RESUMO
A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.
Assuntos
Calcineurina/metabolismo , Proliferação de Células , Proteínas de Homeodomínio/metabolismo , Proteína Meis1/metabolismo , Miócitos Cardíacos/citologia , Animais , Animais Recém-Nascidos , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Coração/fisiologia , Proteínas de Homeodomínio/genética , Masculino , Camundongos , Miocárdio/citologia , Ligação Proteica , RegeneraçãoRESUMO
Defects in mitochondrial RNA metabolism have been linked to sensorineural deafness that often occurs as a consequence of damaged or deficient inner ear hair cells. In this report, we investigated the molecular mechanism underlying a deafness-associated tRNAPhe 593T > C mutation that changed a highly conserved uracil to cytosine at position 17 of the DHU-loop. The m.593T > C mutation altered tRNAPhe structure and function, including increased melting temperature, resistance to S1 nuclease-mediated digestion, and conformational changes. The aberrant tRNA metabolism impaired mitochondrial translation, which was especially pronounced by decreases in levels of ND1, ND5, CYTB, CO1, and CO3 harboring higher numbers of phenylalanine. These alterations resulted in aberrant assembly, instability, and reduced activities of respiratory chain enzyme complexes I, III, IV, and intact supercomplexes overall. Furthermore, we found that the m.593T > C mutation caused markedly diminished membrane potential, and increased the production of reactive oxygen species in the mutant cell lines carrying the m.593T > C mutation. These mitochondrial dysfunctions led to the mitochondrial dynamic imbalance via increasing fission with abnormal mitochondrial morphology. Excessive fission impaired the process of autophagy including the initiation phase, formation, and maturation of the autophagosome. In particular, the m.593T > C mutation upregulated the PARKIN-dependent mitophagy pathway. These alterations promoted an intrinsic apoptotic process for the removal of damaged cells. Our findings provide critical insights into the pathophysiology of maternally inherited deafness arising from tRNA mutation-induced defects in mitochondrial and cellular integrity.
Assuntos
Surdez , Mitocôndrias , RNA de Transferência de Fenilalanina , Humanos , Autofagia , Surdez/genética , Surdez/metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Mitocôndrias/genética , Mitocôndrias/patologia , Dinâmica Mitocondrial , Mutação , Espécies Reativas de Oxigênio/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , RNA de Transferência de Fenilalanina/genéticaRESUMO
BACKGROUND: Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes. METHODS: Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo. RESULTS: We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin. CONCLUSIONS: These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.
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Acetylation, a critical regulator of diverse cellular processes, holds significant implications in various cancer contexts. Further understanding of the acetylation patterns of key cancer-driven proteins is crucial for advancing therapeutic strategies in cancer treatment. This study aimed to unravel the acetylation patterns of Engulfment and Cell Motility Protein 1 (ELMO1) and its relevance to the pathogenesis of colorectal cancer (CRC). Immunoprecipitation and mass spectrometry precisely identified lysine residue 505 (K505) as a central acetylation site in ELMO1. P300 emerged as the acetyltransferase for ELMO1 K505 acetylation, while SIRT2 was recognized as the deacetylase. Although K505 acetylation minimally affected ELMO1's localization and stability, it played a crucial role in mediating ELMO1-Dock180 interaction, thereby influencing Rac1 activation. Functionally, ELMO1 K505 acetylation proved to be a pivotal factor in CRC progression, exerting its influence on key cellular processes. Clinical analysis of CRC samples unveiled elevated ELMO1 acetylation in primary tumors, indicating a potential association with CRC pathologies. This work provides insights into ELMO1 acetylation and its significance in advancing potentially therapeutic interventions in CRC treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Colorretais , Proteínas rac1 de Ligação ao GTP , Humanos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Acetilação , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Progressão da Doença , Sirtuína 2/metabolismo , Sirtuína 2/genética , Movimento Celular , Células HCT116RESUMO
BACKGROUND: Accurately identifying drug-target affinity (DTA) plays a pivotal role in drug screening, design, and repurposing in pharmaceutical industry. It not only reduces the time, labor, and economic costs associated with biological experiments but also expedites drug development process. However, achieving the desired level of computational accuracy for DTA identification methods remains a significant challenge. RESULTS: We proposed a novel multi-view-based graph deep model known as MvGraphDTA for DTA prediction. MvGraphDTA employed a graph convolutional network (GCN) to extract the structural features from original graphs of drugs and targets, respectively. It went a step further by constructing line graphs with edges as vertices based on original graphs of drugs and targets. GCN was also used to extract the relationship features within their line graphs. To enhance the complementarity between the extracted features from original graphs and line graphs, MvGraphDTA fused the extracted multi-view features of drugs and targets, respectively. Finally, these fused features were concatenated and passed through a fully connected (FC) network to predict DTA. CONCLUSIONS: During the experiments, we performed data augmentation on all the training sets used. Experimental results showed that MvGraphDTA outperformed the competitive state-of-the-art methods on benchmark datasets for DTA prediction. Additionally, we evaluated the universality and generalization performance of MvGraphDTA on additional datasets. Experimental outcomes revealed that MvGraphDTA exhibited good universality and generalization capability, making it a reliable tool for drug-target interaction prediction.
