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Machine learning is an emerging tool in clinical psychology and neuroscience for the individualized prediction of psychiatric symptoms. However, its application in non-clinical populations is still in its infancy. Given the widespread morphological changes observed in psychiatric disorders, our study applies five supervised machine learning regression algorithms-ridge regression, support vector regression, partial least squares regression, least absolute shrinkage and selection operator regression, and Elastic-Net regression-to predict anxiety and depressive symptom scores. We base these predictions on the whole-brain gray matter volume in a large non-clinical sample (n = 425). Our results demonstrate that machine learning algorithms can effectively predict individual variability in anxiety and depressive symptoms, as measured by the Mood and Anxiety Symptoms Questionnaire. The most discriminative features contributing to the prediction models were primarily located in the prefrontal-parietal, temporal, visual, and sub-cortical regions (e.g. amygdala, hippocampus, and putamen). These regions showed distinct patterns for anxious arousal and high positive affect in three of the five models (partial least squares regression, support vector regression, and ridge regression). Importantly, these predictions were consistent across genders and robust to demographic variability (e.g. age, parental education, etc.). Our findings offer critical insights into the distinct brain morphological patterns underlying specific components of anxiety and depressive symptoms, supporting the existing tripartite theory from a neuroimaging perspective.
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Depressão , Substância Cinzenta , Humanos , Masculino , Feminino , Substância Cinzenta/diagnóstico por imagem , Depressão/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ansiedade/diagnóstico por imagem , Ansiedade/psicologia , AfetoRESUMO
Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized. Here, we classified CRC into specific glucose metabolic subtypes and identified the key regulators. 2228 carbohydrate metabolism-related genes were screened out from the GeneCards database, 202 of them were identified as prognosis genes in the TCGA database. Based on the expression patterns of the 202 genes, three metabolic subtypes were obtained by the non-negative matrix factorization clustering method. The C1 subtype had the worst survival outcome and was characterized with higher immune cell infiltration and more activation in extracellular matrix pathways than the other two subtypes. The C2 subtype was the most prevalent in CRC and was characterized by low immune cell infiltration. The C3 subtype had the smallest number of individuals and had a better prognosis, with higher levels of NRF2 and TP53 pathway expression. Secreted frizzled-related protein 2 (SFRP2) and thrombospondin-2 (THBS2) were confirmed as biomarkers for the C1 subtype. Their expression levels were elevated in high glucose condition, while their knockdown inhibited migration and invasion of HCT 116 cells. The analysis of therapeutic potential found that the C1 subtype was more sensitive to immune and PI3K-Akt pathway inhibitors than the other subtypes. To sum up, this study revealed a novel glucose-related CRC subtype, characterized by SFRP2 and THBS2, with poor prognosis but possible therapeutic benefits from immune and targeted therapies.
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Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Glucose , Transcriptoma , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glucose/metabolismo , Transcriptoma/genética , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Trombospondinas/genética , Trombospondinas/metabolismo , Movimento Celular/genética , Perfilação da Expressão Gênica , Células HCT116 , Transdução de Sinais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
Thermochemical water-splitting cycles are technically feasible for hydrogen production from water. However, the ultrahigh operation temperature and low efficiency seriously restrict their practical application. Herein, one-step and one-pot thermocatalytic water-splitting process is reported at water boiling condition catalyzed by single atomic Pt on defective In2O3. Water splitting into hydrogen is verified by D2O isotopic experiment, with an optimized hydrogen production rate of 36.4 mmol·h-1·g-1 as calculated on Pt active sites. It is revealed that three-centered Pt1In2 surrounding oxygen vacancy as catalytic ensembles promote the dissociation of the adsorbed water into H, which transfers to singlet atomic Pt sites for H2 production. Remaining OH groups on adjacent In sites from Pt1In2 ensembles undergoes OâO bonding, hyperoxide formation and diminishing via triethylamine oxidation, water re-adsorption for completing the catalytic cycle. Current work represents an isothermal and continuous thermocatalytic water splitting under mild condition, which can re-awaken the research interest to produce H2 from water using low-grade heat and competes with photocatalytic, electrolytic, and photoelectric reactions.
