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Despite many studies focusing on the prognostic biomarkers in pancreatic adenocarcinomas (PAADs), there is ill-informed about the relationships between their genomic features and immune characteristics. Herein, we deeply investigated the involvement of major driver mutation subtypes with immunophenotypes impacting PAAD outcomes. Based on public data analyses of RNA expression-based immune subtypes in PAAD, in contrast to KRAS G12D & TP53 co-mutant patients with poor outcomes, the best immune subtype C3 (inflammatory) characterized by high Th1/Th2 ratio was relatively enriched in KRASnon-G12DTP53wt patients with better survival, whereas the inferior subtype C2 (IFN-γ dominant) with low Th1/Th2 ratio was more common in the former than in the latter. Moreover, contrary to the highly immunosuppressive microenvironment (high Treg, high ratio of Treg to tumor-specific CD4+ T cell) in KRASG12DTP53mut patients, KRASG12VTP53wt individuals exhibited an inflamed context profiled by multiplex immunohistochemistry. It could be responsible for their outstanding survival advantage over others in postsurgical PAAD patients receiving adjuvant chemotherapy as shown by our cohort. Together, KRASG12VTP53wt may be a promising biomarker for prognostic evaluation and screening certain candidates with PAAD to get desirable survival benefit from adjuvant chemotherapy.
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Purpose: Self-deception refers to an individual holding inflated beliefs about their abilities, plays a crucial role in human behavior and decision-making. Individuals may inflate their abilities when subject to comparisons with others. This study examined the impact of social comparison on self-deception through the implementation of two behavioral experiments. Methods: In Experiment 1, we recruited a sample of 152 undergraduate students. Participants were falsely informed that they performed better (downward comparison) and worse (upward comparison) than average on a game. Subsequently, their level of self-deception was assessed by asking them to predict their performance in a future game, with more inflated predictions indicating greater self-deception. In Experiment 2, we gathered 126 undergraduate students to broaden the current study. This experiment examined the combined effects of comparison direction and comparison gap on self-deceptive behavior. Results: The findings showed that self-deception was more common in circumstances of upward comparison than in downward comparison or no comparison (Experiment 1). Furthermore, Individuals were more inclined to participate in self-deception when encountering a notable performance gap relative to others, particularly in scenarios involving upward social comparison (Experiment 2). Conclusion: The findings suggested that when confronted with threatening social comparative information, people tended to use self-deception to protect themselves. Members of the large gap group experienced strong feelings of unfairness and negative emotions, which led to self-protective behaviors and a greater likelihood of self-deception.
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BACKGROUND: The objective of this experiment was to investigate the role of endogenous proteins and lipids in the structural and physicochemical properties of starch in heat-moisture treatment (HMT) rice flour and to reveal their effect on starch digestibility under heat. RESULTS: The findings indicate that, in the absence of endogenous proteins and lipids acting as a physical barrier, especially proteins, the interaction between rice flour and endogenous proteins and lipids diminished. This reduction led to fewer starch-protein inclusion complexes and starch-lipid complexes, altering the granule aggregation structure of rice flour. It resulted in a decrease in particle size, an increase in agglomeration between starch granules, and more surface cracking on rice granules. Under HMT conditions with a moisture content of 30%, slight gelatinization of the starch granules occurred, contributing to an increased starch hydrolysis rate. In addition, the elevated thermal energy effect of HMT enhanced interactions between starch molecular chains. These resulted in a decrease in crystallinity, short-range ordering, and the content of double-helix structure within starch granules. These structural transformations led to higher pasting temperatures, improved hot and cold paste stability, and a decrease in peak viscosity, breakdown, setback, and enthalpy of pasting of the starch granules. CONCLUSION: The combined analysis of microstructure, physicochemical properties, and in vitro digestion characteristics has enabled us to further enhance our understanding of the interaction mechanisms between endogenous proteins, lipids, and starches during HMT. © 2024 Society of Chemical Industry.
