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MOTIVATION: The question of how to construct gene regulatory networks has long been a focus of biological research. Mutual information can be used to measure nonlinear relationships, and it has been widely used in the construction of gene regulatory networks. However, this method cannot measure indirect regulatory relationships under the influence of multiple genes, which reduces the accuracy of inferring gene regulatory networks. APPROACH: This work proposes a method for constructing gene regulatory networks based on mixed entropy optimizing context-related likelihood mutual information (MEOMI). First, two entropy estimators were combined to calculate the mutual information between genes. Then, distribution optimization was performed using a context-related likelihood algorithm to eliminate some indirect regulatory relationships and obtain the initial gene regulatory network. To obtain the complex interaction between genes and eliminate redundant edges in the network, the initial gene regulatory network was further optimized by calculating the conditional mutual inclusive information (CMI2) between gene pairs under the influence of multiple genes. The network was iteratively updated to reduce the impact of mutual information on the overestimation of the direct regulatory intensity. RESULTS: The experimental results show that the MEOMI method performed better than several other kinds of gene network construction methods on DREAM challenge simulated datasets (DREAM3 and DREAM5), three real Escherichia coli datasets (E.coli SOS pathway network, E.coli SOS DNA repair network and E.coli community network) and two human datasets. AVAILABILITY AND IMPLEMENTATION: Source code and dataset are available at https://github.com/Dalei-Dalei/MEOMI/ and http://122.205.95.139/MEOMI/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Biologia Computacional , Redes Reguladoras de Genes , Humanos , Entropia , Biologia Computacional/métodos , Probabilidade , Algoritmos , Escherichia coli/genéticaRESUMO
Tim-1 (T-cell immunoglobulin and mucin domain 1), also known as Kim-1 (kidney injury molecule 1) or hepatitis A virus cellular receptor 1 (HAVCR1), is a transmembrane protein expressed on various immune and epithelial cells. It plays a role in modulating inflammatory and immune responses. In this study, we find that Tim-1 is overexpressed in hepatocellular carcinoma (HCC) samples and that its expression is significantly correlated with postoperative survival. Bulk RNA sequencing reveals a general upregulation of extracellular matrix-related genes in HCC tissues with Tim-1 overexpression. The results of the cell and in vivo experiments reveal that Tim-1 in HCC not only affects biological processes such as the proliferation, migration, and invasion of HCC cells but also broadly promotes extracellular matrix processes by influencing cytokine secretion. Further studies demonstrate that Tim-1 mediates the activation of hepatic stellate cells and upregulates Th1 and Th2 cytokines, thereby promoting HCC progression. Thus, Tim-1 may represent a novel target for future interventions in HCC and liver fibrosis.
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PURPOSE: This study aims to evaluate the effects of prolonged expressive writing on health outcomes in breast cancer patients undergoing chemotherapy to help understand how the dosage of an expressive writing intervention might moderate its effects. METHODS: A total of 112 breast cancer patients undergoing chemotherapy were randomly allocated to the expressive writing group (n = 56) or the prolonged expressive writing group (n = 56). The expressive writing group received the standard expressive writing intervention based on Pennebaker's prompt to write for at least 20 min over four consecutive days (4 sessions). The prolonged expressive writing group used a modified prompt: write for at least 20 min 3 times a week over a 4-week period (12 sessions); patients could choose whether to write on consecutive days or not. All participants were required to write about their stressor-related upsetting or traumatic feelings about breast cancer. Outcomes were assessed and compared at baseline, as well as 1 month, 3 months, and 6 months postintervention. RESULTS: There was no significant difference in the patients' quality of life, or physical and psychological wellbeing between the expressive writing group and the prolonged expressive writing group at any time point (all p > .05). The quality of life of breast cancer patients significantly decreased in the two groups over time (F = 40.64, p < .001). CONCLUSION: Our findings suggest that the writing dosage does not moderate the effects of expressive writing on breast cancer patients undergoing chemotherapy. TRIAL REGISTRATION: ChiCTR1800016278.
