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1.
Synth Syst Biotechnol ; 9(4): 733-741, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38911060

RESUMO

Collagen XVII (COL17) is a transmembrane protein that mediates skin homeostasis. Due to expression of full length collagen was hard to achieve in microorganisms, arising the needs for selection of collagen fragments with desired functions for microbial biosynthesis. Here, COL17 fragments (27-33 amino acids) were extracted and replicated 16 times for recombinant expression in Escherichia coli. Five variants were soluble expressed, with the highest yield of 223 mg/L. The fusion tag was removed for biochemical and biophysical characterization. Circular dichroism results suggested one variant (sample-1707) with a triple-helix structure at >37 °C. Sample-1707 can assemble into nanofiber (width, 5.6 nm) and form hydrogel at 3 mg/mL. Sample-1707 was shown to induce blood clotting and promote osteoblast differentiation. Furthermore, sample-1707 exhibited high capacity to induce mouse hair follicle stem cells differentiation and osteoblast migration, demonstrating a high capacity to induce skin cell regeneration and promote wound healing. A strong hydrogel was prepared from a chitosan and sample-1707 complex with a swelling rate of >30 % higher than simply using chitosan. Fed-batch fermentation of sample-1707 with a 5-L bioreactor obtained a yield of 600 mg/L. These results support the large-scale production of sample-1707 as a biomaterial for use in the skin care industry.

2.
Environ Int ; 178: 108072, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37406371

RESUMO

Though with bioaccumulation and toxicity, chlorinated paraffins (CPs) are still high produced and widely utilized in various daily necessities for extender plasticization and flame retardation. CPs can be released during the reprocessing processes of finishing materials and distributed in multi-environmental media. Herein, concentrations and compositions of CPs in four representative media including interior finishing materials, PM10, total suspended particulate (TSP), and dust samples collected from eight interior finishing stages were studied. Unexpectedly, CP concentrations in ceramic tiles was found to be high with a mean value of 7.02 × 103 µg g-1, which could be attributed to the presence of CPs in the protective wax coated on ceramic tiles surfaces. Furthermore, the pollution characteristics of short-chain and medium-chain CPs (SCCPs and MCCPs) in those samples were inconsistent. According to the investigation regarding Kdust-TSP and [Formula: see text] , the occurrence and distribution of CPs in indoor atmospheric particles (PM10 and TSP) and dust were highly affected by reprocessing processes (cutting, hot melting, etc.) compared to that in the finishing materials. Moreover, dermal contact was the primary pathway of CP exposure for the occupational population (interior construction workers) for most interior finishing stages, and the interior finishing process is the prime CP exposure period for the occupational groups. As suggested by our assessment, though hardly posing an immediate health risk, CPs exposure still presents unneglected adverse health effects, which calls for adequate personal protections during interior finishing, especially in developing countries.


Assuntos
Hidrocarbonetos Clorados , Parafina , Humanos , Parafina/análise , Hidrocarbonetos Clorados/análise , Multimídia , Monitoramento Ambiental , Poeira/análise , China
3.
Int J Mol Sci ; 24(9)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37175632

RESUMO

It is well established that potassium (K+) is an essential nutrient for wheat (Triticum aestivum L.) growth and development. Several microRNAs (miRNAs), including miR166, are reportedly vital roles related to plant growth and stress responses. In this study, a K+ starvation-responsive miRNA (miR166d) was identified, which showed increased expression in the roots of wheat seedlings exposed to low-K+ stress. The overexpression of miR166d considerably increased the tolerance of transgenic Arabidopsis plants to K+ deprivation treatment. Furthermore, disrupting miR166d expression via virus-induced gene silencing (VIGS) adversely affected wheat adaptation to low-K+ stress. Additionally, miR166d directly targeted the calcium-dependent protein kinase 7-D gene (TaCPK7-D) in wheat. The TaCPK7-D gene expression was decreased in wheat seedling roots following K+ starvation treatment. Silencing TaCPK7-D in wheat increased K+ uptake under K+ starvation. Moreover, we observed that the miR166d/TaCPK7-D module could affect wheat tolerance to K+ starvation stress by regulating TaAKT1 and TaHAK1 expression. Taken together, our results indicate that miR166d is vital for K+ uptake and K+ starvation tolerance of wheat via regulation of TaCPK7-D.


