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1.
Nano Lett ; 23(7): 2927-2937, 2023 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-36926930

RESUMEN

Electrotherapy is a promising tissue repair technique. However, electrotherapy devices are frequently complex and must be placed adjacent to injured tissue, thereby limiting their clinical application. Here, we propose a general strategy to facilitate tissue repair by modulating endogenous electric fields with nonadjacent (approximately 44 mm) wireless electrotherapy through a 3D-printed entirely soft and bioresorbable triboelectric nanogenerator based stimulator, without any electrical accessories, which has biomimetic mechanical properties similar to those of soft tissue. In addition, the feasibility of using the stimulator to construct an electrical double layer with tissue for nonadjacent wireless electrotherapy was demonstrated by skin and muscle injury models. The treated groups showed significantly improved tissue repair compared with the control group. In conclusion, we developed a promising electrotherapy strategy and may inspire next-generation electrotherapy for tissue repair.


Asunto(s)
Implantes Absorbibles , Polímeros , Electricidad , Cicatrización de Heridas , Impresión Tridimensional
2.
Pharmacol Res ; 194: 106851, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37453673

RESUMEN

Hypoxia-inducible factor-2α (HIF-2α) is a transcription factor responsible for regulating genes related to angiogenesis and metabolism. This study aims to explore the effect of a previously unreported mutation c.C2473T (p.R825S) in the C-terminal transactivation domain (CTAD) of HIF-2α that we detected in tissue of patients with liver disease. We sequenced available liver and matched blood samples obtained during partial liver resection or liver transplantation performed for clinical indications including hepatocellular carcinoma and liver failure. In tandem, we constructed cell lines and a transgenic mouse model bearing the corresponding identified mutation in HIF-2α from which we extracted primary hepatocytes. Lipid accumulation was evaluated in these cells and liver tissue from the mouse model using Oil Red O staining and biochemical measurements. We identified a mutation in the CTAD of HIF-2α (c.C2473T; p.R825S) in 5 of 356 liver samples obtained from patients with hepatopathy and dyslipidemia. We found that introduction of this mutation into the mouse model led to an elevated triglyceride level, lipid droplet accumulation in liver of the mutant mice and in their extracted primary hepatocytes, and increased transcription of genes related to hepatic fatty acid transport and synthesis in the mutant compared to the control groups. In mutant mice and cells, the protein levels of nuclear HIF-2α and its target perilipin-2 (PLIN2), a lipid droplet-related gene, were also elevated. Decreased lipophagy was observed in mutant groups. Our study defines a subpopulation of dyslipidemia that is caused by this HIF-2α mutation. This may have implications for personalized treatment.


Asunto(s)
Dislipidemias , Neoplasias Hepáticas , Animales , Humanos , Ratones , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Dislipidemias/genética , Lípidos , Mutación
3.
Molecules ; 28(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36838672

RESUMEN

Immunogenicity is a major issue associated with the PK, efficacy, and safety evaluation of therapeutic protein products during pre-clinical and clinical studies. A multi-tiered approach consisting of screening, confirmatory, and titration assays has been widely adopted for anti-drug antibody testing. GQ1001, a recombinant humanized anti-human epidermal growth factor receptor 2 monoclonal antibody covalently linked to a cytotoxin of DM1, possesses a novel format of antibody-drug conjugates. In this study, we reported the development, validation, and application of an acid-dissociation bridging enzyme-linked immunosorbent assay for the detection of antibodies against GQ1001 in cynomolgus monkey serum. The sensitivity of the screening assay was 126.141 ng/mL in undiluted serum. The screening assay and confirmatory assay were neither affected by the naïve monkey serum nor by 2% and 5% (v/v) erythrocyte hemolysates. Moreover, the assay was not subject to interference by 2500 ng/mL of human IgG1 in the samples. Drug interference at low positive control (150 ng/mL) and high positive control (8000 ng/mL) of anti-GQ1001 antibodies was not observed when GQ1001 concentrations were below 3.125 µg/mL and 100 µg/mL, respectively. Furthermore, no hook effect was observed for the positive antibodies in the concentration range of 8 to 64 µg/mL. The validated assay was, thereafter, successfully applied to a single-dose toxicity study of GQ1001. Anti-drug antibody positive rates among dosing animals and testing samples were reported, and no significant impact was found on toxicokinetic outcomes.


