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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165764, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169506

RESUMO

Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32191889

RESUMO

In this paper, we investigate the importance of phase for texture discrimination and similarity estimation tasks. We first use two psychophysical experiments to investigate the relative importance of phase and magnitude spectra for human texture discrimination and similarity estimation. The results show that phase is more important to humans for both tasks. We further examine the ability of 51 computational feature sets to perform these two tasks. In contrast with the psychophysical experiments, it is observed that the magnitude data are more important to these computational feature sets than the phase data. We hypothesise that this inconsistency is due to the difference between the abilities of humans and the computational feature sets to utilise phase data. This motivates us to investigate the application of the 51 feature sets to phase-only images in addition to their use on the original data set. This investigation is extended to exploit Convolutional Neural Network (CNN) features. The results show that our feature fusion scheme improves the average performance of those feature sets for estimating humans' perceptual texture similarity. The superior performance should be attributed to the importance of phase to texture similarity.

3.
J Hazard Mater ; 394: 122562, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32213387

RESUMO

Although the toxic effects of silver nanoparticles (AgNPs) on fish gills have been reported, the underlying mechanism of toxicity remains unclear. The present study aimed to elucidate the mechanism of toxicity in the gills of common carp following exposure to AgNPs and silver nitrate (AgNO3) using histopathology and proteomics. Histopathological findings revealed that both AgNPs and AgNO3 caused telangiectasia and epithelial cell hyperplasia in fish gills; however, the pathological features and location of lesions caused by the two forms of silver were markedly different. Proteomics revealed that AgNPs and AgNO3 induced 139 and 185 differential expression proteins (DEPs) in gills, respectively, and the two forms of silver induced only 42 shared proteins. AgNPs specifically induced 87 DEPs which mainly involved signaling mechanisms, cytoskeleton, and the arachidonic acid metabolism processes. AgNO3 specifically induced 125 DEPs that were mainly clustered in the glutathione metabolism and protease processes. These results suggested that the toxic effects of AgNPs and AgNO3 were dramatically different in terms of protein expression in fish gills, which may provide novel perspectives for understanding the toxicity mechanism of silver nanoparticles in fish gills.

4.
Microorganisms ; 8(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143469

RESUMO

The growth of a large number of poisonous plants is an indicator of grassland degradation. Releasing allelochemicals through root exudates is one of the strategies with which poisonous plants affect neighboring plants in nature. Arbuscular mycorrhizal fungi (AMF) can form a mutualistic symbiosis with most of the higher plants. However, the manner of interaction between root exudates of poisonous plants and AMF on neighboring herbage in grasslands remains poorly understood. Stellera chamaejasme L., a common poisonous plant with approved allelopathy, is widely distributed with the dominant grass of Leymus chinensis in the degradeds of Northern China. In this study, we investigated the addition of S. chamaejasme root exudates (SRE), the inoculation of AMF, and their interaction on the growth and tissue nitrogen contents of L. chinensis, the characteristics of rhizosphere AMF, and soil physicochemical properties. Results showed that SRE had significant effects on ramet number, aboveground biomass, and total nitrogen of L. chinensis in a concentration dependent manner. Additionally, SRE had a significant negative effect on the rate of mycorrhiza infection and spore density of the AMF. Meanwhile, the addition of SRE significantly affected soil pH, electrical conductivity, available nitrogen (AN), available phosphorus (AP), total nitrogen (TN), and total carbon (TC) contents; while neither inoculation of AMF itself nor the interaction of AMF with SRE significantly affected the growth of L. chinensis. The interaction between AMF and SRE dramatically changed the pH, AP, and TC of rhizosphere soil. Therefore, we suggested SRE of S. chamaejasme affected the growth of L. chinensis by altering soil pH and nutrient availability. AMF could change the effect of SRE on soil nutrients and have the potential to regulate the allelopathic effects of S. chamaejasme and the interspecific interaction between the two plant species. We have provided new evidence for the allelopathic mechanism of S. chamaejasme and the regulation effects of AMF on the interspecific relationship between poisonous plants and neighboring plants. Our findings reveal the complex interplay between the root exudates of poisonous plants and rhizosphere AMF in regulating population growth and dynamics of neighboring plants in degraded grassland ecosystems.

