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1.
Am J Pathol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38762117

RESUMO

The evaluation of morphologic features, such as inflammation, gastric atrophy, and intestinal metaplasia, is crucial for diagnosing gastritis. However, artificial intelligence analysis for nontumor diseases like gastritis is limited. Previous deep learning models have omitted important morphologic indicators and cannot simultaneously diagnose gastritis indicators or provide interpretable labels. To address this, an attention-based multi-instance multilabel learning network (AMMNet) was developed to simultaneously achieve the multilabel diagnosis of activity, atrophy, and intestinal metaplasia with only slide-level weak labels. To evaluate AMMNet's real-world performance, a diagnostic test was designed to observe improvements in junior pathologists' diagnostic accuracy and efficiency with and without AMMNet assistance. In this study of 1096 patients from seven independent medical centers, AMMNet performed well in assessing activity [area under the curve (AUC), 0.93], atrophy (AUC, 0.97), and intestinal metaplasia (AUC, 0.93). The false-negative rates of these indicators were only 0.04, 0.08, and 0.18, respectively, and junior pathologists had lower false-negative rates with model assistance (0.15 versus 0.10). Furthermore, AMMNet reduced the time required per whole slide image from 5.46 to only 2.85 minutes, enhancing diagnostic efficiency. In block-level clustering analysis, AMMNet effectively visualized task-related patches within whole slide images, improving interpretability. These findings highlight AMMNet's effectiveness in accurately evaluating gastritis morphologic indicators on multicenter data sets. Using multi-instance multilabel learning strategies to support routine diagnostic pathology deserves further evaluation.

2.
Plant J ; 114(6): 1301-1318, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36932862

RESUMO

Cold stress is a major factor limiting the production and geographical distribution of rice (Oryza sativa) varieties. However, the molecular mechanisms underlying cold tolerance remain to be elucidated. Here, we report that ornithine δ-aminotransferase (OsOAT) contributes to cold tolerance during the vegetative and reproductive development of rice. osoat mutant was identified as a temperature-sensitive male sterile mutant with deformed floral organs and seedlings sensitive to cold stress. Comparative transcriptome analysis showed that OsOAT mutation and cold treatment of the wild-type plant led to similar changes in the global gene expression profiles in anthers. OsOAT genes in indica rice Huanghuazhan (HHZ) and japonica rice Wuyungeng (WYG) are different in gene structure and response to cold. OsOAT is cold-inducible in WYG but cold-irresponsive in HHZ. Further studies showed that indica varieties carry both WYG-type and HHZ-type OsOAT, whereas japonica varieties mostly carry WYG-type OsOAT. Cultivars carrying HHZ-type OsOAT are mainly distributed in low-latitude regions, whereas varieties carrying WYG-type OsOAT are distributed in both low- and high-latitude regions. Moreover, indica varieties carrying WYG-type OsOAT generally have higher seed-setting rates than those carrying HHZ-type OsOAT under cold stress at reproductive stage, highlighting the favorable selection for WYG-type OsOAT during domestication and breeding to cope with low temperatures.


Assuntos
Oryza , Oryza/metabolismo , Melhoramento Vegetal , Desenvolvimento Vegetal , Transaminases/metabolismo , Fertilidade/genética , Ornitina/metabolismo , Temperatura Baixa
3.
Plant Cell Rep ; 38(8): 869-882, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30963238

