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JOURNAL/nrgr/04.03/01300535-202508000-00030/figure1/v/2024-09-30T120553Z/r/image-tiff Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death. However, there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation. Adeno-associated virus (AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa. The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function. To do this, we injected retinal degeneration 10 (rd10) mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark- and light-adapted electroretinogram, optical coherence tomography, and immunofluorescence. Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment, and the results from this analysis were verified by real-time polymerase chain reaction and western blotting. AAV2-PDE6B injection significantly upregulated PDE6ß expression, preserved electroretinogram responses, and preserved outer nuclear layer thickness in rd10 mice. Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception, and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice. Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways. Furthermore, the phototransduction-related proteins Pde6α, Rom1, Rho, Aldh1a1, and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment. Finally, Bax/Bcl-2, p-ERK/ERK, and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment. Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
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Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell-derived sarcomas that are sporadic or associated with Neurofibromatosis 1 (NF1) gene mutations. Traditional therapies are usually ineffective for treating MPNSTs, so new targets need to be identified for the treatment of MPNSTs. In the present study, the role of the mitochondrial translocator protein (TSPO) in the regulation of cell proliferation and the cell cycle in MPNSTs was investigated. TSPO expression was lower in MPNSTs than in NFs. Loss-of-function experiments revealed that TSPO deficiency promoted MPNST cell growth, migration, and invasion and influenced the cell cycle in vitro and in vivo. In addition, TSPO depletion suppressed cell apoptosis by downregulating the expression of caspase-3, caspase-8, HSP60, p27, p53, and BCL-2 and suppressed the cell cycle by upregulating CDK1, CDK2, CCNB1 and CCNA2. Furthermore, CDK1 was determined to be an upstream target of TSPO-mediated regulation via RNA-seq, qPCR, and Western blotting. Specifically, depletion of CDK1 weakened the effect of TSPO deficiency on cell proliferation and migration. More importantly, CDK1 knockdown induced significant cell cycle arrest in the G2/M phase. In summary, TSPO deficiency regulates the cell cycle in MPNSTs by targeting CDK1, which may be an effective molecular target for prognosis evaluation and treatment.
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Proteína Quinase CDC2 , Movimento Celular , Proliferação de Células , Receptores de GABA , Humanos , Proteína Quinase CDC2/metabolismo , Proteína Quinase CDC2/genética , Receptores de GABA/metabolismo , Receptores de GABA/genética , Camundongos , Animais , Movimento Celular/genética , Linhagem Celular Tumoral , Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Progressão da Doença , Masculino , Feminino , Neoplasias de Bainha Neural/genética , Neoplasias de Bainha Neural/patologia , Neoplasias de Bainha Neural/metabolismo , Camundongos NusRESUMO
BACKGROUND: 11ß-hydroxylase deficiency (11ß-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11ß-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11ß-OHD. METHODS: Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants. RESULTS: Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269-143,957,579 (hg19) with the insertion of 'ACAG' (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T. CONCLUSIONS: Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11ß-OHD genetic diagnosis and carrier sequencing.
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Hiperplasia Suprarrenal Congênita , Sequenciamento de Nucleotídeos em Larga Escala , Esteroide 11-beta-Hidroxilase , Humanos , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/sangue , Feminino , Masculino , Esteroide 11-beta-Hidroxilase/genética , Linhagem , Adulto , Prognóstico , Mutação de Sentido IncorretoRESUMO
Inflammation and Schwann cell apoptosis play critical roles in neuropathic pain after sciatic nerve injury. This study aimed to explore the function and mechanism of cimifugin in lipopolysaccharide (LPS)-stimulated rat Schwann cells and sciatic nerves of rats treated with chronic constriction injury (CCI). Thermal, mechanical and cold hyperalgesia of rats in response to cimifugin or mecobalamin (the positive drug control) treatment were evaluated through behavioral tests. H&E staining of sciatic nerves was performed for pathological observation. ELISA was conducted to assess concentrations of inflammatory cytokines in rat serum and sciatic nerves. The intensity of S100ß in sciatic nerves was determined using immunohistochemistry. Flow cytometry analysis was conducted for detection of Schwann cell apoptosis. RT-qPCR was performed to measure mRNA levels of inflammatory factors in Schwann cells. Immunofluorescence staining was performed to detect cellular p65/NF-κB activity. Western blotting was performed to quantify protein levels of apoptotic markers and factors associated with the NF-κB and MAPK pathways in rat nerves and Schwann cells. As shown by experimental data, cimifugin mitigated thermal, mechanical and cold hyperalgesia of CCI rats. Cimifugin repressed inflammatory cell infiltration, reduced proinflammatory cytokine levels while increasing anti-inflammatory factor (IL-10) level in serum or sciatic nerves of CCI rats. Cimifugin enhanced S100ß expression and downregulated apoptotic markers in vivo. The anti-inflammatory and anti-apoptotic properties of cimifugin were verified in the LPS-stimulated Schwann cells. Moreover, cimifugin suppressed nuclear translocation of p65 NF-κB in vitro and repressed the phosphorylation of IκB, p65 NF-κB, p38 MAPK, ERK1/2, as well as JNK in CCI rats. In conclusion, cimifugin alleviates neuropathic pain after sciatica by suppressing inflammatory response and Schwann cell apoptosis via inactivation of NF-κB and MAPK pathways.
