previously, members of our group discovered a signature of three small RNA molecules (specifically: microRNAs) in RCC tissue, which significantly predicted cancer-related survival. In this study, we validated this signature in a larger cohort of patients suffering from RCCs with a tumor thrombus. Notably, stratifying our patients according to this microRNA signature nearly separated our cohort into two halves, which significantly differed in terms of clinical risk. Our research could help identifying high-risk patients in need for additional therapy, while sparing others from unnecessary treatments. (1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCCIVC) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier—containing miR-21-5p, miR-126-3p and miR-221-3p expression—which significantly predicted the cancer-specific survival (CSS) of ccRCCIVC patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCCIVC, we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable Cox regression. Referring to the previously established risk classifier, we performed Kaplan–Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the development of metastasis during follow-up, and cancer-related death. In Kaplan–Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCCIVC according to CSS. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCCIVC cohort. [ABSTRACT FROM AUTHOR]

Several microRNAs have emerged as regulators of pathways that control aging. For example, miR‐228 is required for normal lifespan and dietary restriction (DR) mediated longevity through interaction with PHA‐4 and SKN‐1 transcription factors in Caenorhabditis elegans. miR‐229,64,65, and 66, a cluster of microRNAs located adjacent to each other on chromosome III, are in the same family as miR‐228, albeit with slight differences in the miR‐228 seed sequence. We demonstrate that, in contrast to the anti‐longevity role of miR‐228, the miR‐229‐66 cluster is required for normal C. elegans lifespan and for the longevity observed in mir‐228 mutants. miR‐229‐66 is also critical for lifespan extension observed under DR and reduced insulin signaling (IIS) and by constitutive nuclear SKN‐1. Both DR and low‐IIS upregulate the expression of the miRNA cluster, which is dependent on transcription factors PHA‐4, SKN‐1, and DAF‐16. In turn, the expression of SKN‐1 and DAF‐16 requires mir‐229,64,65,66. miR‐229‐66 targets the odd‐skipped‐related transcription factor, odd‐2 to regulate lifespan. Knockdown of odd‐2 increases lifespan, suppresses the short lifespan of mir‐229,64,65,66(nDf63) III mutants, and alters levels of SKN‐1 in the ASI neurons. Together with SKN‐1, the miRNA cluster also indirectly regulates several genes in the xenobiotic detoxification pathway which increases wild‐type lifespan and significantly rescues the short lifespan of mir‐229,64,65,66(nDf63) III mutants. Thus, by interacting with SKN‐1, miR‐229‐66 transduces the effects of DR and low‐IIS in lifespan extension in C. elegans. Given that this pathway is conserved, it is possible that a similar mechanism regulates aging in more complex organisms. [ABSTRACT FROM AUTHOR]

Since tick-borne diseases (TBDs) incidence, both in human and animal populations, is increasing worldwide, there is the need to assess the presence, distribution and prevalence of tick-borne pathogens. Reliable estimates on tick-borne pathogens (TBPs) prevalence represent the public health foundation to create risk maps and take effective prevention and control actions against TBDs. Tick surveillance consists of collecting and testing (usually in pools) thousands of specimens. Construction and analysis of tick pools represent a challenge due to the complexity of tick-borne pathogens and tick-borne diseases ecology. The aim of this study is to provide a practical guideline on appropriate pooling strategies and statistical analysis of infection prevalence through: (i) reporting the different pooling strategies and statistical methodologies commonly used to calculate pathogen prevalence in tick populations and (ii) practical comparison between statistical methods utilising a real dataset of infection prevalence in ticks collected in Northern Italy. Reporting detailed information on tick pool composition and size is as important as the correct TBPs prevalence estimation. Among the prevalence indexes, we suggest using maximum-likelihood estimates of pooled prevalence instead of minimum infection rate or pool positivity rate given the merits of the method and availability of software. [ABSTRACT FROM AUTHOR]

Copyright of Theological Review / Bogoslovska Smotra is the property of University of Zagreb, Catholic Faculty of Theology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Theological Review / Bogoslovska Smotra is the property of University of Zagreb, Catholic Faculty of Theology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Theological Review / Bogoslovska Smotra is the property of University of Zagreb, Catholic Faculty of Theology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Theological Review / Bogoslovska Smotra is the property of University of Zagreb, Catholic Faculty of Theology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Theological Review / Bogoslovska Smotra is the property of University of Zagreb, Catholic Faculty of Theology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In recent decades, significant progress has been achieved in understanding the mechanisms of disturbance and restoration of consciousness in patients after severe brain damage resulting in prolonged disorders of consciousness (pDOC). MicroRNAs (miRs) may be potential candidates as possible biomarkers for the classification of disease subtypes, and prognosis in patients with pDOC. The aim of the study was to analyze miRs expression levels (hsa-miR-21-5p, hsa-miR-93-5p, hsa-miR-191-5p, mmu-miR-499-5p, hsa-let-7b-5p) by a real-time polymerase chain reaction in plasma and cerebrospinal fluid (CSF) from patients with pDOC and to identify a potential biomarker for dividing patients into groups according to disease severity. We analyzed the levels of investigated miRs in pDOC patients, divided by etiology, CRSI, and the total group compared with controls. Our results showed that dividing patients with pDOC into groups according to the etiology of the disease resulted in the most significant differences in the levels of miR-93, -21, and -191 in CSF and plasma samples between groups of patients. Among the analyzed miRs, we did not find a marker that would help to distinguish VS/UWS patient groups from MCS. Examining of miRs as possible prognostic markers in patients with pDOC, the starting point seems to be the cause that led to the development of the disease. [ABSTRACT FROM AUTHOR]

The scientific review presents the mechanisms of action of cytoplasmic miRNAs, namely posttranscriptional silencing: the TNRC6-associated mechanism of miRNA-mediated mRNA degradation. To write the article, information was searched using databases Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka. It is known that in the cytoplasm of cells in cases of short region, miRNA complementarities cause posttranscriptional silencing, using the first of the main molecular mechanisms: the TNRC6-associated mechanism of miRNA-mediated mRNA degradation. Mammalian AGO proteins have been shown to contain the conserved m7G-cap-binding protein motif (known as the MID domain), which is required to induce microRNA-mediated translation repression. After binding of this AGO motif to ­microRNAs, TNRC6 proteins (GW182) are recruited that, in turn, recruits various proteins (PABPC1, PAN3 and NOT1) involved in the induction of the target gene silencing. The authors state that tryptophan residues, which are placed in the hydrophobic pockets of TNRC6 protein partners, cause a high degree of affinity and specificity of interactions. Scientists believe that the TNRC6 protein when interacting with AGO proteins can simultaneously use three GW/WG repeats (motif 1, motif 2 and hook motif), which are located in the Argonaute-binding domain. Therefore, the TNRC6 protein can bind to three AGO molecules simultaneously. TNRC6 proteins are known to be PABP-interac­ting proteins whose interaction with PABP is mediated by conservative PABP-binding motif 2. TNRC6 proteins have been shown to interact with the cytoplasmic PABPC1 protein during mRNA translation and stabilization. It is shown that the CCR4-NOT protein complex is a highly conserved multifunctional multiprotein formation having 3’-5’-exoribonuclease activity, due to which it controls mRNA metabolism. Thus, the TNRC6-associated me­chanism of miRNA-mediated mRNA degradation in the cytoplasm of the cell causes posttranscriptional silencing. In this mechanism, there is an interaction of TNRC6 with PABPC1 protein, recruitment of deadenylating complexes PAN2-PAN3 and CCR4-NOT by the TNRC6 proteins.

