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G-quadruplexes (G4s) are guanine-rich non-canonical secondary structures of nucleic acids that were identified in vitro almost half a century ago. Starting from the early 1980s, these structures were also observed in eukaryotic cells, first at the telomeric level and later in regulatory regions
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G-quadruplexes (G4s) are guanine-rich non-canonical secondary structures of nucleic acids that were identified in vitro almost half a century ago. Starting from the early 1980s, these structures were also observed in eukaryotic cells, first at the telomeric level and later in regulatory regions of cancer-related genes, in regulatory RNAs and within specific cell compartments such as lysosomes, mitochondria, and ribosomes. Because of the involvement of these structures in a large number of biological processes and in the pathogenesis of several diseases, including cancer, the interest in G4 targeting has exponentially increased in the last few years, and a great number of novel G4 ligands have been developed. Notably, G4 ligands represent a large family of heterogeneous molecules that can exert their functions by recognizing, binding, and stabilizing G4 structures in multiple ways. Regarding anti-cancer activity, the efficacy of G4 ligands was originally attributed to the capability of these molecules to inhibit the activity of telomerase, an enzyme that elongates telomeres and promotes endless replication in cancer cells. Thereafter, novel mechanisms through which G4 ligands exert their antitumoral activities have been defined, including the induction of DNA damage, control of gene expression, and regulation of metabolic pathways, among others. Here, we provided a perspective on the structure and function of G4 ligands with particular emphasis on their potential role as antitumoral agents. In particular, we critically examined the problems associated with the clinical translation of these molecules, trying to highlight the main aspects that should be taken into account during the phases of drug design and development. Indeed, taking advantage of the successes and failures, and the more recent technological progresses in the field, it would be possible to hypothesize the development of these molecules in the future that would represent a valid option for those cancers still missing effective therapies.
Full article
Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation
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Lung cancer (LC) represents the leading cause of global cancer deaths, with cigarette smoking being considered a major risk factor. Nicotine is a major hazardous compound in cigarette smoke (CS), which stimulates LC progression and non-small cell lung cancer (NSCLC) specifically through activation of the nicotinic acetylcholine receptor (α7nAChR)-mediated cell-signaling pathways and molecular genes involved in proliferation, angiogenesis, and metastasis. Chalcones (CHs) and their derivatives are intermediate plant metabolites involved in flavonol biosynthesis. Isoliquiritigenin (ILTG), licochalcone A–E (LicoA–E), and echinatin (ECH) are the most common natural CHs isolated from the root of Glycyrrhiza (also known as licorice). In vitro and/or vivo experiments have shown that licorice CHs treatment exhibits a range of pharmacological effects, including antioxidant, anti-inflammatory, and anticancer effects. Despite advances in NSCLC treatment, the mechanisms of licorice CHs in nicotine-induced NSCLC treatment remain unknown. Therefore, the aim of this paper is to review experimental studies through the PubMed/Medline database that reveal the effects of licorice CHs and their potential mechanisms in nicotine-induced NSCLC treatment.
