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Background: Prognostic factors are complicated and changeable for locally advanced gastric cancer (GC) patients. This study aimed to perform a novel prognostic model on survival for locally advanced GC patients who have received neoadjuvant chemotherapy and radical surgery. Methods: The locally advanced GC patients with neoadjuvant chemotherapy were included in this study from Zhongshan Hospital, Fudan University. A nomogram was developed based on independent prognostic factors identified through a multivariable Cox regression model. Model performance was evaluated in training and independent external cohorts in terms of calibration, discrimination, and clinical usefulness. Results: A total of 273 patients received radical resections. The median progression-free survival (PFS) and overall survival (OS) for all patients were 43.8 and 61.2 months, respectively. Nomogram showed that Lauren type made the greatest contribution to prognosis, followed by ypN. The prognostic nomogram had excellent discriminative ability, with a C-index of 0.689 [95% confidence interval (CI): 0.661-0.716], and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.778, 0.746, and 0.725 for 3-, 5- and 10-year OS, respectively. Similar results were obtained in the external validation cohort. Based on the nomogram, the whole cohort was divided into high-risk and low-risk groups. And risk group classification was significantly associated with clinical characteristics, and produced an AUC value of 0.781, 0.748, and 0.727 for 3-, 5- and 10-year OS, respectively. Furthermore, compared with the tumor-node-metastasis (TNM) staging system (8th edition), Japanese criteria, and German criteria, the decision curve analysis (DCA) graphically demonstrated that the new model had more optimal net benefits in predicting the 3-, 5-, and 10-year OS for GC patients. Both C-index and time-dependent ROC curve demonstrated that the nomogram had a stronger capability for accurately predicting prognosis compared with the other staging system. Conclusions: The nomogram model is an effective support tool to predict OS in GC patients undergoing perioperative chemotherapy followed by radical surgery.
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Radio-immunotherapy driven by radiation-induced immunogenic cell death (ICD) is emerging as a potential opportunity to address conventional radiotherapy (RT) that is only applicable to localized tumor treatment. However, the effective activation of ICD during RT is severely limited by radiation dose, weak tumor immunogenicity, and radio-resistance caused by tumor microenvironment (TME). Herein, a novel bimetallic hybrid nanoscale coordination nanostimulator is first proposed by phosphate backbone doped with copper ions (Cu2+) and hafnium ions (Hf4+), and then modified with polyvinylpyrrolidone (PVP). The PVPylated Cu/Hf-doped phosphate nanostimulator (denoted as CHP) exhibits effective reprogramming of TME, including depletion of tumor endogenous glutathione (GSH), relief of tumor hypoxia and repolarization of M2 phenotypic macrophages, thus achieving tumor radiosensitization at low X-ray irradiation dose, gradually accumulation of tumor endogenous reactive oxygen species (ROS) and augmenting cuproptosis. In addition, cuproptosis can amplify RT-induced anti-tumor immunity through ICD activation, ultimately resulting in a robust anti-tumor immune response and long-term immunity, evidenced by distant tumor growth inhibition of 4T1-tumor-bearing models. More interestingly, it is discovered that CHP-mediated cuproptosis can be intensifiable during X-ray irradiation. Taken together, this work presents a novel radio-cuproptosis-immunotherapy cascade strategy, offering a new perspective for innovation in the treatment field of breast cancer.
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Here we present a compact and precise [2]catenane rotary motor that functions with a single recognition site, capable of achieving a 360° directional rotation powered by chemical fuels. The motor is propelled by an acid-base fueled benzimidazolium pumping cassette and deemed the smallest (molecular weight â¼ 994 Da) catenane rotary motor to date. It can effectively undergo a 180° rotation by transitioning the [24]crown-6 ether (24C6) from the benzimidazolium site to the less favorable alkyl moiety through sequential deprotonation, slipping, and re-protonation operations, generating a meta stable co-conformer. Subsequently, a discharging phase, triggered by de-benzylation and re-benzylation, facilitates the other half-rotation of the motor, returning the 24C6 to its initial position and completing the full directional rotation of the [2]catenane rotary motor within 18 hours. The precision of the motor's operation enables further advances in artificial molecular machines.