Assuntos
Aprendizado Profundo , Descoberta de Drogas/métodos , Biologia Computacional/métodos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismoRESUMO
BACKGROUND: Accurately identifying drug-target interaction (DTI), affinity (DTA), and binding sites (DTS) is crucial for drug screening, repositioning, and design, as well as for understanding the functions of target. Although there are a few online platforms based on deep learning for drug-target interaction, affinity, and binding sites identification, there is currently no integrated online platforms for all three aspects. RESULTS: Our solution, the novel integrated online platform Drug-Online, has been developed to facilitate drug screening, target identification, and understanding the functions of target in a progressive manner of "interaction-affinity-binding sites". Drug-Online platform consists of three parts: the first part uses the drug-target interaction identification method MGraphDTA, based on graph neural networks (GNN) and convolutional neural networks (CNN), to identify whether there is a drug-target interaction. If an interaction is identified, the second part employs the drug-target affinity identification method MMDTA, also based on GNN and CNN, to calculate the strength of drug-target interaction, i.e., affinity. Finally, the third part identifies drug-target binding sites, i.e., pockets. The method pt-lm-gnn used in this part is also based on GNN. CONCLUSIONS: Drug-Online is a reliable online platform that integrates drug-target interaction, affinity, and binding sites identification. It is freely available via the Internet at http://39.106.7.26:8000/Drug-Online/ .
Assuntos
Aprendizado Profundo , Interações Medicamentosas , Sítios de Ligação , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de MedicamentosRESUMO
Most proteins exert their functions by interacting with other proteins, making the identification of protein-protein interactions (PPI) crucial for understanding biological activities, pathological mechanisms, and clinical therapies. Developing effective and reliable computational methods for predicting PPI can significantly reduce the time-consuming and labor-intensive associated traditional biological experiments. However, accurately identifying the specific categories of protein-protein interactions and improving the prediction accuracy of the computational methods remain dual challenges. To tackle these challenges, we proposed a novel graph neural network method called GNNGL-PPI for multi-category prediction of PPI based on global graphs and local subgraphs. GNNGL-PPI consisted of two main components: using Graph Isomorphism Network (GIN) to extract global graph features from PPI network graph, and employing GIN As Kernel (GIN-AK) to extract local subgraph features from the subgraphs of protein vertices. Additionally, considering the imbalanced distribution of samples in each category within the benchmark datasets, we introduced an Asymmetric Loss (ASL) function to further enhance the predictive performance of the method. Through evaluations on six benchmark test sets formed by three different dataset partitioning algorithms (Random, BFS, DFS), GNNGL-PPI outperformed the state-of-the-art multi-category prediction methods of PPI, as measured by the comprehensive performance evaluation metric F1-measure. Furthermore, interpretability analysis confirmed the effectiveness of GNNGL-PPI as a reliable multi-category prediction method for predicting protein-protein interactions.
