Signal Response Research Articles

A single, maximal dose of celecoxib, ibuprofen, or flurbiprofen does not reduce the muscle signalling response to plyometric exercise in young healthy adults.

Non-steroidal anti-inflammatory drugs (NSAIDs) possess analgesic and anti-inflammatory properties by inhibiting cyclooxygenase (COX) enzymes. Conflicting evidence exists on whether NSAIDs influence signaling related to muscle adaptations and exercise with some research finding a reduction in muscle protein synthesis signaling via the AKT-mTOR pathway, changes in satellite cell signaling, reductions in muscle protein degradation, and reductions in cell proliferation. In this study, we determined if a single maximal dose of flurbiprofen (FLU), celecoxib (CEL), ibuprofen (IBU), or a placebo (PLA) affects the short-term muscle signaling responses to plyometric exercise. This was a block randomized, double-masked, crossover design, where 12 participants performed four plyometric exercise bouts consisting of 10 sets of 10 plyometric jumps at 40% 1RM. Two hours before exercise, participants consumed a single dose of celecoxib (CEL 200mg), IBU (800mg), FLU (100mg) or PLA with food. Muscle biopsy samples were collected before and 3-h after exercise from the vastus lateralis. Data were analyzed using a repeated measures (RM) ANOVA, ANOVA, or a Friedman test. Significance was considered at p < 0.05. We found no treatment effects on the mRNA expression of PTSG1, PTSG2, MYC, TBP, RPLOP, MYOD1, Pax7, MYOG, Atrogin-1, or MURF1 (all, p > 0.05). We also found no treatment effects on AKT-mTOR signaling or MAPK signaling measured through the phosphorylation status of mTORS2441, mTORS2448, RPS6 235/236, RPS 240/244, 4EBP1, ERK1/2, p38 T180/182 normalized to their respective total abundance (all, p > 0.05). However, we did find a significant difference between MNK1 T197/202 in PLA compared to FLU (p < .05). A single, maximal dose of IBU, CEL, or FLU taken prior to exercise did not affect the signaling of muscle protein synthesis, protein degradation, or ribosome biogenesis three hours after a plyometric training bout.

Bridge damage identification based on synchronous statistical moment theory of vehicle–bridge interaction

AbstractConsidering the weak noise resistance and low identification efficiency of traditional bridge damage identification methods, a data‐driven approach based on synchronous statistical moment theory and vehicle–bridge interaction vibration theory is proposed. This method involves two main steps. First, a two‐axle test vehicle is used to collect acceleration response signals synchronously from adjacent designated measurement points while stationary. This operation is repeated to calculate the second‐order statistical moment curvature (SOSMC) difference of entire bridge points corresponding signals in different states. By comparing with the reference value, the preliminary damage location of the bridge can be obtained. Second, the first‐order modal shape curve is constructed using the second‐order statistical moment (SOSM). The refined identification of bridge damage is then based on an improved direct stiffness back calculation of the bridge's stiffness. This article proposes the synchronization theory for the first time and combines it with the statistical moment clustering method, forming an innovative approach to obtaining structural vibration modes. The effectiveness of this method has been well validated through numerical simulations with different parameters and on‐site bridge tests. The research results indicate that SOSMC indicators have better noise resistance and higher recognition efficiency in identifying damage locations, compared to modal curvature and flexibility curvature indicators. Additionally, compared to transfer rate and random subspace methods, the SOSM method results in smaller error and higher identification efficiency.

Creating absolute band gap based on frequency locking of three wave modes in a wavy plate

This paper presents an absolute band gap (BG) by overlapping coupled band gaps based on frequency locking mechanism within a wavy structure. We first introduce coupled BG’s trigger conditions, including weak coupling, and then utilize two coupling in a wavy structure to lock three wave modes into two overlapped coupled BGs. A wavy specimen is determined for experimental validation, by selecting the geometric parameters based on their individual effects on the coupled BG. Four testing loads with the capability to excite all guided waves are applied numerically and experimentally to verify the performance of the absolute BG. The response signals validate the existence of a wide attenuation band introduced by the absolute BG. The results exhibit a great potential for utilizing the frequency locking mechanism to construct an absolute BG for applications such as vibration control.

