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1.
J Cosmet Dermatol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957952

RESUMO

PURPOSE: Radiofrequency equipment, including invasive fractional microneedle radiofrequency (FMR) and noninvasive fractional radiofrequency (FR), has facilitated progress in the field of active acne treatment, but clinical data are limited. This study aimed to compare the efficacy and safety of FMR and FR in the treatment of moderate-to-severe acne vulgaris. METHODS: Ten patients with moderate-to-severe acne were enrolled in a 24-week, prospective, single-blind, randomized, comparative clinical trial with a split-face design. Fractional microneedle radiofrequency treatment was provided on one side of the face and FR on the opposite side. Three consecutive treatments were performed at 4-week interval. Objective assessment of efficacy was performed using the Acne Severity Index (ASI), and acne inflammatory lesions and noninflammatory lesions were evaluated. RESULTS: After the first treatment, ASI and both inflammatory and noninflammatory lesions of the FMR-treated side were improved to a greater degree than the FR-treated side. Patients' subjective satisfaction was also better regarding the FMR-treated side. After subsequent treatments, efficacy improves for both groups, and no significant differences in the above efficacy parameters between the two groups were observed. Pain scores were significantly higher for the FR-treated side than the FMR-treated side. CONCLUSION: Fractional microneedle radiofrequency is faster and more effective than FR for the treatment of moderate and severe acne after only one treatment. However, after several treatment sessions, both FMR and FR proved to be safe and effective for long-term treatment of moderate-to-severe acne. Therefore, invasive radiofrequency, such as FMR, or noninvasive radiofrequency, such as FR, can successfully treat active acne.

2.
J Phys Chem Lett ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951412

RESUMO

Double-electron electron resonance (DEER) can be used for tracking the structural dynamics of proteins in their native environment, the cell. This method provides the distance distribution between two spin labels attached at specific, well-defined positions in a protein. For the method to be viable under in-cell conditions, the spin label and its attachment to the protein should exhibit high chemical stability in the cell. Here we present first, low-temperature, trityl-trityl DEER distance measurements on two model proteins, PpiB (prolyl cis-trans isomerase from E. coli) and GB1 (immunoglobulin G-binding protein) doubly labeled with the trityl spin label, CT02MA. Both proteins gave in-cell distance distributions similar to that observed in vitro, with maxima at 4.5-5 nm and the data were further compared with in-cell Gd(III)-Gd(III) DEER obtained for PpiB labeled with BrPSPy-DO3A-Gd(III) at the same positions. These highlight the challenges of designing trityl tags suitable for in-cell distance determination at room temperature on live cells.

3.
PLoS Med ; 17(1): e1003027, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31951613

RESUMO

BACKGROUND: Ambient fine particulate matter pollution (PM2.5) is one leading cause of disease burden, but no study has quantified the association between daily PM2.5 exposure and life expectancy. We aimed to assess the potential benefits in life expectancy by attaining the daily PM2.5 standards in 72 cities of China during 2013-2016. METHODS AND FINDINGS: We applied a two-stage approach for the analysis. At the first stage, we used a generalized additive model (GAM) with a Gaussian link to examine the city-specific short-term association between daily PM2.5 and years of life lost (YLL); at the second stage, a random-effects meta-analysis was used to generate the regional and national estimations. We further estimated the potential gains in life expectancy (PGLE) by assuming that ambient PM2.5 has met the Chinese National Ambient Air Quality Standard (NAAQS, 75 µg/m3) or the ambient air quality guideline (AQG) of the World Health Organization (WHO) (25 µg/m3). We also calculated the attributable fraction (AF), which denoted the proportion of YLL attributable to a higher-than-standards daily mean PM2.5 concentration. During the period from January 18, 2013 to December 31, 2016, we recorded 1,226,849 nonaccidental deaths in the study area. We observed significant associations between daily PM2.5 and YLL: each 10 µg/m3 increase in three-day-averaged (lag02) PM2.5 concentrations corresponded to an increment of 0.43 years of life lost (95% CI: 0.29-0.57). We estimated that 168,065.18 (95% CI: 114,144.91-221,985.45) and 68,684.95 (95% CI: 46,648.79-90,721.11) years of life lost can be avoided by achieving WHO's AQG and Chinese NAAQS in the study area, which corresponded to 0.14 (95% CI: 0.09-0.18) and 0.06 (95% CI: 0.04-0.07) years of gain in life expectancy for each death in these cities. We observed differential regional estimates across the 7 regions, with the highest gains in the Northwest region (0.28 years of gain [95% CI: 0.06-0.49]) and the lowest in the North region (0.08 [95% CI: 0.02-0.15]). Furthermore, using WHO's AQG and Chinese NAAQS as the references, we estimated that 1.00% (95% CI: 0.68%-1.32%) and 0.41% (95% CI: 0.28%-0.54%) of YLL could be attributable to the PM2.5 exposure at the national level. Findings from this study were mainly limited by the unavailability of data on individual PM2.5 exposure. CONCLUSIONS: This study indicates that significantly longer life expectancy could be achieved by a reduction in the ambient PM2.5 concentrations. It also highlights the need to formulate a stricter ambient PM2.5 standard at both national and regional levels of China to protect the population's health.

