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1.
BMC Microbiol ; 20(1): 41, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111156

RESUMO

BACKGROUND: The dogma that urine is sterile in healthy individuals has been overturned by recent studies applying molecular-based methods. Mounting evidences indicate that dysbiosis of the urinary microbiota is associated with several urological diseases. In this study, we aimed to investigate the urinary microbiome of male patients with calcium-based kidney stones and compare it with those of healthy individuals. RESULTS: The diversity of the urinary microbiota in kidney stone patients was significantly lower than that of healthy controls based on the Shannon and Simpson index (P < 0.001 for both indices). The urinary microbiota structure also significantly differed between kidney stone patients and healthy controls (ANOSIM, R = 0.11, P < 0.001). Differential representation of inflammation associated bacteria (e.g., Acinetobacter) and several enriched functional pathways were identified in the urine of kidney stones patients. Meanwhile, we found the species diversity, overall composition of microbiota and predicted functional pathways were similar between bladder urine and renal pelvis urine in kidney stone patients. CONCLUSIONS: A marked dysbiosis of urinary microbiota in male patients with calcium-based kidney stones was observed, which may be helpful to interpret the association between bacteria and calcium-based kidney stones.

2.
Cell Death Dis ; 11(3): 159, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32123165

RESUMO

Hereditary distal renal tubular acidosis (dRTA) is a rare disease of H+ excretion defect of α-intercalated cells in renal collecting duct, caused by decreased V-ATPase function due to mutations in the ATP6V1B1 or ATP6V0A4 genes. In the present study, a genetic family with 5 members of the complete dRTA phenotype were found with distal tubule H+ secretion disorder, hypokalemia, osteoporosis, and kidney stones. A variant NM_020632.2:c.1631C > T (p.Ser544Leu) in exon 16 on an ATP6V0A4 gene associated with dRTA was detected by next generation sequencing target region capture technique and verified by Sanger sequencing, which suggested that except for one of the patients who did not receive the test, the other four patients all carried the p.S544L heterozygote. In transfected HEK293T cells, cells carrying p.S544L-mut showed early weaker ATPase activity and a slower Phi recovery rate after rapid acidification. By immunofluorescence localization, it was observed that the expression level of p.S544L-mut on the cell membrane increased and the distribution was uneven. Co-immunoprecipitation showed the a4 subunit of ATP6V0A4/p.S544L-mut could not bind to the B1 subunit, which might affect the correct assembly of V-ATPase. The present study of dRTA family suggests that the p.S544L variant may be inherited in a dominant manner.

3.
J Hypertens ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32141967

RESUMO

BACKGROUND: Smokers may smoke cigarettes during ambulatory or home blood pressure (BP) monitoring but not clinic measurement. We investigated the prevalence of masked hypertension in relation to cigarette smoking in Chinese outpatients enrolled in a multicenter registry. METHODS: Our study included 1646 men [494 (30.0%) current smokers]. We defined masked hypertension as a normal clinic SBP/DBP (<140/90 mmHg) and elevated daytime (≥135/85 mmHg) or night-time (≥120/70 mmHg) ambulatory or morning or evening home SBP/DBP (≥135/85 mmHg). RESULTS: In all men, multiple logistic regression showed that current cigarette smoking was significantly associated with daytime [prevalence 18.7%, odds ratio (OR) 1.69, 95% confidence interval 1.27-2.25, P = 0.0003] but not night-time (prevalence 27.1%, P = 0.32) ambulatory masked hypertension and associated with evening (prevalence 14.6%, OR 1.81, confidence interval 1.33-2.47, P = 0.0002) but not morning (prevalence 17.6%, P = 0.29) home masked hypertension. The associations were more pronounced for heavy smoking (≥20 cigarettes/day) relative to never smoking for both masked daytime ambulatory (OR 1.97, P = 0.001) and evening home hypertension (OR 2.40, P < 0.0001) or in patients over 55 years of age (P for interaction in relation to daytime ambulatory masked hypertension = 0.005). In men with clinic normotension (n = 742), the associations were also significant (P < 0.01), particularly in those with a normal to high-normal clinic BP (n = 619, P < 0.04). CONCLUSION: Cigarette smoking was associated with increased odds of masked daytime ambulatory and evening home hypertension, especially in heavy smoking or older men.