5.
Insect Sci ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129536

RESUMO

Wings are essential for insect fitness. A number of proteins and enzymes have been identified to be involved in wing terminal differentiation, which is characterized by the formation of the wing cuticle. Here, we addressed the question whether Chitinase 10 (Cht10) may play an important role in chitin organization in the wings of the fruit fly Drosophila melanogaster. Initially, we first found that Cht10 expression coincides with the expression of the chitin synthase coding gene kkv. This suggests that the respective proteins may cooperate during wing differentiation. In tissue-specific RNA interference experiments, we demonstrate that suppression of Cht10 causes an excess in chitin amounts in the wing cuticle. Chitin organization is severely disrupted in these wings. Based on these data, we hypothesize that Cht10 restricts chitin amounts produced by Kkv in order to ensure normal chitin organization and wing cuticle formation. In addition, we found by scanning electron microscopy that Cht10 suppression also affects the cuticle surface. In turn, cuticle inward permeability is enhanced in Cht10-less wings. Moreover, flies with reduced Cht10 function are unable to fly. In conclusion, Cht10 is essential for wing terminal differentiation and function. This article is protected by copyright. All rights reserved.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32163642

RESUMO

BACKGROUND: Ocular involvement can occur at any stage of syphilis. Prompt diagnosis and proper treatment of ocular syphilis are vital to avoid long-term consequences. OBJECTIVES: To describe the risk factors for ocular syphilis and clinical features of blindness caused by syphilis. METHODS: We report risk factors for ocular syphilis amongst patients seen at the Shanghai Skin Disease Hospital between October 2009 to October 2017. We identify patients with ocular syphilis resulting in blindness and report the clinical characteristics, laboratory findings and treatment outcomes of these patients. RESULTS: A total of 8310 new cases of syphilis were seen, of which 213 patients had ocular disease and 50 patients had blindness due to syphilis. Increasing age and higher RPR titers were associated with ocular involvement but there was no association with HIV status. Blindness in syphilis was restricted predominantly to patients with optic nerve involvement and not patients with isolated uveitis. Fifty patients (and a total of 67 eyes) met the WHO definition of blindness prior to treatment for syphilis. At the end of follow-up vision had improved in 24 of 67 eyes (35.8%) after treatment. Successful treatment of uveitis was associated with the best improvement in visual acuity, whilst patient with underlying optic atrophy prior to treatment had the worst visual outcome. CONCLUSIONS: Ocular involvement is an important manifestation of syphilis which may result in blindness. Our data demonstrates outcomes for ocular syphilis are poor if detected late; early recognition and diagnosis is therefore vital to avoid permanent visual loss.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32179132

RESUMO

PURPOSE: To evaluate the effect of hyperthermia (HT) combined with concurrent radiochemotherapy (RCT) and treatment related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS: This study was conducted between 2009 and 2013 in CC patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV. The patients were randomly assigned into two treatment groups: RCT and RCT plus hyperthermia (RCHT) group. 5-year survival, treatment related toxicity and other prognostic factors were evaluated. RESULTS: 373 patients completed treatment and were analyzed by per protocol (PP) analysis. The 5-year overall survival (OS) in RCHT group (81.9%) was better than that in RCT group (72.3%) and the log-rank test showed statistically significant difference between the two groups (p=0.040). Univariate and multivariate COX regression analysis for 5-year OS showed statistically significant difference (p=0.043, p=0.045, respectively). The 5-year local relapse-free survival (LRFS) in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the two groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and relatively poor prognosis in univariate and multivariate analysis. CONCLUSION: The study confirmed that HT combined to RCT yielded a better 5-year OS in CC. Acute or late toxicity was similar between RCT and RCHT group. Clinical stage (FIGO) and tumor size were independent prognostic factor in CC.

