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1.
Nat Commun ; 11(1): 681, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996673

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

2.
Clin Gastroenterol Hepatol ; 18(2): 514-516.e2, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30981007

RESUMO

Hepatitis B surface antigen (HBsAg) seroclearance has been recommended as an optimal endpoint of antiviral treatment by the latest chronic hepatitis B management guideline.1 However, few reports investigated the durability of response after HBsAg seroclearance, because of a lower HBsAg seroclearance rate and the difficulty of obtaining a sufficient number of samples for analysis. Our center has made a long-term commitment to investigate the personalized antiviral therapy for chronic hepatitis B. More than 300 patients achieved HBsAg seroclearance by interferon (IFN)-based antiviral treatment. In this study, the durability and the effects of hepatitis B virus (HBV) surface antibody (Anti-HBs) level on relapse after HBsAg seroclearance were investigated.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31784245

RESUMO

BACKGROUND: Recurrence is common for patients with chronic hepatitis B (CHB) who achieved hepatitis B virus (HBV) surface antigen (HBsAg) clearance after antiviral treatment. The aim of the study is to explore the possibility of quantitative hepatitis B core antibody (Anti-HBc) level as a biomarker to predict recurrence. METHODS: A total of 73 patients with HBsAg clearance were enrolled in this study, 16 cases with recurrence and 57 cases of non-recurrence. A newly developed double-sandwich Anti-HBc immunoassay was used to detect the quantitative Anti-HBc level before therapy (baseline) and at the end of therapy. Logistic regression analysis was used to evaluate the predictive ability of quantitative Anti-HBc levels for recurrence. RESULTS: Quantitative Anti-HBc levels at the end of therapy in both recurrence and non-recurrence groups were significantly lower than those of before therapy (P < 0.001). In addition, the declining trend of the recurrence group was significantly greater than that of the non-recurrence group (0.71 log10 vs. 0.45 log10 IU/mL, P = 0.026). Quantitative Anti-HBc levels in non-recurrence group were higher than those in recurrence group at baseline and drug withdrawal (P = 0.023, P < 0.001). Multivariable analysis showed that Anti-HBc level at drug withdrawal alone was associated with recurrence (OR = 0.116, P = 0.037). At Anti-HBc level >2.3386 log10 IU/mL, the predictive sensitivity and specificity for recurrence were 80.0% and 71.9%. CONCLUSIONS: Quantitative Anti-HBc level can be used as a potential predictor of recurrence after HBsAg clearance. Anti-HBc level at the drug withdrawal has better predictive value than the baseline.

4.
Nat Commun ; 10(1): 5767, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852898

RESUMO

Cancer is a hyper-proliferative disease. Whether the proliferative state originates from the cell-of-origin or emerges later remains difficult to resolve. By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among granulocyte-macrophage progenitors (GMPs) determines their probability of transformation. A fast cell cycle intrinsic to these progenitors provide permissiveness for transformation, with the fastest cycling 3% GMPs acquiring malignancy with near certainty. Molecularly, we propose that MLL-AF9 preserves gene expression of the cellular states in which it is expressed. As such, when expressed in the naturally-existing, rapidly-cycling immature myeloid progenitors, this cell state becomes perpetuated, yielding malignancy. In humans, high CCND1 expression predicts worse prognosis for MLL fusion AMLs. Our work elucidates one of the earliest steps toward malignancy and suggests that modifying the cycling state of the cell-of-origin could be a preventative approach against malignancy.

