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Lipid storage myopathy (LSM) is a heterogeneous group of lipid metabolism disorders predominantly affecting skeletal muscle by triglyceride accumulation in muscle fibers. Riboflavin therapy has been shown to ameliorate symptoms in some LSM patients who are essentially concerned with multiple acyl-CoA dehydrogenation deficiency (MADD). It is proved that riboflavin responsive LSM caused by MADD is mainly due to ETFDH gene variant (ETFDH-RRMADD). We described here a case with riboflavin responsive LSM and MADD resulting from FLAD1 gene variants (c.1588 C > T p.Arg530Cys and c.1589 G > C p.Arg530Pro, FLAD1-RRMADD). And we compared our patient together with 9 FLAD1-RRMADD cases from literature to 106 ETFDH-RRMADD cases in our neuromuscular center on clinical history, laboratory investigations and pathological features. Furthermore, the transcriptomics study on FLAD1-RRMADD and ETFDH-RRMADD were carried out. On muscle pathology, both FLAD1-RRMADD and ETFDH-RRMADD were proved with lipid storage myopathy in which atypical ragged red fibers were more frequent in ETFDH-RRMADD, while fibers with faint COX staining were more common in FLAD1-RRMADD. Molecular study revealed that the expression of GDF15 gene in muscle and GDF15 protein in both serum and muscle was significantly increased in FLAD1-RRMADD and ETFDH-RRMADD groups. Our data revealed that FLAD1-RRMADD (p.Arg530) has similar clinical, biochemical, and fatty acid metabolism changes to ETFDH-RRMADD except for muscle pathological features.
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Proteínas Ferro-Enxofre , Erros Inatos do Metabolismo Lipídico , Deficiência Múltipla de Acil Coenzima A Desidrogenase , Distrofias Musculares , Oxirredutases atuantes sobre Doadores de Grupo CH-NH , Humanos , Acil Coenzima A/genética , Acil Coenzima A/metabolismo , Acil Coenzima A/uso terapêutico , Flavoproteínas Transferidoras de Elétrons/genética , Flavoproteínas Transferidoras de Elétrons/metabolismo , Proteínas Ferro-Enxofre/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Riboflavina/genética , Riboflavina/metabolismo , Riboflavina/uso terapêuticoRESUMO
BACKGROUND: To comprehend the complexities of pathophysiological mechanisms and molecular events that contribute to proliferative diabetic retinopathy (PDR) and evaluate the diagnostic value of aqueous humor (AH) in monitoring the onset of PDR. METHODS: A cohort containing 16 PDR and 10 cataract patients and another validation cohort containing 8 PDR and 4 cataract patients were studied. AH was collected and subjected to proteomics analyses. Bioinformatics analysis and a machine learning-based pipeline called inference of biomolecular combinations with minimal bias were used to explore the functional relevance, hub proteins, and biomarkers. RESULTS: Deep profiling of AH proteomes revealed several insights. First, the combination of SIAE, SEMA7A, GNS, and IGKV3D-15 and the combination of ATP6AP1, SPARCL1, and SERPINA7 could serve as surrogate protein biomarkers for monitoring PDR progression. Second, ALB, FN1, ACTB, SERPINA1, C3, and VTN acted as hub proteins in the profiling of AH proteomes. SERPINA1 was the protein with the highest correlation coefficient not only for BCVA but also for the duration of diabetes. Third, "Complement and coagulation cascades" was an important pathway for PDR development. CONCLUSIONS: AH proteomics provides stable and accurate biomarkers for early warning and diagnosis of PDR. This study provides a deep understanding of the molecular mechanisms of PDR and a rich resource for optimizing PDR management.