RESUMO

KEY MESSAGE: The TPS5 negatively regulates ABA signaling by mediating ROS level and NR activity during seed germination and stomatal closure in Arabidopsis thaliana. Trehalose metabolism is important in plant growth and development and in abiotic stress response. Eleven TPS genes were identified in Arabidopsis, divided into Class I (TPS1-TPS4) and Class II (TPS5-TPS11). Although Class I has been shown to have TPS activity, the function of most members of Class II remains enigmatic. Here, we characterized the biological function of the trehalose-6-phosphate synthase TPS5 in ABA signaling in Arabidopsis. TPS5 expression was induced by ABA and abiotic stress, and expression in epidermal and guard cells was dramatically increased after ABA treatment. Loss-of-function analysis revealed that tps5 mutants (tps5-1 and tps5-cas9) are more sensitive to ABA during seed germination and ABA-mediated stomatal closure. Furthermore, the H2O2 level increased in the tps5-1 and tps5-cas9 mutants, which was consistent with the changes in the expression of RbohD and RbohF, key genes responsible for H2O2 production. Further, TPS5 knockout reduced the amounts of trehalose and other soluble carbohydrates as well as nitrate reductase (NR) activity. In vitro, trehalose and other soluble carbohydrates promoted NR activity, which was blocked by the tricarboxylic acid cycle inhibitor iodoacetic acid. Thus, this study identified that TPS5 functions as a negative regulator of ABA signaling and is involved in altering the trehalose content and NR activity.


Assuntos
Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Glucosiltransferases/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Germinação/fisiologia , Glucosiltransferases/fisiologia , Peróxido de Hidrogênio/metabolismo , Estômatos de Plantas/metabolismo , Estômatos de Plantas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia
4.
BMC Oral Health ; 19(1): 26, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696440

RESUMO

BACKGROUND: It is widely accepted that oral health plays an important role in overall health. Both dental and medical students are expected to possess good oral health awareness and work together for public oral health promotion especially in developing countries like China. The aim of this study was to assess the oral health knowledge, behavior and status of dental and medical undergraduate students in the first (fresh) and third year (before specialized courses) study. METHODS: A self-administered structured questionnaire with 13 questions was designed based on oral health knowledge, behavior and status and a cross-sectional study was conducted among the 1st, 3rd year dental students (1DS, 3DS) and medical students (1MS, 3MS) of Sichuan University in Chengdu, China, in the period of September-December 2017. The data was analyzed by chi-square test using IBM SPSS Statistics v. 21.0. RESULTS: The oral health behavior, consciousness and status of the 1st, 3rd year medical and dental students were not optimistic. Dental freshmen were slightly superior to the medical ones in terms of the brushing methods and the awareness of oral disease-systemic disease relationship. The junior dental students showed highly significant improvement than their counterparts, mainly in the items about frequency of brushing teeth, brushing methods of vertical scrub or Bass technique (66.3%), usage of floss or mouth wash (49.7%), causes of caries, periodontal diseases and system diseases (56.9-83.4%). The rates mentioned above were 36.1, 15.8%, 26.7-43.6% among 3MS, respectively. In terms of oral health status, significant differences were only observed in junior students. The prevalence rates of bad breath, gum bleeding, and tooth discoloration among 3DS were obviously lower than those of 3MS. However, only a total of 17.2% junior students had a good oral health, including 23.8% dental students and 11.4% medical students. CONCLUSIONS: Our study provided a new understanding of oral health knowledge, behavior and status among dental and medical students, which may help to promote the reform of oral health education and establish a model for clinicians and dentists to work together for improving oral health.


Assuntos
Higiene Bucal , Estudantes de Medicina , China , Estudos Transversais , Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Saúde Bucal , Inquéritos e Questionários
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(1): 7-12, 2019 Jan.
Artigo em Zh | MEDLINE | ID: mdl-31037898

