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1.
J Environ Sci (China) ; 149: 301-313, 2025 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-39181644

RESUMEN

Catalytic purification of sulphur-containing malodorous gases has attracted wide attention because of its advantages of high purification efficiency, low energy consumption and lack of secondary pollution. The selection of efficient catalysts is the key to the problem, while the preparation and optimisation of catalysts depend on the analysis of experimental results and in-depth mechanistic analysis. By analysing the published literature, bibliometric analysis can identify existing research hotspots, the areas of interest and predict development trends, which can help to identify hot catalysts in the catalytic purification of sulphur-containing odours and to investigate their catalytic purification mechanisms. Therefore, this paper uses bibliometric analysis, based on Web Of Science and CNKI databases, CiteSpace and VOS viewer software to collate and analyse the literature on the purification of sulphur-containing odour pollutants, to identify the current research hotspots, to summarise the progress of research on the catalytic purification of different types of sulphur-containing odours, and to analyse their reaction mechanisms and kinetics. On this basis, the research progress of catalytic purification of different kinds of sulfur odour is summarized, and the reaction mechanism and dynamics are summarized.


Asunto(s)
Odorantes , Azufre , Odorantes/análisis , Azufre/química , Contaminantes Atmosféricos/análisis , Catálisis , Gases
2.
J Colloid Interface Sci ; 679(Pt A): 634-652, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39388950

RESUMEN

In the selective catalytic reduction of NOx by NH3 (NH3-SCR), conventional Mn-based denitration catalysts often suffered from susceptibility to poisoning by alkali and alkaline earth metals, this paper presented an innovative self-protected Chlorella@Mn denitration catalyst. Remarkably, in the presence of high concentrations (2 wt%) of alkali and alkaline earth metal oxides, the Chlorella@Mn catalyst sustained a NOx conversion exceeding 96 % at 175 °C. At an even higher concentration (4 wt%), NOx conversion above 90 % at 175 °C, surface analysis revealed that POMn sites acted as sacrificial sites, binding to the alkali and alkaline earth metals, the Chlorella@Mn catalyst surface naturally carried a spectrum of acidic species (such as SO42-, PO3-, SiO32-), proficient in capturing alkali/alkaline earth metal effectively, elements such as S, P, and Si formed bonds with K, Na, Ca, and Mg. The synergistic protection of the active sites and the surface elements avoided the deactivation of the catalyst. The detrimental effects of high concentrations of alkali and alkaline earth metals were primarily due to promoting an excessively high valence state of Mn on the catalyst surface and the reduction or loss of NH3 adsorption and activation at Brønsted acid sites. This research provided valuable insights for advancing the development of low-temperature denitration catalysts with improved resistance to alkali and alkaline earth metal poisoning.

3.
BMC Cancer ; 24(1): 1297, 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39434012

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor characterized by a high mortality rate. The occurrence and progression of HCC are linked to oxidative stress. Glyoxalase-1 (GLO1) plays an important role in regulating oxidative stress, yet the underlying mechanism remains unclear. GLO1 may serve as a prognostic biomarker and therapeutic target for HCC. METHODS: Based on TCGA database hepatocellular carcinoma samples, we conducted a bioinformatics analysis to explore the correlation between GLO1 expression and HCC cell proliferation and viability. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) were mainly enriched in the cell cycle pathway. We analyzed the relationships between GLO1 and 24 genes enriched in the cell cycle pathway using a protein-protein interaction (PPI) network. Finally, experimental validation was performed to assess GLO1's impact on the distribution of cells at different cell cycle stages and on the proliferation and migration of HCC cells. RESULTS: Our study demonstrated that GLO1 was overexpressed in HCC tissues and was associated with a poor prognosis. Data analysis indicated that overexpression of GLO1 activated the cell cycle pathway and positively correlated with expression of the majority of key cell cycle genes. Experimental validation showed that GLO1 expression affects the number of HCC cells in G2 and S phases and regulates HCC cell proliferation and migration. CONCLUSIONS: GLO1 represents a promising therapeutic target for HCC, providing valuable insights into its role in the viability and proliferation of HCC cells.