4.
Health Commun ; : 1-11, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931622

RESUMO

Supportive social ties positively impact cancer patients' health; however, little is known about the intertwined links between both offline and online ties, and individual and group ties. Using the common-identity/common-bond approach, we empirically tested the critical difference that individual and group ties exert on health across offline and online settings. Results from 356 female breast cancer patients showed group ties affect quality of life through sequential group identification and social support, while individual ties affect quality of life through sequential interpersonal bonds and social support. Offline group and online individual ties are stronger predictors of quality of life than online group and offline individual ties. A cluster analysis categorized participants into four distinguishable segments. People with stronger offline interpersonal bonds and online group identification reported a better quality of life. This offers insight into the social dynamics that are most consequential for health, and the potential theoretical pathways through which they operate.

5.
Res Vet Sci ; 129: 28-38, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31927467

RESUMO

The ovine rumen is an immune interface with the external environment, participating in host defence responses. Ovine ruminal epithelial cells (ORECs) not only have a physical barrier function, but also secrete sheep ß-defensin-1 (SBD-1), which plays a key role in innate and adaptive immunity. Prebiotics are potential alternatives to infeed antibiotics. Saccharomyces cerevisiae cell wall (S.c.CW) is rich in prebiotics, which play roles in improving the growth performance of animals and regulating immunity. Here, we investigated whether S.c.CW induces SBD-1 expression in ORECs, as well as the underlying mechanism. The regulatory mechanisms of S.c.CW-induced up-regulation of SBD-1 were determined using quantitative real-time PCR, enzyme-linked immunosorbent assay, and western blotting. S.c.CW significantly increased the expression of Toll-like receptor 2 (TLR2) and nuclear factor-kappa B (NF-κB), but had no effect on TLR4 expression. TLR2, MyD88, and NF-κB inhibition attenuated the induction of SBD-1 expression by S.c.CW. However, TLR4 inhibition only resulted in attenuated SBD-1 mRNA, having no effect on SBD-1 protein expression. Thus, we conclude that S.c.CW can induce SBD-1 expression and that this induction is regulated by the TLR2-MyD88-NF-κB pathway.

