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1.
Ann Transplant ; 25: e925126, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33184254

RESUMO

BACKGROUND Pneumocystis carinii is an opportunistic pathogen that can cause severe lung infections after renal transplantation. Trimethoprim-sulfamethoxazole (TMP-SMX) has been recognized as a first-line treatment for chemoprophylaxis of Pneumocystis carinii pneumonia (PCP). This study aimed to establish a personalized chemoprophylaxis prescription specifically for those recipients with renal insufficiency. MATERIAL AND METHODS This retrospective study included 68 patients with confirmed PCP after renal transplantation. Patients were divided into 2 groups: an abnormal renal function (ARF) group (creatinine ≥1.5 ng/dl; n=37) and a normal renal function (NRF) group (creatinine <1.5 ng/dl; n=31). Clinical characteristics and prognosis of PCP in both groups were compared and analyzed. RESULTS Patients in the ARF group had more prophylaxis after transplantation (15 [40.5%] vs. 2 [6.5%], p=0.047), had more biopsy-proven rejections (10 [27%] vs. 1 [3.2%], p=0.008), and had lower lymphocyte counts (0.6 [05-0.9] vs. 1.1 [0.7-1.6], p<0.01). Renal function after treatment was obviously improved in the ARF group, which had a significant decrease rate in creatinine (-13.2% [-22~4.8%] vs. -4.4% [-12.6~20.9%], p=0.043). CONCLUSIONS PCP prophylaxis regimens for recipients after renal transplantation are still needed regardless of whether the renal functions were normal or abnormal, especially for recipients with persistent lymphopenia or rejection after transplantation.

2.
Adv Mater ; : e2005565, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179394

RESUMO

State-of-the-art proton exchange membranes (PEMs) often suffer from significantly reduced conductivity under low relative humidity, hampering their efficient application in fuel cells. Covalent organic frameworks (COFs) with pre-designable and well-defined structures hold promise to cope with the above challenge. However, fabricating defect-free, robust COF membranes proves an extremely difficult task due to the poor processability of COF materials. Herein, a bottom-up approach is developed to synthesize intrinsic proton-conducting COF (IPC-COF) nanosheets (NUS-9) in aqueous solutions via diffusion and solvent co-mediated modulation, enabling a controlled nucleation and in-plane-dominated IPC-COF growth. These nanosheets allow the facile fabrication of IPC-COF membranes. IPC-COF membranes with crystalline, rigid ion nanochannels exhibit a weakly humidity-dependent conductivity over a wide range of humidity (30-98%), 1-2 orders of magnitude higher than that of benchmark PEMs, and a prominent fuel cell performance of 0.93 W cm-2 at 35% RH and 80 °C arising from superior water retention and Grotthuss mechanism-dominated proton conduction.

3.
Biomed Chromatogr ; : e5024, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169405

RESUMO

The present study was designed to explore the bioactive ingredients in the extract with the best neuraminidase inhibition activity of Fallopia denticulata (C.C.Huang) Holub, a folk herb medicine growing in China. Three fractions of ethyl acetate, ethanol, and water were tested on neuraminidase inhibition assay and the best one was conducted by UPLC-TOF/MS in the negative and positive mode to analyze the metabolic components. The results revealed the identification of 21 compounds: 3 organic acids, 11 flavonoids, one coumarin, and 6 others, such as ß-daucosterol, gallic acid, and syringic acid. Wherein 12 compounds were discovered for the first time in F. denticulata. Besides, we utilized the molecular docking technology to support the anti- neuraminidase activity of each compound in the best extract. The results confirmed that the better two bioactive compounds were (-) -Epicatechin gallate and (+)-catechin. Therefore, F. denticulata could be the potential material of new anti-influenza drugs.

4.
J Transl Med ; 18(1): 442, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225954

RESUMO

BACKGROUND: Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer. METHODS: We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan-Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses. RESULTS: A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p = 1.215e - 06 in the training set; p = 0.0069 in the validation set; p = 1.233e - 07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR = 1.432; 95% CI 1.204-1.702, p < 0.001), validation set (HR = 1.162; 95% CI 1.004-1.345, p = 0.044), and whole set (HR = 1.240; 95% CI 1.128-1.362, p < 0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways. CONCLUSIONS: We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.

