Search Results (630)

Long non-coding RNAs (lncRNAs) have been recognized for their crucial roles in the replication processes of various viruses. However, the specific functions and regulatory mechanisms of many lncRNAs in influenza A virus (IAV) pathogenesis remain poorly understood. In this study, we identified lncRNA THRIL and observed a significant reduction in its expression following IAV infection in A549 cells. The treatment of cells with the viral mimic poly (I:C), or with type I and type III interferons, resulted in a substantial decrease in THRIL expression. Furthermore, THRIL overexpression significantly enhanced IAV replication, while its silencing markedly reduced IAV replication. Additionally, IAV infection led to notable reductions in the expression levels of type I and type III interferons in cell lines overexpressing THRIL compared to control groups; conversely, cell lines with THRIL knockdown exhibited significantly higher interferon levels than control groups. Moreover, THRIL was found to inhibit the expression of several critical interferon-stimulated genes (ISGs), which are essential for an effective antiviral response. Notably, our findings demonstrated that THRIL impaired the activation of IRF3, a key transcription factor in the interferon signaling pathway, thereby suppressing host innate immunity. These results highlight THRIL’s potential as a therapeutic target for antiviral strategies. Full article

NLRC3 belongs to the NOD-like receptor family and is recognized as a modulator of innate immune mechanisms. In this study, we firstly report that Ctenopharyngodon idelus NLRC3 (CiNLRC3) acts as a negative regulator in the antiviral immune response. Cinlrc3 is ubiquitously expressed across tested tissues, displaying particularly high expression in the intestine, spleen, gill and kidney. Notably, Cinlrc3 expression is markedly upregulated following grass carp reovirus (GCRV) infection both in vivo and in vitro. Functional assays reveal that the overexpression of CiNLRC3 hampers cellular antiviral responses, thereby facilitating viral replication. Conversely, the silencing of CiNLRC3 through siRNA transfection enhances these antiviral activities. Additionally, CiNLRC3 substantially diminishes the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-mediated interferon (IFN) response in fish. Subsequent molecular investigations indicates that CiNLRC3 interacts with the RLR molecule node, IRF7 but not IRF3, by degrading the IRF7 protein in a proteasome-dependent manner. Furthermore, CiNLRC3 co-localizes with CiIRF7 in the cytoplasm and impedes the IRF7-induced IFN response, resulting in impairing IRF7-mediated antiviral immunity. Summarily, these findings underscore the critical inhibitory role of teleost NLRC3 in innate immunity, offering new perspectives on its regulatory functions and potential as a target for resistant breeding in fish. Full article

Adipose-derived mesenchymal stem cells (ASCs) are commonly employed in clinical treatment for various diseases due to their ability to differentiate into multi-lineage and anti-inflammatory/immunomodulatory properties. Preclinical studies support their use for bone regeneration, healing, and the improvement of functional outcomes. However, a deeper understanding of the molecular mechanisms underlying ASC biology is crucial to identifying key regulatory pathways that influence differentiation and enhance regenerative potential. In this study, we employed the NanoString nCounter technology, an advanced multiplexed digital counting method of RNA molecules, to comprehensively characterize differentially expressed transcripts involved in metabolic pathways at distinct time points in osteogenically differentiating ASCs treated with or without the pan-DNMT inhibitor RG108. In silico annotation and gene ontology analysis highlighted the activation of ethanol oxidation, ROS regulation, retinoic acid metabolism, and steroid hormone metabolism, as well as in the metabolism of lipids, amino acids, and nucleotides, and pinpointed potential new osteogenic drivers like AOX1 and ADH1A. RG108-treated cells, in addition to the upregulation of the osteogenesis-related markers RUNX2 and ALPL, showed statistically significant alterations in genes implicated in transcriptional control (MYCN, MYB, TP63, and IRF1), ethanol oxidation (ADH1C, ADH4, ADH6, and ADH7), and glucose metabolism (SLC2A3). These findings highlight the complex interplay of the metabolic, structural, and signaling pathways that orchestrate osteogenic differentiation. Furthermore, this study underscores the potential of epigenetic drugs like RG108 to enhance ASC properties, paving the way for more effective and personalized cell-based therapies for bone regeneration. Full article