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Water pH is a critical environmental factor for aquaculture. Acidification is a pressing environmental issue that poses significant threats to the aquaculture industry. Since the outbreaks of disease generally accompany with environmental stress, comparative transcriptome analyses were performed to investigate the combined effects of low pH stress and bacterial infection on the transcriptional changes of hemocytes in the economically important crab Eriocheir sinensis. The results revealed that the immune deficiency (IMD) pathway and prophenoloxidase (proPO) system was activated to defense against Vibro parahaemolyticus even when crabs were subjected to low pH stress, whereas low pH stress resulted in the disorder of Toll-like receptor (TLR) pathway upon V. parahaemolyticus infection. Moreover, low pH stress might weaken crabs' defense against V. parahaemolyticus by inhibiting the up-regulation of crustin and suppressing the expression of lysozyme, and disturb the maintaining of protein homeostasis through the transcriptional decrement of a batch of heat shock proteins (HSPs). It is worth noting that both V. parahaemolyticus infection and low pH stress might suppress the energy metabolism in the hemocytes via inhibiting the expression of critical enzymes, dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex and fumarase, in the tricarboxylic acid (TCA) cycle. This study provides novel understandings concerning the transcriptional changes of hemocyte in E. sinensis subjected to a combination of low pH stress and V. parahaemolyticus infection as well as contribute to optimize the management strategies for the prevention and control of diseases in E. sinensis farming.
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Background: Receptor-interacting protein kinases (RIPKs) and mixed-lineage kinase domain-like protein (MLKL) are crucial in regulating innate immune responses and cell death signaling (necroptosis and apoptosis), and are potential candidates for genetic improvement in breeding programs. Knowledge about the RIPK family and MLKL in sea cucumber remains limited. Methods: We searched the genomes of sea cucumber Holothuria leucospilota for genes encoding RIPKs and MLKL, performed phylogenetic tree, motif and functional domain analyses, and examined tissue distribution and embryonic development patterns using qPCR. Results: RIPK5 (Hl-RIPK5), RIPK7 (Hl-RIPK7) and MLKL (Hl-MLKL) were identified in sea cucumber H. leucospilota. Hl-RIPK5 and Hl-RIPK7 were mainly expressed in coelomocytes, suggesting that they play a role in innate immunity, whereas Hl-MLKL exhibited relatively low expression across tissues. During embryonic development, Hl-MLKL was highly expressed from the 2-cell stage to the morula stage, while Hl-RIPK5 and Hl-RIPK7 were primarily expressed after the morula stage, indicating different roles in embryonic development. In primary coelomocytes, Hl-RIPK5 transcriptional activity was significantly depressed by LPS, poly(I:C), or pathogen Vibrio harveyi. Hl-RIPK7 expression levels were unchanged following the same challenges. Hl-MLKL mRNA levels were significantly decreased with poly(I:C) or V. harveyi, but did not change with LPS. Conclusions: These findings provide valuable insights into the evolutionary tree and characterization of RIPK and MLKL genes in sea cucumber, contributing to the broader understanding of the RIPK gene family and MLKL in ancient echinoderms.