Asunto(s)
Anticuerpos Monoclonales , Inmunoconjugados , Animales , Macaca fascicularis , Ensayo de Inmunoadsorción Enzimática , Suero
4.
BMC Public Health ; 22(1): 612, 2022 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-35351105

RESUMEN

BACKGROUND: Adverse childhood experiences (ACEs) are prevalent and associated with negative health and social outcomes. However, our understanding of how patterns of ACEs exposure relate to positive outcomes in adulthood remains limited. This study aims to identify patterns of ACEs and examine associations with flourishing in a sample of Chinese young adults. METHODS: This cross-sectional study was conducted from August to November 2020. Young adults, ages 18-35, enrolled in undergraduate or graduate programs at universities in Mainland China were recruited through convenience and snowball sampling to participate in a survey. The exposure to ACEs was measured by the twelve-item Chinese version of the ACE-International Questionnaire. Additional measures included six domains of flourishing assessed using the Chinese version of the Flourishing Measure, and demographic covariates (i.e., gender, age, year in university, marital status). Descriptive statistical analysis and latent class analysis (LCA) were performed using SPSS 27 and Mplus 8.5. RESULTS: Participants included 9468 young adults (mean age = 20.1 years). Majority of participants were female (75.3%), undergraduate students (96.4%), and single (79.8%). Approximately 56% of participants reported at least one ACE; 7.0% reported four or more ACEs. Emotional neglect (33.2%), household violence (20.6%), and parental separation/divorce (13.9%) were the most frequently reported ACEs. LCA identified three ACEs classes: multiple maltreatment and household violence (4.7%), emotional neglect and household violence (16.2%), and low ACEs (79.1%). Individuals in the low ACEs class had the highest level of flourishing whereas individuals in multiple maltreatment and household violence had the lowest level of flourishing in all six domains. There were no significant differences in flourishing between the multiple maltreatment and household violence and the emotional neglect and household violence classes except in the physical and mental health (means = 6.17 vs 6.51, p = 0.02) and the financial and material stability domains (means = 5.25 vs 5.66, p = 0.04). CONCLUSIONS: Patterns of multiple ACEs exposures were associated with lower levels of flourishing. Our findings have implications for efforts to prevent ACEs exposure through monitoring and promoting family well-being and routine screening to identify those with ACEs exposure to prevent negative social and health sequelae.


Asunto(s)
Experiencias Adversas de la Infancia , Adolescente , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Salud Mental , Encuestas y Cuestionarios , Violencia , Adulto Joven
5.
J Trauma Stress ; 35(4): 1087-1098, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35201638

RESUMEN

Hmong adults who are Vietnam War refugees have been exposed to refugee-related trauma, but little is known about associations between patterns of trauma exposure and mental health outcomes in Hmong adults. We examined patterns of trauma exposure and mental health symptoms (i.e., somatization, depression, anxiety, and probable posttraumatic stress disorder [PTSD]) in three generations of Hmong adults (N = 219). Trauma exposure and probable PTSD were measured using the Harvard Trauma Questionnaire-Hmong Version. Somatization, depression, and anxiety symptoms were measured using the Brief Symptom Inventory. Latent class analysis (LCA) and auxiliary analysis of sociodemographic characteristics and mental health symptoms were performed. The best-fitting LCA model described three distinct classes: complex and pervasive trauma (60.3%), combat situation and deprivation trauma (26.0%), and low exposure to refugee-related trauma (13.7%). Participants in the complex and pervasive trauma class were the oldest, had the shortest U.S. residency, were the least proficient in English, and reported the most severe mental health symptoms; those in the combat situation and deprivation trauma class were the youngest, moderately proficient in English, and reported moderate mental health symptoms; and those in the low exposure to refugee-related trauma class were the most proficient in English, had the longest U.S. residency, and reported the least severe mental health symptoms. Our findings call for surveillance and a trauma-informed approach for Hmong elders with limited English proficiency, who have a high risk of experiencing accumulative effects of refugee-related trauma and are susceptible to poor mental health outcomes.