RESUMO

OBJECTIVE: This study aims to explore the effect of silence of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome on advanced glycation end products (AGEs)-induced myocardial injury. METHODS: The myocardial injury model was indued by AGEs. NLRP3 was silenced by shRNA. H9c2 cells were divided into four groups: H9c2 (control group); AGEs group; AGEs+sh-Ctrl group; AGEs+sh-NLRP3 group. The latter two groups of cells will first shRNA control (sh-Ctrl) and shRNA-NLRP3 (sh-NLRP3) plasmids were transfected into H9c2 cells, the last 3 cells were then treated for 24 h with 100 mg/L AGEs, establishment of H9c2 damage model, control cells were treated with solvent for 24 h; Apoptosis was measured by Hoechst33258 staining. The levels of interleukin (IL)-6, IL-18 and IL-1ß were detected by enzyme-linked immunosorbent assay (ELISA). The protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), Caspase-3, Caspase-9, nuclear factor κB (NF-κB) P65 and p-P65 were tested by Western blot. The nuclear NF-κB P65 levels were detected by immunofluorescent staining. RESULTS: The expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs group and AGEs+sh-Ctrl group was higher than control group ( P<0.05). Compared with AGEs group, the expressions of NLRP3, ASC, Caspase-3 and Caspase-9 in AGEs+sh-NLRP3 group was decreased ( P<0.05). Compared with control group, the apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs group and AGEs+sh-Ctrl group were elevated ( P<0.05). The apoptosis and the levels of IL-6, IL-18 and IL-1ß in AGEs+sh-NLRP3 group were lower than those of AGEs group ( P<0.05). The phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs group and AGEs+sh-Ctrl group were higher than control group ( P<0.05). Compared with AGEs group, the phosphorylation of NF-κB P65 and nuclear NF-κB P65 in AGEs+sh-NLRP3 group were reduced ( P<0.05). Conlusion Silencing of NLRP3 inflammasome alleviates AGEs-induced apoptosis and inflammatory response in myocardial cell via inhibiting NF-κB P65 activation.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Animais , Produtos Finais de Glicação Avançada , Interleucina-1beta , Miócitos Cardíacos , NF-kappa B , RNA Interferente Pequeno , Ratos
6.
Plant Cell ; 26(5): 2234-2248, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24794135

RESUMO

Although magnesium (Mg2+) is the most abundant divalent cation in plant cells, little is known about the mechanism of Mg2+ uptake by plant roots. Here, we report a key function of Magnesium Transport6 (MGT6)/Mitochondrial RNA Splicing2-4 in Mg2+ uptake and low-Mg2+ tolerance in Arabidopsis thaliana. MGT6 is expressed mainly in plant aerial tissues when Mg2+ levels are high in the soil or growth medium. Its expression is highly induced in the roots during Mg2+ deficiency, suggesting a role for MGT6 in response to the low-Mg2+ status in roots. Silencing of MGT6 in transgenic plants by RNA interference (RNAi) resulted in growth retardation under the low-Mg2+ condition, and the phenotype was restored to normal growth after RNAi plants were transferred to Mg2+-sufficient medium. RNAi plants contained lower levels of Mg2+ compared with wild-type plants under low Mg2+ but not under Mg2+-sufficient conditions. Further analysis indicated that MGT6 was localized in the plasma membrane and played a key role in Mg2+ uptake by roots under Mg2+ limitation. We conclude that MGT6 mediates Mg2+ uptake in roots and is required for plant adaptation to a low-Mg2+ environment.

7.
Int J Clin Oncol ; 20(2): 273-81, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24804867

RESUMO

OBJECTIVE: Immune escape plays an important role in tumor progression. In the present study, the expression of B7-H1, B7-H4 and Foxp3 involved in immune escape in gastric carcinoma was investigated and the corresponding clinical significance was evaluated. METHODS: Immunohistochemistry was used to detect the expression of B7-H1, B7-H4 and Foxp3 in 100 gastric cancer specimens, and 30 paracarcinoma tissues were used as the control. RESULTS: Both B7-H1 and B7-H4 showed high expression levels in gastric cancer tissues (65.0 and 71.0 %, respectively), and the expressions of B7-H1 and B7-H4 were positively correlated with the depth of tumor invasion, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage (P < 0.05). The number of Foxp3(+) Tregs was much higher in gastric cancer tissues than control tissues, which was positively correlated with lymph node metastasis (P < 0.05). Similarly, a positive correlation between B7-H1 or B7-H4 expression and the number of Foxp3(+) Tregs was observed. The median overall survival rate of patients with high expression of B7-H1, B7-H4 and Foxp3 was significantly poorer than that of patients with low expression of these proteins (P < 0.05). Cox regression multivariate analysis confirmed that lymph node metastasis, AJCC stage, and B7-H1 and Foxp3 overexpression were independent prognostic factors. CONCLUSION: B7-H1, B7-H4 and Foxp3 were overexpressed in gastric cancer tissues. B7-H1 and Foxp3 are negative prognostic factors for patients with gastric cancer.