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Holothuria , Necroptose , Filogenia , Proteínas Quinases , Proteína Serina-Treonina Quinases de Interação com Receptores , Animais , Holothuria/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Necroptose/genética , Imunidade Inata/genética , Apoptose/genética , Transdução de Sinais/genéticaRESUMO
Purpose: Left ventricular ejection fraction (LVEF) strongly predicts cardiac events. However, conflicting findings exist regarding the prognostic value of the LVEF reserve (ΔLVEF) when measured by gated single-photon emission computed tomography myocardial perfusion imaging (SPECT G-MPI). In particular, data related to the prognostic value of ΔLVEF when measured by SPECT in patients with reduced LVEF are scarce. In this study, we aimed to evaluate the prognostic value of ΔLVEF when acquired by SPECT G-MPI in patients with coronary artery disease (CAD) and a LVEFStress < 60%. Methods: We retrospectively recruited 260 consecutive patients diagnosed with CAD by coronary angiography (CAG) and a LVEFStress < 60%, as determined by SPECT G-MPI. These patients were followed up for 33.4 ± 7.6 months. The patients were divided into two groups (ΔLVEF > 0% and ΔLVEF ≤ 0%), and survival analyses were conducted. The primary endpoints were major adverse cardiac events (MACEs), a composite of all-cause death, nonfatal myocardial infarction, unplanned coronary revascularization, and hospitalization for unstable angina. Results: We observed 69 MACEs (26.5%). The cumulative incidence of MACEs in patients with ΔLVEF ≤ 0% was significantly higher than in patients with ΔLVEF > 0% (P = 0.042). Multivariate Cox regression further revealed that a ΔLVEF ≤ 0% represented an independent predictor of MACEs (adjusted hazard ratio [HR]: 1.276; 95% confidence interval [CI]: (1.006, 1.618), P = 0.045). Adding a ΔLVEF ≤ 0% to traditional myocardial perfusion and function variables evaluated by MPI significantly improved the ability to predict MACEs (P = 0.044). Conclusions: Determining ΔLVEF by SPECT G-MPI was associated with MACEs and improved risk stratification compared to prediction models based on traditional perfusion and functional parameters in CAD patients with left ventricular dysfunction, particularly those with no or mild myocardial ischemia.
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Global warming significantly impacts amphibian populations globally, and modeling helps understand these effects. Here, we used MaxEnt and MigClim models to predict the impact of climate change on habitat suitability for Hoplobatrachus chinensis. Our results indicate that temperature is a key factor affecting H. chinensis distribution. Increasing temperatures positively correlated with habitat suitability, with suitable habitat expanding northward by 2060 while maintaining suitability in the southern parts of the range. We found a 25.18% overlap between the current potential suitable habitat of H. chinensis and agricultural wetlands. Our model indicated that H. chinensis might be able to track shifts in suitable habitats under climate change given a 15 km dispersal ability per generation. Climate change will likely expand suitable habitat for H. chinensis. Our predictions offer important guidance for the conservation of the species, especially for the integrated role of natural and agricultural wetlands such as rice paddies.
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BACKGROUND: Physicians and patients are eager to know likely functional outcomes at different stages of treatment after acute ischemic stroke (AIS). The aim of this study was to develop and validate a 2-step model to assess prognosis at different time points (pre- and posttreatment) in patients with AIS having endovascular thrombectomy (EVT). METHODS: The prediction model was developed using a prospective nationwide Chinese registry (ANGEL-ACT). A total of 1676 patients with AIS who underwent EVT were enrolled into the study and randomly divided into development (n=1351, 80%) and validation (n=325, 20%) cohorts. Multivariate logistic regression, least absolute shrinkage and selection operator regression, and the random forest recursive feature elimination algorithm were used to select predictors of 90-day functional independence. We constructed the model via discrimination, calibration, decision curve analysis, and feature importance. RESULTS: The incidence of 90-day functional independence was 46.3% and 40.6% in the development and validation cohorts, respectively. The area under the curve (AUC) for model 1 which included 5 pretreatment predictors (age, admission National Institutes for Health Stroke Scale score, admission glucose level, admission systolic blood pressure, and Alberta Stroke Program Early Computed Tomography score) was 0.699 (95% confidence interval [CI], 0.668-0.730) in the development cohort and 0.658 (95% CI, 0.592-0.723) in the validation cohort. Two treatment-related predictors (time from stroke onset to puncture and successful reperfusion) were added to model 2 which had an AUC of 0.719 (95% CI, 0.688-0.749) and 0.650 (95% CI, 0.585-0.716) in the development cohort and validation cohorts, respectively. CONCLUSIONS: The 2-step prediction model could be useful for predicting the functional independence in patients with AIS 90-days after EVT.
