Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 428
Filtrar
1.
Oncol Lett ; 28(3): 409, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38988448

RESUMEN

The present study evaluated the efficiency, prognostic factors for and the safety of irinotecan combined with raltitrexed (TOMIRI) in patients with metastatic colorectal cancer (CRC). Outcome data of patients who received TOMIRI as first-, second- and third- or later-line treatment regimens were assessed to compare the efficacy of this regimen. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) were evaluated for each group. Kaplan-Meier curves and univariate and multivariate analyses were performed to evaluate efficacy. From January 2017 to December 2019, TOMIRI was administered as a first-line treatment in 23 patients, second-line treatment in 164 patients and third- or later-line treatment in 18 patients. Irinotecan and 5-fluorouracil (FOLFIRI) was administered to another 50 patients, who served as the control group. The median PFS was 9, 7 and 6 months and the median OS was 37, 21 and 17 months for first-, second- and third- or later-line treatments, respectively. The ORRs of the included patients were 21.7, 13.4 and 11.1%, respectively, and the DCRs were 91.3, 81.7 and 66.7%, respectively. Compared with FOLFIRI, TOMIRI as a second-line chemotherapy treatment was associated with longer survival of the patients with CRC. Further analysis demonstrated that pathologic tumor-node-metastasis category, carcinoembryonic antigen, carbohydrate antigen 19-9, treatment cycles, targeted therapy, treatment of local metastases and first-line PFS were prognostic factors for second-line treatment. Among these, the number of treatment cycles was of vital importance. Hepatic dysfunction was the most commonly reported grade 1-2 (55.1%) and grade 3-4 (7.3%) adverse event. Neutropenia (12.2%), thrombocytopenia (10.2%), anemia (27.3%), proteinuria (38.1%) and hematuria (21.0%) were also common grade 1-2 adverse events. In conclusion, TOMIRI may be recommended as an effective and safe second-line treatment for metastatic CRC in the clinic.

2.
Adv Sci (Weinh) ; : e2404834, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38894547

RESUMEN

Lithium-sulfur (Li-S) batteries have attracted significant attention in the realm of electronic energy storage and conversion owing to their remarkable theoretical energy density and cost-effectiveness. However, Li-S batteries continue to face significant challenges, primarily the severe polysulfides shuttle effect and sluggish sulfur redox kinetics, which are inherent obstacles to their practical application. Metal-organic frameworks (MOFs), known for their porous structure, high adsorption capacity, structural flexibility, and easy synthesis, have emerged as ideal materials for separator modification. Efficient polysulfides interception/conversion ability and rapid lithium-ion conduction enabled by MOFs modified layers are demonstrated in Li-S batteries. In this perspective, the objective is to present an overview of recent advancements in utilizing pristine MOF materials as modification layers for separators in Li-S batteries. The mechanisms behind the enhanced electrochemical performance resulting from each design strategy are explained. The viewpoints and crucial challenges requiring resolution are also concluded for pristine MOFs separator in Li-S batteries. Moreover, some promising materials and concepts based on MOFs are proposed to enhance electrochemical performance and investigate polysulfides adsorption/conversion mechanisms. These efforts are expected to contribute to the future advancement of MOFs in advanced Li-S batteries.

3.
Clin Cosmet Investig Dermatol ; 17: 961-966, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707607

RESUMEN

Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.

4.
Cell Rep ; 43(5): 114192, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38703367

RESUMEN

The preoptic area of the hypothalamus (POA) is essential for sleep regulation. However, the cellular makeup of the POA is heterogeneous, and the molecular identities of the sleep-promoting cells remain elusive. To address this question, this study compares mice during recovery sleep following sleep deprivation to mice allowed extended sleep. Single-nucleus RNA sequencing (single-nucleus RNA-seq) identifies one galanin inhibitory neuronal subtype that shows upregulation of rapid and delayed activity-regulated genes during recovery sleep. This cell type expresses higher levels of growth hormone receptor and lower levels of estrogen receptor compared to other galanin subtypes. single-nucleus RNA-seq also reveals cell-type-specific upregulation of purinergic receptor (P2ry14) and serotonin receptor (Htr2a) during recovery sleep in this neuronal subtype, suggesting possible mechanisms for sleep regulation. Studies with RNAscope validate the single-nucleus RNA-seq findings. Thus, the combined use of single-nucleus RNA-seq and activity-regulated genes identifies a neuronal subtype functionally involved in sleep regulation.