Assuntos
Proteínas de Plantas , Triticum , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Potássio/metabolismo , Plântula/genética , Plântula/metabolismo , Transdução de Sinais/genética , Triticum/metabolismo , MicroRNAs
4.
Sensors (Basel) ; 23(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37050671

RESUMO

Few-shot object detection (FSOD) is proposed to solve the application problem of traditional detectors in scenarios lacking training samples. The meta-learning methods have attracted the researchers' attention for their excellent generalization performance. They usually select the same class of support features according to the query labels to weight the query features. However, the model cannot possess the ability of active identification only by using the same category support features, and feature selection causes difficulties in the testing process without labels. The single-scale feature of the model also leads to poor performance in small object detection. In addition, the hard samples in the support branch impact the backbone's representation of the support features, thus impacting the feature weighting process. To overcome these problems, we propose a multi-scale feature fusion and attentive learning (MSFFAL) framework for few-shot object detection. We first design the backbone with multi-scale feature fusion and channel attention mechanism to improve the model's detection accuracy on small objects and the representation of hard support samples. Based on this, we propose an attention loss to replace the feature weighting module. The loss allows the model to consistently represent the objects of the same category in the two branches and realizes the active recognition of the model. The model no longer depends on query labels to select features when testing, optimizing the model testing process. The experiments show that MSFFAL outperforms the state-of-the-art (SOTA) by 0.7-7.8% on the Pascal VOC and exhibits 1.61 times the result of the baseline model in MS COCO's small objects detection.

5.
Sensors (Basel) ; 23(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36772658

RESUMO

The emergence of Transformer has led to the rapid development of video understanding, but it also brings the problem of high computational complexity. Previously, there were methods to divide the feature maps into windows along the spatiotemporal dimensions and then calculate the attention. There are also methods to perform down-sampling during attention computation to reduce the spatiotemporal resolution of features. Although the complexity is effectively reduced, there is still room for further optimization. Thus, we present the Windows and Linear Transformer (WLiT) for efficient video action recognition, by combining Spatial-Windows attention with Linear attention. We first divide the feature maps into multiple windows along the spatial dimensions and calculate the attention separately inside the windows. Therefore, our model further reduces the computational complexity compared with previous methods. However, the perceptual field of Spatial-Windows attention is small, and global spatiotemporal information cannot be obtained. To address this problem, we then calculate Linear attention along the channel dimension so that the model can capture complete spatiotemporal information. Our method achieves better recognition accuracy with less computational complexity through this mechanism. We conduct extensive experiments on four public datasets, namely Something-Something V2 (SSV2), Kinetics400 (K400), UCF101, and HMDB51. On the SSV2 dataset, our method reduces the computational complexity by 28% and improves the recognition accuracy by 1.6% compared to the State-Of-The-Art (SOTA) method. On the K400 and two other datasets, our method achieves SOTA-level accuracy while reducing the complexity by about 49%.