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Yasar Caliskan, Yasemin Ozluk, Kento Kurashima, Safak Mirioglu, Ahmet Burak Dirim, Ozge Hurdogan, Ozgur Akin Oto, Marzena Syn, Mustafa Nazzal, Ajay Jain, John Edwards, Halil Yazici and Krista L. Lentine
Genes2024, 15(6), 773; https://doi.org/10.3390/genes15060773 (registering DOI) - 13 Jun 2024
Background: Homozygosity for LIMS1 rs893403-GG genotype is linked to an increased risk of allograft rejection after kidney transplantation. Ischemia-reperfusion of the kidney allograft leads to long term infiltration of activated and effector-memory T lymphocytes and resulting in rejection and long-term fibrosis. However, the genotype,
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Background: Homozygosity for LIMS1 rs893403-GG genotype is linked to an increased risk of allograft rejection after kidney transplantation. Ischemia-reperfusion of the kidney allograft leads to long term infiltration of activated and effector-memory T lymphocytes and resulting in rejection and long-term fibrosis. However, the genotype, LIMS1 expression under ischemic conditions and the long-term histopathological relationships remain ill-defined. Methods: We examined the impact of the recipient’s LIMS1-rs893403 genotype with transplant kidney histopathology. The association of the LIMS1-rs893403 genotype and LIMS1 and GCC2 mRNA expression in ischemic donor kidneys were also examined. Recipients who underwent transplant kidney biopsy were genotyped for the LIMS1-rs893403 variant and associated deletion. Histopathological findings were compared between recipients with LIMS1 risk and non-risk genotypes. Real-time PCR and immunofluorescence staining for LIMS1 and GCC2 expression were performed in non-utilized donor kidneys. Results: Demographic, clinical, and treatment characteristics and the histopathological diagnosis were similar between recipients with rs893403 GG and AA/AG genotype. The Banff tubulitis score was higher in GG recipients (n = 24) compared to AA/AG (n = 86) recipients (1.42 ± 0.65 vs. 1.12 ± 0.66, p = 0.03). Ischemic kidneys with GG showed higher LIMS1 and GCC2 mRNA expression than kidneys with AG. Kidneys with rs893403-GG had higher tubular LIMS1 and GCC2 immunohistochemical staining compared to kidneys with rs893403-AG. Conclusions: Our data supports the role of the LIMS1 locus in kidney transplant rejection, particularly in lymphocyte infiltration into the internal aspect of the tubular basement membranes. Increased LIMS1 and GCC2 expression in ischemic donor kidneys with the GG genotype require further studies.
Full article
Purpose: The purpose of this study is to examine the feasibility of a machine learning (ML) system for optimizing a gastric emptying scintigraphy (GES) protocol for the detection of delayed gastric emptying (GE), which is considered a primary indication for the diagnosis of
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Purpose: The purpose of this study is to examine the feasibility of a machine learning (ML) system for optimizing a gastric emptying scintigraphy (GES) protocol for the detection of delayed gastric emptying (GE), which is considered a primary indication for the diagnosis of gastroparesis. Methods: An ML model was developed using the JADBio AutoML artificial intelligence (AI) platform. This model employs the percent GE at various imaging time points following the ingestion of a standardized radiolabeled meal to predict normal versus delayed GE at the conclusion of the 4 h GES study. The model was trained and tested on a cohort of 1002 patients who underwent GES using a 70/30 stratified split ratio for training vs. testing. The ML software automated the generation of optimal predictive models by employing a combination of data preprocessing, appropriate feature selection, and predictive modeling analysis algorithms. Results: The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was employed to evaluate the predictive modeling performance. Several models were developed using different combinations of imaging time points as input features and methodologies to achieve optimal output. By using GE values at time points 0.5 h, 1 h, 1.5 h, 2 h, and 2.5 h as input predictors of the 4 h outcome, the analysis produced an AUC of 90.7% and a balanced accuracy (BA) of 80.0% on the test set. This performance was comparable to the training set results (AUC = 91.5%, BA = 84.7%) within the 95% confidence interval (CI), demonstrating a robust predictive capability. Through feature selection, it was discovered that the 2.5 h GE value alone was statistically significant enough to predict the 4 h outcome independently, with a slightly increased test set performance (AUC = 92.4%, BA = 83.3%), thus emphasizing its dominance as the primary predictor for delayed GE. ROC analysis was also performed for single time imaging points at 1 h and 2 h to assess their independent predictiveness of the 4 h outcome. Furthermore, the ML model was tested for its ability to predict “flipping” cases with normal GE at 1 h and 2 h that became abnormal with delayed GE at 4 h. Conclusions: An AI/ML model was designed and trained for predicting delayed GE using a limited number of imaging time points in a 4 h GES clinical protocol. This study demonstrates the feasibility of employing ML for GES optimization in the detection of delayed GE and potentially shortening the protocol’s time length without compromising diagnostic power.
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The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However,
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The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.