Asunto(s)
Refugiados , Trastornos por Estrés Postraumático , Adulto , Anciano , Ansiedad/epidemiología , Asiático , Humanos , Salud Mental , Refugiados/psicología , Trastornos por Estrés Postraumático/psicología
6.
J Sci Food Agric ; 102(5): 1812-1822, 2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-34460944

RESUMEN

BACKGROUND: Enzymatic esterification is attracting for particular high-acid oil deacidification. In this study, Candida antarctica lipase B (CALB) was encapsulated into a series of nucleotide-hybrid metal coordination polymers (CPs), which were constructed by guanosine 5'-monophosphate (GMP) and various metals. RESULTS: We here found that, most of the present CPs encapsulated CALB (CALB@CPs) samples were highly selective for esterification while poor in glycerolysis reaction. They exhibited quite poor performance in glycerolysis, with triacylglycerols (TAGs) conversion lower than 5%, despite this considerable enzymatic hydrolysis activities were observed. However, they (most of them) showed good performance in esterification of fatty acids and glycerol for TAG synthesis. In addition, the GMP/Tb (CPs constructed by GMP and Tb3+ ) encapsulated CALB (CALB@GMP/Tb) transformed over 98% of oleic acid into glycerides in the high-acid oil deacidification process, and TAG content from 87 to 89% was obtained. Moreover, the CALB@GMP/Tb showed good reusability in the esterification system. CONCLUSION: The present CALB@CPs samples are selective for esterification and suitable for high-acid oils deacidification. This work provides a new system for enzymatic selectivity improvement study. © 2021 Society of Chemical Industry.


Asunto(s)
Nanopartículas , Nucleótidos , Catálisis , Enzimas Inmovilizadas/química , Esterificación , Proteínas Fúngicas/metabolismo , Iones , Lipasa
7.
J Sci Food Agric ; 102(10): 4012-4024, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-34997576

RESUMEN

BACKGROUND: In the present study, lipases of TLL (lipase from Thermomyces lanuginosus), AOL (lipase from Aspergillus oryzae), RML (lipase from Rhizomucor miehei), BCL (lipase from Burkholderia cepacia), CALA (Candida antarctica lipase A) and LU (Lecitase® Ultra) were encapsulated into nucleotide-hybrid metal coordination polymers (CPs). Enzyme concentration was optimized for encapsulation and the enzymatic properties of the obtained lipases were investigated. In addition, their performance in glycerolysis and esterification was evaluated, and glycerolysis conditions (water content, temperature and time) were optimized. RESULTS: Hydrolysis activity over 10 000 U g-1 and activity recovery over 90% were observed from AOL@GMP/Tb, TLL@GMP/Tb and RML@GMP/Tb. GMP/Tb encapsulation (of AOL, TLL, RML and LU) improved their thermostability when incubated in air. The encapsulated lipases exhibited moderate [triacylglycerols (TAG) conversion 30-50%] and considerable glycerolysis activity (TAG conversion over 60%). TAG conversions from 69.37% to 82.35% and diacylglycerols (DAG) contents from 58.62% to 64.88% were obtained from CALA@GMP/metal samples (except for CALA@GMP/Cu). Interestingly, none of the encapsulated lipases initiated the esterification reaction. AOL@GMP/Tb, TLL@GMP/Tb, RML@GMP/Tb and CALA@GMP/Tb showed good reusability in glycerolysis, with 88.80%, 94.67%, 89.85% and 78.16% of their initial glycerolysis activity, respectively, remaining after five cycles of reuse. The relationships between temperature and TAG conversion were LnV0  = 6.5364-3.7943/T and LnV0  = 13.8820-6.4684/T for AOL@GMP/Tb and CALA@GMP/Tb, respectively; in addition, their activation energies were 31.55 and 53.78 kJ mol-1 , respectively. CONCLUSION: Most of the present encapsulated lipases exhibited moderate and considerable glycerolysis activity. In addition, AOL@GMP/Tb, TLL@GMP/Tb, RML@GMP/Tb and CALA@GMP/Tb exhibited good reusability in glycerolysis reactions and potential in practical applications. © 2022 Society of Chemical Industry.


Asunto(s)
Enzimas Inmovilizadas , Lipasa , Enzimas Inmovilizadas/química , Esterificación , Proteínas Fúngicas/química , Lipasa/química , Nucleótidos , Polímeros , Triglicéridos
8.
J Adv Nurs ; 77(12): 4793-4804, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34617614

