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Urban lakes serve as vital ecological and recreational anchors within built environments, essential for enhancing urban resilience. Evaluating lake health predominantly focuses on water quality, assessing indicators such as nutrient levels, toxicity, pH balance, and water clarity to monitor changes. This study proposes a comprehensive evaluation framework that systematically describes specific spatiotemporal manifestations and periodic exogenous regulation characteristics across five dimensions: physical structure, water quality, shoreline dynamics, external regulation, and social service. Furthermore, it introduces an urban lake health assessment model based on synergistic development to evaluate the integrated development and interaction between water environments and social services. This model is applied across urban lakes in various developmental stages in China. Key findings include: 1) Urban development often impacts lake health disparately, with varying degrees of synergy observed between water environments and social services across different urban lakes. However, shifts in urban ideologies and improvements in governance, along with protective policies and project implementations, have contributed to improving water quality to some extent. 2) Engineering interventions do not consistently correspond with improvements in water quality, and governance measures sometimes yield mixed outcomes, underscoring the necessity for systematic solutions to lake health. Restoring hydrological processes emerges as crucial for enhancing sustainability.
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This study investigated the role of Poly (ADP-ribose) Polymerase (PARP) in myocardial ischemia-reperfusion injury (MIRI) in elderly mice. It involves 30 elderly male KM mice divided into three groups: Sham, MIRI, and DPQ, where the MIRI and DPQ groups undergo myocardial ischemia-reperfusion with the DPQ group also receiving DPQ for PARP-1 inhibition. Over three weeks, assessments include histological analysis of myocardial lesions, left ventricular ejection fraction (LVEF) measurements, and evaluations of serum cardiac enzymes and inflammatory markers. This approach aims to understand the protective effects of DPQ in MIRI, focusing on its impact on cardiac health and inflammation via the JAK2/STAT3 pathway. The findings suggest that PARP activation exacerbates cardiac dysfunction and inflammation in MIRI by possibly modulating the JAK2/STAT3 signaling pathway. Inhibition of PARP-1 with DPQ mitigates these effects, as indicated by reduced myocardial lesions and inflammatory infiltration, improved LVEF, and altered levels of inflammatory markers and signaling molecules. However, the differences in STAT3 and p-STAT3 protein expression between the DPQ and MIRI groups were not statistically significant, suggesting that while PARP inhibition affects many aspects of MIRI pathology, its impact on the JAK2/STAT3 pathway may not fully explain the observed benefits. This study contributes to our understanding of the complex mechanisms underlying myocardial ischemia-reperfusion injury, particularly in the context of aging. It highlights the potential of PARP inhibition as a therapeutic strategy to attenuate cardiac dysfunction and inflammation in MIRI, though further research is necessary to fully elucidate the underlying molecular pathways and to explore the clinical relevance of these findings in humans.
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Janus Quinase 2 , Traumatismo por Reperfusão Miocárdica , Miocárdio , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Masculino , Camundongos , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Miocárdio/patologia , Miocárdio/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Envelhecimento , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
In recent years, the integration of radiotherapy and nanocatalytic medicine has gained widespread attention in the treatment of breast cancer. Herein, the glucose oxidase (GOx) and MnO2 nanoparticles co-modified multifunctional liposome of GOx-MnO2@Lip was constructed for enhanced radiotherapy. Introduction of GOx would not only elevate the glucose consumption to starve the cancer cells, but also increased the endogenous H2O2 level. Meanwhile, high intracellular GSH concentration facilitated the release of Mn2+ to amplify the cytotoxic ·OH through cascade catalytic reactions within the tumor microenvironment, resulting in a favorable tumor suppression rate of 74.45â¯%. Furthermore, the blood biochemical and blood routine demonstrated that GOx-MnO2@Lip had no obvious toxic side effects. Therefore, this work provided a potential vehicle for synergistic cancer starving therapy, chemodynamic therapy and radiotherapy for improving therapeutic efficacy of breast cancer.
