Signal Activity Research Articles

A cross-tissue transcriptome-wide association study identifies new susceptibility genes for benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is a prevalent urinary system disorder. Despite evidence of a significant genetic component from previous studies, the specific pathogenic genes and biological mechanisms are still largely unknown. The study utilized the FinnGen R10 dataset, encompassing 177,901 individuals (36,601 cases and 141,300 controls), and the GTEx v8 EQTLs files to conduct single-tissue and cross-tissue transcriptome-wide association studies (TWAS). FUSION method was utilized to validate the findings in specific tissues. Gene Analysis and Multi-marker Analysis of Genomic Annotation (MAGMA) were used to identify potential susceptibility genes. The intersection genes of the above results were analyzed by Mendelian randomization (MR), summary data-based MR (SMR) and colocalization studies. Fine-mapping of causal gene sets (FOCUS) software was employed to accurately locate risk genes. Gene Expression Omnibus (GEO) analysis explores the differential expression of genes. Finally, The GeneMANIA tool was utilized to further understand the functional roles of these susceptibility genes. The cross-tissue TWAS analysis revealed 28 genes associated with BPH susceptibility. Single-tissue TWAS and MAGMA further refined eight genes, and subsequent MR, SMR, FOCUS and colocalization analysis pinpointed INO80B as the key gene. The differential expression of this result was verified by GEO. INO80B may help prevent excessive prostatic cell proliferation by regulating cell cycle-related gene expression. Our research identified the INO80B gene, whose predicted expression is associated with BPH risk and hence provided a new insight into the genetic basis of this disease. However, further functional studies are necessary to elucidate the potential biological activity of these significant signals.

Некоторые цианозамещённые спиросочленённые пиразолины и пирролидины, обладающие антимикробной активностью

This work summarizes one-pot synthetic approaches to spiro-fused (di)azoles, which are promising in terms of studying biological activity. Proposed approaches involve condensation reactions of (hetero)cyclic ketones, methylene active moieties, and N-nucleophiles, occurring under mild conditions by both stepwise and concerted mechanisms. The antimicrobial activity of signals from the proposed approaches of cyanosubstituted spiro-membered pyrazolines and pyrrolidines against gram-negative (P. aeruginosa, E. coli) and gram-positive (S. aureus) losses has been studied (EC50 determination (μg/ml)).The well-known component of broad-spectrum antimicrobial drugs, ciprofloxacin, has been used as a control. It has been found that 3-amino-2-(4-nitrophenyl)-1,2-diazaspiro[4.5]dec-3-ene-4-carbonitrile exhibits the greatest inhibitory effect against selected gram-negative bacteria. In this case, the phenyl substituent at the second nitrogen atom of the pyrazoline ring plays an important role, since its replacement with an aroyl fragment reduces the studied effect by several tens of times, regardless of the type of the second ring. Substituted spiroindolinopyrrolizidinedicarbonitriles, containing cyano groups at the 2nd carbon atom of the pyrrolizidine ring and a phenyl substituent at the first, also exhibit a moderate and high inhibitory effect. For pairs with the same type of substituent position, compounds containing a 3,4 Cl2 substituent in the phenyl fragment have the greatest antimicrobial activity.

Fractional amplitude of low-frequency fluctuations in right dorsal cingulum bundle associated with depression symptoms in AD patients: effects of donepezil intervention.

Our aim was to investigate the mechanisms of spontaneous brain activity of white matter functional signals in Alzheimer's disease (AD) patients after donepezil intervention. We used resting-state functional magnetic resonance imaging and the fractional amplitude of low-frequency fluctuations (fALFF) approach to investigate changes in spontaneous brain activity of white matter functional signals in AD patients before and after donepezil intervention. A total of 32 subjects participated in the study, including 16 healthy subjects (HCs) and 16 AD patients. The 16 AD patients underwent brain imaging and neuropsychological assessment before and after donepezil. ANOVA and post hoc t-test analysis were used to compare the differences in fALFF between the three groups. Pearson correlations were used to investigate the relationships between abnormal fALFF values and clinical variables in AD patients before and after intervention (P < 0.05). Compared to HCs, AD patients before donepezil intervention had an abnormal fALFF in superior longitudinal fasciculus 2; AD patients after donepezil intervention had an abnormal fALFF in right superior longitudinal fasciculus 1,2 and right dorsal cingulum, Compared with baseline, AD patients after donepezil intervention had an abnormal fALFF in the right dorsal cingulum. Compared with the baseline, AD patients after donepezil intervention had significantly decreased depression scores (P < 0.0003). Our study showed that spontaneous activity of functional signalling in the cholinergic pathway was altered in AD patients after donepezil intervention and that this change was associated with depressive symptoms in AD patients.