Asunto(s)
Carcinoma Hepatocelular , Ciclo Celular , Movimiento Celular , Proliferación Celular , Lactoilglutatión Liasa , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Lactoilglutatión Liasa/genética , Lactoilglutatión Liasa/metabolismo , Proliferación Celular/genética , Movimiento Celular/genética , Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica , Pronóstico , Mapas de Interacción de Proteínas , Línea Celular Tumoral , Biología Computacional/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino
4.
Front Cell Dev Biol ; 12: 1431173, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224435

RESUMEN

During the metamorphosis of anuran amphibians, the tail resorption process is a necessary and crucial change. One subject that has received relatively little or no attention is the expression patterns of proteins and metabolites in the different tail portions during metamorphosis, especially in highland amphibians. The mechanisms of tail resorption in three portions (the tip, middle and root) of the tail were investigated in N. pleskei G43 tadpole based on two omics (proteomic and metabolomic). Integrin αVß3 was found to be high expressed in the distal portion of the tail, which could improve the sensitiveness to thyroid hormones in the distal portion of the tail. Muscle regression displayed a spatial pattern with stronger regression in distal and weaker one in proximal portion. Probably, this stronger regression was mainly performed by the proteases of proteasome from the active translation by ribosomes. The suicide model and murder model coexisted in the tail resorption. Meanwhile, fatty acids, amino acids, pyrimidine, and purine which derived from the breakdown of tissues can be used as building blocks or energy source for successful metamorphosis. Our data improved a better comprehension of the tail resorption mechanisms underlying the metamorphism of N. pleskei tadpole through identifying important participating proteins and metabolites.

5.
Surgery ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39261238

RESUMEN

BACKGROUND: The incidence of duodenal adenocarcinoma is increasing, with limited studies on this disease published. This multicenter retrospective study aimed to analyze the clinicopathologic features of duodenal adenocarcinoma and identify prognostic factors for postoperative survival. METHODS: Demographic characteristics, clinicopathologic features, treatment outcomes, and survival of patients with duodenal adenocarcinoma undergoing surgical treatment at 16 Chinese medical centers from 2012 to 2023 were retrospectively analyzed. RESULTS: Among the 2,189 patients with duodenal adenocarcinoma included, 50.07% had extra-ampullary duodenal adenocarcinoma and 49.93% had peri-ampullary duodenal adenocarcinoma. The 1-, 3-, and 5-year overall survival rates for patients who underwent radical surgery were 91.78%, 69.30%, and 55.86%, respectively. The median overall survival was 73 months (range, 64-84), and the median progression-free survival was 64 months (range, 52-76). No differences in survival were observed between the laparotomy and minimally invasive surgery groups (log-rank P = .562); furthermore, no significant between-group differences in operation time, lymph node dissection, postoperative complications, or in-hospital mortality were observed (P > .05). The minimally invasive surgery group experienced less intraoperative blood loss (250 mL vs 100 mL, P < .001), fewer intraoperative blood transfusions (24.97% vs 18.84%, P = .002), and shorter hospital stays (28 days vs 23 days, P < .001). Multivariate Cox regression analysis revealed that advanced age, advanced stage, longer operation time, intraoperative blood transfusion, and postoperative hemorrhage were independent risk factors for poor prognosis. CONCLUSION: Radical surgery was associated with favorable overall survival among patients with duodenal adenocarcinoma, and no difference in survival was observed between patients with extra-ampullary duodenal adenocarcinoma and peri-ampullary duodenal adenocarcinoma. Minimally invasive surgery is a reliable alternative for duodenal adenocarcinoma treatment.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39231052

RESUMEN

Filter pruning has gained widespread adoption for the purpose of compressing and speeding up convolutional neural networks (CNNs). However, the existing approaches are still far from practical applications due to biased filter selection and heavy computation cost. This article introduces a new filter pruning method that selects filters in an interpretable, multiperspective, and lightweight manner. Specifically, we evaluate the contributions of filters from both individual and overall perspectives. For the amount of information contained in each filter, a new metric called information capacity is proposed. Inspired by the information theory, we utilize the interpretable entropy to measure the information capacity and develop a feature-guided approximation process. For correlations among filters, another metric called information independence is designed. Since the aforementioned metrics are evaluated in a simple but effective way, we can identify and prune the least important filters with less computation cost. We conduct comprehensive experiments on benchmark datasets employing various widely used CNN architectures to evaluate the performance of our method. For instance, on ILSVRC-2012, our method outperforms state-of-the-art methods by reducing floating-point operations (FLOPs) by 77.4% and parameters by 69.3% for ResNet-50 with only a minor decrease in an accuracy of 2.64%.