Combining near-infrared (NIR) and mid-infrared (MIR) spectroscopy to cover both the fundamental and overtone combination molecular vibrational resonances allows more robust analytical methods to be used, such as two-dimensional correlation spectroscopy. However, due to the strong differences in molar absorption coefficients and transparency of the optical material, it is inherently difficult to perform NIR and MIR spectroscopy on aqueous samples using a single instrument. Combining spectra from different instruments and sample presentations can result in unwanted spectral variations, which can influence the prediction models and mitigate the advantages of the combination approaches. In this work, a more consistent instrument response is achieved by combining a single supercontinuum (SC) laser spanning from 1000 to 4000 nm as the light source, with an attenuated total reflection crystal and a transmission cuvette in a single-path configuration. Using this approach, NIR–MIR correlation spectroscopy is demonstrated using a set of 22 aqueous samples with varying concentrations of ethanol, sucrose, and ʟ-proline. [ABSTRACT FROM AUTHOR]

The scientific review presents the mechanisms of action of cytoplasmic miRNAs, namely miRNA-mediated posttranslational silencing. To write the article, information was searched ­using Scopus, Web of Science, MedLine, PubMed, Google Scho­lar, EMBASE, Global Health, The Cochrane Library, CyberLe­ninka databases. It is stated that protein synthesis is a complex process which involved many regulators. It is known that the translation process consists of three main stages: initiation, elongation of the polypeptide chain and termination. It is presented that dozens of “basic” factors and numerous accessory proteins, both regulators and repressors of the process, take part in the translation initiation. The authors provide a kinetic model proposed by Christopher S. Fraser. According to this model, translation initiation is a ranked process. It is emphasized that subsequently the ribosome interacts with the beginning of the coding nucleotide sequence of mRNA. Modifications of nucleotides by elongation factors in the anticodon of tRNA regulate the dynamics of ribosome function and, thus, fine-tune the rate of protein synthesis. The authors state that translation termination is induced by the interaction of the decoding A-region of the ribosome with one of the three stop codons (UAA, UAG or UGA) of mRNA. “Termination factors” are also involved in the termination of translation. Scientists say that the main factors that regulate the functional activity of mRNA act on the cap and poly(A)tail, which protects mRNA from exonuclease action. Thus, various proteins surround mRNA molecule in the cell and support the existence and functional activity of mRNA. Each mRNA region interacts with a specific spectrum of RNA-binding proteins. The initiation of translation is a ranked process and is ­inextricably linked with mRNA degradation. It is widely believed that translation is largely controlled during the initiation period. The mechanism of silencing caused by mRNA degradation depends on the size of the complementary region.

The scientific review presents the mechanisms of action of cytoplasmic miRNAs, namely the relationship between miRNA and mRNA molecules and the influence of miRNAs on translation. To write the article, information was searched using Scopus, Web of Science, MEDLINE, PubMed, Google Scholar, Embase, Global Health, The Cochrane Library, CyberLeninka databases. The authors state that the interaction of microRNA and mRNA requires the presence in the region of the 3'-end of the mRNA molecule of small nucleotide sequences — miRNA regulatory elements, which are complementary to the sequences of the “seed” region of microRNA. It is known that only six nucleotide matches in the “seed” region (position 2–8) are required to initiate the interaction of microRNA with the mRNA target. It is emphasized that the interaction of miRNA with mRNA depends on the availability of the mRNA binding site. The authors suggest that accessory proteins are involved in the interaction of microRNA and mRNA. It is known that the process of mRNA and miRNA hybridization depends on the presence of SNP. Scientists believe that the main function of cytoplasmic miRNAs is to regulate the activity of protein synthesis. It is presented that microRNAs can repress and activate the mRNA translation process. In addition, some miRNAs are able to both inhibit and enhance the translation of mRNA depending on specific local conditions and the spectrum of microenvironmental factors. Thus, the mechanism of action of cytoplasmic miRNAs is realized due to the interaction of miRNAs and mRNAs, which is due to the presence of complementary nucleotide sequences of special regions. The interaction of miRNAs with mRNAs depends on the availability of the mRNA binding site, the involvement of accessory proteins, and the presence of SNP. Violations of microRNA-mRNA interactions lead to the development of pathological processes. Cytoplasmic miRNAs perform their main function, namely the regulation of protein synthesis activity, due to miRNA-mediated repression and activation of mRNA translation.

The scientific review presents the mechanisms of action of intranuclear miRNAs, namely microRNA-mediated regulation of the non-coding RNA (ncRNA) transcriptome and alternative splicing. To write the article, information was searched using Scopus, Web of Science, MedLine, PubMed, Google Scholar, EMBASE, Global Health, The Cochrane Library, CyberLeninka databases. It is emphasized that a significant effect on the composition of the transcriptome is provided by microRNAs in the RNA-induced silencing complex that induce posttranscriptional degradation of long ncRNAs localized in the cell nucleus. Scientists believe that long ncRNAs are involved in the epigenetic regulation of gene silencing through chromatin remodeling. It is shown that long ncRNAs are actively involved in the development of some liver diseases. It is reported that the most important mechanism for expanding the spectrum of the transcriptome in the cell is the alternative splicing of pre-mRNA. The authors present the results of scientific studies that show that pre-mRNA of more than 90 % of human genes are subjected to alternative splicing. It is presented that splicing is performed by a specialized macromolecular formation — suprasplicesome, which is a megacomplex (21 MDA) of nuclear ribonucleroprotein. It is shown that scientists have proposed two models of epigenetic regulation of splicing: kinetic and recruitment one. The authors reveal the main provisions of these models. MicroRNAs are actively involved in splicing. Liver disease may be based on a deficiency of splicing factors and deregulation of alternative splicing caused by the action of miRNAs. Disorders of alternative splicing, which stimulate proliferation, prevent apoptosis and support cell transformation, are a pathognomonic phenomenon in malignant tumors. Thus, the constituent mechanisms of action of intranuclear miRNAs are alteration of the ncRNAs transcriptome and participation in the regulation of alternative splicing. MicroRNA-mediated regulation of the stability of long ncRNAs causes a change in the spectrum of activity of expression of epigenetically regulated genes. Long ncRNAs are actively involved in the development of some liver diseases. Alternative splicing is an integral part of cell differentiation and contributes to the formation of tissue specificity. Alternative splicing and generation of various isoforms of proteins determine molecular consequences that cause the deve­lopment of various pathological conditions.