Full article
Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary
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Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary cancer centre in Ontario, Canada, were surveyed using a study-specific instrument regarding the importance of and preferences for accessing support across eight domains of palliative care. Physicians within the circle of care completed a parallel survey for each patient. The concordance between patient and physician responses was analyzed. A total of 66 patients were surveyed (median age 69, 35% female). All had an oncologist, 12% had a specialist palliative care provider (SPC), and 97% had an FD, but only 41% listed the FD as part of the care team. In total, 95 providers responded (oncologist = 68, FD = 21, SPC = 6; response rate 92%; 1–3 physician responses per patient). Disease management and physical concerns were most important to patients. Patients preferred to access care in these domains from oncologists or SPCs. For all other domains, most patients attributed primary responsibility to self or family rather than any healthcare provider. Thus, concordance was poor between patient and physician responses. Across most domains of palliative care, we found low agreement between cancer patients and their physicians regarding responsibilities for care, with FDs appearing to have limited involvement at this stage.
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Matheus Ribeiro Barbosa Oliveira, Rafael Soares Douradinho, Pietro Sica, Layna Amorim Mota, Alana Uchôa Pinto, Tamires Marques Faria and Antonio Sampaio Baptista
Stresses2024, 4(2), 380-392; https://doi.org/10.3390/stresses4020025 (registering DOI) - 13 Jun 2024
Yeast is one of the co-products of ethanol plants, which can be used as a nutritional supplement in animal feed due to its high protein content. Given the importance of yeast contribution to the nutritional properties of DDG (dried distillers’ grains), the aim
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Yeast is one of the co-products of ethanol plants, which can be used as a nutritional supplement in animal feed due to its high protein content. Given the importance of yeast contribution to the nutritional properties of DDG (dried distillers’ grains), the aim of this study was to assess how different levels of aeration affect the biomass production and the quality of yeast providing new insights into yeast production, offering an alternative source of income for the corn ethanol industry. For this purpose, yeasts were grown in a fed-batch process, and different concentrations of aeration in the medium were tested, namely 0.5, 1.0, and 1.5 volume of air per volume of wort per minute (v v−1 min−1). At the end of the cellular biomass production process, yeasts grown with 0.5 (v v−1 min−1) aeration in the reactor showed higher biomass formation (19.86 g L−1), cellular yield (g g−1), and a lower formation of succinic acid (0.70 g L−1) and acetic acid (0.11 g L−1). Aeration influenced an increase of 1.0% in the protein content in yeast. In conclusion, lower levels of aeration in the yeast production process enables more efficient sugar utilization for biomass formation and is a potential strategy to increase the protein content and the commercial value of DDG.
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This study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n = 40; 56.78 ± 6.38 years). The participants were divided into two groups: one rowed in fixed-seat rowing
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This study aimed to analyze the effects of a team rowing-based training program on physical fitness and anthropometric parameters in female breast cancer survivors (n = 40; 56.78 ± 6.38 years). The participants were divided into two groups: one rowed in fixed-seat rowing (FSR) boats (n = 20; 56.35 ± 4.89 years), and the other rowed in sliding-seat rowing (SSR) boats (n = 20; 57.20 ± 7.7 years). Both groups engaged in two 75 min sessions per week for 24 weeks. Significant improvements were observed in both groups in terms of weight (FSR: −1.93 kg, SSR: −1.75 kg), body mass index (FSR: −0.73 kg/m2, SSR: −0.67 kg/m2), waist circumference (FSR: −2.83 cm, SSR: −3.66 cm), and hip circumference (FSR: −2.02 cm, SSR: −2.88 cm). Muscle strength improved in the lower extremities (jump test: FSR: 2.99 cm, SSR: 3.11 cm) and upper extremities (dominant: FSR: 4.13 kgf, SSR: 4.34 kgf; non-dominant: FSR: 3.67 kgf, SSR: 3.32 kgf). Aerobic capacity also improved, with the SSR group showing a greater increase (FSR: 63.05 m, SSR: 93.65 m). Flexibility tests revealed better results in the SSR group for both dominant (SSR: 1.75 cm vs. FSR: −5.55 cm) and non-dominant limbs (SSR: 1.72 cm vs. FSR: −3.81 cm). These findings suggest that the type of rowing modality can influence physical fitness outcomes, with the SSR group showing superior improvements compared to the FSR group.
