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1.
Talanta ; 222: 121678, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33167284

RESUMO

The mycotoxin ochratoxin A (OTA) is a secondary metabolite derived from multiple Aspergillus and Penicillium strains. The development of a rapid, sensitive, and simple method for OTA detection is important to ensure food biosafety and safeguard public health. In this study, we designed a highly specific and sensitive assay for the detection of OTA using copper monosulfide (CuS) nanoparticles conjugated to an anti-OTA antibody (CuS-Ab NPs) and a fluorescent probe for Cu2+. When OTA is present in the solution, the OTA antigen, bound to the microplate, is competed off by the soluble OTA for binding to CuS-Ab NPs. After washing, the CuS-Ab NPs and bound OTA are removed. Subsequently, HCl is added to dissolve the CuS-Ab NPs bound to the OTA antigen, releasing Cu2+ and activating the Cu2+ fluorescent probe. Thus, the resultant fluorescence emission is inversely proportional to the OTA content in the solution. Under optimal conditions, this method detected 0.1-100 ng mL-1 OTA with a limit of detection of 0.01 ng mL-1. The assay was tested using corn, soybean, and coffee samples, with recoveries ranging from 94% to 110%. This strategy provides a new approach for the detection of mycotoxins and other small-molecule analytes with broad application potential in food safety and quality control.

2.
Drug Des Devel Ther ; 14: 4725-4733, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177809

RESUMO

Background: Neuropathic pain seriously affects life quality, and it is urgent to develop novel drugs with high efficacy and few side effects. Sanguinarine (SG) is a natural plant medicine with anti-inflammatory and neuroprotection effects. This study aimed to investigate the effect of SG on chronic constriction injury (CCI)-induced neuropathic pain. Materials and Methods: CCI rat model was established and rats were randomly divided into sham group, sham + SG group (6.25 mg/kg), CCI group, CCI + SG group (1.00, 2.50 and 6.25 mg/kg). The mechanical sensitivity and heat hypersensitivity of rats were monitored at different time points. Immunohistochemical, PCR, Western blot and ELISA were used to analyze p-p38 MAPK, NF-κB p65, TNF-α, IL-1ß, and IL-6 levels. Results: The mechanical sensitivity and heat hypersensitivity significantly reduced in rats of CCI group, but significantly increased in rats of CCI+SG group. TNF-α, IL-1ß, and IL-6 levels significantly increased in the spinal cord of CCI rats, but significantly decreased in rats of CCI+SG group. In addition, p38 MAPK activator antagonized beneficial effects of SG on neuropathic pain. Overexpression of p38 MAPK reduced the mechanical sensitivity and heat hypersensitivity, and enhanced NF-κB activity and the expression of inflammatory factors in CCI rats. Conclusion: SG alleviates neuropathic pain via suppressing p38MAPK signaling and downregulating the expression of TNF-α, IL-1ß, IL-6 and NF-κB activation. SG may be a potential therapeutic agent to treat neuropathic pain.

3.
Science ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154105

RESUMO

Vitamin K antagonists are widely used anticoagulants targeting vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, here we report eleven x-ray crystal structures of human VKOR and pufferfish VKOR-like with substrates and antagonists in different redox states. Substrates entering the active site in a partially oxidized state form a cysteine adduct that induces an open-to-closed conformational change, triggering reduction. Binding and catalysis is facilitated by hydrogen-bonding interactions in a hydrophobic pocket. The antagonists bind specifically to the same hydrogen-bonding residues and induce a similar closed conformation. Thus, vitamin K antagonists act through mimicking the key interactions and conformational changes required for the VKOR catalytic cycle.

