RESUMO
The untranslated region (UTR) of messenger ribonucleic acid (mRNA), including the 5'UTR and 3'UTR, plays a critical role in regulating gene expression and translation. Variants within the UTR can lead to changes associated with human traits and diseases; however, computational prediction of UTR variant effect is challenging. Current noncoding variant prediction mainly focuses on the promoters and enhancers, neglecting the unique sequence of the UTR and thereby limiting their predictive accuracy. In this study, using consolidated datasets of UTR variants from disease databases and large-scale experimental data, we systematically analyzed more than 50 region-specific features of UTR, including functional elements, secondary structure, sequence composition and site conservation. Our analysis reveals that certain features, such as C/G-related sequence composition in 5'UTR and A/T-related sequence composition in 3'UTR, effectively differentiate between nonfunctional and functional variant sets, unveiling potential sequence determinants of functional UTR variants. Leveraging these insights, we developed two classification models to predict functional UTR variants using machine learning, achieving an area under the curve (AUC) value of 0.94 for 5'UTR and 0.85 for 3'UTR, outperforming all existing methods. Our models will be valuable for enhancing clinical interpretation of genetic variants, facilitating the prediction and management of disease risk.
Assuntos
Regiões 3' não Traduzidas , Regiões 5' não Traduzidas , Humanos , Biologia Computacional/métodos , Aprendizado de Máquina , Variação Genética , Regiões não TraduzidasRESUMO
OBJECTIVE: Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis. METHODS: We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies. RESULTS: We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, p < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification. CONCLUSION: Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for future research.
Assuntos
Apoptose , Nefropatias Diabéticas , Aprendizado de Máquina , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Humanos , Biologia Computacional/métodos , Redes Reguladoras de Genes , Mapas de Interação de ProteínasRESUMO
We report a 4.3â µm mid-infrared (mid-IR) high-power amplified spontaneous emission (ASE) fiber source based on CO2-filled nested hollow-core anti-resonant fiber (Nested HC-ARF). The pump source is a homemade hundred-watt-level wavelength-tunable 2â µm single-frequency fiber laser. A 5.7 m long 8-tube Nested HC-ARF is used as the gas cell, with a core diameter of 110â µm and cladding diameter of 400â µm, which exhibits transmission loss of 0.1â dB/m at 2 µm and 0.24â dB/m at 4.3â µm respectively. To improve the coupling efficiency of the high-power pump laser and reduce the influence of the thermal effect at the input end of the hollow-core fiber, the fiber is designed for multimode transmission at the pump wavelength. A continuous wave output power of 6.6 W at 4.3 µm is achieved, and the slope efficiency is 17.05%. To the best of our knowledge, it is the highest output power for such gas-filled HC-ARF ASE sources in 4â¼5â µm. This work demonstrates the great potential of gas-filled HC-ARF generating high-power mid-IR emission.
RESUMO
BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Oclusão do Apêndice Atrial Esquerdo , Veias Pulmonares/cirurgia , Pontuação de Propensão , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Hemorragia/etiologia , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND: In recent decades, China has experienced a rapid increase in the number of elderly individuals and life expectancy, as well as industrialization, which is associated with an increased prevalence of Parkinson's disease (PD). However, inconsistent results have recently been reported. Therefore, this study aimed to investigate the prevalence and distribution characteristics of PD among individuals aged 45 years and older. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), we attempted to estimate the prevalence of PD and its distribution characteristics among 19,034 individuals aged 45 years and older residing in 446 communities/villages within 27 provinces/autonomous regions/municipalities in mainland China. Cases were established based on a doctor's previous diagnosis. Crude and age-adjusted prevalence rates were calculated and stratified by age, sex, area of residence, education level, marital status, and geographic region. Logistic regression models were used to identify risk factors associated with PD. RESULTS: We identified 178 patients with PD among 19,034 residents aged 45 years and older. The crude prevalence was 0.94%, and the age-adjusted prevalence was 0.82% for individuals aged 45 years and older. The prevalence of PD increased with age (P < 0.001). No significant differences were found in terms of sex, area of residence, or education level. Stratified by geographic region, the prevalence of PD was greater in North and Northwest China and lower in southern China (p < 0.001). Multiple regression analyses showed that age was a significant risk factor for PD. CONCLUSION: The prevalence of PD increased with age in the Chinese population.