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Two 6,5,6-fused 1,2,3-triazine-3-oxides (4 and 6) were designed and synthesized via the reaction of o-aminoamidoximes with sodium nitrite. In addition, the ring-opening products (5, 7, and 8) derived from 1,2,3-triazine-3-oxides were isolated and characterized. A comprehensive exploration of the reaction mechanism governing the ring-opening process was performed through a combination of theoretical and experimental studies. Notably, compound 4 exhibited commendable detonation properties and low sensitivity, demonstrating its promising potential as an energetic material.
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BACKGROUND: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy. METHODS: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis. RESULTS: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774). CONCLUSIONS: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP.
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AVC Isquêmico , Pneumonia , Trombectomia , Humanos , Masculino , Feminino , AVC Isquêmico/cirurgia , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , Idoso , Estudos Retrospectivos , Trombectomia/métodos , Pessoa de Meia-Idade , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Valor Preditivo dos Testes , Nomogramas , Idoso de 80 Anos ou mais , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/epidemiologiaRESUMO
BACKGROUND: Implant choice for the fixation of femoral neck fracture is one of the most important management controversies. This study aims to evaluate and compare the short-term outcomes associated with the use of the Femoral Neck System (FNS), Multiple Cancellous Screws (MCS), and Dynamic Hip Screws (DHS) in treating femoral neck fractures in a young patient population. METHODS: From June 2018 to June 2021, a total of 120 surgeries for a primary femoral neck fracture were retrospectively analyzed. This review encompassed demographic details of the patients and the mechanisms behind the injuries. Key surgical parameters such as operation duration, intraoperative blood loss, fluoroscopy duration, and hospital stay were meticulously documented. The employed surgical technique was described. All patients were followed up at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Avascular necrosis of the femoral head (AVN), nonunion, malreduction, implant failure or other complications were noted. The functional status at the last follow-up was assessed using the Harris functional scoring criteria. RESULTS: There were 90 males and 30 females, with a mean age of 40.4 years. As to patient characteristics, there were no significant differences between the three groups. DHS group showed longer operation time(52.15 ± 4.80 min), more blood loss(59.05 ± 5.87 ml) and longer time of hospitalization(7.6 ± 0.90 d) than FNS group (39.65 ± 2.84 min, 45.33 ± 9.63 ml and 4.87 ± 0.48 d) and MCS group (39.45 ± 3.10 min, 48.15 ± 7.88 ml and 5.04 ± 0.49 d) (p < 0.05). In addition, the time of fluoroscopy in FNS group (15.45 ± 3.67) was less than that in MCS group (26.3 ± 4.76) and DHS group (27.1 ± 5.67) (p < 0.05). The cost of FNS group(44.51 ± 2.99 thousand RMB) was significantly higher than the MCS and DHS groups. The FNS, MCS and DHS groups showed a similar mean length of femoral neck shortening (LFNS) and Harris score. The FNS, MCS and DHS groups showed a similar mean rate of AVN and internal fixation failure. CONCLUSIONS: Following successful fracture reduction, FNS, MCS, and DHS are effective for in the young femoral neck fractures. No difference was found in complications between the three groups. However, the reduced fluoroscopy time associated with FNS contributes to shorter operation durations. The adoption of minimally invasive techniques correlates with decreased blood loss and shorter hospital stays. Nevertheless, these advantages may be offset by the potential economic burden they impose.
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Fraturas do Colo Femoral , Colo do Fêmur , Masculino , Feminino , Humanos , Adulto , Estudos Retrospectivos , Parafusos Ósseos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Resultado do TratamentoRESUMO
PURPOSE: To explore whether it is necessary to put drain tubes after posterior pedicle screw fixation of thoracolumbar fractures. METHODS: From April 2020 to January 2023, a total of 291 patients with recent thoracolumbar fractures (AO type-A or type-B) who received the pedicle screw fixation operation were enrolled retrospectively. In 77 patients, drain tubes were used in the pedicle screw fixation surgery, while no drain tubes were placed in the other group. After gleaning demographic information and results of lab examination and imageology examination, all data were put into a database. Independent-sample t-tests, Pearson Chi-Square tests, Linear regression analysis, and correlation analysis were then performed. RESULTS: Compared to the control group, the drainage group had significantly lower postoperative CRP levels (P = 0.047), less use of antipyretics (P = 0.035), higher ADL scores (P = 0.001), and lower NRS scores (P < 0.001) on the 6th day after surgery. Other investigation items, such as demographic information, operation time, intraoperative blood loss, body temperature, and other preoperative and postoperative lab results, showed no significant differences. CONCLUSIONS: The use of a drain tube in the pedicle screw fixation of thoracolumbar fractures is correlated with the improvement of patients' living and activity ability and the reduction of inflammation, postoperative fever and pain.