6.
J Nucl Cardiol ; 30(4): 1427-1436, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36593332

RESUMO

BACKGROUND: Functional assessment of myocardial ischemia is critical for patients with intermediate coronary stenosis. As the diagnosis performance of absolute quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) by single-photon emission tomography (SPECT) has been proven, its prognostic value in patients with intermediate coronary stenosis remains to be evaluated. METHODS: Patients with one or more target lesions of ≥ 50% to ≤ 80% diameter stenoses on invasive coronary angiography were prospectively included in this study. All patients were scheduled for clinically indicated SPECT myocardial perfusion imaging (MPI) within 3 months and agreed to provide informed consent to participate in quantitative SPECT acquisitions to obtain MBF and MFR values. The primary endpoint was defined as a composite of the major adverse cardiac events (MACE): Cardiac death, myocardial infarction, late revascularization and heart failure or unstable angina-related rehospitalization. RESULTS: One hundred and nineteen patients (mean age 57 ± 8 years, 62.2% men) were included in the analysis. The average lumen stenosis of patients was 67.0 ± 10.4%. Over a median follow-up duration of 1408 days (interquartile range 1297-1666 days), 18 patients (15.1%) had MACE. Patients with impaired MFR (MFR < 2) had a significantly higher incidence of events than those with preserved MFR (MFR ≥ 2) in Kaplan-Meier survival analysis (Log-rank = 8.105, P = 0.004), while no significant difference was found between patients with normal relative perfusion and those with relative perfusion abnormalities (log-rank = 0.098, P > 0.05). In a multivariate Cox hazards analysis, the SPECT-derived MFR remained an independent predictor of MACE (HR 0.352, 95% CI 0.145-0.854, P = 0.021). CONCLUSIONS: In a cohort of patients with angiographic intermediate coronary lesions, SPECT-derived MFR was an independent predictor of prognosis.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Prognóstico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Estenose Coronária/diagnóstico por imagem , Angiografia Coronária/métodos , Imagem de Perfusão do Miocárdio/métodos
7.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362290

RESUMO

Potassium (K+) is essential for plant growth and stress responses. A deficiency in soil K+ contents can result in decreased wheat quality and productivity. Thus, clarifying the molecular mechanism underlying wheat responses to low-K+ (LK) stress is critical. In this study, a tandem mass tag (TMT)-based quantitative proteomic analysis was performed to investigate the differentially abundant proteins (DAPs) in roots of the LK-tolerant wheat cultivar "KN9204" at the seedling stage after exposure to LK stress. A total of 104 DAPs were identified in the LK-treated roots. The DAPs related to carbohydrate and energy metabolism, transport, stress responses and defense, and post-translational modifications under LK conditions were highlighted. We identified a high-affinity potassium transporter (TaHAK1-4A) that was significantly up-regulated after the LK treatment. Additionally, TaHAK1-4A was mainly expressed in roots, and the encoded protein was localized in the plasma membrane. The complementation assay in yeast suggested that TaHAK1-4A mediates K+ uptake under extreme LK conditions. The overexpression of TaHAK1-4A increased the fresh weight and root length of Arabidopsis under LK conditions and improved the growth of Arabidopsis athak5 mutant seedlings, which grow poorly under LK conditions. Moreover, silencing of TaHAK1-4A in wheat roots treated with LK stress decreased the root length, dry weight, K+ concentration, and K+ influx. Accordingly, TaHAK1-4A is important for the uptake of K+ by roots exposed to LK stress. Our results reveal the protein metabolic changes in wheat induced by LK stress. Furthermore, we identified a candidate gene potentially relevant for developing wheat lines with increased K+ use efficiency.


Assuntos
Arabidopsis , Deficiência de Potássio , Arabidopsis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Potássio/metabolismo , Deficiência de Potássio/metabolismo , Proteômica , Plântula/genética , Plântula/metabolismo , Triticum/genética , Triticum/metabolismo
8.
Plant Sci ; 318: 111242, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35351310

RESUMO

Cold acclimation (CA) is an important evolutionary adaptive mechanism for wheat freezing resistence. To clarify the molecular basis of wheat CA and freezing tolerance, the effects of CA (4 °C) and non-CA (20 °C) treatments and freezing stress (-5 °C) on the proteins in the wheat crown were characterized via an iTRAQ-based proteomic analysis. A total of 669 differentially accumulated proteins (DAPs) were identified after the CA, of which seven were also DAPs in the CA plants exposed to freezing stress. Additionally, the 15 DAPs in the CA group and the 23 DAPs in the non-CA group after the freezing treatment differed substantially. Functional analyses indicated that CA enhanced freezing tolerance by regulating proteins involved in signal transduction, carbohydrate metabolism, stress and defense responses, and phenylpropanoid biosynthesis. An integrated transcriptomic, proteomic, and metabolomic analysis revealed significant changes in various components of the glutathione metabolic pathway. The overexpression and silencing of Wdhn13 in Arabidopsis and wheat resulted in increased tolerance and sensitivity to freezing stress, respectively, suggesting Wdhn13 promotes freezing tolerance. Overall, our study offers insights into the regulatory network underlying the CA and freezing tolerance of wheat, which may be useful for elucidating wheat freezing resistance.


