Development and validation of a model based on immunogenic cell death related genes to predict the prognosis and immune response to bladder urothelial carcinoma

BackgroundImmunogenic cell death (ICD) has been categorized as a variant of regulated cell death that is capable of inducing an adaptive immune response. A growing body of evidence has indicated that ICD can modify the tumor immune microenvironment by releasing danger signals or damage-associated molecular patterns (DAMPs), potentially enhancing the efficacy of immunotherapy. Consequently, the identification of biomarkers associated with ICD that can classify patients based on their potential response to ICD immunotherapy would be highly advantageous. Therefore the goal of the study is to better understand and identify what patients with bladder urothelial carcinoma (BLCA) will respond to immunotherapy by analyzing ICD signatures and investigate ICD-related prognostic factors in the context of BLCA.MethodsThe data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases regarding BLCA and normal samples was categorized based on ICD-related genes (IRGs). Specifically, we conducted an immunohistochemical (IHC) experiment to validate the expression levels of Calreticulin (CALR) in both tumor and adjacent tissues, and evaluated its prognostic significance using the Kaplan-Meier (KM) curve. Subsequently, the samples from TCGA were divided into two subtypes using consensus clustering. To obtain a more comprehensive comprehension of the biological functions, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The calculation of immune landscape between two subtypes was performed through ESTIMATE and CIBERSORT. Risk models were constructed using Cox and Lasso regression and their prognosis predictive ability was evaluated using nomogram, receiver operating characteristic (ROC), and calibration curves. Finally, Tumor Immune Dysfunction and Exclusion (TIDE) algorithms was utilized to predict the response to immunotherapy.ResultsA total of 34 IRGs were identified, with most of them exhibiting upregulation in BLCA samples. The expression of CALR was notably higher in BLCA compared to the adjacent tissue, and this increase was associated with an unfavorable prognosis. The differentially expressed genes (DEGs) associated with ICD were linked to various immune-related pathways. The ICD-high subtypes exhibited an immune-activated tumor microenvironment (TME) compared to the ICD-low subtypes. Utilizing three IRGs including CALR, IFNB1, and IFNG, a risk model was developed to categorize BLCA patients into high- and low-risk groups. The overall survival (OS) was considerably greater in the low-risk group compared to the high-risk group, as evidenced by both the TCGA and GEO cohorts. The risk score was identified as an independent prognostic parameter (all p < 0.001). Our model demonstrated good predictive ability (The area under the ROC curve (AUC), AUC1-year= 0.632, AUC3-year= 0.637, and AUC5-year =0.653). Ultimately, the lower risk score was associated with a more responsive immunotherapy group.ConclusionThe potential of the ICD-based risk signature to function as a marker for evaluating the prognosis and immune landscape in BLCA suggests its usefulness in identifying the suitable population for effective immunotherapy against BLCA

Nutritional assessment models for Alzheimer's disease: Advances and perspectives

Abstract Alzheimer's disease (AD) is a neurodegenerative disease of uncertain pathogenesis that develops in the elderly population and is characterized by loss of cognitive function, memory loss, and deterioration of everyday behavior. The development of biological models of AD is constrained by the complexity of the pathogenesis and multiple causes. Creating disease models can aid in understanding the pathophysiology of AD and developing effective therapeutic drugs. In this review, the animal and cellular models that are currently being utilized to research AD are outlined and described in detail according to modeling approaches. The main animal models are natural aging models, transgenic models, and drug‐induced models. The main cellular models are traditional 2D cells, human induced pluripotent stem 2D cells (neurons and glial cells), and 3D cells, as well as organoid models, and the benefits and drawbacks of their various biological models are assessed. They do have their limitations due to an incomplete reflection of AD pathology. Therefore, new models for AD research are needed in the future. The summary of existing models is intended to provide a basis for the subsequent development of new disease models and to provide a reference for the study of disease mechanisms, clinical research, and new drug development in AD

Gasification Characteristics of High Moisture Content Lignite under CO₂ and Auto-Generated Steam Atmosphere in a Moving Bed Tubular Reactor

