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1.
Appl Radiat Isot ; 214: 111521, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39277978

RESUMEN

Interlaboratory comparison exercises for determining the gross alpha and beta activity concentrations in drinking water, organized by the National Institute for Radiological Protection (NIRP), China CDC, have been carried out since 2012. The purpose of this study is to assess the accuracy and precision of gross alpha and beta analyses of low-level radioactivity concentrations. Natural water samples were used for the comparison, and the performance of the participating laboratories was evaluated with respect to the reference values using the Z-score performance indicator. The comparison data from 2012 to 2022 were analyzed, where the percentage of laboratories with acceptable results was 80-92%, and the dispersion of the measurement results across laboratories became smaller over time. The results demonstrate that these exercises can help laboratories to resolve issues in gross α/ß analysis and improve the consistency of the measurement results.

2.
Micromachines (Basel) ; 15(9)2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39337760

RESUMEN

We have investigated the electrical properties and reliability of AlGaN/GaN high electron mobility transistors (HEMT) under high-temperature RF overdrive stress. The experimental results show that the drain current and transconductance of the device decrease at 25 °C and 55 °C but do not change significantly at 85 °C before and after the stress. The decline rate of the saturation drain current, the degradation amplitude of transconductance, and the drift amplitude of threshold voltage decrease with the increase in temperature. The results of pulse I-V and low-frequency noise tests show that the current collapse is inhibited, and the trap density is reduced at higher temperatures. The Electroluminescence (EL) test shows that the luminescence characteristics of the device after RF overdrive stress are more scattered and weaker. We believe that the degradation at lower temperatures is mainly due to the influence of the hot electron effect (HEE), while the change in electrical properties at higher temperatures is due to the weakening of HEE and the improvement of the Schottky interface.

3.
Photodiagnosis Photodyn Ther ; 49: 104325, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245305

RESUMEN

BACKGROUND: Acne is a chronic inflammatory skin disease. Photodynamic therapy (PDT) is a highly effective and safe drug-device combination treatment, typically using red and blue light. However, direct comparisons of aminolevulinic acid (ALA)-based PDT using these two light sources are lacking. Therefore, we compared the efficacy and adverse effects of ALA-based 450 nm blue laser-mediated PDT (BL-PDT) and 630 ± 10 nm red light-emitting diode-mediated PDT (RL-PDT) in the treatment of moderate-to-severe acne vulgaris, including analyses of different lesion types. METHODS: Sixteen patients with moderate-to-severe acne vulgaris were recruited. All patients underwent BL-PDT on the left side of the face and RL-PDT on the right side. Treatments were administered thrice at 2-week intervals, and follow-up continued for 2 weeks after the final treatment. The average rates of improvement in inflammatory and non-inflammatory acne lesions, IGA (Investigator's Global Assessment) scales, and IGA success rates were calculated. In addition, adverse effects during and after each treatment were recorded. RESULTS: At the 2-week follow-up after the final treatment, the average rates of improvement in total acne, inflammatory, and non-inflammatory lesions were 48.0 %, 63.0 %, and 30.0 % in the BL-PDT group and 42.2 %, 58.1 %, and 27.5 % in the RL-PDT group, respectively. The IGA scores for the two groups decreased by 1.8 and 1.7 points, respectively, and the IGA success rate was 53.3 % in both groups. There were no significant differences between the BL-PDT and RL-PDT groups in any measure of effectiveness. However, the BL-PDT group exhibited more severe adverse effects, especially pain and hyperpigmentation. CONCLUSIONS: BL-PDT and RL-PDT have similar efficacies in moderate-to-severe acne vulgaris and are particularly effective for inflammatory acne lesions. RL-PDT benefits from milder adverse effects than those of BL-PDT.

4.
EMBO Mol Med ; 16(9): 2146-2169, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39148004

RESUMEN

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.