The first marine pestivirus, Phocoena pestivirus (PhoPeV), isolated from harbor porpoise, has been recently described. To further characterize this unique pestivirus, its host cell tropism and growth kinetics were determined in different cell lines. In addition, the interaction of PhoPeV with innate immunity in porcine epithelial cells and the role of selected cellular factors involved in the viral entry and RNA replication of PhoPeV were investigated in comparison to closely and distantly related pestiviruses. While Bungowannah pestivirus (BuPV), a unique porcine pestivirus closely related to PhoPeV, exhibits a broad cell tropism, PhoPeV only infects cells from pigs, cattle, sheep, and cats, as has been described for classical swine fever virus (CSFV). Viral titers correlate with the amount of intracellular PhoPeV-specific RNA detected in the tested cell lines. PhoPeV replicates most efficiently in the porcine kidney cell line SK6. Pestiviruses generally counteract the cellular innate immune response by degradation of interferon regulatory factor 3 (IRF3) mediated by the viral N-terminal protease (N^pro). No degradation of IRF3 and an increased expression of the type 1 interferon-stimulated antiviral protein Mx1 was observed in porcine cells infected with PhoPeV whose genome lacks the N^pro encoding region. Infection of a CD46-deficient porcine cell line suggested that CD46, which is implicated in the viral entry of several pestiviruses, is not a major factor for the viral entry of PhoPeV. Moreover, the results of this study confirmed that the cellular factor DNAJC14 plays a crucial role in viral RNA replication of non-cytopathic pestiviruses, including PhoPeV. Full article

Fluorescence imaging has been widely used in fields like (pre)clinical imaging and other domains. With advancements in imaging technology and new fluorescent labels, fluorescence lifetime imaging is gradually gaining recognition. Our research department is developing the tauCAM^TM, based on the Current-Assisted Photonic Sampler, to achieve real-time fluorescence lifetime imaging in the NIR (700–900 nm) region. Incorporating fluorescence lifetime into endoscopy could further improve the differentiation of malignant and benign cells based on their distinct lifetimes. In this work, the capabilities of an endoscopic lifetime imaging system are demonstrated using a rigid endoscope involving various phantoms and an IRF-free deep learning-based method with only 6-time points. The results show that this application’s fluorescence lifetime image has better lifetime uniformity and precision with 6-time points than the conventional methods. Full article

This paper presents a new risk assessment methodology called the Integrated Risk Framework (IRF) through the application of Ishikawa diagrams combined with the enhanced Hazard Analysis and Critical Control Point (HACCP) system. This risk investigation technique aims to ensure a significantly higher level of quality, safety, and sustainability in food products by using improved classical methods with strong intercorrelation capabilities. The methodology proposes expanding the typology of basic physical, chemical, and biological risks outlined by the ISO 22000 Food Safety Management System standard, adding other auxiliary risks such as allergens, fraud/sabotage, Kosher/Halal compliance, Rapid Alert System for Food and Feed notification, or additional specific risks such as irradiation, radioactivity, genetically modified organisms, polycyclic aromatic hydrocarbons, African swine fever, peste of small ruminants, etc. depending on the specific technological process or ingredients. Simultaneously, it identifies causes for each operation in the technological flow based on the 5M diagram: Man, Method, Material, Machine, and Environment. For each identified risk and cause, its impact was determined according to its severity and likelihood of occurrence. The final effect is defined as the risk class, calculated as the arithmetic mean of the impact derived at each process stage based on the identified risks and causes. Within the study, the methodology was applied to the spring water bottling process. This provided a new perspective on analyzing the risk factors during the bottling operations by concurrently using Ishikawa diagrams and HACCP principles throughout the product’s technological flow. The results of the study can form new methodologies aimed at enhancing sustainable food safety management strategy. In risk assessment using these two tools, the possibility of cumulative or synergistic effects is considered, resulting in better control of all factors that may affect the manufacturing process. This new perspective on studying the dynamics of risk factor analysis through the simultaneous use of the fishbone diagram and the classical HACCP system can be extrapolated and applied to any manufacturing process in the food industry and beyond. Full article