Assuntos
Antígeno B7-H1/análise , Carcinoma/química , Neoplasias Gástricas/química , Linfócitos T Reguladores/química , Inibidor 1 da Ativação de Células T com Domínio V-Set/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Linfócito CD4 , Carcinoma/secundário , Feminino , Fatores de Transcrição Forkhead/análise , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estômago/química , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Evasão Tumoral
8.
Proc Natl Acad Sci U S A ; 109(36): 14693-8, 2012 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-22908257

RESUMO

Plant growth and development are controlled by a delicate balance of hormonal cues. Growth-promoting hormones and growth-inhibiting counterparts often antagonize each other in their action, but the molecular mechanisms underlying these events remain largely unknown. Here, we report a cross-talk mechanism that enables a receptor-like kinase, FERONIA (FER), a positive regulator of auxin-promoted growth, to suppress the abscisic acid (ABA) response through activation of ABI2, a negative regulator of ABA signaling. The FER pathway consists of a FER kinase interacting with guanine exchange factors GEF1, GEF4, and GEF10 that, in turn, activate GTPase ROP11/ARAC10. Arabidopsis mutants disrupted in any step of the FER pathway, including fer, gef1gef4gef10, or rop11/arac10, all displayed an ABA-hypersensitive response, implicating the FER pathway in the suppression mechanism. In search of the target for the FER pathway, we found that the ROP11/ARAC10 protein physically interacted with the ABI2 phosphatase and enhanced its activity, thereby linking the FER pathway with the inhibition of ABA signaling.


Assuntos
Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/crescimento & desenvolvimento , Ativação Enzimática/fisiologia , Fosfoproteínas Fosfatases/metabolismo , Fosfotransferases/metabolismo , Transdução de Sinais/fisiologia , Ácido Abscísico/antagonistas & inibidores , Proteínas de Arabidopsis/genética , Clonagem Molecular , Primers do DNA/genética , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Vetores Genéticos , Glucuronidase/metabolismo , Microscopia de Fluorescência , Espécies Reativas de Oxigênio/metabolismo , Transformação Genética , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo
9.
Genesis ; 52(4): 341-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24851283

RESUMO

Myelinogenesis is a complex process that involves substantial and dynamic changes in plasma membrane architecture and myelin interaction with axons. Highly ramified processes of oligodendrocytes in the central nervous system (CNS) make axonal contact and then extrapolate to wrap around axons and form multilayer compact myelin sheathes. Currently, the mechanisms governing myelin sheath assembly and axon selection by myelinating cells are not fully understood. Here, we generated a transgenic mouse line expressing the membrane-anchored green fluorescent protein (mEGFP) in myelinating cells, which allow live imaging of details of myelinogenesis and cellular behaviors in the nervous systems. mEGFP expression is driven by the promoter of 2'-3'-cyclic nucleotide 3'-phosphodiesterase (CNP) that is expressed in the myelinating cell lineage. Robust mEGFP signals appear in the membrane processes of oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS), wherein mEGFP expression defines the inner layers of myelin sheaths and Schmidt-Lanterman incisures in adult sciatic nerves. In addition, mEGFP expression can be used to track the extent of remyelination after demyelinating injury in a toxin-induced demyelination animal model. Taken together, the membrane-anchored mEGFP expression in the new transgenic line would facilitate direct visualization of dynamic myelin membrane formation and assembly during development and process remodeling during remyelination after various demyelinating injuries.