An external thermal high-temperature continuous feed moving bed tubular reactor was used for the gasification of high moisture content lignite (30.41 wt.%) under CO2 and an auto-generated steam atmosphere. The objectives of this study are to illustrate the synergistic gasification characteristics of high moisture content lignite and CO2 in the tubular reactor; CO2 and auto-generated steam (steam released from the lignite) were used as gasification agents for lignite gasification. The effects of temperature and CO2 flow rate were also investigated. Experimental results showed that when the gasification temperature increased from 800 °C to 1000 °C, the H2 yield also increased from 8.45 mol kg−1 to 17.86 mol kg−1. This may indicate that the H2O-CO2 gasification of semi-coke was enhanced with the rise in temperature. At 900 °C, the gas yield increased with the increase in CO2 flow rate, while the yield of char and liquid product showed an opposite trend. The lower heating value of the H2-rich syngas varied from 11.73 MJ m−3 to 12.77 MJ Nm−3. The experimental results proved that the high moisture content lignite in-situ CO2 gasification process is an effective methodology for the clean and efficient utilization of lignite

Gasification Characteristics of High Moisture Content Lignite under CO2 and Auto-Generated Steam Atmosphere in a Moving Bed Tubular Reactor

An external thermal high-temperature continuous feed moving bed tubular reactor was used for the gasification of high moisture content lignite (30.41 wt.%) under CO2 and an auto-generated steam atmosphere. The objectives of this study are to illustrate the synergistic gasification characteristics of high moisture content lignite and CO2 in the tubular reactor; CO2 and auto-generated steam (steam released from the lignite) were used as gasification agents for lignite gasification. The effects of temperature and CO2 flow rate were also investigated. Experimental results showed that when the gasification temperature increased from 800 °C to 1000 °C, the H2 yield also increased from 8.45 mol kg−1 to 17.86 mol kg−1. This may indicate that the H2O-CO2 gasification of semi-coke was enhanced with the rise in temperature. At 900 °C, the gas yield increased with the increase in CO2 flow rate, while the yield of char and liquid product showed an opposite trend. The lower heating value of the H2-rich syngas varied from 11.73 MJ m−3 to 12.77 MJ Nm−3. The experimental results proved that the high moisture content lignite in-situ CO2 gasification process is an effective methodology for the clean and efficient utilization of lignite

Strategies Used by 3 to 5 Years Old Children on a Self-imposed Delay of Gratification Task Including a Cross-cultural Comparison Between China and Australia

Using the experiment of self-imposed delay of gratification and situational observation, the developmental characteristics of 3 to 5 years old Chinese children’s self-imposed delay of gratification and the cross-cultural differences between 3.5 to 4.5 years old Chinese and Australian children’s self-imposed delay of gratification were investigated. The results show that the 3 to 5 years old Chinese children’s self-imposed delay of gratification develops with age increasing. 3-year-old children rarely used delay strategies, 4-year-old children’s central delay strategies are the pursuant strategies, 5-year-old children’s central delay strategies are the pursuant strategies and self-distraction and problem-solving strategies, and the self-verbal-control strategies haven’t showed the significant advantage role. In addition, the results also suggest that the 3.5 to 4.5 years old Australian children’s self-imposed delay of gratification is higher than that of the Chinese children of the same age. And there are significant differences and similarities in both between Chinese and Australian children’s development of self-imposed delay of gratification on choosing the delay strategies. The different culture values affect the development of young children’s self-imposed delay of gratification through the different education

Finite element biomechanical analysis of 3D printed intervertebral fusion cage in osteoporotic population