4.
J Dairy Sci ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33131816

RESUMO

Lactobacillus acidophilus LA-5 is a suitable probiotic for food application, but because of its slow growth in milk, an increase in its efficiency is desired. To shorten the time required for fermentation, the nutrient requirements of L. acidophilus LA-5 were analyzed, including the patterns of consumption of amino acids, purines, pyrimidines, vitamins, and metal ions. The nutrients required by L. acidophilus LA-5 were Asn, Asp, Cys, Leu, Met, riboflavin, guanine, uracil, and Mn2+, and when they were added to milk, the fermentation time of fermented milk prepared by L. acidophilus LA-5 alone was shortened by 9 h, with high viable cell counts that were maintained during storage of nutrient-supplemented fermented milk compared with the control. For fermented milk prepared by fermentation with Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, and L. acidophilus LA-5, viable cell counts of L. acidophilus LA-5 increased 1.3-fold and were maintained during storage of nutrient-supplemented fermented milk compared with the control. Adding nutrients had no negative effect on the quality of the fermented milk. The results indicated that suitable nutrients enhanced the growth of L. acidophilus LA-5 and increased its viable cell counts in fermented milk prepared by L. acidophilus LA-5 alone and mixed starter culture, respectively.

5.
J Mol Histol ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33205345

RESUMO

Enteric glial cells are more abundant than neurons in the enteric nervous system. Accumulating evidence has demonstrated that enteric glial cells share many properties with astrocytes and play pivotal roles in intestinal diseases. NDRG2 is specifically expressed in astrocytes and is involved in various diseases in the central nervous system. However, no studies have demonstrated the expression of NDRG2 in enteric glial cells. We performed immunostaining of adult mouse tissue, human colon sections, and primary enteric glial cells and the results showed that NDRG2 was widely expressed in enteric glial cells. Meanwhile, our results showed that NDRG2 was upregulated after treatment with pro-inflammatory cytokines and exposure to oxygen glucose deprivation/reoxygenation, indicating that NDRG2 might be involved in these conditions. Moreover, we determined that NDRG2 translocated to the nucleus after treatment with pro-inflammatory cytokines but not after exposure to oxygen glucose deprivation/reoxygenation. This study is the first to show the expression and distribution of NDRG2 in the enteric glia. Our results indicate that NDRG2 might be involved in the pathogenesis of enteric inflammation and ischemia/reperfusion injury. This study shows that NDRG2 might be a molecular target for enteric nervous system diseases.

6.
Small ; : e2005060, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230912

RESUMO

To deal with the ever-growing toxic benzene-derived compounds in the water system, extensive efforts have been dedicated for catalytic degradation of pollutants. However, the activities and efficiencies of the transition metal-based nanoparticles or single-atom sites are still ambiguous in Fenton-like reactions. Herein, to compare the Fenton-like catalytic efficiencies of the nanoparticles and single atoms, the free-standing nanofibrous catalyst comprising Co nanocrystals and Co-Nx codoped carbon nanotubes (CNTs) or bare Co-Nx doped CNTs is fabricated. It is noteworthy that all these nanofibrous catalysts exhibit efficient activities, mesoporous structures, and conductive carbon networks, which allow a feasible validation of the catalytic effects. Benefiting from the maximized atomic utilization, the atomic Co-Nx centers exhibit much higher reaction kinetic constant (κ = 0.157 min-1 ) and mass activity toward the degradation of bisphenol A, far exceeding the Co nanocrystals (κ = 0.082 min-1 ). However, for the volume activities, the single-atom catalyst does not show apparent advantages compared to the nanocrystal-based catalyst. Overall, this work not only provides a viable pathway for comparing Fenton-like catalytic effects of transition metal-based nanoparticles or single atoms but also opens up a new avenue for developing prominent catalysts for organic pollutants' degradation.

7.
J Sep Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200871

RESUMO

Carotenoids consists of a series of conjugated isoprene units that are characteristically highly conjugated through double bonds, leading to the formation of many isomers that are susceptible to oxidation and other chemical modifications. Extreme hydrophobicity and high complexity make carotenoids difficult to identify and quantify. We implemented the use of a common Syncronis C18 column with strong eluting solvent, here isopropanol, to successfully separate a mixture of 23 carotenoids standards with different structural properties. In addition, the method differentiated between three groups of isomeric carotenoids (lycopene/δ-carotene/γ-carotene/ε-carotene/α-carotene/ß-carotene, α-cryptoxanthin/ß-cryptoxanthin, and zeaxanthin/lutein) by optimizing the gradient profile and using LC-MS. The LOD ranged from 0.05 to 5.51 ng/mL, and the recovery of carotenoids in Mytilus coruscus was from 63.54 to 93.25%, with SDs less than 10%. Twenty-five carotenoids were detected with a total content of 857 ± 55.1 mg/kg, and three isomeric carotenoids were identified: ε-carotene, α-carotene, and ß-carotene. Our results show that this methodology is a significant improvement over other alternatives for analyzing carotenoids because of its compatibility with carotenoids of different categories, and most importantly, its ability to resolve isomeric carotenes, which is significant not only for assessing carotenoid species, but also for the tracing of metabolic pathways of carotenoids. This article is protected by copyright. All rights reserved.