Assuntos
Membrana Celular/metabolismo , Bainha de Mielina/metabolismo , 2',3'-Nucleotídeo Cíclico 3'-Fosfodiesterase/genética , Animais , Membrana Celular/ultraestrutura , Feminino , Expressão Gênica , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Masculino , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos Transgênicos , Microscopia de Fluorescência , Bainha de Mielina/ultraestrutura , Oligodendroglia/metabolismo , Oligodendroglia/ultraestrutura , Sistema Nervoso Periférico/citologia , Células Satélites Perineuronais/metabolismo , Células Satélites Perineuronais/ultraestrutura , Medula Espinal/citologia , Medula Espinal/metabolismo
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 31(5): 628-31, 2014 Oct.
Artigo em Zh | MEDLINE | ID: mdl-25297597

RESUMO

OBJECTIVE: To explore the influence of BCL6, MYC, P53 genes abnormalities can on the prognosis of diffuse large B-cell lymphoma (DLBCL), and to identify independent prognostic factors for DLBCL in order to facilitate clinical prognosis and selection of stratification treatment for the patients. METHODS: Sixty five newly diagnosed DLBCL pathological specimens were collected from 2009 to 2012. Interphase fluorescence in situ hybridization technique (I-FISH) was used to detect the status of BCL6, MYC and P53 genes. Clinical factors were combined with immunohistochemical results for multiple-factor survival analysis. RESULTS: The rates of BCL6 gene rearrangement, P53 gene deletion and MYC rearrangement were 21.5% (14/65), 35.4% (23/65) and 7.7% (5/65), respectively. BCL6 rearrangement group has obviously poorer overall survival (OS)(P< 0.05). COX proportional hazards model analysis showed that gender, BCL6 protein, BCL6 rearrangement, Ki67 index were prognosis factors independent of international prognostic index (IPI). CONCLUSION: BCL6 can influence the prognosis of patients with DLBCL at gene and protein levels and both are independent prognostic factors for DLBCL.


Assuntos
Proteínas de Ligação a DNA/genética , Linfoma Difuso de Grandes Células B/genética , Mutação , Proteínas Proto-Oncogênicas c-myc/genética , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Deleção de Genes , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6 , Análise de Sobrevida , Taxa de Sobrevida , Adulto Jovem
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 30(1): 79-83, 2013 Feb.
Artigo em Zh | MEDLINE | ID: mdl-23450486

RESUMO

OBJECTIVE: To determine the expressions of miR-155, miR-34a and miR-30a in diffuse large B-cell lymphoma (DLBCL) and to explore their potential correlation with clinicopathological characteristics. METHODS: The expression level of miR-155, miR-34a and miR-30a in 46 DLBCL samples were determined with TaqMan real-time polymerase chain reaction. Interphase fluorescence in situ hybridization (I-FISH) was performed to detect MYC and p53 genes' status, and immunohistochemistry (Envision method) was used to evaluate the expression of CD3, CD10, CD20, BCL-6 and MUM-1 in DLBCL. The DLBCLs were classified into germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) subtypes according to Hans' criteria. RESULTS: Compared with normal controls, miR-155 expression level was significantly higher in DLBCL. The expression level of miR-155 in non-GCB type was higher than that in GCB type. It was shown that the patients with MYC rearrangement had lower expression level of miR-155 than the negative controls. Compared with p53 normal group, the expression level of miR-34a was significantly lower in p53 deletion group. It was also shown that the patients with BCL-6 protein expression had lower expression of miR-30a compared with the negative group. CONCLUSION: miR-155 expression level is different in normal controls, DLBCL and patients with subtype DLBCL. It therefore has a diagnosis value for DLBCL. miR-34a is of great prognostic significance. miR-155, miR-34a and miR-30a may be potential therapy targets for DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-37015588