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Sodium iodate (NaIO3) is a commonly used model for age-related macular degeneration (AMD), but its rapid and severe induction of retinal pigment epithelial (RPE) and photoreceptor degeneration can lead to the premature dismissal of potentially effective therapeutics. Additionally, little is known about how sex and age affect the retinal response to NaIO3. This study aims to establish a less severe yet reproducible regimen by testing low doses of NaIO3 while considering age- and sex-related effects, enabling a broader range of therapeutic evaluations. In this study, young (3-5 months) and old (18-24 months) male and female C57Bl/6J mice were given an intraperitoneal (IP) injection of 15, 20, or 25 mg/kg NaIO3. Damage assessment one week post-injection included in vivo imaging, histological examination, and qRT-PCR analysis. The results revealed that young mice showed no damage at 15 mg/kg IP NaIO3, with varying degrees of damage observed at 20 mg/kg. At 25 mg/kg, most young mice displayed widespread retinal damage, with females exhibiting less retinal thinning than males. In contrast, older mice at 20 and 25 mg/kg displayed a more patchy degeneration pattern, outer retinal undulations, and greater variability in degeneration than the young mice. The most effective model for minimizing damage while maintaining consistency utilizes young female mice injected with 25 mg/kg NaIO3. The observed sex- and age-related differences underscore the importance of considering these variables in research, aligning with the National Institutes of Health's guidance. While the model does not fully replicate the complexity of AMD, these findings enhance its utility as a valuable tool for testing RPE/photoreceptor protective or replacement therapies.
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Degeneração Macular , Degeneração Retiniana , Feminino , Masculino , Camundongos , Animais , Retina/patologia , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia , Degeneração Macular/tratamento farmacológico , Degeneração Macular/patologia , Iodatos/toxicidade , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/patologia , Modelos Animais de DoençasRESUMO
BACKGROUND: The purpose of this study is to analyze the influencing factors associated with Long-COVID in patients infected with Omicron variant of COVID-19 in Changchun City, Jilin Province, China three months after discharge in March 2022. METHODS: In this study, we conducted a telephone follow-up based on the real-world data collected from the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun Tongyuan Shelter Hospital and Changchun Infectious Disease Hospital during the COVID-19 epidemic in Changchun in March 2022. We used the Global COVID-19 Clinical Platform Case Report Form for Post COVID condition as a follow-up questionnaire to collect the general information, past medical history, clinical symptoms, COVID-19 vaccine inoculation doses, and other relevant information to analyze the symptom characteristics of COVID-19 patients three months after discharge from the hospital and related factors affecting Long COVID. RESULTS: A total of 1,806 patients with COVID-19 were included in this study, 977 males and 829 females, with a mean age of 38.5 [30.0, 49.4] years, and the number of female patients suffering from Long COVID (50.87%) was greater than male patients (p = 0.023). The binary logistic regression analysis of factors influencing Long COVID showed that smoking history (OR (95%CI) = 0.551(0.425-0.714), p < 0.001, taking never smoking as a reference), allergy history (OR (95%CI) = 1.618 (1.086-2.413), p-value 0.018, taking no allergy as a reference), first symptoms (OR (95%CI) = 0.636 (0.501-0.807), p < 0.001, with no first symptoms as reference) and COVID-19 vaccine inoculation doses (OR (95%CI) = 1.517 (1.190-1.933), p-value 0.001, with ≤ 2 doses of COVID-19 vaccine inoculation doses as reference) constituted its influencing factors. The first symptoms of patients on admission mainly included fever (512 cases, 71.81%), cough (279 cases, 39.13%) and dry or itchy throat (211 cases, 29.59%). The most common symptoms of Long COVID were persistent fatigue (68 cases), amnesia (61 cases), insomnia (50 cases) and excessive sweating (50 cases). CONCLUSION: The first symptoms on admission were predominantly fever, cough and dry or itchy throat. The most common symptoms of Long COVID were persistent fatigue, amnesia, insomnia and excessive sweating, and female patients were at a higher risk of Long COVID.