8.
J Proteome Res ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200940

RESUMO

Rapid early triage and dose estimation is vital for limited medical resource allocation and treatment of a large number of the wounded after radiological accidents. Lipidomics has been utilized to delineate biofluid lipid signatures after irradiation. Here, high-coverage targeted lipidomics was employed to screen radiosensitive lipids after 0, 1, 2, 3, 5, and 8 Gy total body irradiation at 4, 24, and 72 h postirradiation in rat plasma. Ultra-performance liquid chromatography-tandem mass spectrometry with a multiple reaction monitoring method was utilized. In total, 416 individual lipids from 18 major classes were quantified and those biomarkers altered in a dose-dependent manner constituted panel A-panel D. Receiver operator characteristic curve analysis using combined lipids showed good to excellent sensitivity and specificity in triaging different radiation exposure levels (area under curve = 0.814-1.000). The equations for dose estimation were established by stepwise regression analysis for three time points. A novel strategy for radiation early triage and dose estimation was first established and validated using panels of lipids. Our study suggests that it is feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage, which can provide further insights in developing lipidomics strategies for radiation biodosimetry in humans.

9.
J Anim Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201223

RESUMO

Selenium (Se) is an essential trace element for animals, and exists in nature in both inorganic and organic forms. Although organic Se is more bioavailable than inorganic Se, there are inconsistent reports on the effect of organic Se on the reproductive performance of sows. This study was conducted to investigate the effect of maternal organic Se (2-hydroxy-4-methylselenobutanoic, HMSeBA) supplementation on reproductive performance and antioxidant capacity of sows, and the long-term effect on the growth performance and antioxidant capacity of their offspring with or without lipopolysaccharide (LPS) challenge. The experimental design used in this study was a CRD, forty-five Landrace × Yorkshire sows were randomly allocated to receive one of the following three diets during gestation: control diet (Control, basal diet, n = 15), Sodium selenite (Na2SeO3) supplemented diet (Na2SeO3, basal diet + 0.3 mg Se/kg Na2SeO3, n = 15), HMSeBA supplemented diet (HMSeBA, basal diet + 0.3 mg Se/kg HMSeBA, n = 15). On day 21 of age, male offspring from each group were injected with LPS or saline (n = 6). As compared to control group, maternal HMSeBA supplementation increased the number of total born piglets, while decreased birth weight (p < 0.05). In the first week of lactation, maternal HMSeBA supplementation increased litter weight gain compared with Na2SeO3 group (p < 0.05) and increased the average daily gain of piglets compared with control group and Na2SeO3 group (p < 0.05). Meanwhile, maternal HMSeBA supplementation decreased piglet birth interval as compared to control group and Na2SeO3 group (p < 0.05). Besides, plasma GSH-Px activity was higher in the HMSeBA group on farrowing 0 min and 90 min, while MDA concentration was lower on farrowing 0 min, 90 min and 135 min, than those in the control group (p < 0.05). In addition, maternal HMSeBA supplementation increased concentration of SELENOP in colostrum compared with control group (p < 0.05). Further study revealed that LPS challenged HMSeBA group had higher GSH-Px and T-AOC, and lower MDA in weaning piglets compared to the control group (p < 0.05). Taken together, maternal HMSeBA supplementation increased the number of total born piglets, shortened duration of farrowing, improved the antioxidant capacities of sows and their offspring, and improved the growth performance of sucking pigs at first week of lactation. Thus, HMSeBA supplementation during gestation has the potentiality to produce more kilogram of meat.