Aim:MicroRNAs (miR) have an essential role on the regulated gene expression in the human genome. In recent years, a specific miR group was called to angio-miRs due to their role in the angiogenesis, and recent study showed that they involved in the pathogenesis of gliomas. In this study, we investigated the changes in the expression profiles of angio-miRs in glioblastoma cells and identified relationship between these genes and invasion and tumor growth.Materials and Methods:In this study, glioblastoma tumor spheroids were obtained using the human glioblastoma cell line U-87 MG. 50 nM, 100 nM and 200 nM ruxolitinib were applied to tumor spheroids for 48 hours by using Matrigell method. Tumor volume and invasion formation relative % tumor growth and relative % invasion area were measured in glioblastoma tumor spheroids after 48 hours of treatment. At the same time, quantitative real-time polymerase chain reaction (qRT-PZR) analysis was performed and miR expression profiles were determined. The most important (importance features) miRNAs selected along with the heatmap and volcano plot analyzes were used to display the pattern of the differentially expressed miRs using normalized miR expression profiles.Results:When the effect of 50 nM, 100 nM and 200 nM ruxolitinib administration to tumor spheroids on tumor volume and invasion was evaluated, a significant difference was found at each dose applied. However, at the dose of 200 nM ruxolitinib, it was observed that the inhibitory effect of tumor invasion was the highest. When miR expression profiles obtained by qRT-PZR test with 200 nM ruxolitinib adminisration were evaluated, it was determined that the expression profiles of 10 miRs increased and the expression profiles of 4 miRs decreased.Conclusion:In conclusion, angio-miR expression profiles are important because they enable us to better understand the prognostic process of gliomas. Because of their multiple silencing properties, they may contribute to the clinic with further studies in terms of their use as new therapeutic targets and prognostic biomarkers for glioblastoma.

Epiretinal membranes (ERMs) are the result of fibro-cellular proliferation that cause distortion and impairment of central vision. We hypothesized that select microRNAs (miRs) regulate retinal fibro-proliferation and ERM formation. Following IRB approval, a pilot study was performed in patients presenting for retina surgery with and without clinical ERMs. Total RNA was isolated from ERM tissue and controls from non-ERM vitreous and subjected to miR profiling via microarray analysis. MiR-494 was identified as the only miR selectively expressed at significantly greater levels, and in silico analysis identified p27 as a putative fibroproliferative gene target of miR-494. In vitro testing of miR-494 and p27 in fibrotic transformation was assessed in spontaneously immortalized human retinal pigment epithelial (RPE) and human Müller cell lines, stimulated to transform into a fibroproliferative state via transforming growth factor beta (TGFβ). Fibroproliferative transformation was characterized by de novo cellular expression of alpha smooth muscle actin (αSMA). In both RPE and Müller cells, both TGFβ and miR-494 mimic decreased p27 expression. In parallel experiments, transfection with p27 siRNA augmented TGFβ-induced αSMA expression, while only in RPE cells did co-transfection with miR-494 inhibitor decrease αSMA levels. These results demonstrate that miR-494 augments fibrotic transformation in both Müller cells and RPEs, however only in RPEs does miR-494 mediate fibrotic transformation via p27. As p27 is known to regulate cellular proliferation and differentiation, future studies should extend clinical testing of miR-494 and/or p27 as a potential novel non-surgical therapy for ERMs, as well as identify relevant miR-494 targets in Müller cells.

BackgroundPrevious work showed that muscle-derived stem cells (MDSCs) exposed long-term to the milieu of uncontrolled type 2 diabetes (UC-T2D) in male obese Zucker (OZ) rats, were unable to correct the associated erectile dysfunction and the underlying histopathology when implanted into the corpora cavernosa, and were also imprinted with a noxious gene global transcriptional signature (gene-GTS), suggesting that this may interfere with their use as autografts in stem cell therapy.AimTo ascertain the respective contributions of dyslipidemia and hyperglycemia to this MDSC damage, clarify its mechanism, and design a bioassay to identify the damaged stem cells.MethodsEarly diabetes MDSCs and late diabetes MDSCs were respectively isolated from nearly normal young OZ rats and moderately hyperglycemic and severely dyslipidemic/obese aged rats with erectile dysfunction. Monolayer cultures of early diabetic MDSCs were incubated 4 days in DMEM/10% fetal calf serum + or - aged OZ or lean Zucker serum from non-diabetic lean Zucker rats (0.5-5%) or with soluble palmitic acid (PA) (0.5-2 mM), cholesterol (CHOL) (50-400 mg/dL), or glucose (10-25 mM).Main outcome measureFat infiltration was estimated by Oil red O, apoptosis by TUNEL, protein expression by Western blots, and gene-GTS and microRNA (miR)-GTS were determined in these stem cells' RNA.ResultsAged OZ serum caused fat infiltration, apoptosis, myostatin overexpression, and impaired differentiation. Some of these changes, and also a proliferation decrease occurred with PA and CHOL. The gene-GTS changes by OZ serum did not resemble the in vivo changes, but some occurred with PA and CHOL. The miR-GTS changes by OZ serum, PA, and CHOL resembled most of the in vivo changes. Hyperglycemia did not replicate most alterations.Clinical implicationsMDSCs may be damaged in long-term UC-T2D/obese patients and be ineffective in autologous human stem cell therapy, which may be prevented by excluding the damaged MDSCs.Strength & limitationsThe in vitro test of MDSCs is innovative and fast to define dyslipidemic factors inducing stem cell damage, its mechanism, prevention, and counteraction. Confirmation is required in other T2D/obesity rat models and stem cells (including human), as well as miR-GTS biomarker validation as a stem cell damage biomarker.ConclusionSerum from long-term UC-T2D/obese rats or dyslipidemic factors induces a noxious phenotype and miR-GTS on normal MDSCs, which may lead in vivo to the repair inefficacy of late diabetic MDSCs. This suggests that autograft therapy with MDSCs in long-term UT-T2D obese patients may be ineffective, albeit this may be predictable by prior stem cell miR-GTS tests. Masouminia M, Gelfand R, Kovanecz I, et al. Dyslipidemia Is a Major Factor in Stem Cell Damage Induced by Uncontrolled Long-Term Type 2 Diabetes and Obesity in the Rat, as Suggested by the Effects on Stem Cell Culture. J Sex Med 2018;15:1678-1697.