RESUMO

Machine learning based sleep scoring methods aim to automate the process of annotating polysomnograms with sleep stages. Although sleep signals of multiple modalities and channels should contain more information according to sleep guidelines, most multi-channel multi-modal models in the literature showed only a little performance improvement compared to single-channel EEG models and sometimes even failed to outperform them. In this paper, we investigate whether the high performance of single-channel EEG models can be attributed to specific model features in their deep learning architectures and to which extent multi-channel multi-modal models take the information from different channels of modalities into account. First, we transfer the model features from single-channel EEG models, such as combinations of small and large filters in CNNs, to multi-channel multi-modal models and measure their impacts. Second, we employ two explainability methods, the layer-wise relevance propagation as post-hoc and the embedded channel attention network as intrinsic interpretability methods, to measure the contribution of different channels on predictive performance. We find that i) single-channel model features can improve the performance of multi-channel multi-modal models and ii) multi-channel multi-modal models focus on one important channel per modality and use the remaining channels to complement the information of the focused channels. Our results suggest that more advanced methods for aggregating channel information using complementary information from other channels may improve sleep scoring performance for multi-channel multi-modal models.

13.
Pathogens ; 11(5)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35631034

RESUMO

The immune dysregulation induced by periodontal bacteria has important roles in the development of periodontitis. However, the role of key periodontal bacteria in local and systemic immunity has not been comprehensively studied. Herein, to explore immunoregulation maps of key periodontal bacteria, a mono-colonized germ-free mice model with P. gingivalis, F. nucleatum, and T. denticola for two weeks was designed in this study. The alveolar bone loss was determined by micro-CT. A total of 14 types of innate and adaptive immune cells of the gingiva, spleen, and colon were detected by multi-color flow cytometry. P. gingivalis induced the strongest innate immune response in gingiva and mononuclear phagocytes (MNPs) changed most significantly, compared to F. nucleatum and T. denticola. Immune dysregulation of the colon was widely induced by F. nucleatum. T. denticola mainly induced immune disorder in spleen. ILC3s, Tregs, CD11B+ dendritic cells s, MNPs, macrophages, and plasmacytoid dendritic cells were the main types in response to key periodontal bacteria. However, the alveolar bone loss was not induced by key periodontal bacteria. In conclusion, the overall immunoregulation of monomicrobial stimuli to decipher the complexities of periodontitis was provided in this study. P. gingivalis, F. nucleatum, and T. denticola have different effects on local and systemic immunity in gingiva, colon, and spleen of germ-free mice.

14.
Front Microbiol ; 13: 889415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756043

RESUMO

A two-way relationship between diabetes and periodontitis has been discussed recently. Periodontitis microbiota might affect the immune homeostasis of diabetes, but the molecular mechanism of their interactions is still not clear. The aims of this study were to clarify the possible immune regulatory effects of periodontitis microbiota on diabetes and the correlation between immunomodulation and ectopic colonization. A model of germ-free mice with streptozotocin-induced type 1 diabetes mellitus (T1D), which was orally inoculated with mixed saliva samples for 2 weeks, was used in this study. Those mice were randomly divided into two groups, namely, SP (where the T1D mice were orally inoculated with mixed saliva samples from periodontitis patients) and SH (where the T1D mice were orally inoculated with mixed saliva samples from healthy subjects). Ectopic colonization of saliva microbiota was assessed using culture-dependent method and Sanger sequencing, and the composition of gut microbiota was analyzed using 16S rRNA gene sequencing. Changes in 15 types of immune cells and six cytokines either from the small intestine or spleen were detected by multicolor flow cytometry. The correlation between gut microbiota and immune cells was evaluated by redundancy analysis. Although periodontitis microbiota minorly colonized the lungs, spleens, and blood system, they predominantly colonized the gut, which was mainly invaded by Klebsiella. SH and SP differed in beta diversity of the gut bacterial community. Compared to SH, microbial alteration in small intestine occurred with an increase of Lacticaseibacillus, Bacillus, Agathobacter, Bacteroides, and a decrease of Raoultella in SP. More types of immune cells were disordered in the spleen than in the small intestine by periodontitis microbiota, mainly with a dramatical increase in the proportion of macrophages, plasmacytoid dendritic cells (pDCs), monocytes, group 3 innate lymphoid cells, CD4-CD8- T cells and Th17 cells, as well as a decline of αßT cells in SP. Cytokines of IFNγ, IL17, and IL22 produced by CD4 + T cells as well as IL22 produced by ILCs of small intestine rose in numbers, and the intestinal and splenic pDCs were positively regulated by gut bacterial community in SP. In conclusion, periodontitis microbiota invasion leads to ectopic colonization of the extra-oral sites and immune cells infiltration, which might cause local or systemic inflammation. Those cells are considered to act as a "bridge" between T1D and periodontitis.