Assuntos
Proteômica , Triticum , Aclimatação/fisiologia , Congelamento , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Triticum/metabolismo
9.
Int J Cardiovasc Imaging ; 38(10): 2249-2259, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37726464

RESUMO

To investigate the value of ventilation/perfusion (V/Q) scanning and CT pulmonary angiography (PA) in predicting CTEPH development after acute pulmonary embolism (APE). This study was performed in APE patients who had undergone both V/Q and CT PA after 3-month anticoagulation. The residual pulmonary obstructions were assessed based on V/Q and CT PA, and then recorded as pulmonary perfusion detect score (PPDs) and CT pulmonary artery obstruction index (PAOI). The predictive performance of PPDs and CT PAOI for CTEPH were determined and risk factors for predicting CTEPH development were identified. A total of 235 patients with initial diagnosis of APE were included in this study. ROC analysis showed that the AUCs of the PPDs and CT PAOI were 0.957 and 0.895, with corresponding cut-off values of 20.50% and 17.50% for predicting CTEPH development. Neither sensitivity nor specificity differed significantly between PPDs and CT PAOI (Sensitivity: 92.00% vs. 80.00%, P = 0.25; Specificity: 88.10% vs. 89.52%, P = 0.69). The univariable and multivariable logistic regression analysis demonstrated that pulmonary arterial hypertension confirmed by echocardiography at initial APE diagnosis (OR: 6.16, 95%CI: 1.31-29.02, P = 0.02), a PPDs of > 20.50% (OR: 22.95, 95%CI: 2.37-222.19, P = 0.007), and a CT PAOI of > 17.50% (OR: 9.98, 95%CI: 2.06-48.49, P = 0.004) were associated with CTEPH development. Both V/Q and CT PA after 3-month anticoagulation for APE showed great performance in predicting CTEPH development, and V/Q scanning has a tendency to be more sensitive but less specific than CT PA. The residual pulmonary embolism detected by V/Q and CT PA was associated with an increased risk of CTEPH development.


Assuntos
Obstrução das Vias Respiratórias , Hominidae , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Animais , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/etiologia , Seguimentos , Valor Preditivo dos Testes , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Angiografia , Angiografia por Tomografia Computadorizada , Artéria Pulmonar/diagnóstico por imagem , Perfusão , Doença Aguda , Anticoagulantes
10.
Phys Rev Lett ; 126(3): 036401, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33543980

RESUMO

Including prior knowledge is important for effective machine learning models in physics and is usually achieved by explicitly adding loss terms or constraints on model architectures. Prior knowledge embedded in the physics computation itself rarely draws attention. We show that solving the Kohn-Sham equations when training neural networks for the exchange-correlation functional provides an implicit regularization that greatly improves generalization. Two separations suffice for learning the entire one-dimensional H_{2} dissociation curve within chemical accuracy, including the strongly correlated region. Our models also generalize to unseen types of molecules and overcome self-interaction error.

11.
Cell ; 184(1): 272-288.e11, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33378642

RESUMO

Comprehensively resolving neuronal identities in whole-brain images is a major challenge. We achieve this in C. elegans by engineering a multicolor transgene called NeuroPAL (a neuronal polychromatic atlas of landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that resolves all neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. We showcase three applications that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding for these stimuli.