5.
Mediators Inflamm ; 2019: 7898095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736656

RESUMO

Accumulated evidences show that neuroinflammation play a pivotal role in the pathogenesis of depression. Neuropeptide Y (NPY) and its receptors have been demonstrated to have anti-inflammative as well as antidepressant effects. In the present study, the ability of NPY to modulate depressive-like behaviors induced by lipopolysaccharides (LPS) in rats and the receptors and signaling mechanisms involved were investigated. Continuous injection LPS (i.p) for 4 days led to development of depressive-like behaviors in rats, accompanied with M1-type microglia activation and increased levels of IL-1ß as well as decreased levels of NPY and Y2R expression in the mPFC selectively. Local injection of NPY into the medial prefrontal cortex (mPFC) ameliorated the depression-like behaviors and suppressed the NLRP3 inflammasome signaling pathway. Y2R agonist PYY (3-36) mimicked and Y2R antagonist BIIE0246 abolished the NPY effects in the mPFC. All these results suggest that NPY and Y2R in the mPFC are involved in the pathophysiology of depression and NPY plays an antidepressant role in the mPFC mainly via Y2R, which suppresses the NLRP3 signaling pathway, in LPS-induced depression model rats.

6.
Med Mycol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31642483

RESUMO

NADPH oxidases (Nox) generate reactive oxygen species (ROS) such as superoxide anion radical (O2-) and hydrogen peroxide (H2O2). The pathogenic fungi Candida albicans and Candida glabrata enhance cellular transglutaminase 2 (TG2) activity levels in co-cultured human hepatic cells in a ROS-mediated manner. Deletion of NOX1 (CgNOX1) in C. glabrata blocks the ability of C. glabrata to induce TG2 activity. Here, we investigated whether Nox proteins from C. albicans and Saccharomyces cerevisiae are related with induction of TG2 activity in hepatic cells. C. albicans CFL11 (CaCFL11) was identified as a key factor in this fungus for hepatic TG2 induction in the co-cultures. The cfl11 mutant of C. albicans did not induce TG2 activity in hepatocytes. In addition, overexpression of YNO1, a homolog of CgNOX1, in S. cerevisiae led to induction of ROS generation and TG2 activity in hepatic cells in co-incubation experiments. These findings indicated that a fungal Nox plays a role in enhancing TG2 activity in human hepatocytes and leads to apoptosis.

7.
Clin Gastroenterol Hepatol ; 17(12): 2621-2622, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31653317
8.
Anal Chim Acta ; 1088: 45-53, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31623715

RESUMO

To explore suitable sensing materials for sensitive and selective detection of phenolic pollutants, CeO2 nanocubes, nanopolyhedras, and nanorods were synthesized by a hydrothermal method. These CeO2 nanomaterials were further loaded on the support of graphene nanoplatelets. As-synthesized nanomaterials and nanocomposites were characterized using transmission electron microscopy, X-ray diffraction and Raman spectroscopy as well as electrochemical techniques including cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry. The nanocomposite of graphene nanoplatelets with CeO2 nanorods shows the highest electrochemical activity towards soluble species. Highly sensitive and selective determination of tetrabromobisphenol A, catechol, diethylstilbestrol, and nonylphenol was thus achieved at this nanocomposite based electrode. Their limits of detection were as low as 1.8, 42, 1.5 and 2.7 nM, respectively. Such an electrochemical sensor is thus promising for simple, fast and sensitive electrochemical determining of trace-leveled phenolic pollutants in water samples.

9.
J Clin Transl Hepatol ; 7(3): 249-257, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31608217

RESUMO

Background and Aims: Data are limited on the use of pegylated-interferon alpha-2a (peg-IFNα) in Chinese patients with chronic hepatitis B virus (HBV) infection (CHB). We evaluated the effectiveness and safety of peg-IFNα in Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice. Methods: In this prospective, multicenter, observational, non-interventional cohort study, patients were assessed for up to 1 year after peg-IFNα treatment cessation. Treating physicians established the dosing and treatment duration according to Chinese clinical practice. Effectiveness of peg-IFNα treatment was measured by the percentage of: patients with HBV DNA <2000 IU/mL and loss of hepatitis B surface antigen (commonly known as HBsAg); HBV DNA level at end of treatment (EOT), and 6 months and 1 year posttreatment; and time course change in quantitative HBV DNA and HBsAg. Results: At EOT, 6 months posttreatment, and 1 year posttreatment, the percentage of patients with HBV DNA <2000 IU/mL was 90.0%, 81.8%, and 82.2%, and that of patients with HBsAg loss was 6.5%, 9.4%, and 9.5%, respectively. The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment. The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment. The incidence of adverse events was 52.0%. Conclusions: Peg-IFNα has the potential to provide functional cure (HBsAg loss) for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China. Clinical Trial Registration: ClinicalTrials.gov (NCT01730508).