RESUMEN

AIM: The aims of this study were to examine the prevalence of adverse childhood experiences (ACEs) among health science students in China; associations between the number of ACE exposures and severity of depressive and anxiety symptoms; and the extent to which resilience moderates the effect of ACEs on mental health outcomes. DESIGN: This descriptive, cross-sectional study was conducted May-August 2020. METHODS: Five hundred and sixty-six health science students (18-38 years) from China completed online surveys measuring ACEs using the Simplified Chinese version of the ACE-International Questionnaire, depressive and anxiety symptoms and resilience. Descriptive statistical analysis, ANOVA with Tukey HSD post hoc tests and multiple regression analysis were performed using SPSS 27. RESULTS: 88.5% of participants reported at least one ACE; 42.6% reported four or more ACEs. Higher number of ACEs was associated with more symptoms of depression and anxiety. Four or more ACEs were associated with significantly worse mental health outcomes than those with no ACEs and those with one to three ACEs. Greater resilience significantly attenuated the effects of ACEs on mental health symptoms. CONCLUSIONS: ACEs are highly prevalent among Chinese health science students but their impact on mental health can be buffered by higher levels of resilience. IMPACT: Screening for ACEs and strength-based, trauma-informed interventions on fostering resilience is needed to promote mental health among Chinese young adults.


Asunto(s)
Experiencias Adversas de la Infancia , Trastornos Mentales , China , Estudios Transversales , Humanos , Salud Mental , Adulto Joven
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 628-633, 2021 Aug.
Artículo en Zh | MEDLINE | ID: mdl-34494536

RESUMEN

Neurodegenerative diseases are associated with neuroinflammation,oxidative stress,and aging,which can lead to cognitive and motor dysfunctions.Recent studies suggest that the development of neurodegenerative diseases is related to adaptive immunity,in which CD4+T cells are involved as adaptive immune cells.Through different pathways,CD4+T cells differentiate into effector and regulatory subsets,which may have different effects on the progression of neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,multiple sclerosis,and amyotrophic lateral sclerosis.Here,we review the role and research progress of CD4+T cells in neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer , Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Linfocitos T
10.
J Cell Physiol ; 235(10): 6779-6793, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31990045

RESUMEN

The placenta and umbilical cord are pre-eminent candidate sources of mesenchymal stem cells (MSCs). However, placenta-derived MSCs (P-MSCs) showed greater proliferation capacity than umbilical cord-derived MSCs (UC-MSCs) in our study. We investigated the drivers of this proliferation difference and elucidated the mechanisms of proliferation regulation. Proteomic profiling and Gene Ontology (GO) functional enrichment were conducted to identify candidate proteins that may influence proliferation. Using lentiviral or small interfering RNA infection, we established overexpression and knockdown models and observed changes in cell proliferation to examine whether a relationship exists between the candidate proteins and proliferation capacity. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence assays were conducted to elucidate the mechanisms underlying proliferation. Six candidate proteins were selected based on the results of proteomic profiling and GO functional enrichment. Through further validation, yes-associated protein 1 (YAP1) and ß-catenin were confirmed to affect MSCs proliferation rates. YAP1 and ß-catenin showed increased nuclear colocalization during cell expansion. YAP1 overexpression significantly enhanced proliferation capacity and upregulated the expression of both ß-catenin and the transcriptional targets of Wnt signaling, CCND1, and c-MYC, whereas silencing ß-catenin attenuated this influence. We found that YAP1 directly interacts with ß-catenin in the nucleus to form a transcriptional YAP/ß-catenin/TCF4 complex. Our study revealed that YAP1 and ß-catenin caused the different proliferation capacities of P-MSCs and UC-MSCs. Mechanism analysis showed that YAP1 stabilized the nuclear ß-catenin protein, and also triggered the Wnt/ß-catenin pathway, promoting proliferation.


Asunto(s)
Proliferación Celular/fisiología , Células Madre Mesenquimatosas/fisiología , Placenta/fisiología , Cordón Umbilical/fisiología , Núcleo Celular/metabolismo , Núcleo Celular/fisiología , Células Cultivadas , Femenino , Humanos , Células Madre Mesenquimatosas/metabolismo , Placenta/metabolismo , Embarazo , Proteómica/métodos , Factores de Transcripción/metabolismo , Cordón Umbilical/metabolismo , Regulación hacia Arriba/fisiología , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismo
11.
Ecotoxicol Environ Saf ; 204: 111148, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32818843