15.
J Org Chem ; 76(8): 2896-8, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21391621

RESUMO

The target monomer, perfluoroethanesulfonyl fluoride vinyl ether 8, was obtained from the starting material, iodoperfluoroethanesulfonyl fluoride 1, through the intermediate, acyl fluoride 4. Two different synthetic routes were utilized in the conversion of 4 to 8.

16.
Artif Intell Med ; 114: 102038, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33875157

RESUMO

Sleep scoring is an important step for the detection of sleep disorders and usually performed by visual analysis. Since manual sleep scoring is time consuming, machine-learning based approaches have been proposed. Though efficient, these algorithms are black-box in nature and difficult to interpret by clinicians. In this paper, we propose a deep learning architecture for multi-modal sleep scoring, investigate the model's decision making process, and compare the model's reasoning with the annotation guidelines in the AASM manual. Our architecture, called STQS, uses convolutional neural networks (CNN) to automatically extract spatio-temporal features from 3 modalities (EEG, EOG and EMG), a bidirectional long short-term memory (Bi-LSTM) to extract sequential information, and residual connections to combine spatio-temporal and sequential features. We evaluated our model on two large datasets, obtaining an accuracy of 85% and 77% and a macro F1 score of 79% and 73% on SHHS and an in-house dataset, respectively. We further quantify the contribution of various architectural components and conclude that adding LSTM layers improves performance over a spatio-temporal CNN, while adding residual connections does not. Our interpretability results show that the output of the model is well aligned with AASM guidelines, and therefore, the model's decisions correspond to domain knowledge. We also compare multi-modal models and single-channel models and suggest that future research should focus on improving multi-modal models.


Assuntos
Eletroencefalografia , Fases do Sono , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Sono
17.
Science ; 368(6486): 48-53, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241942

RESUMO

Neural stem cells (NSCs) in the developing and postnatal brain have distinct positional identities that dictate the types of neurons they generate. Although morphogens initially establish NSC positional identity in the neural tube, it is unclear how such regional differences are maintained as the forebrain grows much larger and more anatomically complex. We found that the maintenance of NSC positional identity in the murine brain requires a mixed-lineage leukemia 1 (Mll1)-dependent epigenetic memory system. After establishment by sonic hedgehog, ventral NSC identity became independent of this morphogen. Even transient MLL1 inhibition caused a durable loss of ventral identity, resulting in the generation of neurons with the characteristics of dorsal NSCs in vivo. Thus, spatial information provided by morphogens can be transitioned to epigenetic mechanisms that maintain regionally distinct developmental programs in the forebrain.


Assuntos
Impressão Genômica , Histona-Lisina N-Metiltransferase/fisiologia , Proteína de Leucina Linfoide-Mieloide/fisiologia , Células-Tronco Neurais/fisiologia , Neurogênese/genética , Prosencéfalo/citologia , Prosencéfalo/embriologia , Fator Nuclear 1 de Tireoide/genética , Animais , Proteínas Hedgehog/metabolismo , Histona-Lisina N-Metiltransferase/genética , Camundongos , Camundongos Mutantes , Proteína de Leucina Linfoide-Mieloide/genética , Células-Tronco Neurais/citologia , Transcriptoma
18.
Biosci Rep ; 39(5)2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30979830