7.
J Hazard Mater ; 480: 135839, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39298965

RESUMEN

A precious metal catalyst with loaded Pt single atoms was prepared and used for the complete oxidation of C3H6O. Detailed results show that the T100 of the 1.5Pt SA/γ-Al2O3 catalyst in the oxidation process of acetone is 250 °C, the TOF of Pt is 1.09 × 10-2 s-1, and the catalyst exhibits good stability. Characterization reveals that the high dispersion of Pt single atoms and strong interaction with the carrier improve the redox properties of the catalyst, enhancing the adsorption and dissociation capability of gaseous oxygen. DFT calculations show that after the introduction of Pt, the oxygen vacancy formation energy on the catalyst surface is reduced to 1.2 eV, and PDOS calculations prove that electrons on Pt atoms can be quickly transferred to O atoms, increasing the number of electrons on the σp * bond and promoting the escape of lattice oxygen. In addition, in situ DRIFTS and adsorption experiments indicate that the C3H6O oxidation process follows the Mars-van Krevelen reaction mechanism, and CH2 =C(CH3)=O(ads), O* (O2-), formate, acetate, and carbonate are considered as the main intermediate species and/or transients in the reaction process. Particularly, the activation rate of O2 and the cleavage of the -C-C- bond are the main rate-determining steps in the oxidation of C3H6O. This work will further enhance the study of the oxidation mechanism of oxygenated volatile organic pollutants over loaded noble metal catalysts.

8.
iScience ; 27(8): 110417, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39108703

RESUMEN

Glioblastoma (GBM) is characterized by high morbidity, mortality, and low cure rates. Recent studies suggest that TSPAN4 is recognized as a marker protein for migrasomes, a vesicular organelle associated with cell migration. However, the intrinsic role of TSPAN4 in cancers has not been clarified, especially in GBM. Here, we report that TSPAN4 promotes GBM progression by interacting with epidermal growth factor receptor (EGFR) and regulating its stability. Clinically, TSPAN4 is highly expressed in GBM and is significantly correlated with poor prognosis. Functionally, TSPAN4 knockdown dramatically inhibits GBM cell proliferation and invasion in vitro, as well as tumorigenicity in vivo. Conversely, overexpression of TSPAN4 facilitates GBM progression. Mechanistically, TSPAN4 knockdown disrupts interaction with EGFR, destabilizing its expression and inactivating EGFR and downstream signaling pathways, such as MEK/ERK, STAT3, and AKT. Our study reveals that TSPAN4 drives GBM progression through regulating EGFR stability and could be a potential target for cancer therapy.