The Role of IRF9 Upregulation in Modulating Sensitivity to Olaparib and Platinum-Based Chemotherapies in Breast Cancer.

Poly(ADP-ribose) polymerase (PARP) inhibitors are targeted therapies that accumulate DNA damage by interfering with DNA repair mechanisms and are approved for treating several cancers with BRCA1/2 mutations. In this study, we utilized CRISPR-dCas9 interference screening to identify genes regulating sensitivity to PARP inhibitors in breast cancer cell lines. Our findings indicated that the interferon (IFN) signaling gene IRF9 was critically involved in modulating sensitivity to these inhibitors. We revealed that the loss of IRF9 leads to increased resistance to the PARP inhibitor in MDA-MB-468 cells, and a similar desensitization was observed in another breast cancer cell line, MDA-MB-231. Further analysis indicated that while the basal expression of IRF9 did not correlate with the response to the PARP inhibitor olaparib, its transcriptional induction was significantly associated with increased sensitivity to the DNA-damaging agent cisplatin in the NCI-60 cell line panel. This finding suggests a mechanistic link between IRF9 induction and cellular responses to DNA damage. Additionally, data from the METABRIC patient tissue study revealed a complex network of IFN-responsive gene expressions postchemotherapy, with seven upregulated genes, including IRF9, and three downregulated genes. These findings underscore the intricate role of IFN signaling in the cellular response to chemotherapy. Collectively, our CRISPR screening data and subsequent bioinformatic analyses suggest that IRF9 is a novel biomarker for sensitivity to DNA-damaging agents, such as olaparib and platinum-based chemotherapeutic agents. Our findings for IRF9 not only enhance our understanding of the genetic basis of drug sensitivity, but also elucidate the role of IRF9 as a critical effector within IFN signaling pathways, potentially influencing the association between the host immune system and chemotherapeutic efficacy.

Regulation of T Cell Signaling and Immune Responses by PTPN22.

Protein tyrosine phosphatases (PTPs) play central roles in the regulation of cell signaling, organismal development, cellular differentiation and proliferation, and cancer. In the immune system, PTPs regulate the activation, differentiation and effector function of lymphocytes and myeloid cells whilst single-nucleotide polymorphisms (SNPs) in PTP-encoding genes have been identified as risk factors for the development of autoimmunity. In this review we describe the roles for PTP nonreceptor type 22 (PTPN22) in the regulation of T lymphocyte signaling and activation in autoimmunity, infection and cancer. We summarize recent progress in our understanding of the regulation of PTPN22 activity, the impact of autoimmune disease-associated PTPN22 SNPs on T cell responses and describe approaches to harness PTPN22 as a target to improve T cell-based immunotherapies in cancer.

Research on molecular characteristics of ADME-related genes in kidney renal clear cell carcinoma

Genes involved in drug absorption, distribution, metabolism, and excretion (ADME) are named ADME genes. However, the comprehensive role of ADME genes in kidney renal clear cell carcinoma (KIRC) remains unclear. Using the clinical and gene expression data of KIRC patients downloaded from The Cancer Genome Atlas (TCGA), ArrayExpress, and the Gene Expression Omnibus (GEO) databases, we cluster patients into two patterns, and the population with a relatively poor prognosis demonstrated higher level of immunosuppressive cell infiltration and higher proportion of glycolytic subtypes. Then, 17 ADME genes combination identified through the least absolute shrinkage and selection operator algorithm (LASSO, 1000 times) was utilized to calculate the ADME score. The ADME score was found to be an independent predictor of prognosis in KIRC and to be tightly associated with the infiltration level of immune cells, metabolic properties, tumor-related signaling pathways, genetic variation, and responses to chemotherapeutics. Our work revealed the characteristics of ADME in KIRC. Assessing the ADME profiles of individual patients can deepen our comprehension of tumor microenvironment (TME) features in KIRC and can aid in developing more personalized and effective therapeutic strategies.