Background: In this study, we evaluated the incidence of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for different retinal pathologies and assessed the role of optical coherence tomography (OCT) biomarkers in guiding treatment decisions in post-surgical CME patients who were refractory to medical therapy over a follow-up period of 12 months. Methods: Medical records of consecutive pseudophakic patients, who underwent PPV for different retinal pathologies, were retrospectively evaluated in this single-center, uncontrolled study. The incidence of post-PPV CME was assessed. Eyes with post-PPV CME in the first 2 months after surgery, with available clinical and OCT data for 12 months after surgery, were included in the evaluation. The mean best-corrected visual acuity (BCVA; logMAR), mean central macular thickness (CMT; μm) change, and response to different treatments [medical therapy and intravitreal dexamethasone (DEX) implant] were evaluated 1, 3, 6, 9, and 12 months after PPV. The impact of OCT biomarkers on the exposure to DEX implants was assessed. Adverse events, potentially related to the treatment, were investigated as well. Results: Of the 346 pseudophakic patients (352 eyes) who participated in this study, 54 (54 eyes) developed CME within the first 2 months after PPV (incidence of 15.3%). Among them, 48 patients were deemed eligible for the 12-month analysis. Preoperative mean BCVA (1.44 ± 0.99 logMAR) significantly improved to 0.32 ± 0.37 logMAR after 12 months (p < 0.001). The mean baseline CMT of 347 (±123.5) μm significantly decreased to 290 μm (±80.4; p = 0.003) by the end of the follow-up. Twenty-five eyes (52%) required one or more DEX implants for CME, due to being refractory to topical therapy. Significant correlations were found between the mean CMT values at various time points. Additionally, patients who required DEX implants at months 3 and 9 were more likely to present intraretinal fluid (IRF), disorganization of inner retinal layers (DRIL), disorganization of outer retinal layers (DROL), and hyper-reflective foci (HRF) at 1-month OCT. Five patients experienced a slight increase in intraocular pressure (IOP), which was successfully managed with topical medication. Conclusions: Topical therapy alone can be a valuable option for post-PPV CME in approximately 50% of patients. Significant visual recovery and macular thickness reduction at 12 months demonstrated that DEX implants can be a safe and effective second-line treatment for pseudophakic patients with post-PPV CME and who are refractory to medical therapy. Early post-surgical OCT biomarkers may indicate a more severe CME that might benefit from the steroid implant. Full article

We discuss determining a finite sample linear time-invariant (FS-LTI) system’s impulse response function, $h\left[n\right],$ in the frequency domain when the input testing function is a uniform window function with a width of L and the output is limited to a finite number of effective samples, M. Assuming that the samples beyond M are all zeros, the corresponding infinite sample LTI (IS-LTI) system is a marginally stable system. The ratio of the discrete Fourier transforms (DFT) of the output to input of such an FS-LTI system, $H_0\left[k\right]$, cannot be directly used to find $h\left[n\right]$ via inverse DFT (IDFT). Nevertheless, $H_0\left[k\right]$ contains sufficient information to determine the system’s impulse response function (IRF). In the frequency-domain approach, we zero-pad the output array to a length of N. We present methods to recover $h\left[n\right]$ from $H_0\left[k\right]$ for two scenarios: (1) $N\ge \max (L,M+1)$ and N is a coprime of L, and (2) $N\ge L+M+1$. The marginal stable system discussed here is an artifact due to the zero-value assumption on unavailable samples. The IRF obtained applies to any LTI system up to the number of effective data samples, M. In demonstrating the equivalence of $H_0\left[k\right]$ and $h\left[n\right]$, we derive two interesting DFT pairs. These DFT pairs can be used to find trigonometric sums that are otherwise difficult to prove. The frequency-domain approach makes mitigating the effects of interferences and random noise easier. In an example application in radar remote sensing, we show that the frequency-domain processing method can be used to obtain finer details than the range resolution provided by the radar system’s transmitter. Full article

This study investigates the occurrence and persistence of abnormal stock returns surrounding corporate earnings announcements, particularly emphasizing how varying frequencies of financial reporting influence market behavior. Specifically, this research examines the effects of the timing and frequency of disclosures on market reactions and stock price volatility during critical earnings announcement periods. By analyzing firms within the Dow Jones Industrial Average (DJIA) from 2014 to 2024, this study evaluates the interplay between financial reporting schedules and market responses to stock prices. Furthermore, it considers the impact of peer firms’ reporting practices on the assimilation of firm-specific information into stock prices. Using econometric models, including Vector Auto Regression (VAR), Impulse Response Functions (IRFs), and Self-Exciting Threshold Autoregressive (SETAR) models, causal relationships between reporting frequency, stock price volatility, and abnormal return patterns across different volatility regimes are identified. The findings highlight that quarterly reporting practices intensify market responses and contribute to significant variations in stock price behavior in high-volatility periods. These insights provide a deeper understanding of the role of financial disclosure practices and forward-looking guidance in shaping market efficiency. This study contributes to ongoing discussions about balancing the transparency benefits of frequent reporting with its potential to amplify market volatility and sector-specific risks, offering valuable implications for policymakers, investors, and corporate managers. Full article