5.
Nat Commun ; 11(1): 5898, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33214551

RESUMO

O-GlcNAc modification plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regulated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated transcription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O-GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33216702

RESUMO

Thallium (Tl) is a toxic element that exists at trace level in coal. Coal-fired power plants (CFPPs) consume large amounts of coal and can potentially release this element into surrounding environment. However, knowledge of fates of Tl inside CFPPs and associated atmospheric emissions is still very limited. In this study, five CFPPs with pulverized coal boilers (PC) in Guizhou province, southwest China were selected for investigation. All input and output solid materials and the stack flue gas samples were collected simultaneously. Tl concentrations in feed coal (0.10-0.34 mg·kg-1) of the five CFPPS were only a third to one half of the national average value. Tl concentrations were obviously higher in fly ash (0.39-1.13 mg·kg-1) than bottom ash (0.09-0.25 mg·kg-1), indicating notable redistribution of Tl during coal combustion. Tl concentrations were low in limestone (0.01-0.02 mg·kg-1), flue gas desulfurization gypsum (0.01-0.03 mg·kg-1), and the stack flue gas (0.006-0.011 µg·Nm-3). Most Tl inside these CFPPs was captured by electrostatic precipitator or electrostatic precipitator-fabric filter fly ash (88.66 - 97.44%), followed by bottom ash (2.13-10.73%), gypsum (<3.89%), and stack emissions (0.01-0.05%). Atmospheric emission factors of Tl from different CFPPs are in the range of 0.04-0.09 mg Tl·t-1 coal, 0.02-0.04 µg·(kW·h)-1 or 0.002-0.004 g Tl·TJ-1. Using these emission factors, a total of 3.96 ± 1.32 kg (range: 2.64-5.94 kg) Tl is estimated to be released into the atmosphere annually from CFPPs in Guizhou in 2017. To avoid the cross-media contamination from the combustion products, careful treatment of the captured fly ash, bottom ash, and gypsum is needed, considering that a large amount of Tl (average: 728 kg·yr-1; range: 664-792 kg·yr-1) is retained in these solid combustion products and the possibility of formation of more toxic Tl3+ during the combustion process. Implication statement Thallium is rare but toxic element. Identification and quantification its source are a high priority for control its contamination. Coal-fired power plants were thought an important source of Tl, but few field studies had been conducted for this area. In this paper, we investigated the fate of Tl in five pulverized coal utility power plants in Guizhou province, Southwest China, and found the Tl concentration in stack gas is in low levels of 0.006-0.011 µg·Nm-3, and less than 0.05% of total input of Tl is escaped into the ambient atmosphere. The majority of Tl (88.7-97.4% of the total output) is detained by the ESP/ESP-FF fly ashes. Compared to the little amount (~4 kg·yr-1) of Tl that discharged into atmosphere from Guizhuo's coal-fired power plants in 2017, more Tl (over 700 kg) is end up in the solid coal combustion products each year, makes the need of careful disposal of these solid combustion waste to prevent the mobilization of Tl into the environment.

7.
BMC Pharmacol Toxicol ; 21(1): 80, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213527

RESUMO

BACKGROUND: Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out. METHODS: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 h later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded. RESULTS: The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence limits between 80 ~ 125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70 ± 0.49) ng/mL, AUC0-t was (141.32 ± 36.24) ng × h/mL and AUC0-∞ was (157.14 ± 45.65) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.83 ± 0.52) ng/mL, AUC0-t was (153.62 ± 33.96) ng × h/mL and AUC0-∞ was (173.05 ± 41.78) ng × h/mL after a single dose of 10 mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73 ± 0.55) ng/mL, AUC0-t was (166.93 ± 49.96) ng × h/mL and AUC0-∞ was (190.99 ± 70.89) ng × h/mL after a single dose of 5 mg levamlodipine. The mean Cmax was (2.87 ± 0.81) ng/mL AUC0-t was (165.46 ± 43.58) ng × h/mL and AUC0-∞ was (189.51 ± 64.70) ng × h/mL after a single dose of 10 mg amlodipine. Serious adverse event was not observed. CONCLUSION: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasted condition and fed condition. TRIAL REGISTRATION: Cinicaltrials, NCT04411875 . Registered 3 June 2020 - Retrospectively registered.