10.
J Int Med Res ; 48(11): 300060520966439, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33208011

RESUMO

OBJECTIVES: To investigate liver function after pregnancy in women with chronic hepatitis B virus (HBV) and factors related to postpartum abnormalities. METHODS: A total of 317 pregnant women were included in this study and 138 had an HBV DNA level. In this trial, the highest number and proportion of hepatitis B surface antigen-positive mothers with postpartum hepatic inflammation were at 1 month after delivery. RESULTS: Baseline liver function of postpartum women with hepatic inflammation was significantly higher than that in those before delivery. The rates of hepatitis B e-antigen (HBeAg)-positive status, baseline HBV DNA levels, gestational diabetes mellitus, and antiviral therapy during pregnancy were significantly higher in the hepatic inflammation group than in the control group. Among the 138 women who received antiviral therapy, 83 withdrew from antiviral therapy immediately after delivery and 55 continued antiviral therapy for at least 1 month after delivery. Multivariate logistic regression analysis showed that HBeAg-positivity and gestational diabetes mellitus were associated with hepatic inflammation after delivery. Postpartum hepatic inflammation occurred mostly at 1 month after delivery in pregnant women with HBV infection. CONCLUSIONS: Close monitoring of women with HBV during pregnancy is required, especially for those who are HBeAg-positive and have gestational diabetes mellitus.

11.
Blood Adv ; 4(19): 4758-4768, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33007076

RESUMO

As the sole iron exporter in humans, ferroportin controls systemic iron homeostasis through exporting iron into the blood plasma. The molecular mechanism of how ferroportin exports iron under various physiological settings remains unclear. Here we found that purified ferroportin incorporated into liposomes preferentially transports Fe2+ and exhibits lower affinities of transporting other divalent metal ions. The iron transport by ferroportin is facilitated by downhill proton gradients at the same direction. Human ferroportin is also capable of transporting protons, and this activity is tightly coupled to the iron transport. Remarkably, ferroportin can conduct active transport uphill against the iron gradient, with favorable charge potential providing the driving force. Targeted mutagenesis suggests that the iron translocation site is located at the pore region of human ferroportin. Together, our studies enhance the mechanistic understanding by which human ferroportin transports iron and suggest that a combination of electrochemical gradients regulates iron export.

12.
Life Sci ; 263: 118564, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33075374

RESUMO

AIMS: Zika virus (ZIKV) infection causes a public health concern because of its potential association with the development of microcephaly. During viral infections, the host innate immune response is mounted quickly to produce some endogenous functional molecules to limit virus replication and spread. Exosomes contain molecules from their cell of origin following virus infection and can enter recipient cells for intercellular communication. Here, we aim to clarify whether ZIKV-induced exosomes can regulate viral pathogenicity by transferring specific RNAs. MAIN METHODS: In this study, exosomes were isolated from the supernatants of A549 cells with or without ZIKV infection. Human transcriptome array (HTA) was performed to analyze the profiling of RNAs wrapped in exosomes. Then qPCR, western blotting and ELISA were used to determine ZIKV replication. CCK-8 and flow cytometry were used to test the cell proliferation and cell cycles. Co-culture assay was used to analyze the effect of exosomes on the cell cycles of recipient cells. KEY FINDINGS: Through human transcriptome array (HTA) we found the defensin alpha 1B (DEFA1B) expression was significantly increased within exosomes isolated from ZIKV infected A549 cells. Additionally, we found that the extracellular DEFA1B exerts significant anti-ZIKV activity, mainly before ZIKV entering host cells. Interestingly, up-regulated DEFA1B retards the cell cycle of host cells. Further studies demonstrated that DEFA1B interacted with the origin recognition complex 1 (ORC1) which is required to initiate DNA replication during the cell cycle and increased DEFA1B expression decreased the ORC1 level in the cell nuclei. Accordingly, DEFA1B-containing exosomes can be internalized by the recipient cells to retard their cell cycles. SIGNIFICANCE: Together, our results demonstrated that the anti-ZIKV activity of DEFA1B can be mediated by exosomes, and DEFA1B interacts with ORC1 to retard cell cycles. Our study provides a novel concept that DEFA1B not only acts as an antiviral molecule during ZIKV infection but also may correlate with cell proliferation by retarding the progression of cell cycles.