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With the ongoing challenge of air pollution posing serious health and environmental threats, particularly in rapidly industrializing regions, accurate forecasting and effective pollutant identification are crucial for enhancing public health and ecological stability. This study aimed to optimize air quality management through the prediction of the Air Quality Index (AQI) and identification of air pollutants. Our study spans nine representative cities (Hohhot, Yinchuan, Lanzhou, Beijing, Taiyuan, Xi'an, Shanghai, Nanjing, Wuhan) in China, with data collected from January 1, 2015, to November 30, 2021. We proposed a new model for daily AQI prediction, termed VMD-CSA-CNN-LSTM, which employed advanced machine learning techniques, including convolutional neural networks (CNN) and long short-term memory (LSTM) networks, and leveraged the chameleon swarm algorithm (CSA) for hyperparameter optimization, integrated through a variational mode decomposition approach. The model was developed using data from Lanzhou, with a split ratio of 8:1:1 into training, validation, and test sets, achieving an RMSE of 2.25, MAPE of 0.02, adjusted R-squared of 98.91%, and training efficiency of 5.31%. The model was further externally validated in the other eight cities, yielding comparable results, with an adjusted R-squared above 96%, MAPE below 0.1, and RMSE below 7.5. Additionally, we employed a random forest algorithm to identify the primary pollutants contributing to AQI levels. Our results indicated that PM2.5 was the most significant pollutant in Beijing, Taiyuan, and Xi'an, while PM10 was dominant in Hohhot, Yinchuan, and Lanzhou. In Shanghai, Nanjing, and Wuhan, both PM2.5 and PM10 were critical, with ozone also identified as a major air pollutant. This study not only advances the predictive accuracy of AQI models but also aids policymakers by providing a reliable tool for air quality management and strategic planning aimed at pollution reduction. The integration of these advanced computational techniques into environmental monitoring practices offers a promising avenue for enhancing air quality and mitigating pollution-related risks.
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Air Pollutants , Air Pollution , Cities , Environmental Monitoring , China , Air Pollution/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , Particulate Matter/analysis , Neural Networks, Computer , Algorithms , Machine Learning , HumansABSTRACT
OBJECTIVE: The purpose of the present study was to examine the association of oxidative stress markers with sarcopenia in the general United States population under the age of 60. METHODS: We used the National Health and Nutrition Examination Survey data from 2011â2014 and performed Restricted Cubic Spline (RCS) plots, weighted multivariable logistic regression analysis to calculate ratio ratios and 95% Confidence Intervals, and subgroup analysis based on age, sex, hypertension, diabetes mellitus, and body mass index stratification to determine the association of markers of oxidative stress with the prevalence of sarcopenia. RESULTS: The present analysis included a total of 8,782 participants. Firstly, the RCS plots showed a roughly L-shaped curve association of total bilirubin and serum iron with a prevalence of sarcopenia. Secondly, albumin was negatively and linearly associated with the risk of sarcopenia. Finally, with the increase in gamma-glutamyl transferase, the prevalence of sarcopenia showed a trend of first rising and then declining as a result of the iron increase. CONCLUSIONS: We demonstrated a nonlinear association between markers of oxidative stress and sarcopenia. The need to focus more on levels of oxidative stress in the body could provide better prevention strategies for sarcopenia.
Subject(s)
Biomarkers , Nutrition Surveys , Oxidative Stress , Sarcopenia , Humans , Oxidative Stress/physiology , Sarcopenia/epidemiology , Sarcopenia/blood , Female , Male , Biomarkers/blood , Prevalence , Middle Aged , Adult , United States/epidemiology , Risk Factors , Iron/blood , Body Mass Index , gamma-Glutamyltransferase/blood , Young Adult , Bilirubin/blood , Cross-Sectional Studies , Age Factors , Sex FactorsABSTRACT
Background: Bladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses. Results: Six molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups. Conclusions: The study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.