Numerous experimental data shows crucial involvement of mirs in skeletal development in embryos, osteogenic differentiation, and maturation. However, molecular mechanisms of mirs' action—in other words, their target signaling pathways and transcriptional factors that specific drives osteogenic differentiation—is far from being understood. With meta-analysis, the authors identified mirs significantly involved in hMSCs osteogenic differentiation. Statistical analysis revealed a significant trend of upregulation of let-7a, mir-21, mir-26a, mir-29b, mir-101, mir-143, and mir-218 during hMSCs differentiation into osteoblast. And the opposite trend was shown for mir-17, mir-31, mir-138, and mir-222: their content was significantly lower during osteogenic differentiation. Using bioinformatics approaches, the authors identified predictable genes-target for each mirs and analyzed signaling networks and biological process enriched by these genes. Bioinformatic assay shows that mirNAs specifically involved in hMSCs transition into osteogenic differentiation via microenvironment formation (i.e., let-7a, mir-17, mir-21, mir-29b, and mir-101), TGF-β/BMP-SMAD-dependent pathway (i.e., let-7a, mir-17, mir-21, mir-26a, and mir-101) and MAPK signaling pathway (i.e., let-7a, mir-21, mir-26a, mir-29b, mir-143, and mir17). Yap-dependent expression of osteogenic transcriptional factors are modulated by let-7a, mir-31mir-101, mir-138, and mir-222. We predicted that mir-17, mir-26a, mir-29b, mir-101, mir-138, and mir-222 are specifically involved in canonical Wnt sig-naling-dependent osteogenesis as well as in osteoblast maturation, together with let-7a, mir-29b, and mir-218, which modulate AMPK signaling. Additionally, identified mir-101 is likely involved into osteoblast homeostasis via Hedgehog signaling. The data presented here expands knowledge in the field of hMSCs' fate and osteogenesis orchestration by mirs and points to proosteogenic and antiosteogenic mirs and their potential molecular pathways. [ABSTRACT FROM AUTHOR]

Previous studies investigating multi-sensor fusion for the collection of soil information have shown variable improvements, and the underlying prediction mechanisms are not sufficiently understood for spectrally-active and -inactive properties. Our objective was to study prediction mechanisms and benefits of model fusion by measuring mid-infrared (MIR) and X-ray fluorescence (XRF) spectra, texture, total and labile organic carbon (OC) and nitrogen (N) content, pH, and cation exchange capacity (CEC) for n = 117 soils from an arable field in Germany. Partial least squares regression models underwent a three-fold training/testing procedure using MIR spectra or elemental concentrations derived from XRF spectra. Additionally, two sequential hybrid and two high-level fusion approaches were tested. For the studied field, MIR was superior for organic properties (ratio of prediction to interquartile distance of validation (RPIQV) for total OC = 7.7 and N = 5.0)), while XRF was superior for inorganic properties (RPIQV for clay = 3.4, silt = 3.0, and sand = 1.8). Even the optimal fusion approach brought little to no accuracy improvement for these properties. The high XRF accuracy for clay and silt is explained by the large number of elements with variable importance in the projection scores >1 (Fe ≈ Ni > Si ≈ Al ≈ Mg > Mn ≈ K ≈ Pb (clay only) ≈ Cr) with strong spearman correlations (±0.57 < rs < ±0.90) with clay and silt. For spectrally-inactive properties relying on indirect prediction mechanisms, the relative improvements from the optimal fusion approach compared to the best single spectrometer were marginal for pH (3.2% increase in RPIQV versus MIR alone) but more pronounced for labile OC (9.3% versus MIR) and CEC (12% versus XRF). Dominance of a suboptimal spectrometer in a fusion approach worsened performance compared to the best single spectrometer. Granger-Ramanathan averaging, which weights predictions according to accuracy in training, is therefore recommended as a robust approach to capturing the potential benefits of multiple sensors. [ABSTRACT FROM AUTHOR]

Downregulation of microRNA-31 (miR-31) and microRNA-132 (miR-132) has been associated with delayed wound healing. Therefore, it was hypothesised that intracellular delivery of miR-31 and miR-132, both as individual and blend formulations, could promote tissue repair. The use of a blend could minimise potential toxicity and achieve synergistic effects, thus maximising the therapeutic effect. miR-31 and miR-132 were condensed with a 30-mer positively charged amphipathic peptide, RALA, to form nanocomplexes with an average size <200 nm and zeta-potential ≥10 designed to facilitate cellular internalisation. This enabled a fold increase in miR-31 and miR-132 expression of ≥100,000 in a murine fibroblast cell line (NCTC-929) and a skin human keratinocyte cell line (HaCaT), with intracellular delivery >70% for individual and blend formulations. Moreover, incubation with the nanocomplexes increased the migration of HaCaT cells ≥25% at 4 and 8 h post-incubation, as well as downregulation of EMP-1 and RASA1 and HB-EGF and RASA1, target genes for miR-31 and miR-132, respectively. Electrospinning was then employed to produce an alginate/polyvinyl alcohol/ciprofloxacin nanofibrous wound patch to facilitate the controlled delivery of the nanocomplexes. Nanofibres were crosslinked with glutaraldehyde to improve stability in aqueous solvents, and they were proven to be biocompatible with antimicrobial activity without cellular attachment to avoid injury upon removal. RALA/miR nanoparticles were incorporated to the nanofibrous wound dressing and in vivo wound healing studies using C57BL/6J mice demonstrated a >60% acceleration in the wound closure rate at Day 7 post-wounding, a ≥1.5 increase in epidermal thickness, and a ≥2 increase in blood vessel count with respect to commercial and untreated controls. Taken together, this data proves that delivery of RALA/miR-31 and RALA/miR-132 from an alginate/polyvinyl alcohol/ciprofloxacin nanofibrous wound dressing constitutes an advanced therapy for wound healing, by accelerating wound closure and improving healed tissue quality. In this study, we report for the first time the use of the RALA peptide to deliver two miRNA 31 & 132 simultaneously from an electrospun patch. Both miRs have been shown to be downregulated in wounds and this study endeavoured to deliver a blend of the miRs from a nanofibre patch. Electrospinning was used to produce an alginate/polyvinyl alcohol/ciprofloxacin wound patch to enable controlled delivery of the miRs without cellular attachment to the wound with the added benefit of anti-microbial activity. Application of the nanofibre patch loaded with the blended RALA/miR nanoparticles demonstrated a synergistic effect with acceleration of wound closure rate, a significant increase in epidermal thickness and blood vessel count with respect to commercial and untreated controls. [Display omitted] [ABSTRACT FROM AUTHOR]

A readily configurable and scalable 2 µm laser source with multi-channel/wavelength fiber output could be advantageous to 2 µm applications such as spectral-beam combination or fiber communications. We report the first experimental realization and characterization of a two-channel holmium-doped zirconium fluoride glass waveguide array laser pumped by a single thulium fiber laser at 1945 nm. Specific laser wavelengths are selected by fiber Bragg gratings (2076.7 nm and 2074.4 nm), and single channel powers of >100 mW are achieved. Design and assembly details, and considerations for future improvements are discussed, including the potential extension to and beyond a 12 channel source. [ABSTRACT FROM AUTHOR]

