RESUMO
The dysregulation of N(7)-methylguanosine (m7G) modification is increasingly recognized as a key factor in the pathogenesis of cancers. Aberrant expression of these regulatory proteins in various cancers, including lung, liver, and bladder cancers, suggests a universal role in tumorigenesis. Studies have established a strong correlation between the expression levels of m7G regulatory proteins, such as Methyltransferase like 1 (METTL1) and WD repeat domain 4 (WDR4), and clinical parameters including tumor stage, grade, and patient prognosis. For example, in hepatocellular carcinoma, high METTL1 expression is associated with advanced tumor stage and poor prognosis. Similarly, WDR4 overexpression in colorectal cancer correlates with increased tumor invasiveness and reduced patient survival. This correlation underscores the potential of these proteins as valuable biomarkers for cancer diagnosis and prognosis. Additionally, m7G modification regulatory proteins influence cancer progression by modulating the expression of target genes involved in critical biological processes, including cell proliferation, apoptosis, migration, and invasion. Their ability to regulate these processes highlights their significance in the intricate network of molecular interactions driving tumor development and metastasis. Given their pivotal role in cancer biology, m7G modification regulatory proteins are emerging as promising therapeutic targets. Targeting these proteins could offer a novel approach to disrupt the malignant behavior of cancer cells and enhance treatment outcomes. Furthermore, their diagnostic and prognostic value could aid in the early detection of cancer and the selection of appropriate therapeutic strategies, ultimately enhancing patient management and survival rates. This review aims to explore the mechanisms of action of RNA m7G modification regulatory proteins in tumors and their potential applications in cancer progression and treatment. By delving into the roles of these regulatory proteins, we intend to provide a theoretical foundation for the development of novel cancer treatment strategies.
Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patologia , Biomarcadores Tumorais/metabolismo , Guanosina/análogos & derivados , Guanosina/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Metiltransferases/metabolismoRESUMO
Liver cancer is a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form, characterized by high incidence and mortality rates. Despite advances in targeted therapies and immunotherapies, the prognosis for advanced liver cancer remains poor. This underscores the urgent need for a deeper understanding of the molecular mechanisms underlying HCC to enable early detection and the development of novel therapeutic strategies. Post-translational modifications (PTMs) are crucial regulatory mechanisms in cellular biology, affecting protein functionality, interactions, and localization. These modifications, including phosphorylation, acetylation, methylation, ubiquitination, and glycosylation, occur after protein synthesis and play vital roles in various cellular processes. Recent advances in proteomics and molecular biology have highlighted the complex networks of PTMs, emphasizing their critical role in maintaining cellular homeostasis and disease pathogenesis. Dysregulation of PTMs has been associated with several malignant cellular processes in HCC, such as altered cell proliferation, migration, immune evasion, and metabolic reprogramming, contributing to tumor growth and metastasis. This review aims to provide a comprehensive understanding of the pathological mechanisms and clinical implications of various PTMs in liver cancer. By exploring the multifaceted interactions of PTMs and their impact on liver cancer progression, we highlight the potential of PTMs as biomarkers and therapeutic targets. The significance of this review lies in its potential to inform the development of novel therapeutic approaches and improve prognostic tools for early intervention in the fight against liver cancer.
Assuntos
Neoplasias Hepáticas , Processamento de Proteína Pós-Traducional , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , AnimaisRESUMO
BACKGROUND: Cardiovascular disease (CVD) is closely associated with the triglyceride glucose (TyG) index and its related indicators, particularly its combination with obesity indices. However, there is limited research on the relationship between changes in TyG-related indices and CVD, as most studies have focused on baseline TyG-related indices. METHODS: The data for this prospective cohort study were obtained from the China Health and Retirement Longitudinal Study. The exposures were changes in TyG-related indices and cumulative TyG-related indices from 2012 to 2015. The K-means algorithm was used to classify changes in each TyG-related index into four classes (Class 1 to Class 4). Multivariate logistic regressions were used to evaluate the associations between the changes in TyG-related indices and the incidence of CVD. RESULTS: In total, 3243 participants were included in this study, of whom 1761 (54.4%) were female, with a mean age of 57.62 years at baseline. Over a 5-year follow-up, 637 (19.6%) participants developed CVD. Fully adjusted logistic regression analyses revealed significant positive associations between changes in TyG-related indices, cumulative TyG-related indices and the incidence of CVD. Among these changes in TyG-related indices, changes in TyG-waist circumference (WC) showed the strongest association with incident CVD. Compared to the participants in Class 1 of changes in TyG-WC, the odds ratio (OR) for participants in Class 2 was 1.41 (95% confidence interval (CI) 1.08-1.84), the OR for participants in Class 3 was 1.54 (95% CI 1.15-2.07), and the OR for participants in Class 4 was 1.94 (95% CI 1.34-2.80). Moreover, cumulative TyG-WC exhibited the strongest association with incident CVD among cumulative TyG-related indices. Compared to the participants in Quartile 1 of cumulative TyG-WC, the OR for participants in Quartile 2 was 1.33 (95% CI 1.00-1.76), the OR for participants in Quartile 3 was 1.46 (95% CI 1.09-1.96), and the OR for participants in Quartile 4 was 1.79 (95% CI 1.30-2.47). CONCLUSIONS: Changes in TyG-related indices are independently associated with the risk of CVD. Changes in TyG-WC are expected to become more effective indicators for identifying individuals at a heightened risk of CVD.