8.
Crit Care Med ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165026

RESUMO

OBJECTIVES: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury. DESIGN: Experimental study. SETTING: Research laboratory. SUBJECTS: Patients with acute respiratory distress syndrome and control subjects, wild-type C57BL/6 and formyl peptide receptor-1 gene knockout mice, and primary rat alveolar epithelial type II cells. INTERVENTIONS: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated with mitochondrial damage-associated molecular patterns. MEASUREMENTS AND MAIN RESULTS: Patients were divided into direct (pulmonary) and indirect (extrapulmonary) injury groups based on etiology. The release of mitochondrial peptide nicotinamide adenine dinucleotide dehydrogenase 1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. In the lipopolysaccharide-induced lung injury, administration of mitochondrial damage-associated molecular patterns exacerbated the lung fluid imbalance, which was mitigated in formyl peptide receptor-1 knockout mice. Proteomic analysis of mouse lung tissues revealed the involvement of ion channels and tight junction proteins in this process. Treatment with mitochondrial damage-associated molecular patterns decreased the expression of epithelial sodium channel α, zonula occludens-1, and occludin via the formyl peptide receptor-1/p38 pathway in the primary rat alveolar epithelial type II cells. CONCLUSIONS: Mitochondrial damage-associated molecular patterns exacerbate lung fluid imbalance in the experimental acute lung injury model through formyl peptide receptor-1 signaling, the inhibition of which may prevent exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Thus, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome.

9.
Environ Manage ; 66(6): 1105-1119, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070200

RESUMO

Soil heavy metal pollution threatens ecological health and food security. It is significant to classify pollution risk management and control zones, which can effectively cope with soil pollution and scientifically carry out soil remediation projects. In this study, based on 665 soil samples collecting from Ningbo (southeast China), single pollution index and Nemerow composite pollution index (NCPI) were measured to assess soil pollution risk, and self-organization mapping model was applied to classify management and control zones. Results showed that the heavy metal pollution in the northwest part was more serious, while the east part was less polluted. Although more than 75% soil samples had negligible risks, the Hg and Cu pollution was greatly influential and notable as their polluted samples accounted for 24.21% and 12.48% respectively. Moreover, about 55.34% soil samples and more than half study region had pollution grades, and NCPI values were obviously high with the center of northwest study area. Results also showed that the study region could be classified into four zones with good spatial variabilities. Specifically, Monitored Zone with High-risk Pollution had the highest NCPI caused by human activities, while Controlled Zone with Severe Pollution had relatively high NCPI caused by industrial and agricultural production. Protected Zone with Ecological Conservation and Restricted Zone with Potential Pollution had low NCPIs attributing to historical or natural factors. Our study implies that the classified zones can provide fundamental and momentous information for establishing appropriate priorities of heavy metal risk management and control.

10.
Semin Cancer Biol ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33035656

RESUMO

Epigenetic regulation of mitochondrial DNA (mtDNA) is an emerging and fast-developing field of research. Compared to regulation of nucler DNA, mechanisms of mtDNA epigenetic regulation (mitoepigenetics) remain less investigated. However, mitochondrial signaling directs various vital intracellular processes including aerobic respiration, apoptosis, cell proliferation and survival, nucleic acid synthesis, and oxidative stress. The later process and associated mismanagement of reactive oxygen species (ROS) cascade were associated with cancer progression. It has been demonstrated that cancer cells contain ROS/oxidative stress-mediated defects in mtDNA repair system and mitochondrial nucleoid protection. Furthermore, mtDNA is vulnerable to damage caused by somatic mutations, resulting in the dysfunction of the mitochondrial respiratory chain and energy production, which fosters further generation of ROS and promotes oncogenicity. Mitochondrial proteins are encoded by the collective mitochondrial genome that comprises both nuclear and mitochondrial genomes coupled by crosstalk. Recent reports determined the defects in the collective mitochondrial genome that are conducive to breast cancer initiation and progression. Mutational damage to mtDNA, as well as its overproliferation and deletions, were reported to alter the nuclear epigenetic landscape. Unbalanced mitoepigenetics and adverse regulation of oxidative phosphorylation (OXPHOS) can efficiently facilitate cancer cell survival. Accordingly, several mitochondria-targeting therapeutic agents (biguanides, OXPHOS inhibitors, vitamin-E analogues, and antibiotic bedaquiline) were suggested for future clinical trials in breast cancer patients. However, crosstalk mechanisms between altered mitoepigenetics and cancer-associated mtDNA mutations remain largely unclear. Hence, mtDNA mutations and epigenetic modifications could be considered as potential molecular markers for early diagnosis and targeted therapy of breast cancer. This review discusses the role of mitoepigenetic regulation in cancer cells and potential employment of mtDNA modifications as novel anti-cancer targets.