The potential of using spectroscopy for the quantification of soil attributes through its spectral signature is widely documented in the literature. However, a protocol to support formal soil classification systems combining spectral data has not been established. This research proposed a protocol for soil profile classification by combining spectral data from the near visible, shortwave infrared (Vis-NIR-SWIR) and mid infrared (MIR). For this purpose, we used 15 soil profiles located in the Pernambuco State, Brazil. A quantitative analysis between soil attributes and spectral curves was performed for the selection of bands with the best correlations (method 1). In addition, the recursive feature elimination (RFE) function was used for the selection of discriminant bands between soil profiles (method 2). The results of this research indicated that the combined use of spectra is efficient to successfully grouping Ferralsol, Gleysol, and Acrisol. The integrated use of sensors, pedometric techniques, and the expertise of soil scientists can lead to an advanced understanding of soil science. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to investigate the effects of the supplementation of sesame flour in fermented chicken sausages ('S1' containing 800 g kg−1 chicken fillet, 180 g kg−1 veal fat and 20 g kg−1 sesame flour and 'S2' containing 800 g kg−1 chicken fillet, 160 g kg−1 veal fat and 40 g kg−1 sesame flour) compared with control sausages (containing 800 g kg−1 chicken fillet and 200 g kg−1 veal fat) on the physico‐chemical characteristics, texture, and structure during the fermentation stage. RESULTS: The physicochemical parameters of samples belonging to the control, S1, and S2 batches were significantly affected by the addition of sesame flour and the fermentation stage. For instance: (i) the lowest protein content was observed for control samples on day 1 (61.4 ± 6.52 g kg−1) whereas the highest level was noted for S2 samples on day 15 (327.5 ± 22.2 g kg−1), and (ii) an inverse trend was observed for the fat content because the lowest content was observed for samples in the S2 batch on day 1 (129.0 ± 5.30 g kg−1) whereas the highest fat content was noted for samples belonging to control batch on day 15 (332.0 ± 1.29 g kg−1). The application of statistical methods to mid‐infrared spectroscopy allowed clear discrimination between control, S1, and S2 batches. The addition of sesame flour in the recipes induced some modification in the secondary structure because β‐turn levels ranged from 39.30 to 34.50, 36.76 to 34.70, and 38.93 to 34.70 for control, S1, and S2 batches, respectively, throughout the fermentation stage. Sodium dodecyl‐sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) showed a similar protein profile pattern in the three batches on days 1 and 5, but on day 10 control and S2 batches showed the most intense degradation of myofibrillar proteins. CONCLUSION: The results demonstrated that mid‐infrared spectroscopy coupled with chemometric tools could be used as a rapid screening tool to assess and monitor the quality of dry chicken sausages enriched with sesame flour throughout the fermentation stage. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Based on our experimental study of spectral characteristics of an improved compact CO laser system, the prospects of using such a laser system for solving urgent problems of atmospheric sounding were demonstrated. An increase in the number of laser lines due to intracavity generation of the second harmonic and sum-frequencies in a nonlinear zinc germanium phosphide (ZnGeP2) crystal enriches capabilities of the laser. It was shown that such a CO laser system with frequency conversion in ZnGeP2 crystal can be used for detection and measuring concentration of at least 14 minor natural and pollution gases components of the atmosphere. The advantages and disadvantages of various laser operation modes, and the prospects for using its radiation for atmospheric remote sensing in various spectral ranges are discussed. Graphical Abstract [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare changes in circulating microRNAs -126 (c-miR-126) and -222 (c-miR-222) following acute serial concurrent exercise (SCE) and integrated concurrent exercise (ICE) sessions among young, sedentary adults. Ten males and 9 females completed the study procedures. For SCE, participants performed resistance exercise (RE) followed by aerobic exercise (AE), without mixing the two. For ICE, participants performed a brief bout of AE before each set of RE. Blood was collected before, immediately after (IP), and 1 h (1HR) after each exercise session. Expression of c-miR-126 significantly increased from baseline at IP (1.6-fold SCE, 2.1-fold ICE; p = .037) and 1HR (1.8-fold SCE, 1.7-fold ICE; p = .034) following both sessions, with no difference between the two sessions. Expression of c-miR-222 significantly increased from baseline at IP (1.7-fold SCE, 1.9-fold ICE; p = .024) and 1HR (2.0-fold SCE, 1.6-fold ICE; p = .038) following both sessions, with no difference between the two sessions. There were no differences in peak heart rate or average heart rate between the two workout sessions. Both SCE and ICE patterns appear equally effective at acutely increasing c-miR-126 and -222.

Pseudoexfoliation syndrome (PEX) is an important systemic disorder of the extracellular matrix, in which granular amyloid-like protein fibers accumulate in the anterior segment of the eyeball as well as in other organs. PEX is currently considered to be a multifactorial systemic disorder with genetic and environmental risk factors. The aim of this manuscript was to analyze miR expression in PEX. In recent years, an attempt has been made to investigate and describe the level of expression of selected miRs in PEX. Four polymorphisms of genes isolated from the blood that may be related to PEX were identified and miR-122-5p was found to be upregulated in patient blood. Furthermore, 18 miRs were identified with a statistically different expression in the aqueous humor. A significantly elevated expression of miR-125b was found in the anterior lens capsule, and four miRs were described, which may have a significant impact on the development of PEX. Regulatory miR molecules are gaining more and more importance in research aimed at identifying and isolating molecular markers related to the pathogenesis and prognosis of PEX, but further studies are needed. [ABSTRACT FROM AUTHOR]

The present work reports the analysis and determination of 5-hydroxymethylfurfural (HMF) and furfural (FF) contents in 27 honey samples from different geographical regions in Brazil and the storage conditions of these honey samples. The study employed an adapted HPLC-DAD method which consisted of the addition of 2,5 furandicarboxylic acid (FDCA) as internal standard. With the aid of the multi-block chemometric tool ComDim, near-infrared (NIR) and middle-infrared (MIR) spectral analyses of the honey samples were carried out in order to study the regions that corresponded to the HMF and FF compounds. Small contents of HMF (< 36.92 mg kg−1) and FF (< 4.82 mg kg−1) were detected in honey samples collected directly from beehives. The contents of HMF found in honey samples of wildflower and soy flower origin collected from the São José Ocoí apiary were found to meet the defined conditions of freshness and quality as they presented HMF contents ≤ 10 mg kg−1. Commercial samples presented HMF contents ranging from non-detected to 157.34 mg kg−1 and FF contents ranging from non-detected to 5.28 mg kg−1. Although the amount of FF concentration in honey is not regulated by law, the results obtained from Artemia salina and Lactuca sativa assays showed that this organic compound is much more toxic than HMF. The results obtained from the NIR chemometric-based technique applied showed that the honey samples with higher HMF concentration were identified by NIR absorption of functional groups that exhibited lower vibration in the following regions: 950–1100 nm and 1450–1600 nm. [ABSTRACT FROM AUTHOR]