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Objective: The aim of this study was to understand the psychological insulin resistance status among Chinese patients with type 2 diabetes and investigate its associated factors in these patients. Methods: A multi-stage stratified random sampling was performed to randomly select patients with type 2 diabetes from the eastern, central, and western regions in Shandong Province, China, and 660 valid questionnaires were collected. Psychological insulin resistance was assessed by the scale of My Opinion on Insulin (MOI). Factors associated with psychological insulin resistance were examined in a binary logistic model. Results: Four-fifths of the patients with type 2 diabetes (82.1%) had psychological insulin resistance. Being female (OR = 1.770, 95% CI: 1.063-2.950, p < 0.05), having a monthly income of greater than 4,000 Renminbi (approximately $1,540) (OR = 0.444, 95% CI: 0.216-0.915, p < 0.05), living with type 2 diabetes for 11 years or more (OR = 0.387, 95% CI: 0.238-0.630, p < 0.05), self-rated poor health (OR = 1.706, 95% CI: 1.092-2.664, p < 0.05), and moderate discrimination against type 2 diabetes (OR = 1.924, 95% CI: 1.166-3.175, p < 0.05) were associated with psychological insulin resistance. Conclusions: The prevalence of psychological insulin resistance among Chinese patients with type 2 diabetes is relatively high. Approaches are needed to address the issue of psychological insulin resistance of type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Masculino , China/epidemiología , Persona de Mediana Edad , Anciano , Adulto , Estudios Transversales , Encuestas y CuestionariosRESUMEN
In light of the low dissolved oxygen concentration in the deep sea, the corrosion mechanisms of the high entropy alloy (HEA) AlCoCrFeNi in artificial seawater with varying oxygen concentrations (2.0, 4.0, 7.0 mg/L) were studied. As the oxygen concentration decreases, the alloy's free corrosion potential decreases, and at 2.0 mg/L, the corrosion rate is 421 times higher than that at 7.0 mg/L. The corrosion form transforms from pitting to uniform corrosion. The primary reasons for this are the passivation film is thin under low oxygen concentration conditions, as well as the preferential dissolution of the alloy elements Al and Ni due to their high activity and "local acidizing" properties, respectively. In designing a super corrosion-resistant high entropy alloy for use in the deep sea, it is advisable to avoid the use of element Al and to add Ni with caution.
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PURPOSE: To investigate the efficacy of a modified maxillary protraction appliance in patients of skeletal Class â ¢ with crowding. METHODS: Forty patients with skeletal Class â ¢ malocclusion were divided into two groups, with 20 patients in each group. The experimental group had molar in a neutral or distal relationship and applied a modified maxillary protraction appliance, while the control group had molar mesial relationship and applied a conventional maxillary protraction appliance. Lateral cephalometric radiographs were taken before and after treatment in both groups for comparison. SPSS 22.0 software package was used for data analysis. RESULTS: The angle measurements taken before and after treatment showed a significant increase in SNA, ANB, SN-MP and U4-SN(Pï¼0.01), while SNB decreased(Pï¼0.01) in both groups. SN-OL changes were statistically different before and after treatment in the experimental group(Pï¼0.05). The sagittal measurements before and after treatment in both groups showed significant alterations in all(Pï¼0.05) but the length of the maxillary arch in both groups. For vertical measurements, U1-PP, L1-MP, U4-SN, U6-SN, and ANS-ME all increased (Pï¼0.05), while the changes of U4-PP and U6-PP in the two groups before and after treatment were statistically different(Pï¼0.05). Compared with the control group, the experimental group had a significantly increased maxillary arch length, a more remote location at U6, and a less variable molar relationship after treatment(Pï¼0.01). The two groups showed a variable amount of cephalometric measurements before and after treatment: the experimental group had a significant increase in maxillary arch length, a more remote position at U6, and a smaller change in molar relationship compared to the control group(Pï¼0.01). CONCLUSIONS: The modified maxillary protraction appliance showed good results for maxillary protraction and pushing the molar distally in patients with skeletal Class â ¢ with crowding at neutral or distal molar relationship.
