Transit Signal Research Articles

Increased PIEZO1 Expression Is Associated with Worse Clinical Outcomes in Hormone-Receptor-Negative Breast Cancer Patients.

PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. An analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and pathway enrichment analysis. We also analyzed the immune cell composition in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that the PIEZO1 expression levels are higher in hormone-receptor (HR)-negative than in HR-positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR-negative cohorts, especially in triple-negative breast cancer (TNBC), suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR-negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial-mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high-PIEZO1 HR-negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high-PIEZO1 HR-negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR-negative breast cancer.

Self-consistent modeling of metastable helium exoplanet transits

Absorption of stellar X-ray and extreme ultraviolet (EUV) radiation in the upper atmosphere of close-in exoplanets can give rise to hydrodynamic outflows, which may lead to the gradual shedding of their primordial light element envelopes. Excess absorption by neutral helium atoms in the metastable 2 3S state [He I(2 3S)], at ~10 830 Å, has recently emerged as a viable diagnostic of atmospheric escape. Here we present a public add-on module to the 1D photoionization hydrodynamic code ATES, designed to calculate the He I(2 3S) transmission probability for a broad range of planetary parameters. By relaxing the isothermal outflow assumption, the code enables a self-consistent assessment of the He I(2 3S) absorption depth along with the atmospheric mass-loss rate and the outflow temperature profile, which strongly affects the recombination rate of He II into He I(2 3S). We investigate how the transit signal can be expected to depend upon known system parameters, including host spectral type, orbital distance, and planet gravity. At variance with previous studies, which identified K-type stars as favorable hosts, we conclude that late M dwarfs with Neptune-sized planets orbiting at ~0.05–0.1 AU can be expected to yield the strongest transit signal, well in excess of 30% for near-cosmological He-to-H abundances. More generally, we show that the physics that regulates the population and depletion of the metastable state, combined with geometrical effects, can yield somewhat counterintuitive results, such as a nonmonotonic dependence of the transit depth on orbital distance. These are compounded by a strong degeneracy between the stellar EUV flux intensity and the atmospheric He-to-H abundance, both of which are highly uncertain. Compared with spectroscopy data, now available for over 40 systems, our modeling suggests either that a large fraction of the targets have helium-depleted envelopes or that the input stellar EUV spectra are systematically overestimated. The updated code and transmission probability module are available publicly as an online repository.

Molecular phenotypes behind patient stratification based on TP53 and HPV status and potential for treatment personalization with first single-cell RNA sequencing atlas of penile cancer.

8 Background: TP53 mutations and Human papillomavirus (HPV) have been suggested to impact penile squamous cell carcinoma (pSCC) prognosis and may predict treatment outcomes. Insights in differences in tumor micro-environment at single cell resolution may benefit personalized therapeutic development and are currently unavailable. Methods: We performed single cell RNA sequencing and targeted next generation sequencing (for TP53 loss-of-function mutations; p53LOF) on primary HPV-associated and HPV-independent (HPV+/-) pSCC lesions or healthy control samples of the coronal sulcus skin. Cell clusters were annotated based on known marker genes. Gene Set Enrichment Analysis (GSEA) and slingshot trajectory analysis was performed using R/Seurat package. Results: Twenty-two samples were analyzed: 4 tumors harbored p53LOF mutations (1 HPV+ p53LOF, 3 HPV- p53LOF), 6 HPV- p53WT, 6 HPV+ p53WT and 6 healthy controls. A total of 84.394 cells was annotated and we identified 68 distinct cell subtypes in pSCC. In epithelial cells, two distinct pseudotime trajectories stemming from the basal cells were identified characterized by either signals of partial epithelial-mesenchymal transition (pEMT; TGFB, ZEB2, SNAI2) or cornification ( ELF3, KRT19, PPL). Whilst the pEMT trajectory was enriched in p53LOF samples, cornification was enriched in HPV+ p53WT. HPV- p53WT samples displayed increase in metabolic changes and stemness hallmarks ( SOX2, HEY1, ZEB1). GSEA confirmed these findings and showed upregulation of pEMT gene sets in p53LOF; fatty acid metabolism and xenobiotic metabolism in HPV- p53WT, and cornification in HPV+ p53WT. We observed an immune suppressive environment in p53LOF patients with higher regulatory T-cell abundancy, and this correlated with abundancy in the epithelial pEMT clusters. Pseudo-bulk analysis on all T-cell subsets demonstrated a higher expression of inhibitory immune checkpoints ( PD-1, CTLA4, TIM3 and LAG3) in p53LOF and HPV- p53WT while HPV+ p53WT patients displayed higher abundancy of immunomodulatory and cytotoxic natural killer (NK) cells. Conclusions: We established the first comprehensive pSCC transcriptomic atlas at single cell resolution and illustrate differences in molecular phenotypes of pSCC according to TP53 mutation- and HPV status. p53LOF tumors are characterized by pEMT, which is a known driver of invasiveness, therapy resistance and metastasis. HPV- p53WT display hallmarks of stemness, which is related to and may explain chemotherapy-resistance often observed in these patients. p53LOF and HPV- p53WT display immune-evasion and exhaustion, while HPV+ p53WT are characterized by abundant cytotoxic innate-like lymphocytes. These observations provide deeper insights into cancer biology that will help advancing pSCC diagnosis and therapy.