This paper deals with the topics of violence and enmity both in terms of their traditional and cultural characteristics, as well as in light of the transformations undergone between the 16th and 17th centuries following the measures implemented in various European environments to target above all the alarming phenomenon of banditry, and adopted in consideration of the new-found need for safety and tranquillity. Enmity is typical of all human groups everywhere and at any point in time. And since for long it was often closely related to a distinct dimension of violence, its characteristics and changes reveal the symbolic meanings and values that each society ascribes to conflicts and to the methods of their resolution. In fact, the concept of enmity, deeply intertwined with that of revenge, played an essential role within a society in which a peace-centred order was not only pre-eminent but also constituted as the safeguarding of social hierarchies focused on status, kinship, and honour. In the second half of the 16th century, in the wake of widespread social insecurity and the crisis of political polycentrism that had characterised the mediaeval state, the cultural system of enmity lost its traditional stamp and became, often unawares, a means of extreme violence. This passage is clearly noticeable in the ruthless challenge that the central powers mounted against banditry, enacting a legislation that led to a veritable state of emergency, which among other things entailed an explicit mandate for the use of private violence. [ABSTRACT FROM AUTHOR]

Featured Application: With RobustATR, we have developed an exceedingly compact and robust infrared attenuated total reflectance (IR-ATR) accessory uniquely integrating substrate-integrated hollow waveguides (iHWG) facilitating efficient coupling to quantum cascade laser (QCL) light sources. This sensing platform is particularly suited for real-world application scenarios. Small and compact mid-infrared devices are of increasing importance, as there are several applications demanding on-site and real-time measurements in harsh real-world scenarios. The RobustATR, an innovative infrared attenuated total reflectance (IR-ATR) accessory, has been developed and tested with exemplary analytes integrating a single-wavelength Fabry–Pérot quantum cascade laser as light source for testing the feasibility of a potentially miniaturized overall sensor design. Successful direct coupling of the laser radiation via substrate-integrated hollow waveguide (iHWG) coupling elements to the sensor interface could be shown, whereby exemplary analytes of environmental and medical relevance were tested, revealing the future potential for real-world applications. [ABSTRACT FROM AUTHOR]

Music Information Retrieval (MIR) is the task of extracting high-level information, such as genre, artist or instrumentation from music. Genre classification is an important and rapidly evolving research area of MIR. To date, only a small amount of research work has been done on the automatic genre classification of Nigerian songs. Hence, this study presents a new music dataset, namely the ORIN dataset, consisting of only Nigerian songs. The study dataset contains 478 Nigerian traditional songs from five genres: fuji, juju, highlife, waka and apala. The timbral texture and tempo features were mined from 30-second segments of each song using the Librosa Python library. For genre classification, the ORIN datasets was trained on 4 different classifiers- k -Nearest Neighbhour, Support Vector Machine, eXtreme Gradient Boosting (XGBoost) and Random Forest- with 85–15 train-test splits. The results obtained for the five different genres indicates that XGBoost classifier is a better model, having the highest accuracy of 81.94% and recall of 84.57%. This study uses the global mean (Tree SHAP) method to determine feature importance and impact on the classification model. Further analysis on the individual genres found some nearness in the timbral properties between some of the genres. This analysis was confirmed by human observation. [ABSTRACT FROM AUTHOR]

Repetitive elements, including LINE-1 (L1), comprise approximately half of the human genome. These elements can potentially destabilize the genome by initiating their own replication and reintegration into new sites (retrotransposition). In somatic cells, transcription of L1 elements is repressed by distinct molecular mechanisms, including DNA methylation and histone modifications, to repress transcription. Under conditions of hypomethylation (e.g. in tumor cells), a window of opportunity for L1 derepression arises, and additional restriction mechanisms become crucial. We recently demonstrated that the microRNA miR-128 represses L1 activity by directly binding to L1 ORF2 RNA. In this study, we tested whether miR-128 can also control L1 activity by repressing cellular proteins important for L1 retrotransposition. We found that miR-128 targets the 3' UTR of nuclear import factor transportin 1 (TNPO1) mRNA. Manipulation of miR-128 and TNPO1 levels demonstrated that induction or depletion of TNPO1 affects L1 retrotransposition and nuclear import of an L1-ribonucleoprotein complex (using L1-encoded ORF1p as a proxy for L1-ribonucleoprotein complexes). Moreover, TNPO1 overexpression partially reversed the repressive effect of miR-128 on L1 retrotransposition. Our study represents the first description of a protein factor involved in nuclear import of the L1 element and demonstrates that miR-128 controls L1 activity in somatic cells through two independent mechanisms: direct binding to L1 RNA and regulation of a cellular factor necessary for L1 nuclear import and retrotransposition.

Abstract Silica is a versatile material employed in different applications fields including aerospace, especially for rocket engines thermal protections. It is known that particles diameter causes variations in the material properties, and the best-known methods for diameter determination in general consist of several steps in sample preparation such as drying, sieving and the determination of the refractive index according different methods. On the other hand, Fourier transform infrared spectroscopy techniques (FT-IR), in reflectance mode, related to the particle size, are less used for this type of determination. Moreover, methodologies in the near infrared region (NIR) are even less explored. Therefore, the aim of this paper is to present a FTIR methodology for diffuse reflectance (DRIFT) in the middle infrared region (MIR) and reflectance analysis in near infrared region (NIRA) for the determination of the particle diameter on silica samples. Both methodologies showed good results. As proven by a test sample analysis, NIRA methodology indicated better precision. Furthermore, considering small and intermediated particle sizes, a tendency towards smaller errors for the absorbance measurements of the samples was found, consistently with the available literature results.