Assuntos
Atlas como Assunto , Mapeamento Encefálico , Encéfalo/fisiologia , Caenorhabditis elegans/fisiologia , Neurônios/fisiologia , Software , Algoritmos , Pontos de Referência Anatômicos , Animais , Corpo Celular/fisiologia , Linhagem da Célula , Drosophila/fisiologia , Mutação/genética , Rede Nervosa/fisiologia , Fenótipo , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de Neurotransmissores/metabolismo , Olfato/fisiologia , Paladar/fisiologia , Fatores de Transcrição/metabolismo , Transgenes
12.
Front Plant Sci ; 11: 588994, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123186

RESUMO

Potassium (K) is essential for regulating plant growth and mediating abiotic stress responses. Elucidating the biological mechanism underlying plant responses to K-deficiency is crucial for breeding new cultivars with improved K uptake and K utilization efficiency. In this study, we evaluated the extent of the genetic variation among 543 wheat accessions differing in K-deficiency tolerance at the seedling and adult plant stages. Two accessions, KN9204 and BN207, were identified as extremely tolerant and sensitive to K-deficiency, respectively. The accessions were exposed to normal and K-deficient conditions, after which their roots underwent ionomic, transcriptomic, and metabolomic analyses. Under K-deficient conditions, KN9204 exhibited stronger root growth and maintained higher K concentrations than BN207. Moreover, 19,440 transcripts and 162 metabolites were differentially abundant in the roots of both accessions according to transcriptomic and metabolomic analyses. An integrated analysis of gene expression and metabolite profiles revealed that substantially more genes, including those related to ion homeostasis, cellular reactive oxygen species homeostasis, and the glutamate metabolic pathway, were up-regulated in KN9204 than in BN207 in response to low-K stress. Accordingly, these candidate genes have unique regulatory roles affecting plant K-starvation tolerance. These findings may be useful for further clarifying the molecular changes underlying wheat root adaptations to K deprivation.

13.
J Mol Neurosci ; 65(3): 391-399, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29974381

RESUMO

Ischemic stroke is one of the most dangerous acute diseases which causes death or deformity. Apoptosis has been shown to play an important role in the development and pathogenesis of cerebral ischemia-reperfusion injury (I/R injury), but the related mechanism is unclear. Levo-tetrahydropalmatine (L-THP), a bioactive ingredient extracted from the Chinese herb Corydalis, can penetrate the blood-brain barrier and exert various pharmacological effects on neural tissues. The present study examined the neuroprotective effect of L-THP on neuronal apoptosis induced by cerebral I/R injury. Results showed that pretreatment with L-THP (12.5, 25, and 50 mg/kg) improved neurological outcomes and reduced infarct volume and cerebral edema in comparison with the brains of the middle cerebral artery occlusion (MCAO) group. These findings provided evidence for the neuroprotective effects of L-THP against cerebral I/R injury. Furthermore, administration of L-THP enhanced the expression of Bcl-2 and attenuated the content of Bax, cleaved caspase-3, and PARP. L-THP could improve the reduction of NeuN-positive cells induced by I/R injury. These results suggested that L-THP could inhibit neuroapoptosis in cerebral ischemic rats. c-Abl was discovered as the critical protein responsible for neurocyte apoptosis; however, few data have been published on the relation between ischemic stroke and the expression of c-Abl. We found that both c-Abl expression and neuronal apoptosis were significantly increased in the MCAO group, while pretreatment with L-THP could ameliorate this effect. Therefore, we deduced that reduced c-Abl overexpression may play a role in the anti-apoptosis effect of L-THP after cerebral I/R injury. Thus, L-THP may provide a potential therapeutic approach for the treatment of ischemic stroke. Graphical Abstract ᅟ.