Exploring the Relationship Between CAIDE Dementia Risk and EEG Signal Activity in a Healthy Population.

Accounting for dementia risk factors is essential in identifying people who would benefit most from intervention programs. The CAIDE dementia risk score is commonly applied, but its link to brain function remains unclear. This study aims to determine whether the variation in this score is associated with neurophysiological changes and cognitive measures in normative individuals. The sample comprised 38 participants aged between 54 and 79 (M = 67.05; SD = 6.02). Data were collected using paper-and-pencil tests and electroencephalogram (EEG) recordings in the resting state, channels FP1 and FP2. The EEG signals were analyzed using Power Spectral Density (PSD)-based features. The CAIDE score is positively correlated with the relative power activation of the θ band and negatively correlated with the MMSE cognitive test score, and MMSE variations align with those found in distributions of EEG-extracted PSD-based features. The findings suggest that CAIDE scores can identify individuals without noticeable cognitive changes who already exhibit brain activity similar to that seen in people with dementia. They also contribute to the convergent validity between CAIDE and the risk of cognitive decline. This underscores the importance of early monitoring of these factors to reduce the incidence of dementia.

Combined acoustic emission and electrochemical methods for analyzing the uniform corrosion behavior of X90 high-grade steel pipelines

Long-distance, large-diameter, and high-pressure pipelines represent the future of oil and gas pipeline construction. X90 pipeline steel is expected to become the standard steel due to its high transmission efficiency and lower cost in the future, yet corrosion poses the most significant challenge to the development of high-strength pipelines. This study focuses on monitoring the uniform corrosion process of X90 steels using acoustic emission (AE) and electrochemical testing systems. The AE signals from corrosion were processed using wavelet de-noising, decomposition, and reconstruction to extract signal characteristics. Experimental results reveal that the corrosion process of X90 steel can be categorized into three stages: initial metal dissolution, corrosion product accumulation, and corrosion stabilization. Signal activity and strength follow normal distributions throughout these stages. During metal dissolution and corrosion stabilization, AE signals exhibit a frequency range of 100–200 kHz with relatively low amplitude. Conversely, during corrosion product accumulation, signals display a narrow frequency range with higher amplitudes, typically around 3 × 10-4V. Moreover, the appearance of a double-peak signal suggests the presence of two distinct AE sources.

Cry1Ac toxin binding in the velvetbean caterpillar Anticarsia gemmatalis: study of midgut aminopeptidases N.

The velvetbean caterpillar Anticarsia gemmatalis is one of the main soybean defoliators in Brazil. Currently, the main biopesticide used to control insect pests worldwide is the bacteria Bacillus thuringiensis (Bt), which produces entomopathogenic Crystal toxins (Cry) that act in the midgut of susceptible insects, leading them to death. The mode of action of Cry toxins in the midgut involves binding to specific receptors present on the brush border of epithelial cells such as aminopeptidase N (APN), alkaline phosphatase (ALP), cadherin, and others. Mutations in these receptors, among other factors, may be involved in the development of resistance; identification of functional Cry receptors in the midgut of A. gemmatalis is crucial to develop effective strategies to overcome this possible scenario. This study's goal is to characterize APNs of A. gemmatalis and identify a receptor for Cry1Ac in the midgut. The interaction of Bt spores with the midgut epithelium was observed in situ by immunohistochemistry and total aminopeptidase activity was estimated in brush border membrane vesicle (BBMV) samples, presenting higher activity in challenged individuals than in control ones. Ten APN sequences were found in a A. gemmatalis' transcriptome and subjected to different in silico analysis, such as phylogenetic tree, multiple sequence alignment and identification of signal peptide, activity domains and GPI-anchor signal. BBMV proteins from 5th instar larvae were submitted to a ligand blotting using activated Cry1Ac toxin and a commercial anti-Cry polyclonal antibody; corresponding bands of proteins that showed binding to Cry toxin were excised from the SDS-PAGE gel and subjected to mass spectrometry analysis, which resulted in the identification of seven of those APNs. Quantitative PCR was realized to compare expression levels between individuals subjected to sublethal infection with Bt spores and control ones, presenting up- and downregulations upon Bt infection. From these results, we can infer that aminopeptidases N in A. gemmatalis could be involved in the mode of action of Cry toxins in its larval stage.