8.
Ecotoxicol Environ Saf ; 194: 110337, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32120173

RESUMO

Environmental monitoring is important to the health management of an ecosystem. Biomarkers are particularly relevant because they are direct indicators of any toxic effects on organisms and are cheaper to use compared with chemical indicators, especially for extremely low-level organic contaminants. Fish can be significantly affected by pollutants, given their high trophic levels in aquatic food chains. Their immune function is closely related to their survival. The present study compared immune function-related parameters of wild mullet (Liza haematocheila) samples from low (Jinzhou) and high (Yingkou) polluted sites during the pre-winter (PW) and pre-breeding (PB) periods in Liaodong Bay, to evaluate the effect of water pollution on fish health and to explore potential biomarkers of coast water pollution. Compared with Jinzhou mullet, there was a significantly higher level of hematocrit in Yingkou mullet, but a significantly lower serum lysozyme level (P < 0.001), indicating that these fish were immunosuppressed. Significant differences occurred in the spleen between the two site populations. The abnormal: normal fish ratio in Yingkou L. haematochila was significantly higher than that of Jinzhou L. haematochila (2.5 times of that of Jinzhou during PB and nine times during PW). The splenic index of male Yingkou L. haematochila was 47.2% higher than that of Jinzhou L. haematochila in PW (P = 0.001). Moreover, histological observations showed that the spleen of the former was more congestive, with increased numbers (39.6% more) of melanomacrophage centers (MMCs) and changes in pigments (hemosiderin 8.3% higher and melanin 29.4% higher), compared with the latter. The splenic MMC area of Yingkou L. haematochila was significantly smaller than that of Jinzhou L. haematochila (P < 0.05) in PB, but showed no clear difference in PW (P > 0.05). Splenic MMC number was significantly higher in individual Yingkou L. haematochila with abnormal livers compared with normal Yingkou L. haematochila during both sampling periods. The splenic MMC area in abnormal livers was approximately four times those of normal individuals during PB in Yingkou L. haematochila. The number of splenic melanomacrophages (MM) in abnormal livers was approximately nine times those of the normal livers during PW. There were also differences in pigments in normal Yingkou individuals compared with normal Jinzhou samples during PW (melanin 29.4% higher and hemosiderin 8.3% higher). Based on these results, we suggest that serum lysozyme activity, splenic MM number and MMC (both number and area), and melanin of local fish have potential as sensitive biomarkers for the assessment of coastal water pollution.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32172421

RESUMO

Hydrogen generation from food waste anaerobic dark fermentation is identified as a promising strategy for resource recovery. In this work, an innovative strategy of using potassium ferrate (PF), a strong oxidant, to promote anaerobic dark fermentation of food waste to produce hydrogen has been reported. The experimental results revealed that PF enhanced the hydrogen production from food waste, the maximal hydrogen yield was 173.5 mL/g, and the optimal PF dosage was 0.4 g/g total suspended solids. PF shortened the lag phase for hydrogen generation from 120 to 96 h. Mechanisms investigation revealed that PF accelerated the disintegration of organic compounds and increased the soluble organic matter in the liquid phase. The strong oxidation of PF inhibited the processes of hydrolysis, acidification, acetogenesis, homoacetogenesis, and methanogenesis by using synthetic wastewater in the fermentation process. The inhibition of PF on these processes was further verified by the enzyme activity analysis. Economic analysis indicated that 0.1 g/g PF was the optimal dosage. PF treatment is a promising strategy to enhance the production of hydrogen from food waste dark fermentation.