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Cefalometría , Maloclusión de Angle Clase III , Maxilar , Humanos , Maloclusión de Angle Clase III/terapia , Maloclusión/terapiaRESUMEN
With stringent regulations of internal combustion engine on reducing CO2 emission, ammonia has been used as an alternative fuel. Investigating how engine-related performance is affected by partial ammonia replacement of diesel fuel is essential for understanding the combustion. Therefore, in this study, a three-dimensional numerical simulation model is developed for the burning of two fuels of diesel and ammonia based on relevant parameters (i.e., compression ratio, load, ammonia energy fraction, etc.) in a lab-made diesel engine. The consequences of load and compression proportion on combustion and pollutant emissions are investigated for ammonia energy fractions between 50% and 90%. When the ammonia portion rises, the increased ammonia equivalent ratio causes ammonia to move away from the dilute combustion boundary and accelerates the combustion rate of ammonia. An increase in compression ratio significantly increases the specified thermal performance and combustion efficacy. When the compression ratio is 16, as the ammonia energy fractions increases, due to the increase in the proportion of ammonia, that is, the proportion of nitrogen atoms increases, more NOx is generated during the combustion process. When the ammonia substitution rate is 90%, as the compression ratio increases, the cylinder pressure and temperature increase. The combustion efficiency of ammonia increases, generating more NOx and NOx emissions can reach 0.66 mg/m3. At a compression ratio of 18, the NOx emissions can reach 1.59 mg/m3. However, under medium and low load conditions, as the ammonia fraction increases, the total energy of fuel decreases, and the combustion efficiency of ammonia decreases, resulting in a decrease in the heat released during combustion and a decrease in NOx emissions. When the ammonia substitution rate is 90% and the load is 25%, NOx emissions reach 0.1 mg/m3. This research provides theoretical suggestions for the profitable and use ammonia fuel in internal combustion engines in a clean manner.
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The fate of ubiquitous microplastics (MPs) is largely influenced by dissolved organic matter (DOM) in aquatic environments, which has garnered significant attention. The reactivity of DOM is reported to be greatly regulated by molecular weights (MWs), yet little is known about the effects of different MW DOM on MP aging. Here, the aging behavior of polystyrene MPs (PSMPs) in the presence of different MW fulvic acids (FAs) and humic acids (HAs) was systematically investigated. Under ultraviolet (UV) illumination, O/C of PSMPs aged for 96 h surged from 0.008 to 0.146 in the lower MW FA (FA<1kDa) treatment, suggesting significant PSMP aging. However, FA exhibited a stronger effect on facilitating PSMP photoaging than HA, which can be attributed to the fact that FA<1kDa contains more quinone and phenolic moieties, demonstrating a higher redox capacity. Meanwhile, compared to other fractions, FA<1kDa was more actively involved in the increase of different reactive species yields by 50-290%, including â¢OH, which plays a key role in PSMP photoaging, and contributed to a 25% increase in electron-donating capacity (EDC). This study lays a theoretical foundation for a better understanding of the environmental fate of MPs.
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Sustancias Húmicas , Microplásticos , Peso Molecular , Contaminantes Químicos del Agua/química , Rayos Ultravioleta , BenzopiranosRESUMEN
The interaction between cancer cells and immune cells plays critical roles in gastric cancer (GC) progression and immune evasion. Forced legumain (LGMN) is one of the characteristics correlated with poor prognosis in gastric cancer patients. However, the role of gastric-cancer-secreted LGMN (sLGMN) in modulating the tumor immune microenvironment and the biological effect on the immune evasion of gastric cancer remains unclear. In this study, we found that forced expression of sLGMN in gastric cancer serum correlates with increased M2 macrophage infiltration in GC tissues and predicted resistance to anti-PD-1 immunotherapy. Mechanistically, gastric cancer cells secrete LGMN via binding to cell surface Integrin αvß3, then activate Integrin αvß3/PI3K (Phosphatidylinositol-4,5-bisphosphate3-kinase)/AKT (serine/threonine kinase)/mTORC2 (mammalian target of rapamycin complex 2) signaling, promote metabolic reprogramming, and polarize macrophages from the M1 to the M2 phenotype. Either blocking LGMN, Integrin αv, or knocking out Integrin αv expression and abolishing the LGMN/Integrin αvß3 interaction significantly inhibits metabolic reprogramming and polarizes macrophages from the M1 to the M2 phenotype. This study reveals a critical molecular crosstalk between gastric cancer cells and macrophages through the sLGMN/Integrinαvß3/PI3K/AKT/mTORC2 axis in promoting gastric cancer immune evasion and resistance to anti-PD-1 immunotherapy, indicating that the sLGMN/Integrinαvß3/PI3K/AKT/mTORC2 axis may act as a promising therapeutic target.
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[This corrects the article DOI: 10.1007/s11032-024-01474-9.].