Asunto(s)
Neutrófilos , Activador de Tejido Plasminógeno , Animales , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Humanos , Ratones , Activador de Tejido Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Proteínas/metabolismo , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Modelos Animales de Enfermedad , Fibrinolíticos/farmacología , Glicoproteínas/metabolismo , Ratones Endogámicos C57BL , Accidente Cerebrovascular Isquémico/tratamiento farmacológico
5.
Int J Psychophysiol ; 203: 112414, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39134177

RESUMEN

In the present study, we aimed to investigate whether long-term music training could improve audio-visual speech integration in Chinese, using event-related brain potential (ERP) measurements. Specifically, we recruited musicians and non-musicians to participate in our experiment where visual Chinese characters were presented simultaneously with congruent or incongruent speech sounds. In order to maintain participants' focus on both auditory and visual modalities, they were instructed to perform a probe detection task. Our study revealed that for the musicians, audiovisual incongruent stimuli elicited larger N1 and N400 amplitudes compared to audiovisual congruent stimuli. Conversely, for the non-musicians, only a larger N400 amplitude was observed for incongruent stimuli relative to congruent stimuli, without a significant difference in N1 amplitude. Furthermore, correlation analyses indicated that more years of music training was associated with a larger N1 effect for the musicians. These results suggest that musicians were capable of detecting character-speech sound incongruence at an earlier time window compared to non-musicians. Overall, our findings provide compelling evidence that music training is associated with better integration of visual characters and auditory speech sounds in language processing.


Asunto(s)
Electroencefalografía , Música , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Percepción Auditiva/fisiología , Percepción del Habla/fisiología , Potenciales Evocados/fisiología , Estimulación Acústica , Percepción Visual/fisiología , Estimulación Luminosa/métodos
6.
Molecules ; 29(16)2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39202888

RESUMEN

The efficiency and reproducibility of perovskite solar cells (PSCs) are significantly influenced by the purity of lead iodide (PbI2) in the raw materials used. Pb(OH)I has been identified as the primary impurity generated from PbI2 in water-based synthesis. Consequently, a comprehensive investigation into the impact of Pb(OH)I impurities on film and device performance is essential. In this study, PbI2, with varying stoichiometries, was synthesized to examine the effects of different Pb(OH)I levels on perovskite device performance. The characterization results revealed that even trace amounts of Pb(OH)I impede the formation of precursor prenucleation clusters. These impurities also increase the energy barrier of the α-phase and facilitate the transition of the intermediate phase to the δ-phase. These effects result in poor perovskite film morphology and sub-optimal photovoltaic device performance. To address these issues, a cost-effective method for preparing high-stoichiometry PbI2 was developed. The formation of Pb(OH)I was effectively inhibited through several strategies: adjusting solution pH and temperature, modifying material addition order, simplifying the precipitation-recrystallization process, and introducing H3PO2 as an additive. These modifications enabled the one-step synthesis of high-purity PbI2. PSCs prepared using this newly synthesized high-stoichiometry PbI2 demonstrated photovoltaic performance comparable to those fabricated with commercial PbI2 (purity ≥ 99.999%). Our novel method offers a cost-effective alternative for synthesizing high-stoichiometry PbI2, thereby providing a viable option for the production of high-performance PSCs.

7.
J Imaging Inform Med ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39020156

RESUMEN

Meniscal injury is a common cause of knee joint pain and a precursor to knee osteoarthritis (KOA). The purpose of this study is to develop an automatic pipeline for meniscal injury classification and localization using fully and weakly supervised networks based on MRI images. In this retrospective study, data were from the osteoarthritis initiative (OAI). The MR images were reconstructed using a sagittal intermediate-weighted fat-suppressed turbo spin-echo sequence. (1) We used 130 knees from the OAI to develop the LGSA-UNet model which fuses the features of adjacent slices and adjusts the blocks in Siam to enable the central slice to obtain rich contextual information. (2) One thousand seven hundred and fifty-six knees from the OAI were included to establish segmentation and classification models. The segmentation model achieved a DICE coefficient ranging from 0.84 to 0.93. The AUC values ranged from 0.85 to 0.95 in the binary models. The accuracy for the three types of menisci (normal, tear, and maceration) ranged from 0.60 to 0.88. Furthermore, 206 knees from the orthopedic hospital were used as an external validation data set to evaluate the performance of the model. The segmentation and classification models still performed well on the external validation set. To compare the diagnostic performances between the deep learning (DL) models and radiologists, the external validation sets were sent to two radiologists. The binary classification model outperformed the diagnostic performance of the junior radiologist (0.82-0.87 versus 0.74-0.88). This study highlights the potential of DL in knee meniscus segmentation and injury classification which can help improve diagnostic efficiency.