Asunto(s)
Galanina , Neuronas , Área Preóptica , Privación de Sueño , Animales , Galanina/metabolismo , Galanina/genética , Neuronas/metabolismo , Área Preóptica/metabolismo , Ratones , Privación de Sueño/metabolismo , Privación de Sueño/genética , Masculino , RNA-Seq , Ratones Endogámicos C57BL , Sueño/genética , Sueño/fisiología , Análisis de la Célula Individual
5.
Mar Pollut Bull ; 203: 116421, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38713927

RESUMEN

Intensive aquaculture production generates large amounts of sludge. This waste could be considered as a potential source of nutrients that can be recovered and utilized. Little attention has been paid to nutrient recovery from fish sludge. In this study, bioconversion of sludge was evaluated in lab scale under anaerobic (AN), facultative anaerobic (FA) and aerobic (AE) conditions. After 40 days of fermentation, AN recovered the highest values of dissolved total nitrogen (82.7 mg L-1), while AE showed the highest dissolved total phosphorus (11.8 mg L-1) and the highest reduction of total suspended solids (36.0 %). Microbial analysis showed that AN exhibited a distinct bacterial community than that of FA and AE. Furthermore, C. sorokiniana grown in AN effluents collected after 12 days of fermentation achieved the highest biomass production (1.96 g L-1). These results suggest that AN has the best potential to recover nutrients from sludge for production of C. sorokiniana.


Asunto(s)
Chlorella , Microalgas , Nitrógeno , Nutrientes , Fósforo , Aguas del Alcantarillado , Chlorella/crecimiento & desarrollo , Animales , Peces , Acuicultura , Eliminación de Residuos Líquidos/métodos , Biomasa , Anaerobiosis , Fermentación
6.
ACS Appl Mater Interfaces ; 16(19): 24703-24711, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38710046

RESUMEN

Cost-effective bulk scintillators with high density, large-area, and long-term stability are desirable for high-energy radiation detections. Conventional bulk polycrystalline or single-crystal scintillators are generally synthesized by high-temperature approaches, and it is challenging to realize simultaneously high detectivity/responsivity, spatial resolution, and rapid time response. Here, we report the cold sintering of bulk scintillators (at 90 °C) based on an "emitter-in-matrix" principle, in which emissive CsPbBr3 nanocrystals are embedded in a durable and transparent Cs4PbBr6 matrix. These bulk scintillators exhibit high light yield (33,800 photons MeV-1), low detection limit (79 nGyair s-1), fast decay time (9.8 ns), and outstanding spatial resolution of 8.9 lp mm-1 to X-ray radiation and an energy resolution of 19.3% for γ-ray (59.6 keV) detection. The composite scintillator also shows exceptional stability against environmental degradation and cyclic X-ray radiation. Our results demonstrate a cost-effective strategy for developing perovskite-based bulk transparent scintillators with exceptional performance and high radioluminescence stability for high-energy radiation detection and imaging.

7.
World J Oncol ; 15(3): 482-491, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38751703

RESUMEN

Background: Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Methods: Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Results: Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Conclusions: Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

8.
RSC Adv ; 14(20): 13997-14007, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38686284

RESUMEN

Amorphous, α, ß, and γ-phase yttrium disilicate Y2Si2O7 pellets were synthesized by spark plasma sintering, and their chemical durability and degradation mechanisms were investigated via semi-dynamic leaching test in pH = 3 nitric acid at 90 °C. All crystalline phases displayed relatively congruent dissolution with a slight preferential release of Y. The amorphous sample showed clear incongruent dissolution with preferential release of Y, leading to a surface reorganization reaction and the formation of a SiO2 passivation layer 20-25 µm thick on the surface of the sample. This passivation layer led to a continuous decrease in the elemental release rates of the amorphous sample. The γ-phase sample displayed the lowest short-term and long-term leaching rates of Y and Si, followed by the ß, α, and then amorphous sample. The crystalline samples showed increasing release rates over time indicating a dissolution-controlled reaction mechanism. Post-leaching microstructural characterization of the ß and γ samples revealed variations in the corrosion levels of the surface grains, indicating a dependence on grain orientation.