10.
Int J Nanomedicine ; 14: 7515-7531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571861

RESUMO

Background: Glioblastoma mutliforme is the most common and has the poorest prognosis of any malignant tumor of the central nervous system. Luteolin, the most abundant xanthone extracted from vegetables and medicinal plants, has been shown to have treatment effects in various cancer cell types. Luteolin is however, hydrophobic and has poor biocompatibility, which leads to low bioavailability. Patients and methods: In this study, folic acid modifiedpoly(ethylene glycol)-poly(e-caprolactone) (Fa-PEG-PCL) nano-micelles was used to encapsulate the luteolin, creating luteolin loaded PEG-PCL (Lut/Fa-PEG-PCL) micelles to treat glioma both in vitro and in vivo. Results: When compared with the free luteolin and Lut/MPEG-PCL, Lut/Fa-PEG-PCL induced a significant cell growth inhibition and more apoptosis of GL261 cells both in vitro and in vivo. The safety assessment also showed no obvious side effects were observed in mice which were administrated with free luteolin or Lut/MPEG-PCL and Lut/Fa-PEG-PCL. Conclusion: These results suggested Lut/Fa-PEG-PCL may be used as an excellent intravenously injectable formulation for the treatment and chemoprevention.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Glioma/tratamento farmacológico , Luteolina/uso terapêutico , Nanopartículas/química , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Glioma/irrigação sanguínea , Humanos , Luteolina/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Micelas , Modelos Moleculares , Nanopartículas/ultraestrutura , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Poliésteres/química , Polietilenoglicóis/química , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Sprague-Dawley
11.
J Fungi (Basel) ; 5(4)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546626

RESUMO

The lipophilic fungal pathogen Malassezia spp. must acquire long-chain fatty acids (LCFAs) from outside the cell. To clarify the mechanism of LCFA acquisition, we investigated fatty acid uptake by this fungus and identified the long-chain acyl-CoA synthetase (ACS) gene FAA1 in three Malassezia spp.: M. globosa, M. pachydermatis, and M. sympodialis. These FAA1 genes could compensate for the double mutation of FAA1 and FAA4 in Saccharomyces cerevisiae, suggesting that Malassezia Faa1 protein recognizes exogenous LCFAs. MgFaa1p and MpFaa1p utilized a medium-chain fatty acid, lauric acid (C12:0). Interestingly, the ACS inhibitor, triacsin C, affected the activity of the Malassezia Faa1 proteins but not that of S. cerevisiae. Triacsin C also reduced the growth of M. globosa, M. pachydermatis, and M. sympodialis. These results suggest that triacsin C and its derivatives are potential compounds for the development of new anti-Malassezia drugs.