Purpose: Bones are largely influenced by nutrition, activity levels and lifestyle, and structural adaptations in the form and size of the bone occur by the forces of weight bearing and forces applied by the muscles. Therefore, the aim of the present study was to determine whether different resistance training intensities affect on expression of mir-204 and transcription factors of osteogenic, Runx2 and biomechanical properties on bone in old male wistar rats. Methods: This experimental study was done on 24 Wistar male rats (23 months old and with an average weight of 437.93 gram). They were randomly divided into three equal groups (n=8) include moderate (60% maximum voluntary carrying capacity: MVCC) and high intensity (80% MVCC) resistance training and control according to initial weight. The two training groups completed eight weeks of training program, five days a week according to resistance protocols. After completing training, expression of mir-204 on bone marrow were measured RT-PCR and Three – point bending test was used to determine bone biomechanical properties. The statistical analysis was performed using Kruskal-Wallis and one-way ANOVA test with significance level of P < 0.05Results: There was no significance in expression of mir-204 (P = 0.539), Runx2 (P = 0.960), module (P = 0.82), stress (P = 0.80), fracture energy (P = 0.99) and bone force (P = 0.81) between the intervention groups and control group.Conclusion: It seems that considering the lack of meaning in the results of this study, it seems that the duration of exercise was not sufficient to influence bone variables. then longer periods of this type of exercise exercise will be investigated in future research.Keywords: Biomechanical properties, Resistance training, Mir-204, Runx2

Vibrational spectroscopy methods such as mid-infrared (MIR), near-infrared (NIR), and Raman spectroscopies have been shown to have great potential for in vivo biomedical applications, such as arthroscopic evaluation of joint injuries and degeneration. Considering that these techniques provide complementary chemical information, in this study, we hypothesized that combining the MIR, NIR, and Raman data from human osteochondral samples can improve the detection of cartilage degradation. This study evaluated 272 osteochondral samples from 18 human knee joins, comprising both healthy and damaged tissue according to the reference Osteoarthritis Research Society International grading system. We established the one-block and multi-block classification models using partial least squares discriminant analysis (PLSDA), random forest, and support vector machine (SVM) algorithms. Feature modeling by principal component analysis was tested for the SVM (PCA-SVM) models. The best one-block models were built using MIR and Raman data, discriminating healthy cartilage from damaged with an accuracy of 77.5% for MIR and 77.8% for Raman using the PCA-SVM algorithm, whereas the NIR data did not perform as well achieving only 68.5% accuracy for the best model using PCA-SVM. The multi-block approach allowed an improvement with an accuracy of 81.4% for the best model by PCA-SVM. Fusing three blocks using MIR, NIR, and Raman by multi-block PLSDA significantly improved the performance of the single-block models to 79.1% correct classification. The significance was proven by statistical testing using analysis of variance. Thus, the study suggests the potential and the complementary value of the fusion of different spectroscopic techniques and provides valuable data analysis tools for the diagnostics of cartilage health. [ABSTRACT FROM AUTHOR]

The Mid-Infrared (MIR) spectral regime has gained interest in biosensor research due to the unique excitation of specific molecular vibrational, rovibrational, and rotational modes of biomarkers and biological molecules, offering inherent selectivity for biomarker detection, which is a key asset for biomedical applications. This review focuses on the role of mid-infrared sensing technologies in biomedicine, emphasizing the crucial requirement for accurate detection and real-time monitoring of biological processes in early disease diagnosis and monitoring of disease progression. Highlighted examples provide insight into the effectiveness of MIR optical biosensors for addressing key biomarkers, underscoring their potential impact in areas including but not limited to personalized medicine and clinical research. Furthermore, we discuss how recently designed and implemented microstructures enhance the sensitivity within these application scenarios. These advancements will be complemented by technical challenges inherent to this evolving field, addressing further sensitivity enhancement, device miniaturization, and system integration, along with advanced data analysis. Future strategies discussed in this review contextualize the convergence of MIR sensing, biomedicine, and the integration of artificial intelligence for comprehensive data analysis and interpretation. • Current development of high-resolution analytical methods for biomolecules. • Recent improvements to selectivity and detection efficiency. • Importance of accurate, sensitive and real-time sensors in biomedical applications. • Challenges in miniaturization and automation of analytical equipment. • The role of advanced chemometrics/IA in spectral data analysis. [ABSTRACT FROM AUTHOR]

In this paper, based on the Hodgkin–Huxley (H-H) neuron model, three distinct types of noises are introduced into the input of the neuron. The noises are Gaussian white noise (GWN), Lévy noise and Colored noise, separately. The phenomenon of stochastic resonance under and above threshold in one-dimensional H-H neuron is discussed. First, the responses of H-H neuron to different input signal frequency, amplitude and constant offset stimulation are researched. The neuron membrane potential diagram and spectrum diagram are given. Then, the mutual information rate (MIR) is taken as the evaluation index. The results show that adding a noise of certain intensity can increase the response of neuron to the orignal signal and the MIR between the output and input of neuron has unimodal property, which proves the existence of stochastic resonance under and above the threshold. We also find that neurons have frequency selectivity and different transmission performance for different amplitude of input signals. In addition, the constant offset stimulus should not be too large. Finally, it is discovered that the adaptability of subthreshold stochastic resonance and suprathreshold stochastic resonance (SSR) characteristics characteristics of one-dimensional H-H neurons induced by three distinct types of noises is different. What is more important is that the results of this paper will be instrumental in the future researching on the affect of these three noises in the stochastic resonance of neuron networks. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is described as an immune disorder with inflammation and neurodegeneration. Relapsing–remitting MS (RRMS) is one of the most common types of MS. The diagnostic manner for this disorder typically includes the usage of magnetic resonance imaging (MRI); however, this is not always a very precise diagnostic method. Identification of molecular biomarkers in RRMS body fluids samples compared to healthy subjects can be useful to indicate the normal and pathogenic biological processes or pharmacological responses to drug interaction. In this regard, this study evaluated different miRNAs in isolated peripheral blood mononuclear cells (PBMCs) of RRMS compared to controls and their correlations with altered T regulatory type 1 (Tr1) cells, osteopontin (OPN), and interleukin 10 (IL-10) levels. The frequency of Tr1 cells was measured using flow cytometry. Also, the expressions of different miRNAs were evaluated via quantitative real-time polymerase chain reaction (RT-qPCR) and plasma levels of IL-10 and OPN were tested by enzyme-linked immunosorbent assay (ELISA). The obtained results showed the Tr1 cells' frequency, Let7c-5p, and miR-299-5p levels decreased in RRMS patients to about 59%, 0.69%, and 20% of HCs, respectively, (P < 0.05). The miR-106a-5p levels increased about 7.5-fold in RRMS patients in comparison to HCs (P < 0.05). Moreover, the results showed that there was an increased negative association between Tr1 frequency and plasma-OPN levels in RRMS patients in comparison to HCs and also, we found a moderate positive correlation between plasma-IL-10 and miR-299-5p expression of RRMS patients. Overall, it may be possible to use these biomarkers to improve the diagnostic process. These biomarkers may also be considered for clinical and therapeutic studies in the future. [ABSTRACT FROM AUTHOR]