9.
Microorganisms ; 12(4)2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38674689

RESUMEN

The increasing production and utilization of polycyclic aromatic hydrocarbons (PAHs) and commercial silver nanoparticles (AgNPs) have raised concerns about their potential environmental release, with coastal sediments as a substantial sink. To better understanding the effects of these contaminants on denitrification processes in coastal marine sediments, a short-term exposure simulation experiment was conducted. We investigated the effects of single and combined contamination of phenanthrene (Phe) and AgNPs on denitrification processes in a coastal marine sediment. Results showed that all contaminated treatment groups had different degrees of inhibitory effect on denitrification activity, denitrifying enzyme activity, total bacteria count and denitrifying genes. The inhibitory effect sequence of each treatment group was combined treatment > AgNPs treatment > Phe treatment. Moreover, the inhibitory effects of denitrifying genes were much larger than that of total bacteria count, indicating that the pollutants had specific toxic effects on denitrifying bacteria. The sequence of sensitivity of three reduction process to pollutants was N2O > NO2- > NO3-. All contaminated treatment groups could increase NO3-, NO2- and N2O accumulation. Furthermore, according to the linear relationship between functional gene or reductase and denitrification process, we also found that the abundance of denitrifying genes could better predict the influence of Phe and AgNPs on sediment denitrification than the denitrifying bacterial diversity. In addition, at the genus level, the community structure of nirS- and nosZ-type denitrifying bacteria changed dramatically, while changes at the phylum level were comparatively less pronounced. Single and combined contamination of Phe and AgNPs could reduce the dominance of Pseudomonas, which may lead to a potential slow-down in the degradation of Phe and inhibition of denitrification, especially the combined contamination. Overall, our study revealed that combined contamination of Phe and AgNPs could lead to an increase in NO3-, NO2- and N2O accumulation in coastal sediment, which poses a risk of eutrophication in coastal areas, exacerbates the greenhouse effect and has adverse effects on global climate change.

10.
Eur J Med Res ; 29(1): 219, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38576045

RESUMEN

PURPOSE: Colorectal cancer (CRC) is a highly heterogeneous malignancy with an unfavorable prognosis. The purpose of this study was to address the heterogeneity of CRC by categorizing it into ion channel subtypes, and to develop a predictive modeling based on ion channel genes to predict the survival and immunological states of patients with CRC. The model will provide guidance for personalized immunotherapy and drug treatment. METHODS: A consistent clustering method was used to classify 619 CRC samples based on the expression of 279 ion channel genes. Such a method was allowed to investigate the relationship between molecular subtypes, prognosis, and immune infiltration. Furthermore, a predictive modeling was constructed for ion channels to evaluate the ion channel properties of individual tumors using the least absolute shrinkage and selection operator. The expression patterns of the characteristic genes were validated through molecular biology experiments. The effect of potassium channel tetramerization domain containing 9 (KCTD9) on CRC was verified by cellular functional experiments. RESULTS: Four distinct ion channel subtypes were identified in CRC, each characterized by unique prognosis and immune infiltration patterns. Notably, Ion Cluster3 exhibited high levels of immune infiltration and a favorable prognosis, while Ion Cluster4 showed relatively lower levels of immune infiltration and a poorer prognosis. The ion channel score could predict overall survival, with lower scores correlated with longer survival. This score served as an independent prognostic factor and presented an excellent predictive efficacy in the nomogram. In addition, the score was closely related to immune infiltration, immunotherapy response, and chemotherapy sensitivity. Experimental evidence further confirmed that low expression of KCTD9 in tumor tissues was associated with an unfavorable prognosis in patients with CRC. The cellular functional experiments demonstrated that KCTD9 inhibited the proliferation, migration and invasion capabilities of LOVO cells. CONCLUSIONS: Ion channel subtyping and scoring can effectively predict the prognosis and evaluate the immune microenvironment, immunotherapy response, and drug sensitivity in patients with CRC.