Cronkhite‒Canada syndrome as inflammatory hamartomatous polyposis: new evidence from whole transcriptome sequencing of colonic polyps

BackgroundCronkhite-Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although it has been proposed to be a chronic inflammatory condition, direct evidence of its pathogenesis is lacking. This study aims to investigate the pathophysiology of CCS by analyzing transcriptomic changes in the colonic microenvironment.MethodsNext-generation sequencing-based genome-wide transcriptional profiling was performed on colonic hamartomatous polyps from four CCS patients and normal colonic mucosa from four healthy volunteers. Analyses of differential expression and multiple enrichment analyses were conducted from the molecular level to the cellular level. Quantitative real-time PCR (qRT-PCR) was carried out to validate the sequencing accuracy in samples from six CCS patients and six healthy volunteers.ResultsA total of 543 differentially expressed genes were identified, including an abundance of CC- and CXC-chemokines. Innate immune response-related pathways and processes, such as leukocyte chemotaxis, cytokine production, IL-17, TNF, IL-1 and NF-kB signaling pathways, were prominently enhanced in CCS colonic polyps. Upregulation of wound healing, epithelial-mesenchymal transition, Wnt, and PI3K-Akt signaling pathways were also observed. Enrichment analyses at different levels identified extracellular structure disorganization, dysfunction of the gut mucosal barrier, and increased angiogenesis. Validation by qRT-PCR confirmed increased expression of the LCN2, IL1B, CXCL1, and CXCL3 genes in CCS colonic polyps.ConclusionsThis case-control whole transcriptome analysis of active CCS colonic hamartomatous polyps revealed intricate molecular pathways, emphasizing the role of the innate immune response, extracellular matrix disorganization, inflammatory cell infiltration, increased angiogenesis, and potential epithelial to mesenchymal transition. These findings supports CCS as a chronic inflammatory condition and sheds light on potential therapeutic targets, paving the way for more effective and personalized management of CCS in the future.

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma.