10.
Prog Chem Org Nat Prod ; 111: 81-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32114663

RESUMO

Marine-derived fungi play an important role in the search for structurally unique secondary metabolites, some of which show promising pharmacological activities that make them useful leads for drug discovery. Marine natural product research in China in general has made enormous progress in the last two decades as described in this chapter on fungal metabolites. This contribution covers 613 new natural products reported from 2001 to 2017 from marine-derived fungi obtained from algae, sponges, corals, and other marine organisms from Chinese waters. The genera Aspergillus (170 new natural products, 28%) and Penicillium (70 new natural products, 11%) were the main fungal producers of new natural products during the time period covered, whereas sponges (184 new natural products, 30%) were the most abundant source of new natural products, followed by corals (154 new natural products, 25%) and algae (130 new natural products, 21%). Close to 40% of all natural products covered in this contribution displayed various bioactivities. The major bioactivities reported were cytotoxicity against different cancer cell lines, antimicrobial (mainly antibacterial) activity, and antiviral activity, which accounted for 13%, 9%, and 3% of all natural products reported. In terms of structural classes, polyketides (188 new natural products, 31%) play a dominant role, and if prenylated polyketides and nitrogen-containing polyketides (included in meroterpenes and alkaloids in this contribution) are taken into account, their total number even exceeds 50%. Nitrogen-containing compounds including peptides (65 new natural products, 10%) and alkaloids (103 new natural products, 17%) are the second largest group.


Assuntos
Produtos Biológicos/farmacologia , Fungos/química , Policetídeos/farmacologia , Animais , Antozoários/microbiologia , Anti-Infecciosos , Antineoplásicos , Organismos Aquáticos/microbiologia , Aspergillus/química , Produtos Biológicos/química , China , Penicillium/química , Policetídeos/química , Poríferos/microbiologia , Metabolismo Secundário
11.
Environ Int ; 138: 105607, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32142915

RESUMO

Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60-69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 µg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 µg/m3) (p < 0.001). Strong correlation (Spearman's r = 0.63, p < 0.001) was found between personal and ambient BC concentrations. The fixed-site monitoring ambient concentration cannot fully reflect the actual personal exposure concentration. Ambient BC concentration, ambient temperature, relative humidity, education level and air purifier use were significant determinants of personal BC exposure. Our findings highlight the need for detailed assessment of personal exposure on health risk assessment of BC and also help develop strategies for targeted risk reduction.

12.
13.
Cardiovasc Diabetol ; 19(1): 36, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32192491

RESUMO

BACKGROUND: The present cohort study aims to examine the relationship between fibrinogen (Fib) levels and glucose metabolism [fasting blood glucose (FBG) and hemoglobin A1c (HbA1c)] and investigate the impact of high Fib on cardiovascular outcomes in patients with stable CAD and pre-diabetes mellitus (pre-DM) or diabetes mellitus (DM). METHODS: This study included 5237 patients from March 2011 to December 2015. Patients were distributed into three groups according to Fib levels (low Fib, median Fib, high Fib) and further categorized by glucose metabolism status [normal glucose regulation (NGR), Pre-DM, DM]. All patients were followed up for the occurrences of major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal MI, stroke, and unplanned coronary revascularization. RESULTS: Linear regression analyses showed that FBG and HbA1c levels were positively associated with Fib in overall CAD participants, either with or without DM (all P < 0.001). During an average of 18,820 patient-years of follow-up, 476 MACEs occurred. High Fib was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.57, 95% confidence interval (CI) 1.26-1.97, P < 0.001]. Furthermore, DM but not pre-DM was a significant predictor of MACEs (P < 0.001 and P > 0.05, respectively). When patients were stratified by both glucose metabolism status and Fib levels, high Fib was associated with a higher risk of MACEs in pre-DM (HR 1.66, 95% CI 1.02-2.71, P < 0.05). Medium and high Fib levels were associated with an even higher risk of MACEs in DM (HR 1.86, 95% CI 1.14-3.05 and HR 2.28, 95% CI 1.42-3.66, all P < 0.05). After adding the combination of Fib and glucose status to the Cox model, the C-statistic was increased by 0.015 (0.001-0.026). CONCLUSIONS: The present study suggested that Fib levels were associated with FBG and HbA1c in stable CAD patients. Moreover, elevated Fib was independently associated with MACEs in CAD patients, especially among those with pre-DM and DM, suggesting that Fib may provide incremental value in the cardiovascular risk stratification of pre-DM and DM patients.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32086220