9.
Front Immunol ; 15: 1427380, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39188712

RESUMEN

Background and objective: Extracellular adenosine (eAdo) bridges tumor metabolism and immune regulation. CD39-CD73-eAdo/A2aR axis regulates tumor microenvironment (TME) and immunotherapy response. In the era of immunotherapy, exploring the impact of the CD39-CD73-eAdo/A2aR axis on TME and developing targeted therapeutic drugs to enhance the efficacy of immunotherapy are the current research hotspots. This study summarizes and explores the research trends and hotspots of the adenosine axis in the field of TME to provide ideas for further in-depth research. Methods: Literature information was obtained from the Web of Science core collection database. The VOS viewer and the bibliometric tool based on R were used to quantify and identify cooperation information and individual influence by analyzing the detailed information of the global annual publication volume, country/region and institution distribution, article authors and co-cited authors, and journal distribution of these articles. At the same time, the distribution of author keywords and the co-occurrence of author keywords, highly cited articles, and highly co-cited references of CD39-CD73-eAdo/A2aR in the field of TME were analyzed to determine research hotspots and trends. Result: 1,721 articles published in the past ten years were included in this study. Through bibliometric analysis, we found that (1) 69 countries and regions explored the effect of the CD39-CD73-eAdo/A2aR on TME, and the research was generally on the rise. Researchers in the United States dominated research in this area, with the highest total citation rate. China had the most significant number of publications. (2) Harvard University has published the most articles in this field. (3) 12,065 authors contributed to the publication of papers in this field, of which 23 published at least eight papers. STAGG J had significant academic influence, with 24 published articles and 2,776 citations. Co-cited authors can be clustered into three categories. Stagg J, Allard B, Ohta A, and Antonioli, L occupied a central position in the network. (4) 579 scholarly journals have published articles in this field. The journal FRONTIERS IN IMMUNOLOGY published the most significant number of papers, with 97 articles and a total of 2,317 citations, and the number of publications increased year by year. (5) "The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets" was the most frequently local cited article (163 times). The "A2A adenosine receptor protects tumors from antitumor T cells" was the most co-cited reference (224 times). (6) Through the analysis of author keywords, we found that the relationship between adenosine and immunotherapy was a core concept for many researchers in this field. Breast cancer, melanoma, colorectal cancer, ovarian cancer, glioblastoma, pancreatic cancer, hepatocellular carcinoma, and lung cancer were the most frequent cancer types in adenosine-related tumor studies. Immunotherapy, immunosuppression, immune checkpoint, and immune checkpoint inhibitors were the hot keywords in the research, reflecting the importance of the adenosine metabolic pathway in tumor immunotherapy. The keywords such as Immunogenic cell death, T cells, Sting, regulatory T cells, innate immunity, and immune infiltration demonstrated the pathways by which adenosine affected the TME. The famous author keywords in recent years have been immunotherapy, immunogenic cell death, inflammation, lung cancer, and gastric cancer. Conclusion: The effect of CD39-CD73-eAdo/A2aR on the infiltration and function of various immune cells in TME, tumor immunotherapy response, and patient prognosis has attracted the attention of researchers from many countries/regions. American scholars still dominate the research in this field, but Chinese scholars produce the most research results. The journal FRONTIERS IN IMMUNOLOGY has published the wealthiest research in the field. Stagg J was a highly influential researcher in this field. Further exploration of targeted inhibition of CD39-CD73-eAdo/A2aR alone or in combination with other immunotherapy, radiotherapy, and chemotherapy in treating various cancer types and developing effective clinical therapeutic drugs are continuous research hotspots in this field.


Asunto(s)
5'-Nucleotidasa , Adenosina , Apirasa , Bibliometría , Neoplasias , Microambiente Tumoral , Animales , Humanos , 5'-Nucleotidasa/metabolismo , Adenosina/metabolismo , Apirasa/metabolismo , Proteínas Ligadas a GPI/inmunología , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Receptor de Adenosina A2A/metabolismo , Microambiente Tumoral/inmunología
10.
Oncogene ; 43(35): 2635-2646, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39060439

RESUMEN

Gastric cancer (GC) is a substantial global health concern, and the development of liver metastasis (LM) in GC represents a critical stage linked to unfavorable patient prognoses. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the immune landscape of GC liver metastasis, revealing several immuno-suppressive components within the tumor immune microenvironment (TIM). Our findings unveiled an increased presence of cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cell (MDSC)-like macrophages, tumor-associated macrophage (TAM)-like macrophages, and naive T cells, while conventional dendritic cells (cDCs) and effector CD8 T cells declined in LM. Additionally, we identified two distinct natural killer (NK) cell clusters exhibiting differential cytotoxicity-related gene expression, with cytotoxic NK cells notably reduced in LM. Strikingly, TGFß was identified as an inducer of NK cell dysfunction, potentially contributing to immune evasion and tumor metastasis. In preclinical LM models, the combined approach of inhibiting TGFß and transferring NK cells exhibited a synergistic impact, resulting in a significant reduction in liver metastasis. This work highlights the importance of understanding the complex immune dynamics within GC liver metastasis and presents a promising strategy combining TGFß inhibition and NK-based immunotherapy to improve patient outcomes.


Asunto(s)
Células Asesinas Naturales , Neoplasias Hepáticas , Análisis de la Célula Individual , Neoplasias Gástricas , Microambiente Tumoral , Células Asesinas Naturales/inmunología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/patología , Humanos , Microambiente Tumoral/inmunología , Análisis de la Célula Individual/métodos , Animales , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Fibroblastos Asociados al Cáncer/inmunología , Fibroblastos Asociados al Cáncer/patología , Fibroblastos Asociados al Cáncer/metabolismo , Células Dendríticas/inmunología , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo
11.
J Colloid Interface Sci ; 675: 935-946, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39002243