RESUMO

We assessed the relationship between the volume of epicardial adipose tissue and long-term outcomes in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). The patients with CHD were followed for at least 2 years after PCI. The epicardial adipose tissue volume (EATV) was measured using multi-slice computed tomography. Cox regression analysis was used to examine the relationship between EATV and clinical outcome. In this study, 500 patients were enrolled and followed up for a median of 25.2 months. The incidence of adverse cardiovascular events was 12.4%. No significant differences were observed in age, sex, proportion of patients with hypertension or diabetes, smoking, drinking, total cholesterol, triglyceride, high-density lipoprotein, or unstable angina pectoris among different EATV quartiles (P>0.05). The EATV was associated with body mass index (P<0.0001), low-density lipoprotein level (P=0.039), high-sensitivity C-reactive protein level (P<0.001), uric acid level (P=0.004), adiponectin level (P<0.001), and left ventricular ejection fraction (P<0.001). Kaplan-Meier analysis indicated a significant difference in survival rate of patients in EATV quartile 1 versus 4 (P=0.019). After adjusting for confounding factors, EATV quartile 4 (>216.15 cm3) was still associated with adverse cardiovascular outcomes (HR = 1.98, 95% CI: 1.15-4.47, P=0.023) compared with quartile 1 (<101.58 cm3). Our data suggest that EATV is an independent predictor of long-term major adverse cardiovascular events in CHD patients after PCI. Therefore, assessment of EATV using multi-slice computed tomography may contribute to risk stratification in these patients.


Assuntos
Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/métodos , Pericárdio/metabolismo , Tecido Adiposo/diagnóstico por imagem , Idoso , Índice de Massa Corporal , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/metabolismo , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Intervenção Coronária Percutânea/efeitos adversos , Pericárdio/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
19.
Int J Oral Sci ; 11(2): 13, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31263096

RESUMO

The biodiversity of the mycobiome, an important component of the oral microbial community, and the roles of fungal-bacterial and fungal-immune system interactions in the pathogenesis of oral lichen planus (OLP) remain largely uncharacterized. In this study, we sequenced the salivary mycobiome and bacteriome associated with OLP. First, we described the dysbiosis of the microbiome in OLP patients, which exhibits lower levels of fungi and higher levels of bacteria. Significantly higher abundances of the fungi Candida and Aspergillus in patients with reticular OLP and of Alternaria and Sclerotiniaceae_unidentified in patients with erosive OLP were observed compared to the healthy controls. Aspergillus was identified as an "OLP-associated" fungus because of its detection at a higher frequency than in the healthy controls. Second, the co-occurrence patterns of the salivary mycobiome-bacteriome demonstrated negative associations between specific fungal and bacterial taxa identified in the healthy controls, which diminished in the reticular OLP group and even became positive in the erosive OLP group. Moreover, the oral cavities of OLP patients were colonized by dysbiotic oral flora with lower ecological network complexity and decreased fungal-Firmicutes and increased fungal-Bacteroidetes sub-networks. Third, several keystone fungal genera (Bovista, Erysiphe, Psathyrella, etc.) demonstrated significant correlations with clinical scores and IL-17 levels. Thus, we established that fungal dysbiosis is associated with the aggravation of OLP. Fungal dysbiosis could alter the salivary bacteriome or may reflect a direct effect of host immunity, which participates in OLP pathogenesis.


Assuntos
Bactérias/isolamento & purificação , Disbiose/microbiologia , Líquen Plano Bucal/microbiologia , Microbiota , Mucosa Bucal/microbiologia , Micobioma , Saliva/microbiologia , Adulto , Estudos de Casos e Controles , Disbiose/complicações , Feminino , Humanos , Líquen Plano Bucal/complicações , Masculino , Pessoa de Meia-Idade
20.
Chem Commun (Camb) ; (2): 208-10, 2008 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-18092089

RESUMO

The preparation of a variety of optically pure peptides containing an N-1H,1H-perfluoroalkyl label on a selected backbone amide bond is now possible.


Assuntos
Flúor/química , Peptídeos/química , Alquilação , Isomerismo , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Peptídeos/síntese química , Prótons , Solventes , Temperatura
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