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Biomarkers, Tumor , Precision Medicine , Urinary Bladder Neoplasms , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/therapy , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/immunology , Humans , Prognosis , Biomarkers, Tumor/genetics , Single-Cell Analysis , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Female , MaleABSTRACT
This investigation sought to reveal the effects of heat stress on the meat quality of geese. Wuzong geese were subjected to heat stress at 35°C for 25 d or 4 h to examine different heat stress time on meat quality. Short-time heat stress reduced muscle drip loss and meat color L* value while increasing pH value and meat color a* and b* values. Long-time heat stress decreased body weight and increased leg muscle pH value and meat color b* value. Amino acid profile of geese breast muscle revealed that both LHS and SHS can induce L-Cystine but reduced L-Cystathionine, which were positive correlated with cooking loss and meat color lightness, respectively. Lipidome analysis indicated that heat stress would alter the synthesis of unsaturated fatty acids, and the difference between LHS and SHS on lipids mainly focused on Hex1Cer and TG. Non-target metabolome analysis indicated effects of heat stress on Glycerolipid metabolism, Arachidonic acid metabolism, and Pyrimidine metabolism. Proteome analysis showed that heat stress mainly affects cellular respiration metabolism and immune response. These findings highlight the diverse effects of heat stress on meat quality, amino acid composition, lipidome, metabolome, and proteome in geese.
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AIMS: To explore the pathogenic mechanisms of Candida albicans (C. albicans), focusing on its impact on human health, particularly through invasive infections in the gastrointestinal and respiratory tracts. METHODS: In this study, we evaluated the demographic and clinical profiles of 7 pneumonia patients. Meanwhile, we used Gene Set Enrichment Analysis (GSEA) and Evolutionary Dynamics method to analyze the role of candidalysin in C. albicans pathogenicity. RESULTS: By analyzing genomic data and conducting biomedical text mining, we identified novel mutation sites in the candidalysin coding gene ECE1-III, shedding light into the genetic diversity within C. albicans strains and their potential implications for antifungal resistance. Our results revealed significant associations between C. albicans and respiratory as well as gastrointestinal diseases, emphasizing the fungus's role in the pathogenesis of these diseases. Additionally, we identified a new mutation site in the C. albicans strain YF2-5, isolated from patients with pneumonia. This mutation may be associated with its heightened pathogenicity. CONCLUSION: Our research advances the understanding of C. albicans pathogenicity and opens new avenues for developing targeted antifungal therapies. By focusing on the molecular basis of fungal virulence, we aim to contribute to the development of more effective treatment strategies, addressing the challenge of multidrug resistance in invasive fungal infections.
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This study explores the association between LE8 scores and mortality risks among individuals diagnosed with cardiovascular disease (CVD). Utilizing data from the NHANES conducted between 2005 and 2018, survey-weighted multivariable Cox proportional hazards regression models were utilized. Life's Essential 8 (LE8) scores dose-response associations were assessed using restricted cubic spline regression. Sub-analyses were performed for different categories of CVD. The study consisted of 2164 participants diagnosed with CVD, ranging in age from 20 to 80 years (weighted mean [SE] age, 61.47 [0.34] years; The average total LE8 was 64.97 [0.54]. 499 participants experienced mortality, with 350 deaths attributed to CVD. After accounting for potential covariates, LE8 score was found to be associated with a decreased both all-cause mortality (OR 0.34, CI 0.22-0.51) and CVD mortality (OR 0.40, CI 0.23-0.68). A survey-weighted multivariable Cox model with restricted cubic splines identified the lowest all-cause mortality (P < 0.001) and CVD mortality (P < 0.001) risk when LE8 reach at 63.75 (P < 0.001). The results highlight the association between LE8 scores and reduced mortality in CVD patient population. The implementation of comprehensive initiatives that prioritize healthy dietary patterns, will play a crucial role in alleviating the impact of cardiovascular disease and improving cardiovascular health outcomes.