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

MODELING THE TRANSITION TO THE FOURTH EPIDEMIOLOGIC STAGE OF INFLAMMATORY BOWEL DISEASE: PREVALENCE EQUILIBRIUM

Abstract BACKGROUND A theoretical framework for population-level transition across four epidemiologic stages has been proposed for inflammatory bowel disease (IBD): 1. Emergence (low incidence/prevalence); 2. Acceleration in Incidence (rapid rising incidence); 3. Compounding Prevalence (stabilizing incidence, rapid rising prevalence); and 4. Prevalence Equilibrium (decelerated prevalence), which no region has entered yet. Many regions of the early-industrialized world (North America, Europe, Oceania) are currently in stage 3. AIM To model the transition to the 4th epidemiologic stage of IBD based on real-world data. METHODS Transition to stage 4 involves deceleration of prevalence after a period of rapid increase. Age-specific, population-based incidence and prevalence data from Canada (2007–2014, &amp;gt;97% of population) were used to model changing prevalence using a partial differential equation (PDE) derived from a compartment model (Figure 1). The PDE is built on an average historical incidence value (2007–2014) and accounts for changing population age distributions over time. The PDE prevalence output was internally validated by comparing observed historical prevalence values with model outputs. After validation, the model was used to forecast future age-stratified prevalence and provide an estimate for when the transition to stage 4 is expected. Although incidence is predicted to stabilize in stage 3, the PDE was run on five scenarios to account for variability in future incidence values; therefore, we modeled annual incidence increases of 2% and 1%, stable incidence, and annual incidence decreases of 1% and 2%. RESULTS Internal validation of the model compared observed to predicted prevalence values in 2014: The observed prevalence was 0.677%; the model output was 0.678%. The model predicts gradual prevalence deceleration across 2020–2043 (Figure 2). In 2043, prevalence is modeled to range between 1.101% and 1.293% across incidence scenarios (−2% to 2%). Assuming a stable incidence, as predicted by stage 3, the increase in prevalence slows from a difference in annual percent change of 0.021% in 2020 to 0.011% in 2043, signalling transition towards stage 4 (Figure 2). DISCUSSION Stage 3 (Compounding Prevalence) is characterized by a stabilizing incidence trend, and rapid growth in prevalence. Without a growing incidence rate, the IBD population continues to age until mortality approximates incidence, thereby allowing prevalence to stabilize (Stage 4). Understanding the markers of epidemiologic transition and predicting the future population distribution (age, prevalence) of IBD allows healthcare administrators to anticipate the future needs of gastroenterology clinics to continue offering timely, high-quality care and prepare for an aging IBD population with complications from long-standing disease, age-related comorbidities, and polypharmacy. Figure 1 Compartment model that feeds the partial differential equation. The compartment model has three states: healthy (H), diseased (S), and dead (D); the i = incidence; r = remission, and m0 = mortality rates are dependent on age (a) and time (i), where as m1 = mortality rate is dependent on age, time, and possibly duration of disease (d). Figure 2 Modeled time-dependent prevalence of IBD in Canada for 2%, 1%, 0%, −1%, and −2% change in annual incidence (2015–2043).

Increasing Long-Term Memory as an Early Warning Signal for a Critical Transition

Abstract In recent years, various early warning signals of critical transition have been presented, such as autocorrelation at lag 1 [AR(1)], variance, the propagator based on detrended fluctuation analysis (DFA-propagator), and so on. Many studies have shown that the climate system has the characteristics of long-term memory (LTM). Will the LTM characteristics of the climate system change as it approaches possible critical transition points? In view of this, the present paper first studies whether the LTM of several folding (folded bifurcation) models changes consistently as they approach their critical points slowly by the rescaled range (R/S) analysis. The results of numerical experiments show that when the control parameters of the folding model are close to its critical threshold, the Hurst exponent H exhibits an almost monotonic increase (significance level α = 0.05). We compare the performance of R/S with the existing indicators, including AR(1), variance, and DFA-propagator, and find that R/S is a perfectly valid alternative. When there is no extra false noise, AR(1) and variance have good early warning effects. After the addition of extra Gaussian white noise of different intensities, the values of AR(1) and variance change significantly. As a result, the DFA-propagator based on AR(1) calibration also changed significantly. Compared with the other three indicators, the early warning effect of H has stronger ability to resist the interference of external false signals. To further verify the validity of increasing H, paleoclimate reconstruction of Cariaco Basin sediment core grayscale record with long trends filtered out is studied by R/S analysis. The other three early warning signals are calculated in the same way. The data contain a well-known abrupt climate change: the transition between the Younger Dryas (YD) and the Holocene. We find that approximately 300 years before this abrupt climate change occurred, before 11.7 kyr BP, the LTM exponents for Cariaco Basin deglacial grayscale data present an obvious increasing trend at a significant level of α = 0.05. Meanwhile, the variation trend of H and DFA-propagator is basically similar. This shows that increasing H by R/S analysis is an effective early warning signal, which indicates that a dynamic system is approaching its possible critical transition points; H is a completely valid alternative signal for AR(1) and DFA-propagator. The main conclusion of this paper is based on numerical experiments. The precise relationship between H and the stability of the underlying state approaching the transition needs to be further studied. Significance Statement Dynamic systems have critical transition points, and these systems will suddenly change from a stable state to another alternative one beyond these points. Using several simple theoretical models and paleoclimate data, we study whether the characteristics of long-term memory, which are ubiquitous in complex systems in nature and society, change as a system approaches its critical transition point. The results show that the long-term memory of a dynamic system increases significantly with the approach of the critical point, whether in theoretical models or in paleoclimate data.