Assuntos
Doença de Parkinson , Humanos , China/epidemiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Estudos Longitudinais , Prevalência , Doença de Parkinson/epidemiologia , Idoso de 80 Anos ou mais , Fatores de Risco , Aposentadoria/estatística & dados numéricosRESUMO
BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. METHOD: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. CONCLUSION: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.
Assuntos
Necrose da Cabeça do Fêmur , Mapas de Interação de Proteínas , Animais , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Necrose da Cabeça do Fêmur/imunologia , Humanos , Biomarcadores/metabolismo , Perfilação da Expressão Gênica , Modelos Animais de Doenças , Biologia Computacional , Redes Reguladoras de Genes , Camundongos , Masculino , Esteroides , Aprendizado de Máquina , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: To investigate the genetic causes of 22 patients with clinically high suspicion of X-linked hypohidrotic ectodermal dysplasia from 20 unrelated Chinese families, expand the spectrum of ectodysplasin-A mutations, and provide more evidence for variants of uncertain significance. SUBJECTS AND METHODS: Whole-exome sequencing was performed and potentially pathogenic variants were verified by Sanger sequencing. Western blotting, real-time PCR and immunofluorescence analyses were performed to investigate the preliminary functions of the candidate variants. RESULTS: Nineteen ectodysplasin-A variants were identified, six of which were not previously reported. Among these variants, we identified a patient who carried two mutations in ectodysplasin-A and exhibited more severe phenotypes. Additionally, mutant protein expression levels decreased, whereas mRNA transcription levels increased. Cellular sublocalisation of the variants located in the tumour necrosis factor homologous domain showed that the proteins accumulated in the nucleus, whereas wild-type proteins remained in the cell membrane. A rare indel variant and two classical splicing variants that lead to exon 7 skipping were detected. CONCLUSIONS: This study provides definitive diagnoses for 20 families with suspected X-linked hypohidrotic ectodermal dysplasia and additional information on clinical heterogeneity and genotype-phenotype relationships.
RESUMO
Ensuring bird diversity can secure key ecosystem services within cities. Building ecological corridors into urban planning is an effective way to protect urban birds, but existing corridor construction methods often ignore locality and diversity of species, leading to homogenization of corridor construction results and orientation. We proposed a corridor construction model that combines local bird surveys and bird threat levels. After constructing differentiated corridors for each bird species by assessing their habits and flight abilities, we used three weighted scenarios (original, weighted abundance, weighted abundance, and phylogeny) to assess the conservation priorities of birds and overlaid them to derive a comprehensive bird corridor model. Our results show significant differences in conservation priority and corridor pattern among different bird species, thus demonstrating the importance of local bird surveys and knowledge of threat levels in accurate corridor simulations. This study provides differential simulation of corridors for each bird species and the identification of important conservation species, and uses these to extend the theory of ecological corridor planning to urban bird populations. These results can be applied to guide biodiversity management, evaluate green space policies, and provide practical assistance for sustainable urban development and management.