4.
Sci Adv ; 6(8): eaay6812, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32128412

RESUMO

Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disease caused by mutations in the dystrophin gene (DMD). Previously, we applied CRISPR-Cas9-mediated "single-cut" genome editing to correct diverse genetic mutations in animal models of DMD. However, high doses of adeno-associated virus (AAV) are required for efficient in vivo genome editing, posing challenges for clinical application. In this study, we packaged Cas9 nuclease in single-stranded AAV (ssAAV) and CRISPR single guide RNAs in self-complementary AAV (scAAV) and delivered this dual AAV system into a mouse model of DMD. The dose of scAAV required for efficient genome editing were at least 20-fold lower than with ssAAV. Mice receiving systemic treatment showed restoration of dystrophin expression and improved muscle contractility. These findings show that the efficiency of CRISPR-Cas9-mediated genome editing can be substantially improved by using the scAAV system. This represents an important advancement toward therapeutic translation of genome editing for DMD.

5.
Int J Biol Sci ; 16(6): 970-980, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32140066

RESUMO

Osteoarthritis (OA) is a whole-joint disease characterized by cartilage destruction, subchondral bone sclerosis, osteophyte formation, and synovitis. However, it remains unclear which part of the joint undergoes initial pathological changes that drives OA onset and progression. In the present study, we investigated the longitudinal alterations of the entire knee joint using a surgically-induced OA mouse model. Histology analysis showed that synovitis occurred as early as 1 week after destabilization of the medial meniscus (DMM), which preceded the events of cartilage degradation, subchondral sclerosis and osteophyte formation. Importantly, key pro-inflammatory cytokines such as IL-1ß, IL-6, TNFα, and Ccl2, major matrix degrading enzymes including Adamts4, Mmp3 and Mmp13, as well as nerve growth factor (NGF), all increased significantly in both synovium and articular cartilage. It is notable that the inductions of these factors in synovium are far more extensive than those in articular cartilage. Results from behavioral tests demonstrated that sensitization of knee joint pain developed after 8 weeks, later than histological and molecular changes. In addition, the nanoindentation modulus of the medial tibiae decreased 4 weeks after DMM surgery, simultaneous with histological OA signs, which is also later than appearance of synovitis. Collectively, our data suggested that synovitis precedes and is associated with OA, and thus synovium may be an important target to intervene in OA treatment.

6.
Ann Rheum Dis ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156705

RESUMO

OBJECTIVES: In this study, we aim to determine the effect of metformin on osteoarthritis (OA) development and progression. METHODS: Destabilisation of the medial meniscus (DMM) surgery was performed in 10-week-old wild type and AMP-activated protein kinase (AMPK)α1 knockout (KO) mice. Metformin (4 mg/day in drinking water) was given, commencing either 2 weeks before or 2 weeks after DMM surgery. Mice were sacrificed 6 and 12 weeks after DMM surgery. OA phenotype was analysed by micro-computerised tomography (µCT), histology and pain-related behaviour tests. AMPKα1 (catalytic alpha subunit of AMPK) expression was examined by immunohistochemistry and immunofluorescence analyses. The OA phenotype was also determined by µCT and MRI in non-human primates. RESULTS: Metformin upregulated phosphorylated and total AMPK expression in articular cartilage tissue. Mild and more severe cartilage degeneration was observed at 6 and 12 weeks after DMM surgery, evidenced by markedly increased Osteoarthritis Research Society International scores, as well as reduced cartilage areas. The administration of metformin, commencing either before or after DMM surgery, caused significant reduction in cartilage degradation. Prominent synovial hyperplasia and osteophyte formation were observed at both 6 and 12 weeks after DMM surgery; these were significantly inhibited by treatment with metformin either before or after DMM surgery. The protective effects of metformin on OA development were not observed in AMPKα1 KO mice, suggesting that the chondroprotective effect of metformin is mediated by AMPK signalling. In addition, we demonstrated that treatment with metformin could also protect from OA progression in a partial medial meniscectomy animal model in non-human primates. CONCLUSIONS: The present study suggests that metformin, administered shortly after joint injury, can limit OA development and progression in injury-induced OA animal models.