Phenotypic and transcriptional changes in lens epithelial cells following acute and fractionated ionizing radiation exposure

Purpose Exposure to ionizing radiation is one of the known risk factors for the development of lens opacities. It is believed that radiation interactions with lens epithelial cells (LEC) are the underlying cause of cataract development, however, the exact mechanisms have yet to be identified. The aim of this study was to investigate how different radiation dose and fractionation impact normal LEC function. Materials and methods A human derived LEC cell line (HLE-B3) was exposed to a single acute x-ray dose (0.25 Gy) and 6 fractionated doses (total dose of 0.05, 0.1, 0.25, 0.5, 1, and 2 Gy divided over 5 equal fractions). LEC were examined for proliferation using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and migration using a Boyden chamber assay at various time points (0.25, 0.5, 1, 2, 4, 7, 9, 11, and 14 d) post-irradiation. Transcriptomic analysis through RNA sequencing was also performed to identify differentially expressed genes and regulatory networks in cells following 4 different acute exposures and 1 fractionated exposure. Results Exposure to an acute dose of 0.25 Gy significantly increased proliferation and migration rates, peaking at 7 d post irradiation (20% and 240% greater than controls, respectively), before returning to baseline levels by day 14. Fractionated exposures had minimal effects up to a dose of 0.5 Gy, but significantly reduced proliferation and migration after 1 and 2 Gy by up to 50%. The largest transcriptional response occurred 12 h after an acute 0.25 Gy dose, with 362 genes up-regulated and 288 genes down-regulated. A unique panel of differentially expressed genes was observed between moderate versus high dose exposures, suggesting a dose-dependent transcriptional response in LEC that is more pronounced at lower doses. Gene ontology and upstream regulator analysis identified multiple biological processes and molecular functions implicated in the radiation response, in particular differentiation, motility, receptor/ligand binding, cell signaling and epithelial-mesenchymal cell transition. Conclusions Overall, this research provides novel insights into the dose and fractionation effects on functional changes and transcriptional regulatory networks in LEC, furthering our understanding of the mechanisms behind radiation induced cataracts.

Application of Intelligent Maintenance Management System for Urban Rail Transit Communication and Signaling

Application of Intelligent Maintenance Management System for Urban Rail Transit Communication and Signaling

ARTN-GFRA3 axis induces epithelial-mesenchymal transition phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

Neural invasion underlies the local spread of gastric cancer and is associated with poor prognosis. This process has been receiving increasing attention in recent years. However, the relationship between neural invasion and the malignant phenotypes of gastric cancer cells, as well as the molecular mechanism involved in this process, remain unclear. In this study, bioinformatics analysis was performed using a dataset obtained from The Cancer Genome Atlas-Stomach Adenocarcinoma. The results revealed that high expression of GDNF family receptor alpha 3 (GFRA3) was associated with a poor prognosis of patients with gastric cancer. GFRA3 is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). This association was indicated by short overall/disease-free survival, as well as the presence of high-stage and high-grade disease. Gene set enrichment analysis showed that two cancer-associated pathways, namely KRAS signaling and epithelial-mesenchymal transition (EMT), were activated when GFRA3 was highly expressed in gastric cancer. Further studies confirmed that GFRA3 activated KRAS downstream signaling phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) or extracellular signal-regulated kinase (ERK) and induced EMT markers, as well as promoted the migration and invasion of gastric cancer cells. As a ligand of GFRA3, ARTN induced the EMT, migration, and invasion of gastric cancer cells via GFRA3. Notably, the effects of the ARTN-GFRA3 axis were attenuated by treatment with a KRAS inhibitor. The present findings indicated that, during the neural invasion of gastric cancer, ARTN-mediated activation of GFRA3 induces EMT phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling.