11.
Int J Clin Pract ; : e13759, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098255

RESUMO

AIMS: To investigate current awareness and practices of neurological prognostication in comatose cardiac arrest (CA) patients. METHODS: An anonymous questionnaire was distributed to 1600 emergency physicians in 75 hospitals which were selected randomly from China between January and July 2018. RESULTS: 92.1% respondents fulfilled the survey. The predictive value of brain stem reflex, motor response and myoclonus was confirmed by 63.5%, 44.6% and 31.7% respondents respectively. Only 30.7% knew that GWR value <1.1 indicated poor prognosis and only 8.1% know the most commonly used SSEP N20. Status epilepticus, burst suppression, suppression was considered to predict poor outcome by only 35.0%, 27.4%, 20.9% respondents respectively. 46.7% knew NSE, and only 24.7% knew S-100. Only a few respondents knew that neurological prognostication should be performed later than 72h from CA either in TTM or non-TTM patients. In practice, the most commonly used method was clinical examination (85.4%). 67.9% had used brain CT for prognosis, and 18.4% for MRI. NSE (39.6%) was a little more widely used than S-100ß (18.0%). However, SSEP (4.4%) and EEG (11.4%) were occasionally performed. CONCLUSIONS: Neurological prognostication in CA survivors had not been well understood and performed by emergency physicians in China. They were more likely to use clinical examination rather than objective tools, especially SSEP and EEG, which also illustrated that multimodal approach was not well performed in practice.

12.
Drug Des Devel Ther ; 14: 4327-4342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116419

RESUMO

Proteasome is vital for intracellular protein homeostasis as it eliminates misfolded and damaged protein. Inhibition of proteasome has been validated as a powerful strategy for anti-cancer therapy, and several drugs have been approved for treatment of multiple myeloma. Recent studies indicate that proteasome has potent therapeutic effects on a variety of diseases besides cancer, including parasite infectious diseases, bacterial/fungal infections diseases, neurodegenerative diseases and autoimmune diseases. In this review, recent developments of proteasome inhibitors for various diseases and related structure activity relationships are going to be summarized.

13.
Clin Interv Aging ; 15: 1951-1961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116449

RESUMO

Background: The Barthel index (BI) is a widely used assessment tool for evaluating physical performance in activities of daily living (ADL). The association between BI scores and mortality in hospital and during follow-up of acute coronary syndrome (ACS) patients remains unclear. The present study investigated whether the BI score could be used as a predictor for mortality of ACS. Methods: We investigated ACS patients from the multi-center Retrospective Evaluation of Acute Chest Pain (REACP) study. The association between BI scores and all-cause mortality of patients with ACS was analyzed by Cox proportional hazards models. The primary endpoint was all-cause death and the secondary endpoint was cardiac death during follow-up. Results: Among 2908 patients with ACS enrolled, 277 (9.5%) patients died within a median follow-up time of 10.6 months. Patients with lower BI had higher risks of mortality, compared with those with higher BI in ACS patients. Kaplan-Meier analysis revealed that patients with lower BI had worse survival rates than patients with higher BI (P < 0.001). After adjustment for potential influencing factors, multivariate Cox regression analysis showed that the BI was independently associated with all-cause mortality and cardiac mortality, respectively. Conclusion: The BI at admission has the powerful potential to provide useful prognostic information of early risk stratification, and routine recording of the BI at the ED visit may help in decision-making and health care planning for patients with ACS.