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Cardiovascular Diseases , Humans , Cardiovascular Diseases/mortality , Middle Aged , Male , Female , Aged , Adult , Aged, 80 and over , Proportional Hazards Models , Young Adult , Risk Factors , Nutrition SurveysABSTRACT
Age-related macular degeneration (AMD) is one of the most common causes of irreversible vision loss in the elderly. Its pathogenesis is likely multifactorial, involving a complex interaction of metabolic and environmental factors, and remains poorly understood. Previous studies have shown that mitochondrial dysfunction and oxidative stress play a crucial role in the development of AMD. Oxidative damage to the retinal pigment epithelium (RPE) has been identified as one of the major mediators in the pathogenesis of age-related macular degeneration (AMD). Therefore, this article combines transcriptome sequencing (RNA-seq) and single-cell sequencing (scRNA-seq) data to explore the role of mitochondria-related genes (MRGs) in AMD. Firstly, differential expression analysis was performed on the raw RNA-seq data. The intersection of differentially expressed genes (DEGs) and MRGs was performed. This paper proposes a deep subspace nonnegative matrix factorization (DS-NMF) algorithm to perform a multi-layer nonlinear transformation on the intersection of gene expression profiles corresponding to AMD samples. The age of AMD patients is used as prior information at the network's top level to change the data distribution. The classification is based on reconstructed data with altered distribution. The types obtained significantly differ in scores of multiple immune-related pathways and immune cell infiltration abundance. Secondly, an optimal AMD diagnosis model was constructed using multiple machine learning algorithms for external and qRT-PCR verification. Finally, ten potential therapeutic drugs for AMD were identified based on cMAP analysis. The AMD subtypes identified in this article and the diagnostic model constructed can provide a reference for treating AMD and discovering new drug targets.
Subject(s)
Biomarkers , Macular Degeneration , Transcriptome , Humans , Macular Degeneration/genetics , Macular Degeneration/metabolism , Biomarkers/metabolism , Machine Learning , Single-Cell Analysis/methods , Mitochondria/genetics , Mitochondria/metabolism , MultiomicsABSTRACT
OBJECTIVE: To explore the clinical phenotype and genetic variant in a Chinese pedigree affected with Hunter syndrome and create immortalized cell lines for the affected pedigree members. METHODS: A pedigree of six members who had visited Xi'an Children's Hospital in July 2022 was selected as the study subject. Clinical data was collected. Whole exome sequencing was carried out for the pedigree members. Candidate variant was verified by Sanger sequencing. In addition, peripheral B lymphocytes were transfected with Epstein-Barr virus to create immortalized cell lines, which were then subjected to enzyme activity analysis. RESULTS: The patient, a five-year-and-seven-month-old boy, had exhibited stiff limbs and enlarged joints. He had developed hernia, scaphocephaly, and barrel chest from 3 months of age. His uncle also had stiff limbs, poor hearing, blindness, and right oblique inguinal hernia. Above features had resembled those of Hunter syndrome. Genetic testing revealed that both the child and his uncle had harbored an IDS (NM_000202.8): c.823G>A (p.D275N) variant, which was unreported previously. Bioinformatic analysis indicated that the D275 to be a highly conserved site, and the D275N variant may affect the stability of the protein's spatial conformation, thereby decrease the catalytic activity of the enzyme. The successfully constructed immortalized lymphoblastoid cell lines for the child and his parents showed increased volume, irregular shape, burr structure and cluster growth. And the value of IDS activity of the patient's immortalized lymphoblastoid cells was below the limit of detection. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PS3+PM2_Supporting+PM5+PP1+PP3). CONCLUSION: Above finding has enriched the phenotypic and mutational spectra of Hunter syndrome, and provided a basis for the genetic counseling for this pedigree. The creation of immortalized cell lines has offered a model for further investigation of the impact of variant on the function of IDS and development of targeted drugs.
Subject(s)
Mucopolysaccharidosis II , Cells, Cultured , Pedigree , Cell Separation , Cell Culture Techniques , Child, Preschool , Mucopolysaccharidosis II/genetics , Genetic Counseling , Female , Phenotype , Hernia/genetics , Exosomes/genetics , Exome Sequencing , Craniosynostoses/genetics , MutationABSTRACT
Cordyceps militaris (L.) Fr. Has long been recognized as a valuable functional food consumed in numerous countries. However, biosynthetic gene clusters of this species and safety regarding mycotoxin production remain largely unexplored. In this study, a ribosomally synthesized and post-translationally modified peptide (RiPP) cluster responsible for the production of cyclopeptide mycotoxins in Cordyceps was unveiled via genome mining. Ustiloxin B and a novel, predominant and Cordyceps specific ustiloxin I were confirmed by extraction and structural analysis. The difference between Ustiloxins I and B lied in the side chain at C19, where an additional methyl substituent in Ustiloxin I resulted in an alanine moiety substitution for glycine of Ustiloxin B. The simultaneous deletion of the two adjacent core genes, CmustYb and CmustYa, using a single guide RNA designed in the intergenic region, and subsequent in-situ complementation via AMA-mediated CRISPR/Cas9 system confirmed the RiPP cluster's responsibility for ustiloxin production. The cultivation of the edited strain yielded ustiloxin-free fruiting bodies without affecting agronomic characters. PCR and genome resequencing confirmed the absence of any off-target events or foreign sequence remnants. This study marks a significant advancement in utilizing CRISPR technology to control ustiloxins in food, underscoring its broader implications for food safety and quality improvement.