A Comprehensive Exploration of Metabolism and Tumor Microenvironment and Immunotherapy Response: Evidence From Large Populations in Non-small Cell Lung Cancer

Aims: The study aimed to explore the effect of metabolism on lung cancer. Background: The tumor microenvironment is largely influenced by metabolism, tightly involved in tumor progression. Objective: We try to investigate the effect of tumor metabolism terms on non-small cell lung cancer (NSCLC) prognosis, drug and immunotherapy sensitivity, as well as its underlying mechanisms. Methods: All the data was obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. R software was used to perform all statistical analyses and plots. Results: This study conducted 21 metabolism statuses in NSCLC to identify their underlying roles. We found that alpha-linolenic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, fatty acid degradation, linoleic acid metabolism, primary bile acid biosynthesis, and fatty acid metabolism were protective factors for NSCLC. Next, we constructed a prognosis model based on primary bile acid biosynthesis, glycerophospholipid, and sphingolipid metabolism. Results in the present study showed that our model could effectively predict patients' prognosis in both training and validation cohorts. A clinical correlation revealed that patients at high-risk exhibited more progressive clinical characteristics. Biological enrichment indicated that MYC targets, E2F targets, mTORC1 signaling, G2/M checkpoint, and epithelial-mesenchymal transition were activated in the high-risk group. Immune relation analysis showed that risk score positively correlated with Th2 cells, yet a negative correlation with CD56 bright NK, Th17, mast and CD8+ T cells. Moreover, our model was related to NSCLC patients' sensitivity to immunotherapy and chemotherapy. Ultimately, eight characteristic genes were identified to distinguish the patients' risk group in the real application. Conclusions: The model we developed is a useful tool to predict NSCLC patients' prognosis and is associated with the sensitivity of immunotherapy and chemotherapy. Meanwhile, our results can guide the following metabolism-related studies in NSCLC.

Coordinated Transit Signal Priority and Vehicle Guidance for Automated Buses

Coordinated Transit Signal Priority and Vehicle Guidance for Automated Buses

Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

Analysing the Environmental and Social Impacts of a Novel User‐Based Transit Signal Priority Strategy in a Connected Vehicle Environment

Transit signal priority (TSP) is a traffic control strategy aiming at prioritising public transit vehicles at signalised intersections. The emergence of connected vehicles (CVs) provides the opportunity to enhance TSP operation, mitigating challenges such as the negative impact on nontransit users and the management of conflicting priority requests. Furthermore, traffic control policies produce environmental impacts, whilst TSP strategies are typically evaluated based on common traffic flow indicators, such as average vehicle speed, delay and/or the number of stops. In light of the recent progress made in CV technology, we propose and assess two user‐based TSP strategies. The first approach aims to minimise total user delay at a signalised intersection, whilst the second considers both reducing bus schedule delay and total user delay. We also measure the environmental effects of these TSP strategies. A microscopic simulation environment is used to compare the proposed methods’ performance against a conventional TSP ring‐and‐barrier controller in a case study involving two adjacent signalised intersections in Helsinki, Finland. The findings indicate that implementing the proposed strategies effectively enhances TSP performance whilst also lowering adverse environmental impacts.

Manipulation of ferromagnetic ordering in magnetic semiconductor Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;)As by In doping