9.
ACS Biomater Sci Eng ; 10(8): 5274-5289, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39056174

RESUMEN

Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein-protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.


Asunto(s)
Neoplasias de la Mama , Perfilación de la Expresión Génica , Inmunoterapia , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Inmunoterapia/métodos , Pronóstico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología
10.
Artículo en Inglés | MEDLINE | ID: mdl-38916765

RESUMEN

The present study aimed to explore the potential neural correlates during feedback evaluation during decision-making under risk and ambiguity in MCI. Nineteen individuals with MCI and twenty age-matched HCs were enrolled. Decision-making performance under risk and ambiguity was examined with the modified game of dice task (GDT) and an Iowa gambling task (IGT). Using task-related EEG data, reward positivity (RewP) and feedback P3 (fb-P3) were used to characterize participants' motivation and allocation of cognitive resources. Also, response time and event-related oscillation (ERO) were used to evaluate information processing speed, and the potent of post-feedback information integration and behavioral modulation. MCI patients had lower RewP (p = 0.022) and fb-P3 (p = 0.045) amplitudes in the GDT than HCs. Moreover, the amount and valence of feedback modulated the RewP (p = 0.008; p = 0.017) and fb-P3 (p < 0.001; p < 0.001). In the IGT, in addition to the significantly reduced fb-P3 observed in MCI patients (p = 0.010), the amount and valence of feedback modulated the RewP (p = 0.002; p = 0.020). Furthermore, MCI patients took longer to make decisions (t = 2.15, p = 0.041). The ERO analysis revealed that delta power was reduced in MCI (GDT: p = 0.045; p = 0.011). The findings suggest that, during feedback evaluation when making risky and ambiguous decisions, motivation, allocation of cognitive resources, information processing and neuronal excitability were attenuated in MCI. It implies that neural activity related to decision making was compromised in MCI.

11.
Toxicol Lett ; 398: 69-81, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38909920

RESUMEN

Sodium para-aminosalicylic acid (PAS-Na) treatment for manganese (Mn) intoxication has shown efficacy in experimental and clinical studies, giving rise to additional studies on its efficacy for lead (Pb) neurotoxicity and its associated mechanisms of neuroprotection. The difference between PAS-Na and other metal complexing agents, such as edetate calcium sodium (CaNa2-EDTA), is firstly that PAS-Na can readily pass through the blood-brain barrier (BBB), and complex and facilitate the excretion of manganese and lead. Secondly, PAS-Na has anti-inflammatory effects. Recent studies have broadened the understanding on the mechanisms associated with efficacy of PAS-Na. The latter has been shown to modulate multifarious manganese- and lead- induced neurotoxicity, via its anti-apoptotic and anti-inflammatory effects, as well as its ability to inhibit pyroptosis, and regulate abnormal autophagic processes. These observations provide novel scientific bases and new concepts for the treatment of lead, mercury, copper, thallium, as well as other toxic encephalopathies, and implicate PAS-Na as a compound with greater prospects for clinical medical application.