Asunto(s)
Neoplasias Colorrectales , Canales Iónicos , Humanos , Canales Iónicos/genética , Nomogramas , Inmunoterapia , Neoplasias Colorrectales/genética , Pronóstico , Microambiente Tumoral
11.
Ying Yong Sheng Tai Xue Bao ; 35(1): 25-30, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38511436

RESUMEN

We systematically elaborated and compared the spatial scope and landscape changes of Horqin Grassland and Horqin Sand Land from their definitions and ranges. Horqin Grassland is an area with geographical units named after Mongolian tribes, but the boundary is unclear. Horqin Sand Land is also an area that borrows tribal names, but has independent topographic and geomorphic units, and clear boundaries. Horqin Grassland and Horqin Sand Land belong to two spatial regions that are both cross and different. The area and range of Horqin Grassland are larger than that of Horqin Sand Land which has obvious regional characteristics, and is a typical and research object area to study the development and restoration of aeolian desertification. Based on those cognition, we summarized the technologies and example models of comprehensive land management and desertification controlling over the years, and finally sorted out what should be focused on in the future to serve the annihilation war against desertification for Horqin Sand Land.


Asunto(s)
Conservación de los Recursos Naturales , Arena , Pradera , China
12.
J Am Chem Soc ; 146(13): 9404-9412, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38504578

RESUMEN

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable and potentially versatile approach is the coupling of a C-C bond through an outer-sphere mechanism, accompanied by the realization of enantiocontrol through cooperative catalysis; however, examples of such processes are yet to be identified. Herein, we present such a method for creating different compounds with quaternary stereocenters by photoredox/Fe/chiral primary amine triple catalysis. This approach facilitates the connection of an unactivated alkyl source with a tertiary alkyl moiety, which is also rare. The scalable process exhibits mild conditions, does not necessitate the use of a base, and possesses a good functional-group tolerance. Preliminary investigations into the underlying mechanisms have provided valuable insights into the reaction pathway.

13.
Fish Shellfish Immunol ; 148: 109503, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38479567

RESUMEN

Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses and cell proliferation. However, the function of the PHBs in immune regulation has largely not been determined. In the present study, we identified PHB2 in the red swamp crayfish Procambarus clarkii. PHB2 was found to be widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge. PHB2 significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. Here, we observed that PHB2 promotes the nuclear translocation of STAT by binding to STAT. After blocking PHB2 or STAT with antibodies or interfering with PHB2 or STAT, the expression levels of the antiviral genes ß-thymosin (PcThy-4) and crustin2 (Cru2) decreased. The gene sequence of PHB2 was analyzed and found to contain a nuclear introgression sequence (NIS). After in vivo injection of PHB2 with deletion of NIS (rΔNIS-PHB2), the nuclear translocation of STAT did not change significantly compared to that in the control group. These results suggest that PHB2 promoted the nuclear translocation of STAT through NIS and mediated the expression of antiviral proteins to inhibit WSSV infection.


Asunto(s)
Timosina , Virus del Síndrome de la Mancha Blanca 1 , Animales , Virus del Síndrome de la Mancha Blanca 1/fisiología , Astacoidea , Alimentos Marinos , Antivirales
14.
Ear Nose Throat J ; : 1455613241230843, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38411122