15.
Oral Dis ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128313

RESUMO

OBJECTIVES: Dental tissue-derived mesenchymal stem cell (MSC)-mediated tooth regeneration may be a useful therapeutic tool for repairing tooth loss. However, the low success rate of tooth regeneration restricts its clinical application. Identifying key factors for enhancing dentinogenesis in MSCs is crucial for promoting tooth regeneration. MATERIALS AND METHODS: Human dental pulp stem cells (DPSCs) were transfected with retrovirus to obtain SFRP2-over-expressing DPSCs. Alkaline phosphatase (ALP) activity assay, Alizarin red staining, quantitative analysis of calcium, and dentinogenesis-related genes were detected. Additionally, transplantation in a rabbit tooth extraction model was used to explore the role of SFRP2 in dentin regeneration. RESULTS: We found SFRP2 over-expression greatly enhanced ALP activity, and mineralization in DPSCs. Real-time RT-PCR revealed SFRP2 over-expression promoted the expressions of OSX, RUNX2, DSPP, DMP1, and BSP. Moreover, Micro CT analysis showed high-density calcification occurred to a much higher extent in SFRP2 over-expressing group compared to control group in vivo. Additionally, HE staining, immmunohistochemistry staining, and scanning electron microscopy results showed much more dentin-like tissue formed in SFRP2 over-expressing group compared to control group. CONCLUSIONS: Our findings revealed SFRP2 is an important regulator that enhances the dentinogenesis of DPSCs and dentin regeneration in the jaw, which may have clinical applications.

16.
Ecotoxicol Environ Saf ; 208: 111412, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33039872

RESUMO

Cadmium (Cd) is a severely toxic and carcinogenic heavy metal. Cigarette smoking is one of the major source of Cd exposure in humans. Nicotiana tabacum is primarily a leaf Cd accumulator, while Nicotiana rustica is a root Cd accumulator among Nicotiana species. However, little is known about the mechanisms of differential Cd translocation and accumulation in Nicotiana. To find the key factors, Cd concentration, Cd chemical forms, and transcriptome analysis were comparatively studied between N. tabacum and N. rustica under control or 10 µM Cd stress. The leaf/root Cd concentration ratio of N. tabacum was 2.26 and that of N. rustica was 0.14. The Cd concentration in xylem sap of N. tabacum was significantly higher than that of N. rustica. The root of N. tabacum had obviously higher proportion of ethanol extractable Cd (40%) and water extractable Cd (16%) than those of N. rustica (16% and 6%). Meanwhile the proportion of sodium chloride extracted Cd in N. rustica (71%) was significantly higher than that in N. tabacum (30%). A total of 30710 genes expressed differentially between the two species at control, while this value was 30,294 under Cd stress, among which 27,018 were collective genes, manifesting the two species existed enormous genetic differences. KEGG pathway analysis showed the phenylpropanoid biosynthesis pathway was overrepresented between the two species under Cd stress. Several genes associated with pectin methylesterase, suberin and lignin synthesis, and heavy metal transport were discovered to be differential expressed genes between two species. The results suggested that the higher accumulation of Cd in the leaf of N. tabacum depends on a comprehensive coordination of Cd transport, including less cell wall binding, weaker impediment by the Casparian strip, and efficient xylem loading.

17.
Nat Commun ; 11(1): 5405, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106493

RESUMO

Epstein-Barr virus (EBV) is a γ-herpesvirus associated with the occurrence of several human malignancies. BBRF2 and BSRF1 are two EBV tegument proteins that have been suggested to form a hetero-complex and mediate viral envelopment, but the molecular basis of their interaction and the functional mechanism of this complex remains unknown. Here, we present crystal structures of BBRF2 alone and in complex with BSRF1. BBRF2 has a compact globular architecture featuring a central ß-sheet that is surrounded by 10 helices, it represents a novel fold distinct from other known protein structures. The central portion of BSRF1 folds into two tightly associated antiparallel α-helices, forming a composite four-helix bundle with two α-helices from BBRF2 via a massive hydrophobic network. In vitro, a BSRF1-derived peptide binds to BBRF2 and reduces the number of viral genome copies in EBV-positive cells. Exogenous BBRF2 and BSRF1 co-localize at the Golgi apparatus. Furthermore, BBRF2 binds capsid and capsid-associated proteins, whereas BSRF1 associates with glycoproteins. These findings indicate that the BBRF2-BSRF1 complex tethers EBV nucleocapsids to the glycoprotein-enriched Golgi membrane, facilitating secondary envelopment.