Improvement of shoulder peak effect in graphene/silicone rubber strain sensors by nanosilica

Conducting polymer composites (CPCs) typically exhibit shoulder peak phenomena in their resistive response signals, which greatly limits their practical application as strain sensors in the field of vibration damping. In this paper, nanosilica (SiO2) nanoparticles were incorporated into graphene (GR)/methyl vinyl silicone rubber (VMQ) composites to obtain the optimum content of SiO2 to eliminate the shoulder peak phenomenon. The results showed that the shoulder peak phenomenon of the resistance response signal of the composites disappeared after the addition of 30 % SiO2, which explained the mechanism of eliminating the shoulder peak phenomenon. Meanwhile, the tensile strength and Young's modulus of the composites were improved, and excellent resistance-strain response properties were obtained, including a wide sensing range (＞200 %), high sensitivity (GF = 839.02), fast response time (37 ms), and good durability and stability (9000 cycles at 50 % strain). It shows that the strain sensor has great potential for health monitoring in the field of vibration damping.

Dual-responsive electrochemical immunosensor for CYFRA21-1 detection based on Au/Co Co-loaded 3D ordered macroporous carbon interconnected framework

Cytokeratin 19 fragment antigen 21–1 (CYFRA21–1) is a protein fragment released into the bloodstream during the death of lung epithelial cells, serving as a predictive biomarker in diagnosing non-small cell lung cancer (NSCLC) and need to be accurately detected. Herein, a dual-responsive label-free electrochemical immunosensor was developed based on a three-dimensional ordered interconnecting macroporous carbon skeleton material modified with gold-cobalt nanoparticles (Au/Co NPs-3D MCF) to detect cytokeratin-19 fragment (CYFRA21–1). The three-dimensional ordered interconnect macroporous structure, by providing a high specific surface area and an electrochemically active area, not only enhances the electron transport channel and reduces mass transfer resistance, but also offers a confined region that elevates the collision frequency with the active site. In addition to exhibiting excellent biocompatibility for antibody binding, gold-cobalt nanoparticles contribute significantly to the overall robustness of the immunosensor. By capitalizing on the 3D network structure and collective effect of Au and Co NPs, the Au/Co NPs-3D MCF immunosensors exhibit exceptional response signals in both chronocurrent testing and square-wave voltammetry, allowing for a wide linear response range of 0.0001–100 ng/mL and a low detection limit. Moreover, the constructed immunosensor is capable of detecting CYFRA21–1 in human serum and has the potential for further extension to detect multiple biomarkers. This work opens up new avenues for the construction of other highly selective 3D network immunosensors.

Investigation of the Electrical Impedance Signal Behavior in Rolling Element Bearings as a New Approach for Damage Detection

The opportunities of impedance-based condition monitoring for rolling bearings have been shown earlier by the authors: Changes in the impedance signal and the derived features enable the detection of pitting damages. Localizing and measuring the pitting length in the raceway direction is possible. Furthermore, the changes in features behavior are physically explainable. These investigations were focused on a single bearing type and only one load condition. Different bearing types and load angles were not considered yet. Thus, the impedance signals and their features of different bearing types under different load angles are investigated and compared. The signals are generated in fatigue tests on a rolling bearing test rig with conventional integrated vibration analysis based on structural borne sound. The rolling bearing impedance is gauged using an alternating current measurement bridge. Significant changes in the vibration signals mark the end of the fatigue tests. Therefore, comparing the response time of the impedance can be compared to the vibration signal response time. It can be shown that the rolling bearing impedance is an instrument for condition monitoring, independently from the bearing type. In case of pure radial loads, explicit changes in the impedance signal are detectable, which indicate a pitting damage. Under combined loads, the signal changes are detectable as well, but not as significant as under radial load. Damage-indicating signal changes occur later compared to pure radial loads, but nevertheless enable an early detection. Therefore, the rolling bearing impedance is an instrument for pitting damage detection, independently from bearing type and load angle.