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Drenagem , Fixação Interna de Fraturas , Vértebras Lombares , Parafusos Pediculares , Fraturas da Coluna Vertebral , Vértebras Torácicas , Humanos , Masculino , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/efeitos adversos , Drenagem/instrumentação , Drenagem/métodos , Resultado do Tratamento , IdosoRESUMO
Several studies have examined the neural substrates of probabilistic decision-making, but few have systematically investigated the neural representations of the two objective attributes of probabilistic rewards, that is, the reward amount and the probability. Specifically, whether there are common or distinct neural activity patterns to represent the objective attributes and their association with the neural representation of the subjective valuation remains largely underexplored. We conducted two studies (nStudy1 = 34, nStudy2 = 41) to uncover distributed neural representations of the objective attributes and subjective value as well as their association with individual probability discounting rates. The amount and probability were independently manipulated to better capture brain signals sensitive to these two attributes and were presented simultaneously in Study 1 and successively in Study 2. Both univariate and multivariate pattern analyses showed that the brain activities in the superior parietal lobule (SPL), including the postcentral gyrus, were modulated by the amount of rewards and probability in both studies. Further, representational similarity analysis revealed a similar neural representation between these two objective attributes and between the attribute and valuation. Moreover, the SPL tracked the subjective value integrated by the hyperbolic function. Probability-related brain activations in the inferior parietal lobule were associated with the variability in individual discounting rates. These findings provide novel insights into a similar neural representation of the two attributes during probabilistic decision-making and perhaps support the common neural coding of stimulus objective properties and subjective value in the field of probabilistic discounting.
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Encéfalo , Recompensa , Humanos , Encéfalo/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Mapeamento Encefálico , Sistema Límbico , Imageamento por Ressonância MagnéticaRESUMO
This study explored whether amygdala reactivity predicted the greed personality trait (GPT) using both task-based and resting-state functional connectivity analyses (ntotal = 452). In Cohort 1 (n = 83), task-based functional magnetic resonance imaging (t-fMRI) results from a region-of-interest (ROI) analysis revealed no direct correlation between amygdala reactivity to fearful and angry faces and GPT. Instead, whole-brain analyses revealed GPT to robustly negatively vary with activations in the right ventromedial prefrontal cortex (vmPFC), supramarginal gyrus, and angular gyrus in the contrast of fearful + angry faces > shapes. Moreover, task-based psychophysiological interaction (PPI) analyses showed that the high GPT group showed weaker functional connectivity of the vmPFC seed with a top-down control network and visual pathways when processing fearful or angry faces compared to their lower GPT counterparts. In Cohort 2, resting-state functional connectivity (rs-FC) analyses indicated stronger connectivity between the vmPFC seed and the top-down control network and visual pathways in individuals with higher GPT. Comparing the two cohorts, bilateral amygdala seeds showed weaker associations with the top-down control network in the high group via PPI analyses in Cohort 1. Yet, they exhibited distinct rs-FC patterns in Cohort 2 (e.g., positive associations of GPT with the left amygdala-top-down network FC but negative associations with the right amygdala-visual pathway FC). The study underscores the role of the vmPFC and its functional connectivity in understanding GPT, rather than amygdala reactivity.