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COVID-19 , Distúrbios do Início e da Manutenção do Sono , Adulto , Feminino , Humanos , Masculino , Amnésia , Tosse , COVID-19/epidemiologia , Vacinas contra COVID-19 , Estudos Transversais , Fadiga , Febre/epidemiologia , Alta do Paciente , Síndrome de COVID-19 Pós-Aguda , SARS-CoV-2 , Pessoa de Meia-IdadeRESUMO
Age-related hearing loss (ARHL), is a pervasive health problem worldwide. ARHL seriously affects the quality of life and reportedly leads to social isolation and dementia in the elderly. ARHL is caused by the degeneration or disorders of cochlear hair cells and auditory neurons. Numerous studies have verified that genetic factors contributed to this impairment, however, the mechanism behind remains unclear. In this study, we analyzed an mRNA expression dataset (GSE49543) from the GEO database. Differentially expressed genes (DEGs) between young control mice and presbycusis mice were analyzed using limma in R and weighted gene co-expression network analysis (WGCNA) methods. Functional enrichment analyses of the DEGs were conducted with the clusterProfiler R package and the results were visualized using ggplot2 R package. The STRING database was used for the construction of the protein-protein interaction (PPI) network of the screened DEGs. Two machine learning algorithms LASSO and SVM-RFE were used to screen the hub genes. We identified 54 DEGs in presbycusis using limma and WGCNA. DEGs were associated with the synaptic vesicle cycle, distal axon, neurotransmitter transmembrane transporter activity in GO analysis, and alcoholic liver disease, pertussis, lysosome pathway according to KEGG analyses. PPI network analysis identified three significant modules. Five hub genes (CLEC4D, MS4A7, CTSS, LAPTM5, ALOX5AP) were screened by LASSO and SVM-RFE. These hub genes were highly expressed in presbycusis mice compared with young control mice. We screened DEGs and identified hub genes involved in ARHL development, which might provide novel clues to understanding the molecular basis of ARHL.
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Perfilação da Expressão Gênica , Presbiacusia , RNA Mensageiro , Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Camundongos , Perfilação da Expressão Gênica/métodos , Presbiacusia/genética , Presbiacusia/metabolismo , Presbiacusia/patologia , Redes Reguladoras de Genes , Mapas de Interação de Proteínas/genética , Transcriptoma/genética , Envelhecimento/genética , Bases de Dados Genéticas , Biologia Computacional/métodosRESUMO
PURPOSE: To investigate the changes in aqueous humor (AH) protein profiles before and after intravitreal aflibercept (IVA) treatment in patients with proliferative diabetic retinopathy (PDR). METHODS: 5 PDR patients provided 10 samples of AH before and after IVA treatment (pre-group vs. post-group). Proteins were identified using liquid chromatography-tandem mass spectrometry. Then, bioinformatics was employed to investigate the functional significance of differentially expressed proteins (DEPs) and hub proteins. RESULTS: A total of 16 DEPs were identified, consisting of 8 downregulated proteins and 8 upregulated proteins. Bioinformatics analysis indicated that the most significantly enriched biological process was "blood coagulation, intrinsic pathway." The most significantly enriched signaling pathway was "complement and coagulation cascades." HBB, HPX, VEGFA, and CA1 were identified as hub proteins for IVA treatment. CONCLUSIONS: Together with the downregulation of the intravitreal vascular endothelial growth factor level, IVA may also change the AH protein composition in PDR patients, with DEPs involved in the blood coagulation, intrinsic pathway, complement, and coagulation cascades. IVA treatment may protect against PDR by regulating HBB, HPX, VEGFA, and CA1 expression.
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Diabetes Mellitus , Retinopatia Diabética , Proteínas Recombinantes de Fusão , Humanos , Humor Aquoso , Retinopatia Diabética/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
BACKGROUND: The role of adipokines in the development of lung diseases is significant, yet their specific relationship with different lung diseases remains unclear. METHODS: In our research, we analyzed genetic variations associated with adipokines and various lung conditions such as interstitial lung disease, chronic obstructive pulmonary disease, asthma, lung cancer, sleep apnea, pneumonia, and tuberculosis, using data from public genome-wide studies. We employed Mendelian randomization techniques, including inverse variance weighting, weighted median, and MR-Egger regression methods, and conducted sensitivity checks to validate our findings. RESULTS: A study using the FinnGen database, which included 198,955 participants, identified 13 SNPs associated with adiponectin. Notably, adiponectin was found to significantly reduce the risk of interstitial lung disease and idiopathic pulmonary fibrosis. However, little evidence was found to establish a direct cause-effect relationship between the six adipokines and several other lung conditions, including sarcoidosis, asthma, chronic obstructive pulmonary disease, lung cancer, tuberculosis, pneumonia, and sleep apnea syndrome. CONCLUSION: This study reveals a reverse link between adiponectin levels and the likelihood of interstitial lung disease, including idiopathic pulmonary fibrosis.