6.
Sci Total Environ ; 712: 136470, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31931190

RESUMO

OBJECTIVES: Prenatal exposure to air pollutant has been associated with congenital heart defect (CHD). However, no study has investigated this effect in pre-pregnancy overweighted women. This study aimed to evaluate gestational exposure to particulate pollutant (PM2.5) and gaseous air pollutants (O3 and NO2) on the risk of CHD, and explore the potential effect modifiers including maternal age, pre-pregnancy BMI and pregestational diseases. METHODS: In this birth cohort study, a total of 63,213 pregnant women in Foshan, China were initially recruited and followed from their first hospital visit for pregnancy to delivery during 2015-2019. CHD cases were confirmed by the records in hospital- and population- based birth defect surveillance systems. Air pollutant exposures were estimated by the daily concentrations measured in air monitoring stations in each participant's residential county. Mixed-effects regression models, adjusted for potential confounding factors were applied to estimate the associations between air pollutant and CHD during the first three months of the pregnancy. RESULTS: A total of 985 (1.6%) newborns were identified as CHD cases. For each 10 µg/m3 increase in ambient O3 during the 1st month, the OR values for CHD were 1.03 (95% CI: 0.94, 1.13) in pre-pregnancy normal weighted women and 1.24 (95% CI: 1.01, 1.53) in pre-pregnancy overweighted women. For each 10 µg/m3 increase in NO2 during the 3rd month, the OR values for CHD were 1.09 (95% CI: 1.01, 1.18) in pre-pregnancy normal weighted women and 1.27 (95% CI: 1.07, 1.51) in pre-pregnancy overweighted women. No significant associations were found between PM2.5 exposure and CHD in our analysis. CONCLUSIONS: This study demonstrates that gaseous air pollutants (O3 and NO2) exposure during the cardiac embryogenesis period is associated with an increased risk of CHD, particularly for pre-pregnancy overweighted women.

7.
Neuroscience ; 424: 72-85, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785358

RESUMO

This study examines binaural response properties and sensitivity to interaural level difference of single neurons in the primary auditory cortex (AC) of the big brown bat, Eptesicus fuscus under earphone stimulation conditions. Contralateral sound stimulation always evoked response from all 306 AC neurons recorded but ipsilateral sound stimulation either excited, inhibited or did not affect their responses. High best frequency (BF) neurons typically had high minimum threshold (MT) and low BF neurons had low MT. However, both BF and MT did not correlate with their recording depth. The BF of these AC neurons progressively changed from high to low along the anteromedial-posterolateral axis of the AC. Their number of impulses and response latency varied with sound level and inter-aural level differences (ILD). Their number of impulses typically increased either monotonically or non-monotonically to a maximum and the latency shortened to a minimum at a specific sound level. Among 205 AC neurons studied at varied ILD, 178 (87%) and 127 (62%) neurons discharged maximally and responded with the shortest response latency at a specific ILD, respectively. Neurons sequentially isolated within an orthogonal electrode puncture shared similar BF, MT, binaurality and ILD curves. However, the response latency of these AC neurons progressively shortened with recording depth. Species-specific difference among this bat, the mustached bat and the pallid bat is discussed in terms of frequency and binaurality representation in the AC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31810239

RESUMO

Being a globally emerging mite-borne zoonotic disease, scrub typhus is a serious public health concern in Nepal. Mapping environmental suitability and quantifying the human population under risk of the disease is important for prevention and control efforts. In this study, we model and map the environmental suitability of scrub typhus using the ecological niche approach, machine learning modeling techniques, and report locations of scrub typhus along with several climatic, topographic, Normalized Difference Vegetation Index (NDVI), and proximity explanatory variables and estimated population under the risk of disease at a national level. Both MaxEnt and RF technique results reveal robust predictive power with test The area under curve (AUC) and true skill statistics (TSS) of above 0.8 and 0.6, respectively. Spatial prediction reveals that environmentally suitable areas of scrub typhus are widely distributed across the country particularly in the low-land Tarai and less elevated river valleys. We found that areas close to agricultural land with gentle slopes have higher suitability of scrub typhus occurrence. Despite several speculations on the association between scrub typhus and proximity to earthquake epicenters, we did not find a significant role of proximity to earthquake epicenters in the distribution of scrub typhus in Nepal. About 43% of the population living in highly suitable areas for scrub typhus are at higher risk of infection, followed by 29% living in suitable areas of moderate-risk, and about 22% living in moderately suitable areas of lower risk. These findings could be useful in selecting priority areas for surveillance and control strategies effectively.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31804937

RESUMO

We present a computational design system that assists users to model, optimize, and fabricate quad-robots with soft skins. Our system addresses the challenging task of predicting their physical behavior by fully integrating the multibody dynamics of the mechanical skeleton and the elastic behavior of the soft skin. The developed motion control strategy uses an alternating optimization scheme to avoid expensive full space time-optimization, interleaving space-time optimization for the skeleton and frame-by-frame optimization for the full dynamics. The output are motor torques to drive the robot to achieve a user prescribed motion trajectory. We also provide a collection of convenient engineering tools and empirical manufacturing guidance to support the fabrication of the designed quad-robot. We validate the feasibility of designs generated with our system through physics simulations and with a physically-fabricated prototype.