RESUMEN

To disclose how phosphorus deficiency influence phytoremediation of Cd contamination using poplars, root architecture, Cd absorption, Cd translocation and antioxidant defense in poplar roots were investigated using a clone of Populus × euramericana. Root growth was unaltered by Cd exposure regardless of P conditions, while the degree of root proliferation upon P deficiency was changed by high level of Cd exposure. The concentration and content of Cd accumulation in roots were increased by P deficiency. This can be partially explained by the increased expression of genes encoding PM H + -ATPase under the combined conditions of P deficiency and high Cd exposure, which enhanced Cd2+-H+ exchanges and led to an increment of Cd uptake under P deficiency. Despite of the increasing Cd accumulation in roots, the translocation of Cd from roots to aerial tissues sharply decreased upon P deficiency. The relative expression of genes responsible for Cd translocation (HMA4) decreased upon P deficiency and thus inhibited Cd translocation via xylem. GR activity was decreased by P deficiency, which can inhibit the form of GSH and GSH-Cd complexes and decrease Cd translocation via GSH-Cd complexes. The transportation of PC-Cd complexes into vacuole decreased under P deficiency as a result of the low expression of PCS and ABCC1, and thus suppressed Cd tolerance and Cd detoxification in roots. Moreover, P deficiency decreased the levels of antioxidase (GR and CAT) and phytohormones including JA, ABA and GA3, which synchronously reduced antioxidant capacity in roots.


Asunto(s)
Cadmio/metabolismo , Fósforo/metabolismo , Populus/fisiología , Adaptación Fisiológica , Antioxidantes/metabolismo , Biodegradación Ambiental , Transporte Biológico , Cadmio/toxicidad , Proliferación Celular , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/metabolismo , Populus/metabolismo , Xilema/metabolismo
13.
Nucleic Acids Res ; 45(12): 7432-7440, 2017 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-28525600

RESUMEN

RNase P is primarily responsible for the 5΄ maturation of transfer RNAs (tRNAs) in all domains of life. Archaeal RNase P is a ribonucleoprotein made up of one catalytic RNA and five protein cofactors including L7Ae, which is known to bind the kink-turn (K-turn), an RNA structural element that causes axial bending. However, the number and location of K-turns in archaeal RNase P RNAs (RPRs) are unclear. As part of an integrated approach, we used native mass spectrometry to assess the number of L7Ae copies that bound the RPR and site-specific hydroxyl radical-mediated footprinting to localize the K-turns. Mutagenesis of each of the putative K-turns singly or in combination decreased the number of bound L7Ae copies, and either eliminated or changed the L7Ae footprint on the mutant RPRs. In addition, our results support an unprecedented 'double K-turn' module in type A and type M archaeal RPR variants.


Asunto(s)
Proteínas Arqueales/química , Regulación de la Expresión Génica Arqueal , Methanocaldococcus/enzimología , Pyrococcus furiosus/enzimología , ARN de Archaea/química , ARN de Transferencia/química , Ribonucleasa P/química , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Secuencia de Bases , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Methanocaldococcus/genética , Methanococcus/enzimología , Methanococcus/genética , Mutación , Conformación de Ácido Nucleico , Unión Proteica , Pyrococcus furiosus/genética , Precursores del ARN , ARN de Archaea/genética , ARN de Archaea/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Ribonucleasa P/genética , Ribonucleasa P/metabolismo
14.
Stem Cells ; 35(10): 2138-2149, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28710827

RESUMEN

Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived CMs (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here, we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into CMs using small molecule inhibitors. Fluorescence-activated cell sorting analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable with the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because, unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. Stem Cells 2017;35:2138-2149.


Asunto(s)
Células Madre Embrionarias Humanas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Miocitos Cardíacos/metabolismo , Diferenciación Celular , Células Cultivadas , Exosomas , Humanos
15.
Virus Genes ; 54(1): 41-47, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29119303