Assuntos
Conservação dos Recursos Naturais , Ecossistema , Animais , Conservação dos Recursos Naturais/métodos , Biodiversidade , Cidades , Desenvolvimento Sustentável , AvesRESUMO
The development of unconventional long-wavelength fluorescent polymer hydrogels without using polycyclic aromatic hydrocarbons or extended π-conjugation is a fundamental challenge in luminescent materials owing to a lack of understanding regarding the spatial interactions induced inherent clustering-triggered emission under water-rich conditions. Inspired by the color change of protein astaxanthin as a result of heat-induced denaturation, we propose a thermodynamically driven strategy to develop red fluorescence (~610 nm) by boiling multiple hydrogen-bonded poly(N-acryloylsemicarbazide) hydrogels in a water bath. We reveal that thermodynamically driven conformational changes of polymer chains from isolated hydrogen bonding donor-acceptor structures to through-space interaction structures induce intrinsic fluorescence shifts from blue to red during clustering-triggered emission. The proposed multiple hydrogen-bonding supramolecular hydrogel shows good fluorescence stability, mechanical robustness, and 3D printability for customizable shaping. We provide a viable method to prepare nonconventional long-wavelength fluorescent hydrogels towards soft fluorescent devices without initially introducing any fluorescent components.
RESUMO
Traditional chemiluminescence (CL) imaging immunoassays usually rely on natural enzymes as catalytic probes, which has hampered their extensive application due to the susceptibility to inactivation of natural enzymes. In response, a gold brocade coated CoFe Prussian blue analogue (CoFe PBA@Au brocade) with enhanced peroxidase-like activity was synthesized and utilized as a powerful label probe for constructing a highly sensitive CL imaging immunosensor targeting disease biomarkers with excellent performance. This research offers a universal strategy for enhancing the sensitivity of CL imaging immunoassays and further expands the application of PBA nanozymes.
Assuntos
Cobalto , Ferrocianetos , Ouro , Medições Luminescentes , Ouro/química , Imunoensaio/métodos , Cobalto/química , Ferrocianetos/química , Humanos , Peroxidase/metabolismo , Peroxidase/químicaRESUMO
Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus that has become a great concern to tomato production industry. Due to the lack of resistant cultivars, precise detection of ToBRFV is essential to prevent the spread of ToBRFV. In this study, we produced highly sensitive and specific monoclonal antibodies against ToBRFV and established dot-enzyme-linked immunosorbent assay (dot-ELISA) and colloidal gold immunochromatographic strip (CGICS)-based methods for ToBRFV detection. These two methods could specifically detect ToBRFV without cross-reaction with seven tested tobamoviruses and three frequently occurring tomato-infecting viruses. Sensitivity analysis showed that the limit of detection of the established dot-ELISA and CGICS methods reached up to 1:6400 and 1:10,000 (w/v, g/mL) dilution of ToBRFV-infected tomato tissue, respectively. Further analyses using field-collected tomato foliar and fruit samples showed that the results obtained by dot-ELISA and CGICS were consistent with those obtained by reverse transcription polymerase chain reaction. The established methods here allow for specific, sensitive, and robust detection of ToBRFV, and will be helpful for precise monitoring and early warning of ToBRFV.
Assuntos
Solanum lycopersicum , Tobamovirus , Anticorpos Monoclonais , Coloide de Ouro , Frutas , Doenças das Plantas , Ensaio de Imunoadsorção Enzimática/métodosRESUMO
In this paper, a combination of theoretical modeling, finite element simulation, and experimental methods is employed to investigate the forming mechanism and evolutionary pattern of the stagnant region during mechanical scratching with a diamond wedge tool. The study is structured as follows: Firstly, a theoretical calculation model for the geometric parameters of the stagnant region on the formed groove surface is established based on the contact friction partition mechanism and slip-line field theory. The model indicates that the geometric parameters lB-sg, lV-sg, and ∆lsg of the stagnant region are determined by the length of the stagnant region lp-sg in the plastic flow plane and the transformation parameters. Secondly, the formation process of the stagnant region in mechanical scratching is investigated using an orthogonal cutting simulation model with a negative rake angle tool. The results reveal that the stagnant region is a plastic deformation region formed due to the geometrical characteristics of the negative front surface of the scratching tool and its excessive extrusion, which leads to the formation of adhesive friction within the material. Thirdly, the characteristics of the stagnant region are determined through scratching experiments. Compared to the material in the plastic flow region, the material within the stagnant region exhibits finer and denser microstructures, reduced surface hardening peaks and hardened layer depths, and significantly improved surface roughness. Finally, the evolutionary pattern of the stagnant region under the influence of scratching processing parameters is examined based on the theoretical calculation model of the geometric parameters and the scratching experiment. The findings indicate that as the wedge angle of the scratching tool decreases, the relief angle increases, the absolute value of the rotation angle around the Y-axis decreases, the scratching speed decreases, and the material's plastic adherence improves, the PI/k value decreases, the lp-sg value increases, and consequently, the geometric parameters lB-sg, lV-sg, and ∆lsg of the stagnant region on the formed groove surface also increase. The deviation analysis of the geometric parameters of the stagnant region reveals a consistent trend between the theoretical and experimental values of lV-sg and ∆lsg, with maximum deviations of 15 µm and 4.13%, respectively. This study provides theoretical and experimental evidence for the establishment of the theoretical model of the stagnant region in mechanical scratching, the analysis of its forming mechanism, and the control of the stagnant region geometric parameters on the formed groove surface.