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The growth rate of young ruminants has been associated with production performance in later life, with recent studies highlighting the importance of rumen microbes in supporting the health and growth of ruminants. However, the specific role of rumen epithelium bacteria and microbiota-host interactions in influencing the early life growth rate of ruminants remains poorly understood. In this study, we investigated the rumen fermentation pattern, microbiota characteristics, and global gene expression profiles of the rumen epithelium in 6-month-old goats with varying growth rates. Our results showed that goats with high average daily gain (HADG) exhibited higher rumen propionate concentrations. Goats with low average daily gain (LADG) had the higher relative abundances of rumen epithelium bacteria genera U29-B03 and Quinella, while exhibiting a lower relative abundance of Lachnospiraceae UCG-009. In the rumen fluid, the relative abundances of bacteria genus Alloprevotella were lower and Desulfovibrio were higher in LADG goats compared to HADG goats. Additionally, the relative abundance of fungal genus Symmetrospora was lower in LADG goats compared to HADG goats. Transcriptome analysis showed that 415 genes were differentially expressed between LADG and HADG goats, which were enriched in functions related to cell junction and cell adhesion, etc. Correlation analysis revealed that rumen epithelium bacteria genera UCG-005 and Candidatus Saccharimonas were negatively associated, while Lachnospiraceae NK3A20 group and Oscillospiraceae NK4A214 group were positively associated with average daily gain (ADG) and genes related to barrier function. The rumen fluid bacteria genus Alloprevotella was positively correlated, while Desulfovibrio was negatively correlated with rumen propionate and ammoniacal nitrogen (NH3-N) concentrations, as well as genes related to barrier function and short chain fatty acids (SCFAs) transport. In summary, our study reveals that the higher ruminal fermentation efficiency, improved rumen epithelial barrier functions, and enhanced SCFAs transport in HADG goats could be attributed to the rumen microbiota, particularly the rumen epithelium bacteria, such as Lachnospiraceae and Oscillospiraceae NK4A214 group.
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BACKGROUND: The C-reactive protein-to-albumin ratio (CAR) is a novel prognostic biomarker of systemic inflammation and nutritional status. The association between CAR and the long-term outcome of spontaneous intracerebral hemorrhage (ICH) remains unclear. METHODS: From January 2014 to September 2016, 497 patients with spontaneous ICH were enrolled in our study from 13 hospitals in Beijing. According to the CAR quartiles, patients were classified into four groups (Q1-Q4). Logistic regression was applied to analyze the relationship between different CAR levels and main outcome (90-day and 1-year mRS 4-6). Restricted cubic splines and receiver operating characteristic (ROC) curves of CAR for poor clinical outcomes were assessed. RESULTS: In the multivariate logistic regression model, compared with the lowest quartile of CAR, the adjusted odds ratios of the Q2, Q3, and Q4 group for 90-day mRS score of 4-6 were 3.64 (1.61-8.23), 3.83 (1.67-8.77), and 8.91 (3.85-20.64). In terms of 1-year mRS score of 4-6, compared with the lowest quartile of CAR, the adjusted odds ratios of the Q3 and Q4 group were 3.31 (1.33-8.22) and 6.87 (2.81-16.78). CONCLUSIONS: A high CAR level was associated with a high risk of long-term adverse prognosis in patients with ICH, and the risk of ICH poor outcome increased steadily with CAR rising in a certain range, and maintained in a high level thereafter.
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BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.