7.
Chem Commun (Camb) ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32193523

RESUMO

Designing new semiconductors with an extremely low thermal conductivity is of considerable significance. In this study, we successfully synthesized a new semiconductor SrOCuBiSe2 with an intrinsically low thermal conductivity via the molten salt method. It possesses a typical multicomponent layered structure which is composed of alternatively stacked [CuBiSe2] (electronic conduction unit, ECU) and [SrO] (electronic insulation unit, EIU) layers. Its intrinsically low thermal conductivity (κ = 0.45 W m-1 K-1 at 700 K) is attributed to the dual effects of high atomic displacement parameter and extremely large Grüneisen parameter, which are caused by rattling vibration of Cu atoms and lone-pair electrons of Bi atoms, respectively. Such knowledge highlights the importance of lone-pair electrons in impelling the phonon anharmonicity and multicomponent structure design concept, providing a stepping stone to the design of new semiconductors with a low thermal conductivity.

8.
Gut ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32213556

RESUMO

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

9.
Pharmacol Res ; 155: 104752, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169656

RESUMO

As a potential drug for treating inflammatory, autoimmune diseases and cancers, triptolide (TP) is greatly limited in clinical practice due to its severe toxicity, particularly for liver injury. Recently, metabolic homeostasis was vitally linked to drug-induced liver injury and gut microbiota was established to play an important role. In this study, we aimed to investigate the functions of gut microbiota on TP-induced hepatotoxicity using metabolomics in mice. Here, predepletion of gut microbiota by antibiotic treatment strikingly aggravated liver injury and caused mortality after treated with a relatively safe dosage of TP at 0.5 mg/kg, which could be reversed by gut microbial transplantation. The loss of gut microbiota prior to TP treatment dramatically elevated long chain fatty acids and bile acids in plasma and liver. Further study suggested that gut microbiota-derived propionate contributed to the protective effect of gut microbiota against TP evidenced by ameliorative inflammatory level (Tnfa, Il6 and Cox2), ATP, malondialdehyde and hepatic histology. Supplementing with propionate significantly decreased the mRNA levels of genes involved in fatty acid biosynthesis (Srebp1c, Fasn and Elovl6), resulting in the decreased long chain fatty acids in liver. Moreover, TP restricted the growth of Firmicutes and led to the deficiency of short chain fatty acids in cecum content. In conclusion, our study warns the risk for TP and its preparations when antibiotics are co-administrated. Intervening by foods, prebiotics and probiotics toward gut microbiota or supplementing with propionate may be a clinical strategy to improve toxicity induced by TP.

10.
Biol Psychiatry ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32220499

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are widely prescribed antihypertensive agents. Intriguingly, case reports and clinical trials have indicated that ACEIs, including captopril and lisinopril, may have a rapid mood-elevating effect in certain patients, but few experimental studies have investigated their value as fast-onset antidepressants. METHODS: The present study consisted of a series of experiments using biochemical assays, immunohistochemistry, and behavioral techniques to examine the effect and mechanism of captopril on depressive-like behavior in 2 animal models, the chronic unpredictable stress model and the chronic social defeat stress model. RESULTS: Captopril (19.5 or 39 mg/kg, intraperitoneal injection) exerted rapid antidepressant activity in mice treated under the chronic unpredictable stress model and mice treated under the chronic social defeat stress model. Pharmacokinetic analysis revealed that captopril crossed the blood-brain barrier and that lisinopril, another ACEI with better blood-brain barrier permeability, exerted a faster and longer-lasting effect at a same molar equivalent dose. This antidepressant effect seemed to be independent of the renin-angiotensin system, but dependent on the bradykinin (BK) system, since the decreased BK detected in the stressed mice could be reversed by captopril. The hypofunction of the downstream effector of BK, Cdc42 (cell division control protein 42) homolog, contributed to the stress-induced loss of dendritic spines, which was rapidly reversed by captopril via activating the mTORC1 (mammalian target of rapamycin complex 1) pathway. CONCLUSIONS: Our findings indicate that the BK-dependent activation of mTORC1 may represent a promising mechanism underlying antidepressant pharmacology. Considering their affordability and availability, ACEIs may emerge as a novel fast-onset antidepressant, especially for patients with comorbid depression and hypertension.