Asunto(s)
Ácido Aminosalicílico , Intoxicación por Plomo , Intoxicación por Manganeso , Humanos , Animales , Ácido Aminosalicílico/uso terapéutico , Intoxicación por Manganeso/tratamiento farmacológico , Intoxicación por Plomo/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Manganeso/toxicidad
12.
Acta Psychol (Amst) ; 248: 104340, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38870685

RESUMEN

Numerous studies have demonstrated the influence of musical expertise on spoken language processing; however, its effects on reading comprehension remain largely unexplored. This study aims to investigate the role of musical expertise in sentence comprehension, particularly concerning the processing of temporal order. Using two self-paced reading experiments, we examined individuals' responses to two-clause sentences connected by the temporal connectives "before" or "after". "After" sentences consistently presented events in their actual order of temporal occurrence, while "before" sentences described events in reverse temporal order. In both experiments, our analyses of reading times consistently uncovered a significant temporal order effect, with words immediately following the temporal connectives being processed slower in "before" sentences compared to "after" sentences. This suggests the presence of immediate online processing costs associated with "before" sentences. Notably, these processing costs were found to be attenuated in individuals with musical expertise compared to those without. However, analyses of comprehension accuracy showed no advantage of musicians over non-musicians. Specifically, in Experiment 1, the two groups showed no difference in comprehension accuracy, while in Experiment 2, musicians exhibited lower accuracy rates compared to non-musicians in both "before" and "after" sentences. These results suggest that musical expertise may attenuate online processing costs associated with complex linguistic constructs, but could not promote reading accuracy. We concluded that music training is associated with a restricted effect on written sentence comprehension.


Asunto(s)
Comprensión , Música , Lectura , Humanos , Comprensión/fisiología , Masculino , Femenino , Adulto , Adulto Joven , Tiempo de Reacción/fisiología
13.
Brain Res ; 1838: 148988, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38729332

RESUMEN

Poly (ADP-ribose) polymerase (PARP) inhibitors have potent anti-inflammatory effects, including the suppression of brain microglial activation. Veliparib, a well-known PARP1/2 inhibitor, exhibits particularly high brain penetration, but its effects on stroke outcome is unknown. Here, the effects of veliparib on the short-term outcome of intracerebral hemorrhage (ICH), the most lethal type of stroke, were investigated. Collagenase-induced mice ICH model was applied, and the T2-weighted magnetic resonance imaging was performed to evaluate lesion volume. Motor function and hematoma volume were also measured. We further performed immunofluorescence, enzyme linked immunosorbent assay, flow cytometry, and blood-brain barrier assessment to explore the potential mechanisms. Our results demonstrated veliparib reduced the ICH lesion volume dose-dependently and at a dosage of 5 mg/kg, veliparib significantly improved mouse motor function and promoted hematoma resolution at days 3 and 7 post-ICH. Veliparib inhibited glial activation and downregulated the production of pro-inflammatory cytokines. Veliparib significantly decreased microglia counts and inhibited peripheral immune cell infiltration into the brain on day 3 after ICH. Veliparib improved blood-brain barrier integrity at day 3 after ICH. These findings demonstrate that veliparib improves ICH outcome by inhibiting inflammatory responses and may represent a promising novel therapy for ICH.


Asunto(s)
Bencimidazoles , Hemorragia Cerebral , Hematoma , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Animales , Bencimidazoles/farmacología , Hemorragia Cerebral/tratamiento farmacológico , Ratones , Hematoma/tratamiento farmacológico , Masculino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inflamación/tratamiento farmacológico , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Ratones Endogámicos C57BL , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Citocinas/metabolismo
14.
Basic Clin Pharmacol Toxicol ; 135(1): 81-97, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38780039

RESUMEN

We established experimental models of manganese (Mn) and iron (Fe) exposure in vitro and in vivo, and addressed the effects of manganese and iron combined exposure on the synaptic function of pheochromocytoma derived cell line 12 (PC12) cells and rat cortex, respectively. We investigated the protective effect of sodium para-aminosalicylate (PAS-Na) on manganese and iron combined neurotoxicity, providing a scientific basis for the prevention and treatment of ferromanganese combined neurotoxicity. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of protein and mRNA related to synaptic damage. Y-maze novelty test and balance beam test were used to evaluate the motor and cognitive function of rats. Haematoxylin and eosin (H&E) and Nissl staining were performed to observe the cortical damage of rats. The results showed that the combined exposure of Mn and Fe in rats led to a synergistic effect, attenuating growth and development, and altering learning and memory as well as motor function. The combination of Mn and Fe also caused damage to the synaptic structure of PC12 cells, which is manifested as swelling of dendrites and axon terminals, and even lead to cell death. PAS-Na displayed some antagonistic effects against the Mn- and Fe-induced synaptic structural damage, growth, learning and memory impairment.