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Biomarcadores Tumorais , Carcinoma de Células Renais , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Prognóstico , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Biomarcadores Tumorais/genética , Transdução de Sinais/genética , Masculino , Feminino , Biologia Computacional , Perfilação da Expressão Gênica , Bases de Dados Genéticas , Pessoa de Meia-Idade , Estimativa de Kaplan-MeierRESUMO
BACKGROUND: Melasma is a common and chronic pigmentary disorder with complex pathogenesis, and the relationship between melasma and metabolic syndrome remains elusive. Thus, metabolomics might contribute to the early detection of potential metabolic abnormalities in individuals with melasma. OBJECTIVE: The present study aims to analyze changes in plasma metabolites of female melasma patients and identify disease markers as well as explore potential therapeutic targets. METHODS: Plasma samples from 20 female patients with melasma and 21 healthy female controls that were comparable in terms of age and body mass index were collected for untargeted metabolomics investigations. Ultra-high performance liquid chromatography-mass spectrometry was used to analyze metabolites in the plasma. Metabolic pathway analyses were employed to identify significantly differentially expressed metabolites in melasma patients. Receiver operating characteristic curves were constructed, and correlation analyses were performed using the modified Melasma Area and Severity Index and oxidative stress levels. RESULTS: In contrast to healthy subjects, melasma patients showed significant alterations in 125 plasma metabolites, including amino acids, lipids, and carbohydrate-related metabolites. KEGG pathway analysis suggested that primary pathways associated with the development of melasma include tryptophan metabolism, as well as the biosynthesis of phenylalanine, tyrosine, and tryptophan. Importantly, based on receiver operating characteristic curves and correlation analyses, several metabolites were identified as robust biomarkers for melasma. CONCLUSION: Collectively, this study identified significant changes in plasma metabolites in melasma patients, providing new insights into the pathogenesis of melasma and opening novel therapeutic avenues.
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BACKGROUND: The significant morbidity and mortality rates of acute intracerebral hemorrhage (ICH) are well-known around the world. The link between gut microbiota and different types of strokes is becoming more studied. The goal of this study was to look at the relationships between intestinal flora and early-stage mild-to-moderate ICH (emICH), and to provide a new perspective for adjunctive treatment of emICH. METHODS: Fecal samples from 100 participants with emICH (n=50) and healthy individuals (n=50) in this study were collected as well as analyzed utilizing 16S rRNA gene amplicon sequencing in order to characterize the gut microbial community. RESULTS: Distinct microbial communities are present within each group, with emICH patients exhibiting a diminished diversity and uniformity in their microbial profiles. A notable shift in the gut microbiota composition of emICH patients has been observed, characterized by an upsurge in pro-inflammatory microbes belonging to the Euryarchaeota phylum and a concurrent decline in beneficial Bacteroidetes species. Concurrently, significant associations and patterns among operational taxonomic units (OTUs) were identified in emICH patients. A panel of biomarkers (WAL_1855D, Methanobrevibacter, Streptococcus, Bacteroides, Coprococcus, Lachnospira) has been effectively utilized to distinguish emICH patients from healthy individuals, with an area under the curve (AUC) of 0.845. Additionally, an analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation uncovered several perturbed pathways in emICH patients, predominantly those related to metabolic processes and the inflammatory response. Moreover, predictive profiling of the microbiome's phenotypic traits suggests that emICH patients are likely to harbor a higher prevalence of Gram-negative bacteria and potential opportunistic pathogens compared to healthy controls. CONCLUSIONS: The gut microbiota ecosystem of emICH patients is disrupted, characterized primarily by an increase in pro-inflammatory microbiota, elevated inflammatory signaling pathways, and metabolic dysregulation. Furthermore, microbiota modulation may be seen as a novel approach for the adjunctive treatment of emICH.
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Bactérias , Hemorragia Cerebral , Disbiose , Fezes , Microbioma Gastrointestinal , Ribotipagem , Humanos , Projetos Piloto , Masculino , Feminino , Fezes/microbiologia , Pessoa de Meia-Idade , Hemorragia Cerebral/microbiologia , Idoso , Estudos de Casos e Controles , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Índice de Gravidade de Doença , RNA Ribossômico 16S/genética , Eixo Encéfalo-IntestinoRESUMO
With the development of educational technology, machine learning and deep learning provide technical support for traditional classroom observation assessment. However, in real classroom scenarios, the technique faces challenges such as lack of clarity of raw images, complexity of datasets, multi-target detection errors, and complexity of character interactions. Based on the above problems, a student classroom behavior recognition network incorporating super-resolution and target detection is proposed. To cope with the problem of unclear original images in the classroom scenario, SRGAN (Super Resolution Generative Adversarial Network for Images) is used to improve the image resolution and thus the recognition accuracy. To address the dataset complexity and multi-targeting problems, feature extraction is optimized, and multi-scale feature recognition is enhanced by introducing AKConv and LASK attention mechanisms into the Backbone module of the YOLOv8s algorithm. To improve the character interaction complexity problem, the CBAM attention mechanism is integrated to enhance the recognition of important feature channels and spatial regions. Experiments show that it can detect six behaviors of students-raising their hands, reading, writing, playing on their cell phones, looking down, and leaning on the table-in high-definition images. And the accuracy and robustness of this network is verified. Compared with small-object detection algorithms such as Faster R-CNN, YOLOv5, and YOLOv8s, this network demonstrates good detection performance on low-resolution small objects, complex datasets with numerous targets, occlusion, and overlapping students.