The N-acetylglucosaminyltransferase Radical fringe contributes to defects in JAG1-dependent turnover and signaling of NOTCH3 CADASIL mutants

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic vascular dementia characterized by age-related degeneration of vascular mural cells and accumulation of a NOTCH3 mutant protein. NOTCH3 functions as a signaling receptor, activating downstream gene expression in response to ligands like JAG1 and DLL4, which regulate the development and survival of mural cells. This signal transduction process is thought to be connected with NOTCH3 endocytic degradation. However, the specific cellular circumstances that modulate turnover and signaling efficacy of NOTCH3 mutant protein remain largely unknown. Here, we found elevated NOTCH3 and Radical fringe (RFNG) expression in senescent human pericyte cells. We then investigated impacts of RFNG on glycosylation, degradation, and signal activity of three NOTCH3 CADASIL mutants (R90C, R141C, and C185R) in EGF-like repeat-2, 3, and 4, respectively. LC–MS/MS analysis showed that RFNG modified NOTCH3 WT and C185R to different degrees. Additionally, coculture experiments demonstrated that RFNG significantly promoted JAG1-dependent degradation of NOTCH3 WT but not that of R141C and C185R mutants. Furthermore, RFNG exhibited a greater inhibitory effect on JAG1-mediated activity of NOTCH3 R141C and C185R compared to that of NOTCH3 WT and R90C. In summary, our findings suggest that NOTCH3 R141C and C185R mutant proteins are relatively susceptible to accumulation and signaling impairment under cellular conditions of RFNG and JAG1 coexistence.

Ultrasensitive carbon nanotube-bridged MXene conductive network arrays for one-step homogeneous electrochemical immunosensing of tumor markers

Developing non-passivating and fully integrated electrode arrays for point-of-care testing of carcinoembryonic antigen (CEA) is crucial, as the serum level of CEA is closely associated with colorectal cancer. Herein, we propose a simple, low-cost, and eco-friendly template-assisted filtration method for the scalable preparation of carbon nanotube-bridged Ti3C2Tx MXene (MX@CNT) electrode arrays with a conductive network. Furthermore, we fabricate a homogeneous electrochemical (HEC) sensor for CEA detection by integrating a magnetic-bead-based alkaline phosphatase-linked immunoassay (MB-aElisa), which enables the in-situ generation of the electroactive substance 1-naphthol (1-NP). Benefiting from the unique electrochemical characteristics of a MX@CNT electrode array, such as ultra-low background signal and superior electrocatalytic activity towards the hydrolyzed 1-NP, the MB-aElisa-based HEC sensor specifically measures CEA within a detection range spanning from 0.005 to 1.0 ng mL−1, achieving a detection limit of 1.6 pg mL−1. Subsequently, this biosensing prototype is successfully utilized for the detection of CEA in serum specimens obtained from colorectal cancer patients. More importantly, the integration of MB-aElisa with a MX@CNT electrode array not only marks a significant advancement but also enables the creation of a one-step homogeneous electrochemical immunosensing platform, serving as a paradigm for the highly sensitive and selective measurement of trace tumor markers in complex biological samples.