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Keratoconus is a bilateral ocular condition characterized by irregularities and the thinning of the cornea. Decreased central corneal thickness is a hallmark of the condition, and numerous genes have played a role in altering corneal thickness and the subsequent development of keratoconus. Variants
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Keratoconus is a bilateral ocular condition characterized by irregularities and the thinning of the cornea. Decreased central corneal thickness is a hallmark of the condition, and numerous genes have played a role in altering corneal thickness and the subsequent development of keratoconus. Variants in the structural and regulatory genes of the extracellular matrix have been highly associated with keratoconus, as well as with pectus excavatum, a chest wall deformity commonly seen in connective tissue disorders. This report describes a patient with a c.1720-11T>A intronic variant in the collagen-encoding gene, COL5A1, who was diagnosed with early-onset keratoconus and demonstrated a significant pectus excavatum. This report associates a COL5A1 variant with these seemingly unrelated phenotypic associations, further advancing the literature on the topic.
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(1) Introduction: Cancer diagnosis has been related to depression, anxiety, and distress, as well as to post-traumatic growth (PTG). One of the mediating variables for emotional response is thought style (rumination, cognitive avoidance, and cognitive engagement). (2) Aim: To identify the relationship between
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(1) Introduction: Cancer diagnosis has been related to depression, anxiety, and distress, as well as to post-traumatic growth (PTG). One of the mediating variables for emotional response is thought style (rumination, cognitive avoidance, and cognitive engagement). (2) Aim: To identify the relationship between thought style and emotional responses to cancer. A secondary aim was to identify the relationship between emotional responses and inflammatory immunological biomarkers. (3) Method: A total of 115 patients with cancer were included in the study. Before initiating cancer treatment, patients were assessed using the Hospital Anxiety and Depression Scale (HADS), distress thermometer, and Post-Traumatic Growth Inventory (PTGI). Patients provided their most recent blood biometry. (4) Results: Rumination correlated with anxiety, depression, and distress. Cognitive avoidance correlated with PTG (−0.240) and distress (−0.209). Cognitive engagement correlated with PTG (0.393). Regarding thought style and biomarkers, a negative correlation was observed for absolute neutrophils with cognitive avoidance (−0.271) and rumination (0.305). Regarding biomarkers and emotional responses, there was a negative correlation between PTG and absolute lymphocytes (−0.291). There was also a correlation between PTG and neutrophils (0.357) and neutrophil-to-lymphocyte ratio (NLR) (0.295). (5) Conclusions: Thought style is related to the emotional response to a cancer diagnosis; rumination is related to depression, distress, and anxiety; and cognitive engagement is related to PTG. PTG is related to inflammation and immunological biomarkers.
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As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports
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As vaccinations against the SARS-CoV-2 virus have become a crucial tool in controlling the spread of the disease, reports of rare health complications have emerged, including new-onset antineutrophil cytoplasmic autoantibodies (ANCA)-associated vasculitis (AAV). We systematically reviewed new-onset AAV following COVID-19 vaccination case reports and case series published in three databases before January 2024 following PRISMA guidelines to understand the characteristics of possible causal relationships or coincidences. In total, 404 articles were screened respectively by title, abstracts, and full-texts. Thirty-four papers fulfilled the inclusion criteria and have been analyzed, covering 44 patients with new-onset AAV after COVID-19 vaccination with no prior history of COVID-19 infection. Data regarding patients’ metrics, comorbidities, vaccination characteristics, symptoms, diagnostics, treatment, and outcomes were investigated and summarized. The cohort consisted predominantly of females. AAV diagnosis was confirmed via biopsy, with renal dysfunction as a prevailing manifestation. In most cases, the first symptoms of AAV developed after the second dose; moreover, Pfizer-BioNTech was the most frequently administered vaccine among the analyzed cohort. Primary treatment involved glucocorticoid therapy, with a mostly favourable response. This systematic review aims to raise awareness among clinicians in the field regarding this rare but possible complication, to promote the prompt recognition and diagnosis of de novo ANCA-positive small-vessel vasculitis in timely association with SARS-CoV-2 vaccination.