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Neoplasias da Mama/psicologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Qualidade de Vida/psicologia , Redação , Feminino , Humanos , Estudos ProspectivosRESUMO
The radiation force of modified circular Airy beams (MCAB) exerted on both a high-refractive-index particle and a low-refractive-index particle are analyzed in this paper. Our results show that the two kinds of particles can be simultaneously stably trapped by MCAB at different positions. Compared with the common circular Airy beams (CAB) with the same parameters, trapping forces on the two kinds of particles are greatly increased because of the enhanced abruptly autofocusing property and the appearance of hollow region in MCAB. The trapping forces can be modulated by varying parameters of MCAB, and it is important to choose appropriate parameters to trap particles in practice.
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We have proposed a kind of modified circular Airy beam (MCAB) based upon a modification of the Fourier spectrum of circular Airy beams (CAB) in this paper. Unlike most abruptly autofocusing beams, the position of peak intensity of MCAB can be moved to any rings behind. Two apodization parameters are introduced to describe the propagation characteristics of MCAB. It is found that the focal position, focal trajectory and the size of focal spot do not change with the apodization parameters; but the abruptly autofocusing property will be greatly enhanced if appropriately apodization parameters are chosen. Comparing with the common CAB and the previous blocked CAB, the MCAB shows better abruptly autofocusing property. It may have more applications in various fields.
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Background: Triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane immunoglobulin-superfamily receptor, is expressed primarily on cells such as macrophages and dendritic cells. TREM2 has been shown to be associated with diseases such as neurodegeneration, fatty liver, obesity, and atherosclerosis. Currently, it has become one of the hotspots in oncology research. However, the role of TREM2 in pan-cancer, especially pancreatic cancer, remains unclear. Methods: We used the Tumor-immune System Interactions Database (TISIDB) to explore TREM2 expression differences, Tumor Immune Single-cell Hub 2 (TISCH2) to explore TREM2 expression distribution, Tumor IMmune Estimation Resource 2.0 (TIMER 2.0) to explore immune infiltration, cBio Cancer Genomics Portal (cBioPortal) to explore genetic variation, Genomics of Drug Sensitivity in Cancer (GDSC) to explore drug resistance, and Kaplan-Meier plotter database to explore the relationship between TREM2 and prognosis in pancreatic cancer. In addition, we used The Cancer Genome Atlas-pancreatic adenocarcinoma (TCGA-PAAD) and normal pancreas samples from the Genotype-Tissue Expression (GTEx) databases to explore the relationship between TREM2 and lymph node metastasis. We verified the protein level of TREM2 in pancreatic cancer by Human Protein Atlas (HPA) and western blotting and detected the colocalization of TREM2 with malignant cell markers by multiplex immunohistochemistry (mIHC). Finally, we identified the tumor-promoting role of TREM2 in pancreatic cancer via in vitro experiments, such as cell cycle assays, colony formation assays, and transwell migration and invasion assays. Results: Our results showed that TREM2 was differentially expressed in various tumors according to different molecular and immune subtypes of pan-cancer. It was found that TREM2 was mainly expressed in monocytes/macrophages. In addition, our study showed that TREM2 expression was closely associated with macrophages in the tumor microenvironment (TME) of pan-cancer. TREM2 was shown to be related to anti-inflammatory and immunosuppressive effects in most cancers. Furthermore, we found that amplification was the main somatic mutation of TREM2 in pan-cancer. Further correlational analysis revealed a significant negative association of TREM2 expression with sensitivity to AZD8186, which is a selective inhibitor of PI3K, but not gemcitabine and paclitaxel. Finally, through the knockdown and overexpression of TREM2, our findings verified that TREM2 on cancer cells promoted the progression of PAAD. Conclusions: In conclusion, our comprehensive analysis identified that TREM2 expression level was correlated with the TME and the immunosuppressive effects. In particular, our study indicated that TREM2 was involved in the progression of pancreatic cancer.