Bioinspired Core-shell nanospheres integrated in multi-signal immunochromatographic sensor for high throughput sensitive detection of Bongkrekic acid in food

Nowadays, notable progress has been achieved in detecting foodborne toxins by employing nanoenzyme-based lateral flow immunoassay (NLFIA) sensors in point-of-care testing (POCT). It continues to be a major challenge to maximize the enzyme-like performance of nanozymes for educe any potential uncertainties in catalytic process. In this study, we employed a facile and efficient self-assembly approach to fabricate nucleoid-shell structured biomimetic nanospheres CuS@Au-Pt (CAP), which demonstrates enhanced brightness of the colorimetric signal, excellent affinity, and excellent peroxidase activity. The integration of CAP with a competitive-assay NLFIA platform enabled sensitive immunochromatographic detection of bongkrekic acid (BA), with LOD as low as 0.66 ng/mL. After signal amplification through enzyme-like reaction, the detection range was extended around 1-fold. Additionally, CAP-NLFIA effectively detected BA with a recovery rate of 80.96–119.36% for real samples. The study proposes using CAP as a signal reporter in a dual-readout LFIA, which can establish a high throughput sensitive detection platform.

Comprehensive analysis of distinct circadian clock subtypes of adult diffuse glioma and their associations with clinicopathological, genetic, and epigenetic profiles.

The circadian clock (CC) has biological and clinical implications in gliomas. Most studies focused on CC effects on the tumor microenvironment and the application of chronotherapy. The present study focused on CC gene expression patterns and intracellular oncogenic activities. Glioma gene expression data were collected from The Human Cancer Genome Atlas (TCGA) project. After applying inclusion and exclusion criteria, we selected 666 patients from TCGA-GBM and TCGA-LGG projects and included important clinicopathological variables. The entire cohort was subjected to clustering analysis and divided into CC1 and CC2 subtypes based on statistical, biological, and clinical criteria. CC2 gliomas showed higher expression of BMAL1 and CRY1 and lower expression of CRY2 and PER2 (adjusted P < .001). CC2 gliomas had q higher activity of cell proliferation, metabolic reprogramming, angiogenesis, hypoxia, and many oncogenic signals (P < .001). The CC2 subtype contained a higher proportion of glioblastomas (P < .001) and had a worse prognosis (P < .001). Stratified Kaplan-Meier and multivariable Cox analyses illustrated that the CC subtype is an independent prognostic factor to clinicopathological characteristics (P < .001), genetic aberrations (P = .006), and biological processes (P < .001). Thus, this study shows statistical evidence of CC subtypes and their biological, and clinicopathological significance in adult gliomas.

The Caspase-Activated DNase drives inflammation and contributes to defense against viral infection

Mitochondria react to infection with sub-lethal signals in the apoptosis pathway. Mitochondrial signals can be inflammatory but mechanisms are only partially understood. We show that activation of the caspase-activated DNase (CAD) mediates mitochondrial pro-inflammatory functions and substantially contributes to host defense against viral infection. In cells lacking CAD, the pro-inflammatory activity of sub-lethal signals was reduced. Experimental activation of CAD caused transient DNA-damage and a pronounced DNA damage response, involving major kinase signaling pathways, NF-κB and cGAS/STING, driving the production of interferon, cytokines/chemokines and attracting neutrophils. The transcriptional response to CAD-activation was reminiscent of the reaction to microbial infection. CAD-deficient cells had a diminished response to viral infection. Influenza virus infected CAD-deficient mice displayed reduced inflammation in lung tissue, higher viral titers and increased weight loss. Thus, CAD links the mitochondrial apoptosis system and cell death caspases to host defense. CAD-driven DNA damage is a physiological element of the inflammatory response to infection.

Mechanism of miR-126 Loaded in Albumin Nanoparticles for Reversing the Multidrug Resistance in Breast Carcinoma Cells

This study discussed the mechanism of miR-126 loaded in albumin nanoparticles in reversing the multi drug resistance (MDR) in breast carcinoma cells through EGFR-MEK-ERK signal pathway. MCF-7/ADM cells were divided into blank set, empty vector set, miR-126 set and set of vector and miR-126 randomly. The change of drug susceptibility, protein expression of P-gp, BCRP, EGFR, p-EGFR, MEK, p-MEK, ERK and p-ERK, correlation between miR-126 and EGFR-MEK- ERK signal pathway were observed. miR-126 expression in set of vector was the highest. The second was in miR-126 set. IC50 of ADM in miR-126 set was 4.6 µg/mL. The reversion times were two times. The reversion times in set of vector and miR-126 set was 2.8 times. The presentation of BCRP and P-gp in miR-126 set and set of vector and miR-126 was reduced notably. The activity of EGFR-MEK-ERK signal pathway was restrained by miR-126. The content of p-EGFR, p-MEK and p-ERK in miR-126 set and set of vector and miR-126 was reduced notably compared with blank set. EGFR-MEK-ERK signal activity was targeting regulated by miR-126 loaded in albumin nanoparticles. The level of phosphoric acid activators was reduced abnormally. The expression of BCRP and P-gp was reduced notably. The MDR in breast carcinoma cells was reversed and the drug susceptibility was elevated notably.