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Neoplasias da Mama , Glucose Oxidase , Lipossomos , Compostos de Manganês , Óxidos , Radiossensibilizantes , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Glucose Oxidase/metabolismo , Feminino , Óxidos/química , Óxidos/farmacologia , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Radiossensibilizantes/farmacologia , Animais , Humanos , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos BALB C , Catálise , Camundongos , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacosRESUMO
Objectives: This study aims to assess the predictive capability of synthetic MRI in assessing neurodevelopmental outcomes for extremely preterm neonates with low-grade Germinal Matrix-Intraventricular Hemorrhage (GMH-IVH). The study also investigates the potential enhancement of predictive performance by combining relaxation times from different brain regions. Materials and methods: In this prospective study, 80 extremely preterm neonates with GMH-IVH underwent synthetic MRI around 38 weeks, between January 2020 and June 2022. Neurodevelopmental assessments at 18 months of corrected age categorized the infants into two groups: those without disability (n = 40) and those with disability (n = 40), with cognitive and motor outcome scores recorded. T1, T2 relaxation times, and Proton Density (PD) values were measured in different brain regions. Logistic regression analysis was utilized to correlate MRI values with neurodevelopmental outcome scores. Synthetic MRI metrics linked to disability were identified, and combined models with independent predictors were established. The predictability of synthetic MRI metrics in different brain regions and their combinations were evaluated and compared with internal validation using bootstrap resampling. Results: Elevated T1 and T2 relaxation times in the frontal white matter (FWM) and caudate were significantly associated with disability (p < 0.05). The T1-FWM, T1-Caudate, T2-FWM, and T2-Caudate models exhibited overall predictive performance with AUC values of 0.751, 0.695, 0.856, and 0.872, respectively. Combining these models into T1-FWM + T1-Caudate + T2-FWM + T2-Caudate resulted in an improved AUC of 0.955, surpassing individual models (p < 0.05). Bootstrap resampling confirmed the validity of the models. Conclusion: Synthetic MRI proves effective in early predicting adverse outcomes in extremely preterm infants with GMH-IVH. The combination of T1-FWM + T1-Caudate + T2-FWM + T2-Caudate further enhances predictive accuracy, offering valuable insights for early intervention strategies.
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BACKGROUND: Epidemiological studies have demonstrated that periodontitis is an independent risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the association between these two diseases remains unclear. The lung microbiota shares similarities with the oral microbiota, and there is growing evidence to suggest that the lung microbiome could play a role in the pathogenesis of COPD. This study aimed to investigate whether periodontal pathogens could contribute to the pathogenesis of COPD in a mouse model. METHODS: We established mouse models with oral infection by typical periodontal pathogens, porphyromonas gingivalis (Pg group) or fusobacterium nucleatum (Fn group), over a three-month period. Mice that did not receive oral infection were set as the control group (C group). We assessed the level of alveolar bone resorption, lung function, and histological changes in the lungs of the mice. Additionally, we measured the levels of inflammatory factors and tissue damage associated factors in the lung tissues. RESULTS: Lung function indices, including airway resistance, peak inspiratory/expiratory flow and expiratory flow-50%, were significantly reduced in the Fn group compared to the C group. Additionally, histological examination revealed an increased number of inflammatory cells and bullae formation in the lung tissue sections of the Fn group. Meanwhile, levels of inflammatory factors such as IL-1ß, IL-6, IFN-γ, and TNF-α, as well as tissue damage associated factors like matrix metalloproteinase-8 and neutrophil elastase, were significantly elevated in the lung tissue of the Fn group in comparison to the C group. The Pg group also showed similar but milder lung changes compared to the Fn group. Pg or Fn could be detected in the lungs of both oral infected groups. CONCLUSION: The results indicated that oral periodontal pathogens infection could induce COPD-like lung changes in mice, and they may play a biological role in the association between periodontitis and COPD.