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Asma , Fibrose Pulmonar Idiopática , Neoplasias Pulmonares , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Síndromes da Apneia do Sono , Tuberculose , Humanos , Adipocinas , Adiponectina , Análise da Randomização MendelianaRESUMO
Artemisia argyi is a perennial herb native to East Asia. It is an important traditional Chinese medicinal plant known for its strong flavor and medicinal effects. It is rich in active ingredients and has a wide range of biological activities, including anti-inflammatory, antioxidant, and immune regulation properties. From May to July in 2023, a serious leaf rot outbreak occurred on A. argyi in several farms (approximately 200 acres) in Tanghe county (32°46'44" N, 112°43'13" E), Henan Province, China. The incidence rate reached 65% (n=200). Pale yellow spots (1-2 cm in diameter) first appeared on the leaves, then expanded to form irregular yellowish-brown lesions, eventually causing the entire leaves to wither. Diseased leaves (30) were collected and cut into 5 x 5 mm2 pieces in the areas between infected and healthy tissues. The excised plant tissues were sterilized in 75% ethanol and 1% sodium hypochlorite solution for 30 seconds and one minute, respectively. The tissues were then rinsed with sterile water and placed on potato dextrose agar (PDA) followed by incubating at 25 °C for 3 days. The isolated strains belonged to the genera Fusarium and Alternaria. After pathogenicity verification, 25 purified Fusarium strains were obtained. Three representative strains (AC-Q, AC-X, AC-Y) from different regions were used for further studies. Each strain formed abundant aerial mycelium that was initially white and later developed into purple pigments. Aerial conidiophores were sparsely branched, terminating with verticillate phialides. Macroconidia were slender, straight, and measured 21.8 to 47.5 × 3.1 to 4.4 µm, with two to four septa. Microconidia were clavate and measured 8.31 to 11.6 × 2.1 to 3.5 µm. Morphological characteristics were consistent with the species description of Fusarium verticillioides (Sacc.) Nirenberg 1976 (Leslie and Summerell, 2006). The rDNA internal transcribed spacer (ITS), ß-tubulin gene (tub2), translation elongation factor 1-alpha gene (tef1), calmodulin (cmdA), RNA polymerase II largest subunit (rpb1) and RNA polymerase II second largest subunit (rpb2) were amplified for molecular identification (O'Donnell et al., 2022). The sequences were deposited in GenBank with accession Nos. OR960548, OR960552, OR960555 (ITS), OR972413, OR972414, OR972415 (tub2), OR797685, OR797686, OR797687 (tef1), OR972410, OR972411, OR972412 (cmdA), PP035106, PP035107, PP035108 (rpb1), and PP035109, PP035110, PP035111 (rpb2). BLASTn analysis of AC-Q sequences exhibited 99 to 100% similarity with F. verticillioides sequences (strains CBS 576.78) MT010888 of cmdA, MT0109566 of rpb1, and MT010972 of rpb2. A phylogenetic tree was constructed with concatenated sequences (tub2, tef1, cmdA, rpb1, rpb2), alongside the sequences of the type strains using the neighbor-joining method. The three strains formed a clade with the type strain CBS 576.78 of F. verticillioides, and were separated from other Fusarium spp. These morphological and molecular identifications indicated that the pathogen was F. verticillioides. Pathogenicity was tested on 10 healthy 2-month-old potted seedlings by spraying them with a conidial suspension (106 conidia ml-1), and 5 seedlings were sprayed with sterilized water as a control. The plants were placed in a climate incubator at 28°C and a relative humidity of approximately 90%. Ten days after seedling inoculation, typical lesions were observed on the treated plants, except in the control group. The reisolated strains were identified as F. verticillioides by morphological and molecular characterization, fulfilling Koch's postulates. F. verticillioides is known to cause Fusarium ear rot on maize, as well as diseases on other plants in China such as Brassica rapa (Akram et al., 2020) and Schizonepeta tenuifolia (Li et al., 2024). This is the first report of F. verticillioides causing leaf rot on A. argyi worldwide. Identification of the pathogen is crucial for implementing management approaches to reduce yield losses.