RESUMEN

Generally, sulfur poisoning is considered to be one of the main factors contributing to the deactivation of selective catalytic reduction of NOx by CO (CO-SCR) catalysts, while the promotional effect of SO2 on NO reduction over Ir/SiO2 is observed which is an interesting scientific phenomenon. After the introduction of 20 ppm SO2, NOx conversion increased from âˆ¼ 40 % to âˆ¼ 90 % at 275 °C, and N2 selectivity increased from âˆ¼ 80 % to 100 % at 200 âˆ¼ 300 °C. Furthermore, the promoting effect could remain unchanged after 24 h of continuous reaction. However, the temperature point for achieving complete conversion of CO increased from 225 °C to 275 °C after the introduction of SO2. Experimental characterization and theoretical calculation jointly proved that the inhibition of CO oxidation by the generation of sulfate was the main reason for promoting NO reduction. Under the coexistence of O2 and SO2, SO2 was firstly oxidized to SO3 on the iridium surface and generated sulfate species on surface hydroxyl groups of SiO2. Some active sites for O2 adsorption were covered by the generated surface sulfate, and adsorbed CO was hard to react with adsorbed O2, resulting in Langmuir-Hinshelwood (L-H) reaction pathways for CO oxidation being inhibited. Therefore, unoxidized CO reacted with NO adsorbed species and generated N2O to generate N2 and CO2, improving NO reduction. This new insight has implications for understanding the promotional effect of SO2 on NO reduction with CO in the presence of O2.

12.
J Therm Biol ; 123: 103895, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38996476

RESUMEN

Global warming may affect the early developmental stages of high-altitude amphibians, thereby influencing their later fitness. Yet, this has been largely unexplored. To investigate whether and how the temperatures experienced by embryonic and larval stages affect their fitness at later developmental stages, we designed two experiments in which the embryos and larvae were treated with three temperatures (24, 18 and 12 °C), respectively. Then, the life history traits of the tadpoles during the metamorphotic climax in all treatments were evaluated, including growth rate, survival rate, morphology, thermal physiology, swimming performance, standard metabolic rate (SMR), oxidative and antioxidative system, and metabolic enzyme activities. The results revealed that elevated temperature accelerated metamorphosis but decreased body size at metamorphosis. Additionally, warming during the embryonic and larval stages decreased the thermal tolerance range and induced increased oxidative stress. Furthermore, high embryonic temperature significantly decreased the hatching success, but had no significant effect on swimming performance and SMR. Warming during larval periods was harmful to the survival and swimming performance of tadpoles. The effect size analysis revealed that the negative impacts of embryonic temperature on certain physiological traits, such as growth and development, survival and swimming performance, were more pronounced than those of larval temperature. Our results highlight the necessity for particular attention to be paid to the early stages of amphibians, notably the embryonic stages when evaluating the impact of global warming on their survival.


Asunto(s)
Larva , Ranidae , Natación , Animales , Larva/crecimiento & desarrollo , Larva/fisiología , Ranidae/fisiología , Ranidae/crecimiento & desarrollo , Ranidae/embriología , Calentamiento Global , Altitud , Metamorfosis Biológica , Embrión no Mamífero/fisiología , Estrés Oxidativo , Termotolerancia , Temperatura
13.
Cell Death Dis ; 15(6): 455, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937435

RESUMEN

ADGRF5 (GPR116) has been identified as a facilitator of breast cancer cell migration and metastasis, yet the underlying mechanisms remain largely elusive. Our current study reveals that the absence of ADGRF5 in breast cancer cells impairs extracellular matrix (ECM)-associated cell motility and impedes in vivo tumor growth. This correlates with heightened expression of matrix metalloproteinase 8 (MMP8), a well-characterized antitumorigenic MMP, and a shift in the polarization of tumor-associated neutrophils (TANs) towards the antitumor N1 phenotype in the tumor microenvironment (TME). Mechanistically, ADGRF5 inhibits ERK1/2 activity by enhancing RhoA activation, leading to decreased phosphorylation of C/EBPß at Thr235, hindering its nuclear translocation and subsequent activation. Crucially, two C/EBPß binding motifs essential for MMP8 transcription are identified within its promoter region. Consequently, ADGRF5 silencing fosters MMP8 expression and CXCL8 secretion, attracting increased infiltration of TANs; simultaneously, MMP8 plays a role in decorin cleavage, which leads to trapped-inactivation of TGF-ß in the TME, thereby polarizing TANs towards the antitumor N1 neutrophil phenotype and mitigating TGF-ß-enhanced cell motility in breast cancer. Our findings reveal a novel connection between ADGRF5, an adhesion G protein-coupled receptor, and the orchestration of the TME, which dictates malignancy progression. Overall, the data underscore ADGRF5 as a promising therapeutic target for breast cancer intervention.