Assuntos
Biomarcadores , Glicemia , Doenças Cardiovasculares , Obesidade , Triglicerídeos , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/sangue , Estudos Prospectivos , Triglicerídeos/sangue , Incidência , Medição de Risco , China/epidemiologia , Glicemia/metabolismo , Obesidade/epidemiologia , Obesidade/diagnóstico , Obesidade/sangue , Idoso , Biomarcadores/sangue , Estudos Longitudinais , Fatores de Tempo , Prognóstico , Fatores de Risco de Doenças Cardíacas , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Non-line-of-sight (NLOS) imaging retrieves the hidden scenes by utilizing the signals indirectly reflected by the relay wall. Benefiting from the picosecond-level timing accuracy, time-correlated single photon counting (TCSPC) based NLOS imaging can achieve theoretical spatial resolutions up to millimeter level. However, in practical applications, the total temporal resolution (also known as total time jitter, TTJ) of most current TCSPC systems exceeds hundreds of picoseconds due to the combined effects of multiple electronic devices, which restricts the underlying spatial resolution of NLOS imaging. In this paper, an instrument response function deconvolution (IRF-DC) method is proposed to overcome the constraints of a TCSPC system's TTJ on the spatial resolution of NLOS imaging. Specifically, we model the transient measurements as Poisson convolution process with the normalized IRF as convolution kernel, and solve the inverse problem with iterative deconvolution algorithm, which significantly improves the spatial resolution of NLOS imaging after reconstruction. Numerical simulations show that the IRF-DC facilitates light-cone transform and frequency-wavenumber migration solver to achieve successful reconstruction even when the system's TTJ reaches 1200 ps, which is equivalent to what was previously possible when TTJ was about 200 ps. In addition, the IRF-DC produces satisfactory reconstruction outcomes when the signal-to-noise ratio (SNR) is low. Furthermore, the effectiveness of the proposed method has also been experimentally verified. The proposed IRF-DC method is highly applicable and efficient, which may promote the development of high-resolution NLOS imaging.
RESUMO
The increasing risk posed by space debris highlights the need for accurate localization techniques. Spaceborne single photon Lidar (SSPL) offers a promising solution, overcoming the limitations of traditional ground-based systems by providing expansive coverage and superior maneuverability without being hindered by weather, time, or geographic constraints. This study introduces a novel approach leveraging non-parametric Bayesian inference and the Dirichlet process mixture model (DPMM) to accurately determine the distance of space debris in low Earth orbit (LEO), where debris exhibits nonlinear, high dynamic motion characteristics. By integrating extended Kalman filtering (EKF) for range gating, our method captures the temporal distribution of reflected photons, employing Markov chain Monte Carlo (MCMC) for iterative solutions. Experimental outcomes demonstrate our method's superior accuracy over conventional statistical techniques, establishing a clear correlation between radial absolute velocity and ranging error, thus significantly enhancing monostatic space debris localization.
RESUMO
BACKGROUND: Epidemiologic studies have indicated an association of motoric cognitive risk syndrome (MCR), a pre-dementia stage characterized by the presence of cognitive complaints and a slow gait, with increased risk of incident dementia. OBJECTIVES: We aimed to clarify this association using meta-analysis. METHODS: We systematically searched the PubMed, Embase, and Web of Science databases up to December 2022 for relevant studies that investigated the association between MCR and incident all-cause dementia and Alzheimer's disease (AD). The random-effects model was used to determine a pooled-effect estimate of the association. RESULTS: We identified seven articles that corresponded with nine cohort studies investigating the association between MCR and the risk of dementia. Pooled analysis showed that MCR was associated with a significantly increased risk of incident all-cause dementia (HR = 2.28; 95% CI: 1.90-2.73) and AD (HR = 2.05; 95% CI: 1.61-2.61). Sensitivity analysis showed that there was no evidence that individual studies influenced the pooled-effect estimate, verifying the robustness of the results. CONCLUSIONS: Our results confirm that MCR is an independent risk factor of incident all-cause dementia and AD. Future studies are needed to better understand the mechanisms underlying this association.