13.
Braz J Cardiovasc Surg ; 35(5): 666-674, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33118731

RESUMO

OBJECTIVE: To describe insulin use and postoperative glucose control in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: We examined 2,390 patients with and without diabetes enrolled in the Contemporary Analysis of Perioperative Cardiovascular Surgical Care (CAPS-Care) Study who underwent CABG surgery (01/2004 - 06/2005) to describe postoperative insulin use, variation in insulin use across different hospitals, and associated in-hospital complications and clinical outcomes. Logistic regression was used to assess the adjusted relationship between insulin use and clinical outcomes. RESULTS: Overall, insulin was used in 82% (n=1,959) of patients, including 95% (n=1,203) with diabetes (n=1,258) and 67% (n=756) without diabetes (n=1,132). Continuous insulin was used in 35.5% of patients in the operating room and in 56% in the intensive care unit. Continuous insulin use varied significantly among centers from 8-100% in patients with diabetes. When compared with all patients not receiving insulin, insulin use in patients without diabetes was associated with a higher rate of death or major complication (adjusted odds ratio [OR]=1.54; 95% confidence interval [CI] 1.15-2.04; P=0.003). In patients with diabetes, insulin use was not associated with a higher risk of adverse outcomes (adjusted OR=1.01; 95% CI 0.52-1.98; P=0.98). CONCLUSION: The postoperative use of insulin is high among CABG patients in the United States of America. Insulin use in patients without diabetes was associated with worse clinical outcomes compared to patients (both with and without diabetes) who did not receive insulin. Further investigation is needed to determine the optimal use of postoperative insulin after CABG.

14.
Huan Jing Ke Xue ; 41(8): 3518-3526, 2020 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124324

RESUMO

In order to understand the emission characteristics of common greening trees in Beijing and analyze their correlations with photosynthetic parameters, including the net photosynthetic rate (Pn), stomatal conductance (gs), intercellular CO2 concentration (ci), and transpiration rate (Tr), we collected samples of biogenic volatile organic compounds (BVOCs) using a dynamic sampling technique from 14 species of deciduous trees. The results showed that there were significant differences in isoprene and total BVOC emissions between family or genus levels (P<0.01). With the exception of Lonicera maackii Maxim and Ulmus pumila L., all species were found to emit isoprene, monoterpenes, and sesquiterpenes, of which, species from the Salicaceae (e.g., Populus deltoides cv. '55/56'× P.deltoides cv. 'Imperial', P. euramericana cv. '74/76', Populus simonii Carr, and Salix babylonica) and Legume (Sophora japonica, Robinia pseudoacacia, and S. japonica Linn. var. japonica f. pendula Hort) families were the higher isoprene emitters, with emission rates that ranged from (30.1±4.3) µg·(g·h)-1 to (91.8±10.0) µg·(g·h)-1. Plants from the Oleaceae (e.g., Fraxinus chinensis Roxb and Syringa oblata Lindl), Begonia (Malus prunifolia), Sapindaceae (Koelrenteria paniculate), and Aceraceae (Acer truncatum Bunge) families mainly emitted monoterpenes and sesquiterpenes. Among them, Fraxinus chinensis Roxb and Acer truncatum Bunge were the highest emitters with emission rates of (10.6±4.8) µg·(g·h)-1 and (11.8±6.4) µg·(g·h)-1, respectively. Ocimene and ß-pinene were the two main monoterpenes emitted from greening tree species. No significant correlations were found between the emission of BVOCs and Pn or gs, while the emission rate of isoprene (r=0.681; P<0.01) and the total BVOC (r=0.698; P<0.01) from the Salicaceae family increased with increasing Tr. Moreover, leguminous plants showed a significant positive correlation between the total BVOC emission rate and ci (P=0.04). This study provides a scientific reference for the selection and configuration of urban greenery, and a theoretical basis for exploring the mechanism of BVOC emissions.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Pequim , China , Árvores , Compostos Orgânicos Voláteis/análise
15.
Sci Total Environ ; 748: 142330, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33113707