RESUMO
BACKGROUND: Chronic overexposure to manganese (Mn) may result in neurotoxicity, which is characterized by motor and cognitive dysfunctions. This study aimed to utilize multivariate source-based morphometry (SBM) to explore the biomarkers for distinguishing Mn-exposed welders from healthy controls (HCs). METHODS: High-quality 3D T1-weighted MRI scans were obtained from 45 Mn-exposed full-time welders and 33 age-matched HCs in this study. After extracting gray matter structural covariation networks by SBM, multiple classic interaction linear models were applied to investigate distinct patterns in welders compared to HCs, and Z-transformed loading coefficients were compared between the two groups. A receiver operating characteristic (ROC) curve was used to identify potential biomarkers for distinguishing Mn-exposed welders from HCs. Additionally, we assessed the relationships between clinical features and gray matter volumes in the welders group. RESULTS: A total of 78 subjects (45 welders, mean age 46.23±4.93 years; 33 HCs, mean age 45.55±3.40 years) were evaluated. SBM identified five components that differed between the groups. These components displayed lower loading weights in the basal ganglia, thalamus, default mode network (including the lingual gyrus and precuneus), and temporal lobe network (including the temporal pole and parahippocampus), as well as higher loading weights in the sensorimotor network (including the supplementary motor cortex). ROC analysis identified the highest classification power in the thalamic network. CONCLUSIONS: Altered brain structures might be implicated in Mn overexposure-related disturbances in motivative modulation, cognitive control and information integration. These results encourage further studies that focus on the interaction mechanisms, including the basal ganglia network, thalamic network and default mode network. Our study identified potential neurobiological markers in Mn-exposed welders and illustrated the utility of a multivariate method of gray matter analysis.
Assuntos
Biomarcadores , Substância Cinzenta , Imageamento por Ressonância Magnética , Manganês , Exposição Ocupacional , Humanos , Substância Cinzenta/efeitos dos fármacos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Masculino , Pessoa de Meia-Idade , Manganês/toxicidade , Adulto , Exposição Ocupacional/efeitos adversos , Soldagem , Feminino , Intoxicação por Manganês/patologia , Intoxicação por Manganês/diagnóstico por imagem , Ferreiros , Estudos de Casos e ControlesRESUMO
Chronic hepatitis B virus infection (HBV) infection appears to be associated with extrahepatic cancers. This study aims to evaluate the causality and evolutionary mechanism of chronic HBV infection and gastric cancer through Mendelian randomization (MR) analysis and bioinformatics analysis. We conducted 2-sample MR to investigate the causal relationship between chronic HBV infection and gastric cancer. We identified 5 independent genetic variants closely associated with exposure (chronic HBV infection) as instrumental variables in a sample of 1371 cases and 2938 controls of East Asian descent in Korea. The genome wide association study (GWAS) data for the outcome variable came from the Japanese Biobank. Bioinformatics analysis was used to explore the evolutionary mechanism of chronic HBV infection and gastric cancer. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify key targets that are commonly associated with both diseases, and their biological functions were investigated. Multiple machine-learning models were employed to select hub genes. The MR analysis showed a positive causal relationship between chronic HBV infection and gastric cancer (IVW: ORâ =â 1.165, 95% CIâ =â 1.085-1.250, Pâ <â .001), and the result was robust in sensitivity analysis. According to the bioinformatics analysis, the 5 key targets were mainly enriched in Toll-like receptor signaling and PI3K-Akt signaling. Two hub genes, CXCL9 and COL6A2, were identified, and a high-performing predictive model was constructed. Chronic HBV infection is positively associated with gastric cancer, and the evolutionary mechanism may be related to Toll-like receptor signaling. Prospective studies are still needed to confirm these findings.