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While the supplementation of methionine (Met) sources in broiler feeds has been established for several decades, there is debate on the nutritional value of the methionine hydroxy analogue of methionine (MHA) relative to DL-Met. Based on a recommendation suggesting that MHA is 65%
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While the supplementation of methionine (Met) sources in broiler feeds has been established for several decades, there is debate on the nutritional value of the methionine hydroxy analogue of methionine (MHA) relative to DL-Met. Based on a recommendation suggesting that MHA is 65% as effective as DL-Met, many feeding trials have been conducted to challenge this recommendation. A literature search found 25 publications contributing 95 data sets suitable to compute Hedges’ g effect sizes used in the meta-analysis. The data had very little heterogeneity of almost zero and the small effect sizes of the DL-Met results were not significantly different from MHA. Data were split in various subgroups, finally suggesting that neither broiler strain (Cobb 500, Ross 308), diet type (corn, wheat based), origin of data (peer-reviewed, grey literature), nor MHA product (MHA-free acid, MHA-calcium salt) impacted the outcome of the meta-analysis. Moreover, distinguishing data in groups with dietary Met+Cysteine (Cys) levels below, at, or above requirement demonstrated that there was no interaction with general Met+Cys supply. It is therefore concluded that MHA products can be replaced by DL-Met in a weight-to-weight ratio of 100:65 in any production condition without compromising broiler performance
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This work is the first one that provides not only evidence for the existence of free volumes in the human stratum corneum but also focuses on comparing these experimental data, obtained through the unique positron annihilation lifetime spectroscopy (PALS) method, with theoretical values
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This work is the first one that provides not only evidence for the existence of free volumes in the human stratum corneum but also focuses on comparing these experimental data, obtained through the unique positron annihilation lifetime spectroscopy (PALS) method, with theoretical values published in earlier works. The mean free volume of 0.269 nm was slightly lower than the theoretical value of 0.4 nm. The lifetime τ3 (1.83 ns with a coefficient of variation CV of 3.21%) is dependent on the size of open sites in the skin. This information was used to calculate the free volume radius R (0.269 nm with CV 2.14%), free volume size Vf (0.081 nm3 with CV 4.69%), and the intensity I3 (9.01% with CV 10.94%) to estimate the relative fractional free volume fv (1.32 a.u. with CV 13.68%) in human skin ex vivo. The relation between the lifetime of o-Ps (τ3) and the radius of free volume (R) was formulated using the Tao–Eldrup model, which assumes spherical voids and applies to sites with radii smaller than 1 nm. The results indicate that PALS is a powerful tool for confirming the existence of free volumes and determining their size. The studies also focused on describing the probable locations of these nanospaces in SC lipid bilayers. According to the theory, these play an essential role in dynamic processes in biological systems, including the diffusion of low-molecular-weight hydrophobic and moderately hydrophilic molecules. The mechanism of their formation has been determined by the molecular dynamics of the lipid chains.
Full article
Barley is rich in phenolic compounds, providing health benefits and making it a valuable addition to a balanced diet. However, most studies focus on these compounds at barley’s final maturity, neglecting their synthesis during grain development and its impact on barley quality for
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Barley is rich in phenolic compounds, providing health benefits and making it a valuable addition to a balanced diet. However, most studies focus on these compounds at barley’s final maturity, neglecting their synthesis during grain development and its impact on barley quality for food applications. This study investigates phenolic profiles during grain development in four hull-less barley genotypes with different grain colors, specifically bred for food applications. The objectives were to determine the phenolic profile and identify the optimal maturity stage for maximum phenolic content and antioxidant capacity. Using UPLC-MS/MS and in vitro antioxidant capacity assays, results show that total phenolic compounds decrease as grain matures due to increased synthesis of reserve components. Flavan-3-ols, phenolic acids, and flavone glycosides peaked at immature stages, while anthocyanins peaked at physiological maturity. The harvest stage had the lowest phenolic content, with a gradient from black to yellow, purple, and blue genotypes. Antioxidant capacity fluctuated during maturation, correlating positively with phenolic compounds, specially bound phenolic acids and anthocyanins. These findings suggest that early harvesting of immature grain can help retain bioactive compounds, promoting the use of immature barley grains in foods. To support this market, incentives should offset costs associated with decreased grain weight.