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Mapeamento Encefálico , Emoções , Humanos , Emoções/fisiologia , Mapeamento Encefálico/métodos , Córtex Pré-Frontal/diagnóstico por imagem , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Imageamento por Ressonância Magnética , Personalidade , Vias Neurais/diagnóstico por imagemRESUMO
Glioma is a highly aggressive primary malignant tumor. Migration-inducing gene-7 (Mig-7) is closely related to tumor invasion and metastasis. However, the detailed molecular mechanism of Mig-7-mediated promotion of glioma cell invasion requires further investigation. Therefore, this study aimed to investigate the molecular mechanism by which Mig-7 promotes invasion and growth of glioma tumor cells. After collecting 65 glioma tissues and 16 non-tumor tissues, the expression difference of Mig-7 between tumor tissues and non-tumor tissues was analyzed. The molecular mechanism of Mig-7 in tumor cells was investigated by knockdown or overexpression of Mig-7 in U87MG cells. Specifically, the expression levels of mitogen-activated protein kinase (MAPK) signaling pathway-related molecules were detected in cells that knocked down Mig-7. MTT, Transwell, and three-dimensional cell culture assays were used to detect the survival, migration, invasion, and tube formation of U87MG cells that overexpressed Mig-7 were treated with the MAPK signaling pathway inhibitors (SP600125, SCH772984, and SB202190). The effect of Mig-7 on the tumorigenic ability of U87MG cells was investigated by subcutaneous tumorigenic experiment in nude mice. The corresponding results indicated that Mig-7 expression was significantly higher in glioma tissues and cell lines compared to that in non-neoplastic brain tissues and normal glial cell lines. In U87MG cells, downregulation or overexpression of Mig-7 inhibited or promoted the expression of MMP-2, MMP-9, LAMC2, EphA2, and VE-cadherin, and phosphorylation levels of ERK1/2, JNK, and p38. Mig-7 overexpression promoted migration, invasion, cell viability, and tube formation, which were reversed by the MAPK signaling pathway inhibitors. Mig-7 overexpression promoted subcutaneous tumor growth in mice and upregulated the phosphorylation levels of ERK1/2, JNK, and p38 and the expression of Ki-67. These effects of Mig-7 overexpression were reversed by MAPK pathway inhibitors. Overall, these results suggest that Mig-7 may be a novel biomarker and potential therapeutic target for glioma, with the MAPK pathway playing a key role in the corresponding Mig-7 mechanism of action.
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Glioma , Proteínas Quinases Ativadas por Mitógeno , Animais , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Sistema de Sinalização das MAP Quinases , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Invasividade Neoplásica/genética , Transdução de Sinais , HumanosRESUMO
BACKGROUND: N6-methyladenosine (m6A) RNA modification regulators play an important role in many human diseases, and its abnormal expression can lead to the occurrence and development of diseases. However, their significance in pulpitis remains largely unknown. Here, we sought to identify and validate the m6A RNA regulatory network in pulpitis. METHODS: Gene expression data for m6A regulators in human pulpitis and normal pulp tissues from public GEO databases were analyzed. Bioinformatics analysis including Gene ontology (GO) functional, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed by R package, and Cytoscape software was used to study the role of m6A miRNA-mRNA regulatory network in pulpitis. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of key m6A regulators in collected human pulpitis specimens. RESULTS: Differential genes between pulpitis and normal groups were found from the GEO database, and further analysis found that there were significant differences in the m6A modification-related genes ALKBH5, METTL14, METTL3, METTL16, RBM15B and YTHDF1. And their interaction relationships and hub genes were determined. The hub m6A regulator targets were enriched in immune cells differentiation, glutamatergic synapse, ephrin receptor binding and osteoclast differentiation in pulpitis. Validation by qRT-PCR showed that the expression of methylases METTL14 and METTL3 was decreased, thus these two genes may play a key role in pulpitis. CONCLUSION: Our study identified and validated the m6A RNA regulatory network in pulpitis. These findings will provide valuable resource to guide the mechanistic and therapeutic analysis of the role of key m6A modulators in pulpitis.
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MicroRNAs , Pulpite , Humanos , Pulpite/genética , RNA Mensageiro/genética , Polpa Dentária , Biologia Computacional , Metiltransferases/genéticaRESUMO
Obesity increases the risk of colorectal cancer (CRC) by 30%. The obese tumor microenvironment compromises antitumor immunity by eliciting exhausted T cells (Tex). Hypothesizing that Dahuang Fuzi Baijiang decoction (DFB) is a combined classical prescription from the "Synopsis of Prescriptions of the Golden Chamber". We first determined that DFB regresses tumor growth in high-fat diet-induced obese mice by expanding the TIM3- subset with intermediate expression of programmed cell death-1 (PD-1int TIM3- ) and restricting the PD-1hi TIM3+ subset. Transcription factor 1 (TCF1) is highly expressed in the PD-1int TIM3- subset but is absent in PD-1hi TIM3+ cells. We next confirmed that progenitor PD-1int TCF+ cells robustly produce tumor necrosis factor-α (TNFα) and interferon-γ, whereas terminally differentiated PD-1int TCF+ cells have defects in generating TNFα. With transgenic ob/ob mice, we found that DFB produces cooperative efficacy with anti-PD-1 (αPD-1) by limiting the PD-1hi Tim3+ subset and amplifying the PD-1int TCF+ population. Finally, we defined the recombinant chemokine C-C-motif receptor 2 (CCR2)+ CD8+ subset as terminal Tex and identified that the differentiation from progenitor to terminal Tex is driven, at least in part, by the chemokine (C-C motif) ligand 2 (CCL2)/CCR2 axis. The CCR2 inhibitor enhances the response to αPD-1 by promoting the counts of progenitor Tex. Altogether, DFB dampens CCL2 and preserves progenitor Tex in the obese microenvironment to restrain CRC progression. These findings provide unambiguous evidence that the traditional Chinese formula DFB can prevent tumor progression by modulating adaptive immunity and establish a strong rationale for further clinical verification.