Revealing patterns in Be12O12-metal nanocages as a nitrosourea drug delivery system: DFT, SERS, solvent effects and the role of periods and groups

The use of targeted drugs has emphasized the potential of nanomaterials as carriers for decreasing therapeutic side effects, and cancer therapy has long been an area of study. In this work, we used density functional theory (DFT) and time dependent-DFT simulations to examine the decorating of different metals on Be12O12 as parameters for nitrosourea (NUA) delivery carriers. We looked at the electrical and adsorption characteristics, as well as spectrum analysis and docking. Drugs on nanocages have the potential to adsorb with less energy gap and hardness than the free drug, which could facilitate electron transfer and signal activity at the target location. The drug’s adsorption characteristics can be efficiently changed by charge transfer between the NUA and the nanocages. This study assessed metal-decorated BeO nanocages’ ability to deliver nitrosourea in both vacuum and aqueous settings, offering a logical framework for creating new nitrosourea drug carriers. The present work can be extended to investigate the effect of other various types of nanorings and nanocages to study doping effects and drug delivery carrier properties.

Transfer of polarity information via diffusion of Wnt ligands in C. elegans embryos

Different signaling mechanisms concur to ensure robust tissue patterning and cell fate instruction during animal development. Most of these mechanisms rely on signaling proteins that are produced, transported, and detected. The spatiotemporal dynamics of signaling molecules are largely unknown, yet they determine signal activity's spatial range and time frame. Here, we use the Caenorhabditis elegans embryo to study how Wnt ligands, an evolutionarily conserved family of signaling proteins, dynamically organize to establish cell polarity in a developing tissue. We identify how Wnt ligands, produced in the posterior half of the embryos, spread extracellularly to transmit information to distant target cells in the anterior half. With quantitative live imaging and fluorescence correlation spectroscopy, we show that Wnt ligands diffuse through the embryo over a timescale shorter than the cell cycle, in the intercellular space, and outside the tissue below the eggshell. We extracted diffusion coefficients of Wnt ligands and their receptor Frizzled and characterized their co-localization. Integrating our different measurements and observations in a simple computational framework, we show how fast diffusion in the embryo can polarize individual cells through a time integration of the arrival of the ligands at the target cells. The polarity established at the tissue level by a posterior Wnt source can be transferred to the cellular level. Our results support a diffusion-based long-range Wnt signaling, which is consistent with the dynamics of developing processes.

An optimized high-throughput SARS-CoV-2 dual reporter trans-complementation system for antiviral screening in vitro and in vivo

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still epidemic around the world. The manipulation of SARS-CoV-2 is restricted to biosafety level 3 laboratories (BSL-3). In this study, we developed a SARS-CoV-2 ΔN-GFP-HiBiT replicon delivery particles (RDPs) encoding a dual reporter gene, GFP-HiBiT, capable of producing both GFP signal and luciferase activities. Through optimal selection of the reporter gene, GFP-HiBiT demonstrated superior stability and convenience for antiviral evaluation. Additionally, we established a RDP infection mouse model by delivering the N gene into K18-hACE2 KI mouse through lentivirus. This mouse model supports RDP replication and can be utilized for in vivo antiviral evaluations. In summary, the RDP system serves as a valuable tool for efficient antiviral screening and studying the gene function of SARS-CoV-2. Importantly, this system can be manipulated in BSL-2 laboratories, decreasing the threshold of experimental requirements.

Primary Cilium in Neural Crest Cells Crucial for Anterior Segment Development and Corneal Avascularity.