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OBJECTIVE: The 5-year survival rate of early-stage non-small cell lung cancer (NSCLC) is still not optimistic. We aimed to construct prognostic tools using clinicopathological (CP) and serum 8-miRNA panel to predict the risk of overall survival (OS) in early-stage NSCLC. MATERIALS AND METHODS: A total of 799 patients with early-stage NSCLC, treated between April 2008 and September 2019, were included in this study. A sub-group of patients with serum samples, 280, were analyzed for miRNA profiling. The primary endpoint of the study was OS. The CP panel for prognosis was developed using multivariate and forward stepwise selection analyses. The serum 8-miRNA panel was developed using the miRNAs that were significant for prognosis, screened using real-time quantitative PCR (qPCR) followed by differential, univariate and Cox regression analyses. The combined model was developed using CP panel and serum 8-miRNA panel. The predictive performance of the panels and the combined model was evaluated using the area under curve (AUC) values of receiver operating characteristics (ROC) curves and Kaplan-Meier survival analysis. RESULT: The prognostic panels and the combined model (comprising CP panel and serum 8-miRNA panel) was used to classify the patients into high-risk and low-risk groups. The OS rates of these two groups were significantly different (P<0.05). The two panels had higher AUC than the two guidelines, and the combined model had the highest AUC. The AUC of the combined model (AUC=0.788; 95 %CI 0.706-0.871) was better than that of the National Comprehensive Cancer Network (NCCN) guideline (AUC=0.601; 95 %CI 0.505-0.697) and Chinese Society of Clinical Oncology (CSCO) guideline (AUC=0.614; 95 %CI 0.520-0.708). CONCLUSION: The combined model based on CP panel and serum 8-miRNA panel allows better prognostic risk stratification of patients with early-stage NSCLC to predict risk of OS.
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Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level. METHODS: We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses. RESULTS: LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. CONCLUSIONS: Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. HIGHLIGHT: Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.
Subject(s)
Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Single-Cell Gene Expression Analysis , Humans , Antigens, Differentiation, B-Lymphocyte/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Immune Evasion/genetics , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/immunology , Single-Cell Gene Expression Analysis/methods , Tumor Microenvironment/genetics , Tumor Microenvironment/immunologyABSTRACT
Background: Increasing evidence have highlighted the biological significance of mRNA N6-methyladenosine (m6A) modification in regulating tumorigenicity and progression. However, the potential roles of m6A regulators in tumor microenvironment (TME) formation and immune cell infiltration in liver hepatocellular carcinoma (LIHC or HCC) requires further clarification. Method: RNA sequencing data were obtained from TCGA-LIHC databases and ICGC-LIRI-JP databases. Consensus clustering algorithm was used to identify m6A regulators cluster subtypes. Weighted gene co-expression network analysis (WGCNA), LASSO regression, Random Forest (RF), and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were applied to identify candidate biomarkers, and then a m6Arisk score model was constructed. The correlations of m6Arisk score with immunological characteristics (immunomodulators, cancer immunity cycles, tumor-infiltrating immune cells (TIICs), and immune checkpoints) were systematically evaluated. The effective performance of nomogram was evaluated using concordance index (C-index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC). Results: Two distinct m6A modification patterns were identified based on 23 m6A regulators, which were correlated with different clinical outcomes and biological functions. Based on the constructed m6Arisk score model, HCC patients can be divided into two distinct risk score subgroups. Further analysis indicated that the m6Arisk score showed excellent prognostic performance. Patients with a high m6Arisk score was significantly associated with poorer clinical outcome, lower drug sensitivity, and higher immune infiltration. Moreover, we developed a nomogram model by incorporating the m6Arisk score and clinicopathological features. The application of the m6Arisk score for the prognostic stratification of HCC has good clinical applicability and clinical net benefit. Conclusion: Our findings reveal the crucial role of m6A modification patterns for predicting HCC TME status and prognosis, and highlight the good clinical applicability and net benefit of m6Arisk score in terms of prognosis, immunophenotype, and drug therapy in HCC patients.