Signal response model in PandaX-4T

Signal response model in PandaX-4T

An adversarial network used for drift correction in electronic nose

The electronic nose (E-nose) is an important means for machines to sense odor signals, but it faces a serious problem that limits its development: sensor drift. Drift refers to the long-time and irregular changes in the response signal of the gas sensor to the same analyte, and it will bring serious performance degradation to the E-nose. To reduce the effect of drift, we proposed an entropy minimization model based on adversarial networks (EMAD) which reduced the distribution difference between data with and without drift through adversarial training. EMAD consists of a generator and a classifier. To simplify the structure and improve the prediction diversity, the classifier is reused as a discriminator for adversarial training while learning the domain invariant features from the source domain. EMAD reduced the distribution difference between original data and drift data while preserving the features for classification. Experiment results on the public dataset showed that EMAD effectively eliminated the performance degradation caused by drift and achieved the highest classification accuracy compared with other advanced methods.

In-depth phosphoproteomic profiling of the insulin signaling response in heart tissue and cardiomyocytes unveils canonical and specialized regulation

BackgroundInsulin signaling regulates cardiac substrate utilization and is implicated in physiological adaptations of the heart. Alterations in the signaling response within the heart are believed to contribute to pathological conditions such as type-2 diabetes and heart failure. While extensively investigated in several metabolic organs using phosphoproteomic strategies, the signaling response elicited in cardiac tissue in general, and specifically in the specialized cardiomyocytes, has not yet been investigated to the same extent.MethodsInsulin or vehicle was administered to male C57BL6/JRj mice via intravenous injection into the vena cava. Ventricular tissue was extracted and subjected to quantitative phosphoproteomics analysis to evaluate the insulin signaling response. To delineate the cardiomyocyte-specific response and investigate the role of Tbc1d4 in insulin signal transduction, cardiomyocytes from the hearts of cardiac and skeletal muscle-specific Tbc1d4 knockout mice, as well as from wildtype littermates, were studied. The phosphoproteomic studies involved isobaric peptide labeling with Tandem Mass Tags (TMT), enrichment for phosphorylated peptides, fractionation via micro-flow reversed-phase liquid chromatography, and high-resolution mass spectrometry measurements.ResultsWe quantified 10,399 phosphorylated peptides from ventricular tissue and 12,739 from isolated cardiomyocytes, localizing to 3,232 and 3,128 unique proteins, respectively. In cardiac tissue, we identified 84 insulin-regulated phosphorylation events, including sites on the Insulin Receptor (InsrY1351, Y1175, Y1179, Y1180) itself as well as the Insulin receptor substrate protein 1 (Irs1S522, S526). Predicted kinases with increased activity in response to insulin stimulation included Rps6kb1, Akt1 and Mtor. Tbc1d4 emerged as a major phosphorylation target in cardiomyocytes. Despite limited impact on the global phosphorylation landscape, Tbc1d4 deficiency in cardiomyocytes attenuated insulin-induced Glut4 translocation and induced protein remodeling. We observed 15 proteins significantly regulated upon knockout of Tbc1d4. While Glut4 exhibited decreased protein abundance consequent to Tbc1d4-deficiency, Txnip levels were notably increased. Stimulation of wildtype cardiomyocytes with insulin led to the regulation of 262 significant phosphorylation events, predicted to be regulated by kinases such as Akt1, Mtor, Akt2, and Insr. In cardiomyocytes, the canonical insulin signaling response is elicited in addition to regulation on specialized cardiomyocyte proteins, such as Kcnj11Y12 and DspS2597. Details of all phosphorylation sites are provided.ConclusionWe present a first global outline of the insulin-induced phosphorylation signaling response in heart tissue and in isolated adult cardiomyocytes, detailing the specific residues with changed phosphorylation abundances. Our study marks an important step towards understanding the role of insulin signaling in cardiac diseases linked to insulin resistance.Graphical