Asunto(s)
Ácido Aminosalicílico , Manganeso , Sinapsis , Animales , Ratas , Células PC12 , Sinapsis/efectos de los fármacos , Masculino , Ácido Aminosalicílico/farmacología , Manganeso/toxicidad , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Corteza Cerebral/metabolismo , Ratas Sprague-Dawley , Hierro/metabolismo , Fármacos Neuroprotectores/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Síndromes de Neurotoxicidad/prevención & control , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/patología , Modelos Animales de Enfermedad
15.
Nat Commun ; 15(1): 3557, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38670944

RESUMEN

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.


Asunto(s)
Pueblo Asiatico , Neoplasias Colorrectales , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Población Blanca , Humanos , Neoplasias Colorrectales/genética , Pueblo Asiatico/genética , Población Blanca/genética , Secuenciación del Exoma , Estudios de Casos y Controles , Transcriptoma , Mapeo Cromosómico , Masculino , Femenino , Pueblos del Este de Asia
16.
Food Chem ; 450: 139266, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-38653045

RESUMEN

90Sr and 210Pb are considered to be key radionuclides in internal exposure resulting from dietary intake, however, the established methods employed for their detection are time-comsuming. A method for the sequential separation of 90Sr and 210Pb using a Sr·spec resin by LSC measurement is developed, which is highly suitable for food safety monitoring as its minimal sample requirements. The sequential separation of Sr and Pb from the sample was using 0.05 mol/L HNO3 and 0.05 mol/L C6H5O7(NH4)3. The chemical recoveries of Sr and Pb measured using ICP-OES were 72-83% and 80-88%, respectively. The minimum detectable activities of 90Sr and 210Pb in the food sample were 36.2 mBq/kg and 28.6 mBq/kg, respectively, obtained from a 0.1 kg fresh sample and 300 min counting time. The method was validated using reference materials and compared with other methods. The feasibility of the developed method for other highly complex food matrices needs further investigation.


Asunto(s)
Radioisótopos de Plomo , Conteo por Cintilación , Radioisótopos de Estroncio , Radioisótopos de Estroncio/análisis , Radioisótopos de Estroncio/aislamiento & purificación , Conteo por Cintilación/instrumentación , Radioisótopos de Plomo/análisis , Contaminación Radiactiva de Alimentos/análisis , Análisis de los Alimentos
17.
J Neuroinflammation ; 21(1): 73, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528529

RESUMEN

BACKGROUND: Guillain-Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. METHODS: Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 - 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. RESULTS: P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. CONCLUSIONS: Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.


Asunto(s)
Síndrome de Guillain-Barré , Neuritis Autoinmune Experimental , Antagonistas del Receptor Purinérgico P2X , Animales , Humanos , Ratas , Linfocitos T CD8-positivos , Diferenciación Celular/efectos de los fármacos , Síndrome de Guillain-Barré/tratamiento farmacológico , Inflamasomas/efectos de los fármacos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Antagonistas del Receptor Purinérgico P2X/farmacología , Antagonistas del Receptor Purinérgico P2X/uso terapéutico , Nervio Ciático/metabolismo , Células Th17/efectos de los fármacos , Células Th17/metabolismo , Células TH1/efectos de los fármacos , Células TH1/metabolismo
18.
Hum Genomics ; 18(1): 25, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38486307

RESUMEN

With the development of next-generation sequencing technology, de novo variants (DNVs) with deleterious effects can be identified and investigated for their effects on birth defects such as congenital heart disease (CHD). However, statistical power is still limited for such studies because of the small sample size due to the high cost of recruiting and sequencing samples and the low occurrence of DNVs. DNV analysis is further complicated by genetic heterogeneity across diseased individuals. Therefore, it is critical to jointly analyze DNVs with other types of genomic/biological information to improve statistical power to identify genes associated with birth defects. In this review, we discuss the general workflow, recent developments in statistical methods, and future directions for DNV analysis.