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Microbially induced carbonate precipitation (MICP) has been used to cure rare earth slags (RES) containing radionuclides (e.g. Th and U) and heavy metals with favorable results. However, the role of microbial extracellular polymeric substances (EPS) in MICP curing RES remains unclear. In this study, the EPS of Lysinibacillus sphaericus K-1 was extracted for the experiments of adsorption, inducing calcium carbonate (CaCO3) precipitation and curing of RES. The role of EPS in in MICP curing RES and stabilizing radionuclides and heavy metals was analyzed by evaluating the concentration and morphological distribution of radionuclides and heavy metals, and the compressive strength of the cured body. The results indicate that the adsorption efficiencies of EPS for Th (IV), U (VI), Cu2+, Pb2+, Zn2+, and Cd2+ were 44.83%, 45.83%, 53.7%, 61.3%, 42.1%, and 77.85%, respectively. The addition of EPS solution resulted in the formation of nanoscale spherical particles on the microorganism surface, which could act as an accumulating skeleton to facilitate the formation of CaCO3. After adding 20 mL of EPS solution during the curing process (Treat group), the maximum unconfined compressive strength (UCS) of the cured body reached 1.922 MPa, which was 12.13% higher than the CK group. The contents of exchangeable Th (IV) and U (VI) in the cured bodies of the Treat group decreased by 3.35% and 4.93%, respectively, compared with the CK group. Therefore, EPS enhances the effect of MICP curing RES and reduces the potential environmental problems that may be caused by radionuclides and heavy metals during the long-term sequestration of RES.
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Bacillaceae , Carbonato de Cálcio , Matriz Extracelular de Substâncias Poliméricas , Metais Pesados , Tório , Urânio , Urânio/química , Urânio/metabolismo , Carbonato de Cálcio/química , Tório/química , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Matriz Extracelular de Substâncias Poliméricas/química , Bacillaceae/metabolismo , Metais Terras Raras/química , Adsorção , Precipitação QuímicaRESUMO
We aim to screen and analyze the ferroptosis inflammation-related hub genes associated with idiopathic pulmonary fibrosis (IPF). The GSE52463 and GSE110147 datasets were obtained from the GEO database and merged. The DEGs were selected by differential analysis and intersected with inflammation-related genes and ferroptosis-related genes to acquire the ferroptosis-related differentially expressed genes (FRDEGs). GO, KEGG, GSEA, and GSVA were performed to investigate the features of FRDEGs. The key module genes were selected by WGCNA and employed to generate the PPI network using Cytoscape. Subsequently, the hub genes were identified using cytoHubba and validated by ROC curves generated by survivalROC. Finally, the correlations of hub genes were analyzed through Spearman and the subtypes of IPF were constructed using ConsensusClusterPlus. A total of 1814 DEGs were screened out and 18 FRDEGs were acquired from the intersection of DEGs, ferroptosis-related genes, and inflammation-related genes. GO and KEGG analysis revealed that FRDEGs were primarily involved in bacterial-origin molecular, response infectious disease, and iron ion transport. GSEA results suggested a predominant association with autoimmune diseases and GSVA identified ten different pathways between PF and control. Through WGCNA, three highly correlated modules were identified and ten key module genes were obtained by intersecting genes in the three modules with FRDEGs. Finally, employing three algorithms within the cytoHubba led to the identification of eight hub genes: CCND1, TP53, STAT3, CTNNB1 CDH1, ESR1, HSP90AA1, and EP300. Eventually, two distinct subtypes of IPF were identified. The present research successfully identified the hub genes associated with ferroptosis and inflammation and their biological effects on IPF. Furthermore, two disease subtypes of IPF were constructed.