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Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, which uniquely recognizes unanchored polyubiquitin chains to maintain the homeostasis of monoubiquitin chains. USP5 participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins
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Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, which uniquely recognizes unanchored polyubiquitin chains to maintain the homeostasis of monoubiquitin chains. USP5 participates in a wide range of cellular processes by specifically cleaving isopeptide bonds between ubiquitin and substrate proteins or ubiquitin itself. In the process of immune regulation, USP5 affects important cellular signaling pathways, such as NF-κB, Wnt/β-catenin, and IFN, by regulating ubiquitin-dependent protein degradation. These pathways play important roles in immune regulation and inflammatory responses. In addition, USP5 regulates the activity and function of immunomodulatory signaling pathways via the deubiquitination of key proteins, thereby affecting the activity of immune cells and the regulation of immune responses. In the present review, the structure and function of USP5, its role in immune regulation, and the mechanism by which USP5 affects the development of diseases by regulating immune signaling pathways are comprehensively overviewed. In addition, we also introduce the latest research progress of targeting USP5 in the treatment of related diseases, calling for an interdisciplinary approach to explore the therapeutic potential of targeting USP5 in immune regulation.
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Alzheimer’s disease (AD), the leading cause of dementia worldwide, remains a challenge due to its complex origin and degenerative character. The need for accurate biomarkers and treatment targets hinders early identification and intervention. To fill this gap, we used a novel longitudinal proteome
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Alzheimer’s disease (AD), the leading cause of dementia worldwide, remains a challenge due to its complex origin and degenerative character. The need for accurate biomarkers and treatment targets hinders early identification and intervention. To fill this gap, we used a novel longitudinal proteome methodology to examine the temporal development of molecular alterations in the cortex of an intracerebroventricular streptozotocin (ICV-STZ)-induced AD mouse model for disease initiation and progression at one, three-, and six-weeks post-treatment. Week 1 revealed metabolic protein downregulation, such as Aldoa and Pgk1. Week 3 showed increased Synapsin-1, and week 6 showed cytoskeletal protein alterations like Vimentin. The biological pathways, upstream regulators, and functional effects of proteome alterations were dissected using advanced bioinformatics methods, including Ingenuity Pathway Analysis (IPA) and machine learning algorithms. We identified Mitochondrial Dysfunction, Synaptic Vesicle Pathway, and Neuroinflammation Signaling as disease-causing pathways. Huntington’s Disease Signaling and Synaptogenesis Signaling were stimulated while Glutamate Receptor and Calcium Signaling were repressed. IPA also found molecular connections between PPARGC1B and AGT, which are involved in myelination and possible neoplastic processes, and MTOR and AR, which imply mechanistic involvements beyond neurodegeneration. These results help us comprehend AD’s molecular foundation and demonstrate the promise of focused proteomic techniques to uncover new biomarkers and therapeutic targets for AD, enabling personalized medicine.
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Cochlear implantation is the therapy used for patients with severe to profound sensorineural hearing loss. For the success of the surgery, it is important that each surgical step is performed with meticulous precision, starting from the correct patient position on the operating table.
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Cochlear implantation is the therapy used for patients with severe to profound sensorineural hearing loss. For the success of the surgery, it is important that each surgical step is performed with meticulous precision, starting from the correct patient position on the operating table. In elderly or obese patients, this can be difficult to achieve due to cervical rigidity. With this technical note, we want to describe a new position from orthopedic surgery to perform a posterior tympanotomy accurately, ensuring a safe procedure and avoiding unpleasant complications.