Assuntos
Doença de Alzheimer , Demência , Humanos , Demência/epidemiologia , Demência/etiologia , Fatores de Risco , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Estudos de Coortes , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Incidência , IdosoRESUMO
OBJECTIVES: This study aimed to explore the associations between different types of meat consumption and mortality risk among people with frailty. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: We included 19,913 physically frail participants from the UK Biobank. MEASUREMENTS: We used the validated brief food frequency questionnaire (FFQ) to measure meat consumption. Baseline diet data from 2006 to 2010 were collected, and participants were followed up until March 23, 2021. Cox proportional hazards regression models were conducted to examine the associations of meat consumption with mortality risk. RESULTS: We identified 3,622 all-cause deaths, 1,453 cancer deaths, and 1,663 cardiovascular deaths during a median follow-up time of 11.2 years. Higher consumption of unprocessed poultry (per 25 g/day increment) was associated with a lower risk of all-cause mortality (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.75-0.88), cancer mortality (HR 0.84, 95% CI 0.74-0.96), and cardiovascular mortality (HR 0.72, 95% CI 0.63-0.81). Consumption of unprocessed red meat had a U-shaped relationship with mortality. Moderate consumption of unprocessed red meat 1.0-1.9 times/week was associated with a 14% (95% CI: 3 %-24%) lower risk of all-cause mortality than the lowest consumption frequency group (0-0.9 times/week). The hazard of cancer and CV mortality was also lower in the 1.0-1.9 times/week group, though the associations were not statistically significant. More frequent consumption of processed meat was associated with an increased risk of all-cause mortality (HR 1.20, 95% CI 1.07-1.34) and cardiovascular mortality (HR 1.20, 95% CI 1.02-1.42). Fish consumption was not associated with all types of mortality. CONCLUSIONS: Higher consumption of processed meat, not fish, was associated with increased all-cause and cardiovascular mortality. In contrast, higher consumption of unprocessed poultry and moderate consumption of unprocessed red meat was associated with reduced all-cause, cancer, and cardiovascular mortality. These findings warrant further investigation to establish optimal dietary patterns for frail individuals.
Assuntos
Doenças Cardiovasculares , Causas de Morte , Dieta , Fragilidade , Carne , Neoplasias , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Longitudinais , Dieta/estatística & dados numéricos , Dieta/efeitos adversos , Doenças Cardiovasculares/mortalidade , Neoplasias/mortalidade , Fragilidade/mortalidade , Reino Unido/epidemiologia , Modelos de Riscos Proporcionais , Fatores de Risco , Idoso Fragilizado/estatística & dados numéricos , Carne Vermelha/efeitos adversos , Idoso de 80 Anos ou mais , Aves DomésticasRESUMO
Background: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored. Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA. Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15-0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19-0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14-0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19-0.75; P = 0.007). Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.
Assuntos
Fragilidade , Apneia Obstrutiva do Sono , Humanos , Idoso , Pessoa de Meia-Idade , Estudos de Coortes , Pressão Positiva Contínua nas Vias Aéreas , Fragilidade/epidemiologia , Fragilidade/complicações , Pontuação de Propensão , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapiaRESUMO
The growth parameters of the underground coal gasification (UCG) combustion cavity are important for the regulation of its gasification process. The irregular cavities formed in the early stages of ignition can affect the stability of the gasification process. In this study, a heat-solid coupling model is used to determine the combustion cavity boundary at the early stage of coal seam ignition to simulate the movement of the combustion cavity boundary by indirectly inheriting the coal seam temperature. It reveals the evolution of the temperature field, stress field, and plasticity zone at the combustion cavity boundary at the early stage of ignition in the UCG process and compares with the ex situ small-scale experiments. The simulation results show that in the early stage of ignition, the temperature transfer to the top of the coal seam and the direction of the gasification agent outlet pipeline is faster, while the transfer rate to the direction of the gasification agent inlet pipeline is slower. The main stresses are mainly distributed in the left and right sides of the combustion cavity and gradually increase directly above. The plastic zone is mainly distributed directly above the combustion cavity and arc-shaped plastic zones. The experimental results show that the temperature directly above the combustion cavity is higher than in the other directions, and the ash layer hinders the temperature transfer to the bottom. Therefore, the combustion cavity has a longer elliptical shape in the upper part, which is consistent with the simulation results. The model better reveals the extension law of the combustion cavity at the early stage of UCG ignition and provides theoretical guidance for the study of combustion cavity formation.