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Neoplasias Colorretais , Receptor Celular 2 do Vírus da Hepatite A , Animais , Linfócitos T CD8-Positivos , Diferenciação Celular , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Diterpenos , Medicamentos de Ervas Chinesas , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Camundongos , Obesidade/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Microambiente Tumoral , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Endovascular treatment is widely used in the treatment of intracranial aneurysms. However, neurosurgeons are sceptical about endovascular access via the radial artery. We performed a systematic review and meta-analysis to compare the effectiveness and safety of transradial and transfemoral artery access in patients with intracranial aneurysms. We systematically searched the PubMed, Embase, and Cochrane databases for studies comparing the two approaches. The primary outcome was total complications, and the secondary outcomes were access site complications, intracranial haemorrhage, stroke, thromboembolism, silent infarct, re-treatment rate, mortality, complete occlusion of intracranial aneurysms, procedure duration, and length of hospital stay. A random-effects model was used to assess the pooled data. Of the 100 identified studies, 6 were eligible (a total of 3764 participants). There were no significant differences in total complications(odds ratio [OR] = 0.69, 95% confidence interval [CI] [0.33, 1.45], p = 0.32), complete occlusion of intracranial aneurysms (OR = 1.02, 95%CI [0.77,1.37], p = 0.87), procedure duration (mean difference [MD] = - 6.24, 95%CI [- 14.75, - 1.54], p = 0.95), or length of hospital stay (MD = 2.204, 95%CI [- 0.05, 4.45], p = 0.95), access site complications (OR = 0.49, 95%CI [0.16, 1.52], p = 0.22), intracranial haemorrhage (OR = 1.07, 95%CI [0.49, 2.34], p = 0.86), stroke (OR = 0.59, 95%CI [0.20, 1.77], p = 0.35), thromboembolism (OR = 0.85, 95%CI [0.33, 2.17], p = 0.74), silent infarct (OR = 0.69, 95%CI [0.04, 11.80], p = 0.80), retreatment rate (OR = 1.32, 95%CI [0.70, 2.48], p = 0.39), mortality (OR = 1.41, 95%CI [0.06, 5.20], p = 0.61), immediate occlusion (OR = 0.99, 95%CI [0.64, 1.51], p = 0.95), and occlusion during follow-up (OR = 1.10, 95%CI [0.56, 2.16], p = 0.74) between the transradial and transfemoral groups. This study showed comparable safety and efficacy outcomes between transradial and transfemoral access in patients with intracranial aneurysms treated endovascularly. Future large randomised trials are warranted to confirm these findings.
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Procedimentos Endovasculares , Aneurisma Intracraniano , Acidente Vascular Cerebral , Tromboembolia , Humanos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Artéria Femoral/cirurgia , Resultado do Tratamento , Estudos de Coortes , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/etiologia , Hemorragias Intracranianas/etiologia , Infarto/etiologiaRESUMO
The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the larger loop B, of Qnr proteins are essential for quinolone protection of DNA gyrase. The specific QnrB1 interaction sites on DNA gyrase are not known. In this study, we investigated the interaction between GyrA and QnrB1 using site-specific photo-cross-linking of QnrB1 loop B combined with mass spectrometry. We found that amino acid residues 286 to 298 on the tower domain of GyrA interact with QnrB1 and play a key role in QnrB1 protection of gyrase from quinolone inhibition. Alanine replacement of arginine at residue 293 and a small deletion of amino acids 286 to 289 of GyrA resulted in a decrease in the QnrB1-mediated increase in quinolone MICs and also abolished the QnrB1 protection of purified DNA gyrase from ciprofloxacin inhibition.