Asunto(s)
Neoplasias de la Mama , Movimiento Celular , Metaloproteinasa 8 de la Matriz , Receptores Acoplados a Proteínas G , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Matriz Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Interleucina-8/metabolismo , Metaloproteinasa 8 de la Matriz/metabolismo , Metaloproteinasa 8 de la Matriz/genética , Ratones Desnudos , Neutrófilos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Microambiente Tumoral
14.
Int Immunopharmacol ; 134: 112152, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38761777

RESUMEN

BACKGROUND: The efficacy and prognosis of immune checkpoint inhibitors (ICIs) remain unresolved issues. Here, we assessed the treatment characteristics and efficacy of ICIs in non-small cell lung cancer (NSCLC) using real-world data and evaluated the predictive value of factors, including programmed death-ligand 1 (PD-L1) expression, for the clinical outcome of ICIs in NSCLC. METHODS: Analyzed data was collected from hospitalized patients in the West China Hospital of Sichuan University between January 2017 and March 2023. The Kaplan-Meier method was utilized for analyzing real-world progression-free survival (rwPFS), while Cox regression models was employed to access the correlation between the efficacy of immunotherapy and sociodemographic characteristics, disease information, and characteristics of ICI treatment. RESULTS: A total of 545 patients were included in the retrospective study and characteristics of immunotherapy varied significantly among PD-L1 expression groups. The median rwPFS for the entire population was 9.76 months. Subgroup analyses revealed that patients with high PD-L1 expression, early TNM stage, first-line immunotherapy, EGFR wild-type and those who have not received radiotherapy and targeted therapy previously were more likely to have better rwPFS. Furthermore, multivariate Cox regression analyses identified PD-L1 expression, EGFR mutation status and previous radiotherapy as the most influential predictors of the response to ICI treatment. CONCLUSIONS: This study presents the real-world experience of Chinese NSCLC patients undergoing ICI treatment, offering guidance for clinical decision-making based on various patient conditions, preferences, and indications for ICIs, through the evaluation of immunotherapy efficacy and predictors in NSCLC patients.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Resultado del Tratamiento , Adulto , China , Anciano de 80 o más Años , Supervivencia sin Progresión
15.
Transl Res ; 272: 19-40, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38815898

RESUMEN

HCC is a malignancy characterized by high incidence and mortality rates. Traditional classifications of HCC primarily rely on tumor morphology, phenotype, and multicellular molecular levels, which may not accurately capture the cellular heterogeneity within the tumor. This study integrates scRNA-seq and bulk RNA-seq to spotlight HP as a critical gene within a subgroup of HCC malignant cells. HP is highly expressed in HCC malignant cells and lowly expressed in T cells. Within malignant cells, elevated HP expression interacts with C3, promoting Th1-type responses via the C3/C3AR1 axis. In T cells, down-regulating HP expression favors the expression of Th1 cell-associated marker genes, potentially enhancing Th1-type responses. Consequently, we developed a "HP-promoted Th1 response reclassification" gene set, correlating higher activity scores with improved survival rates in HCC patients. Additionally, four predictive models for neoadjuvant treatment based on HP and C3 expression were established: 1) Low HP and C3 expression with high Th2 cell infiltration; 2) High HP and low C3 expression with high Th2 cell infiltration; 3) High HP and C3 expression with high Th1 cell infiltration; 4) Low HP and high C3 expression with high Th1 cell infiltration. In conclusion, the HP gene selected from the HCC malignant cell subgroup (Malignant_Sub 6) might serve as a potential ally against the tumor by promoting Th1-type immune responses. The establishment of the "HP-promoted Th1 response reclassification" gene set offers predictive insights for HCC patient survival prognosis and neoadjuvant treatment efficacy, providing directions for clinical treatments.


Asunto(s)
Carcinoma Hepatocelular , Haptoglobinas , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Haptoglobinas/genética , Haptoglobinas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Células TH1/inmunología , Células TH1/metabolismo
16.
J Asian Nat Prod Res ; 26(9): 1041-1048, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38758009

RESUMEN

Macrophorins H (4) and L (5), two rare HMG-conjugate macrophorins along with three known macrophorins (1-3), three DMOA-derived meroterpenoids (6-8) and two ergosterol derivates (9-10) were isolated from sterilized rice medium cultured Penicillium sp. NX-05-G-3. Their structures were elucidated by 1D and 2D NMR. The cytotoxicities of all compounds were evaluated, and compounds 1 and 2 showed extensive cytotoxicity against human cancer cell lines Hela, SCC15, MDA-MB-453 and A549, with IC50 values ranging from 17.6 to 32.8 µM.