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Modelos Animais de Doenças , Fusobacterium nucleatum , Porphyromonas gingivalis , Doença Pulmonar Obstrutiva Crônica , Animais , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Camundongos , Perda do Osso Alveolar/microbiologia , Perda do Osso Alveolar/patologia , Pulmão/patologia , Pulmão/microbiologia , Periodontite/microbiologia , Periodontite/patologia , Periodontite/complicações , Masculino , Infecções por Bacteroidaceae/complicações , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/patologia , Infecções por Fusobacterium/complicações , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/patologia , Camundongos Endogâmicos C57BLRESUMO
Introduction: Sensorineural hearing loss (SNHL) can arise from a diverse range of congenital and acquired factors. Detecting it early is pivotal for nurturing speech, language, and cognitive development in children with SNHL. In our study, we utilized synthetic magnetic resonance imaging (SyMRI) to assess alterations in both gray and white matter within the brains of children affected by SNHL. Methods: The study encompassed both children diagnosed with SNHL and a control group of children with normal hearing {1.5-month-olds (n = 52) and 3-month-olds (n = 78)}. Participants were categorized based on their auditory brainstem response (ABR) threshold, delineated into normal, mild, moderate, and severe subgroups.Clinical parameters were included and assessed the correlation with SNHL. Quantitative analysis of brain morphology was conducted using SyMRI scans, yielding data on brain segmentation and relaxation time.Through both univariate and multivariate analyses, independent factors predictive of SNHL were identified. The efficacy of the prediction model was evaluated using receiver operating characteristic (ROC) curves, with visualization facilitated through the utilization of a nomogram. It's important to note that due to the constraints of our research, we worked with a relatively small sample size. Results: Neonatal hyperbilirubinemia (NH) and children with inner ear malformation (IEM) were associated with the onset of SNHL both at 1.5 and 3-month groups. At 3-month group, the moderate and severe subgroups exhibited elevated quantitative T1 values in the inferior colliculus (IC), lateral lemniscus (LL), and middle cerebellar peduncle (MCP) compared to the normal group. Additionally, WMV, WMF, MYF, and MYV were significantly reduced relative to the normal group. Additionally, SNHL-children with IEM had high T1 values in IC, and LL and reduced WMV, WMF, MYV and MYF values as compared with SNHL-children without IEM at 3-month group. LL-T1 and WMF were independent risk factors associated with SNHL. Consequently, a prediction model was devised based on LL-T1 and WMF. ROC for training set, validation set and external set were 0.865, 0.806, and 0.736, respectively. Conclusion: The integration of T1 quantitative values and brain volume segmentation offers a valuable tool for tracking brain development in children affected by SNHL and assessing the progression of the condition's severity.
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Pest management technology has been a promising bioconversion method for waste resource utilization. Unlike many pests that consume waste, the larvae of Lucilia sericata, also known as maggots, have many outstanding advantages as following: with their strong adaption to environment and not easily infected and exhibiting a medicinal nutritional value. Herein, the potential efficacies of maggot polysaccharides (MP), as well as their underlying mechanisms, were explored in Dextran sulfate sodium (DSS)-induced colitis mice and TNF-α-elicited Caco-2 cells. We extracted two bioactive polysaccharides from maggots, MP-80 and MP-L, whose molecular weights were 4.25 × 103 and 2.28 × 103 g/mol, respectively. MP-80 and MP-L contained nine sugar residues: 1,4-α-Arap, 1,3-ß-Galp, 1,4,6-ß-Galp, 1,6-α-Glcp, 1-α-Glcp, 1,4-ß-Glcp, 1-ß-Xylp, 1,2-α-Manp, and 1-ß-Manp. We demonstrated that MP-80 and MP-L significantly ameliorated DSS-induced symptoms and histopathological damage. Immuno-analysis revealed that compared with MP-L, MP-80 could better restore intestinal barrier and reduced inflammation by suppressing NLRP3/NF-κB pathways, which might be attributed to its enriched galactose fraction. Moreover, 16S rRNA sequencing revealed that MP-80 and MP-L both improved the dysbiosis and diversity of gut microbiota and acted on multiple microbial functions. Our study sheds new light on the possibility of using maggot polysaccharides as an alternative therapy for colitis.