RESUMO

Non-negative matrix factorization (NMF) is a dimensionality reduction technique based on high-dimensional mapping. It can effectively learn part-based representations. In this paper, we propose a method called Dual Hyper-graph Regularized Supervised Non-negative Matrix Factorization (HSNMF). To encode the geometric information of the data, the hyper-graph is introduced into the model as a regularization term. The advantage of hyper-graph learning is to find higher order data relationship to enhance data relevance. This method constructs the data hyper-graph and the feature hyper-graph to find the data manifold and the feature manifold simultaneously. The application of hyper-graph theory in cancer datasets can effectively find pathogenic genes. The discrimination information is further introduced into the objective function to obtain more information about the data. Supervised learning with label information greatly improves the classification effect. Furthermore, the real datasets of cancer usually contain sparse noise, so the -norm is applied to enhance the robustness of HSNMF algorithm. Experiments under The Cancer Genome Atlas (TCGA) datasets verify the feasibility of the HSNMF method.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32086224

RESUMO

Non-negative Matrix Factorization (NMF) is a dimensionality reduction approach for learning a parts-based and linear representation of non-negative data. It has attracted more attention because of that. In practice, NMF not only neglects the manifold structure of data samples, but also overlooks the priori label information of different classes. In this paper, a novel matrix decomposition method called Hyper-graph regularized Constrained Non-negative Matrix Factorization (HCNMF) is proposed for selecting differentially expressed genes and tumor sample classification. The advantage of hyper-graph learning is to capture local spatial information in high dimensional data. This method incorporates a hyper-graph regularization constraint to consider the higher order data sample relationships. The application of hyper-graph theory can effectively find pathogenic genes in cancer datasets. Besides, the label information is further incorporated in the objective function to improve the discriminative ability of the decomposition matrix. Supervised learning with label information greatly improves the classification effect. We also provide the iterative update rules and convergence proofs for the optimization problems of HCNMF. Experiments under The Cancer Genome Atlas (TCGA) datasets confirm the superiority of HCNMF algorithm compared with other representative algorithms through a set of evaluations.

16.
Cardiovasc Diabetol ; 19(1): 15, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041617

RESUMO

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a novel marker of myocardial injury and has been reported to be associated with cardiovascular diseases (CVD) including patients with diabetes mellitus (DM). Unfortunately, its prognostic value in patients with CVD and impaired glucose metabolism (IGM) is unclear. The objective of this study was to investigate the prognostic value of H-FABP in CVD patients with IGM. METHODS: A total of 4594 patients with angiography-proven coronary artery disease (CAD) were enrolled and divided into subgroup according to glucose metabolism status (normal glucose regulation [NGR], pre-DM, and DM). Baseline levels of H-FABP were measured using latex immunoturbidimetric method. The cardiovascular events (CVE) were defined as cardiovascular death, myocardial infarction, stroke and coronary revascularization. Cox regression and Kaplan-Meier analysis were used to evaluate the relations of H-FABP and glucose metabolism status to CVEs. RESULTS: During the follow-up period with up to 7.1 years, 380 CVEs occurred. Patients with CVE had higher levels of H-FABP compared to those without CVE (p < 0.001). Interestingly, H-FABP levels were also elevated in DM and pre-DM groups compared with NGR group (p < 0.001), when combined glucose metabolism status with H-FABP stratification, patients in the highest tertile of H-FABP appeared to have higher risk of CVEs with pre-DM (adjusted hazard ratio [HR]: 1.855, 95% confidential intervals [CIs] 1.076-3.214; p = 0.033) and DM (adjusted HR: 2.560, 95% CIs 1.409-4.650; p = 0.002). The Kaplan-Meier curve indicated that DM patients with the highest H-FABP levels were associated with the greatest risk of CVEs (p < 0.05). CONCLUSIONS: Our data firstly showed that elevated H-FABP levels were associated with worse outcomes in CAD patients with pre-DM and DM, which provided the novel information that H-FABP might be a prognostic marker for clinical outcomes among patients with CAD and IGM.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32075321