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DNA Girase , Proteínas de Escherichia coli , Quinolonas , Ciprofloxacina/farmacologia , DNA Girase/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Mutação , Quinolonas/farmacologiaRESUMO
OBJECTIVE: This systematic review and meta-analysis were performed to investigate the efficacy and safety of Tripterygium wilfordii glycosides (TG) for rheumatoid arthritis (RA) from the current literature. METHODS: An electronic search was conducted in eight databases (PubMed, EMBASE, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese VIP Database, and Wanfang Database) from inception until September 2020. Randomized controlled trials (RCTs) with risk of bias (RoB) score ≥ 4 according to the Cochrane RoB tool were included for the analyses. The primary outcome measures were duration of morning stiffness (DMS), tender joint count (TJC), swollen joint count (SJC), visual analog score (VAS), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). The secondary outcome measures were the total clinical effective rate and adverse events. All the analyses were used by the random effects models. The meta-analysis was performed using RevMan 5.3 and STATA 14.0. RESULTS: A total of 40 RCTs with 3092 patients met our inclusion criteria. This meta-analysis showed that TG plus DMARDs for RA could decrease the DMS (p < .001), TJC (p < .001), SJC (p < .001), VAS (p < .001), serum CRP (p < .001), ESR (p < .001), and RF (p < .001) and improve total effective rate (p < .001). In addition, TG was generally safe and well tolerated in RA patients. CONCLUSION: Despite the limitations, the present evidence supports, at least to an extent, that TG can be recommended for routine use for RA patients. More large multicenter and high-quality RCTs are required for further research.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Fitoterapia , Tripterygium/química , Antirreumáticos/farmacologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Proteína C-Reativa/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Hierarchically porous MOFs (HP-MOFs) present advantageous synergism of micro- and mesopore but challenging in synthetic control at molecular scale. Herein, we present the first example of reversible and controllable mesopore generation and renovation in a microporous MOF of HKUST-1 via synthetic manipulation at molecular scale. An ammonia-gas etching strategy is proposed to create mesopores in carboxylate-based microporous MOFs and thus produce HP-MOFs. Gas-phase etching ensures uniform mesopore formation inside the MOF crystals via plane-oriented cutting the carboxylate-metal bonds off without affecting the crystal size and morphology. The mesopore size is controlled by the etching temperature, while the mesopore volume could be tuned by adjusting etchant pressure. The generated mesopores could be renovated using MOF precursors solutions so that to achieve controllable mesopore generation/closure, and encapsulation of the adsorbed molecules. This work demonstrates a powerful protocol for precisely tailoring and tuning the properties of MOF materials at molecular scale.
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Resting-state functional connectivity profiles have been increasingly shown to be important endophenotypes that are tightly linked to human cognitive functions and psychiatric diseases, yet the genetic architecture of this multidimensional trait is barely understood. Using a unique sample of 1,704 unrelated, young and healthy Chinese Han individuals, we revealed a significant heritability of functional connectivity patterns in the whole brain and several subnetworks. We further proposed a partitioned heritability analysis for multidimensional functional connectivity patterns, which revealed the common and unique enrichment patterns of the genetic contributions to brain connectivity patterns for several gene sets linked to brain functions, including the genes expressed preferentially in the central nervous system and those associated with intelligence, educational attainment, attention-deficit/hyperactivity disorder, and schizophrenia. These results for the first time reveal the genetic architecture of multidimensional brain connectivity patterns across different networks and advance our understanding of the complex relationship between gene sets, neural networks, and behaviors.
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Sucesso Acadêmico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Encéfalo , Conectoma , Inteligência/fisiologia , Herança Multifatorial/fisiologia , Rede Nervosa , Esquizofrenia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Conectoma/métodos , Feminino , Humanos , Inteligência/genética , Imageamento por Ressonância Magnética , Masculino , Herança Multifatorial/genética , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/metabolismo , Rede Nervosa/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Executive function (EF) is vital to human beings. It has been linked to many genes and family environmental factors in separate studies, but few studies have examined the potential interactions between gene(s) and environmental factor(s). The current study explored the whole genome to identify SNPs, genes, and pathways that interacted with parental warmth (PW) on EF. RESULTS: Nine EF tasks were used to measure its three components (common EF, updating, shifting) based on the model proposed by Miyake et al. (2000). We found that rs111605473, LAMP5, SLC4A7, and LRRK1 interacted significantly with PW to affect the updating component of EF, and the GSE43955 pathway interacted significantly with PW to affect the common EF component. CONCLUSIONS: The current study is the first to identify genes that interacted with PW to affect EF. Further studies are needed to reveal the underlying mechanism.