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Lignin-derived carbon nanodots (LCNs) are nanometer-scale carbon spheres fabricated from naturally abundant lignin. Owing to rich and highly heritable graphene like π-π conjugated structure of lignin, to fabricate LCNs from it not only endows LCNs with on-demand tunable size and optical features, but also further broadens the green and chemical engineering of carbon nanodots. Recently, they have become increasingly popular in sensing, bioimaging, catalysis, anti-counterfeiting, energy storage/conversion, and others. Despite the enormous research efforts put into the ongoing development of lignin value-added utilization, few commercial LCNs are available. To have a deeper understanding of this issue, critical impacts on the preparation, properties, and applications of state-of-the-art LCNs are carefully reviewed and discussed. A concise analysis of their unique advantages, limitations for specific applications, and current challenges and outlook is conducted. We hope that this review will stimulate further advances in the functional material-oriented production of lignin.
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Carbono , Lignina , Lignina/química , Carbono/química , Nanopartículas/química , Catálisis , Nanoestructuras/químicaRESUMEN
BACKGROUND: The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. RESULTS: We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. CONCLUSIONS: Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.
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Elementos Transponibles de ADN , Hematopoyesis , Células Madre Hematopoyéticas , Análisis de la Célula Individual , Animales , Elementos Transponibles de ADN/genética , Análisis de la Célula Individual/métodos , Ratones , Hematopoyesis/genética , Humanos , Células Madre Hematopoyéticas/metabolismo , Células Endoteliales/metabolismoRESUMEN
Cancer invasion and migration play a pivotal role in tumor malignancy, which is a major cause of most cancer deaths. Rotating magnetic field (RMF), one of the typical dynamic magnetic fields, can exert substantial mechanical influence on cells. However, studying the effects of RMF on cell is challenging due to its complex parameters, such as variation of magnetic field intensity and direction. Here, we developed a systematic simulation method to explore the influence of RMF on tumor invasion and migration, including a finite element method (FEM) model and a cell-based hybrid numerical model. Coupling with the data of magnetic field from FEM, the cell-based hybrid numerical model was established to simulate the tumor cell invasion and migration. This model employed partial differential equations (PDEs) and finite difference method to depict cellular activities and solve these equations in a discrete system. PDEs were used to depict cell activities, and finite difference method was used to solve the equations in discrete system. As a result, this study provides valuable insights into the potential applications of RMF in tumor treatment, and a series of in vitro experiments were performed to verify the simulation results, demonstrating the model's reliability and its capacity to predict experimental outcomes and identify pertinent factors. Furthermore, these findings shed new light on the mechanical and chemical interplay between cells and the ECM, offering new insights and providing a novel foundation for both experimental and theoretical advancements in tumor treatment by using RMF.
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OBJECTIVE: To investigate the characteristics and treatment modalities of malignant tumors originating from the sublingual gland, as well as evaluate the therapeutic outcomes following free flap reconstruction. METHODS: A retrospective statistical analysis was conducted on the clinical data of nine patients diagnosed with malignant neoplasms tumor of the sublingual gland. RESULTS: Nine case of malignant tumors originated from the sublingual glandular tissue, encompassing eight adenoid cystic carcinoma (ACC) and a single case of bipartite differentiated carcinoma-a hybrid of epithelial-myoepithelial carcinoma and adenoid cystic carcinoma. Among the nine patients, four anterolateral thigh flaps were used (three of which were thin flaps), and five forearm flaps were also empoyed. The size of flaps varied, with the lengths ranging from 4 cm to 9 cm, and the widths ranging from 2.5 cm to 6 cm. The vessels chosen for anastomosis were the superior thyroid artery in seven cases, the facial artery in one case, and the lingual artery in one case. Among the eight patients who underwent dissection of cervical lymph nodes, metastasis were found in one case. Two patients underwent adjuvant radiotherapy. Upon postoperative follow-up, there was no recurrence in any of the nine patients . CONCLUSION: The anterolateral thigh perforator flap thinning technique can be employed for postoperative reconstruction of malignant sublingual gland tumors.
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Apyrase is a class of enzyme that catalyzes the hydrolysis of nucleoside triphosphates/diphosphates (NTP/NDP), which widely involved in regulation of plant growth and stress responses. However, apyrase family genes in maize have not been identified, and their characteristics and functions are largely unknown. In this study, we identified 16 apyrases (named as ZmAPY1-ZmAPY16) in maize genome, and analyzed their phylogenetic relationships, gene structures, chromosomal distribution, upstream regulatory transcription factors and expression patterns. Analysis of the transcriptome database unveiled tissue-specific and abiotic stress-responsive expression of ZmAPY genes in maize. qPCR analysis further confirmed their responsiveness to drought, heat, and cold stresses. Association analyses indicated that variations of ZmAPY5 and ZmAPY16 may regulate maize agronomic traits and drought responses. Our findings shed light on the molecular characteristics and evolutionary history of maize apyrase genes, highlighting their roles in various biological processes and stress responses. This study forms a basis for further exploration of apyrase functions in maize. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01474-9.