RESUMO

Monitoring of low-level analytes are typical examples for analytical challenges. Salbutamol (SAL), a phenol-ß2-agonist, has a very low residual content in the environment. Here, we present an ultrasensitive complete antigen-bridged PCR assay for detecting salbutamol (SAL). These DNA probes modified SAL complete antigens target recognition SAL antibodies and agglutinate synthetic DNA conjugates, thus enabling ligation of DNA probes to form a full-length DNA amplicon that contained a recognition site for cleavage endonuclease and subsequent quantification by qPCR. Moreover, SAL antibodies were modified with magnetic beads which were used to reduce the background noise and sample matrix effect, and the DNA signals were isothermally amplified by strand displacement amplification technology. Some key parameters which influence assay performance were optimized: the length of the bridge oligonucleotide, the concentration of immunomagnetic beads, SAL probes, and initiation chain, etc. Under the optimum conditions, the signal amplification of proposed Immuno-PCR assay for the detection of SAL was exponential, resulting in high potential sensitivity(~1 fg/mL) and a broad detection dynamic range (> 105 fold). Using this proposed method, we detected SAL in spiked tap water and urine samples with acceptable recoveries ranging from 88.1 to 103.3%. Theoretically, the method developed here has broad applicability and practical utility in immunoassays of a wide variety of analytes.


Assuntos
Albuterol , DNA , Anticorpos , Reação em Cadeia da Polimerase em Tempo Real
16.
J Infect Dis ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33049037

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is one of the main leading causes of hepatocellular carcinoma (HCC) worldwide. However, how reverse transcriptase (rt) gene contributes to HCC progression remains uncertain. METHODS: We enrolled a total of 307 chronic hepatitis B (CHB) and 237 HBV related HCC patients from 13 medical centers. Sequence features comprised multi-dimensional attributes of rt nucleic acid and rt/s amino acid sequences. Machine learning (ML) models were used to establish HCC predictive algorithms. Model performances were tested in the training and independent validation cohorts using receiver operating characteristic (ROC) and calibration plots. RESULTS: Random forest (RF) model based on combined metrics (10 features) demonstrated the best predictive performances in both cross and independent validation (RFAUC=0.96, RFACC=0.90), irrespective of HBV genotypes and sequencing depth. Moreover, HCC risk score for individuals obtained from the RF model (AUC =0.966, 95% CI=0.922-0.989) outperformed α-fetal protein (AUC=0.713, 95% CI=0.632-0.784) in identifying HCC from CHB patients. CONCLUSIONS: Our study provides evidence for the first time that HBV rt sequences contain vital HBV quasispecies features in predicting HCC. Integrating deep sequencing with feature extraction and ML models benefits the longitudinal surveillance of CHB and HCC risk assessment.

17.
Thorac Cancer ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058504

RESUMO

BACKGROUND: Immunotherapy has afforded new treatment options for extensive small cell lung cancer (ES-SCLC). However, reports on the effectiveness of immune checkpoint inhibitors (ICIs) combined with chemotherapy on survival in ES-SCLC patients are inconsistent. Therefore, we conducted a meta-analysis on the efficacy and safety of ICI combined with chemotherapy for ES-SCLC. METHODS: We searched for randomized controlled clinical trials related to first-line treatment of ES-SCLC with ICI combined with chemotherapy in PUBMED, ESMO, ASCO, and WCLC since 2018. The primary outcome was overall survival (OS). RESULTS: Four studies were included. Compared to chemotherapy alone, ICI in combination with chemotherapy as first-line treatment reduced the risk of death (hazard ratio [HR]: 0.76; 95% CI: 0.68-0.86; P < 0.00001) and disease progression (HR: 0.76; 95% CI: 0.68-0.84; P < 0.00001). The objective response rate (ORR) with ICI plus chemotherapy was significantly higher than that with chemotherapy alone (HR: 1.10; 95% CI: 1.02-1.19, P = 0.01). The duration of response (DoR) rate at one year was also better with ICI plus chemotherapy (HR: 3.46; 95% CI: 2.24-5.33; P < 0.00001). Security analysis revealed that the incidence of immune-mediated adverse events (imAEs) (HR: 3.77; 95% CI: 1.99-7.15, P < 0.0001) and grade 3/4 imAEs (HR: 7.01; 95% CI: 2.48-19.81; P = 0.0002) increased significantly with ICI plus chemotherapy. CONCLUSIONS: ICI combined with chemotherapy as first-line treatment can significantly improve the OS and progression-free survival (PFS) of ES-SCLC patients, but the toxicity caused by immunotherapy should be carefully considered. KEY POINTS: Significant findings of the studyOur meta-analysis shows that PD-L1/PD-1 plus chemotherapy can significantly improve the OS and PFS of ES-SCLC patients when used as first-line therapy. WHAT THIS STUDY ADDS: This study fills gaps regarding the efficacy of immunotherapy combined with chemotherapy as first-line treatment for ES-SCLC, and provides better evidence for the use of PD-L1/PD-1 immunotherapy plus chemotherapy for patients with ES-SCLC.