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To develop a more accurate prognostic model that incorporates indicators of multi-organ involvement for immunoglobulin light-chain (AL) Amyloidosis patients. Biopsy-proven AL amyloidosis patients between January 1, 2012, and February 28, 2023, were enrolled and randomly divided into a training set and a test set at a ratio of 7:3. Prognostic indicators that comprehensively cover cardiac, renal, and hepatic involvement were identified in the training set by random survival forest (RSF). Then, RSF and Cox models were established. The Concordance index (C-index) and integrated brier scores (IBS) were applied to evaluate the models' performance in the test set. Besides, the net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated. A total of 173 eligible patients were included. After a median follow-up of 25.9 (9.2, 50.3) months, 48 (27.7%) patients died. Creatine kinase-MB, estimated glomerular filtration rate ≤ 50 mL/min/1.73 m2, interventricular septum ≥ 15 mm, ejection fraction, alanine aminotransferase and Live involved were selected to develop prediction models. The RSF model based on the above indicators achieved C-index and IBS values of 0.834 (95% CI 0.725-0.915) and 0.151 (95% CI 0.1402-0.181), respectively. At last, the NRI and IDI of the RSF model were 0.301 (95% CI 0.048-0.546, P = 0.012) and 0.157 (95% CI 0.041-0.269, P < 0.001) at 5-year by comparing the RSF model with the Cox model which is based on the Mayo 2012 staging system. The RSF model that incorporates indicators of multi-organ involvement had a great performance, which may be helpful for physicians' decision-making and more accurate overall survival prediction.
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Amiloidose de Cadeia Leve de Imunoglobulina , Medicina de Precisão , Humanos , Feminino , Masculino , Amiloidose de Cadeia Leve de Imunoglobulina/fisiopatologia , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Pessoa de Meia-Idade , Prognóstico , Medicina de Precisão/métodos , Idoso , Estudos Retrospectivos , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Advancements in treatment regimens have led to improved outcomes in renal Immunoglobulin light-chain amyloidosis. Nevertheless, a subset of patients may still experience renal adverse events despite achieving hematologic very good partial response or better. This discrepancy may be attributed to the deposition pattern of amyloid in renal tissue. To enhance prognostic assessment, a staging system that incorporates both pathological characteristics and clinical indicators should be developed. METHODS: Patients newly diagnosed through renal biopsy between January 1, 2017, and December 31, 2022, were included. The renal pathology of patients was evaluated according to amyloid score (AS). Risk factors for end-stage renal disease or renal progression were identified by the competing risk model, then to develop a renal staging system. The Concordance index (C-index), internal cross-validation and Decision Curve Analysis (DCA) were used to evaluate the performance of the new staging system. RESULTS: 74 patients were included, and 16 (21.6%) patients had end-stage renal disease or renal progression within 24.7 (11.9, 50.7) months. AS and estimated glomerular filtration rate (eGFR) were identified as independent risk factors and the staging system based on them, which the C-index was 0.81 (95%CI, 0.73-0.89), had greater improvement than previous staging systems. The internal cross-validation and DCA also confirmed its great clinical benefits. CONCLUSION: The AS demonstrated its prognostic significance in Chinese patients, and the novel renal staging system based on AS and eGFR may provide great prognostic guidance for these patients.
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The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (nCase = 3,418, nControl = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (P BH = 3.28e-5, 0.05/1,525). These proteins were involved in amino acids and organic acid synthesis pathways. Colocalization analysis further identified six proteins associated with TCs (VCAM1, LGMN, NPTX1, PLEKHA7, TNFAIP3, and BMP1). Tissue validation confirmed BMP1, LGMN, and PLEKHA7's differential expression between normal and TC tissues. We found limited evidence for linking circulating proteins and the risk of TCs. Our study highlighted the contribution of proteins, particularly those involved in amino acid metabolism, to TCs.
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OBJECTIVE: To evaluate the inhibitory effect of cordycepin on oral cancer xenograft in nude mice and explore the underlying mechanisms. METHODS: Sixteen BALB/c mice bearing subcutaneous human tongue squamous cell carcinoma (TSCC) TCA-8113 cell xenografts were randomized into model group and cordycepin treatment group for daily treatment with saline and cordycepin for 4 weeks. After the treatment, the tumor xenografts were dissected and weighed to assess the tumor inhibition rate. Histological changes in the heart, spleen, liver, kidney, and lung of the mice were evaluated with HE staining, and tumor cell apoptosis was examined using TUNEL staining; The expressions of Bax, Bcl-2, GRP78, CHOP, and caspase-12 in the xenografts were detected using RT-qPCR and Western blotting. RESULTS: Cordycepin treatment resulted in a tumor inhibition rate of 56.09% in the nude mouse models, induced obvious changes in tumor cell morphology and significantly enhanced apoptotic death of the tumor cells without causing pathological changes in the vital organs. Cordycepin treatment also significantly reduced Bcl-2 expression (P < 0.05) and increased Bax, GRP78, CHOP, and caspase-12 expressions at both the RNA and protein levels in the tumor tissues. CONCLUSION: Cordycepin treatment can induce apoptotic death of TCA-8113 cell xenografts in nude mice via the endogenous mitochondrial pathway and endoplasmic reticulum stress pathways.