11.
Sci Rep ; 10(1): 5494, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32218502

RESUMO

The hand explores the environment for obtaining tactile information that can be fruitfully integrated with other functions, such as vision, audition, and movement. In theory, somatosensory signals gathered by the hand are accurately mapped in the world-centered (allocentric) reference frame such that the multi-modal information signals, whether visual-tactile or motor-tactile, are perfectly aligned. However, an accumulating body of evidence indicates that the perceived tactile orientation or direction is inaccurate; yielding a surprisingly large perceptual bias. To investigate such perceptual bias, this study presented tactile motion stimuli to healthy adult participants in a variety of finger and head postures, and requested the participants to report the perceived direction of motion mapped on a video screen placed on the frontoparallel plane in front of the eyes. Experimental results showed that the perceptual bias could be divided into systematic and nonsystematic biases. Systematic bias, defined as the mean difference between the perceived and veridical directions, correlated linearly with the relative posture between the finger and the head. By contrast, nonsystematic bias, defined as minor difference in bias for different stimulus directions, was highly individualized, phase-locked to stimulus orientation presented on the skin. Overall, the present findings on systematic bias indicate that the transformation bias among the reference frames is dominated by the finger-to-head posture. Moreover, the highly individualized nature of nonsystematic bias reflects how information is obtained by the orientation-selective units in the S1 cortex.

12.
Int J Biol Macromol ; 154: 182-187, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32179116

RESUMO

Polysaccharide is the main active compound of Lilium, and showed many activities, such as hypoglycemic, antioxidant, immune-modulatory. There are three types' Lilium in China market, i.e. Lilium lancifolium Thunb (JD), Lilium davidiivar. Unicolor Salisb (L. davidii var)(LZBH), and Lilium brownii F.E. Brown var. viridulum Baker (BH). Near infrared spectroscopy (NIR) technique has become popular in the fields of quality control, due to its advantages, such as fast, non-destructive, and can detect several ingredients, simultaneously. In this study, a classification model was established based on NIR technique and random forest method to accurately distinguish three types' Lilium species, and the classification accuracy reached 94.37%. Furthermore, taking the effects of neighbor wavelength into account, a new weighted partial least square algorithm was proposed to establish an accurate and quantitative model for predicting the polysaccharide contents of these samples. In the model establishing process, some signal pre-treatment methods were optimized, and the validation results with highest determination coefficient (R2) and low root mean square errors of prediction (RMSEP) were, 0.9455 and 0.9098, respectively. The obtained results showed that combined NIR technique with chemometrics was an effective and green method for quality control.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32191424

RESUMO

The reliable sensing of bacteria by surface-enhanced Raman scattering (SERS) technology necessitates a rational design of a substrate with high sensitivity, stability, and minimal invasion. Hence, a bimetallic Ta@Ag film with a porous array is developed by the magnetron sputtering technique and the structure could be controlled by a Ta dopant. A porous array connected by ligaments with compact granular nanoprotrusions is a fascinating substrate for SERS sensing. It makes steady SERS signals even in harsh chemical environments due to its high structural and chemical stability. The configuration of binary Ta@Ag has higher surface free energy than that of pure Ag, and the strong bactericidal activity of Ag is suppressed efficiently. Using E. coli as a model pathogen, the Ta@Ag porous film could maintain the long-term survival rate of E. coli up to 95% and a limit of SERS detection of E. coli down to 102 CFU/mL, which is measured by the standard colony-counting method. In sum, this work provides a promising strategy to fabricate a corrosion-resistant and biocompatible bimetallic Ta@Ag film with a porous array for the SERS sensing of microbial cells.