Assuntos
Hepatite B Crônica , Hepatite B , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Fosfatidilinositol 3-Quinases , Biologia Computacional , Receptores Toll-LikeRESUMO
Background: Single-branched stent grafts and the chimney technique are widely used in the treatment of type B aortic dissection (TBAD). The main objective of this study was to compare the outcomes of single-branched stent grafts and the chimney technique in the treatment of TBAD. Methods: From January 2019 to December 2021, the retrospective cohort study contained a cohort of 91 patients with TBAD undergoing thoracic endovascular aortic repair (TEVAR) using single-branched stent grafts and the chimney technique. Group A included 55 patients treated with single-branched covered stents, and Group B included 36 patients treated with the chimney technique. We compared the effects of the procedures on peri-/post-operative outcomes between the two groups. The primary endpoint is clinical death, and the secondary endpoints include the patency of branch stents, the incidence of cerebral infarction, false lumen thrombosis, and the proportion of paraplegia. Results: For the baseline data, the two groups of patients show no differences in terms of age, gender, and associated symptoms. All procedures were successfully performed in both groups. The median follow-up period was 17.6 months (range, 10-34 months). During TEVAR, 5 (9.1%) type I endoleaks occurred in group A, and 11 (30.6%) occurred in group B (P<0.05). During follow-up, there were 2 cases (3.6%) of paraplegia and 1 case (1.8%) of cerebral infarction in Group A, while Group B had 1 case (2.8%) of paraplegia. Three patients in group B reported retrograde type A aortic dissection (RTAD), and 1 of them died (2.8%); however, there were no RTAD cases in group A. Complete thrombosis of the false lumen in the thoracic aorta was observed in 45.5% (25/55) of patients in group A and in 41.7% (15/36) in group B (P=0.72). No significant difference in the thrombosis-volume ratio in the whole false lumen was found during follow-up between group A (81.0%±2.9%) and group B (81.8%±2.6%; P=0.23). Conclusions: Branched stent grafts can be used in cases with insufficient proximal landing zones and reduce the occurrence of type 1 endoleak compared to the chimney technique. This may help to prevent RTAD. Further research, including more cases and longer follow-up periods, is needed to substantiate these results.
RESUMO
To investigate whether Mandarin fish developed oxidative stress after being domesticated with artificial feed, we conducted a series of experiments. Oxidative stress is an important factor leading to diseases and aging in the body. The liver integrates functions such as digestion, metabolism, detoxification, coagulation, and immune regulation, while the gills are important respiratory organs that are sensitive to changes in the water environment. Therefore, we used the liver and gills of Mandarin fish as research materials. The aim of this study was to investigate the effects of short-term artificial feed domestication on the expression of oxidative stress genes and the changes in oxidative-stress-related enzyme activity in the liver and gills of Mandarin fish. We divided the Mandarin fish into two groups for treatment. The control group was fed with live bait continuously for 14 days, while the experimental group was fed with half artificial feed and half live bait from 0 to 7 days (T-7 d), followed by solely artificial feed from 7 to 14 days (T-14 d). The experimental results showed that there was no difference in the body weight, length, and standard growth rate of the Mandarin fish between the two groups of treatments; after two treatments, there were differences in the expression of genes related to oxidative stress in the gills (keap1, kappa, gsta, gstt1, gstk1, SOD, and CAT) and in the liver (GPx, keap1, kappa, gsta, gstt1, gr, and SOD). In the liver, GPx activity and the content of MDA were significantly upregulated after 7 days of domestication, while in the gills, SOD activity was significantly upregulated after 7 days of domestication and GPx activity was significantly downregulated after 14 days of domestication. These results suggest that artificial feed domestication is associated with oxidative stress. Moreover, these results provide experimental basic data for increasing the production of aquaculture feed for Mandarin fish.