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Carcinoma de Células Escamosas , Cordyceps , Neoplasias da Língua , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas/tratamento farmacológico , Xenoenxertos , Camundongos Nus , Neoplasias da Língua/tratamento farmacológico , Caspase 12 , Chaperona BiP do Retículo Endoplasmático , Proteína X Associada a bcl-2 , LínguaRESUMO
N-glycolylneuraminic acid (Neu5Gc) is a specific factor in red meat that induces intestinal disease. Our aim was to investigate the effect of Neu5Gc on the intestinal barrier as well as its mechanism of endocytosis and exocytosis. Ten specific inhibitors were used to explore the mechanism of Neu5Gc endocytosis and exocytosis by Caco-2 cells. Amiloride hydrochloride and cytochalasin D had the strongest inhibitory effect on the endocytosis of Neu5Gc. Sodium azide, dynasore, chlorpromazine hydrochloride, and nystatin also inhibited Neu5Gc endocytosis. Dynasore exhibited a stronger inhibitory effect than that of chlorpromazine hydrochloride or nystatin alone. Exocytosis inhibitors, including nocodazole, brefeldin A, monensin, and bafilomycin A, inhibited the transmembrane transport of Neu5Gc. Monensin promoted the exocytosis of Neu5Gc from Caco-2 cells. In another experiment, we observed no significant inhibitory effects of monensin and brefeldin A. Dietary concentrations of Neu5Gc induced prominent damage to intestinal tight junction proteins zonula occludens-1 (ZO-1), occludin, and claudin-1 and promoted the phosphorylation of IκB-α and P65 to activate the canonical Nuclear Factor kappa-B (NF-κB) pathway. Neu5Gc increased the RNA levels of pro-inflammatory factors IL-1ß, IL-6, and TNF-α and inhibited those of anti-inflammatory factors TGF-ß and IL-10. BAY, an NF-κB signaling pathway inhibitor, attenuated these changes. Reductions in the levels of ZO-1, occludin, and claudin-1 were recovered in response to BAY. Our data reveal the endocytosis and exocytosis mechanism of Neu5Gc and prove that Neu5Gc can activate the canonical NF-κB signaling pathway, regulate the transcription of inflammatory factors, thereby damaging intestinal barrier function.
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Clorpromazina , NF-kappa B , Humanos , NF-kappa B/metabolismo , Células CACO-2 , Ocludina , Claudina-1/metabolismo , Brefeldina A/metabolismo , Brefeldina A/farmacologia , Clorpromazina/metabolismo , Clorpromazina/farmacologia , Monensin/metabolismo , Monensin/farmacologia , Nistatina/metabolismo , Nistatina/farmacologia , Transdução de Sinais , Mucosa IntestinalRESUMO
INTRODUCTION: Burkholderia pseudomallei is a gram-negative environmental bacterium and aetiological agent of melioidosis, a tropical infectious disease with diverse clinical presentations. We aimed to describe the epidemiological and clinical characteristics of melioidosis in northern Hainan and to determine the meteorological factors affecting its morbidity. METHODS: We conducted a retrospective, multicentre, observational cohort study of 90 patients with melioidosis admitted to four general hospitals in northern Hainan from 2010 to 2020. Epidemiological, clinical presentation, laboratory and treatment outcome data were collected and analysed. The monthly incidence of melioidosis and meteorological data, including precipitation, temperature, humidity, air pressure and wind speed, for the same period were collected to analyse the relationship between meteorological factors and the incidence of melioidosis. RESULTS: Of the 90 patients included in the study, 79 (87.78%) were male. Patient age ranged from 10 to 81 years old, but most patients, namely, 78 (86.67%), were middle-aged and elderly people aged 41-81 years old. Forty-six patients (51.11%) were farmers. The number of cases increased significantly after 2014, with the highest numbers occurring in 2014 and 2016. The highest number of cases occurred in summer and autumn and were associated with abundant rainfall, and 58 cases (64.44%) occurred from July to December. The patients showed diverse presentations and abnormal laboratory parameters: 69 patients (76.67%) had a history of diabetes mellitus; bacteremia was present in 50 patients (55.56%), sepsis was present in 39 patients (43.33%) and pneumonia in 19 patients (21.11%). An average high-sensitivity C-reactive protein (hs-CRP) level of 149.57 ± 13.65 mg/L and a median procalcitonin (PCT) level of 1.31 (0.39, 6.21) ng/mL were observed. Among all the cases, 21 (23.33%) were identified as acute infections, 51 (56.67%) as subacute infections and 18 (20.00%) as chronic infections. Six patients (6.67%) died of illness; five of these patients were male, and five of these patients were middle-aged and elderly patients. The monthly average precipitation was significantly positively correlated with the monthly average incidence of melioidosis (r = 0.74, P < 0.01). CONCLUSION: Male patients, farmers and especially middle-aged and elderly individuals with a history of diabetes mellitus accounted for most of the patients. The majority of cases were concentrated in coastal areas. Most cases of melioidosis occurred during the rainy seasons, and the monthly average precipitation was an independent factor affecting the average monthly incidence of melioidosis.