Intraflagellar transport 46 (IFT46) is an integral subunit of the IFT-B complex, playing a key role in the assembly and maintenance of primary cilia responsible for transducing signaling pathways. Despite its predominant expression in the basal body of cilia, the precise role of Ift46 in ocular development remains undetermined. This study aimed to elucidate the impact of neural crest (NC)-specific deletion of Ift46 on ocular development. NC-specific conditional knockout mice for Ift46 (NC-Ift46F/F) were generated by crossing Ift46F mice with Wnt1-Cre2 mice, enabling the specific deletion of Ift46 in NC-derived cells (NCCs). Sonic Hedgehog (Shh) and Notch signaling activities in NC-Ift46F/F mice were evaluated using Gli1lacZ and CBF:H2B-Venus reporter mice, respectively. Cell fate mapping was conducted using ROSAmTmG reporter mice. The deletion of Ift46 in NCCs resulted in a spectrum of ocular abnormalities, including thickened corneal stroma, hypoplasia of the anterior chamber, irregular iris morphology, and corneal neovascularization. Notably, this deletion led to reduced Shh signal activity in the periocular mesenchyme, sustained expression of key transcription factors Foxc1, Foxc2 and Pitx2, along with persistent cell proliferation. Additionally, it induced increased Notch signaling activity and the development of ectopic neovascularization within the corneal stroma. The absence of primary cilia due to Ift46 deficiency in NCCs is associated with anterior segment dysgenesis (ASD) and corneal neovascularization, suggesting a potential link to Axenfeld-Rieger syndrome, a disorder characterized by ASD. This underscores the pivotal role of primary cilia in ensuring proper anterior segment development and maintaining an avascular cornea.

Abstract B025: IL6 signaling in pre-malignant obese endometrium and endometrial cancer

Abstract Objective: Obesity associated chronic inflammatory status plays a role in the increased endometrial cancer incidences, IL-6 is one of those inflammatory molecules. To explore the potential of targeting pro-inflammation factors for endometrial cancer prevention, using multi-platform and multi-model analysis, we investigated IL6 and its associated signaling in pre-malignant endometrium and low-grade endometrial cancer. Methods: Illumina microarray and Nanostring nCounter® Pancancer Immune profiling panel gene expression profiling was performed on pre-malignant obese endometrium from diet induced obese Wistar rats, and endometrium from obese patients, lean endometrium was used as control. Clariom D assay was performed on RNA extracted from the gland and stroma of human obese endometrial carcinoma (OEC) and obese normal endometrium (ONE). IPA, nSolver, Transcriptome Analysis Console (TAC), and CIBERSORTx were used for data analysis. Ishikawa cells were 2D and 3D cultured, or 3D co-cultured with endometrial stroma cell line SHT290. Western blot was used for testing cell signal activity. Results: Pronounced IL-6 signaling (Z-score:2.3333, p=2.48E-02) was shown in pre-malignant obese endometrium of diet induced obese rats compared with lean littermates: NF-kB signaling (Z-score:2.714, p=3.47E-02), STAT3 signaling (Z-score:2.53, p=6.56E-04), and tumor microenvironment pathway (Z-score: 3.441, p=6.81E-05) were enhanced; PTEN signaling (Z-score:-1.997, p=2.76E-03) was attenuated. IL6R (FC=1.64, p=0.017), MMP2 (FC=1.938, p=0.026), IL1R2 (FC=1.75, p&amp;lt;0.0001), and CCL2 (FC=2.251, p=0.002) expression were increased. IL6 induced stronger STAT3 signaling, and weaker activation of MAPK signaling in Ishikawa cells 3D co-cultured with stroma cells, compared with 3D cultured Ishikawa cells without stroma cells. No IL-6 induced activation of MAPK signaling was observed with activation of Stat3 signaling in 2D-cultured Ishikawa cells. In pre-malignant obese endometrium from patients with high serum IL-6 levels, attenuated pro-inflammation signaling was seen compared with that from patients with low serum IL6 level: expression of IL1A (FC=-2.21, p=0.001), IRF8 (FC=-1.83, p=0.012), GAGE1 (FC=-3.49, p=0.028), and LBP (FC=-2.03, p=0.038) were decreased. Compared with pre-malignant obese endometrium, more regulatory T cell (Tregs, 0.1276 vs 0.077, p=0.04), and less eosinophils (0.003 vs 0.022, p=0.028) in the stroma, and more neutrophils (0.0145 vs. 0, p=0.02) in the tumor glands were observed in obese EC, implicating immuno-suppression in OEC. Conclusion: Due to the elevated systemic pro-inflammation status, pre-malignant obese endometrium demonstrated activated IL-6 signaling. IL-6 induced cell signaling varied by cellular microenvironment. In pre-malignant endometrium from obese women with high systemic IL-6 level, attenuated inflammation signaling was observed compared to those with low serum IL6 levels. Immuno-suppression was implicated in obese EC. Citation Format: Qian Zhang, Brenda Melendez, Xiaoping Su, Mikayla Bowen, Joseph Celestino, Melinda Sue Yates, Karen Lu. IL6 signaling in pre-malignant obese endometrium and endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B025.