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Flow cytometry-based measurement techniques have been widely used for single-cell characterizations, such as impedance, size, and dielectric properties. However, in the measurement process, the reliability of the output measurement signal directly affects the ability of the microsystem to judge the characteristics of single cells. Here, we designed a multiple nonparallel electrode structure for single-cell 3D localization. The performance of the structures was studied by analyzing the changes in electric field strength and the output differential current. The effects of microchannel height, sensing electrode distance, electrode inclination angle, and electrode width on output signals are investigated by analyzing the current change and electric field strength of single cells passing from the center of the microchannel. The numerical simulation results indicate that, when the microchannel height is 20 µm, the distance of the sensing electrodes is 100 µm, the inclination angle is 30°, the electrode width is 20 µm, and the optimal signal quality can be obtained. Reducing the height of the flow channel and shortening the sensing electrode spacing can significantly improve the signal amplitude. When the channel height is 20 µm, the signal intensity increases by 80% than that of 30 µm. The signal intensity of induced current with the sensing electrode spacing of 100 µm is 42% higher than that with the spacing of 120 µm. We analyzed the presence of multiple independent cells and adherent cells in the detection area and demonstrated through simulation that the signal changes caused by multi-cells can be superimposed by multiple single-cell signals. The induced current signal intensity of the same volume of cells with an ellipticity of 1 is 49% lower than that of cells with an ellipticity of 4. Based on the numerical investigation, we expect that the optimal geometry structure design will aid in the development of better performance signal cell impedance cytometry microsystems.
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Eletricidade , Microfluídica , Reprodutibilidade dos Testes , Simulação por Computador , Impedância ElétricaRESUMO
BACKGROUND: Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6-methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD. METHODS: This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP-seq), as well as RNA stability tests to ascertain the half-life and stability of the target genes. RESULTS: The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP-seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis. CONCLUSION: This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.
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Adenocarcinoma de Pulmão , Proliferação de Células , Proteínas Ativadoras de GTPase , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas c-akt , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Animais , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Hialuronoglucosaminidase/genética , Hialuronoglucosaminidase/metabolismo , Transdução de Sinais , Proteínas de Ligação a RNARESUMO
A novel analytical strategy was proposed to simultaneously quantify two advanced glycation end products (AGEs) including Nε-(Carboxymethyl)lysine (CML), Nε-(Carboxyethyl)lysine (CEL) and eight heterocyclic amines (HAs) including IQ, MeIQ, MeIQx, 4,8-DiMeIQx, 7,8-DiMeIQx, PhIP, Harman, and Norharman. The procedure was based on a two-step extraction, solid phase extraction (SPE) purification followed by ultra performance liquid chromatography tandem mass spectrometry. The established method showed a good linearity (R2 ≥ 0.9950), rapid processing time (8 min per sample), satisfactory recoveries (matrix spiked recoveries range from 72.2% to 119.6%) and precision (intra-day and inter-day RSDs were <19.3%). The limit of quantification (LOQ) and limit of detection (LOD) resulted to be between 0.05-15 ng/g and 0.2-50 ng/g, respectively. The validated technique was further applied to determine HAs and AGEs in eight stewed meat product samples consumed in Shanghai, with the amount of HAs and AGEs ranging from 2.851 to 18.289 ng/g and 118.158-543.493 ng/g, respectively.
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Aminas , Produtos Finais de Glicação Avançada , Compostos Heterocíclicos , Produtos da Carne , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Produtos Finais de Glicação Avançada/química , Produtos Finais de Glicação Avançada/análise , Aminas/análise , Aminas/química , Cromatografia Líquida de Alta Pressão/métodos , Produtos da Carne/análise , Animais , Compostos Heterocíclicos/análise , Compostos Heterocíclicos/química , Extração em Fase Sólida/métodos , Limite de Detecção , Suínos , Espectrometria de Massa com Cromatografia LíquidaRESUMO
With the global incidence of non-small cell lung cancer (NSCLC) on the rise, the development of innovative treatment strategies is increasingly vital. This review underscores the pivotal role of precision medicine in transforming NSCLC management, particularly through the integration of genomic and epigenomic insights to enhance treatment outcomes for patients. We focus on the identification of key gene mutations and examine the evolution and impact of targeted therapies. These therapies have shown encouraging results in improving survival rates and quality of life. Despite numerous gene mutations being identified in association with NSCLC, targeted treatments are available for only a select few. This paper offers an exhaustive analysis of the pathogenesis of NSCLC and reviews the latest advancements in targeted therapeutic approaches. It emphasizes the ongoing necessity for research and development in this domain. In addition, we discuss the current challenges faced in the clinical application of these therapies and the potential directions for future research, including the identification of novel targets and the development of new treatment modalities.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular/métodos , Medicina de Precisão , MutaçãoRESUMO
The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities-including surgery, radiotherapy, chemotherapy, and targeted therapy-face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.