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BACKGROUND: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a serious and potentially life-threatening disease. Mandibular advancement device (MAD) has the characteristics of non-invasive, comfortable, portable and low-cost, making it the preferred treatment for mild-to-moderate OSAHS. Our previous studies found that abnormal contractility and fibre type distribution of the genioglossus could be caused by OSAHS. However, whether the mitochondria participate in these tissue changes is unclear. The effect of MAD treatment on the mitochondria of the genioglossus in OSAHS is also uncertain. OBJECTIVE: To examine the morphology and function of mitochondria from the genioglossus in a rabbit model of obstructive sleep apnea-hypopnea syndrome (OSAHS), as well as these factors after insertion of a mandibular advancement device (MAD). METHODS: Thirty male New Zealand white rabbits were randomised into three groups: control, OSAHS and MAD, with 10 rabbits in each group. Animals in Group OSAHS and Group MAD were induced to develop OSAHS by injection of gel into the submucosal muscular layer of the soft palate. The rabbits in Group MAD were fitted with a MAD. The animals in the control group were not treated. Further, polysomnography (PSG) and cone-beam computed tomography (CBCT) scan were used to measure MAD effectiveness. CBCT of the upper airway and PSG suggested that MAD was effective. Rabbits in the three groups were induced to sleep for 4-6 h per day for eight consecutive weeks. The genioglossus was harvested and detected by optical microscopy and transmission electron microscopy. The mitochondrial membrane potential was determined by laser confocal microscopy and flow cytometry. Mitochondrial complex I and IV activities were detected by mitochondrial complex assay kits. RESULTS: OSAHS-like symptoms were induced successfully in Group OSAHS and rescued by MAD treatment. The relative values of the mitochondrial membrane potential, mitochondrial complex I activity and complex IV activity were significantly lower in Group OSAHS than in the control group; however, there was no significant difference between Group MAD and the control group. The OSAHS-induced injury and the dysfunctional mitochondria of the genioglossus muscle were reduced by MAD treatment. CONCLUSION: Damaged mitochondrial structure and function were induced by OSAHS and could be attenuated by MAD treatment.
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Modelos Animales de Enfermedad , Avance Mandibular , Mitocondrias , Apnea Obstructiva del Sueño , Animales , Conejos , Apnea Obstructiva del Sueño/terapia , Apnea Obstructiva del Sueño/fisiopatología , Avance Mandibular/instrumentación , Avance Mandibular/métodos , Masculino , Lengua/fisiopatología , Lengua/patologíaRESUMEN
The crab-eating macaques ( Macaca fascicularis ) and rhesus macaques ( M. mulatta ) are widely studied nonhuman primates in biomedical and evolutionary research. Despite their significance, the current understanding of the complex genomic structure in macaques and the differences between species requires substantial improvement. Here, we present a complete genome assembly of a crab-eating macaque and 20 haplotype-resolved macaque assemblies to investigate the complex regions and major genomic differences between species. Segmental duplication in macaques is â¼42% lower, while centromeres are â¼3.7 times longer than those in humans. The characterization of â¼2 Mbp fixed genetic variants and â¼240 Mbp complex loci highlights potential associations with metabolic differences between the two macaque species (e.g., CYP2C76 and EHBP1L1 ). Additionally, hundreds of alternative splicing differences show post-transcriptional regulation divergence between these two species (e.g., PNPO ). We also characterize 91 large-scale genomic differences between macaques and humans at a single-base-pair resolution and highlight their impact on gene regulation in primate evolution (e.g., FOLH1 and PIEZO2 ). Finally, population genetics recapitulates macaque speciation and selective sweeps, highlighting potential genetic basis of reproduction and tail phenotype differences (e.g., STAB1 , SEMA3F , and HOXD13 ). In summary, the integrated analysis of genetic variation and population genetics in macaques greatly enhances our comprehension of lineage-specific phenotypes, adaptation, and primate evolution, thereby improving their biomedical applications in human diseases.