Assuntos
Algoritmos , Biologia Computacional , Redes Neurais de Computação , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Biologia Computacional/métodos , Mapas de Interação de Proteínas , Humanos , Proteínas/metabolismoRESUMO
Osteoarthritis (OA) is a joint pain and dysfunction syndrome resulting from severe joint degeneration. Inflammation and degeneration of the articular cartilage are two main features of OA and have tight interactions during OA progression. Conventional treatment with nonsteroidal anti-inflammatory drugs has been widely utilized clinically, whereas the side effects have restricted their application. Forsythoside B has been found with anti-inflammatory effects and antiapoptosis in inflammatory diseases, whereas in OA it remains poorly understood. Interleukin (IL)-1ß (10 ng/mL) was taken to induce an OA cell model on HC-A chondrocytes and an OA rat model was constructed for in vivo experiments. Forsythoside B was adopted to treat HC-A chondrocytes and OA rats. As shown by the data, Forsythoside B hampered IL-1ß-elicited rat chondrocyte apoptosis, oxidative stress, and facilitated proliferation. The profiles of inflammatory factors, NOD-like receptor family pyrin domain containing 3 inflammasomes, Kelch-like epichlorohydrin-associated protein-1 (Keap1), and nuclear factor-κB (NF-κB) phosphorylation were suppressed by Forsythoside B, whereas the nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels were promoted. Further, Forsythoside B mitigated cartilage damage and degeneration. Moreover, the oxidative stress and inflammation mediators in the cartilage tissue of OA rats were remarkably abated. Collectively, Forsythoside B hinders the NF-κB and Keap1/Nrf2/HO-1 pathways to curb IL-1ß-elicited OA rat oxidative stress and inflammation both in vivo and ex vivo, ameliorating OA development. All over, this study provides an underlying strategy for treating OA, which might help the clinical treatment of OA patients.
Assuntos
Ácidos Cafeicos , Glucosídeos , Proteína HMGB1 , Osteoartrite , Humanos , Animais , Ratos , NF-kappa B/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Receptor 4 Toll-Like/metabolismo , Epicloroidrina/farmacologia , Epicloroidrina/uso terapêutico , Transdução de Sinais , Heme Oxigenase-1/metabolismo , Proteína HMGB1/metabolismo , Células Cultivadas , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Interleucina-1beta/metabolismoRESUMO
BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.
Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , População do Leste Asiático , Humanos , Idoso , Transtornos Cognitivos/diagnóstico , Estudos Transversais , 8-Hidroxi-2'-Desoxiguanosina , Longevidade , Envelhecimento/psicologia , Fatores de Risco , Cognição , Disfunção Cognitiva/epidemiologiaRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of lower motor neurons, resulting in progressive muscle weakness and atrophy. However, little is known regarding the cardiac function of children with SMA. METHODS: We recruited SMA patients younger than 18 years of age from January 1, 2022, to April 1, 2022, in the First Affiliated Hospital of Sun Yat-sen University. All patients underwent a comprehensive cardiac evaluation before treatment, including history taking, physical examination, blood tests of cardiac biomarkers, assessment of echocardiography and electrocardiogram. Age/gender-matched healthy volunteers were recruited as controls. RESULTS: A total of 36 SMA patients (26 with SMA type 2 and 10 with SMA type 3) and 40 controls were enrolled in the study. No patient was clinically diagnosed with heart failure. Blood tests showed elevated values of creatine kinase isoenzyme M and isoenzyme B (CK-MB) mass and high-sensitivity cardiac troponin T (hs-cTnT) in spinal muscular atrophy (SMA) patients. Regarding echocardiographic parameters, SMA children were detected with lower global left and right ventricular longitudinal strain, abnormal diastolic filling velocities of trans-mitral and trans-tricuspid flow. The results revealed no clinical heart dysfunction in SMA patients, but subclinical ventricular dysfunction was seen in SMA children including the diastolic function and myocardial performance. Some patients presented with elevated heart rate and abnormal echogenicity of aortic valve or wall. Among these SMA patients, seven patients (19.4%) had scoliosis. The Cobb's angles showed a significant negative correlation with LVEDd/BSA, but no correlation with other parameters, suggesting that mild scoliosis did not lead to significant cardiac dysfunction. CONCLUSIONS: Our findings warrant increased attention to the cardiac status and highlight the need to investigate cardiac interventions in SMA children.