Background/Objectives: Eversion carotid endarterectomy (CEA) in awake patients is performed using cervical plexus blocks (CPBs) with or without carotid artery sheath infiltration (CASI) under ultrasound guidance. Although adequacy of anesthesia (AoA) guidance monitors nociception/antinociception balance, its impact on intraoperative analgesia quality and perioperative outcomes in awake CEA remains unexplored. Existing literature lacks evidence on whether AoA-guided anesthesia enhances clinical outcomes over standard techniques. This study aimed to assess the role of AoA guidance in improving intraoperative analgesia and perioperative outcomes in patients undergoing CEA with CPBs alone or with CASI compared to standard practice. Methods: A randomized controlled trial included 184 patients divided into three groups: CPBs with intravenous rescue fentanyl (IRF) and lidocaine (LID) guided by hemodynamic observation (C group), AoA-guided IRF and LID (AoA group), and AoA-guided IRF, LID, and CASI (AoA-CASI group). Primary outcomes included perioperative adverse events, and secondary outcomes assessed rescue medication demand and hemodynamic stability. Results: Analysis of 172 patients revealed no significant differences between groups in perioperative adverse events or hemodynamic parameters (p > 0.05). However, the AoA-CASI group demonstrated significantly reduced IRF and LID usage compared to the C and AoA groups (p < 0.001). No significant advantage was observed between the AoA and C groups regarding adverse events (p = 0.1). Conclusions: AoA-guided anesthesia with or without CASI does not significantly reduce perioperative adverse events or improve hemodynamic stability in awake CEA. Clinical implications suggest that focusing on surgical technique optimization may yield greater benefits in reducing adverse events compared to advanced anesthetic monitoring. Further studies are warranted to explore alternative approaches to enhance clinical outcomes. Full article

Background: Gegen Qinlian Decoction (GQD), is used for intestinal disorders like ulcerative colitis, irritable bowel syndrome, and colorectal cancer. But the precise mechanisms underlying its anti-inflammatory and anti-tumor effects are not fully elucidated. Methods: Use network pharmacology to identify targets and pathways of GQD. In vivo (azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mouse model) and in vitro (lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages) experiments were conducted to explore GQD’s anti-inflammatory and anti-tumor effects. We monitored mouse body weight and disease activity index (DAI), and evaluated colon cancer tissues using hematoxylin and eosin staining. Expression of Ki67 and F4/80 was determined by immunohistochemistry analysis. The protein levels of TLR4 signaling pathway were assessed by western blotting analysis. Enzyme-linked immunosorbent assay measured IL-1β, IL-6, and TNF-α levels. Immunofluorescence (IF) staining visualized NF-κB and IRF3 translocation. Results: There were 18, 9, 24 and 77 active ingredients in the four herbs of GQD, respectively, targeting 435, 156, 485 and 691 genes. Through data platform analysis, it was concluded that there were 1104 target genes of GQD and 2022 target genes of CAC. Moreover, there were 99 intersecting genes between GQD and CAC. The core targets of GQD contained NFKB1, IL1B, IL6, TLR4, and TNF, and GQD reduced inflammation by inhibiting the TLR4 signaling pathway. In vivo experiment, GQD increased mouse body weight, lowered DAI scores, while also alleviating histopathological changes in the colon and decreasing the expressions of Ki67 and F4/80 in the AOM/DSS-induced mice. GQD reduced IL-1β, IL-6, and TNF-α levels in the serum and downregulated TLR4, MyD88, and phosphorylation of IκBα, P65, and IRF3 in the colon tissue from AOM/DSS-induced mice. In vitro, GQD suppressed pro-inflammatory cytokines and TLR4 signaling pathway in the LPS-induced RAW264.7 cells, and combined with TAK242, it further reduced the phosphorylation of IκBα, P65. Conclusions: GQD mitigated CAC by inhibiting the TLR4 signaling pathway, offering a potential therapeutic approach for CAC management. Full article

Inflammation can positively and negatively affect tumorigenesis based on the duration, scope, and sequence of related events through the regulation of signaling pathways. A transcriptomic analysis of five pulmonary arterial hypertension, twelve Crohn’s disease, and twelve ulcerative colitis high throughput sequencing datasets using R language specialized libraries and gene enrichment analyses identified a regulatory network in each inflammatory disease. IRF9 and LINC01089 in pulmonary arterial hypertension are related to the regulation of signaling pathways like MAPK, NOTCH, human papillomavirus, and hepatitis c infection. ZNF91 and TP53TG1 in Crohn’s disease are related to the regulation of PPAR, MAPK, and metabolic signaling pathways. ZNF91, VDR, DLEU1, SATB2-AS1, and TP53TG1 in ulcerative colitis are related to the regulation of PPAR, AMPK, and metabolic signaling pathways. The activation of the transcriptomic network and signaling pathways might be related to the interaction of the characteristic microbiota of the inflammatory disease, with the lung and gut cell receptors present in membrane rafts and complexes. The transcriptomic analysis highlights the impact of several coding and non-coding RNAs, suggesting their relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during lung and gut cell adaptation to inflammatory phenotypes. Full article