18.
Anal Chim Acta ; 1134: 96-105, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33059870

RESUMO

Sensitive and reliable analytical methods for monitoring of microcystin-LR (MC-LR) are urgently necessary due to its great harm to human health and aquatic organisms. In this work, a novel Cu/Au/Pt trimetallic nanoparticles (Cu/Au/Pt TNs)-encapsulated DNA hydrogel was prepared for colorimetric detection of MC-LR. The Cu/Au/Pt TNs were captured and released with precise control by the target-responsive 3D DNA hydrogels, which combined dual advantages of the target responsive DNA hydrogel and Cu/Au/Pt TNs of enhanced peroxidase-like activity. The DNA hydrogel network was constructed by hybridizing MC-LR aptamer with two complementary DNA strands on linear polyacrylamide chains. As long as MC-LR presented, the aptamer competitively binds with the MC-LR, causing the hydrogel to dissolve and release the preloaded Cu/Au/Pt TNs which could catalyze the reaction between H2O2 and TMB to produce color changes. In view of this sensitive strategy, this Cu/Au/Pt TNs-encapsulated DNA hydrogel-based colorimetric biosensor can achieve quantitative determination of MC-LR. The results showed that as-proposed colorimetric biosensor could sensitively detect MC-LR with a linear range of 4.0-10000 ng L-1 and a detection limit of 3.0 ng L-1. This work proved that the sensor had great potential to be applied in MC-LR detection and also provided the opportunity to develop colorimetric biosensor for other targets using this target-responsive and signal-amplification strategy.

19.
Soc Cogn Affect Neurosci ; 15(8): 861-873, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33007783

RESUMO

The current study investigates how long-term Tai Chi experience affects the neural and emotional response to regret in elders. Participants perform the sequential risk-taking task while undergoing functional magnetic resonance imaging (fMRI) scanning. In the task, participants opened a series of boxes consecutively and decided when to stop. Each box contained a reward, except for one which contained a devil. If the devil was revealed, then this served to zero the participant's gain in that trial. Once stopped, participant's gains and missed chances were revealed. Behaviorally, the Tai Chi group showed less regret, reduced risk taking, higher levels of nonjudgment of inner experience and less emotional sensitivity to outcome. fMRI results showed that the Tai Chi group demonstrated stronger fronto-striatal functional connectivity in trials with numerous missed chances. The nonjudgment of inner experience mediated the impact of fronto-striatal functional connectivity on Tai Chi practitioners' emotional sensitivity to outcome. These results highlight that long-term Tai Chi exercise may be effective in alleviating feelings of regret in elders by promoting reduced judgment of inner experience and enhanced emotion regulation through the strengthening of fronto-striatal functional connectivity.

20.
Technol Cancer Res Treat ; 19: 1533033820965574, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33084530

RESUMO

BACKGROUND: Tissue differentiation-inducing non-protein coding RNA (TINCR) has been shown to play a crucial role in pathogenesis of various types of human cancer including breast cancer (BC). The purpose of this study was to determine the potential prognostic value of serum lncRNA TINCR in BC. METHODS: Quantitative reverse transcription PCR (qRT-PCR) was performed to detect serum lncRNA TINCR levels in 72 triple-negative BC (TNBC) patients, 105 non-TNBC patients, 60 benign breast disease patients and 86 healthy subjects. RESULTS: The results showed that serum lncRNA TINCR level was significantly increased in BC, especially in TNBC. High circulating lncRNA TINCR was significantly correlated with worse clinicopathological features and clinical outcome of TNBC. Multivariate analysis revealed that serum lncRNA TINCR was an independent prognostic factor for overall survival of TNBC. However, little association was found between serum lncRNA TINCR and the prognosis of non-TNBC. CONCLUSIONS: Taken together, our findings demonstrate that serum lncRNA TINCR might be a useful novel and non-invasive biomarker for the prognosis prediction of TNBC.

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