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The genomes of positive-sense (+) single-stranded RNA (ssRNA) viruses are believed to be subjected to a wide range of RNA modifications. In this study, we focused on the chikungunya virus (CHIKV) as a model (+) ssRNA virus to study the landscape of viral
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The genomes of positive-sense (+) single-stranded RNA (ssRNA) viruses are believed to be subjected to a wide range of RNA modifications. In this study, we focused on the chikungunya virus (CHIKV) as a model (+) ssRNA virus to study the landscape of viral RNA modification in infected human cells. Among the 32 distinct RNA modifications analysed by mass spectrometry, inosine was found enriched in the genomic CHIKV RNA. However, orthogonal validation by Illumina RNA-seq analyses did not identify any inosine modification along the CHIKV RNA genome. Moreover, CHIKV infection did not alter the expression of ADAR1 isoforms, the enzymes that catalyse the adenosine to inosine conversion. Together, this study highlights the importance of a multidisciplinary approach to assess the presence of RNA modifications in viral RNA genomes.
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Climate change might benefit water-stress-adapted weeds, further impairing their management. To evaluate the impact of soil moisture regimes on the growth and reproductive behaviour of ACCase-resistant and ACCase-susceptible phenotypes of sterile oat (Avena sterilis subsp. ludoviciana (Durieu) Nyman), a greenhouse experiment was carried
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Climate change might benefit water-stress-adapted weeds, further impairing their management. To evaluate the impact of soil moisture regimes on the growth and reproductive behaviour of ACCase-resistant and ACCase-susceptible phenotypes of sterile oat (Avena sterilis subsp. ludoviciana (Durieu) Nyman), a greenhouse experiment was carried out in 2020 and 2021. The factors were soil moisture regimes (100% field capacity (FC) as well-watered, 75% FC, 50% FC, and 25% FC) and ACCase-resistant and ACCase-susceptible phenotypes of sterile oat. Increased drought stress conditions reduced the number of tillers per plant by 34, 55, and 83% and the number of seeds per plant by 36, 61, and 89% in the 75% FC, 50% FC, and 25% FC conditions, respectively, compared to the well-watered treatment. Notably, both phenotypes reacted similarly to water stress, with no interactions between the two factors. Regardless of water stress, the resistant phenotypes produced fewer seeds per plant, indicating fitness costs. However, due to their high plasticity, both phenotypes will still produce seeds even when facing severe water stress conditions. Thus, sterile oat is expected to continue infesting crop fields in the near future, but with ACCase-resistant phenotypes being less successful than susceptible ones in the absence of herbicide application.
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Potentiometric titration in a fast and simultaneously high-resolution modality was proposed for the identification and quantification of protolytic groups of variable strength at the surface of primary soil particles. The method is implemented by titrimetric data processing as multicomponent spectra (pKa [...] Read more.
Potentiometric titration in a fast and simultaneously high-resolution modality was proposed for the identification and quantification of protolytic groups of variable strength at the surface of primary soil particles. The method is implemented by titrimetric data processing as multicomponent spectra (pKa spectrotitrimetry). Due to the high resolution, the error of acidity-constant assessment (3–5%) is lower, compared to existing approaches; due to the fast titration, the effect of soil hydrolysis is minimized. The soil profiles for acidic Retisols (podzolic soils)—under a spruce crown and in the intercrown space—were studied. These soils, which have similar bulk properties and genesis but developed under different plant covers, were distinguished by pKa spectral features at 4–5; 5.5–6.5; 6.5–8.5; 7.5–8.5; and 9–10, as well as total group concentrations. Differences in acidic and basic-group distribution (carboxyl groups, amorphous aluminosilicates, carbonate species, amino groups, soluble (poly)phenolic compounds, phospholipids) and Al and Fe complex compounds within the same soil profiles and between two Retisols were found and quantified. The acidity constants and group concentrations found by pKa spectrotitrimetry were compared with conventional soil-composition indicators (total organic carbon, oxalate-soluble Fe and Al, and phosphorus), using principal component analysis. The main correlations are between the concentrations of oxalate-soluble Al and groups with pKa values of 5.0–6.5 and 8.5; oxalate-soluble Fe and pKa values of 9.0–10.0; and P2O5 and pKa values of 4.0–6.0 and 6.5–8.5. The method provides a set of major acidity values without a priori information on a soil sample and can be used for screening and identifying similar soils.