Uterine infections reduce ruminant reproductive efficiency. Reproductive dysfunction caused by infusion of Gram-negative bacteria is characterized by the failure of embryo implantation and reduced conception rates. Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, is highly abortogenic. In this study, the effects of LPS infusion on the endometrial receptivity of sheep were studied during three critical periods of embryo implantation. The results showed that LPS infusion on d12, d16, and d20 of pregnancy in vivo interfered with the expression of prostaglandins (PGs) and affected the expression of adhesion-related factors (ITGB1/3/5, SPP1), key implantation genes (HOXA10, HOXA11 and LIF), and progestational elongation genes (ISG15, RSAD2 and CXCL10) during embryo implantation. In addition, after LPS infusion on d12, d16, and d20, the phosphorylation level of STAT1 significantly decreased and the protein expression level of IRF9 significantly increased on d12, suggesting that LPS infusion in sheep impairs endometrial receptivity through the JAK2/STAT1 pathway. Sheep endometrial epithelial cells were treated with 17 β-estrogen, progesterone, and/or interferon-tau in vitro to mimic the receptivity of the endometrium during early pregnancy for validation. LPS and the p-STAT1 inhibitor fludarabine were both added to the model, which resulted in reduced p-STAT1 protein expression, significant inhibition of PGE2/PGF2α, and significant suppression of the expression of key embryo implantation genes. Collectively, these results indicate that LPS infusion in sheep on d12, d16, and d20 impairs endometrial receptivity through the JAK2/STAT1 pathway, which is responsible for LPS-associated pregnancy failure. Full article

Objectives: The objectives of this study were to evaluate the structural and functional outcomes after the loading phase with brolucizumab in switched patients with diabetic macular edema (DME) and to identify potential predictive biomarkers of treatment response. Methods: A total of 28 eyes with DME, switched to brolucizumab, were retrospectively reviewed. Main outcomes during the follow-up period, up to 6 weeks after the fifth injection, included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), macular volume, subfoveal choroidal thickness, intraretinal and subretinal fluid (IRF and SRF), cyst dimension including maximal horizontal cyst diameter (MHCD), maximal vertical cyst diameter (MVCD), width-to-height ratio (WHR), foveal avascular zone (FAZ) dimension, and vessel density (VD). Results: At the last follow-up, BCVA was significantly improved (p = 0.003). Significant reduction of CST was demonstrated after each injection time point (p < 0.05), and a dry macula was detected in 64.3% of patients at the last follow-up. The WHR was 1.23 ± 0.46, and a negative correlation to final CST (p < 0.0001) was found. In FAZ and VD analysis, no significant variation was detected. At the last disease activity assessment, the treatment regimen was q12 in 64% of patients. Conclusions: Brolucizumab leads to anatomical and functional improvements in switched eyes affected by DME. WHR may represent a predictive biomarker of treatment response. Full article

Heywood cases and other improper solutions occur frequently in latent variable models, e.g., factor analysis, item response theory, latent class analysis, multilevel models, or structural equation models, all of which are models with response variables taken from an exponential family. They have important consequences for scoring with the latent variable model and are indicative of issues in a model, such as poor identification or model misspecification. In the context of the 2PL and 3PL models in IRT, they are more frequently known as Guttman items and are identified by having a discrimination parameter that is deemed excessively large. Other IRT models, such as the newer asymmetric item response theory (AsymIRT) or polytomous IRT models often have parameters that are not easy to interpret directly, so scanning parameter estimates are not necessarily indicative of the presence of problematic values. The graphical examination of the IRF can be useful but is necessarily subjective and highly dependent on choices of graphical defaults. We propose using the derivatives of the IRF, item Fisher information functions, and our proposed Item Fraction of Total Information (IFTI) decomposition metric to bypass the parameters, allowing for the more concrete and consistent identification of Heywood cases. We illustrate the approach by using empirical examples by using AsymIRT and nominal response models. Full article