14.
Xenobiotica ; : 1-14, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32174209

RESUMO

Coumarins have aroused high interests due to their diverse bioactivities. Understanding of its metabolism contributes to determine the druggability of coumarin in vivo.A sensitive and efficient strategy based on ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) analysis combined with various data-processing techniques including metabolomics and multiple mass defect filter (MMDF) was established for the comprehensive screening and elucidation of potential coumarin metabolites.Total 20 metabolites of scoparone were identified in this study, including 14 undescribed metabolites. The metabolism of two other similar coumarins scopoletin and esculetin also could be determined using this strategy.By the established strategy, this study gives the insights about the major metabolic pathways of scoparone in vivo and in vitro metabolism, including demethylation, hydroxylation, hydration, cysteine conjugation, glucuronide conjugation and sulfate conjugation. Additionally, the metabolic pathways of scopoletin and esculetin were determined as hydroxylation, glucuronidation and sulfation. These results contribute to the understanding of metabolic characterization of coumarins, and demonstrate that the combination of UPLC-MS-based metabolomics and MMDF is a powerful approach to determine the metabolic pathways of coumarin compounds.

16.
Pediatr Obes ; : e12634, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32196990

RESUMO

BACKGROUND: The intake of sugar-sweetened beverages (SSBs) has been linked to an increased risk of cardiometabolic diseases. OBJECTIVES: This study aims to examine associations between SSB intake and cardiometabolic risks among Chinese children and adolescences. METHODS: Data from 3958 participants aged 6-17 years old were obtained in Shanghai, China, from September to October 2015. A 3-day dietary record and a food-frequency questionnaire (FFQ) were applied to assess SSB consumption and frequency. Anthropometric and laboratory measurements were conducted to measure cardiometabolic indicators. RESULTS: After adjusting for age, sex, daily energy intake, pubertal stage, sedentary time, maternal education, and household income, SSB consumption was positively associated with serum total cholesterol and low-density lipoprotein-cholesterol (LDL-C), while it was inversely associated with systolic blood pressure (P < .05). The participants in the highest intake category (≥201.7 mL/day) of SSB consumption had 0.10 (95%CI, 0.02-0.18) mmol/L higher total cholesterol and 0.09 (95%CI, 0.03-0.16) mmol/L higher LDL-C levels than the nonconsumption group (0 mL/day). There was a quasi-U-shaped trend in LDL-C across the categories of >0 mL/day SSB consumption. SSB frequency was positively associated with BMI (P = .04). CONCLUSIONS: SSB intake was positively associated with serum cholesterol and was weakly associated with BMI in Chinese children and adolescents, independent of energy intake.

17.
EBioMedicine ; 53: 102695, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32143182

RESUMO

BACKGROUND: Left ventricular noncompaction cardiomyopathy (LVNC) is a hereditary heart disease characterized by an excessive trabecular meshwork of deep intertrabecular recesses within the ventricular myocardium. The guidelines for management of LVNC patients aim to improve quality of life by preventing cardiac heart failure. However, the mechanism underlying LVNC-associated heart failure remains poorly understood. METHODS: Using protein mass spectrometry analysis, we established that Sorbin And SH3 Domain Containing 2 (SORBS2) is up-regulated in LVNC hearts without changes to structure proteins. We conducted in vivo experiments wherein the heart tissues of wild-type mice were injected with an AAV9 vector to overexpress SORBS2, followed by analysis using echocardiography, T-tubule analysis and Ca2+ imaging to identify functional and morphological changes. In addition, we analyzed the function and structure of SORBS2 overexpressing human embryonic stem cell (hESC) derived cardiomyocytes (hESC-CM) via immunoblotting, immunohistochemistry, immunofluorescence, and confocal Ca2+ imaging. FINDINGS: LVNC myocardial tissues feature strongly elevated expression of SORBS2, microtubule densification and redistribution of Junctophilin 2 (JP2). SORBS2 interacts with ß-tubulin, promoting its polymerization in 293T cells and hESC-derived CMs. In vivo, cardiac dysfunction, ß-tubulin densification, JP2 translocation, T-tubule disorganization and Ca2+ handling dysfunction were observed in mice overexpressing SORBS2. INTERPRETATION: We identified a novel mechanism through which SORBS2 interacts with ß-tubulin and promotes microtubule densification, eventually effecting JP2 distribution and T-tubule, potentially contributing to heart failure in LVNC disease. FUND: This work was supported by a CAMS Initiative for Innovative Medicine grant (CAMS-I2M, 2016-I2M-1-015 to Y.J.Wei).