Magnetic semiconductors (MSs) that can manipulate both spin degree of freedom and charge degree of freedom have become an important research field in semiconductor spintronics. In recent years, a new series of bulk form MSs, which are iso-structure to the iron-based superconductors were reported. In these new materials, spins and carriers are separately introduced, and can be precisely manipulated. Li(Zn, Mn)As with &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; ~50 K is the first bulk MS with spins and charges separated. The Li(Zn, Mn)As has p-type carriers, which is in contradiction with the theoretical calculation results by Mašek et al., who claimed that doping extra Li will induce n-type carriers. So, it is necessary to study the formation reason of hole carriers in Li(Zn, Mn)As and their effect on ferromagnetic ordering. In this work, a series of Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925–&lt;i&gt;y&lt;/i&gt;&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;, In&lt;sub&gt;&lt;i&gt;y&lt;/i&gt;&lt;/sub&gt;)As (&lt;i&gt;y&lt;/i&gt; = 0, 0.05, 0.075, 0.1) new materials are successfully synthesized by introducing n-type carriers into the p-type bulk MS Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;)As through (Zn&lt;sup&gt;2+&lt;/sup&gt;, In&lt;sup&gt;3+&lt;/sup&gt;) substitution. Magnetization measurements reveal that all the samples still maintain a ferromagnetic transition signal similar to MS Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;)As, and the Curie temperature &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;C&lt;/sub&gt; is obviously suppressed with the increase of In-doping concentration. Clear hysteresis loops demonstrate the ferromagnetic ordering state. The resistivity increases gradually with the increase of In-doping concentration. Our results show that the (Zn&lt;sup&gt;2+&lt;/sup&gt;, In&lt;sup&gt;3+&lt;/sup&gt;) substitution successfully introduces n-type carriers into Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;)As, and the original p-type carriers in Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;)As, which are partial neutralized, resulting in the decrease of p-type carrier concentrations, which obviously suppresses the ferromagnetic ordering of Li(Zn, Mn)As. It reflects the important roles played by carriers in forming ferromagnetic ordering in MS materials. The fabrication of Li&lt;sub&gt;1.05&lt;/sub&gt;(Zn&lt;sub&gt;0.925–&lt;i&gt;y&lt;/i&gt;&lt;/sub&gt;, Mn&lt;sub&gt;0.075&lt;/sub&gt;, In&lt;sub&gt;&lt;i&gt;y&lt;/i&gt;&lt;/sub&gt;)As material gives us a better understanding of the mechanism of ferromagnetic ordering in Li(Zn, Mn)As, and these results will be helpful in searching for more novel magnetic semiconductor materials.

Transit Signal Priority Strategy With Heterogeneous Graph-Based Deep Reinforcement Learning for Autonomous Public Transit Vehicles

Transit Signal Priority Strategy With Heterogeneous Graph-Based Deep Reinforcement Learning for Autonomous Public Transit Vehicles

Effect of Diosmin on The Expression of Epithelial-Mesenchymal Transition Signaling Molecules in Ndea-Induced Hepato-Cellular Carcinoma in Experimental Rats

Hepatocellular carcinoma (HCC) is a primary liver cancer, distinct from other cancers originating in other organs. Previous study demonstrated that diosmin exhibits anticancer effects by influencing the expression of apoptotic signaling molecules in NDEA-induced hepatocellular carcinoma in rats. However, its impact on the epithelial-mesenchymal transition (EMT) signaling pathway, crucial in liver cancer progression, remains unknown. The research aimed to investigate diosmin’s effects on EMT signaling molecule expression in NDEA-induced hepatocellular carcinoma in rats. In this experiment, adult male albino rats were categorized into three groups: a control group, NDEA-induced hepatocellular carcinogenic rats and rats with HCC treated with diosmin orally for 28 days. Liver function markers (AST and ALT) were done by biochemical analysis while mNRA expression analysis of EMT-signaling molecules ( E-cadherin and vimentin) were analyzed by Real Time-RT-PCR analysis. One-Way-ANOVA was used for the statistical analysis and significance was considered at p&lt;0.05. Diosmin treatment resulted in a significant decrease in liver function markers compared to the control group (p&lt;0.05). Moreover, diosmin administration led to a notable reduction in mRNA levels of EMT signaling molecules, specifically E-cadherin and vimentin, indicating its potential chemopreventive role against liver cancer. Findings of the present study concludes that diosmin, an alkaloid, may merge as a promising candidate for hepatocellular carcinoma treatment based on its demonstrated efficacy in this experimental model. Keywords: Novel method, Hepatocellular carcinoma, EMT signaling, diosmin, wistar rats, liver function, innovative technique.

An evolutionary view of vanillylamine synthase pAMT, a key enzyme of capsaicinoid biosynthesis pathway in chili pepper.