A novel biomass carbon dots ratiometric fluorescence probe coupled with molecularly imprinted polymer for selective detection of aflatoxin B1

The accumulation of Aflatoxin B1 (AFB1) in food and crops can pose significant hazards to human health. Consequently, there has been extensive attention paid to the development of a rapid and reliable method for detecting AFB1 in food. In this context, a ratiometric fluorescence probe (DE-MIPs) was prepared using dual-emission fluorescent carbon dots (CDs) coupled with the molecular imprinting technique for visual detection of AFB1. The dual-emission CDs consisted of red fluorescence biomass CDs (R-CDs) wrapped by molecularly imprinted cavities (R-CDs@MIPs), which served as a response signal, and pure blue emission biomass CDs (B-CDs) as a reference signal. Due to the specific quenching effect of AFB1 on red fluorescence while leaving blue fluorescence unaffected, there was a gradual decrease in the fluorescence intensity ratio (I670/I437) and a distinct shift in fluorescence color from red to blue as the concentration of AFB1 increased. The ratiometric probe demonstrated excellent linearity in detecting AFB1 within the concentration range of 0.1–200 ng/mL, with a detection limit (LOD) of 0.05 ng/mL. Furthermore, the practicality of DE-MIPs was validated by successfully detecting AFB1 in vegetable oil, with desirable recoveries from 89.0% to 107.4%. Furthermore, the integration of a smartphone as colorimetric reader enabled rapid AFB1 detection by capturing changes in fluorescence color. Overall, the development of this ratiometric probe offers a novel perspective for the facile and efficient identification of AFB1 in complex food samples.

Experimental study on strengthening the magneto-mechanical coupling effect of X80 steel by weak magnetic excitation

Abstract Current magnetic stress detection techniques are significantly impacted by external noise signals. The magnetic stress detection technology under excitation magnetic fields is proposed to weaken the external noise signals on the detection results. In this study, the uniaxial tensile magnetic signal testing system with the excitation magnetic field was built. The enhancement of the weak magnetic excitation on magnetic signals has been quantitatively analyzed and the concept of optimal weak excitation magnetic field has been proposed. The response law between triaxial magnetic induction intensity and stress under the excitation magnetic field is determined. The results indicate that the weak excitation magnetic field significantly enhances the magnetic induction signal intensity, more importantly, the linearity of the magnetic signal and stress response is also enhanced. Furthermore, the optimal excitation magnetic field under uniaxial stress states is 600 A/m, and the corresponding stress-magnetic change rate is 0.002 Oe/MPa. This study provides a theoretical basis for the long-distance detection of pipelines under weak magnetic excitation. The long-distance magnetic stress detection results of pipelines will become more accurate with the weak magnetic excitation which has a good engineering significance.&amp;#xD;

Coevolution of larval signalling and worker response can trigger developmental caste determination in social insects.

Eusocial insects belong to distinct queen and worker castes, which, in turn, can be divided into several morphologically specialized castes of workers. Caste determination typically occurs by differential nutrition of developing larvae. We present a model for the coevolution of larval signalling and worker task allocation-both modelled by flexible smooth reaction norms-to investigate the evolution of caste determination mechanisms and worker polymorphism. In our model, larvae evolve to signal their nutritional state to workers. The workers evolve to allocate time to foraging for resources versus feeding the brood, conditional on the larval signals and their body size. Worker polymorphism evolves under accelerating foraging returns of increasing body size, which causes selection to favour large foraging and small nursing workers. Worker castes emerge because larvae evolve to amplify their signals after obtaining some food, which causes them to receive more food, while the other larvae remain unfed. This leads to symmetry-breaking among the larvae, which are either well-nourished or malnourished, thus emerging as small or large workers. Our model demonstrates the evolution of nutrition-dependent caste determination and worker polymorphism by a self-reinforcement mechanism that evolves from the interplay of larval signalling and worker response to the signals.