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Chinese medicinal herbal residues (CMHRs) are waste generated after extracting Chinese medicinal materials, and they can be used as a renewable bioresource. This study aimed to evaluate the potential of aerobic composting (AC), anaerobic digestion (AD), and aerobic-anaerobic coupling composting (AACC) for the treatment of CMHRs. CMHRs were mixed with sheep manure and biochar, and composted separately under AC, AD, and AACC conditions for 42 days. Physicochemical indices, enzyme activities, and bacterial communities were monitored during composting. Results showed that AACC- and AC-treated CMHRs were well-rotted, with the latter exhibiting the lowest C/N ratio and maximal germination index (GI) values. Higher phosphatase and peroxidase activities were detected during the AACC and AC treatments. Better humification was observed under AACC based on the higher catalase activities and lower E4/E6. AC treatment was effective in reducing compost toxicity. This study provides new insights into biomass resource utilisation.
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Compostagem , Medicamentos de Ervas Chinesas , Animais , Ovinos , Anaerobiose , Bactérias , Esterco , Medicamentos de Ervas Chinesas/química , SoloRESUMO
Background: Receiving a breast cancer diagnosis and treatment is both a physical and emotional journey. Previous studies using single-source data have revealed common and culture-specific emotional experiences of patients living with breast cancer. However, few studies have combined such data from multiple sources. Thus, using a variety of data sources, the current study sought to explore the emotional experiences of women in China newly diagnosed, post-operative, or undergoing chemotherapy. We posited that even though women living with breast cancer in China have multiple channels through which they can express these emotional experiences, little variance would be found in their emotional expressivity and the themes they want to express due to cultural inhibitions. Methods: Text data from female patients newly diagnosed, post-operative, or undergoing chemotherapy were collected between June 2021 and January 2022 via a Python web crawler, semi-structured interviews, and an expressive writing intervention. Data were transcribed and subjected to thematic analysis. Reporting followed the consolidated criteria for reporting qualitative studies (COREQ) guidelines. Results: Analyses were based on 5,675 Weibo posts and comments published by 448 posters and 1,842 commenters, transcription texts from 17 semi-structured interviews, and 150 expressive writing texts. From this total collection of 461,348 Chinese characters, three major themes emerged: (i) conflicting emotions after diagnosis; (ii) long-term suffering and treatment concerns; and (iii) benefit finding and cognitive reappraisal. Conclusions: Despite gathering information from various sources, we found that distress from body-image disturbances, gender role loss and conflict, and changes in sexuality and fertility, were consistent among this sample of female Chinese patients with breast cancer. However, when women engaged actively in benefit finding and cognitive reappraisal with strong social support, patients were able to find ways to adapt and reported post-traumatic growth. Strong social support was an important facilitator in this growth. These study findings emphasize that healthcare professionals ought to increase cultural sensitivity, provide multiple channels to encourage patients to express their emotions, and incorporate screening for patients' emotional distress at all diagnostic and treatment phases as part of routine nursing care.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Emoções , ChinaRESUMO
With the rapid development of curricula, a large number of studies are emerging to assist in the development of curricula. But in an information society, in the face of rapid learning and increased life expectancy, students face the pressure not to forget; the mental health status as a result of our curricula is closely related to our learning. The research and application of the integration algorithm plays an important role in the analysis of the mental health education system. The purpose of this work is to study the application analysis algorithm in the students' context. This work applies the integration analysis algorithm to students' mental health analysis and identifies students' mental health problems using the integration analysis algorithm so that students are well informed and guided. Based on the system engineering method, using the data mining clustering method, a detailed analysis and research on the mental health of college students is done. In this work, a method of student behavior analysis and statistical tools are used to collect mental health data to find common features of different groups of students, in order to better visualize and investigate the mental health of these students on a scientific basis. The results of this study are as follows: a general analysis algorithm application on the analysis of students' mental health education system allows for an effective understanding of scientific data. FCM and FCM algorithms based on the density of information entropy characteristics were used to investigate the effect of mental health factors on the results of the study and the practicality of the algorithm used, which provided an effective method for the prevention of student mental problems. Assisting the school in formulating corresponding new methods of early prevention and intervention of college students' psychological disorders will create a good and healthy atmosphere for college students' study and life. The research results provide a reliable basis for managing and cultivating students.