RESUMEN

Objective: We examined the relationship between factors of middle ear conditions and the outcome of ossiculoplasty in chronic otitis media (COM) by measuring the improvement in the air-bone gap (ABG) and air conduction threshold (TAC). Methods: This retrospective study analyzed 76 patients (77 ears) who underwent ossiculoplasty from among 520 COM patients who underwent tympanoplasty based on the maximum preservation of the original ossicles. The reconstructed ossicular chain was performed by preserving or utilizing the remaining malleus in all cases with the presence of the malleus manubrium. Patients with eardrum adhesion, cholesteatoma, and cholesterol granuloma were defined as having a compromised middle ear condition (Group A), and those without as having an uncompromised middle ear condition (Group B). In each group, pure-tone audiometry was performed preoperatively and postoperatively, and improvements in the ABG and TAC were compared. The effects of the types of tympanoplasty and the method of ossiculoplasty (columella versus incus interposition) on postoperative ABG and TAC were also compared. Results: The postoperative ABG improvement in Group B was significantly higher than that in Group A [ß = 7.31, 95% confidence interval (CI) = 1.93-12.69, P < .05]. Type III minor columella tympanoplasty yielded significantly better results than type III major and type Vb tympanoplasty (ß = 11.42, 95% CI = 5.16-17.68, P < .01). There were no significant differences in the postoperative ABG or TAC between the reconstruction groups with and without preservation of malleus. Conclusions: Our results indicate that complex cases compromised by adhesions, cholesteatoma, and cholesterol granuloma have worse outcomes regarding hearing improvement and success rates, while those with intact stapes suprastructure have better outcomes. Malleus was maximally preserved in the patients of this study; however, this showed no significant prognostic benefit in hearing.

15.
J Orthop Surg Res ; 19(1): 116, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38310246

RESUMEN

BACKGROUND: Although prior observational studies indicate an association between cardiovascular diseases (CVDs) and frozen shoulder (FS), the potential causal relationship between them remains uncertain. This study aims to explore the genetic causal relationship between CVDs and FS using Mendelian randomization (MR). METHODS: Genetic variations closely associated with FS were obtained from the FinnGen Consortium. Summary data for CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), stroke, and ischemic stroke (IS), were sourced from several large-scale genome-wide association studies (GWAS). MR analysis was performed using inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW, as the primary MR analysis method, complemented by other sensitivity analyses, was utilized to validate the robustness of the results. Further reverse MR analysis was conducted to explore the presence of reverse causal relationships. RESULTS: In the forward MR analysis, genetically determined risk of stroke and IS was positively associated with FS (OR [95% CI] = 1.58 (1.23-2.03), P < 0.01; OR [95% CI] = 1.46 (1.16-1.85), P < 0.01, respectively). There was no strong evidence of an effect of genetically predicted other CVDs on FS risk. Sensitivity analyses confirmed the robustness of the results. In the reverse MR analysis, no causal relationships were observed between FS and various CVDs. CONCLUSION: The study suggests that stroke increases the risk of developing FS. However, further basic and clinical research is needed to substantiate our findings.


Asunto(s)
Bursitis , Enfermedades Cardiovasculares , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/genética , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética
16.
CNS Neurosci Ther ; 30(2): e14567, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38421106

RESUMEN

AIMS: This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation. METHODS: Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment. RESULTS: Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation. CONCLUSION: Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Hesperidina , Humanos , Microglía , Citrato (si)-Sintasa/metabolismo , Citrato (si)-Sintasa/farmacología , Lisina/metabolismo , Ácido Cítrico/metabolismo , Ácido Cítrico/farmacología , Enfermedades Neuroinflamatorias , Hesperidina/metabolismo , Hesperidina/farmacología , Citratos , Lesiones Traumáticas del Encéfalo/metabolismo
17.
Front Oncol ; 14: 1335670, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38327746