Abstract Objective To study the biomechanical characteristics of each tissue structure when using different 3D printing Cage in osteoporotic patients undergoing interbody fusion. Methods A finite element model of the lumbar spine was reconstructed and validated with regarding a range of motion and intervertebral disc pressure from previous in vitro studies. Cage and pedicle screws were implanted and part of the lamina, spinous process, and facet joints were removed in the L4/5 segment of the validated mode to simulate interbody fusion. A 280 N follower load and 7.5 N·m moment were applied to different postoperative models and intact osteoporotic model to simulate lumbar motion. The biomechanical characteristics of different models were evaluated by calculating and analyzing the range of motion of the fixed and cephalic adjacent segment, the stress of the screw-rod system, the stress at the interface between cage and L5 endplate, and intervertebral disc pressure of the adjacent segment. Results After rigid fixation, the range of motion of the fixed segment of model A-C decreased significantly, which was much smaller than that of the osteoporotic model. And with the increase of the axial area of the interbody fusion cages, the fixed segment of model A-C tended to be more stable. The range of motion and intradiscal pressure of the spinal models with different interbody fusion cages were higher than those of the complete osteoporosis model, but there was no significant difference between the postoperative models. On the other hand, the L5 upper endplate stress and screw-rod system stress of model A-C show a decreasing trend in different directions of motion. The stress of the endplate is the highest during flexion, which can reach 40.5 MPa (model A). The difference in endplate stress between models A-C was the largest during lateral bending. The endplate stress of models A and B was 150.5% and 140.9% of that of model C, respectively. The stress of the screw-rod system was the highest during lateral bending (model A, 102.0 MPa), which was 108.4%, 102.4%, 110.4%, 114.2% of model B and 158.5%, 110.1%, 115.8%, 125.4% of model C in flexion, extension, lateral bending, and rotation, respectively. Conclusions For people with osteoporosis, no matter what type of cage is used, good immediate stability can be achieved after surgery. Larger cage sizes provide better fixation without significantly increasing ROM and IDP in adjacent segments, which may contribute to the development of ASD. In addition, larger cage sizes can disperse endplate stress and reduce stress concentration, which is of positive significance in preventing cage subsidence after operation. The cage and screw rod system establish a stress conduction pathway on the spine, and a larger cage greatly enhances the stress-bearing capacity of the front column, which can better distribute the stress of the posterior spine structure and the stress borne by the posterior screw rod system, reduce the stress concentration phenomenon of the nail rod system, and avoid exceeding the yield strength of the material, resulting in the risk of future instrument failure

<i>Late Elongated Hypocotyl</i> Positively Regulates Salt Stress Tolerance in <i>Medicago truncatula</i>

Abiotic stress, such as drought, osmotic, and salinity stresses, seriously affects plant growth and crop production. Studying stress-resistant genes that enhance plant stress tolerance is an efficient way to facilitate the breeding of crop species with high stress tolerance. In this study, we reported that the core circadian clock component, the LATE ELONGATED HYPOCOTYL (LHY) orthologue MtLHY, plays a positive role in salt stress response in Medicago truncatula. The expression of MtLHY was induced by salt stress, and loss-of-function mutants of MtLHY were shown to be hypersensitive to salt treatment. However, overexpression of MtLHY improved salt stress tolerance through a higher accumulation of flavonoids. Consistently, exogenous flavonol application improved the salt stress tolerance in M. truncatula. Additionally, MtLHY was identified as a transcriptional activator of the flavonol synthase gene, MtFLS. Our findings revealed that MtLHY confers plant salt stress tolerance, at least by modulating the flavonoid biosynthesis pathway, which provides insight into salt stress tolerance that links the circadian clock with flavonoid biosynthesis

Recent advances of natural pigments from algae

Pigment is an important food additive that plays a major role in the sensory impact of food. And natural sources, healthy and non-toxic edible pigments are receiving a lot of attention. Algae is an important source of natural pigments, and contain chlorophyll, phycoerythrin, carotene, and other natural pigments. Besides staining, the pigment also has powerful physiological activities such as antioxidants, anti-inflammatory, anti-obesity, and lipid-lowering. In this paper, three pigments in seaweed were reviewed, and their main structural properties and functions are presented, filling the gap in the review of pigments with seaweed as the main object of introduction. This review provides research basis for the development of new health foods, a new direction for the use of seaweed chlorophyll in the food and pharmaceutical industries