12.
FASEB J ; 33(11): 12768-12779, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31490705

RESUMO

Zoledronic acid (ZOL) is an antiresorptive drug used to prevent bone loss in a variety of conditions, acting mainly through suppression of osteoclast activity. There is growing evidence that ZOL can also affect cells of the mesenchymal lineage in bone. We present novel data revealing significant changes in the abundance of perivascular mesenchymal stromal cells (MSCs)/osteoprogenitors and osteoblasts following the injection of ZOL, in vivo. In young mice with high bone turnover and an abundance of perivascular osteoprogenitors, ZOL significantly (P < 0.0001) increased new bone formation. This was accompanied by a decline in osterix-positive osteoprogenitors and a corresponding increase in osteoblasts. However, these effects were not observed in mature mice with low bone turnover. Interestingly, the ZOL-induced changes in cells of the mesenchymal lineage occurred independently of effects on the osteogenic vasculature. Thus, we demonstrate that a single, clinically relevant dose of ZOL can induce new bone formation in microenvironments enriched for perivascular MSC/osteoprogenitors and high osteogenic potential. This arises from the differentiation of perivascular osterix-positive MSC/osteoprogenitors into osteoblasts at sites that are innately osteogenic. Collectively, our data demonstrate that ZOL affects multiple cell types in bone and has differential effects depending on the level of bone turnover.-Hughes, R., Chen, X., Hunter, K. D., Hobbs, J. K., Holen, I., Brown, N. J. Bone marrow osteoprogenitors are depleted whereas osteoblasts are expanded independent of the osteogenic vasculature in response to zoledronic acid.

13.
Mycoses ; 62(12): 1154-1163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31519064

RESUMO

Candida glabrata represents the second-most frequent cause of candidiasis infections of the mucosa, bloodstream and genito-urinary tract in immunocompromised individuals. The incidence of C glabrata infection has increased significantly in the last two decades, mainly due to this species' abilities to resist various antifungal drugs and to form biofilms. We focused on the relationship between biofilm formation and the product of QDR2, a C glabrata member of the major facilitator superfamily (MFS) gene family, given that fungal biofilm formation limits drug penetration and is associated with persistent infection. The fungal cells in biofilms were compared between a C glabrata ∆qdr2 mutant and its wild-type strain. Cells were analysed for metabolism activity and drug susceptibility (using tetrazolium assay), adhesion activity, growth assay and intracellular pH (using flow cytometry). Compared to the wild type, the C glabrata ∆qdr2 showed lower adhesion activity and higher fluconazole susceptibility when assessed as a biofilm. The mutant also showed decreased metabolic activity during biofilm formation. Furthermore, the mutant grew more slowly under neutral-basic pH conditions. The qdr2 deletion in C glabrata resulted in an impaired ability to maintain pH homeostasis, which led in turn to a reduction of cell growth and of adherence to an artificial matrix. These results suggested that the Qdr2p function is needed for proper biofilm formation and biofilm maintenance in C glabrata as well as biofilm drug resistance towards fluconazole. Qdr2p may play an important role in C glabrata's ability to form biofilms on implanted medical devices in human bodies.

14.
Medicine (Baltimore) ; 98(33): e16778, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415381

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , China , Método Duplo-Cego , Esquema de Medicação , Composição de Medicamentos , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/administração & dosagem , Resultado do Tratamento , Adulto Jovem
15.
World J Clin Cases ; 7(14): 1784-1794, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31417924

RESUMO

The goal of chronic hepatitis B (CHB) therapy is to improve the patient prognosis through the sustained inhibition of viral replication. However, due to the uncertainty and potentially unlimited duration of the treatment course, nucleus(t)ide analogue (NA) resistance and safety, financial costs and patient compliance, different endpoints of antiviral treatment have been proposed in CHB prevention and treatment guidelines. Different treatment endpoints are closely associated with the safety of drug withdrawal and improvements in prognosis. Antiviral treatment suppresses HBV DNA replication, drug withdrawal leads to relapse, and long-term treatment causes drug safety and resistance issues. Although hepatitis B e antigen seroconversion based on HBV DNA inhibition is considered as "a satisfactory endpoint", drug withdrawal still leads to high relapse rates. Hepatitis B surface antigen (HBsAg) clearance is the "ideal endpoint" in terms of the safety of drug withdrawal and improvements in prognosis. However, the HBsAg clearance rate is low using the conventional single drug treatment and fixed course regimens. Recently, the application of an "optimized antiviral treatment strategy" has improved the HBsAg clearance rate, and make an "ideal endpoint" possible. This article reviews the different antiviral treatment endpoints in terms of the safety of drug withdrawal, improvements in prognosis and relevant advances.