Assuntos
Ração Animal , Domesticação , Brânquias , Fígado , Estresse Oxidativo , Animais , Fígado/metabolismo , Brânquias/metabolismo , Ração Animal/análise , Antioxidantes/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Peixes/genética , Peixes/metabolismo , Aquicultura/métodosRESUMO
BACKGROUND: D-dimer to lymphocyte ratio (DLR) is a novel composite metric. This study investigated the association between DLR and major adverse cardiovascular events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention. MATERIALS AND METHODS: This retrospective study included 683 STEMI cases treated between January 2018 and June 2021 at a single center. DLR was calculated for each patient. Receiver operating characteristic curves assessed the predictive value of in-hospital and long-term MACEs, with calculated AUC. Based on the optimal DLR cutoff value, the population was categorized into groups for clinical characteristic analysis. Multivariate logistic and COX regression analyses determined factors independently associated with MACEs. Kaplan-Meier estimation method and log-rank tests assessed event-free survival among different DLR groups. Spearman's test explored the correlation between DLR and Gensini score. RESULTS: DLR demonstrated an AUC of 0.792 for predicting in-hospital MACEs and 0.708 for long-term MACEs in patients with STEMI. Multivariate logistic regression analysis revealed that a high DLR (cutoff value, 0.47) independently increased the risk of MACEs during hospitalization in patients with STEMI (P = 0.003; odds ratio: 3.015; 95 % CI: 1.438-6.321). Multivariate COX regression showed that a high DLR (cutoff value, 0.34) independently predicted MACEs during long-term follow-up in patients with STEMI (P = 0.011; hazard ratio: 1.724; 95 % CI: 1.135-2.619). Furthermore, DLR exhibited a positive correlation with the Gensini score (P < 0.001). CONCLUSIONS: DLR is a valuable predictor for MACEs occurrence in patients with STEMI during hospitalization and long-term follow-up after PCI.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Linfócitos , PrognósticoRESUMO
Green-blue spaces (GBS) are pivotal in mitigating thermal discomfort. However, their management lacks guidelines rooted in epidemiological evidence for specific planning and design. Here we show how various GBS types modify the link between non-optimal temperatures and cardiovascular mortality across different thermal extremes. We merged fine-scale population density and GBS data to create novel GBS exposure index. A case time series approach was employed to analyse temperature-cardiovascular mortality association and the effect modifications of type-specific GBSs across 1085 subdistricts in south-eastern China. Our findings indicate that both green and blue spaces may significantly reduce high-temperature-related cardiovascular mortality risks (e.g., for low (5%) vs. high (95%) level of overall green spaces at 99th vs. minimum mortality temperature (MMT), Ratio of relative risk (RRR) = 1.14 (95% CI: 1.07, 1.21); for overall blue spaces, RRR = 1.20 (95% CI: 1.12, 1.29)), while specific blue space types offer protection against cold temperatures (e.g., for the rivers at 1st vs MMT, RRR = 1.17 (95% CI: 1.07, 1.28)). Notably, forests, parks, nature reserves, street greenery, and lakes are linked with lower heat-related cardiovascular mortality, whereas rivers and coasts mitigate cold-related cardiovascular mortality. Blue spaces provide greater benefits than green spaces. The severity of temperature extremes further amplifies GBS's protective effects. This study enhances our understanding of how type-specific GBS influences health risks associated with non-optimal temperatures, offering valuable insights for integrating GBS into climate adaptation strategies for maximal health benefits.