18.
Food Chem Toxicol ; 138: 111250, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32156566

RESUMO

Caffeoylquinic acids are well known for their prominent antiviral activities. Beyond our expectations, we initially found 3,4,5-Tri-O-caffeoylquinic acid methyl ester (3,4,5-CQME) from L. japonica can facilitate HBV DNA and antigens secretion. This study aimed to investigate its underlying molecular mechanism. The results indicate that 3,4,5-CQME signally increased intracellular and secreted HBsAg levels by more than two times in HepG2.2.15 cells and HepAD38 cells. Furthermore, levels of HBeAg, HBV DNA and RNA were significantly enhanced by 3-day 3,4,5-CQME treatment; it didn't directly affect intracellular cccDNA amount, although it slightly increased cccDNA accumulation as a HBV DNA replication feedback. In addition, treatment with 3,4,5-CQME significantly induced HBx protein expression for viral replication. We utilized a phospho-antibody assay to profile the signal transduction change by 3,4,5-CQME to illuminate its molecular mechanism. The results indicate that treatment with 3,4,5-CQME activated AKT/mTOR, MAPK and NF-κB pathways verified by immunoblot. Moreover, 3,4,5-CQME upregulated the expression of nuclear transcriptional factors PGC1α and PPARα. In short, 3,4,5-CQME promotes HBV transcription and replication by upregulating HBx expression and activating HBV transcriptional regulation-related signals. As caffeoylquinic acids are widely present in traditional Chinese medicines, the risk of intaking caffeoylquinic acids-containing herbs for hepatitis B treatment requires more evaluation and further research.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32159327

RESUMO

Silicon and PbS colloidal quantum dot heterojunction photodetectors combine the advantages of the Si device and PbS CQDs, presenting a promising strategy for infrared light detecting. However, the construction of a high-quality CQDs:Si heterojunction remains a challenge. In this work, we introduce an inverted structure photodetector based on n-type Si and p-type PbS CQDs. Compared with the existing normal structure photodetector with p-type Si and n-type PbS CQDs, it has a lower energy band offset that provides more efficient charge extraction for the device. With the help of Si wafer surface passivation and the Si doping density optimization, the device delivers a high detectivity of 1.47 × 1011 Jones at 1540 nm without working bias, achieving the best performance in Si/PbS photodetectors in this region now. This work provides a new strategy to fabricate low-cost high-performance PbS CQDs photodetectors compatible with silicon arrays.

20.
Orphanet J Rare Dis ; 15(1): 74, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32183854

RESUMO

BACKGROUND: Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia that is caused by pathogenic mutations in the adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2) gene, which encodes multidrug resistance-associated protein 2 (MRP2). However, little is known about the causative mutation of DJS in China. Recently, we have reported ABCC2 p.G693R mutation in two unrelated cases. In the present study, we investigated the pathogenicity of the ABCC2 p.G693R mutation in DJS in China. METHODS: Clinical and genetic analysis was conducted for the two patients with the ABCC2 p.G693R mutation. Whole exome sequencing for mutations in other known hyperbilirubinemia-related genes was conducted for the cases with ABCC2 p.G693R. Expression and cellular localization of the mutant MRP2 p.G693R were analyzed by Western blotting and immunofluorescence assay, respectively. Organic anion transport activity was evaluated by the analysis of glutathione-conjugated-monochlorobimane. RESULTS: The two DJS patients with ABCC2 p.G693R mutation, which was conserved among different species, showed typical hyperbilirubinemia phenotype. No pathogenic mutation was identified in the other known hyperbilirubinemia related genes. Functional studies in three cell lines showed that the expression, localization and the organic anion transport activity were significantly compromised by MRP2 p.G693R mutation compared with wild-type MRP2. CONCLUSIONS: The recurrent ABCC2 p.G693R mutation is associated with loss of function of the MRP2 protein and may result in hyperbilirubinemia in DJS in China.

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