Subject(s)
Adenosine , Biomarkers, Tumor , Carcinoma, Hepatocellular , Liver Neoplasms , Tumor Microenvironment , Humans , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Liver Neoplasms/immunology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Liver Neoplasms/diagnosis , Prognosis , Biomarkers, Tumor/genetics , Adenosine/analogs & derivatives , Adenosine/metabolism , Nomograms , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Female , Transcriptome , MaleABSTRACT
Recently, aluminum ion batteries (AIBs) have attracted more attention due to the reliable, cost-effective, and air-stable Al metal anode. Among various cathode materials of AIBs, graphite was paid more attention owing to its high-voltage plateau and stable properties in storing chloroaluminate anions (AlCl4 -). However, its low capacity limits the real application and can not satisfy the requirements of modern society. To solve the above issue, herein, boron (B)-doping expanded graphite (B-EG) was prepared by thermal treatment of expanded graphite and boric acid together in a reduction atmosphere. Based on the structural and electrochemical characterization, the results show that B-doping amplifies the interlayer space of expanded graphite (EG), introduces more mesoporous structures, and induces electron deficiency, which is beneficial to accelerating the transfer and adsorption of active ions. The results indicate that the B-EG electrode exhibits excellent rate capability and a high specific capacity of 84.9 mA h g-1 at 500 mA g-1. Compared with the EG electrode, B-EG shows better cycle stability with the specific capacity of 87.7 mA h g-1 after 300 cycles, which could be attributed to lower pulverization and higher pseudo-capacitance contribution of B-EG after the introduction of B species.
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BACKGROUND: Currently, the prevalence of obesity is on the rise annually. Bariatric surgery stands out as the most efficacious approach for addressing obesity. Obese patients are more prone to experience moderate to severe pain after surgery due to lower pain thresholds. Regional block, as an important component of multimodal analgesia in bariatric surgery, is crucial in reducing opioid consumption and alleviating postoperative pain in patients undergoing bariatric surgery. Transversus abdominis plane block (TAPB) has gained widespread utilization in bariatric surgery; however, its limitation of inadequate reduction of visceral pain in obese patients remains a significant concern. Therefore, it is imperative to explore new and more efficient strategies for analgesia. Quadratus lumborum block (QLB) has emerged as a popular nerve block in recent years, frequently utilized in conjunction with general anesthesia for abdominal surgery. In the cadaver study of QLB, it was confirmed that the dye level could reach up to T6 when using the subcostal anterior quadratus lumborum muscle approach, which could effectively reduce the incision pain and visceral pain of bariatric surgery patients during the perioperative period. However, there is currently a lack of research on the use of subcostal anterior QLB in patients undergoing bariatric surgery. Our study aims to investigate whether subcostal anterior QLB can provide superior perioperative analgesic efficacy for bariatric surgery under general anesthesia compared to TAPB, leading to reduced postoperative opioid consumption and a lower incidence of postoperative nausea and vomiting (PONV). METHODS AND DESIGN: This study is a prospective, randomized controlled trial aiming to recruit 66 patients undergoing bariatric surgery. The participants will be randomly allocated into two groups in a 1:1 ratio: subcostal anterior QLB group (n = 33) and TAPB group (n = 33). The study aims to investigate the efficacy of subcostal anterior QLB and TAPB in obese patients who are scheduled to undergo bariatric surgery. Our primary outcome is to observe the amount of opioids used in the two groups 24 h after operation. The secondary outcomes included VAS of pain during rest/activity after operation, the type and dose of additional analgesics, the occurrence and severity of PONV, the type and dose of additional antiemetic drugs, postoperative anesthesia care unit (PACU) time, time of first postoperative exhaust, time to first out of bed activity, time to first liquid diet and postoperative admission days. DISCUSSION: Opioid analgesics are prone to causing adverse reactions such as nausea, vomiting, and respiratory depression, especially in obese patients. Multimodal analgesia, including nerve block, can effectively reduce the dose of opioids and alleviate their adverse effects. Currently, TAPB is the most prevalent nerve block analgesia method for abdominal surgery. Recent studies have indicated that subcostal anterior QLB offers advantages over TAPB, including a wider block plane, faster onset, and longer maintenance time. It is not clear which of the two nerve block analgesia techniques is better for postoperative analgesia in patients undergoing bariatric surgery. Our objective in this investigation is to elucidate the superior method between TAPB and subcostal anterior QLB for postoperative pain management in bariatric surgery. TRIAL REGISTRATION: ChiCTR ChiCTR2300070556. Registered on 17 April 2023.