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Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Larva , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Larva/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Humanos , Camundongos , Células CACO-2 , Dípteros/química , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Modelos Animais de Doenças , MasculinoRESUMO
OBJECTIVES: The evidence connecting polyunsaturated fatty acids (PUFAs) to biliary problems is still highly contested and speculative despite the fact that biliary diseases are common and PUFAs have long been studied for their potential health benefits. This work used Mendelian randomization (MR) techniques in conjunction with genome-wide association study (GWAS) data to clarify the causal relationships between PUFAs and biliary tract diseases. METHODS: We compiled data on PUFAs, including Omega-3 fatty acids, Omega-6 fatty acids, and the ratio of Omega-6 to Omega-3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR-Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MR-Egger intercept test and Cochrane's Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses. RESULTS: We found that Omega-3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P = 0.009), cholelithiasis (OR: 0.787, P = 8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P = 1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P = 0.004). There was no significant association between Omega-3 fatty acids and risk of gallbladder cancer (OR: 3.127, P = 0.530) and primary sclerosing cholangitis (OR: 0.919, P = 0.294). Omega-6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P = 0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P = 0.14), gallbladder cancer (OR: 4.670, P = 0.515), primary sclerosing cholangitis (OR: 0.993, P = 0.962), primary cholestatic biliary cholangitis (OR: 1.404, P = 0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P = 0.009, OR:1.191, P = 1.60e-6, and OR:1.160, P = 4.11e-6, respectively). But (OR: 0.315, P = 0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P = 0.078) or gallbladder cancer (OR: 0.046, P = 0.402). According to the MR-Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P > 0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation. CONCLUSION: Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega-3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega-3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega-3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega-6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases.
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Doenças Biliares , Ácidos Graxos Ômega-3 , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Doenças Biliares/genéticaRESUMO
Triple-negative breast cancer (TNBC) is a highly invasive and metastatic subtype of breast cancer that often recurs after surgery. Herein, we developed a cyclodextrin-based tumor-targeted nano delivery system that incorporated the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent lonidamine (LND) to form the R6RGD-CMßCD-se-se-Ce6/LND nanoparticles (RCC/LND NPS). This nanosystem could target cancer cells, avoid lysosomal degradation and further localize within the mitochondria. The RCC/LND NPS had pH and redox-responsive to control the release of Ce6 and LND. Consequently, the nanosystem had a synergistic effect by effectively alleviating hypoxia, enhancing the production of cytotoxic reactive oxygen species (ROS) and amplifying the efficacy of photodynamic therapy (PDT). Furthermore, the RCC/LND NPS + light weakened anoikis resistance, disrupted extracellular matrix (ECM), activated both the intrinsic apoptotic pathway (mitochondrial pathway) and extrinsic apoptotic pathway (receptor death pathway) of anoikis. In addition, the nanosystem showed significant anti-TNBC efficacy in vivo. These findings collectively demonstrated that RCC/LND NPS + light enhanced the anticancer effects, induced anoikis and inhibited tumor cell migration and invasion through a synergistic effect of chemotherapy and PDT. Overall, this study highlighted the promising potential of the RCC/LND NPS + light for the treatment of TNBC.
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Anoikis , Apoptose , Clorofilídeos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Humanos , Fotoquimioterapia/métodos , Feminino , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Animais , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Anoikis/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/uso terapêutico , Apoptose/efeitos dos fármacos , Indazóis/farmacologia , Indazóis/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , CamundongosRESUMO
Tumors are one of the main diseases threatening human life and health. The emergence of nanotechnology in recent years has introduced a novel therapeutic avenue for addressing tumors. Through the amalgamation of nanotechnology's inherent attributes with those of natural enzymes, nanozymes have demonstrated the ability to initiate catalytic reactions, modulate the biological microenvironment, and facilitate the adoption of multifaceted therapeutic approaches, thereby exhibiting considerable promise in the realm of cancer treatment. In this Review, the application of nanozymes in chemodynamic therapy, radiotherapy, photodynamic therapy, photothermal therapy, and starvation therapy are summarized. Moreover, a detailed discussion regarding the mechanism of conferring physiotherapeutic functionality upon catalytic nanosystems is provided. It is posited that this innovative catalytic treatment holds significant potential to play a crucial role within the domain of nanomedicine.