Damage imaging in plates by evaluating local entropy in guided wavefield data

This paper presents a new algorithm called broadband entropy-based two-stage damage imaging (BE2DI) for the detection and imaging of defects in multi-layer plates.The method differentiates defects from either local scattering phenomena of propagating Lamb waves or locally increased vibrational activity for stimulated global plate resonances by exploiting the higher vibrational activity of full-field broadband vibration signals at defective regions and the distinct spatial behavior of defects and artifacts. Using these features, first, a candidate damage map is constructed by means of iterative thresholding based on descriptive statistics of broadband data. Afterwards, an adaptive regional damage index based on local entropy is introduced, which utilizes operational deflection shapes to process previously identified candidate regions and subsequently reveal both shallow and deep defects. BE2DI can be seen as an automated local defect resonance identification approach in the case of shallow defects. Multiple plates having various defect types with different sizes and depths are investigated. Broadband chirp signals are used to excite the plates using low-power piezoelectric actuators, and vibrational data is registered by 3D scanning laser Doppler vibrometry. The obtained results quantitatively and qualitatively demonstrate that the proposed method can effectively detect different kinds of damage, regardless of being shallow or deep.

Deep learning and predictive modelling for generating normalised muscle function parameters from signal images of mandibular electromyography.

Challenges arise in accessing archived signal outputs due to proprietary software limitations. There is a notable lack of exploration in open-source mandibular EMG signal conversion for continuous access and analysis, hindering tasks such as pattern recognition and predictive modelling for temporomandibular joint complex function. To Develop a workflow to extract normalised signal parameters from images of mandibular muscle EMG and identify optimal clustering methods for quantifying signal intensity and activity durations. A workflow utilising OpenCV, variational encoders and Neurokit2 generated and augmented 866 unique EMG signals from jaw movement exercises. k-means, GMM and DBSCAN were employed for normalisation and cluster-centric signal processing. The workflow was validated with data collected from 66 participants, measuring temporalis, masseter and digastric muscles. DBSCAN (0.35 to 0.54) and GMM (0.09 to 0.24) exhibited lower silhouette scores for mouth opening, anterior protrusion and lateral excursions, while K-means performed best (0.10 to 0.11) for temporalis and masseter muscles during chewing activities. The current study successfully developed a deep learning workflow capable of extracting normalised signal data from EMG images and generating quantifiable parameters for muscle activity duration and general functional intensity.

The regulatory network comprising ArcAB-RpoS-RssB influences motility in Vibrio cholerae.

The diarrheal disease cholera is caused by the versatile and responsive bacterium Vibrio cholerae, which is capable of adapting to environmental changes. Among others, the alternative sigma factor RpoS activates response pathways, including regulation of motility- and chemotaxis-related genes under nutrient-poor conditions in V. cholerae. Although RpoS has been well characterised, links between RpoS and other regulatory networks remain unclear. In this study, we identified the ArcAB two-component system to control rpoS transcription and RpoS protein stability in V. cholerae. In a manner similar to that seen in Escherichia coli, the ArcB kinase not only activates the response regulator ArcA but also RssB, the anti-sigma factor of RpoS. Our results demonstrated that, in V. cholerae, RssB is phosphorylated by ArcB, which subsequently activates RpoS proteolysis. Furthermore, ArcA acts as a repressor of rpoS transcription. Additionally, we determined that the cysteine residue at position 180 of ArcB is crucial for signal recognition and activity. Thus, our findings provide evidence linking RpoS response to the anoxic redox control system ArcAB in V. cholerae.