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Fetal cervical teratoma is a rare congenital neck tumor. Here, we report a case of a fetus with an anterior solid neck tumor that was confirmed to have an immature teratoma by histology. A duplication was found at chromosome 14q24.1-q24.3 of the fetus in chromosome microarray (CMA) and whole exome sequencing (WES), which was a copy number variation (CNV) and a probably new-onset. Ultrasound coupled with magnetic resonance imaging (MRI) can be considered to be a relatively reliable diagnostic tool, whereas ex-utero intrapartum therapy or resection of the tumor mass on placental support may improve the chances of the newborn's survival. Strangely, the same duplication occurred on her next fetus that was found with complex congenital heart malformations. CNV at chromosome 14q24.1-q24.3 needs to be paid more attention.
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BACKGROUND: Rheumatoid arthritis (RA) is an chronic autoimmune disease and characterized by high incidence. However, there is no effective therapies for RA. Therefore, it is urgent to discover new drugs for RA treatment. Nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) can effectively protect against arthritic inflammatory diseases through diverse stages, such as regulating redox balance, detoxification, metabolism and inflammation. Dimethyl fumarate (DMF), targets the Nrf2 pathway, was approved by FDA for the clinical treatment of multiple sclerosis (MS), which is another autoimmune disease. The latest report shown that DMF ameliorates complete Freund's adjuvant-induced arthritis in rats through activation of the Nrf2/HO-1 signaling pathway. Hence, Nrf2 serves as an important target for inflammation interference and oxidative stress of macrophages and RASFs in RA; therefore, it can be adopted as an effective therapeutic approach in the future. Rheumatoid arthritis synovial fibroblasts (RASFs) play crucial roles in the RA pathogenesis. Our results revealed that 7-deacetyl-gedunin (7-d-GDN), derived from fruits of Toona sinensis (A. Juss.) Roem, significantly inhibited RASFs proliferation in dose- and time- dependent manners and inhibited cell viability in MH7A cells, which is a kind of immortal cell line from joints of patients with RA. Additionally, 7-d-GDN remarkably down-regulated MMP-1/3/9/13 in RASFs, IL-6 and IL-33 in MH7A cells. Besides, 7-d-GDN sharply inhibited reactive oxygen species (ROS) in RASFs. Further mechanistic study demonstrated that 7-d-GDN induced heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone 1(NQO1), which all participated in suppressing of oxidative stress. Additionally, 7-d-GDN increased sequestosome 1 (SQSTM1, p62), causing down-regulating Kelch-like ECH-associated protein 1 (Keap1), which resulting in NF-E2-related factor 2 (Nrf2) cytoplasm accumulation and subsequently translocation into nucleus. Collectively, 7-d-GDN exerts the anti-inflammatory effect through regulating anti-oxidative enzymes via p62/ Nrf2/ARE signaling. All suggest that the potential of 7-d-GDN in suppression of inflammation, especially antagonizing RA severity. Our works support for drugs discovery in RA treatment.