Asunto(s)
Heterogeneidad Genética , Genómica , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento , Tamaño de la Muestra , Flujo de Trabajo
19.
bioRxiv ; 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38464054

RESUMEN

Alternative splicing is an important cellular process in eukaryotes, altering pre-mRNA to yield multiple protein isoforms from a single gene. However, our understanding of the impact of alternative splicing events on protein structures is currently constrained by a lack of sufficient protein structural data. To address this limitation, we employed AlphaFold 2, a cutting-edge protein structure prediction tool, to conduct a comprehensive analysis of alternative splicing for approximately 3,000 human genes, providing valuable insights into its impact on the protein structural. Our investigation employed state of the art high-performance computing infrastructure to systematically characterize structural features in alternatively spliced regions and identified changes in protein structure following alternative splicing events. Notably, we found that alternative splicing tends to alter the structure of residues primarily located in coils and beta-sheets. Our research highlighted a significant enrichment of loops and highly exposed residues within human alternatively spliced regions. Specifically, our examination of the Septin-9 protein revealed potential associations between loops and alternative splicing, providing insights into its evolutionary role. Furthermore, our analysis uncovered two missense mutations in the Tau protein that could influence alternative splicing, potentially contributing to the pathogenesis of Alzheimer's disease. In summary, our work, through a thorough statistical analysis of extensive protein structural data, sheds new light on the intricate relationship between alternative splicing, evolution, and human disease.

20.
Neuropharmacology ; 250: 109908, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38492883

RESUMEN

Decreased hippocampal synaptic plasticity is an important pathological change in stress-related mood disorders, including major depressive disorder. However, the underlying mechanism is unclear. PGC-1α, a transcriptional coactivator, is a key factor in synaptic plasticity. We investigated the relationships between changes in hippocampal PGC-1α expression and depressive-like and stress-coping behaviours, and whether they are related to hippocampal synapses. Adeno-associated virus was used to alter hippocampal PGC-1α expression in male C57BL/6 mice. The sucrose preference test and forced swimming test were used to assess their depressive-like and stress-coping behaviours, respectively. Immunohistochemistry and stereology were used to calculate the total number of excitatory synapses in each hippocampal subregion (the cornu ammonis (CA) 1, CA3, and dentate gyrus). Immunofluorescence was used to visualize the changes in dendritic structure. Western blotting was used to detect the expression of hippocampal PGC-1α and mitochondrial-associated proteins, such as UCP2, NRF1 and mtTFAs. Our results showed that mice with downregulated PGC-1α expression in the hippocampus exhibited depressive-like and passive stress-coping behaviours, while mice with upregulated PGC-1α in the hippocampus exhibited increased stress-coping behaviours. Moreover, the downregulation of hippocampal PGC-1α expression resulted in a decrease in the number of excitatory synapses in the DG and in the protein expression of UCP2 in the hippocampus. Alternatively, upregulation of hippocampal PGC-1α yielded the opposite results. This suggests that hippocampal PGC-1α is involved in regulating depressive-like and stress-coping behaviours and modulating the number of excitatory synapses in the DG. This provides new insight for the development of antidepressants.


Asunto(s)
Habilidades de Afrontamiento , Trastorno Depresivo Mayor , Animales , Masculino , Ratones , Giro Dentado , Trastorno Depresivo Mayor/metabolismo , Hipocampo/metabolismo , Ratones Endogámicos C57BL , Sinapsis/metabolismo
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