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1.
Eur J Cancer Prev ; 33(4): 347-354, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38375832

RESUMO

OBJECTIVE: To evaluate the correlation between metabolic syndrome (MetS) and its components on the incidence of colorectal cancer (CRC) based on data from Jinchang Cohort. METHODS: This is a large prospective cohort study. Between 2011 and 2020, a total of 43 516 individuals from Jinchang Cohort were included for this study. Hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC according to MetS were calculated with the Cox proportional hazard models. The restricted cubic spine models with four knots were conducted to fit the dose-response relationships. RESULTS: MetS was associated with increased risk of CRC (n = 141; HR: 1.64, 95% CI: 1.15-2.33) after adjusting for confounding factors (age, sex, education level, family history of CRC, smoking index and alcohol index). Participants with hyperglycemia had a significantly higher risk of developing incident CRC (HR: 1.70; 95% CI: 1.19-2.43). The positive association between MetS and CRC was observed in males (HR: 1.76; 95% CI: 1.17-2.63), but not in females (HR: 1.24; 95% CI: 0.59-2.64). Furthermore, linear dose-response relationship was found between fasting plasma glucose (FPG) and CRC risk in males ( Poverall < 0.05, Pnon-linear = 0.35). When stratified by smoke and drink, MetS was found to increase the incidence of CRC only in the smoke (HR: 2.07, 95% CI: 1.35-3.18) and drink (HR: 2.93, 95% CI: 1.51-5.69) groups. CONCLUSION: MetS was associated with a higher risk of CRC incidence. Hyperglycemia lended strong support to the role of MetS in new-onset CRC, especially in males. Other components of MetS were not found to be associated with increased risk of CRC.


Assuntos
Neoplasias Colorretais , Síndrome Metabólica , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Masculino , Feminino , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Estudos Prospectivos , China/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Incidência , Adulto , Idoso , Seguimentos
2.
Sci Data ; 11(1): 242, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409278

RESUMO

Endoscopic optical coherence tomography (OCT) offers a non-invasive approach to perform the morphological and functional assessment of the middle ear in vivo. However, interpreting such OCT images is challenging and time-consuming due to the shadowing of preceding structures. Deep neural networks have emerged as a promising tool to enhance this process in multiple aspects, including segmentation, classification, and registration. Nevertheless, the scarcity of annotated datasets of OCT middle ear images poses a significant hurdle to the performance of neural networks. We introduce the Dresden in vivo OCT Dataset of the Middle Ear (DIOME) featuring 43 OCT volumes from both healthy and pathological middle ears of 29 subjects. DIOME provides semantic segmentations of five crucial anatomical structures (tympanic membrane, malleus, incus, stapes and promontory), and sparse landmarks delineating the salient features of the structures. The availability of these data facilitates the training and evaluation of algorithms regarding various analysis tasks with middle ear OCT images, e.g. diagnostics.


Assuntos
Orelha Média , Tomografia de Coerência Óptica , Humanos , Algoritmos , Orelha Média/diagnóstico por imagem , Redes Neurais de Computação , Tomografia de Coerência Óptica/métodos
3.
Int J Comput Assist Radiol Surg ; 19(1): 139-145, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37328716

RESUMO

PURPOSE: Middle ear infection is the most prevalent inflammatory disease, especially among the pediatric population. Current diagnostic methods are subjective and depend on visual cues from an otoscope, which is limited for otologists to identify pathology. To address this shortcoming, endoscopic optical coherence tomography (OCT) provides both morphological and functional in vivo measurements of the middle ear. However, due to the shadow of prior structures, interpretation of OCT images is challenging and time-consuming. To facilitate fast diagnosis and measurement, improvement in the readability of OCT data is achieved by merging morphological knowledge from ex vivo middle ear models with OCT volumetric data, so that OCT applications can be further promoted in daily clinical settings. METHODS: We propose C2P-Net: a two-staged non-rigid registration pipeline for complete to partial point clouds, which are sampled from ex vivo and in vivo OCT models, respectively. To overcome the lack of labeled training data, a fast and effective generation pipeline in Blender3D is designed to simulate middle ear shapes and extract in vivo noisy and partial point clouds. RESULTS: We evaluate the performance of C2P-Net through experiments on both synthetic and real OCT datasets. The results demonstrate that C2P-Net is generalized to unseen middle ear point clouds and capable of handling realistic noise and incompleteness in synthetic and real OCT data. CONCLUSIONS: In this work, we aim to enable diagnosis of middle ear structures with the assistance of OCT images. We propose C2P-Net: a two-staged non-rigid registration pipeline for point clouds to support the interpretation of in vivo noisy and partial OCT images for the first time. Code is available at: https://gitlab.com/nct_tso_public/c2p-net.


Assuntos
Orelha Média , Tomografia de Coerência Óptica , Humanos , Criança , Tomografia de Coerência Óptica/métodos , Orelha Média/diagnóstico por imagem , Orelha Média/patologia , Endoscopia
4.
Environ Manage ; 73(2): 378-394, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37365302

RESUMO

Ecosystem services (ESs) play a crucial connecting role between human well-being and natural ecosystems. Investigating ESs and their interrelationships can aid in the rational distribution of resources and benefits and inform planning decisions that align with the principles of ecological civilization. Nonetheless, our current understanding of these relationships remains limited; thus, further theoretical exploration is required. This study employs the InVEST model to assess the key ESs in Guangdong Province for 2000 and 2018 and applies the multi-scale geographically weighted regression (MGWR) method to identify the primary drivers of ES changes and capture trends in spatial variations. The results showed that (1) from 2000 to 2018, the total carbon storage (CS) and habitat quality (HQ) decreased while the water yield (WY) and net primary productivity (NPP) increased. These ESs also showed spatial differences, with higher values observed in the hilly and mountainous areas of the north compared with the coastal and plain areas of the south. (2) Although the spatial distribution of ES trade-off strength varied, the overall pattern remained consistent from 2000 to 2018. The pairwise trade-off strength of CS-WY and WY-HQ decreased significantly in the northern region of Guangdong due to low rainfall, while that of CS-HQ decreased significantly in the Pearl River delta as a result of urbanization. Cultivated and forested land displayed higher and lower levels of NPP and WY, respectively, with forested land exhibiting greater trade-off strength than the other land use types. (3) Evident spatial heterogeneity was observed in the properties and intensity of the correlations between driving factors and changes in ES trade-offs. Natural factors were the primary determinants of trade-offs among ESs. However, at a regional scale, the landscape index and socioeconomic factors tended to represent stronger drivers. Based on these findings, we suggest that ecological management should be adjusted based on the geographic scale. This study offers a valuable approach to understanding the relationship between ES trade-offs and their drivers in geographic space and serves as a reference for the sustainable provisioning of ESs both locally and globally.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Conservação dos Recursos Naturais/métodos , China , Florestas , Qualidade da Água
5.
Eur J Prev Cardiol ; 30(14): 1482-1491, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37315161

RESUMO

AIMS: To quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cardiovascular death, and the effects of risk factors on the rates of transition. METHODS AND RESULTS: We used data from the Jinchang Cohort of 42 585 adults aged 20-88 free of coronary heart disease (CHD) and stroke at baseline. A multistate model was applied for analysing the progression of CVD and its relation to various risk factors. During a median follow-up of 7 years, 7498 participants developed pre-diabetes, 2307 developed T2DM, 2499 developed CVD, and 324 died from CVD. Among 15 postulated transitions, transition from comorbid CHD and stroke to cardiovascular death had the highest rate (157.21/1000 person-years), followed by transition from stroke alone to cardiovascular death (69.31/1000 person-years) and transition from pre-diabetes to normoglycaemia (46.51/1000 person-years). Pre-diabetes had a sojourn time of 6.77 years, and controlling weight, blood lipids, blood pressure, and uric acid within normal limits may promote reversion to normoglycaemia. Among transitions to CHD alone and stroke alone, transition from T2DM had the highest rate (12.21/1000 and 12.16/1000 person-years), followed by transition from pre-diabetes (6.81/1000 and 4.93/1000 person-years) and normoglycaemia (3.28/1000 and 2.39/1000 person-years). Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions. CONCLUSION: Pre-diabetes was the optimal intervention stage in the disease trajectory. The derived transition rates, sojourn time, and influence factors could provide scientific support for the primary prevention of both T2DM and CVD.


Former single-outcome studies on the relationship between glycaemia and cardiovascular disease (CVD) may ignore the complexity and multi-transformations across the multiple stages from normoglycaemia to CVD in real-world setting. We aimed to quantify the trajectories from normoglycaemia to pre-diabetes, subsequently to type 2 diabetes, CVD, and cardiovascular death. Pre-diabetes was the optimal intervention stage in the disease trajectory. Transitions from CVD to death had much higher rates than other transitions. Age and hypertension were associated with an accelerated rate for most transitions. Overweight/obesity, smoking, dyslipidaemia, and hyperuricaemia played crucial but different roles in transitions.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Acidente Vascular Cerebral , Adulto , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Prospectivos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Fatores de Risco
6.
Food Funct ; 14(9): 4392-4405, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37092895

RESUMO

Oxidative stress is generally considered inseparable from the development and exacerbation of ulcerative colitis (UC). Therefore, reducing oxidative stress has become a possible way to alleviate UC. In this study, the therapeutic effects of different doses of liposome-embedded superoxide dismutase (L-SOD) on mice with DSS-induced UC were systematically investigated. The results showed that L-SOD significantly attenuated the signs of colitis in mice, including colonic shortening, diarrhoea, bloody stools, and histopathological changes. L-SOD ameliorated DSS-induced oxidative damage, increased SOD, catalase (CAT), and glutathione (GSH) activities, and decreased malondialdehyde (MDA) levels. In addition, L-SOD ameliorated the inflammatory response by inhibiting the expression of myeloperoxidase (MPO) and pro-inflammatory cytokines and protected barrier function by promoting the expression of the tight junction proteins occludin and ZO-1 in the colon. Importantly, the results demonstrated a bell-shaped distribution of therapeutic effects relative to the administered dose, with an optimal dose of 150 000 U kg-1. These results indicate that L-SOD has great potential as an ingredient in functional foods for the prevention and mitigation of UC.


Assuntos
Colite Ulcerativa , Colite , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Lipossomos/farmacologia , Colite/induzido quimicamente , Colo/metabolismo , Estresse Oxidativo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Glutationa/metabolismo , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
7.
Cancer Epidemiol ; 84: 102362, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37027905

RESUMO

BACKGROUND: The risk of hepatocellular carcinoma (HCC) is associated with a variety of factors. However, the possible association between the abnormal metabolism of fasting plasma glucose (FPG) and alanine aminotransferase (ALT) and the risk of HCC has not been widely studied. We examined this relationship based on a prospective cohort study. METHODS: 162 first-attack HCC cases during three follow-up periods (2014-2020) were selected as the case group. A control group of 648 participants was obtained by 1:4 matching of age (± 2 years) and sex with noncancer participants in the same period. Conditional logistic regression models, restricted cubic spline models, additive interaction models, and generalized additive models were used to explore the effects of FPG and ALT on the risk of HCC. RESULTS: After correction for confounding factors, we found that abnormal FPG and elevated ALT increased the risk of HCC, respectively. Compared with the normal FPG group, the risk of HCC was significantly increased in the impaired fasting glucose (IFG) (OR = 1.91, 95 %CI: 1.04, 3.50) and diabetes groups (OR = 2.12, 95 %CI: 1.24, 3.63). Compared with the lowest quartile of ALT, subjects in the fourth quartile had an 84 % increased risk of HCC (OR = 1.84, 95 %CI: 1.05-3.21). Moreover, there was an interaction between FPG and ALT on the risk of HCC, and 74 % of the HCC risk could be attributed to their synergistic effect (AP = 0.74, 95 %CI: 0.56-0.92). CONCLUSION: Abnormal FPG and elevated ALT are independent risk factors for HCC, and they have a synergistic effect on the risk of HCC. Therefore, serum FPG and ALT levels should be monitored to prevent the development of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Alanina Transaminase , Glicemia , Estudos Prospectivos , Estudos de Casos e Controles , Neoplasias Hepáticas/epidemiologia , Fatores de Risco , Jejum
8.
Cell Rep Methods ; 3(3): 100415, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-37056376

RESUMO

Quantifying animal behavior is important for biological research. Identifying behaviors is the prerequisite of quantifying them. Current computational tools for behavioral quantification typically use high-level properties such as body poses to identify the behaviors, which constrains the information available for a holistic assessment. Here we report LabGym, an open-source computational tool for quantifying animal behaviors without this constraint. In LabGym, we introduce "pattern image" to represent the animal's motion pattern, in addition to "animation" that shows all spatiotemporal details of a behavior. These two pieces of information are assessed holistically by customizable deep neural networks for accurate behavior identifications. The quantitative measurements of each behavior are then calculated. LabGym is applicable for experiments involving multiple animals, requires little programming knowledge to use, and provides visualizations of behavioral datasets. We demonstrate its efficacy in capturing subtle behavioral changes in diverse animal species.


Assuntos
Comportamento Animal , Redes Neurais de Computação , Animais , Computadores , Movimento (Física)
9.
Nutr Metab Cardiovasc Dis ; 33(2): 315-322, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36599782

RESUMO

BACKGROUND AND AIMS: Studies have shown that elevated serum uric acid (SUA) may increase the risk of coronary heart disease (CHD). However, it is still disputable how mediate effects between metabolic diseases and hyperuricemia affect the incidence of CHD. This study aimed to explore whether metabolic diseases may mediate the connection from hyperuricemia at baseline to the elevated incidence risk of CHD during follow-ups. METHODS AND RESULTS: Based on the Jinchang cohort, 48 001 subjects were followed for 9 years between June 2011 and December 2019. Multivariate-adjusted Cox regression models were applied to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). Significantly increased risks of CHD were observed in hyperuricemia (HR:1.46, 95%CI:1.28, 1.67) when compared with normouricemia population. The mediating effect model further demonstrated that metabolic diseases could mediate the association between hyperuricemia and CHD pathogenesis, partially for the combined metabolic diseases with mediation effects of 45.12%, 25.24% for hypertension, 28.58% for overweight or obese status, 29.05% for hypertriglyceridemia, 6.70% for hypercholesterolemia, 3.52% for low high density lipoprotein cholesterol (HDL-C), and 6.51% for high low density lipoprotein cholesterol (LDL-C), respectively. CONCLUSIONS: Hyperuricemia significantly increased the risk of incident CHD, and this association was partly mediated by metabolic diseases.


Assuntos
Doença das Coronárias , Hiperlipidemias , Hiperuricemia , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Fatores de Risco , Ácido Úrico , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , HDL-Colesterol
10.
Exp Ther Med ; 24(3): 562, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35978917

RESUMO

In December 2019, there was an outbreak of pneumonia of unknown causes in Wuhan, China. The etiological pathogen was identified to be a novel coronavirus, named severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). The number of infected patients has markedly increased since the 2019 outbreak and COVID-19 has also proven to be highly contagious. In particular, the elderly are among the group of patients who are the most susceptible to succumbing to COVID-19 within the general population. Cross-infection in the hospital is one important route of SARS-CoV-2 transmission, where elderly patients are more susceptible to nosocomial infections due to reduced immunity. Therefore, the present study was conducted to search for ways to improve the medical management workflow in geriatric departments to ultimately reduce the risk of nosocomial infection in elderly inpatients. The present observational retrospective cohort study analysed elderly patients who were hospitalised in the Geriatric Department of the First Affiliated Hospital with Nanjing Medical University (Nanjing, China). A total of 4,066 elderly patients, who were admitted between January and March in 2019 and 2020 and then hospitalised for >48 h were selected. Among them, 3,073 (75.58%) patients hospitalised from January 2019 to March 2019 were allocated into the non-intervention group, whereas the remaining 933 (24.42%) patients hospitalised from January 2020 to March 2020 after the COVID-19 outbreak were allocated into the intervention group. Following multivariate logistic regression analysis, the risk of nosocomial infections was found to be lower in the intervention group compared with that in the non-intervention group. After age stratification and adjustment for sex, chronic disease, presence of malignant tumour and trauma, both inverse probability treatment weighting and standardised mortality ratio revealed a lower risk of nosocomial infections in the intervention group compared with that in the non-intervention group. To rule out interference caused by changes in the community floating population and social environment during this 1-year study, 93 long-stay patients in stable condition were selected as a subgroup based on 4,066 patients. The so-called floating population refers to patients who have been in hospital for <2 years. Patients aged ≥65 years were included in the geriatrics program. The incidence of nosocomial infections during the epidemic prevention and control period (24 January 2020 to 24 March 2020) and the previous period of hospitalisation (24 January 2019 to 24 March 2019) was also analysed. In the subgroup analysis, a multivariate analysis was also performed on 93 elderly patients who experienced long-term hospitalisation. The risk of nosocomial and pulmonary infections was found to be lower in the intervention group compared with that in the non-intervention group. During the pandemic, the geriatric department took active preventative measures. However, whether these measures can be normalised to reduce the risk of nosocomial infections among elderly inpatients remain unclear. In addition, the present study found that the use of an indwelling gastric tube is an independent risk factor of nosocomial pulmonary infection in elderly inpatients. However, nutritional interventions are indispensable for the long-term wellbeing of patients, especially for those with dysphagia in whom an indwelling gastric tube is the most viable method of providing enteral nutrition. To conclude, the present retrospective analysis of the selected cases showed that enacting preventative and control measures resulted in the effective control of the incidence of nosocomial infections.

11.
NPJ Sci Food ; 6(1): 36, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-35987753

RESUMO

Superoxide dismutase (SOD) is an enzyme found in most food sources, might be a candidate to reduce oxidative damage to intestinal barrier, thereby ameliorating the vicious circle between hyperglycemia and the oxidative damage. Here we report the oral administration of SOD, liposome-embedded SOD (L-SOD), and SOD hydrolysate to type 2 diabetic model rats to confirm this hypothesis. Oxidative damage severity in model rat intestine was indicated by malondialdehyde level, GSSG/GSH ratio, and antioxidant enzyme activity. The damage was significantly repaired by L-SOD. Furthermore, blood glucose and related indexes correlated well not only with oxidative damage results but also with indexes indicating physical intestinal damage such as colon density, H&E staining, immunohistochemical analysis of the tight junction proteins occludin and ZO-1 in the colon, as well as lipopolysaccharide and related inflammatory cytokine levels. The order of the magnitude of the effects of these SOD preparations was L-SOD > SOD > SOD hydrolysate. These data indicate that orally administered SOD can exhibit glucose-lowering effect via targeting the intestine of diabetic rats and systemic lipopolysaccharide influx.

12.
Eur J Epidemiol ; 37(6): 641-649, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35713795

RESUMO

The Jinchang Cohort was an ongoing 20-year ambispective cohort with unique metal exposures to an occupational population. From January 2014 to December 2019, the Jinchang Cohort has completed three phases of follow-up. The baseline cohort was completed from June 2011 to December 2013, and a total of 48 001 people were included. Three phases of follow-ups included 46 713, 41 888, and 40 530 participants, respectively. The death data were collected from 2001 to 2020. The epidemiological, physical examination, physiological, and biochemical data of the cohort were collected at baseline and during follow-up. Biological specimens were collected on the baseline to establish a biological specimen bank. The concentrations of metals in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The new areas of research aim to study the all-cases mortality, the burden of diseases, heavy metals and diseases, and the course of the chain from disease to high-risk outcomes using a combination of macro and micro means, which provided a scientific basis to explore the pathogenesis of multi-etiology and multi-disease and to evaluate the effects of the intervention measures in the population.


Assuntos
Bancos de Espécimes Biológicos , China/epidemiologia , Estudos de Coortes , Humanos
13.
Nutr Metab Cardiovasc Dis ; 32(3): 648-657, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35123857

RESUMO

BACKGROUND AND AIMS: There is still inconsistent evidence over the protective effect of total bilirubin on the development of coronary heart disease (CHD). Therefore, we aimed to investigate the association between bilirubin in population subtypes and the risks of CHD between different gender and menstruation subgroups. METHODS AND RESULTS: In this prospective cohort study, 29,750 participants free of CHD with an average age of 47 ± 14 years were recruited at baseline; of these, 720 CHD first-attack cases were collected after 7-years of follow up. The covariate-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). The serum bilirubin concentration was quarterly stratified based on the distribution of healthy population without CHD onset. The HRs of incident CHD decreased with elevated bilirubin in females (ρ trend<0.05), but not males. In postmenopausal females, compared with the lowest quartile of total bilirubin, the adjusted HRs for the third and fourth quartiles were 0.64 (95% CI: 0.45, 0.93) and 0.59 (95% CI: 0.42, 0.86), the adjusted HRs in the third and fourth quartiles of direct bilirubin were 0.56 (0.39, 0.82) and 0.56 (0.38, 0.81), and for indirect bilirubin, corresponding HR in the highest quartile was 0.56 (0.38, 0.83). CONCLUSION: Elevated serum bilirubin was inversely associated with adjusted HRs of CHD in females, especially postmenopausal females. The relationship between elevated direct bilirubin and reduced HRs of CHD may be closer than indirect bilirubin in postmenopausal females.


Assuntos
Doença das Coronárias , Adulto , Bilirrubina , Doença das Coronárias/diagnóstico , Doença das Coronárias/epidemiologia , Doença das Coronárias/prevenção & controle , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
14.
Genes (Basel) ; 12(9)2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34573367

RESUMO

Enhancer-promoter interactions (EPIs) play a significant role in the regulation of gene transcription. However, enhancers may not necessarily interact with the closest promoters, but with distant promoters via chromatin looping. Considering the spatial position relationship between enhancers and their target promoters is important for predicting EPIs. Most existing methods only consider sequence information regardless of spatial information. On the other hand, recent computational methods lack generalization capability across different cell line datasets. In this paper, we propose EPIsHilbert, which uses Hilbert curve encoding and two transfer learning approaches. Hilbert curve encoding can preserve the spatial position information between enhancers and promoters. Additionally, we use visualization techniques to explore important sequence fragments that have a high impact on EPIs and the spatial relationships between them. Transfer learning can improve prediction performance across cell lines. In order to further prove the effectiveness of transfer learning, we analyze the sequence coincidence of different cell lines. Experimental results demonstrate that EPIsHilbert is a state-of-the-art model that is superior to most of the existing methods both in specific cell lines and cross cell lines.


Assuntos
Elementos Facilitadores Genéticos , Modelos Genéticos , Regiões Promotoras Genéticas , Linhagem Celular , Visualização de Dados , Bases de Dados Factuais , Humanos
15.
Cell Rep ; 33(6): 108361, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33176150

RESUMO

Protein isoforms generated by alternative splicing contribute to proteome diversity. Because of the lack of effective techniques, the isoform-specific function, expression, localization, and signaling of endogenous proteins are unknown for most genes. Here, we report a genetic method, isoTarget, for multi-purpose studies of targeted isoforms in select cells. Applying isoTarget to two isoforms of Drosophila Dscam, Dscam[TM1] and [TM2], we found that, in neurons, endogenous Dscam[TM1] is in dendrites, whereas Dscam[TM2] is in both dendrites and axons. We demonstrate that the difference in subcellular localization, rather than biochemical properties, leads to the two isoforms' functional differences. Moreover, we show that the subcellular enrichment of functional partners results in a DLK/Wallenda-Dscam[TM2]-Dock signaling cascade in axons. We further apply isoTarget to study two isoforms of a GABA receptor to demonstrate its general applicability. isoTarget is an effective technique for studying how alternative splicing enhances proteome complexity.


Assuntos
Processamento Alternativo/genética , Isoformas de Proteínas/metabolismo , Humanos
16.
Curr Biol ; 30(24): 4896-4909.e6, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33065003

RESUMO

Sensory stimuli with graded intensities often lead to yes-or-no decisions on whether to respond to the stimuli. How this graded-to-binary conversion is implemented in the central nervous system (CNS) remains poorly understood. Here, we show that graded encodings of noxious stimuli are categorized in a decision-associated CNS region in Drosophila larvae, and then decoded by a group of peptidergic neurons for executing binary escape decisions. GABAergic inhibition gates weak nociceptive encodings from being decoded, whereas escalated amplification through the recruitment of second-order neurons boosts nociceptive encodings at intermediate intensities. These two modulations increase the detection accuracy by reducing responses to negligible stimuli whereas enhancing responses to intense stimuli. Our findings thus unravel a circuit mechanism that underlies accurate detection of harmful stimuli.


Assuntos
Sistema Nervoso Central/fisiologia , Drosophila melanogaster/fisiologia , Reação de Fuga/fisiologia , Nociceptores/fisiologia , Animais , Sistema Nervoso Central/citologia , Tomada de Decisões , Feminino , Larva/fisiologia , Masculino , Modelos Animais , Modelos Neurológicos , Nociceptividade/fisiologia
17.
Cell Death Dis ; 10(12): 893, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772150

RESUMO

Cell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.


Assuntos
Apoptose , Drosophila melanogaster/citologia , Drosophila melanogaster/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Olho/citologia , Olho/metabolismo , Genes Dominantes , Testes Genéticos , Larva/metabolismo , Sistema de Sinalização das MAP Quinases , Fenótipo , Fatores de Transcrição da Família Snail/genética , Transcrição Gênica , Asas de Animais/citologia , Asas de Animais/metabolismo
18.
Biophys Chem ; 253: 106214, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31272076

RESUMO

Cold atmospheric plasma (CAP) has attracted substantial attention in the field of medical disinfection because its main components, reactive oxygen species (ROS), have a strong destructive effect on various cell components. The cell membrane plays an important role in maintaining proper cellular function by blocking harmful substances such as ROS. In this paper, we used molecular dynamics simulations to study the behaviour of different ROS at the membrane-water interface. The results showed that the cell membrane presented a weak barrier to hydrophobic ROS (O2) but effectively prevented hydrophilic ROS (OH, HO2, H2O2) from entering the cell. The plasma treatment significantly enhanced the permeability of the cell membrane to HO2, while the energetic barrier to other types of ROS changed only slightly. O2 very likely stopped in the centre of the lipid bilayer when crossing the membrane and there attacked the unsaturated region of the phospholipid. Cholesterol was most likely oxidized by HO2, causing a condensing effect that destroyed the integrity and fluidity of the cell membrane. The study also found that large amounts of ROS decreased the thickness of the cell membrane, and the phospholipid arrangement became disordered.


Assuntos
Membrana Celular/química , Simulação de Dinâmica Molecular , Espécies Reativas de Oxigênio/química , Membrana Celular/metabolismo , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/química , Fosfolipídeos/química , Gases em Plasma , Espécies Reativas de Oxigênio/metabolismo
19.
Sensors (Basel) ; 18(10)2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297677

RESUMO

The behavior of fiber reinforced polymer (FRP) composites at high temperature is a critical issue that needs to be clearly understood for their structural uses in civil engineering. However, due to technical difficulties during testing at high temperature, limited experimental investigations have been conducted regarding the thermal behavior of basalt fiber reinforced polymer (BFRP) composites, especially for the in-plane shear modulus of BFRP laminates. To this end, both an analytical derivation and an experimental program were carried out in this work to study the in-plane shear modulus of BFRP laminates. After the analytical derivation, the in-plane shear modulus was investigated as a function of the elastic modulus in different directions (0°, 45° and 90° of the load-to-fiber angle) and Poisson's ratio in the fiber direction. To obtain the in-plane shear modulus, the four parameters were tested at different temperatures from 20 to 250 °C. A novel non-contacting digital image correlation (DIC) sensing system was adopted in the high-temperature tests to measure the local strain field on the FRP samples. Based on the test results, it was found that the elastic moduli in different directions were reduced to a very low level (less than 20%) from 20 to 250 °C. Furthermore, the in-plane shear modulus of BFRP at 250 °C was only 3% of that at 20 °C.

20.
IET Syst Biol ; 11(6): 182-189, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29125127

RESUMO

In electronic systems, dynamic random access memory (DRAM) is one of the core modules in the modern silicon computer. As for a bio-computer, one would need a mechanism for storage of bio-information named 'data', which, in binary logic, has two levels, logical high and logical low, or in the normalised form, '1' and '0'. This study proposes a possible genetic DRAM based on the modified electronic configuration, which uses the biological reaction to fulfil an equivalent RC circuit constituting a memory cell. The authors implement fundamental functions of the genetic DRAM by incorporating a genetic toggle switch for data hold. The results of simulation verify that the basic function can be used on a bio-storage module for the future bio-computer.


Assuntos
Lógica , Redes Neurais de Computação
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