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BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder. Microglia-mediated neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels can protect dopaminergic neurons from damage. Sodium butyrate (NaB) shows anti-inflammatory and neuroprotective effects in some animal models of brain injury and regulates the KATP channels in islet ß cells. In this study, we aimed to verify the anti-inflammatory effect of NaB on PD and further explored potential molecular mechanisms. METHODS: We established an in vitro PD model in BV2 cells using 1-methyl-4-phenylpyridinium (MPP+ ). The effects of MPP+ and NaB on BV2 cell viability were detected by cell counting kit-8 assays. The morphology of BV2 cells with or without MPP+ treatment was imaged via an optical microscope. The expression of Iba-1 was examined by the immunofluorescence staining. The intracellular ATP content was estimated through the colorimetric method, and Griess assay was conducted to measure the nitric oxide production. The expression levels of pro-inflammatory cytokines and KATP channel subunits were evaluated by reverse transcription-quantitative polymerase chain reaction and western blot analysis. RESULTS: NaB (5 mM) activated the KATP channels through elevating Kir6.1 and Kir6.1 expression in MPP+ -challenged BV2 cells. Both NaB and pinacidil (a KATP opener) suppressed the MPP+ -induced activation of BV2 cells and reduced the production of nitrite and pro-inflammatory cytokines in MPP+ -challenged BV2 cells. CONCLUSION: NaB treatment alleviates the MPP+ -induced inflammatory responses in microglia via activation of KATP channels.
Assuntos
Doença de Parkinson , Animais , Doença de Parkinson/metabolismo , Ácido Butírico/farmacologia , Ácido Butírico/metabolismo , Microglia/metabolismo , 1-Metil-4-fenilpiridínio/metabolismo , 1-Metil-4-fenilpiridínio/farmacologia , Inflamação/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Magnetic particle imaging (MPI) is an emerging imaging technology in medical tomography that utilizes the nonlinear magnetization response of superparamagnetic iron oxide (SPIO) particles to determine the in vivo spatial distribution of nanoparticle contrast agents. The reconstruction image quality of MPI is determined by the characteristics of magnetic particles, the setting of the MPI scanner parameters, and the hardware interference of MPI systems. We explore a feasible method to systematically and quickly analyze the impact of these factors on MPI reconstruction image quality. METHODS: We propose a systematic 3-D MPI simulation model. The MPI simulation model has the capability of quickly producing the simulated reconstruction images of a scanned phantom, and quantitative analysis of MPI reconstruction image quality can be achieved by comparing the differences between the input image and output image. These factors are mainly classified as imaging parameters and interference parameters in our model. In order to reduce the computational time of the simulation model, we introduce GPU parallel programming to accelerate the processing of large complex matrix data. For ease of use, we also construct a reliable, high-performance, and open-source 3-D MPI simulation software tool based on our model. The efficiency of our model is evaluated by using OpenMPIData. To demonstrate the capabilities of our model, we conduct simulation experiments using parameters consistent with a real MPI scanner for improving MPI image quality. RESULTS: The experimental results show that our simulation model can systematically and quickly evaluate the impact of imaging parameters and interference parameters on MPI reconstruction image quality. CONCLUSIONS: We developed an easy-to-use and open-source 3-D MPI simulation software tool based on our simulation model incorporating all the stages of MPI formation, from signal acquisition to image reconstruction. In the future, our simulation model has potential guiding significance to practical MPI images.