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Cobalt (Co) is widely used in Fischer-Tropsch synthesis (FTS), converting synthesis gas, carbon monoxide + hydrogen (CO + H2), to long-chain hydrocarbons. The adsorption of CO on the Co surface is the key step in FTS. In this work, the effect of CO adsorption sites on the reactions between CO and H2 was investigated by using density functional theory (DFT). The energetics and structures of the reactions between the adsorbed CO (CO*) and H2/adsorbed H2 (H2*)/adsorbed H atom (H*) were calculated. The results show that the reaction between CO* and H2 is initiated by the molecular adsorption of H2 on the Co surface. The reactions between CO* and H2*/H* are influenced by CO adsorption sites. For the reaction system of CO* + H2*, it has the lowest reaction barrier when CO is adsorbed at the hcp site, while for CO* + H*, it has the lowest reaction barrier when CO is adsorbed on the top site. Kinetic analysis indicates that to improve the reactivity of CO + H2 in FTS, the adsorption of CO should be controlled to favour the top and bridge sites. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'.
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Interfacial engineering is of great concern in photovoltaic devices. Metal halide perovskite solar cells (PSCs) have garnered much attention due to their impressive development in power conversion efficiencies (PCEs). Benefiting from high electron mobility and good energy-level alignment with perovskite, aqueous SnO2 as an electron transport layer has been widely used in n-i-p perovskite solar cells. However, the interfacial engineering of an aqueous SnO2 layer on PSCs is still an obscure and confusing process. Herein, we proposed the preparation of n-i-p perovskite solar cells with different concentrations of SnO2 as electron transport layers and achieved optimized PCE with an efficiency of 20.27%. I Interfacial engineering with regard to the SnO2 layer is investigated by observing the surface morphology, space charge-limited current (SCLC) with the use of an electron-only device, and time-resolved photoluminescence (TRPL) of perovskite films.
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BACKGROUND: To establish the pathological diagnosis of UTUC before treatment is profitable. At present, the conventional pathological diagnostic methods have certain problems. Besides, the urine-based DNA methylation test have been already utilized to detect bladder cancer. OBJECTIVE: To evaluate the sensitivity and specificity of DNA methylation plus 17 genes mutation test and compare the combined test with cytology. MATERIALS AND METHODS: We included 45 patients from April 2019 to May 2022, all of whom underwent radical nephroureterectomy (RNU), nephrectomy, diagnostic ureteroscopy or tissue biopsy. Before surgery, the urine samples were collected for DNA methylation plus 17 genes mutation test and cytology. The test performance was calculated, and comparative ROC curves were drawn. RESULTS: The median age of the patients was 67 years. The Kappa value of the DNA methylation plus 17 genes mutation test and tissue pathology was 0.59 (p<0.001). The sensitivity/specificity/PPV/NPV of DNA methylation plus 17 genes mutation test was 86/80/94/62% compared with 29/100/100/29% for cytology. The AUC of DNA methylation plus 17 genes mutation test was 0.829 (p<0.001).The mutated gene proportion of UTUC patients was 51.43% for TERT and 25.71% for TP53. CONCLUSION: The test performance of DNA methylation plus 17 genes mutation test was satisfactory, which may replace cytology in the future. Further multicenter studies with larger samples are needed to confirm the clinical value of this promising method. NOVELTY & IMPACT STATEMENTS: We evaluated the diagnostic efficacy of a urine-based liquid biopsy for the detection of UTUC and compared the combined test with cytology. We found satisfactory results and concluded that the test could partly replace cytology. Further studies are needed.