RESUMEN

Background: Being the most widely used biomarker for immunotherapy, the microsatellite status has limitations in identifying all patients who benefit in clinical practice. It is essential to identify additional biomarkers to guide immunotherapy. Aberrant DNA methylation is consistently associated with changes in the anti-tumor immune response, which can promote tumor progression. This study aims to explore immunotherapy biomarkers for colon cancers from the perspective of DNA methylation. Methods: The related data (RNA sequencing data and DNA methylation data) were obtained from The Cancer Genome Atlas (TCGA) and UCSC XENA database. Methylation-driven genes (MDGs) were identified through the Pearson correlation analysis. Unsupervised consensus clustering was conducted using these MDGs to identify distinct clusters of colon cancers. Subsequently, we evaluated the immune status and predicted the efficacy of immunotherapy by tumor immune dysfunction and exclusion (Tide) score. Finally, The Quantitative Differentially Methylated Regions (QDMR) software was used to identify the specific DNA methylation markers within particular clusters. Results: A total of 282 MDGs were identified by integrating the DNA methylation and RNA-seq data. Consensus clustering using the K-means algorithm revealed that the optimal number of clusters was 4. It was revealed that the composition of the tumor immune microenvironment (TIME) in Cluster 1 was significantly different from others, and it exhibited a higher level of tumor mutation burdens (TMB) and stronger anti-tumor immune activity. Furthermore, we identified three specific hypermethylation genes that defined Cluster 1 (PCDH20, APCDD1, COCH). Receiver operating characteristic (ROC) curves demonstrated that these specific markers could effectively distinguish Cluster 1 from other clusters, with an AUC of 0.947 (95% CI 0.903-0.990). Finally, we selected clinical samples for immunohistochemical validation. Conclusion: In conclusion, through the analysis of DNA methylation, consensus clustering of colon cancer could effectively identify the cluster that benefit from immunotherapy along with specific methylation biomarkers.

18.
J Inflamm Res ; 17: 655-667, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38328562

RESUMEN

Purpose: The Nutritional Prognostic Score (NPS) is a composite indicator that effectively reflects the preoperative nutritional and inflammation status of patients. Its prognostic value has been extensively confirmed in various types of tumors. Our study aims to investigate the clinical implications of the NPS in the postoperative patients with cholangiocarcinoma (CCA). Patients and Methods: Data on clinicopathological characteristics were collected from CCA patients who underwent radical surgery between 2014 and 2019 at Harbin Medical University Cancer Hospital. NPS was calculated using relevant indicators to categorize the patients, and association of NPS with clinicopathological characteristics and survival outcomes were analyzed. To assess differences in survival rates between different groups, we utilized the Kaplan-Meier method. Independent prognostic risk factors were identified by Cox regression analysis. A CONomogram was created, and its accuracy in survival prediction was evaluated using receiver operating characteristic (ROC) curves. Independent verification was conducted in the validation group. Results: For this study, a cohort of 232 patients was enlisted and subsequently divided into training group (N=162) and validation group (N=70). An evident correlation was detected between NPS and preoperative malnutrition. Patients with higher NPS exhibited a worse overall survival (OS), with 5-year OS rates of 79.1%, 33.1%, and 10.6%. Multivariate analysis revealed that NPS was an independent risk factor for OS in resected CCA patients (P<0.001). The NPS-based Nomogram was developed to accurately assess the risk of patients. Conclusion: The NPS was identified as a significant risk factor that impacts the prognosis of patients with resected CCA. In order to improve prognosis management, the NPS-based Nomogram has been demonstrated to be a precise and efficient tool.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38347690

RESUMEN

Hyperspectral anomaly detection (HAD) aims to distinguish between the background and anomalies in a scene, which has been widely adopted in various applications. Deep neural network (DNN)-based methods have emerged as the predominant solution, wherein the standard paradigm is to discern the background and anomalies based on the error of self-supervised hyperspectral image (HSI) reconstruction. However, current DNN-based methods cannot guarantee correspondence between the background, anomalies, and reconstruction error, which limits the performance of HAD. In this article, we propose a novel gated transformer network for HAD (GT-HAD). Our key observation is that the spatial-spectral similarity in HSI can effectively distinguish between the background and anomalies, which aligns with the fundamental definition of HAD. Consequently, we develop GT-HAD to exploit the spatial-spectral similarity during HSI reconstruction. GT-HAD consists of two distinct branches that model the features of the background and anomalies, respectively, with content similarity as constraints. Furthermore, we introduce an adaptive gating unit to regulate the activation states of these two branches based on a content-matching method (CMM). Extensive experimental results demonstrate the superior performance of GT-HAD. The original code is publicly available at https://github.com/jeline0110/ GT-HAD, along with a comprehensive benchmark of state-of-the-art HAD methods.

20.
Open Life Sci ; 19(1): 20220806, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38283117

RESUMEN

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA