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1.
BMC Med Inform Decis Mak ; 21(1): 45, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557818

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused health concerns worldwide since December 2019. From the beginning of infection, patients will progress through different symptom stages, such as fever, dyspnea or even death. Identifying disease progression and predicting patient outcome at an early stage helps target treatment and resource allocation. However, there is no clear COVID-19 stage definition, and few studies have addressed characterizing COVID-19 progression, making the need for this study evident. METHODS: We proposed a temporal deep learning method, based on a time-aware long short-term memory (T-LSTM) neural network and used an online open dataset, including blood samples of 485 patients from Wuhan, China, to train the model. Our method can grasp the dynamic relations in irregularly sampled time series, which is ignored by existing works. Specifically, our method predicted the outcome of COVID-19 patients by considering both the biomarkers and the irregular time intervals. Then, we used the patient representations, extracted from T-LSTM units, to subtype the patient stages and describe the disease progression of COVID-19. RESULTS: Using our method, the accuracy of the outcome of prediction results was more than 90% at 12 days and 98, 95 and 93% at 3, 6, and 9 days, respectively. Most importantly, we found 4 stages of COVID-19 progression with different patient statuses and mortality risks. We ranked 40 biomarkers related to disease and gave the reference values of them for each stage. Top 5 is Lymph, LDH, hs-CRP, Indirect Bilirubin, Creatinine. Besides, we have found 3 complications - myocardial injury, liver function injury and renal function injury. Predicting which of the 4 stages the patient is currently in can help doctors better assess and cure the patient. CONCLUSIONS: To combat the COVID-19 epidemic, this paper aims to help clinicians better assess and treat infected patients, provide relevant researchers with potential disease progression patterns, and enable more effective use of medical resources. Our method predicted patient outcomes with high accuracy and identified a four-stage disease progression. We hope that the obtained results and patterns will aid in fighting the disease.


Assuntos
Aprendizado Profundo , Progressão da Doença , /diagnóstico , China , Previsões , Humanos
2.
Sensors (Basel) ; 21(2)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33419025

RESUMO

With the rapid development of the global navigation satellite system (GNSS), high-rate GNSS has been widely used for high-precision GNSS coseismic displacement retrieval. In recent decades, relative positioning (RP) and precise point positioning (PPP) are mainly adopted to retrieve coseismic displacements. However, RP can only obtain relative coseismic displacements with respect to a reference station, which might be subject to quaking during a large seismic event. While PPP needs a long (re)convergence period of tens of minutes. There is no convergence time needed in the variometric approach for displacements analysis standalone engine (VADASE) but the derived displacements are accompanied by a drift. Temporal point positioning (TPP) method adopts temporal-differenced ionosphere-free phase measurements between a reference epoch and the current epoch, and there is almost no drift in the displacement derived from TPP method. Nevertheless, the precise orbit and clock products should be applied in the TPP method. The studies in recent years are almost based on the postprocessing precise orbits and clocks or simulated real-time products. Since 2013, international GNSS service (IGS) has been providing an open-access real-time service (RTS), which consists of orbit, clock and other corrections. In this contribution, we evaluated the performance of real-time coseismic displacement retrieval based on TPP method with IGS RTS correction products. At first, the real-time precise orbit and clock offsets are derived from the RTS correction products. Then, the temporal-differenced ionosphere-free (IF) combinations are formed and adopted as the TPP measurements. By applying real-time precise orbit and clock offsets, the coseismic displacement can be real-timely retrieved based on TPP measurements. To evaluate the accuracy, two experiments including a stationary experiment and an application to an earthquake event were carried out. The former gives an accuracy of 1.8 cm in the horizontal direction and 4.1 cm in the vertical direction during the whole period of 15-min. The latter gives an accuracy of 1.2 cm and 2.4 cm in the horizontal and vertical components, respectively.

3.
Chemosphere ; 272: 129564, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33476792

RESUMO

OBJECTIVE: Air particulate matter (PM) pollution is associated with the alterations in circulating pulmonary damage proteins. But there are not consistent results among the epidemiological studies. The aim of this study is to investigate the alteration of surfactant protein (SP) from PM exposure. METHODS: We conducted a comprehensive meta-analysis by searching the databases of PubMed, Medline, EMBASE, Web of Science and CNKI before October 2020 which reported PM pollutants and surfactant protein in the population. The sources of heterogeneity were assessed by subgroup (smoking, particulate matter with different aerodynamic diameter, exposure duration) analysis. We also used the publication bias tests for the comprehensive assessment. RESULTS: This meta-analysis consisted of 10 studies with 1985 subjects. The results showed that the combined standardized mean difference (SMD) value was 0.05, 95% confidence interval (CI) was -0.07 to 0.17 for serum SP-A and -0.81 (95% CI: -1.41 to -0.21) for circulating SP-D. Among smokers, the combined SMD value of SP-A were 0.29 (95% CI: 0.05 to 0.52). We did not find the correlation between publication year of SP-A and SP-D and study heterogeneity. CONCLUSIONS: Circulating SP-D was significantly decreased by air particulate matter. Serum SP-A was significantly increased by PM exposure among smokers. Circulating surfactant protein may be considered as a biomarker for respiratory injury caused by air particulate matter.

4.
Environ Res ; 192: 110300, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33038368

RESUMO

Airborne particulate matter (PM) is a complex mixture containing various kinds of harmful components. Exposure to air PM is associated with childhood respiratory disease, but epidemiological data are limited concerning the circulating respiratory injury protein on the etiology of childhood respiratory disease. Specifically, the role of PM toxic components or its biological effective dose (adduct) in respiratory injury remains unclear. To demonstrate the dose-response relationship and the main mechanism on circulating club cell secretory protein (CC16) from PM compositions among children, we enrolled 273 boarding schoolchildren in China, including 110 and 163 children of whom were in the low- and high-PM exposed areas, respectively. In this study, we measured the internal exposure levels, including serum polycyclic aromatic hydrocarbons (PAH) adduct, urinary metals, and AhR expression, and detected the serum CC16 level as a lung injury marker. Environmental tobacco exposure in children was assessed by urinary cotinine. We found that significantly higher levels of serum CC16, benzo[a]pyridin-7,8-dihydroglycol-9,10-epoxide (BPDE)-albumin adduct, urinary molybdenum, selenium, arsenic, cadmium and barium, and lower level of AhR expression in high-PM exposed group. There was a good association between serum BPDE-albumin adduct and CC16 (ß = 0.222, P = 0.006). There was no association on urinary metals and serum CC16. BPDE-albumin adduct was directly associated with serum CC16 alternation [direct effect = 0.2044, 95% confidence interval (CI) = (0.0426, 0.36)]. PM could cause serum CC16 increased in children. PAH and its adduct might play a key role in lung injury during PM exposure.

5.
Anim Cells Syst (Seoul) ; 24(5): 253-259, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33209198

RESUMO

Gastric cancer, one of the most common malignant tumors of the digestive tract, is devoid of effective treatment owing to its highly invasive ability. Aquaporins (AQPs), transmembrane water channel proteins, has been shown to be involved in the malignancy of gastric cancer. This study aims to investigate the pathophysiological roles of AQP-1 in gastric cancer. We first demonstrated quantitative real-time polymerase chain reaction analysis and found up-regulation of AQP-1 in gastric cancer cell lines. Additionally, silence of AQP-1 inhibited cell proliferation via decrease of proliferating cell nuclear antigen (PCNA) and minichromosome maintenance complex component 2 (MCM2). Moreover, migration and invasion of gastric cancer cells were also suppressed by the interference of AQP-1. However, the tumorigenic mechanism of AQP-1 on gastric cancer is yet to be found. We demonstrated western blot analysis and found that knockdown of AQP-1 decreased protein expression of phospho (p)-GRB7 (growth factor receptor-bound protein 7) and led to a remarkable reduction of p-extracellular signal-regulated kinase (ERK) via inactivation of RAS. In general, our findings indicated that AQP-1 facilitates proliferation and invasion of gastric cancer cells via GRB7-mediated ERK and Ras activation, illuminating a novel AQP-1-RAS/ERK molecular axis as regulator in gastric cancer progression and suggesting potential implications in the treatment of gastric cancer.

6.
Org Lett ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33236913

RESUMO

A visible-light photoredox-catalyzed formal [5 + 1] cycloaddition of N-tosyl vinylaziridines with difluoroalkyl halides as unique C1 synthons was developed. The procedure provides an efficient and practical method to synthesize diverse pyridines in moderate to good yields. The reaction underwent a radical-initiated kinetically controlled ring-opening of vinylaziridines and involved a key α,ß-unsaturated imine intermediate, followed by an E2 elimination, a 6π electrocyclization, and defluorinated aromatization.

7.
Sensors (Basel) ; 20(21)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33114036

RESUMO

An accurate observation model and statistical model are critical in underwater integrated navigation. However, it is often the case that the statistical characteristics of noise are unknown through the ultra-short baseline (USBL) system/Doppler velocity log (DVL) integrated navigation in the deep-sea. Additionally, the velocity of underwater vehicles relative to the bottom of the sea or the currents is commonly provided by the DVL, and an adaptive filtering solution is needed to correctly estimate the velocity with unknown currents. This paper focuses on the estimation of unknown currents and measurement noise covariance for an underwater vehicle based on the USBL, DVL, and a pressure gauge (PG), and proposes a novel unbiased adaptive two-stage information filter (ATSIF) for the underwater vehicle (UV) with an unknown time-varying currents velocity. In the proposed algorithm, the adaptive filter is decomposed into a standard information filter and an unknown currents velocity information filter with interconnections, and the time-varying unknown ocean currents and measurement noise covariance are estimated. The simulation and experimental results illustrate that the proposed algorithm can make full use of high-precision observation information and has better robustness and navigation accuracy to deal with time-varying currents and measurement outliers than existing state-of-the-art algorithms.

8.
Sensors (Basel) ; 20(20)2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33050510

RESUMO

Recently, some smartphone manufacturers have subsequently released dual-frequency GNSS smartphones. With dual-frequency observations, the positioning performance is expected to be significantly improved. Cycle-slip detection and correction play an important role in high-precision GNSS positioning, such as precise point positioning (PPP) and real-time kinematic (RTK) positioning. The TurboEdit method utilizes Melbourne-Wübbena (MW) and phase ionospheric residual (PIR) combinations to detect cycle-slips, and it is widely used in the data processing applications for geodetic GNSS receivers. The smartphone pseudorange observations are proved to be much noisier than those collected with geodetic GNSS receivers. Due to the poor pseudorange observation, the MW combination would be difficult to detect small cycle-slips. In addition, some specific cycle-slip combinations, where the ratio of cycle-slip values at different carrier frequencies is close to the frequency ratio, are also difficult to be detected by PIR combination. As a consequence, the traditional TurboEdit method may fail to detect specific small cycle-slip combinations. In this contribution, we develop a modified TurboEdit cycle-slip detection and correction method for dual-frequency smartphone GNSS observations. At first, MW and PIR combinations are adopted to detect cycle-slips by comparing these two combinations with moving-window average values. Then, the epoch-differenced wide-lane combinations are used to estimate the changes of smartphone position and clock bias, and the cycle-slip is identified by checking the largest normalized residual whether it exceeds a predefined threshold value. The process of estimation and cycle-slip identification is implemented in an iterative way until there is no over-limit residual or there is no redundant measurement. At last, the cycle-slip values at each frequency are estimated with the epoch-differenced wide-lane and ionosphere-free combinations, and the least-square ambiguity decorrelation adjustment (LAMBDA) method is adopted to further obtain an integer solution. The proposed method has been verified with 1 Hz dual-frequency smartphone GNSS data. The results show that the modified TurboEdit method can effectively detect and correct even for specific small cycle-slip combinations, e.g., (4, 3), which is difficult to be detected with the traditional TurboEdit method.

9.
Int J Pharm ; 587: 119680, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32712250

RESUMO

Along with the malignant proliferation of tumor requiring nutrients, the expression of L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) in cancer cells is up-regulated that can be used as new targets for active targeting of tumor. However, since normal cells also express amino acid transporters in small amounts, traditional ligand-exposure drug delivery systems are potentially toxic to the body. Therefore, we designed a smart-response drug delivery system that buries the tyrosine ligand in PEG hydration layer at normal tissues and exposes the ligand by cleaving the pH-sensitive bond of PEG at the tumor site. Irinotecan (CPT-11) is actively loaded into the inner aqueous phase of liposomes via a copper ion gradient mechanism which has high encapsulation efficiency and stable drug release profile. Smart-response liposomes showed the strongest cytotoxicity and the maximum cellular uptake in vitro, the largest amount of tumor site accumulation and the best antitumor effect in vivo, compared with non-targeted liposomes and non-sensitive liposomes. It is worth noting that smart-response liposomes not only achieved enhanced antitumor effect but also attenuated side effects compared to ligand-exposure liposomes. This provides a smart responsive drug delivery system for precise treatment and shows a good application prospect.

10.
Lipids Health Dis ; 19(1): 151, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32586390

RESUMO

BACKGROUND: Coronary artery stenosis induces heart diseases including acute coronary syndrome (ACS). Some studies reported the ceramide species are associated with the ACS and major adverse cardia and cerebrovascular events (MACE). However, few studies investigated the association between plasma ceramide levels and the severity of stenosis, together with the onset of diseases. This aim of the present study was to investigate the association betweencertain ceramide species, coronary artery stenosis and acute coronary syndrome. METHODS: Five hundred fifty-three patients with definite or suspected CAD were recruited and received angiography. Subjects were assigned into 4 groups according to the severity of coronary artery stenosis. The measurements of 4 plasma ceramide species, namely, Cer (d18:1/16:0), Cer (d18:1/18:0), Cer (d18:1/24:1), Cer (d18:1/24:0) were carried out by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the ratio of Cer (d18:1/16:0), Cer (d18:1/18:0) and Cer (d18:1/24:1) to Cer (18:1/24:0), respectively, were calculated as index to evaluate the association between plasma ceramides levels and coronary artery stenosis. Multiple logistic regression analysis was used to establish the prognostic model for the prediction of ACS risk. RESULTS: After the adjustment by multiple clinical risk factors including age, gender, pre-existing myocardial/cerebral infarction, hemoglobin A1c% (HbA1c%), smoking and the diagnosis during index hospitalization, multiple logistic regression analysis showed that the high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c%, unstable angina (UAP) and acute myocardial infarction (AMI) diagnosis (compared with atherosclerosis) during index hospitalization were associated with more severe coronary artery stenosis. Furthermore, the prognostic model was established after adjustment of risk factors and the area under curve (AUC) of receiver operating characteristics (ROC) for the prognostic model was 0.732 and 95% CI was 0.642-0.822. CONCLUSION: The severity of coronary artery stenosis is associated with high ratio of Cer (d18:1/24:1) to Cer (d18:1/24:0), female gender, HbA1c% and AMI. Although the reported prognostic model showed a good discrimination, further investigation on long term MACE is needed to evaluate the role of ceramide for the prediction of MACE risk.

11.
BMC Public Health ; 20(1): 968, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560710

RESUMO

BACKGROUND: Although some studies have reported the association between life negative events and depressive disorders, very limited studies have examined the association between life negative events exposure and depressive symptoms risk among Chinese older adults. METHODS: Data were obtained from the China Longitudinal Ageing Social Survey (CLASS), which was a stratified, multi-stage, probabilistic sampling survey, conducted in 2014. General linear regression and logistic regression were used to examine the association between life negative events exposure and depressive symptoms among Chinese older adults. RESULTS: Life negative events showed statistical dose-response association with depressive symptoms risk after adjustment for the confounding factors (Ptrend < 0.001). Under consideration of life negative events exposure, participants who lived in rural areas, without a spouse or live alone were vulnerable to depressive symptoms. CONCLUSIONS: Life negative events played a risk role of depressive symptoms among Chinese older adults, especially among those in rural areas, females or without a spouse. Our current study is valuable for the development of special prevention depressive symptoms programs among elderly individuals, especially those who have experienced negative events.


Assuntos
Envelhecimento/psicologia , Grupo com Ancestrais do Continente Asiático/psicologia , Depressão/epidemiologia , Acontecimentos que Mudam a Vida , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
12.
Molecules ; 25(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218351

RESUMO

Lactoferrin (Lf) is a conserved iron-binding glycoprotein with antimicrobial activity, which is present in secretions that recover mucosal sites regarded as portals of invaded pathogens. Although numerous studies have focused on exogenous Lf, little is known about its expression of endogenous Lf upon bacterial infection. In this study, we investigated the distribution of Lf in mice intestine during Escherichia coli (E. coli) K88 infection. PCR and immunohistology staining showed that mRNA levels of Lf significantly increased in duodenum, ileum and colon, but extremely decreased in jejunum at 8 h and 24 h after infection. Meanwhile, endogenous Lf was mostly located in the lamina propria of intestine villi, while Lf receptor (LfR) was in the crypts. It suggested that endogenous Lf-LfR interaction might not be implicated in the antibacterial process. In addition, it was interesting to find that the infiltration of neutrophils into intestine tissues was changed similarly to Lf expression. It indicated that the variations of Lf expression were rather due to an equilibrium between the recruitment of neutrophils and degranulation of activated neutrophils. Thus, this new knowledge will pave the way to a more effective understanding of the role of Lf in intestinal mucosal immunity.

13.
J Coll Physicians Surg Pak ; 30(1): 96-98, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931943

RESUMO

To explore the efficacy of microecopharmaceutics combined with early enteral nutrition support to the treatment of severe acute pancreatitis (SAP). A total of 26 patients diagnosed with SAP in our hospital were retrospectively reviewed. Microecopharmaceutics, the living microbial food supplements that are beneficial to the host by improving the balance of intestinal microorganisms, were combined with early enteral nutrition group, and used as the treatment group; and delayed enteral nutrition was used as the control group. Two weeks after both treatments, variables of C-reactive protein (CRP), albumin (Alb), total serum protein (TP), urinary amylase recovery time, hemodiastase recovery time, acute physiology and chronic health evaluation (APCHE) score, and hospitalisation time in both groups were compared. Alb and TP of the treatment group were significantly higher than those in the control group (p <0.05). The APCHE score and CRP in the treatment group were significantly lower than those in the control group (p <0.05). The urinary amylase recovery time, hemodiastase amylase recovery time, and hospitalisation time in the treatment group were significantly shorter than those in the control group. The use of microecopharmaceutics combined with early enteral nutrition can effectively protect the intestinal barrier function, which is an effective treatment in patients with SAP.

14.
Environ Int ; 134: 105296, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759273

RESUMO

BACKGROUND: There is a paucity of mechanistic information on the DNA methylation and particulate matter (PM) exposure. This study aimed to investigate the association of PM and its component with DNA methylation, and the roles of DNA methyltransferase (DNMTs). METHODS: There were 240 high-exposed, 318 low-exposed and 210 non-exposed participants in this study. Individual concentrations of PM, polycyclic aromatic hydrocarbons (PAHs) and metals were identified by the monitoring data in their workplaces. Urinary 1-OHP and metals were determined as exposure markers. The global DNA methylation (% 5mC) and the mRNA expression of DNMT1, DNMT3A and DNMT3B were measured. We used mediation analysis to evaluate the role of DNMTs expression on DNA methylation alteration induced by PAHs and metals components. RESULTS: The decreasing trend of % 5mC was associated with increment of PM exposure in all subjects. We found that one IQR increase in total PAHs (3.82 µg/m3) and urinary 1-OHP (1.06 µmol/mol creatinine) were associated with a separate 6.08% and 7.26% decrease in % 5mC (P = 0.009, P < 0.001), and one IQR increase in urinary Ni (27.75 µmol/mol creatinine) was associated with a 3.29% decrease in % 5mC (P = 0.03). The interaction of urinary 1-OHP with Ni on global DNA methylation (%5mC) was not found (P interaction = 0.89). PM exposure was significantly associated with decreased mRNA level of DNMT3B, but the mediated effect of the PAHs and Ni levels on % 5mC through the DNMT3B pathway was not observed. CONCLUSIONS: We found the decrement of global DNA methylation and DNMT3B expression with elevated PM levels in population. The independent mode of action on DNA hypomethylation was found from PAHs and metal components. Global DNA hypomethylation might be a potential biomarker for evaluation of adverse health effects in response to PM exposure.


Assuntos
Metilação de DNA , DNA , Epidemiologia Molecular , Material Particulado , Hidrocarbonetos Policíclicos Aromáticos
15.
J Hazard Mater ; 389: 121843, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-31843406

RESUMO

Exposure to particulate matter (PM) has been associated with increased risk of various diseases, possibly through its effect on inflammatory response. MicroRNAs (miRNAs), an epigenetic mechanism regulating gene expression, can affect the expression of pro-inflammatory genes. However, few epidemiological studies have examined the impact of PM on inflammation-related miRNAs and their target mRNAs, especially among vulnerable population. We recruited 160 and 113 children from areas with different PM level in Jinan, China. We measured benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts in serum and the expression of 5 candidate miRNAs involved in inflammation regulation and 7 pro-inflammatory genes predicted to be their targets in leukocytes. Generally, children in the polluted area had higher miRNAs and lower mRNAs expression than those in the control area. An interquartile increase of BPDE-Alb adducts was associated with 12.66 %, 14.13 %, and 12.76 % higher of let-7a, miR-146a-5p, and miR-155-5p, as well as 21.61 %, 20.16 %, and 12.49 % lower of IL-6, CXCL8, and TLR2 mRNAs at false discovery rate<0.05, respectively. Additionally, let-7a, miR-146a-5p, and miR-155-5p were found to mediate the associations of BPDE-Alb adducts with IL-6 and/or TLR2 expression. Our findings suggested that PM exposure might attenuate inflammatory response among children in China, which was partly mediated by miRNAs regulating pro-inflammatory genes.

16.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1232-1238, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801723

RESUMO

OBJECTIVE: To investigate the effect of ulinastatin on the inflammatory mediators and their signaling pathways miR-146a/TLR4/NF-κB in rats with hemorrhagic shock. METHODS: Seventy-two SD rats were randomly assigned into shock without resuscitation group (SR group, n=24), acetated Ringer's solution resuscitation group (AR group, n=24) and ulinastatin treatment group (n=24). In all the 3 groups hemorrhagic shock models were established by femoral artery bleeding (with the mean arterial pressure maintained at 30-40 mmHg) without resuscitation (in SR group) or with resuscitation (in AR and ulinastatin groups) using acetated Ringer's solution for 30 min at 60 min after the onset of shock. At 1, 4, and 6 h after the shock onset or immediately after shock if the rats died, the lung tissues were taken for measurement of mRNA expressions of miR-146a, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-4, IL-6 and IL-10 using real-time quantitative PCR and the protein expressions of TLR4, MyD88, IκB-α, p-IκB-α, NF-κB p65, IRAK4, p-IRAK4 (Thr345, Ser346), p-IRAK4 (Thr342) and TRAF6 using Western blotting. The lung histopathology of the rats was examined under optical microscope with HE staining. RESULTS: Compared with the SR group, the rats in the AR group showed slightly alleviated inflammatory infiltration in the lung tissues with significantly increased mRNA levels of miR-146a, IL-4 and IL-10 (P < 0.05) and protein expressions of IκB-α, p-IRAK4 (Thr342) and p-IRAK4 (Thr345, ser346) (P < 0.05), and decreased mRNA levels of TNF-α, IL-1 and IL-6 (P < 0.05) and protein expressions of TLR4, MyD88, NF-κB p65, p-IκB-α, IRAK-4 and TRAF6 (P < 0.05). Compared with those in AR group, the rats in ulinastatin group showed further alleviation of inflammatory lung tissue injury, with increased mRNA levels of miR-146a, IL-4 and IL-10 (P < 0.01) and protein expressions of IκB-α, p-IRAK4 and p-IRAK4 (P < 0.01) and decreased mRNA levels of TNF-α, IL-1 and IL-6 (P < 0.01) and protein expressions of TLR4, MyD88, NF-κB p65, p-IκB-α, IRAK-4 and TRAF6 (P < 0.01). CONCLUSIONS: Ulinastatin combined with acetated Ringer's solution resuscitation alleviates lung inflammations in rats with hemorrhagic shock possibly by enhancing miR-146a expression to regulate TLR4/NF-κB signaling pathway through a negative feedback mechanism and thus modulate the balance of pro-inflammatory and anti-inflammatory factors.


Assuntos
Glicoproteínas/farmacologia , Inflamação/tratamento farmacológico , Pulmão/patologia , Choque Hemorrágico/tratamento farmacológico , Transdução de Sinais , Animais , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , MicroRNAs/genética , NF-kappa B/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/complicações , Receptor 4 Toll-Like/metabolismo
17.
Sensors (Basel) ; 20(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861917

RESUMO

Autonomous underwater vehicle (AUV) acoustic navigation is challenged by unknown system noise and gross errors in the acoustic observations caused by the complex marine environment. Since the classical unscented Kalman filter (UKF) algorithm cannot control the dynamic model biases and resist the influence of gross errors, an adaptive robust UKF based on the Sage-Husa filter and the robust estimation technique is proposed for AUV acoustic navigation. The proposed algorithm compensates the system noise by adopting the Sage-Husa noise estimation technique in an online manner under the condition that the system noise matrices are kept as positive or semi positive. In order to control the influence of gross errors in the acoustic observations, the equivalent gain matrix is constructed to improve the robustness of the adaptive UKF for AUV acoustic navigation based on Huber's equivalent weight function. The effectiveness of the algorithm is verified by the simulated long baseline positioning experiment of the AUV, as well as the real marine experimental data of the ultrashort baseline positioning of an underwater towed body. The results demonstrate that the adaptive UKF can estimate the system noise through the time-varying noise estimator and avoid the problem of negative definite of the system noise variance matrix. The proposed adaptive robust UKF based on the Sage-Husa filter can further reduce the influence of gross errors while adjusting the system noise, and significantly improve the accuracy and stability of AUV acoustic navigation.

18.
J Control Release ; 316: 22-33, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31676386

RESUMO

As the demand for nutrients in malignant proliferation of tumors increases, the L-type amino acid transporter 1(LAT1) and amino acid transporter B0,+ (ATB0,+) of tumor cells are more highly expressed than normal cells which can be used as new targets for active targeting of cancer. However, drug delivery systems often require multi-target design to achieve simultaneous targeting of different receptors or transporters due to the heterogeneity of the tumor. Here we utilized triethylamine-sucrose octasulfate gradient to actively encapsulate irinotecan into the introliposomal aqueous phase. Targeted ability was achieved through inserting different amino acids modified polyethylene glycol monostearate into the liposomes, and found that glutamate-liposomes can be targeted to LAT1, lysine-liposomes can be targeted to ATB0,+, and inspiringly, tyrosine-liposomes can be simultaneously targeted to LAT1 and ATB0,+. The tyrosine-modified liposomes showed the highest cellular uptake in BxPC-3 and MCF-7 cells which were highly expressed both LAT1 and ATB0,+. Moreover, we validated their targeting capabilities and elucidated the transport mechanism of LAT1 and ATB0,+-mediated endocytosis. The tumor inhibition rate of tyrosine-modified liposomes greatly increased from 39% to 87% compared with commercially available liposomes loaded CPT-11(Onivyde®). Overall, it showed a good application prospect for efficient tumor therapy and industrial production.


Assuntos
Antineoplásicos/administração & dosagem , Irinotecano/administração & dosagem , Neoplasias/tratamento farmacológico , Tirosina/química , Sistemas de Transporte de Aminoácidos/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Humanos , Irinotecano/farmacologia , Transportador 1 de Aminoácidos Neutros Grandes/metabolismo , Lipossomos , Células MCF-7 , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/patologia
19.
Curr Drug Metab ; 20(11): 855-866, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31631816

RESUMO

BACKGROUND: Monocarboxylate Transporter 1 (MCT1), an important membrane transport protein, mediates the translocation of monocarboxylates together with protons across biological membranes. Due to its pathological significance, MCT1 plays an important role in the progression of some diseases, such as brain diseases and cancers. METHODS: We summarize the general description of MCT1 and provide a comprehensive understanding of the role of MCT1 in brain diseases and cancers. Furthermore, this review discusses the opportunities and challenges of MCT1- targeting drug-delivery systems in the treatment of brain diseases and cancers. RESULTS: In the brain, loss of MCT1 function is associated with pathologies of degeneration and injury of the nervous system. In tumors, MCT1 regulates the activity of signaling pathways and controls the exchange of monocarboxylates in aerobic glycolysis to affect tumor metabolism, proliferation and invasion. Meanwhile, MCT1 also acts as a good biomarker for the prediction and diagnosis of cancer progressions. CONCLUSION: MCT1 is an attractive transporter in brain diseases and cancers. Moreover, the development of MCT1- based small molecule drugs and MCT1 inhibitors in the clinic is promising. This review systematically summarizes the basic characteristics of MCT1 and its role in brain diseases and cancers, laying the foundation for further research on MCT1.


Assuntos
Encefalopatias/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Neoplasias/metabolismo , Simportadores/metabolismo , Encéfalo/metabolismo , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/química , Transportadores de Ácidos Monocarboxílicos/fisiologia , Simportadores/antagonistas & inibidores , Simportadores/química , Simportadores/fisiologia
20.
BMC Psychiatry ; 19(1): 310, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646992

RESUMO

BACKGROUND: The aim of the current study is to assess the cross-sectional association of chronic non-communicable diseases (hypertension, diabetes mellitus, arthritis, and cerebrovascular) with depressive symptoms among older adults in China. METHODS: Data was obtained from the China Longitudinal Ageing Social Survey (CLASS) conducted in 2014. A total of 7505 participants were included. Depressive symptoms status was assessed by 9-item Center for Epidemiological Studies Depression Scale (CES-D) Associations between depressive symptoms and chronic diseases, adjusting for so, demographics and chronic diseases risk factors were assessed by using logistic regression model. RESULTS: We found negative associations between depressive symptoms and several socioeconomic factors, including education attainment and economic level. Widowed/divorced/ unmarried individuals are more likely to suffer from depressive symptoms. Hypertension (Odds ratio:1.29 [95%CI:1.16, 1.42]), diabetes (1.41 [95%CI:1.19,1.67]), arthritis (1.72 [1.52, 1.96]), and cerebrovascular disease (1.69 [1.41, 2.02]) were found to be associated with depressive symptoms. CONCLUSIONS: Most depressive symptoms cases were found to be significantly associated with chronic diseases. Our findings have provided evidence for understanding co-morbid depressive symptoms with chronic diseases, which could help clinicians to evaluate, diagnose and manage depression promptly.


Assuntos
Doença Crônica/epidemiologia , Depressão/epidemiologia , Idoso , Envelhecimento/psicologia , China/epidemiologia , Doença Crônica/psicologia , Comorbidade , Estudos Transversais , Demografia , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Socioeconômicos , Inquéritos e Questionários
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