Assuntos
Ecocardiografia , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Criança , Pré-Escolar , Adolescente , Eletrocardiografia , Lactente , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/fisiopatologia , Atrofia Muscular Espinal/sangue , Biomarcadores/sangue , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/fisiopatologia , Atrofias Musculares Espinais da Infância/sangue , Atrofias Musculares Espinais da Infância/complicações , Testes de Função Cardíaca/métodosRESUMO
Keshan disease (KD) is a type of endemic cardiomyopathy with an unknown cause. It is primarily found in areas in China with low selenium levels, from northeast to southwest. The nutritional biogeochemical etiology hypothesis suggests that selenium deficiency is a major factor in KD development. Selenium is important in removing free radicals and protecting cells and tissues from peroxide-induced damage. Thus, low environmental selenium may affect the selenium level within the human body, and selenium level differences are commonly observed between healthy people in KD and nonKD areas. From the 1970s to the 1990s, China successfully reduced KD incidence in endemic KD areas through a selenium supplementation program. After years of implementing prevention and control measures, the selenium level of the population in the KD areas has gradually increased, and the prevalence of KD in China has remained low and stable in recent years. Currently, the pathogenesis of KD remains vague, and the effect of selenium supplementation on the prognosis of KD still needs further study. This paper comprehensively reviews selenium deficiency and its connection to KD. Thus, this study aims to offer novel ideas and directions to effectively prevent and treat KD in light of the current situation.
Assuntos
Cardiomiopatias , Infecções por Enterovirus , Desnutrição , Selênio , Humanos , Selênio/análise , Cardiomiopatias/epidemiologia , Cardiomiopatias/etiologia , Cardiomiopatias/prevenção & controle , Infecções por Enterovirus/complicações , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/prevenção & controle , China/epidemiologiaRESUMO
The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.
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Insuficiência Adrenal , Insuficiência Cardíaca , Hipoglicemia , Recém-Nascido , Humanos , Masculino , Hidrocortisona/uso terapêutico , Hipoglicemia/etiologia , Insuficiência Adrenal/congênito , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/genética , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Hormônio AdrenocorticotrópicoRESUMO
Functional reprogramming of tumor-associated macrophages (TAMs) is crucial to their potent tumor-supportive capacity. However, the molecular mechanism behind the reprogramming process remains poorly understood. Here, we identify engulfment and cell motility protein 1 (ELMO1) as a crucial player for TAM reprogramming in colorectal cancer (CRC). The expression of ELMO1 in stromal but not epithelial tumor cells was positively associated with advanced clinical stage and poor disease-free survival in CRC. An increase in ELMO1 expression was specifically found in TAMs, but not in other multiple nonmalignant stromal cells. Gain- and loss-of-function assays indicated ELMO1 reprogrammed macrophages to a TAM-like phenotype through Rac1 activation. In turn, ELMO1-reprogrammed macrophages were shown to not only facilitate the malignant behaviors of CRC cells but exhibited potent phagocytosis of tumor cells. Taken together, our work underscores the importance of ELMO1 in determining functional reprogramming of TAMs and could provide new insights on potential therapeutic strategies against CRC.
Assuntos
Neoplasias Colorretais , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular/genética , Macrófagos/metabolismo , Neoplasias Colorretais/patologiaRESUMO
Non-invasive diagnostic method based on radiomic features in patients with non-small cell lung cancer (NSCLC) has attracted attention. This study aimed to develop a CT image-based model for both histological typing and clinical staging of patients with NSCLC. A total of 309 NSCLC patients with 537 CT series from The Cancer Imaging Archive (TCIA) database were included in this study. All patients were randomly divided into the training set (247 patients, 425 CT series) and testing set (62 patients, 112 CT series). A total of 107 radiomic features were extracted. Four classifiers including random forest, XGBoost, support vector machine, and logistic regression were used to construct the classification model. The classification model had two output layers: histological type (adenocarcinoma, squamous cell carcinoma, and large cell) and clinical stage (I, II, and III) of NSCLC patients. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence interval (CI) were utilized to evaluate the performance of the model. Seven features were selected for inclusion in the classification model. The random forest model had the best classification ability compared with other classifiers. The AUC of the RF model for histological typing and clinical staging of NSCLC patients in the testing set was 0.700 (95% CI, 0.641-0.759) and 0.881 (95% CI, 0.842-0.920), respectively. The CT image-based radiomic feature model had good classification ability for both histological typing and clinical staging of patients with NSCLC.
Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Adenocarcinoma/patologiaRESUMO
Photoreceptors in the retina are highly specialized neurons with photosensitive molecules in the outer segment that transform light into chemical and electrical signals, and these signals are ultimately relayed to the visual cortex in the brain to form vision. Photoreceptors are composed of rods and cones. Rods are responsible for dim light vision, whereas cones are responsible for bright light, color vision, and visual acuity. Photoreceptors undergo progressive degeneration over time in many hereditary and age-related retinal diseases. Despite the remarkable heterogeneity of disease-causing genes, environmental factors, and pathogenesis, the progressive death of rod and cone photoreceptors ultimately leads to loss of vision/blindness. There are currently no treatments available for retinal degeneration. Cyclic guanosine 3', 5'-monophosphate (cGMP) plays a pivotal role in phototransduction. cGMP governs the cyclic nucleotide-gated (CNG) channels on the plasma membrane of the photoreceptor outer segments, thereby regulating membrane potential and signal transmission. By gating the CNG channels, cGMP regulates cellular Ca2+ homeostasis and signal transduction. As a second messenger, cGMP activates the cGMP-dependent protein kinase G (PKG), which regulates numerous targets/cellular events. The dysregulation of cGMP signaling is observed in varieties of photoreceptor/retinal degenerative diseases. Abnormally elevated cGMP signaling interferes with various cellular events, which ultimately leads to photoreceptor degeneration. In line with this, strategies to reduce cellular cGMP signaling result in photoreceptor protection in mouse models of retinal degeneration. The potential mechanisms underlying cGMP signaling-induced photoreceptor degeneration involve the activation of PKG and impaired Ca2+ homeostasis/Ca2+ overload, resulting from overactivation of the CNG channels, as well as the subsequent activation of the downstream cellular stress/death pathways. Thus, targeting the cellular cGMP/PKG signaling and the Ca2+-regulating pathways represents a significant strategy for photoreceptor protection in retinal degenerative diseases.
Assuntos
Degeneração Retiniana , Camundongos , Animais , Degeneração Retiniana/patologia , Transdução de Sinais , Retina/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , GMP Cíclico/metabolismoRESUMO
Their unique layered structure, large specific surface area, good stability, high negative charge density between layers, and customizable composition give layered double hydroxides (LDHs) excellent adsorption and detection performance for heavy metal ions (HMIs). However, their easy aggregation and low electrical conductivity limit the practical application of untreated LDHs. In this work, a ternary MgZnFe-LDHs engineered porous biochar (MgZnFe-LDHs/PBC) heterojunction was proposed as a sensing and adsorption material for the effective detection and removal of Cd2+ from wastewater. The growth of MgZnFe-LDHs in the PBC pores not only reduces the accumulation of MgZnFe-LDHs, but also improves the electrical conductivity of the composite. The synergistic effect between MgZnFe-LDHs and PBC enables the composite to achieve a maximum adsorption capacity of up to 293.4 mg/g for Cd2+ in wastewater. Meanwhile, the MgZnFe-LDHs/PBC-based electrochemical sensor shows excellent detection performance for Cd2+, presenting a wide linear range (0.01 ng/L-1 mg/L), low detection limit (3.0 pg/L), good selectivity, and stability. The results indicate that MgZnFe-LDHs/PBC would be a potential material for detecting and removing Cd2+ from wastewater.