16.
J Pharm Anal ; 9(4): 266-273, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31452965

RESUMO

The traditional Chinese medicine of Radix Hedysari plays an important role in invigorating gas for ascending, benefiting blood for promoting production of fluid, and promoting circulation for removing obstruction in collaterals, which is consistent with the principle of treatment for osteoporosis. This study is designed to investigate the bioactive components on increasing peak bone mass (PBM) by exploring the spectrum-effect relationship between chromatography fingerprints and effect. Multiple indicators are selected to evaluate the pharmacological activity. In fingerprints, 21 common peaks are obtained, five of which are identified. Furthermore, gray relational analysis (GRA) is a quantitative method of gray system theory and is used to describe the correlation degree of common peaks and pharmacological activities with relational value. 21 components are then divided into three different regions, of which ononin and calycosin play an extremely significant role in increasing PBM. In addition, factor analysis and hierarchical cluster analysis (HCA) are used to screen the optimal producing area for Radix Hedysari. This provides a comprehensive and efficient method to improve the quality evaluation of Radix Hedysari, confirming the bioactive components for PBM-enhancement and further develop its medicinal value.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31362119

RESUMO

BACKGROUND & AIMS: There is no satisfactory way to identify patients who will maintain a response after discontinuation of nuleos(t)ide analogue therapy for chronic hepatitis B virus (HBV) infection. We investigated whether patients with negative results from tests for HBV DNA and HBV RNA (double negative) at the end of treatment maintain a long-term response to treatment. METHODS: We performed a post-hoc analysis of data from a 2-year multi-center randomized controlled trial, and its long-term extension trials, on 130 patients with chronic HBV infection who were positive for the HB e antigen (HBeAg-positive; mean age, 30.8 ± 6.9 years; 72.3% male) and received telbivudine with or without adefovir and stopped therapy after they had HBeAg seroconversion and levels of HBV DNA <300 copies/mL for at least 48 weeks (evaluation cohort). Clinical and laboratory assessments were made every 12 or 16 weeks until clinical relapse (defined as HBV DNA > 2000 IU/mL and level of alanine aminotransferase more than 2-fold the upper limit of normal) or until 4 years off treatment. We validated our findings in a cohort of 40 HBeAg-positive patients (36.5 ± 9.4 years old; 72.5% male) treated with entecavir or tenofovir, and followed after discontinuation for up to 5.5 years. Patients were considered to be negative for HBV DNA if it was not detected in the COBAS Taqman assay. Patients were considered to be negative for HBV RNA if it was not detected by quantitative real-time PCR with 2 different pairs of primers. RESULTS: After 4 years off treatment, in the evaluation cohort, 30.8% of patients had a clinical relapse, 54.7% had virologic relapse (HBV DNA >2000 IU/mL in 2 tests), and 16.8% had reappearance of HBeAg in 2 tests (reversion). A significantly lower proportion of double negative patients had a clinical relapse 4 years later (2/35; 8.0%) than of patients who tested positive for either HBV DNA or RNA (32/102; 31.4%; P = .018). In the validation cohort, after 5.5 years of follow up, a lower proportion of double negative patients had clinical relapse (2/13; 15.4%) than of patients who tested positive for either HBV DNA or RNA at the end of treatment (9/27; 33.3%; P = .286) CONCLUSIONS: In an analysis of data from 2 independent cohorts, we associated negative results from tests for HBV DNA and RNA (double negative) at the end of treatment with continued response 4 or more years after discontinuation of therapy in HBeAg-positive patients. These results might be used to identify the best candidates for discontinuation of nuleos(t)ide analogue therapy.