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Artrite Reumatoide , Fator 2 Relacionado a NF-E2 , Animais , Humanos , Ratos , Artrite Reumatoide/metabolismo , Proliferação de Células , Fibroblastos , Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Limoninas , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de SinaisRESUMO
Traditional Chinese Medicine (TCM) clinical intelligent decision-making assistance has been a research hotspot in recent years. However, the recommendations of TCM disease diagnosis based on the current symptoms are difficult to achieve a good accuracy rate because of the ambiguity of the names of TCM diseases. The medical record data downloaded from ancient and modern medical records cloud platform developed by the Institute of Medical Information on TCM of the Chinese Academy of Chinese Medical Sciences (CACMC) and the practice guidelines data in the TCM clinical decision supporting system were utilized as the corpus. Based on the empirical analysis, a variety of improved Naïve Bayes algorithms are presented. The research findings show that the Naïve Bayes algorithm with main symptom weighted and equal probability has achieved better results, with an accuracy rate of 84.2%, which is 15.2% higher than the 69% of the classic Naïve Bayes algorithm (without prior probability). The performance of the Naïve Bayes classifier is greatly improved, and it has certain clinical practicability. The model is currently available at http://tcmcdsmvc.yiankb.com/.
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In filled-duration illusion, a continuous (long) tone or an auditory sequence with multiple clicks is typically perceived as longer than the same physical duration (i.e., empty interval) enclosed by two auditory clicks. The auditory sequence is composed of multiple empty intervals. However, the individual empty interval in an auditory sequence, compared with the empty interval presented alone, could be biased in duration perception. In the current study, we implemented five experiments to reveal that the time perception of a single empty interval versus that of (mean) empty intervals in an auditory sequence depends on the task demands and contextual information. Specifically, we observed that the empty interval (140 ms) was perceived as longer than the same physical inter-stimulus interval in a sound sequence (Experiments 1 and 3). However, the empty interval (140 ms) was perceived as shorter than a continuous beep (i.e., filled duration of 140 ms) (Experiment 2). We observed a robust compression effect, in which the target empty interval (bounded by two oddball clicks) was perceived as shorter than the other physically equivalent intervals in a sound sequence (Experiment 4). In addition to the 'compression', perception of the target empty interval was assimilated by the other, task-irrelevant empty intervals in the sound sequence (Experiment 5). We explained the observed contextually modulated temporal illusions within a Bayesian inference framework.
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Percepção Auditiva , Ilusões/psicologia , Som , Estimulação Acústica , Adulto , Teorema de Bayes , Feminino , Humanos , Masculino , Percepção do TempoRESUMO
OBJECTIVE: To explore the effects of intervention with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on vaginal Group B Streptococcus (GBS) colonization, pregnancy outcome and vaginal microbiome in GBS-positive women in the third trimester of pregnancy. METHODS: This study were conducted among 155 women in the third trimester of pregnancy with positive results of GBS culture in the Outpatient Department of Zhujiang Hospital from March to November, 2019. After excluding 32 patients who received lactobacillus intervention for less than 2 weeks or underwent postpartum GBS retesting, the women were divided into oral probiotics intervention group (60 cases) and non-intervention group (63 cases). According to the results of GBS retesting, the 60 women in the intervention group were divided into GBS-negative group (18 cases) and persistent GBS-positive group (42 cases). At the end of the intervention, the rates of negative GBS culture result were calculated and the pregnancy outcomes were compared. From 5 women randomly selected from the intervention group, samples of vaginal secretions were collected before and after the intervention for amplicon sequencing and bioinformatics analysis. RESULTS: At the end of the intervention, the GBS-negative rate in the intervention group was 30% (18/60), as compared with 23% (3/13) in the non-intervention group. Probiotic intervention significantly reduced the incidence of premature rupture of membranes (P < 0.05) and reduced the use of antibiotics during pregnancy (P < 0.05). OTU analysis of the vaginal secretions suggested probiotic intervention decreased the total sequence number and GBS sequence number, increased the species composition, and significantly decreased GBS abundance (P < 0.05). Probiotics intervention also significantly decreased the species abundance of Enterococcus, Staphylococcus and Streptococcus in the vaginal flora (P < 0.05). CONCLUSIONS: Intervention with oral probiotics can reduce vaginal GBS colonization in late pregnancy and improve the pregnancy outcome. Lactobacillus is capable of reducing the abundance of GBS and other pathogenic bacteria to improve the microbiome of vaginal flora.