The aims of this study were to: (1) estimate genetic correlation for milk production traits (milk, fat and protein yields and fat and protein contents) and fatty acids (FA: C16:0, C18:1 cis-9, LCFA, SFA, and UFA) over days in milk, (2) investigate the performance of genomic predictions using single-step GBLUP (ssGBLUP) based on random regression models (RRM), and (3) identify the optimal scaling and weighting factors to be used in the construction of the H matrix. A total of 302 684 test-day records of 63.875 first lactation Walloon Holstein cows were used. Positive genetic correlations were found between milk yield and fat and protein yield (rg from 0.46 to 0.85) and between fat yield and milk FA (rg from 0.17 to 0.47). On the other hand, negative correlations were estimated between fat and protein contents (rg from −0.22 to −0.59), between milk yield and milk FA (rg from −0.22 to −0.62), and between protein yield and milk FA (rg from −0.11 to −0.19). The selection for high fat content increases milk FA throughout lactation (rg from 0.61 to 0.98). The test-day ssGBLUP approach showed considerably higher prediction reliability than the parent average for all milk production and FA traits, even when no scaling and weighting factors were used in the H matrix. The highest validation reliabilities (r2 from 0.09 to 0.38) and less biased predictions (b1 from 0.76 to 0.92) were obtained using the optimal parameters (i.e., ω = 0.7 and α = 0.6) for the genomic evaluation of milk production traits. For milk FA, the optimal parameters were ω = 0.6 and α = 0.6. However, biased predictions were still observed (b1 from 0.32 to 0.81). The findings suggest that using ssGBLUP based on RRM is feasible for the genomic prediction of daily milk production and FA traits in Walloon Holstein dairy cattle. [ABSTRACT FROM AUTHOR]

In this work, we present the new photodetector based on snowflake quantum rings (QRs) structure utilizing a two-dimensional tight-binding model. Optical absorption has calculated and compared with different usual geometries of rectangular, triangular and circular QRs. There are narrow dominant peaks in the absorption spectrum with a low FHWM of 15 meV in the range of 50 meV in the far-infrared (FIR) regime to 300 meV in the mid-infrared (FIR) regime. The two-dimensional confining potential for Koch shaped quantum ring had been described in previous work was inserted in the tight-binding method and probability density of nine lowest electron energy states and absorption have calculated for the first time. Using these results, some properties of QRs were predicted and their validity was examined and displayed further. For a Koch shape quantum ring, there is fine displacement about 3 meV in absorption peak in long-wavelength infrared regime with changing iteration number that can be used for fine-tuning of the absorption spectrum. Also, a circular ring with minimal energy states has absorption peaks with an average full width at half maximum of 12.5 meV that can be tuned with the resolution of 13 meV in the FIR regime. These results are more applicable for an experimentalist to design a new photodetector with a narrower sharp peak for applications like night-vision, a thermal detector, and total IR absorbers. [ABSTRACT FROM AUTHOR]

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This systematic review of literature highlights the different microRNAs circulating in the serum or plasma of endometrial cancer patients and their association with clinical and prognostic characteristics in endometrial cancer. This study also investigates the molecular functions of these circulating microRNAs. According to this systematic review, a total of 33 individual circulating miRs (-9, -15b, -20b-5p, -21, -27a, -29b, -30a-5p, -92a, -99a, -100, -135b, -141, -142-3p, -143-3p, -146a-5p, -150-5p, -151a-5p, -186, -195-5p, -199b, -200a, -203, -204, -205, -222, -223, -301b, -423-3p, -449, -484, -887-5p, -1228, and -1290) and 6 different panels of miRs ("miR-222/miR-223/miR-186/miR-204", "miR-142-3p/miR-146a-5p/miR-151a-5p", "miR-143-3p/miR-195-5p/miR-20b-5p/miR-204-5p/miR-423-3p/miR-484", "mir-9/miR-1229", "miR-9/miR-92a", and "miR-99a/miR-199b") had a significant expression variation in EC patients compared to healthy patients. Also, seven individual circulating miRs (-9, -21, -27a, -29b, -99a, -142-3p, and -449a) had a significant expression variation according to EC prognostic factors such as the histological type and grade, tumor size, FIGO stage, lymph node involvement, and survival rates. One panel of circulating miRs ("-200b/-200c/-203/-449a") had a significant expression variation according to EC myometrial invasion. Further studies are needed to better understand their function and circulation. [ABSTRACT FROM AUTHOR]

Resumen: Introducción: El objetivo del estudio es reflejar la realidad sobre los descansos obligatorios (libranza de guardias) de los médicos residentes en la provincia de Valencia. Material y métodos: Se ha diseñado una encuesta online adaptada del único estudio similar realizado en España para evaluar distintas variables en relación a los descansos obligatorios. Resultados: El 35% de los residentes encuestados no realizan sus descansos obligatorios tal y como establece la ley, ascendiendo a un 50-60% en los hospitales de tercer nivel y a un 70% en las especialidades quirúrgicas. Un 70% de los residentes encuestados refieren que esto es debido a «Necesidades del servicio por falta de personal», un 15% a «Presión y miedo a las consecuencias» y un 11% a «Falta de tiempo de aprendizaje o interés docente». El factor principal para realizar o no el descanso obligatorio es el servicio donde se realiza la residencia y no la voluntad individual del residente. Los servicios quirúrgicos, en hospital de tercer nivel y con mayor presión asistencial son los que menos respetan los descansos obligatorios. Existe bibliografía previa que señala el gran perjuicio docente que supone la sobrecarga laboral, en los ámbitos de salud física y mental, y de las habilidades clínicas, comunicativas y éticas de los residentes. Conclusiones: Los residentes ven vulnerado su derecho a realizar los descansos obligatorios, en su mayoría por razones ajenas a su voluntad. Esto puede acarrear importantes consecuencias en su salud y su formación. Es necesario continuar investigando en este ámbito para cuidar la salud y mejorar la formación de los profesionales del futuro. Abstract: Introduction: The aim of this descriptive study is to investigate the absence of the mandatory day-off after an on-call period and its impact in the resident's medical education in the Province of Valencia. Material and methods: We carried out an online survey adapted from a previous study carried out in Spain designed to evaluate different variables in relation to the mandatory rest after being on-call. Results: 35% of the surveyed residents were not able to take their mandatory days-off. This figure rise to 50-60% of residents in tertiary level hospitals and up to 70% in surgical specialties. 70% of the residents claimed this was due to «Service needs related to staff shortages», 15% due to «the pressure and the fear of consequences» and 11% to «the improvement learning opportunities or lack of allocated learning time». The main factor which contributed to the inability to take mandatory days-off was the hospital and the specialty where the residence was being carried out rather than factors related to the individual will of the resident. Surgical services in tertiary-level hospital which presented with higher healthcare demand where the ones where the mandatory day-off were most frequently neglected. Published evidence shows the substantial harm caused by work overload on the physical and mental health as well as on the clinical, communication and ethical skills of residents. Conclusion: A violation of the right to take a day-off after being on-call was observed in a number of residents in the Province of Valencia. This can have important deleterious consequences in their health as well as in their training. Further research in this area is necessary to improving residents’ medical education, health and wellbeing.