Assuntos
Herpesvirus Humano 4/metabolismo , Capsídeo/química , Capsídeo/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Genoma Viral , Herpesvirus Humano 4/química , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Ligação Proteica , Conformação Proteica em alfa-Hélice
18.
Artigo em Inglês | MEDLINE | ID: mdl-33112477

RESUMO

Molecular self-assembly has been widely used to develop nanocarriers for drug delivery; however, most have unsatisfactory drug loading capacity (DLC) and the dilemma between stimuli-responsiveness and stability, stagnating their translational process. Here we overcame these drawbacks using dynamic combinatorial chemistry. A carrier molecule was spontaneously and quantitatively synthesized, aided by co-self-assembly with a template molecule and an anti-cancer drug doxorubicin (DOX) from a dynamic combinatorial library that was operated by disulfide exchange under thermodynamic control. The highly selective synthesis guaranteed a stable yet pH- and redox- responsive nanocarrier with a maximized DLC of 40.1% and an enhanced drug potency to fight DOX resistance in vitro and in vivo . Our findings suggested that harnessing the interplay between synthesis and self-assembly in complex chemical systems could yield functional nanomaterials for advanced applications.

19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5378-5381, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019197

RESUMO

This paper investigates the association between consecutive ambient air pollution and Chronic Obstructive Pulmonary Disease (COPD) hospitalization in Chengdu China. The three-year (2015-2017) time series data for both ambient air pollutant concentrations and COPD hospitalizations in Chengdu are approved for the study. The big data statistic analysis shows that Air Quality Index (AQI) exceeded the lighted air polluted level in Chengdu region are mainly attributed to particulate matters (i.e., PM2.5 and PM10). The time series study for consecutive ambient air pollutant concentrations reveal that AQI, PM2.5, and PM10 are significantly positive correlated, especially when the number of consecutive polluted days is greater than nine days. The daily COPD hospitalizations for every 10 µg/m3 increase in PM2.5 and PM10 indicate that consecutive ambient air pollution can lead to an appearance of an elevation of COPD admissions, and also present that dynamic responses before and after the peak admission are different. Support Vector Regression (SVR) is then used to describe the dynamics of COPD hospitalizations to consecutive ambient air pollution. These findings will be further developed for region specific, hospital early notifications of COPD in responses to consecutive ambient air pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , China/epidemiologia , Hospitalização , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia
20.
Zhongguo Zhen Jiu ; 40(10): 1061-4, 2020 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-33068346

RESUMO

OBJECTIVE: To observe effect of "Zhibian (BL 54) through Shuidao (ST 28)" acupuncture for quality of life of female patients with stress urinary incontinence. METHODS: A total of 90 female patients were randomly divided into an observation group and a control group, 45 cases in each group. The patients in the observation group were treated with "Zhibian (BL 54) through Shuidao (ST 28)" acupuncture method, and the patients in the control group were treated with non-permeable sham acupuncture at Zhibian (BL 54). The needles were retained for 30 min in both groups, once a day, and the treatment was totally given 10 times. The score of urinary incontinence quality of life questionnaire (I-QOL) was recorded before and after treatment and during the follow-up 1 month after treatment in the two groups, and the 1 h urine pad test and the 72 h urination diary card were used to evaluate the 1 h urine leakage and the 24 h urine leakage frequency of the two groups. RESULTS: After treatment and during follow-up, the I-QOL scores in the observation group were higher than those before treatment (P<0.05), and were higher than those in the control group (P<0.05). After treatment and during follow-up, the 1 h urine leakage and the 24 h urine leakage frequency in the observation group were lower than those before treatment (P<0.05), and less than those in the control group (P<0.05). CONCLUSION: Acupuncture of "Zhibian (BL 54) through Shuidao (ST 28)" can improve the quality of life of female patients with stress urinary incontinence, and improve the volume and frequency of urine leakage.

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