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It is crucial to employ scientifically sound models for assessing the quality of the ecological environment and revealing the strengths and weaknesses of ecosystems. This process is vital for identifying regional ecological and environmental issues and devising relevant protective measures. Among the widely acknowledged models for evaluating ecological quality, the ecological index (EI) and remote sensing ecological index (RSEI) stand out; however, there is a notable gap in the literature discussing their differences, characteristics, and reasons for selecting either model. In this study, we focused on Fangshan District, Beijing, China, to examine the differences between the two models from 2017 to 2021. We summarized the variations in evaluation indices, importance, quantitative methods, and data acquisition times, proposing application scenarios for both models. The results indicate that the ecological environment quality in Fangshan District, Beijing, remained favorable from 2017 to 2021. There was a discernible trend of initially declining quality followed by subsequent improvement. The variation in the calculation results is evident in the overall correlation between the RSEI and EI. Particularly noteworthy is the significantly smaller correlation between EI and the RSEI in 2021 than in the other two years. This discrepancy is attributed to shifts in the contribution of the evaluation indices within the RSEI model. The use of diverse quantitative methods for evaluating indicators has resulted in several variations. Notably, the evaluation outcomes of the EI model exhibit a stronger correlation with land cover types. This correlation contributes to a more pronounced fluctuation in RSEI levels from 2017 to 2021, with the EI model's evaluation results in 2019 notably surpassing those of the RSEI model. Ultimately, the most prominent disparities lie in the calculation results for water areas and construction land. The substantial difference in water areas is attributed to the distinct importance assigned to evaluation indicators between the two models. Moreover, the notable difference in construction land arises from the use of different quantification methods for evaluation indicators. In general, the EI model has suggested to be more comprehensive and effectively captures the annual comprehensive status of the ecological environment and the multiyear change characteristics of the administrative region. On the other hand, RSEI models exhibit greater flexibility and ease of implementation, independent of spatial and temporal scales. These findings contribute to a clearer understanding of the models' advantages and limitations, offering guidance for decision makers and valuable insights for the improvement and development of ecological environmental quality evaluation models.
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OBJECTIVE: We aimed to explore the value of magnetoencephalography in the presurgical evaluation of patients with posterior cortex epilepsy. METHODS: A total of 39 patients with posterior cortex epilepsy (PCE) and intact magnetoencephalography (MEG) images were reviewed from August 2019 to July 2022. MEG dipole clusters were classified into single clusters, multiple clusters, and scatter dipoles based on tightness criteria. The association of the surgical outcome with MEG dipole classifications was evaluated using Fisher's exact tests. RESULTS: Among the 39 cases, there were 24 cases of single clusters (61.5%), nine cases of multiple clusters (23.1%), and six cases of scattered dipoles (15.4%). Patients with single dipole clusters were more likely to become seizure-free. Among single dipole cluster cases (n = 24), complete MEG dipole resection yielded a more favorable surgical outcome than incomplete resection (83.3% vs. 16.7%, p = 0.007). Patients with concordant MRI and MEG findings achieved a significantly more favorable surgical outcome than discordant patients (66.7% vs. 33.3%, p = 0.044), especially in single dipole cluster patients (87.5% vs. 25.0%, p = 0.005). SIGNIFICANCE: MEG can provide additional valuable information regarding surgical candidate selection, epileptogenic zone localization, electrode implantation schedule, and final surgical planning in patients with posterior cortex epilepsy.
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Epilepsia , Magnetoencefalografia , Humanos , Magnetoencefalografia/métodos , Eletroencefalografia/métodos , Resultado do Tratamento , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Prognóstico , Imageamento por Ressonância MagnéticaRESUMO
Medical image segmentation is crucial for accurate diagnosis and treatment in the medical field. In recent years, convolutional neural networks (CNNs) and Transformers have been frequently adopted as network architectures in medical image segmentation. The convolution operation is limited in modeling long-range dependencies because it can only extract local information through the limited receptive field. In comparison, Transformers demonstrate excellent capability in modeling long-range dependencies but are less effective in capturing local information. Hence, effectively modeling long-range dependencies while preserving local information is essential for accurate medical image segmentation. In this paper, we propose a four-axis fusion framework called FAFuse, which can exploit the advantages of CNN and Transformer. As the core component of our FAFuse, a Four-Axis Fusion module (FAF) is proposed to efficiently fuse global and local information. FAF combines Four-Axis attention (height, width, main diagonal, and counter diagonal axial attention), a multi-scale convolution, and a residual structure with a depth-separable convolution and a Hadamard product. Furthermore, we also introduce deep supervision to enhance gradient flow and improve overall performance. Our approach achieves state-of-the-art segmentation accuracy on three publicly available medical image segmentation datasets. The code is available at https://github.com/cczu-xiao/FAFuse.