Subject(s)
Abdominal Muscles , Bariatric Surgery , Nerve Block , Pain, Postoperative , Humans , Pain, Postoperative/prevention & control , Pain, Postoperative/etiology , Pain, Postoperative/diagnosis , Nerve Block/methods , Nerve Block/adverse effects , Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Prospective Studies , Abdominal Muscles/innervation , Pain Measurement , Randomized Controlled Trials as Topic , Treatment Outcome , Adult , Male , Female , Middle Aged , Obesity/surgery , Postoperative Nausea and Vomiting/prevention & control , Postoperative Nausea and Vomiting/etiologyABSTRACT
Mimicking hierarchical assembly in nature to exploit atomically precise artificial systems with complex structures and versatile functions remains a long-standing challenge. Herein, we report two single-crystal supramolecular organic frameworks (MSOF-4 and MSOF-5) based on custom-designed atomically precise gold nanoclusters Au11(4-Mpy)3(PPh3)7, showing distinct and intriguing host-guest adaptation behaviors toward 1-/2-bromopropane (BPR) isomers. MSOF-4 exhibits sev topology and cylindrical channels with 4-mercaptopyridine (4-Mpy) ligands matching well with guest 1-BPR. Due to the confinement effect, solid MSOF-4 undergoes significant structural change upon selective adsorption of 1-BPR vapor over 2-BPR, resulting in strong near-infrared fluorescence. Single-crystal X-ray diffraction reveals that Au11(4-Mpy)3(PPh3)7 in MSOF-4 transforms into Au11Br3(PPh3)7 upon ligand exchange with 1-BPR, resulting in 1-BPR@MSOF-6 single crystals with a rarely reported helical assembly structure. Significantly, the double-helical structure of MSOF-6 facilitates efficient catalysis of the electron transfer (ET) reaction, resulting in a nearly 6 times increase of catalytic rates compared with MSOF-4. In sharp contrast, solid MSOF-5 possesses chb topology and cage-type channels with narrow windows, showing excellent selective physical adsorption toward 1-BPR vapor but a nonfluorescent feature upon guest adsorption. Our results demonstrate a powerful strategy for developing advanced assemblies with high-order complexity and engineering their functions in atomic precision.
ABSTRACT
Straw, as a kind of biomass waste, has the advantages of low cost and abundant storage, which makes it a promising renewable resource. Using rice straw as a carbon source, carbon nanosheets were prepared by a two-step carbonization method combining low-temperature pyrolysis and low-temperature hydrothermal, and they were used as H2S removal agents. The results showed that during the two-step carbonization process, the adsorption performance of carbon nanosheets for H2S showed a tendency of enhancing and then weakening with the increase of pyrolysis temperature in the first step, and the sulfur capacity could reach 3.1 mg/g at the maximum of the pyrolysis temperature of 200 °C, which was superior to or close to that of the modified or activated carbon. The XPS, EPR, and CO2-TPD tests showed that the surface of carbon nanosheets was alkaline, containing a large number of hydroxyl groups and the presence of phenoxy persistent free radicals or semiquinone persistent free radicals. It was analyzed that the direct or indirect oxidation of H2S by the persistent radicals under an alkaline environment could convert the -2-valent sulfur into -1-, 0- and +6-valent sulfur to realize the adsorption and removal of H2S. This work, while offering the possibility of utilizing carbon nanosheets made from straw as a material for H2S adsorption and removal, also expands the application of straw waste in exhaust gas treatment.