RESUMO
OBJECTIVE: Changes in brain structure and neurotransmitter systems are involved in pain in Parkinson's disease (PD), and emotional factors are closely related to pain. Our study applied electroencephalography (EEG) to investigate the role of emotion in PD patients with chronic musculoskeletal pain. METHODS: Forty-two PD patients with chronic musculoskeletal pain and 38 without were enrolled. EEG data were recorded under resting conditions, and while viewing pictures with neutral, positive, and negative content. We compared spectrum power, functional connectivity, and late positive potential (LPP), an event-related potential (ERP), between the groups. RESULTS: PD patients with pain tended to have higher scores for the Hamilton Rating Scale for Depression (HRSD). In the resting EEG, mean ß-band amplitude was significantly higher in patients with pain than in those without. Logistic regression analysis showed that higher HRSD scores and higher mean ß-band amplitude were associated with pain. ERP analysis revealed that the amplitudes of LPP difference waves (the absolute difference between positive and negative condition LPP and neutral condition LPP) at the central-parietal region were significantly reduced in patients with pain (P = 0.029). Spearman correlation analysis showed that the amplitudes of late (700-1000 ms) negative versus neutral condition LPP difference waves were negatively correlated with pain intensity, assessed by visual analogue scale, (r = -0.393, P = 0.010) and HRSD scores (r = -0.366, P = 0.017). CONCLUSION: Dopaminergic and non-dopaminergic systems may be involved in musculoskeletal pain in PD by increasing ß-band activity and weakening the connection of the θ-band at the central-parietal region. PD patients with musculoskeletal pain have higher cortical excitability to negative emotions. The changes in pain-related EEG may be used as electrophysiological markers and therapeutic targets in PD patients with chronic pain.
Assuntos
Dor Crônica , Dor Musculoesquelética , Doença de Parkinson , Humanos , Dor Musculoesquelética/complicações , Doença de Parkinson/complicações , Eletroencefalografia , Potenciais Evocados/fisiologia , Emoções/fisiologiaRESUMO
AIMS: To investigate the association between mitochondrial events and immune response in periodontitis and related regulatory genes. MAIN METHODS: Gene expression profiles in gingival tissues were retrieved from the Gene Expression Omnibus. Mitochondria-immune response-related differentially expressed genes (MIR-DEGs) between the healthy and periodontitis samples were determined. WGCNA, GO, and KEGG were used to investigate the function and the enriched pathways of MIR-DEGs. The correlation between MIR-DEGs expression and clinical probing pocket depth was analyzed. The MIR-DEGs were further identified and verified in animal samples. A periodontitis model was established in C57BL/6 mice with silk ligation. Micro-computed tomography was used to assess alveolar bone loss. Western blot, quantitative real-time polymerase chain reaction, and immunohistochemical analyses further validated the differential expression of the MIR-DEGs. KEY FINDINGS: A total of ten MIR-DEGs (CYP24A1, PRDX4, GLDC, PDK1, BCL2A1, CBR3, ARMCX3, BNIP3, IFI27, and UNG) were identified, the expression of which could effectively distinguish patients with periodontitis from the healthy controls. Enhanced immune response was detected in the periodontitis group with that in the healthy controls, especially in B cells. PDK1 was a critical MIR-DEG correlated with B cell immune response and clinical periodontal probing pocket depth. Both animal and clinical periodontal samples presented higher gene and protein expression of PDK1 than the control samples. Additionally, PDK1 colocalized with B cells in both animal and clinical periodontal tissues. SIGNIFICANCE: Mitochondria participate in the regulation of the immune response in periodontitis. PDK1 may be the key mitochondria-related gene regulating B-cell immune response in periodontitis.