Pungent capsaicinoid is synthesized only in chili pepper (Capsicum spp.). The production of vanillylamine from vanillin is a unique reaction in the capsaicinoid biosynthesis pathway. Although putative aminotransferase (pAMT) has been isolated as the vanillylamine synthase gene, it is unclear how Capsicum acquired pAMT. Here, we present a phylogenetic overview of pAMT and its homologs. The Capsicum genome contained 5 homologs, including pAMT, CaGABA-T1, CaGABA-T3, and two pseudogenes. Phylogenetic analysis indicated that pAMT is a member of the Solanaceae cytoplasmic GABA-Ts. Comparative genome analysis found that multiple copies of GABA-T exist in a specific Solanaceae genomic region, and the cytoplasmic GABA-Ts other than pAMT are located in the region. The cytoplasmic GABA-T was phylogenetically close to pseudo-GABA-T harboring a plastid transit peptide (pseudo-GABA-T3). This suggested that Solanaceae cytoplasmic GABA-Ts occurred via duplication of a chloroplastic GABA-T ancestor and subsequent loss of the plastid transit signal. The cytoplasmic GABA-T may have been translocated from the specific Solanaceae genomic region during Capsicum divergence, resulting in the current pAMT locus. A recombinant protein assay demonstrated that pAMT had higher vanillylamine synthase activity than those of other plant GABA-Ts. pAMT was expressed exclusively in the placental septum of mature green fruit, whereas tomato orthologs SlGABA-T2/4 exhibit a ubiquitous expression pattern in plants. These findings suggested that both the increased catalytic efficiency and transcriptional changes in pAMT may have contributed to establish vanillylamine synthesis in the capsaicinoid biosynthesis pathway. This study provides insights into the establishment of pungency in the evolution of chili peppers.

Bi-Resolution Hash Encoding in Neural Radiance Fields: A Method for Accelerated Pose Optimization and Enhanced Reconstruction Efficiency

NeRF has garnered extensive attention from researchers due to its impressive performance in three-dimensional scene reconstruction and realistic rendering. It is perceived as a potential pivotal technology for scene reconstruction in fields such as virtual reality and augmented reality. However, most NeRF-related research and applications heavily rely on precise pose data. The challenge of effectively reconstructing scenes in situations with inaccurate or missing pose data remains pressing. To address this issue, we examine the relationship between different resolution encodings and pose estimation and introduce BiResNeRF, a scene reconstruction method based on both low and high-resolution hash encoding modules, accompanied by a two-stage training strategy. The training strategy includes setting different learning rates and sampling strategies for different stages, designing stage transition signals, and implementing a smooth warm-up learning rate scheduling strategy after the phase transition. The experimental results indicate that our method not only ensures high synthesis quality but also reduces training time. Compared to other algorithms that jointly optimize pose, our training process is sped up by at least 1.3×. In conclusion, our approach efficiently reconstructs scenes under inaccurate poses and offers fresh perspectives and methodologies for pose optimization research in NeRF.

Identification of the six-hormone secretion-related gene signature as a prognostic biomarker for colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a globally prevalent cancer, with hormone secretion playing a crucial role in its progression. Despite this, there is limited understanding of the impact of hormone secretion on COAD prognosis. This study aimed to establish a prognostic signature based on hormone secretion-related genes and to elucidate the potential functional mechanisms of these genes in COAD. Using data from The Cancer Genome Atlas COAD cohort (TCGA-COAD), six hormone secretion-related genes were identified (CYP19A1, FOXD1, GRP, INHBB, SPP1, and UCN). These genes were used to develop a Hormone secretion score (HSS), which was then evaluated using the Kaplan-Meier curve and multivariable Cox analysis. The HSS model was further validated with external GEO cohorts (GSE41258, GSE39582, and GSE87211). Functional enrichment analyses were performed, and the CIBERSORT and TIDE algorithms were used to assess tumor infiltration. The study developed a prognostic signature, dividing patients into HSS-high and HSS-low groups. The HSS-high group showed a notably worse prognosis within the TCGA-COAD dataset and in three independent datasets: GSE41258, GSE39582, and GSE87211. Moreover, the HSS-high group predicted a shorter overall survival rate in patients maintaining microsatellite stability (MSS). The functional analysis associated HSS-high with the hypoxic, epithelial-mesenchymal transition (EMT), and TGF-β signaling pathways and correlated with distant and lymph node metastases. The tumor immune microenvironment analysis revealed an elevated CIBERSORT score in the HSS-high group, suggesting an association with tumor metastasis. Further, the HSS-high group showed a higher TIDE score, indicating that patients with high HSS scores are less likely to benefit from Immune Checkpoint Inhibitor (ICI) therapy. This study demonstrated the prognostic significance of a HSS signature based on six hormone secretion-related genes in COAD. The findings suggest that this gene signature may serve as a reliable biomarker for predicting survival outcomes in COAD patients.