Assuntos
Função Executiva , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Pais , Adulto , Alelos , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
This meta-analysis was performed to investigate the efficacy and safety of tranexamic acid (TXA) in the elderly patients undergoing intertrochanteric fracture surgery from the current literatures. The electronic literature database of PubMed, Embase and Cochrane library were searched in October 2019. The intraoperative blood loss, hidden blood loss, postoperative drainage and total blood loss, postoperative hemoglobin, length of stay, transfusion rate, mortality rate, thromboembolic events and wound complications were extracted. Stata 14.0 software was used for our meta-analysis. A total of 11 RCTs (3 new RCTs in 2019) with 1202 patients met our inclusion criteria. This meta-analysis showed that administration of TXA can reduce intraoperative blood loss (P = 0.009), hidden blood loss (P = 0.000), total blood loss (P = 0.000), length of stay (P = 0.003), transfusion rate (P = 0.000) and the occurrence of wound complications (P = 0.006). Furthermore, administration of TXA was associated with an increase in the postoperative Hb level at day 1, 2 and 3 (P = 0.000, P = 0.000 and P = 0.000, respectively) after surgery. However, no significant difference was found between the TXA group and control group regarding the occurrence of thromboembolic events (P = 0.978, including deep vein thrombosis, P = 0.850; pulmonary embolism, P = 0.788; cerebrovascular accident, P = 0.549; myocardial infarction, P = 0.395) and mortality rate (P = 0. 338). Our meta-analysis suggested that administration of TXA is effective in reducing intraoperative blood loss, hidden blood loss, total blood loss, length of stay, transfusion rate, wound complications and enhancing postoperative Hb without increasing the risk of thromboembolic events and mortality rate in intertrochanteric fracture surgery. More large multi-center and high-quality RCTs are required for further research.
Assuntos
Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Fixação de Fratura , Fraturas do Quadril/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Ácido Tranexâmico/uso terapêutico , Idoso , Antifibrinolíticos/efeitos adversos , Feminino , Fixação de Fratura/efeitos adversos , Fraturas do Quadril/diagnóstico por imagem , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Ácido Tranexâmico/efeitos adversos , Resultado do TratamentoRESUMO
Background: Previous researches indicate that Itpr2 -/- mice (inositol 1,4,5-trisphosphate receptor type 2 knockout mice) show depressive-like symptoms; however, little is known regarding the in vivo neurobiological effect of Itpr2 as well as the specific pattern of brain abnormalities in Itpr2 -/- mice. Methods/Materials. First, behavioral tests, structural magnetic resonance imaging (MRI), and resting-state functional MRI were performed on Itpr2 -/- mice and matched healthy controls. Voxel-based morphometry and seed-based voxel-wise functional connectivity (FC) were, respectively, calculated to assess the gray matter volume and the functional activities of the brain in vivo. Second, the sample of relevant changed brain regions was extracted to detect the expression of BDNF. Finally, to further validate the relationship between Itpr2 deficiency and the observed brain abnormalities, we performed Western blotting to detect the expression of pro-BDNF and mBDNF in Itpr2 -/- C8-D1A (a type of astrocyte). Results: Compared with controls, Itpr2 -/- mice showed depressive-like behaviors as well as significantly lower gray matter volume in striatums mainly, periaqueductal GM, and the right frontoparietal cortices as well as lower striatal-hippocampal and striatal-right parietal cortex (mainly for the primary and secondary somatosensory cortex) FC. Moreover, decreased expression of mBDNF was found in both sample tissues of the striatum in Itpr2 -/- mice and Itpr2 -/- C8-D1A. Conclusion: By combining biochemistry and MR analyses, this study provides evidences to support that the Itpr2-related neuropathological effect is possibly mediated by the striatal abnormality associated with dysfunctional astrocytes in Itpr2 -/- mice in vivo, thus may help us better understand underlying mechanisms of Itpr2 deficiency as well as its relation to depressive-like behavior.