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BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. OBJECTIVES: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. METHODS: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. RESULTS: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). CONCLUSION: These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.
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Núcleos Anteriores do Tálamo , Conectoma , Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Humanos , Epilepsia Resistente a Medicamentos/terapia , Projetos Piloto , Núcleos Anteriores do Tálamo/fisiologia , Convulsões/terapia , Biomarcadores , Epilepsias Parciais/terapiaRESUMO
Further applications of electric vehicles (EVs) and energy storage stations are limited because of the thermal sensitivity, volatility, and poor durability of lithium-ion batteries (LIBs), especially given the urgent requirements for all-climate utilization and fast charging. This study comprehensively reviews the thermal characteristics and management of LIBs in an all-temperature area based on the performance, mechanism, and thermal management strategy levels. At the performance level, the external features of the batteries were analyzed and compared in cold and hot environments. At the mechanism level, the heat generation principles and thermal features of LIBs under different temperature conditions were summarized from the perspectives of thermal and electrothermal mechanisms. At the strategy level, to maintain the temperature/thermal consistency and prevent poor subzero temperature performance and local/global overheating, conventional and novel battery thermal management systems (BTMSs) are discussed from the perspective of temperature control, thermal consistency, and power cost. Moreover, future countermeasures to enhance the performance of all-climate areas at the material, cell, and system levels are discussed. This study provides insights and methodologies to guarantee the performance and safety of LIBs used in EVs and energy storage stations.
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Given the problem of considerable livestock and poultry pollution and the differentiation of the regional agricultural layout in China, the combination of planting and breeding (CPB) forms an agricultural co-agglomeration to recycle manure waste into croplands to reduce livestock and poultry pollution. This study aims to evaluate CPB co-agglomeration and empirically examine its effects on livestock and poultry pollution. Based on provincial data from 1997 to 2020 in China, this study constructed three indicators to evaluate CPB co-agglomeration, summarized its temporal and spatial characteristics, and conducted a spatial analysis using the Spatial Lag Model (SLM) to empirically investigate its effect on livestock and poultry pollution. The results showed that: first, from 1997 to 2020, the overall level of CPB co-agglomeration in China declined and the region with higher CPB co-agglomeration level transferred from the central provinces to the west provinces. Second, livestock and poultry pollution in most provinces had significantly positive spatial correlations with adjacent regions. The co-agglomeration of CPB had a significantly positive effect on reducing livestock and poultry pollution; however, the effect had no significant spatial spillover. Third, the breeding industry agglomeration and the moderate expansion of breeding industry scale significantly reduced pollution. These findings provide a reference for reducing livestock and poultry pollution by promoting CPB co-agglomeration to establish a waste recycling system. Optimizing the layout of the planting and breeding industry helps achieve the goal of long-term sustainable development of the breeding industry.
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Due to the demand for sample observation, optical microscopy has become an essential tool in the fields of biology and medicine. In addition, it is impossible to maintain the living sample in focus over long-time observation. Rapid focus prediction which involves moving a microscope stage along a vertical axis to find an optimal focus position, is a critical step for high-quality microscopic imaging of specimens. Current focus prediction algorithms, which are time-consuming, cannot support high frame rate imaging of dynamic living samples, and may introduce phototoxicity and photobleaching on the samples. In this paper, we propose Lightweight Densely Connected with Squeeze-and-Excitation Network (LDSE-NET). The results of the focusing algorithm are demonstrated on a public dataset and a self-built dataset. A complete evaluation system was constructed to compare and analyze the effectiveness of LDSE-NET, BotNet, and ResNet50 models in multi-region and multi-multiplier prediction. Experimental results show that LDSE-NET is reduced to 1E-05 of the root mean square error. The accuracy of the predicted focal length of the image is increased by 1 ~ 2 times. Training time is reduced by 33.3%. Moreover, the volume of the model only reaches the KB level, which has the characteristics of being lightweight.