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Cádmio , Poluentes Químicos da Água , Cádmio/química , Águas Residuárias , Adsorção , Porosidade , Poluentes Químicos da Água/química , Hidróxidos/químicaRESUMO
OBJECTIVE: To analyze the intake of energy and macronutrients in the elderly aged 75 years and above in China. METHODS: The data was sourced from the China National Chronic Non-communicable Disease and Nutrition Surveillance, which adopted a multi-stage stratified clustered random sampling method and selected 298 monitoring points from 31 provinces across the country to carry out chronic non-communicable disease and nutrition surveillance of Chinese adults. The condiments weighting method and 3-day 24-hour dietary review method were used to collect dietary data for residents. Based on the dietary survey result of 3368 elderly people aged 75 years and above in the surveillance, the intake of energy and macro nutrients of elderly people was analyzed. RESULTS: Among the elderly aged 75 years and above included in the analysis, there were 1727 males and 1641 females, 1511 people in urban areas and 1857 people in rural areas, 1956 people aged 75-79, 1412 people aged ≥ 80. The average energy intake of the elderly aged 75 years and above in China was(1601.0±473.4)kcal, and the average intakes of carbohydrate, protein and fat were(219.6±76.6)g, (48.2±18.6)g and(60.2±31.5)g, respectively. The energy supply ratios of carbohydrate, protein and fat were 54.9%, 12.0% and 33.1% respectively. The carbohydrate intake and its energy supply ratio of the urban elderly((200.0±74.0)g and 51.8%) were significantly lower than those of the rural elderly((235.5±75.0) and 57.4%), while the protein intake and its energy supply ratio((50.2±18.9)g and 13.0%), fat intake and its energy supply ratio((61.2±30.2)g and 35.2%)of the urban elderly were significantly higher than those of the rural elderly((46.5±18.2)g and 11.2% for protein, and(59.4±32.5)g and 31.4% for fat). According to Chinese dietary reference intake standard, only 28.1% of the elderly aged 75 and above reached the recommended value of energy, 71.9% of the elderly did not take enough energy, the proportion of insufficient protein intake was 72.2%, 68.5% in urban areas and 75.2% in rural areas, the proportion of people with fat to energy ratio more than 30% was 58.5%, 65.3% in urban areas and 52.9% in rural areas. CONCLUSION: The energy intake of the elderly aged 75 years and above in China was insufficient, the protein intake was low, the fat to energy ratio was too high, and the dietary structure was unreasonable.
Assuntos
Doenças não Transmissíveis , Adulto , Masculino , Idoso , Feminino , Humanos , Inquéritos Nutricionais , Dieta , Ingestão de Energia , Nutrientes , China , CarboidratosRESUMO
OBJECTIVE: To get a better knowledge of the current situation of screen time among primary and secondary school students in all provinces of China from 2016 to 2017. METHODS: Data was from the China National Nutrition and Health Surveillance of Children and Lactating Women(2016-2017).275 monitoring points were selected from 31 provinces of China by multi-stage stratified cluster random sampling. A total of 280 primary and secondary school students from 2 primary schools, 2 junior middle schools and 1 senior high school were randomly selected from each monitoring point to complete the survey.73629 primary and secondary school students(except grade 9 and grade 12) were included in this study. RESULTS: From 2016 to 2017, the average daily screen time of Chinese primary and secondary school students was(1.65±1.54) hours, M(P25, P75) was 1.29(0.58, 2.21) h. In terms of provinces, the average daily electronic screen time of primary and secondary school students in Beijing, Tianjin, Jilin, Fujian, Guangdong and Hainan is more than 2 hours. In terms of rural and urban areas, the screen time of students in Beijing's rural and urban areas, Tianjin's rural areas, Hebei's urban areas, Liaoning's rural areas, Jilin's rural areas, Fujian's urban areas, Guangdong's urban areas, Guangxi's urban areas, Hainan's rural and urban areas, and Xinjiang's urban areas all exceeds 2 hours/day. Besides, screen times of rural primary and secondary school students in Beijing(Z=2.62, P<0.01), Tianjin(Z=5.94, P<0.01), Liaoning(Z=11.56, P<0.01), Jilin(Z=-7.59, P<0.01), Shanghai(Z=3.19, P<0.01), Jiangsu(Z=12.00, P<0.01), Zhejiang(Z=-4.80, P<0.01), Anhui(Z=-4.67, P<0.01), Jiangxi(Z=-3.29, P=0.01), and Sichuan(Z=-4.53, P<0.01) are longer than that of urban students. CONCLUSION: There are urban-rural differences in the average daily electronic screen time and different types of electronic screen time of primary and secondary school students in China's provinces from 2016 to 2017.