10.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878244

RESUMO

Magnaporthe grisea is the causal agent of rice blast disease, which is the most serious disease of cultivated rice. Aromatic polyketides are its typical metabolites and are involved in the infection process. In the search for novel lead compounds, chemical investigation of the fungus M. grisea M639 has led to the isolation of four new aromatic polyketides (salicylaldehyde skeleton bearing an unsaturated side chain), griseaketides A-D (1-4), as well as 15 known compounds (5-19). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses, including HR-MS, 2D NMR. Compound 12 showed prominent activity that killed 94.5% of C. elegans at 400 ppm and 66.9% at 200 ppm over 24 h. This is the first report describing the nematicidal activity of this type aromatic polyketide.

11.
Neural Netw ; 122: 174-182, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31683145

RESUMO

Fine-grained image classification is a challenging task due to the large inter-class difference and small intra-class difference. In this paper, we propose a novel Cascade Attention Model using the Deep Convolutional Neural Network to address this problem. Our method first leverages the Spatial Confusion Attention to identify ambiguous areas of the input image. Two constraint loss functions are proposed: the Spatial Mask loss and the Spatial And loss; Second, the Cross-network Attention, applying different pre-train parameters to the two stream architecture. Also, two novel loss functions called Cross-network Similarity loss and Satisfied Rank loss are proposed to make the two-stream networks reinforce each other and get better results. Finally, the Network Fusion Attention merges intermediate results with the novel entropy add strategy to obtain the final predictions. All of these modules can work together and can be trained end to end. Besides, different from previous works, our model is fully weak-supervised and fully paralleled, which leads to easier generalization and faster computation. We obtain the state-of-the-art performance on three challenge benchmark datasets (CUB-200-2011, FGVC-Aircraft and Flower 102) with results of 90.8%, 92.1%, and 98.5%, respectively. The model will be publicly available at https://github.com/billzyx/LCA-CNN.

12.
Eye Vis (Lond) ; 6: 33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687416

RESUMO

Background: Fibroblast growth factor 10 (FGF10) is implicated in the growth and development of the eye. Four singles nucleotide polymorphisms (SNPs) in the FGF10 gene (including rs1384449, rs339501, rs12517396 and rs10462070) were found to be associated with extreme myopia (EM, refractive error ≤ - 10.0 diopters) in Japanese and Chinese Taiwan population. This case-control association study was conducted to explore the relationship between these four SNPs and high myopia in a western Chinese population. Methods: A total of 869 high myopia patients (HM, including 485 EM patients) and 899 healthy controls were recruited. These four SNPs were genotyped using the ABI SNaPshot method. Five genetic models (allelic, homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the SNPs and high myopia. The linkage-disequilibrium block (LD) structure was tested by Haploview Software. Results: In our study, no statistically significant differences were found between HM/EM patients and controls after Bonferroni multiple-correction (P > 0.05) in the allele frequencies of these four SNPs in the FGF10 gene. We further found that rs12517396AA and rs10462070GG carriers showed a decreased risk of HM/EM compared with rs12517396AC + CC and rs10462070GA + AA carriers (P = 0.045, OR = 0.366; P = 0.021, OR = 0.131; P = 0.03, OR = 0.341; P = 0.015, OR = 0.122; respectively). Additionally, rs12517396AA and rs10462070GG carriers showed the same decreased risk of HM/EM compared with rs12517396CC and rs10462070AA carriers (P = 0.048, OR = 0.370; P = 0.023, OR = 0.133; P = 0.032, OR = 0.346; P = 0.017, OR = 0.126). However, these significant associations between rs12517396/rs10462070 and HM/EM disappeared after Bonferroni multiple-correction (P > 0.05). Conclusion: Our findings indicate that rs12517396 and rs10462070 had marginal association with HM and EM. The other two common polymorphisms in FGF10 unlikely have significant effects in the genetic predisposition to HM/EM in western Chinese population. Further replication studies are needed to validate our findings in both animal models and human genetic epidemiologic studies.