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BACKGROUND: N1-methyladenosine (m1A), among the most common internal modifications on RNAs, has a crucial role to play in cancer development. The purpose of this study were systematically investigate the modification characteristics of m1A in hepatocellular carcinoma (HCC) to unveil its potential as an anticancer target and to develop a model related to m1A modification characteristics with biological functions. This model could predict the prognosis for patients with HCC. METHODS: An integrated analysis of the TCGA-LIHC database was performed to explore the gene signatures and clinical relevance of 10 m1A regulators. Furthermore, the biological pathways regulated by m1A modification patterns were investigated. The risk model was established using the genes that showed differential expression (DEGs) between various m1A modification patterns and autophagy clusters. These in vitro experiments were subsequently designed to validate the role of m1A in HCC cell growth and autophagy. Immunohistochemistry was employed to assess m1A levels and the expression of DEGs from the risk model in HCC tissues and paracancer tissues using tissue microarray. RESULTS: The risk model, constructed from five DEGs (CDK5R2, TRIM36, DCAF8L, CYP26B, and PAGE1), exhibited significant prognostic value in predicting survival rates among individuals with HCC. Moreover, HCC tissues showed decreased levels of m1A compared to paracancer tissues. Furthermore, the low m1A level group indicated a poorer clinical outcome for patients with HCC. Additionally, m1A modification may positively influence autophagy regulation, thereby inhibiting HCC cells proliferation under nutrient deficiency conditions. CONCLUSIONS: The risk model, comprising m1A regulators correlated with autophagy and constructed from five DEGs, could be instrumental in predicting HCC prognosis. The reduced level of m1A may represent a potential target for anti-HCC strategies.
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Autofagia , Carcinoma Hepatocelular , Regulación Neoplásica de la Expresión Génica , Metilación de ARN , Femenino , Humanos , Masculino , Adenosina/análogos & derivados , Adenosina/metabolismo , Autofagia/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Línea Celular Tumoral , Proliferación Celular , Metilación de ADN , Perfilación de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Pronóstico , Metilación de ARN/genéticaRESUMEN
Understanding gene expression variations between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques ( Macaca mulatta, MMU) and crab-eating macaques ( M. fascicularis, MFA) serve as crucial nonhuman primate biomedical models with different phenotypes. To date, however, large-scale comparative transcriptome research between these two species has not yet been fully explored. Here, we conducted systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples (41 MFA samples and 43 MMU samples) encompassing 14 common tissues. Our findings revealed a small fraction of genes (3.7%) with differential expression between the two species, as well as 36.5% of genes with tissue-specific expression in both macaques. Comparison of gene expression between macaques and humans indicated that 22.6% of orthologous genes displayed differential expression in at least two tissues. Moreover, 19.41% of genes that overlapped with macaque-specific structural variants showed differential expression between humans and macaques. Of these, the FAM220A gene exhibited elevated expression in humans compared to macaques due to lineage-specific duplication. In summary, this study presents a large-scale transcriptomic comparison between MMU and MFA and between macaques and humans. The discovery of gene expression variations not only enhances the biomedical utility of macaque models but also contributes to the wider field of primate genomics.
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Genómica , Transcriptoma , Humanos , Animales , Macaca mulatta/genética , Macaca fascicularis/genética , Perfilación de la Expresión Génica/veterinariaRESUMEN
Pancreatic cancer is a highly malignant and metastatic cancer. Pancreatic cancer can lead to liver metastases, gallbladder metastases, and duodenum metastases. The identification of pancreatic cancer cells is essential for the diagnosis of metastatic cancer and exploration of carcinoma in situ. Organelles play an important role in maintaining the function of cells, the various cells show significant differences in organelle microenvironment. Herein, six probes are synthesized for targeting mitochondria, lysosomes, cell membranes, endoplasmic reticulum, Golgi apparatus, and lipid droplets. The six fluorescent probes form an organelles-targeted sensor array (OT-SA) to image pancreatic metastatic cancer cells and cell spheroids. The homology of metastatic cancer cells brings the challenge for identification of these cells. The residual network (ResNet) model has been proven to automatically extract and select image features, which can figure out a subtle difference among similar samples. Hence, OT-SA is developed to identify pancreatic metastasis cells and cell spheroids in combination with ResNet analysis. The identification accuracy for the pancreatic metastasis cells (> 99%) and pancreatic metastasis cell spheroids (> 99%) in the test set is successfully achieved respectively. The organelles-targeting sensor array provides a method for the identification of pancreatic cancer metastasis in cells and cell spheroids.