Assuntos
População do Leste Asiático , Tempo de Tela , Criança , Feminino , Humanos , China/epidemiologia , Lactação , Estudantes , Adolescente , População Urbana , População RuralRESUMO
OBJECTIVE: To analyze the intakes of main food among the children of 6-17 years in different regions of China from 2019 to 2021, and to provide a scientific basis for evaluation and guiding Chinese children to make reasonable diet. METHODS: Multistage stratified random sampling method was used to collect data in east China, north China, central China, south China, southwest, northwest and northeast seven areas of each random two provinces, randomly selected from each province one urban survey site and one rural survey site, 28 sites of the 13th Five Year National Science and Technology Basic Resources Survey Project-Chinese children aged 0-18 investigation and application of nutrition and health system in 14 provinces of China. The study included 6413 children aged 6 to 17. Three consecutive 24-hour recalls method combined with weighing were used to collect the information of food intake. According to the food classification in the standard version of the food composition list, the food was divided into cereals, tubers, fresh vegetables, fresh fruits, meat and poultry, fish and shrimp, eggs, milk, etc. , and the intake of various foods was calculated for boys and girls aged 6-8, 9-11, 12-14 and 15-17 in different regions. RESULTS: Compared with the average daily food intake of children of the same sex and age in the urban and rural, The average daily intake of cereals and tubers for boys aged 9-17, cereals for girls aged 9-17, tubers for girls aged 12-17, and fish and shrimp for boys of edible population aged 15-17 were higher in rural areas than in urban areas. There were differences in the average daily food intake and consumption rate of fresh vegetables, fresh fruits, meat and poultry, eggs and milk of the same sex and age, which were higher in urban than in rural areas(P<0.05). Compared with the average daily food intake of children of the same sex and age in the south and the north, the average daily intake of cereals and eggs for boys aged 9-14, cereals for girls aged 6-8, and fresh fruits for boys and girls of edible population aged 6-17 were higher in the north than in the south. There were differences in average daily intake and consumption rates of tubers, fresh vegetables, meat and poultry, milk and fish and shrimp of the same sex and age, which were higher in the south than in the north(P<0.05). Compared with the average daily food intake of children of the same sex and age in the eastern, central and western regions, the average daily intake of cereals for boys aged 6-14, cereals for girls aged 6-17, fresh fruits for boys and girls of edible population aged 6-17, and fish and shrimp for boys and girls of edible population aged 15-17 were lower in the eastern region than in the central and western regions. The average daily intake of tubers for boys aged 9-11 and 15-17, for girls aged 9-17 were higher in the western regions than the eastern and central regions. The average daily intake of eggs for boys and girls aged 12-17 was lower in western regions than the eastern and central regions. There were differences in average daily intake and consumption rates of fresh vegetables, meat and poultry and milk of the same sex and age, which were higher in the eastern region than in the central and western regions. (P<0.05). The proportion of coarse grains to cereals was low, between 3.7% and 10.1%. The proportion of pork to meat and poultry was high, between 56.1% and 71.4%. CONCLUSION: In China, there are differences in daily intake of main food for children aged 6 to 17 years old in urban and rural areas, north and south areas, east, central and west areas.
Assuntos
Dieta , Verduras , Animais , China , Frutas , Estado Nutricional , Grão Comestível , Inquéritos NutricionaisRESUMO
The female infant in this case study was admitted to the hospital 4 hours after birth due to preterm birth and respiratory distress. On the third day after birth, peripherally inserted central venous catheter (PICC) catheterization was performed. On day 42, thrombus was found at the entrance of the right atrium from the inferior vena cava during a cardiac ultrasound, and it was considered to be related to PICC placement. Low-molecular-weight heparin and urokinase were given. After two weeks of treatment, ultrasonic monitoring showed thrombus shrinkage. No bleeding or pulmonary embolism occurred during the treatment. The patient discharged after improvement. This article mainly introduces a multidisciplinary team approach to diagnosis and treatment of PICC-related thrombosis in neonates.