Assuntos
Apoptose , Alcaloides de Berberina/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Proto-Oncogênicas c-abl/metabolismo , Ratos , Ratos Sprague-Dawley
14.
Life Sci ; 206: 117-124, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800538

RESUMO

BACKGROUND: Current evidence supports that inflammatory reaction in the hippocampus is a potential cause of major depressive disorder (MDD). Perilla aldehyde (PAH), a major constituent from Perilla frutescens, has been reported to have anti-inflammatory and anti-oxidant activity. The aim of this study is to explore the antidepressant-like effect and the underlying mechanism of PAH on the rats model induced by chronic unpredictable mild stress (CUMS). METHODS: CUMS rats model was built to tested their depressive-like behaviors. The levels of pro-inflammatory cytokines were tested. Proteins were analyzed by Western blot and Immunohistochemistry. RESULTS: We found that treatment with PAH (20, 40 mg/kg) and fluoxetine (FLU, 10 mg/kg) significantly improved the sucrose consumption, immobility time in forced swim test (FST), as well as locomotor activity in open-field test (OFT). The levels of pro-inflammatory cytokines in hippocampus were also suppressed effectively by PAH and FLU administration. Western blot analysis showed the up-regulated levels of TXNIP, NLRP3, Cleaved caspase-1 and p-NF-κB p65 in the hippocampus in rats exposed to CUMS paradigm, while different degrees of down-regulation in their expression were detected after PAH (20, 40 mg/kg) and FLU (10 mg/kg) treatment respectively. The results from histopathological examination further demonstrated that PAH (20, 40 mg/kg) and FLU (10 mg/kg) treatment reversed the alteration of TRX, NLRP3 and Cleaved caspase-1 induced by CUMS procedure. CONCLUSIONS: Our results demonstrated that PAH exhibited antidepressant-like effect in CUMS-induced rats model of depression, which might be mediated by TXNIP/TRX/NLRP3 pathway.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Depressão/etiologia , Depressão/prevenção & controle , Monoterpenos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Perilla/química , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/complicações , Tiorredoxinas/antagonistas & inibidores , Animais , Antidepressivos de Segunda Geração/farmacologia , Inibidores de Caspase/farmacologia , Proteínas de Ciclo Celular , Doença Crônica , Citocinas/metabolismo , Depressão/psicologia , Fluoxetina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/prevenção & controle , Inflamação/psicologia , Masculino , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/psicologia , Natação/psicologia
15.
Eur J Pharmacol ; 815: 118-126, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28743390

RESUMO

Cerebral ischemia/reperfusion (I/R) is a lethal and disabling disease. Studies have suggested that hyperglycemia is a risk factor for cerebral I/R. Baicalin is a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi with neuroprotective activity. In the present study, we investigated the effects of baicalin on hyperglycemia-exacerbated cerebral I/R injury. Streptozotocin (STZ) injection aggravated the brain damage induced by middle cerebral artery occlusion (MCAO) surgery, while baicalin administration reduced blood glucose, relieved neurological deficit and decreased infarct volume. In vitro, Oxygen-glucose deprivation/ reperfusion (OGD/REP) induced inordinate reactive oxygen species (ROS) production and mitochondrial dynamic impairments were markedly increased under high glucose (HG) condition. Baicalin treatment in PC12 cells inhibited dynamin-related protein 1 (Drp-1) expression, decreased mitochondrial fission, promoted mitofusin-2 (MFN2) generation, increased Drp-1 Ser637 phosphorylation, and elevated mitochondrial membrane potential (Δψm) via the suppression of ROS production. However, AMPKα1 knockdown abolished the protective effects of baicalin. Baicalin also suppressed cell apoptosis and enhanced mitophagy. These results suggested that baicalin protected against hyperglycemia aggravated I/R injury by regulating mitochondrial functions in a manner dependent on AMPK.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Flavonoides/farmacologia , Hiperglicemia/complicações , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Quinases Associadas com Morte Celular/metabolismo , Ativação Enzimática/efeitos dos fármacos , Flavonoides/uso terapêutico , GTP Fosfo-Hidrolases , Infarto da Artéria Cerebral Média/complicações , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Mitocôndrias/patologia , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo
16.
Ticks Tick Borne Dis ; 8(4): 631-639, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28461151