Assuntos
Simulação por Computador , Imageamento Tridimensional , Imagens de Fantasmas , Imageamento Tridimensional/métodos , Software , Processamento de Imagem Assistida por Computador/métodos , Nanopartículas de Magnetita , Algoritmos , Meios de Contraste , HumanosRESUMO
The ecotoxic endocrine-disrupting chemical di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in agricultural soil, posing a serious threat to human health. Here, we report efficient soil-borne DEHP degradation and plant growth promotion by a microbial organic fertilizer GK-PPB prepared by combining a recycled garden waste-kitchen waste compost product with ternary compound microbial agent PPB-MA, composed of Penicillium oxalic MB08F, Pseudomonas simiae MB751, and Bacillus tequilensis MB05B. The combination of MB08F and MB751 provided synergistic phosphorus solubilization, and MB05B enhanced the DEHP degradation capacity of MB08F via bioemulsification. Under optimal conditions (25.70 °C and pH 7.62), PPB-MA achieved a 96.81 % degradation percentage for 1000 mg L-1 DEHP within 5 days. The degradation curve followed first-order kinetics with a half-life of 18.24 to 24.76 h. A complete mineralization pathway was constructed after identifying the degradation intermediates of 2H-labeled DEHP. Evaluation in Caenorhabditis elegans N2 showed that PPB-MA eliminated the ecological toxicity of DEHP. A pakchoi (Brassica chinensis L.) pot experiment demonstrated that GK-PPB promoted phosphorus solubilization and plant growth, reduced soil DEHP residue, and decreased DEHP accumulation in pakchoi, suggesting its potential practical utility in environmentally responsible and safe cultivation of vegetables.
Assuntos
Dietilexilftalato , Ácidos Ftálicos , Poluentes do Solo , Humanos , Dietilexilftalato/metabolismo , Fosfatos , Solo , Fósforo , Poluentes do Solo/análiseRESUMO
Background: Sharp esophageal foreign body (SEFB) impaction can cause varying degrees of damage to the esophagus. There are few studies analyzing the postoperative fasting time in SEFB patients. Methods: We retrospectively collected 835 SEFB patients. According to the fasting time after the endoscopic removal (ER) of SEFBs, the patients were divided into two groups: short fasting time (SFT, fasted ≤24 h) and long fasting time (LFT, fasted >24 h). Results: There were 216 and 619 patients in the SFT and LFT group, respectively. The average age of the SFT group (52.97 years) was younger than that of the LFT group (55.96 years) (p = 0.025). The LFT group had lower proportion of duration of impaction (DOI) within 12 hours (14.2% vs 22.2%, p = 0.006) and erosion rates (89.0% vs 94.0%, p = 0.034) as well as higher proportion of esophageal perforation (19.5 vs 6.5%, p = 0.010) and patients who got intravenous anesthesia (63.78% vs 31.9%, p = 0.000) than the SFT group. The longest diameter of the foreign body (Lmax) in the LFT group (2.60 ± 1.01 cm) was greater than that in the SFT group (2.41 ± 0.83 cm; p = 0.01). Multivariate regression analysis found that age (OR = 1.726[1.208-2.465], p = 0.003), DOI (OR = 1.793[1.175-2.737], p = 0.007), Lmax (OR = 1.477[1.033-2.111], p = 0.032), perforation (OR = 3.698[2.038-6.710]; p < 0.01) and intravenous anesthesia (OR = 3.734[2.642-5.278]; p < 0.01) were the independent factors that prolonged fasting time in patients with SEFBs, while esophageal mucosal erosion (OR = 0.433[0.229-0.820]; p = 0.01) was the influencing factor leading to shortened fasting time. Conclusion: For the first time, we analyzed factors influencing the fasting time after ER in SEFB patients. Age, DOI, Lmax, perforation and intravenous anesthesia were risk factors for a prolonged postoperative fasting time.
RESUMO
To improve detection efficiency and reduce cost consumption in fishery surveys, target detection methods based on computer vision have become a new method for fishery resource surveys. However, the specialty and complexity of underwater photography result in low detection accuracy, limiting its use in fishery resource surveys. To solve these problems, this study proposed an accurate method named BSSFISH-YOLOv8 for fish detection in natural underwater environments. First, replacing the original convolutional module with the SPD-Conv module allows the model to lose less fine-grained information. Next, the backbone network is supplemented with a dynamic sparse attention technique, BiFormer, which enhances the model's attention to crucial information in the input features while also optimizing detection efficiency. Finally, adding a 160 × 160 small target detection layer (STDL) improves sensitivity for smaller targets. The model scored 88.3% and 58.3% in the two indicators of mAP@50 and mAP@50:95, respectively, which is 2.0% and 3.3% higher than the YOLOv8n model. The results of this research can be applied to fishery resource surveys, reducing measurement costs, improving detection efficiency, and bringing environmental and economic benefits.