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Introduction: Mitochondria are a significant target of lonidamine (LND). However, its limited solubility and inability to specifically target mitochondria, LND can lead to hepatic toxicity and has shown only modest anticancer activity. The objective of this study is to establish a glutathione programmed mitochondria targeted delivery of LND for the effective treatment of triple negative breast cancer (TNBC). Methods: In this study, LND was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) wrapped with mitochondria-targeting short-chain triphenylphosphonium-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and tumor-targeting long-chain 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-S-S-polyethylene glycol-R6RGD (DSPE-S-S-PEG2000-R6RGD, DSSR), which were designated as LND-PLGA/TPS/DSSR NPs. The release behavior was evaluated, and cellular uptake, in vitro and in vivo antitumor activity of nanoparticles were investigated. The mechanism, including apoptosis of tumor cells and mitochondrial damage and respiratory rate detection, was also further investigated. Results: LND-PLGA/TPS/DSSR NPs were successfully prepared, and characterization revealed that they are globular particles with smooth surfaces and an average diameter of about 250 nm. Long-chain DSSR in LND-PLGA/TPS/DSSR NPs prevented positively charged LND-PLGA/TPS NPs from being cleared by the reticuloendothelial system. Furthermore, LND release rate from NPs at pH 8.0 was significantly higher than that at pH 7.4 and 5.5, which demonstrated specific LND release in mitochondria and prevented LND leakage in cytoplasm and lysosome. NPs could locate in mitochondria, and the released LND triggered apoptosis of tumor cells by damaging mitochondria and releasing apoptosis-related proteins. In addition, in TNBC mice model, programmed mitochondria targeted NPs improved efficacy and reduced LND toxicity. Conclusion: LND-PLGA/TPS/DSSR NPs may be a useful system and provide an effective approach for the treatment of TNBC.
Assuntos
Antineoplásicos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Linhagem Celular Tumoral , Nanopartículas/química , Mitocôndrias/metabolismo , Glutationa/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/metabolismoRESUMO
Our understanding of cingulate cortex function is limited. As a method for locating the epileptogenic zone, direct electrical cortical stimulation (ECS) provides an opportunity to understand the functional localization of the cingulate cortex. This study aimed to learn more about the function of the cingulate cortex by analyzing a large body of data from our center and by reviewing existing literature on cortical mapping. We retrospectively analyzed the ECS data of 124 patients with drug-resistant epilepsy who had undergone electrode implantation in the cingulate cortex. The standard stimulation parameters included a biphasic pulse and bipolar stimulation at 50 Hz. Furthermore, we reviewed existing studies on cingulate responses elicited by the ECS and compared them with our results. A total of 329 responses were evoked in 276 contacts using ECS. Of these, 196 were physiological functional responses, which included sensory, affective, autonomic, language, visual, vestibular, and motor responses, along with a few other sensations. Sensory, motor, vestibular, and visual responses were concentrated in the cingulate sulcus visual area (CSv). Furthermore, 133 epilepsy-related responses were evoked, most of which were concentrated in the ventral cingulate cortex. No responses were evoked by 498 contacts. Furthermore, the comparison of our ECS results with those reported in 11 comprehensive reviews revealed that the cingulate cortex is involved in complicated functions. The cingulate cortex is involved in sensory, affective, autonomic, language, visual, vestibular, and motor functions. The CSv is an integrating node of sensory, motor, vestibular, and visual systems.
Assuntos
Epilepsia , Giro do Cíngulo , Humanos , Giro do Cíngulo/fisiologia , Estudos Retrospectivos , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Epilepsia/terapia , Estimulação Elétrica , EletroencefalografiaRESUMO
Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.