RESUMO

Tick-borne encephalitis (TBE) has become an increasing public health threat in recent years, ranging from Europe, through far-eastern Russia to Japan and northern China. However, the neglect of its expansion and scarce analyses of the dynamics have made the overall disease burden and the risk distribution of the disease being unclear in mainland China. In this study, we described epidemiological characteristics of 2117 reported human TBE cases from 2006 to 2013 in mainland China. About 99% of the cases were reported in forest areas of northeastern China, and 93% of reported infections occurred during May-July. Cases were primarily male (67%), mostly in 30-59 years among all age-gender groups. Farmers (31.6%), domestic workers (20.1%) and forest workers (17.9%) accounted for the majority of the patients, and the proportions of patients from farmers and domestic workers were increasing in recent years. The epidemiological features of TBE differed slightly across the affected regions. The distribution and features of the disease in three main endemic areas of mainland China were also summarized. Using the Boosted Regression Trees (BRT) model, we found that the presence of TBE was significantly associated with a composite meteorological index, altitude, the coverage of broad-leaved forest, the coverage of mixed broadleaf-conifer forest, and the distribution of Ixodes persulcatus (I. persulcatus) ticks. The model-predicted probability of presence of human TBE cases in mainland China was mapped at the county level. The spatial distribution of human TBE in China was largely driven by the distributions of forests and I. persulcatus ticks, altitude, and climate. Enhanced surveillance and intervention for human TBE in the high-risk regions, particularly on the forest areas in north-eastern China, is necessary to prevent human infections.


Assuntos
Distribuição Animal , Vírus da Encefalite Transmitidos por Carrapatos/isolamento & purificação , Encefalite Transmitida por Carrapatos/epidemiologia , Florestas , Ixodes/fisiologia , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , China/epidemiologia , Encefalite Transmitida por Carrapatos/virologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Ixodes/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
17.
Proc Natl Acad Sci U S A ; 113(16): 4488-93, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27035948

RESUMO

Sierra Leone is the most severely affected country by an unprecedented outbreak of Ebola virus disease (EVD) in West Africa. Although successfully contained, the transmission dynamics of EVD and the impact of interventions in the country remain unclear. We established a database of confirmed and suspected EVD cases from May 2014 to September 2015 in Sierra Leone and mapped the spatiotemporal distribution of cases at the chiefdom level. A Poisson transmission model revealed that the transmissibility at the chiefdom level, estimated as the average number of secondary infections caused by a patient per week, was reduced by 43% [95% confidence interval (CI): 30%, 52%] after October 2014, when the strategic plan of the United Nations Mission for Emergency Ebola Response was initiated, and by 65% (95% CI: 57%, 71%) after the end of December 2014, when 100% case isolation and safe burials were essentially achieved, both compared with before October 2014. Population density, proximity to Ebola treatment centers, cropland coverage, and atmospheric temperature were associated with EVD transmission. The household secondary attack rate (SAR) was estimated to be 0.059 (95% CI: 0.050, 0.070) for the overall outbreak. The household SAR was reduced by 82%, from 0.093 to 0.017, after the nationwide campaign to achieve 100% case isolation and safe burials had been conducted. This study provides a complete overview of the transmission dynamics of the 2014-2015 EVD outbreak in Sierra Leone at both chiefdom and household levels. The interventions implemented in Sierra Leone seem effective in containing the epidemic, particularly in interrupting household transmission.


Assuntos
Bases de Dados Factuais , Ebolavirus , Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Doença pelo Vírus Ebola/transmissão , Modelos Biológicos , Feminino , Humanos , Masculino , Serra Leoa/epidemiologia
18.
Sci Rep ; 5: 18610, 2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26691585

RESUMO

It has been documented that the epidemiological characteristics of human infections with H7N9 differ significantly between H5N1. However, potential factors that may explain the different spatial distributions remain unexplored. We use boosted regression tree (BRT) models to explore the association of agro-ecological, environmental and meteorological variables with the occurrence of human cases of H7N9 and H5N1, and map the probabilities of occurrence of human cases. Live poultry markets, density of human, coverage of built-up land, relative humidity and precipitation were significant predictors for both. In addition, density of poultry, coverage of shrub and temperature played important roles for human H7N9 infection, whereas human H5N1 infection was associated with coverage of forest and water body. Based on the risks and distribution of ecological characteristics which may facilitate the circulation of the two viruses, we found Yangtze River Delta and Pearl River Delta, along with a few spots on the southeast coastline, to be the high risk areas for H7N9 and H5N1. Additional, H5N1 risk spots were identified in eastern Sichuan and southern Yunnan Provinces. Surveillance of the two viruses needs to be enhanced in these high risk areas to reduce the risk of future epidemics of avian influenza in China.