13.
Neuroscience ; 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689489

RESUMO

Acceleration of cytoskeletal remodeling in regenerated axons is crucial for a fully functional recovery following peripheral nerve injury (PNI). Melatonin plays important roles in cell differentiation and protection of cytoskeleton stability, thus, the present study aimed to investigate whether melatonin can enhance neurite outgrowth and promote cytoskeletal remodeling in a PNI animal model and in differentiated neurons. End-to-side neurorrhaphy (ESN) rat model was used for assessing cytoskeletal rearrangement in regenerated axon. Subject rats received 1 mg/kg/day melatonin injection for one month. The amplitude of compound muscle action potentials and the number of re-innervated motor end plates on target muscles were assessed to represent the functional recovery after ESN. Melatonin treatment enhanced functional recovery after ESN, compared to the saline treated group. Additionally, in spinal cord and peripheral nerve tissue, animals receiving melatonin displayed enhanced expression of GAP43 and ß3-tubulin one month after ESN, and an increased number of re-innervated motor end plates on their target muscle. In vitro analysis revealed that melatonin treatment significantly promoted neurite outgrowth, and increased expression of melatonin receptors as well as ß3-tubulin in mouse neuroblastoma Neuro-2a (N2a) cells. Treatment with a melatonin receptor antagonist, luzindole, significantly suppressed melatonin receptors and ß3-tubulin expression. Importantly, we found that melatonin treatment suppressed activation of calmodulin-dependent protein kinase II (CaMKII) in vitro and in vivo, suggesting that the ß3-tubulin remodeling may occur via CaMKII-mediated Ca2+ signaling. These results suggested that melatonin may promote functional recovery after PNI by accelerating cytoskeletal remodeling through the melatonin receptor-dependent pathway.

14.
Biol Reprod ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31621835

RESUMO

Anti-androgenic endocrine-disrupting chemicals (EDCs) can cross the placenta to modify early offspring sexual dimorphic markers. These changes are linked to Anogenital Distance (AGD), which is an androgen sensitive anthropometric parameter used as a biomarker of perineal growth and caudal migration of the genital tubercle. This review aimed to summarize strength of evidence for associations of in utero exposure to EDCs with AGD and to identify gaps and limitations in the literature so as to inform future research. We performed an electronic search of English literature through September 2019 in MEDLINE, Web of Science and Toxline. We included epidemiological studies that examined in utero exposure to persistent and non-persistent EDCs, and considered AGD in offspring as an outcome. Our review contained 16 investigations examining exposure to persistent EDCs (9 studies) and non-persistent EDCs (7 studies). Some individual studies reported an inverse association between exposure to BPA, dioxins, perfluoroalkyl substances and organochlorides, and AGD in both male and female offspring. Meta-analysis of 3 studies found a small reduction of AGD in female offspring exposed to BPA. The number of studies per chemical is small and number of subjects examined is limited; so, replication of these results is needed. To achieve more specificity and better replication of results, future studies should establish the association of non-persistent EDCs using multiple urine samples, evaluate the cumulative impact of exposure to a mixture of anti-androgenic chemicals, and offer adequate consideration of more maternal- and children-related confounding factors.

15.
PeerJ ; 7: e7614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534852

RESUMO

Light pollution has become one of the top issues in environmental pollution, especially concerning how secondary light pollution, such as from traffic reflective materials, influences animal distribution and behavior. In this study, 15 camera traps were set up at sites with or without reflective warning markers (RWM) in coniferous forests on Cangshan Mountain located in Dali Prefecture, China. The results showed that the number of independent photographs and species at sites without RWMs were significantly higher than those at sites with RWMs. Significant differences were found between daytime and nighttime composition of bird species and non-flying mammals between two sites. This study found that RWMs had negative effects on wildlife, with the avoidance response of birds to RWMs being more obvious than that of animals at daytime. It is recommended that the use of reflective materials be carefully considered, especially in protected areas.