RESUMO
Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability. However, the local cellular-level effects of mTOR inhibition on glioma-induced neuronal alterations are not well understood. Here we employed neuron-specific profiling of ribosome-bound mRNA via 'RiboTag,' morphometric analysis of dendritic spines, and in vivo calcium imaging, along with pharmacological mTOR inhibition to investigate the impact of glioma burden and mTOR inhibition on these neuronal alterations. The RiboTag analysis of tumor-associated excitatory neurons showed a downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development, and an upregulation of transcripts encoding cytoskeletal proteins involved in dendritic spine turnover. Light and electron microscopy of tumor-associated excitatory neurons demonstrated marked decreases in dendritic spine density. In vivo two-photon calcium imaging in tumor-associated excitatory neurons revealed progressive alterations in neuronal activity, both at the population and single-neuron level, throughout tumor growth. This in vivo calcium imaging also revealed altered stimulus-evoked somatic calcium events, with changes in event rate, size, and temporal alignment to stimulus, which was most pronounced in neurons with high-tumor burden. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed the glioma-induced alterations on the excitatory neurons, including the alterations in ribosome-bound transcripts, dendritic spine density, and stimulus evoked responses seen by calcium imaging. These results point to mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma - manifested by alterations in ribosome-bound mRNA, dendritic spine density, and stimulus-evoked neuronal activity. Collectively, our work identifies the pathological changes that tumor-associated excitatory neurons experience as both hyperlocal and reversible under the influence of mTOR inhibition, providing a foundation for developing therapies targeting neuronal signaling in glioma.
RESUMO
Background: Frailty is a risk factor for acute myocardial infarction (AMI). This study examined the association between the modified frailty index (MFI) and adverse outcomes in patients with critical AMI. Methods: Data were obtained from the Medical Information Mart for Intensive Care IV database. Logistic and Cox regression models and a competing risk model were applied. Results: Of 5003 patients, 1496 were non-frail and 3507 were frail. Frailty was significantly associated with in-hospital mortality (per point, OR 1.13, 95% CI: 1.05-1.21; frail vs non-frail, OR 1.31, 95% CI: 1.04-1.65) and 1-year mortality (per point, HR 1.15, 95% CI: 1.11-1.20; frail vs non-frail, HR 1.37, 95% CI: 1.20-1.58). Frailty was significantly associated with post-discharge care needs (per point, OR 1.23, 95% CI: 1.14-1.33; frail vs non-frail, OR 1.47, 95% CI: 1.22-1.78). In the competing risk models, frailty was significantly associated with a lower probability of being discharged from the ICU (per point, HR 0.87, 95% CI: 0.85-0.90; frail vs non-frail, HR 0.73, 95% CI: 0.68-0.79) and hospital (per point, HR 0.82, 95% CI: 0.80-0.85; frail vs non-frail, HR 0.62, 95% CI: 0.57-0.68). Subgroup analyses showed the association of frailty with in-hospital and 1-year mortality was stronger in patients with a SOFA score ≤2 than in those with a SOFA score >2 (both p<0.05 for interaction). Conclusion: Frailty assessed by the MFI was an independent predictor of adverse outcomes in patients with critical AMI and may be helpful for prognostic risk stratification.
Assuntos
Fragilidade , Infarto do Miocárdio , Humanos , Idoso , Idoso Fragilizado , Estudos Retrospectivos , Assistência ao Convalescente , Alta do PacienteRESUMO
Black and odorous water is an extreme pollution phenomenon. This article reviews the formation process, formation conditions, and evaluation methods of black and odorous water. The results indicate that N, P, and TOC are the key nutrients inducing black and odorous water while S, Fe, and Mn are key elements forming blackening and odorizing pollutants. In addition, Cyanobacteria, Proteobacteria, Firmicutes, Verrucomicrobia, Planctomycetes, and Actinobacteria participate in the biogeochemistry cycles of key elements and play important roles in the blackening and odorizing process of water. The black and odorous thresholds that need further verification are as follows: 1.0 g/L of organic matrix, 2.0-8.0 mg/L of NH3-N, 0.6-1.2 mg/L of TP, 0.05 mg/L of Fe2+, 0.3 mg/L of Mn2+, 1.2-2.0 mg/L of DO, and -50 to 50 mV of the ORP. In order to propose a universal assessment method, it is suggested that NH3-N, DO, COD, BOD, and TP serve as the assessment indicators, and the levels of pollutions are I (not black odor), II (mild black odor), III (moderate black odor), IV (severe black odor), and inferior IV (extremely black odor).
Assuntos
Cianobactérias , Água , Monitoramento Ambiental , Odorantes , Poluição da ÁguaRESUMO
Ellipse fitting is widely used in the extraction of the differential phase between atom interferometers amid substantial common phase noise. This study meticulously examines the dependency of extraction noise on the differential phase between atom interferometers during ellipse fitting. It reveals that the minimum extraction noise can manifest at distinct differential phases, contingent upon the dominance of different noise types. Moreover, the outcomes are influenced by whether the interferometers undergo simultaneous detection or not. Our theoretical simulations find empirical validation in a compact horizontal atom gravity gradiometer. The adjustment of the differential phase significantly enhances measurement sensitivity, culminating in a differential gravity resolution of 1.6 × 10-10â g @ 4800 s.