Assuntos
Virus da Influenza A Subtipo H5N1/fisiologia , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Animais , Aves/virologia , China/epidemiologia , Geografia , Humanos , Incidência , Modelos Biológicos , Probabilidade , Análise de Regressão , Fatores de Risco
19.
Lancet Infect Dis ; 15(12): 1467-1479, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26453241

RESUMO

Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia, and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.


Assuntos
Infecções por Anaplasmataceae/epidemiologia , Vetores Aracnídeos/microbiologia , Babesiose/epidemiologia , Doença de Lyme/epidemiologia , Infecções por Rickettsia/epidemiologia , Doenças Transmitidas por Carrapatos/epidemiologia , Carrapatos/microbiologia , Anaplasmataceae/patogenicidade , Anaplasmataceae/fisiologia , Infecções por Anaplasmataceae/microbiologia , Animais , Vetores Aracnídeos/classificação , Babesia/patogenicidade , Babesia/fisiologia , Babesiose/microbiologia , Grupo Borrelia Burgdorferi/patogenicidade , Grupo Borrelia Burgdorferi/fisiologia , China/epidemiologia , Humanos , Doença de Lyme/microbiologia , Saúde Pública/estatística & dados numéricos , Rickettsia/patogenicidade , Rickettsia/fisiologia , Infecções por Rickettsia/microbiologia , Doenças Transmitidas por Carrapatos/microbiologia , Carrapatos/classificação
20.
Int J Environ Res Public Health ; 12(5): 5026-45, 2015 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-26006118

RESUMO

Highly pathogenic avian influenza (HPAI) H5N1 has posed a significant threat to both humans and birds, and it has spanned large geographic areas and various ecological systems throughout Asia, Europe and Africa, but especially in mainland China. Great efforts in control and prevention of the disease, including universal vaccination campaigns in poultry and active serological and virological surveillance, have been undertaken in mainland China since the beginning of 2006. In this study, we aim to characterize the spatial and temporal patterns of HPAI H5N1, and identify influencing factors favoring the occurrence of HPAI H5N1 outbreaks in poultry in mainland China. Our study shows that HPAI H5N1 outbreaks took place sporadically after vaccination campaigns in poultry, and mostly occurred in the cold season. The positive tests in routine virological surveillance of HPAI H5N1 virus in chicken, duck, goose as well as environmental samples were mapped to display the potential risk distribution of the virus. Southern China had a higher positive rate than northern China, and positive samples were mostly detected from chickens in the north, while the majority were from duck in the south, and a negative correlation with monthly vaccination rates in domestic poultry was found (R = -0.19, p value = 0.005). Multivariate panel logistic regression identified vaccination rate, interaction between distance to the nearest city and national highway, interaction between distance to the nearest lake and wetland, and density of human population, as well as the autoregressive term in space and time as independent risk factors in the occurrence of HPAI H5N1 outbreaks, based on which a predicted risk map of the disease was derived. Our findings could provide new understanding of the distribution and transmission of HPAI H5N1 in mainland China and could be used to inform targeted surveillance and control efforts in both human and poultry populations to reduce the risk of future infections.


Assuntos
Galinhas , Patos , Virus da Influenza A Subtipo H5N1 , Influenza Aviária/virologia , Animais , China/epidemiologia , Surtos de Doenças , Influenza Aviária/epidemiologia , Modelos Logísticos , Fatores de Risco , Vacinação
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