Asunto(s)
Ensayos de Selección de Medicamentos Antitumorales , Penicillium , Penicillium/química , Humanos , Estructura Molecular , Células HeLa , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Terpenos/farmacología , Terpenos/química
17.
Clin Exp Med ; 24(1): 112, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38795162

RESUMEN

Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales , Familia 4 del Citocromo P450 , Trampas Extracelulares , Neoplasias Hepáticas , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/genética , Familia 4 del Citocromo P450/genética , Familia 4 del Citocromo P450/metabolismo , Pronóstico , Trampas Extracelulares/metabolismo , Biomarcadores de Tumor/genética , Nomogramas , Perfilación de la Expresión Génica , Masculino , Femenino , Regulación Neoplásica de la Expresión Génica , Neutrófilos/metabolismo
19.
Animals (Basel) ; 14(10)2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38791658

RESUMEN

The functional adaptation and underlying molecular mechanisms of hemoglobins (Hbs) have primarily concentrated on mammals and birds, with few reports on reptiles. This study aimed to investigate the convergent and species-specific high-altitude adaptation mechanisms of Hbs in two Eremias lizards from the Qinghai-Tibet Plateau. The Hbs of high-altitude E. argus and E. multiocellata were characterized by significantly high overall and intrinsic Hb-O2 affinity compared to their low-altitude populations. Despite the similarly low Cl- sensitivities, the Hbs of high-altitude E. argus exhibited higher ATP sensitivity and ATP-dependent Bohr effects than that of E. multiocellata, which could facilitate O2 unloading in respiring tissues. Eremias lizards Hbs exhibited similarly low temperature sensitivities and relatively high Bohr effects at lower temperatures, which could help to stably deliver and release O2 to cold extremities at low temperatures. The oxygenation properties of Hbs in high-altitude populations might be attributed to varying ratios of ß2/ß1 globin and substitutions on the ß2-type globin. Notably, the Asn12Ala in lowland E. argus could cause localized destabilization of the E-helix in the tetrameric Hb by elimination of hydrogen bonds, thereby resulting in its lowest O2 affinity. This study provides a valuable reference for the high-altitude adaptation mechanisms of hemoglobins in reptiles.

20.
BMC Genomics ; 25(1): 363, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609871

RESUMEN

BACKGROUND: Cold hardiness is fundamental for amphibians to survive during the extremely cold winter on the Qinghai-Tibet plateau. Exploring the gene regulation mechanism of freezing-tolerant Rana kukunoris could help us to understand how the frogs survive in winter. RESULTS: Transcriptome of liver and muscle of R. kukunoris collected in hibernation and spring were assisted by single molecule real-time (SMRT) sequencing technology. A total of 10,062 unigenes of R. kukunoris were obtained, and 9,924 coding sequences (CDS) were successfully annotated. Our examination of the mRNA response to whole body freezing and recover in the frogs revealed key genes concerning underlying antifreeze proteins and cryoprotectants (glucose and urea). Functional pathway analyses revealed differential regulated pathways of ribosome, energy supply, and protein metabolism which displayed a freeze-induced response and damage recover. Genes related to energy supply in the muscle of winter frogs were up-regulated compared with the muscle of spring frogs. The liver of hibernating frogs maintained modest levels of protein synthesis in the winter. In contrast, the liver underwent intensive high levels of protein synthesis and lipid catabolism to produce substantial quantity of fresh proteins and energy in spring. Differences between hibernation and spring were smaller than that between tissues, yet the physiological traits of hibernation were nevertheless passed down to active state in spring. CONCLUSIONS: Based on our comparative transcriptomic analyses, we revealed the likely adaptive mechanisms of R. kukunoris. Ultimately, our study expands genetic resources for the freezing-tolerant frogs.


Asunto(s)
Respuesta al Choque por Frío , Transcriptoma , Animales , Respuesta al Choque por Frío/genética , Tibet , Perfilación de la Expresión Génica , Ranidae/genética , Anuros
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