16.
Cell Death Differ ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31406303

RESUMO

Deregulation of E3 ubiquitin ligases is intimately implicated in breast cancer pathogenesis and progression, but the underlying mechanisms still remain elusive. Here we report that RING finger protein 144A (RNF144A), a poorly characterized member of the RING-in-between-RING family of E3 ubiquitin ligases, functions as a tumor suppressor in breast cancer. RNF144A was  downregulated in a subset of primary breast tumors and restoration of RNF144A suppressed breast cancer cell proliferation, colony formation, migration, invasion in vitro, tumor growth, and lung metastasis in vivo. In contrast, knockdown of RNF144A promoted malignant phenotypes of breast cancer cells. Quantitative proteomics and biochemical analysis revealed that RNF144A interacted with and targeted heat-shock protein family A member 2 (HSPA2), a putative oncoprotein that is frequently upregulated in human cancer and promotes tumor growth and progression, for ubiquitination and degradation. Notably, the ligase activity-defective mutants of RNF144A impaired its ability to induce ubiquitination and degradation of HSPA2, and to suppress breast cancer cell proliferation, migration, and invasion as compared with its wild-type counterpart. Moreover, RNF144A-mediated suppression of breast cancer cell proliferation, migration, and invasion was rescued by ectopic HSPA2 expression. Clinically, low RNF144A and high HSPA2 expression in breast cancer patients was correlated with aggressive clinicopathological characteristics and decreased overall and disease-free survival. Collectively, these findings reveal a previously unappreciated role for RNF144A in suppression of breast cancer growth and metastasis, and identify RNF144A as the first, to our knowledge, E3 ubiquitin ligase for HSPA2 in human cancer.

17.
Environ Res ; 177: 108581, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323395

RESUMO

Although myopia has been largely ignored among the elderly population, there is an increased risk of myopia with advancing age. Ambient air pollution is one potential contributor to vision impairments, but few epidemiological studies have demonstrated such an association. This cross-sectional survey collected the information of 33,626 subjects aged ≥50 years in six developing countries during 2007-2010. Myopia was identified based on questions related to symptoms of myopia. The annual concentrations of fine particulate matter (PM2.5) and ozone (O3) were estimated with the satellite data and chemical transport model. We examined the associations between the two pollutants and myopia using mixed-effect Poisson regression models with robust variance estimation (sandwich estimation). We observed J-shaped associations between the two pollutants and myopia, and identified 12 and 54 µg/m3 as the threshold concentrations. The adjusted prevalence ratio was 1.12 (95% CI: 1.05, 1.21) and 1.26 (95% CI: 1.14, 1.38) for each standard deviation (SD) increase in PM2.5 and O3 concentrations above their threshold, respectively. In addition, the interaction analysis suggested a synergistic interaction of these two pollutants on myopia in the additive model, with a synergistic index of 1.81 (Bootstrapping 95% CI: 0.92, 4.94). Our results indicate that long-term exposures to PM2.5 and O3 might be important environmental risk factors of myopia in the elderly, and suggest that more efforts should be taken to reduce airborne PM2.5 and O3 levels to protect vision health.

18.
J Antibiot (Tokyo) ; 72(10): 752-758, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31324892

RESUMO

Two new diketopiperazines (1, 2), one new polyprenol (3), together with 19 known compounds (4-22) were obtained from the EtOAc extract of Bionectria sp. Y1085, an endophytic fungus isolated from the plant Huperzia serrata. Their structures were elucidated by extensive NMR and MS analysis. Bionectin D (1) is a rare diketopiperazine with a single methylthio substitution at the α-carbon of cyclized amino acid residue. The antibacterial activity of compounds was assayed against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium ATCC 6539, and some metabolites (1, 2, 10, 11, and 14) exhibited evident antibacterial activity.