RESUMO

Rice (Oryza sativa L.), a major staple food for billions of people, was assessed for its phytotoxicity of copper oxide nanoparticle (CuO NPs, size < 50 nm). Under hydroponic condition, seven days of exposure to 62.5, 125, and 250 mg/L CuO NPs significantly suppressed the growth rate of rice seedlings compared to both the control and the treatment of supernatant from 250 mg/L CuO NP suspensions. In addition, physiological indexes associated with antioxidants, including membrane damage and antioxidant enzyme activity, were also detected. Treatment with 250 mg/L CuO NPs significantly increased malondialdehyde (MDA) content and electrical conductivity of rice shoots by 83.4% and 67.0%, respectively. The activity of both catalase and superoxide dismutase decreased in rice leaves treated with CuO NPs at the concentration of 250 mg/L, while the activity of the superoxide dismutase significantly increased by 1.66 times in rice roots exposed to 125 mg/L CuO NPs. The chlorophyll, including chlorophyll a and chlorophyll b, and carotenoid content in rice leaves decreased with CuO NP exposure. Finally, to explain potential molecular mechanisms of chlorophyll variations, the expression of four related genes, namely, Magnesium chelatase D subunit, Chlorophyll synthase, Magnesium-protoporphyrin IX methyltransferase, and Chlorophyllide a oxygenase, were quantified by qRT-PCR. Overall, CuO NPs, especially at 250 mg/L concentration, could affect the growth and development of rice seedlings, probably through oxidative damage and disturbance of chlorophyll and carotenoid synthesis.

18.
J Mol Biol ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32087196

RESUMO

Cells have evolved molecular chaperones that modulate phase separation and misfolding of amyloidogenic proteins to prevent neurodegenerative diseases. Protein disulfide isomerase (PDI), mainly located at the endoplasmic reticulum and also present in the cytosol, acts as both an enzyme and a molecular chaperone. PDI is observed to be S-nitrosylated in the brain of Alzheimer's disease patients, but the mechanism has remained elusive. We herein report that both wild-type PDI and its quadruple cysteine mutant only having chaperone activity, significantly inhibit pathological phosphorylation and abnormal aggregation of Tau in cells, and significantly decrease the mitochondrial damage and Tau cytotoxicity resulting from Tau aberrant aggregation, highlighting the chaperone property of PDI. More importantly, we show that wild-type PDI is selectively recruited by liquid droplets of Tau, which significantly inhibits phase separation and stress granule formation of Tau, whereas S-nitrosylation of PDI abrogates the recruitment and inhibition. These findings demonstrate how phase separation of Tau is physiologically regulated by PDI and how S-nitrosylation of PDI, a perturbation in this regulation, leads to disease.

19.
Food Chem ; 316: 126370, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32062229

RESUMO

Castanopsis lamontii is used as functional herbal tea in southwest China. Usually, only buds rather than mature leaves are applied. To figure out whether mature leaves were suitable for producing herbal tea, chemical composition, sensory properties and bioactivities of Castanopsis lamontii bud infusion (CLB) and mature leaf infusion (CLM) were investigated. According to the results, CLB and CLM had similar non-volatile composition, but in different proportion. Meanwhile, CLB contained more types of volatiles than CLM, leading to distinguishable volatile profiles between them. Sensory assessment showed that CLB had sweet aftertaste and floral aroma. CLM tasted astringent and smelled grassy. Bioactivity evaluation indicated that CLB exhibited higher activities in scavenging free radicals and suppressing lipopolysaccharide-induced inflammation. Taken together, CLB had better overall acceptability in sensory quality and higher bioactivity, implying that Castanopsis lamontii buds were more suitable for producing herbal tea.

20.
Planta Med ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32018306

RESUMO

Three new (alterchothecenes A - C, 1:  -3: ) and 3 known (4:  -6: ) trichothecenes, along with 9 known compounds (7:  -15: ), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1: -3: were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1: -6: against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4: -6: exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1: -6: as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1: -6: synergistically decreased cell viability compared with the sole treatment with those compounds.

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