18.
Hepatol Int ; 13(5): 573-586, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172415

RESUMO

BACKGROUND: Switching from nucleos(t)ide analogues to interferon (IFN) improves hepatitis B surface antigen (HBsAg) loss. We aimed to evaluate whether combining immunomodulators such as interleukin-2 (IL-2) and therapeutic vaccine with IFN enhances HBsAg loss in entecavir (ETV)-suppressed patients. METHODS: Ninety-four patients exhibiting virological suppression and hepatitis B e antigen (HBeAg) loss following ETV treatment were randomized 1:1:1 to receive ETV (group I) or IFN (group II) for 48 weeks, or IFN and vaccine for 48 weeks plus IL-2 for 12 weeks (group III). The primary endpoint was HBsAg loss at week 48. Peripheral natural killer (NK) cells and regulatory T cells (Treg) were measured as immune checkpoint indicators. RESULTS: Mean HBsAg decline at week 48 was significantly greater in group III (0.85 log 10 IU/mL) and group II (0.74 log 10 IU/mL), than in group I (0.13 log 10 IU/mL). At week 48, 9.38%, 3.03%, and 3.70% of subjects in group III, II, and I, respectively, achieved HBsAg loss. Among patients with baseline HBsAg titers ranging from 100 to 1500 IU/mL, HBsAg loss rate was 27.3, 7.1, and 0% in group III, II, and I, respectively. Responders in group III showed a significantly higher increase in CD56bright CD16-NK cells from week 24 to 36, and a significant decline in Treg from week 12 to 24 than non-responders. CONCLUSION: For ETV-suppressed patients, particularly those with low baseline HBsAg levels, combination therapy with IFN and other immunomodulators may enhance HBsAg loss, while successful response correlates with partial restoration of NK cells and Tregs.

19.
Nanoscale ; 11(16): 7952-7958, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30946420

RESUMO

Cheap and high-performance electrocatalysts are required for fuel cells. Herein, we present the application of three-dimensional (3D) catalyst systems for electrocatalytic oxidation of formic acid and methanol. These systems consist of cost-effective boron-doped expanded graphite (B-EG) as the support and palladium nanoparticles (NPs) or platinum/palladium bimetal NPs as the catalysts. The characterization of these 3D catalyst systems using scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray, and electrochemical techniques reveals that stable and efficient electrocatalytic methanol oxidation, achieved in a 3D catalyst system of B-EG and PdPt bimetal NPs (with a mass ratio of 1 : 1), is due to its big surface area, high conductivity, and an enhanced amount of exposed active sites from bimetal NPs. This price-reduced, stable, and efficient 3D catalyst system is thus promising to be employed for a large scale production of industrial direct methanol fuel cells.

20.
Nat Commun ; 10(1): 1695, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30979898

RESUMO

Actin cytoskeleton is well-known for providing structural/mechanical support, but whether and how it regulates chromatin and cell fate reprogramming is far less clear. Here, we report that MKL1, the key transcriptional co-activator of many actin cytoskeletal genes, regulates genomic accessibility and cell fate reprogramming. The MKL1-actin pathway weakens during somatic cell reprogramming by pluripotency transcription factors. Cells that reprogram efficiently display low endogenous MKL1 and inhibition of actin polymerization promotes mature pluripotency activation. Sustained MKL1 expression at a level seen in typical fibroblasts yields excessive actin cytoskeleton, decreases nuclear volume and reduces global chromatin accessibility, stalling cells on their trajectory toward mature pluripotency. In addition, the MKL1-actin imposed block of pluripotency can be bypassed, at least partially, when the Sun2-containing linker of the nucleoskeleton and cytoskeleton (LINC) complex is inhibited. Thus, we unveil a previously unappreciated aspect of control on chromatin and cell fate reprogramming exerted by the MKL1-actin pathway.


Assuntos
Reprogramação Celular , Cromatina/química , Transativadores/metabolismo , Citoesqueleto de Actina/metabolismo , Animais , Diferenciação Celular , Núcleo Celular/metabolismo , Citoesqueleto/metabolismo , Feminino , Fibroblastos/citologia , Transferência Ressonante de Energia de Fluorescência , Genótipo , Proteínas de Fluorescência Verde/metabolismo , Masculino , Camundongos , Proteínas de Fusão Oncogênica/metabolismo , Células-Tronco Pluripotentes/citologia
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