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Cystic fibrosis (CF) is a disease characterized by long-term and troublesome symptoms that affect the patient’s life. This study aimed to assess and compare the health-related quality of life (HRQoL) of Polish CF patients and identify factors influencing it. The study group consisted
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Cystic fibrosis (CF) is a disease characterized by long-term and troublesome symptoms that affect the patient’s life. This study aimed to assess and compare the health-related quality of life (HRQoL) of Polish CF patients and identify factors influencing it. The study group consisted of 79 patients (6 to 42 years old), who filled in an age-appropriate Cystic Fibrosis Questionnaire-Revised. Medical data were collected from each patient’s medical records. The domains with the highest HRQoL median were eating problems (88.89), digestive symptoms (77.78) and physical functioning (75.00). The lowest-rated domain was social functioning (61.90). Age negatively correlated with eight domains, and most strongly with treatment burden (rho = −0.474). Physical functioning positively correlated with all spirometry parameters, and most strongly with FEV1% (rho = 0.588). Treatment burden, body image and respiratory symptoms were positively correlated with all spirometry parameters except PEF%. Present exacerbations reduced scores in almost all domains, and in the MANCOVA model they were a significant factor differentiating patients’ HRQoL. The univariate analysis of MANCOVA showed the significant effects of both health condition (F = 8.32, p = 0.005) and the COVID-19 pandemic (F = 5.89, p = 0.018) on social functioning domain, and of the place of residence on body image (F = 5.60, p = 0.21). A decreasing HRQoL with increasing age and during exacerbations indicates that it is important to focus on these aspects of patients’ lives and ensure they received the necessary support from their healthcare providers.
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The management of large medical files poses a critical challenge in the health sector, with conventional systems facing deficiencies in security, scalability, and efficiency. Blockchain ensures the immutability and traceability of medical records, while the cloud allows scalable and efficient storage. Together, they
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The management of large medical files poses a critical challenge in the health sector, with conventional systems facing deficiencies in security, scalability, and efficiency. Blockchain ensures the immutability and traceability of medical records, while the cloud allows scalable and efficient storage. Together, they can transform the data management of electronic health record applications. The method used was the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to choose and select the relevant studies that contribute to this research, with special emphasis set on maintaining the integrity and security of the blockchain while tackling the potential and efficiency of cloud infrastructures. The study’s focus is to provide a comprehensive and insightful examination of the modern landscape concerning the integration of blockchain and cloud advances, highlighting the current challenges and building a solid foundation for future development. Furthermore, it is very important to increase the integration of blockchain security with the dynamic potential of cloud computing while guaranteeing information integrity and security remain uncompromised. In conclusion, this paper serves as an important resource for analysts, specialists, and partners looking to delve into and develop the integration of blockchain and cloud innovations.
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Future thermoacoustic cryocoolers employing hydrogen as a working fluid can reduce reliance on helium and improve hydrogen liquefaction processes. Traditional thermoacoustic modeling methods often assume ideal-gas thermophysical properties and neglect finite-amplitude effects. However, these assumptions are no longer valid for hydrogen near saturated
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Future thermoacoustic cryocoolers employing hydrogen as a working fluid can reduce reliance on helium and improve hydrogen liquefaction processes. Traditional thermoacoustic modeling methods often assume ideal-gas thermophysical properties and neglect finite-amplitude effects. However, these assumptions are no longer valid for hydrogen near saturated states. In this study, a comparison between the results of computational fluid dynamics simulations using actual hydrogen properties and a low-amplitude, ideal-gas thermoacoustic theory was carried out in a canonical plate-based stack configuration at a mean pressure of 5 bar. It was found that the simplified analytical theory significantly underpredicts the cooling power of hydrogen-filled thermoacoustic setups, especially at lower temperatures in high-amplitude, traveling-wave arrangements. In addition, a thermoacoustic prime mover was modeled at higher temperatures, demonstrating very close agreement with the ideal-gas-based theory. The CFD approach is recommended for the design of future hydrogen-based cryocoolers at temperatures below 80 K.
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