19.
Anal Bioanal Chem ; 411(23): 6067-6080, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273413

RESUMO

Rapid detection of trace Salmonella is urgently needed to ensure food safety. We present an innovative pretreatment strategy, based on a two-step enrichment culture and immunomagnetic separation, combined with a chemiluminescence microparticle immunoassay to detect at least one proliferative Salmonella cell in 25 mL (25 g) food. The capture performance of immunomagnetic beads (IMBs) of sizes for Salmonella was investigated, and the IMBs of size 2.8 µm showed a high capture efficiency of 60.7% in 25 mL milk and 74.5% in 25 mL chicken culture filtrate, which ensured the successful capture of trace Salmonella after 2.5 h in situ enrichment even from only one Salmonella cell. The separated Salmonella cells, reaching an amount of 103 colony-forming units (CFU) by a secondary enrichment for 3 h, were detected by a horseradish peroxidase chemiluminescence reaction with 4-(1-imidazolyl)phenol as an enhancer, which evidenced a linear response for Salmonella concentrations ranging from 2.3 × 102 to 7.8 × 104 CFU/mL. The entire detection process was completed within 8 h, with a very low detection limit of 1 CFU/25 mL (25 g), which was verified by colony counting, and a small degree of interference of 0.17-1.06%. Trace Salmonella from five different serovars in milk and chicken was successfully detected without false negative or false positive results. Furthermore, this study provides a basis to develop a fully automated instrument based on IMBs that includes all steps from sample preparation to chemiluminescence microparticle immunoassay for high-throughput screening of foodborne pathogens. Graphical abstract.


Assuntos
Contaminação de Alimentos/análise , Medições Luminescentes/métodos , Leite/microbiologia , Aves Domésticas/microbiologia , Salmonella/isolamento & purificação , Animais , Galinhas/microbiologia , Contaminação de Alimentos/economia , Inocuidade dos Alimentos/métodos , Imunoensaio/economia , Imunoensaio/métodos , Separação Imunomagnética/economia , Separação Imunomagnética/métodos , Limite de Detecção , Medições Luminescentes/economia , Infecções por Salmonella/microbiologia , Fatores de Tempo
20.
JAMA Oncol ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31318392

RESUMO

Importance: New therapeutic options for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) are needed. This study evaluated dual checkpoint combination therapy in patients with mPDAC. Objective: To evaluate the safety and efficacy of the anti-PD-L1 (programmed death-ligand 1) antibody using either durvalumab monotherapy or in combination with the anticytotoxic T-lymphocyte antigen 4 antibody using durvalumab plus tremelimumab therapy in patients with mPDAC. Design, Setting, and Participants: Part A of this multicenter, 2-part, phase 2 randomized clinical trial was a lead-in safety, open-label study with planned expansion to part B pending an efficacy signal from part A. Between November 26, 2015, and March 23, 2017, 65 patients with mPDAC who had previously received only 1 first-line fluorouracil-based or gemcitabine-based treatment were enrolled at 21 sites in 6 countries. Efficacy analysis included the intent-to-treat population; safety analysis included patients who received at least 1 dose of study treatment and for whom any postdose data were available. Interventions: Patients received durvalumab (1500 mg every 4 weeks) plus tremelimumab (75 mg every 4 weeks) combination therapy for 4 cycles followed by durvalumab therapy (1500 mg every 4 weeks) or durvalumab monotherapy (1500 mg every 4 weeks) for up to 12 months or until the onset of progressive disease or unacceptable toxic effects. Main Outcomes and Measures: Safety and efficacy were measured by objective response rate, which was used to determine study expansion to part B. The threshold for expansion was an objective response rate of 10% for either treatment arm. Results: Among 65 randomized patients, 34 (52%) were men and median age was 61 (95% CI, 37-81) years. Grade 3 or higher treatment-related adverse events occurred in 7 of 32 patients (22%) receiving combination therapy and in 2 of 32 patients (6%) receiving monotherapy; 1 patient randomized to the monotherapy arm did not receive treatment owing to worsened disease. Fatigue, diarrhea, and pruritus were the most common adverse events in both arms. Overall, 4 of 64 patients (6%) discontinued treatment owing to treatment-related adverse events. Objective response rate was 3.1% (95% CI, 0.08-16.22) for patients receiving combination therapy and 0% (95% CI, 0.00-10.58) for patients receiving monotherapy. Low patient numbers limited observation of the associations between treatment response and PD-L1 expression or microsatellite instability status. Conclusion and Relevance: Treatment was well tolerated, and the efficacy of durvalumab plus tremelimumab therapy and durvalumab monotherapy reflected a population of patients with mPDAC who had poor prognoses and rapidly progressing disease. Patients were not enrolled in part B because the threshold for efficacy was not met in part A. Trial Registration: ClinicalTrials.gov identifier: NCT02558894.

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