Microbial Matryoshka: Addressing the Relationship between Pathogenic Flagellated Protozoans and Their RNA Viral Endosymbionts (Family Totiviridae).

Three genera of viruses of the family Totiviridae establish endosymbiotic associations with flagellated protozoa responsible for parasitic diseases of great impact in the context of One Health. Giardiavirus, Trichomonasvirus, and Leishmaniavirus infect the protozoa Giardia sp., Trichomonas vaginalis, and Leishmania sp., respectively. In the present work, we review the characteristics of the endosymbiotic relationships established, the advantages, and the consequences caused in mammalian hosts. Among the common characteristics of these double-stranded RNA viruses are that they do not integrate into the host genome, do not follow a lytic cycle, and do not cause cytopathic effects. However, in cases of endosymbiosis between Leishmaniavirus and Leishmania species from the Americas, and between Trichomonasvirus and Trichomonas vaginalis, it seems that it can alter their virulence (degree of pathogenicity). In a mammalian host, due to TLR3 activation of immune cells upon the recognition of viral RNA, uncontrolled inflammatory signaling responses are triggered, increasing pathological damage and the risk of failure of conventional standard treatment. Endosymbiosis with Giardiavirus can cause the loss of intestinal adherence of the protozoan, resulting in a benign disease. The current knowledge about viruses infecting flagellated protozoans is still fragmentary, and more research is required to unravel the intricacies of this three-way relationship. We need to develop early and effective diagnostic methods for further development in the field of translational medicine. Taking advantage of promising biotechnological advances, the aim is to develop ad hoc therapeutic strategies that focus not only on the disease-causing protozoan but also on the virus.

CPLANE protein INTU regulates growth and patterning of the mouse lungs through cilia-dependent Hh signaling

Congenital lung malformations are fatal at birth in their severe forms. Prevention and early intervention of these birth defects require a comprehensive understanding of the molecular mechanisms of lung development. We find that the loss of inturned (Intu), a cilia and planar polarity effector gene, severely disrupts growth and branching morphogenesis of the mouse embryonic lungs. Consistent with our previous results indicating an important role for Intu in ciliogenesis and hedgehog (Hh) signaling, we find greatly reduced number of primary cilia in both the epithelial and mesenchymal tissues of the lungs. We also find significantly reduced expression of Gli1 and Ptch1, direct targets of Hh signaling, suggesting disruption of cilia-dependent Hh signaling in Intu mutant lungs. An agonist of the Hh pathway activator, smoothened, increases Hh target gene expression and tubulogenesis in explanted wild type, but not Intu mutant, lungs, suggesting impaired Hh signaling response underlying lung morphogenetic defects in Intu mutants. Furthermore, removing both Gli2 and Intu completely abolishes branching morphogenesis of the lung, strongly supporting a mechanism by which Intu regulates lung growth and patterning through cilia-dependent Hh signaling. Moreover, a transcriptomics analysis identifies around 200 differentially expressed genes (DEGs) in Intu mutant lungs, including known Hh target genes Gli1, Ptch1/2 and Hhip. Genes involved in muscle differentiation and function are highly enriched among the DEGs, consistent with an important role of Hh signaling in airway smooth muscle differentiation. In addition, we find that the difference in gene expression between the left and right lungs diminishes in Intu mutants, suggesting an important role of Intu in asymmetrical growth and patterning of the mouse lungs.

A Damaging COL6A3 Variant Alters the MIR31HG-Regulated Response of Chondrocytes in Neocartilage Organoids to Hyperphysiologic Mechanical Loading.

The pericellular matrix (PCM), with its hallmark proteins collagen type VI (COLVI) and fibronectin (FN), surrounds chondrocytes and is critical in transducing the biomechanical cues. To identify genetic variants that change protein function, exome sequencing is performed in a patient with symptomatic OA at multiple joint sites. A predicted damaging variant in COL6A3 is identified and introduced by CRISPR-Cas9 genome engineering in two established human induced pluripotent stem cell-derived in-vitro neocartilage organoid models. The downstream effects of the COL6A3 variant on the chondrocyte phenotypic state are studied by a multi-omics (mRNA and lncRNA) approach in interaction with hyper-physiological mechanical loading conditions. The damaging variant in COL6A3 results in significantly lower binding between the PCM proteins COLVI and FN and provokes an osteoarthritic chondrocyte state. By subsequently exposing the neocartilage organoids to hyperphysiological mechanical stress, it is demonstrated that the COL6A3 variant in chondrocytes abolishes the characteristic inflammatory signaling response after mechanical loading with PTGS2, PECAM1, and ADAMTS5, as central genes. Finally, by integrating epigenetic regulation, the lncRNA MIR31HG is identified as key regulator of the characteristic inflammatory signaling response to mechanical loading.

Endoplasmic reticulum stress and associated apoptosis are linked with the pathogenesis of white striping in broiler breast muscles

White striping (WS) that appears as white stripes parallel to the muscle fibrils is an emerging growth-related abnormality of broiler breast meat. The pathomechanism of this defect has not been fully understood despite intensive studies over the past decade. In the present study, endoplasmic reticulum (ER) stress and its associated apoptotic pathways were investigated to elucidate the potential role of these pathways in the development of WS. To this end, a total of 60 Pectoralis major (Pm) muscle samples were collected from 55-d-old Ross 308 male broiler chickens according to the severity of gross WS lesions (normal, mild, and severe). Histopathological and molecular analyses were conducted to evaluate the lesions and genes involved in the ER stress and related apoptosis. All the Pm samples, both with and without macroscopic WS lesions, showed varying degrees of myodegenerative lesions. Molecular analysis revealed that the transcript abundances of many components related to protein kinase R-like ER kinase (PERK) and inositol-requiring enzyme type 1 (IRE-1) signals of the ER stress response were significantly greater in severely WS-affected breast tissues compared to their mildly affected and normal counterparts. Similarly, the transcript abundances of apoptotic markers related to both signaling pathways were significantly greater in severe WS lesions than those of mildly affected and normal Pm tissues. Besides these, a significant increase in caspase-3 transcript abundance was seen in severe WS lesions in comparison with mild WS and normal breast muscles. Findings of this study suggest that ER stress response and its related apoptotic pathways are possibly activated in the breast muscle of broiler chickens with severe WS lesions. Based on these findings, it is speculated that ER stress-mediated apoptosis occupies a central role in the progression of WS in broiler chickens.

Comprehensive metabolic modulations of sphingolipids are promising severity indicators in COVID-19.

The COVID-19 pandemic, caused by SARS-CoV-2, has had a significant worldwide impact, affecting millions of people. COVID-19 is characterized by a heterogenous clinical phenotype, potentially involving hyperinflammation and prolonged tissue damage, although the exact underlying mechanisms are yet to be fully understood. Sphingolipid metabolites, which govern cell survival and proliferation, have emerged as key players in inflammatory signaling and cytokine responses. Given the complex metabolic pathway of sphingolipids, this study aimed to understand their potential role in the pathogenesis of COVID-19. We conducted a comprehensive examination of sphingolipid modulations across groups classified based on disease severity, incorporating a time-course in serum and urine samples. Several sphingolipids, including sphingosine, lactosylceramide, and hexosylceramide, emerged as promising indicators of COVID-19 severity, as validated by correlation analyses conducted on both serum and urine samples. Other sphingolipids, such as sphingosine 1-phosphate, ceramides, and deoxy-dihydroceramides, decreased in both COVID-19 patients and individuals with non-COVID infectious diseases. This suggests that these sphingolipids are not specifically associated with COVID-19 but rather with pathological conditions caused by infectious diseases. Our analysis of urine samples revealed elevated levels of various sphingolipids, with changes dependent on disease severity, potentially highlighting the acute kidney injury associated with COVID-19. This study illuminates the intricate relationship between disturbed sphingolipid metabolism, COVID-19 severity, and clinical factors. These findings provide valuable insights into the broader landscape of inflammatory diseases.