RESUMEN

The objective of this study was to analyze the prevalence of drug-resistant HBV mutants in patients with treatment failure during the past seven years (2010-2016). 4055 HBV-infected patients who underwent HBV polymerase gene mutation test from 2010 to 2016 were enrolled. The nucleos(t)ide analogues (NAs) resistance mutation positions, including rtL180, rtA181, rtT184, rtS202, rtM204, rtI233, rtN236, rtI169, rtV173, and rtM250 were analyzed. Genotypic resistance mutations were detected in 30.8% (1248/4055) of the patients with treatment failure. Rates of drug-resistant mutations associated with LAM, ADV, ETV, and multidrug were 27.23% (1104/4055), 9.67% (392/4055), 3.69% (150/4055), and 0.79% (32/4055). Among the primary NA-resistant mutations, rtM204I (13.44%, 545/4055) occurred more frequently, followed by rtM204V, rtN236T, rtA181T, and rtA181V. For single-base mutations, rtL180M and rtA181V increased gradually during the past seven years, while rtM204I/V and rtN236T decreased after 2015. The development of drug-resistant mutations positively correlated with the consumption of ETV (r = 0.964, P = 0.002), and weakly correlated with that of LAM (r = 0.679, P = 0.109) and ADV (r = 0.429, P = 0.354). Moreover, single-base mutation rtA181V and multi-base mutations (rtL180M + M204I and rtL180M + M204V + M204I) were more common in HBV genotype C than those in genotype B (1.94% vs. 0.66%, 1.84% vs. 0.16%, 1.02% vs. 0.16%, respectively). NA-related mutations in HBV RT region increased in the past seven years, especially for LAM. Frequencies of rtL180M and rtA181T/V increased gradually in the past seven years, to which we should pay more attention.


Asunto(s)
Antivirales/uso terapéutico , Farmacorresistencia Viral , Evolución Molecular , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/virología , Frecuencia de los Genes , Genoma Viral , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Mutación , Insuficiencia del Tratamiento
16.
J Am Chem Soc ; 139(24): 8212-8221, 2017 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-28541686

RESUMEN

Carbon nanotubes (CNTs) are of great interest for many potential applications because of their extraordinary electronic, mechanical and structural properties. However, issues of chaotic staking, high cost and high energy dissipation in the synthesis of CNTs remain to be resolved. Here we develop a facile, general and high-yield strategy for the oriented formation of CNTs from metal-organic frameworks (MOFs) through a low-temperature (as low as 430 °C) pyrolysis process. The selected MOF crystals act as a single precursor for both nanocatalysts and carbon sources. The key to the formation of CNTs is obtaining small nanocatalysts with high activity during the pyrolysis process. This method is successfully extended to obtain various oriented CNT-assembled architectures by modulating the corresponding MOFs, which further homogeneously incorporate heteroatoms into the CNTs. Specifically, nitrogen-doped CNT-assembled hollow structures exhibit excellent performances in both energy conversion and storage. On the basis of experimental analyses and density functional theory simulations, these superior performances are attributed to synergistic effects between ideal components and multilevel structures. Additionally, the appropriate graphitic N doping and the confined metal nanoparticles in CNTs both increase the densities of states near the Fermi level and reduce the work function, hence efficiently enhancing its oxygen reduction activity. The viable synthetic strategy and proposed mechanism will stimulate the rapid development of CNTs in frontier fields.

17.
Angew Chem Int Ed Engl ; 56(41): 12687-12691, 2017 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-28809454

RESUMEN

Through serendipitous discovery, a palladium bis(phosphine) complex was identified as a catalyst for the selective transformation of sp2 C-F and sp2 C-H bonds of fluoroarenes and heteroarenes to sp2 C-Al bonds (19 examples, 1 mol % Pd loading). The carbon-fluorine bond functionalization reaction is highly selective for the formation of organoaluminium products in preference to hydrodefluorination products (selectivity=4.4:1 to 27:1). Evidence is presented for a tandem catalytic process in which hydrodefluorination is followed by sp2 C-H alumination.

18.
Circulation ; 132(8): 762-771, 2015 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-26304668

RESUMEN

BACKGROUND: Human induced pluripotent stem cells (iPSCs) are attractive candidates for therapeutic use, with the potential to replace deficient cells and to improve functional recovery in injury or disease settings. Here, we test the hypothesis that human iPSC-derived cardiomyocytes (iPSC-CMs) can secrete cytokines as a molecular basis to attenuate adverse cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Human iPSCs were generated from skin fibroblasts and differentiated in vitro with a small molecule-based protocol. Troponin(+) iPSC-CMs were confirmed by immunohistochemistry, quantitative polymerase chain reaction, fluorescence-activated cell sorting, and electrophysiological measurements. Afterward, 2×10(6) iPSC-CMs derived from a cell line transduced with a vector expressing firefly luciferase and green fluorescent protein were transplanted into adult NOD/SCID mice with acute left anterior descending artery ligation. Control animals received PBS injection. Bioluminescence imaging showed limited engraftment on transplantation into ischemic myocardium. However, magnetic resonance imaging of animals transplanted with iPSC-CMs showed significant functional improvement and attenuated cardiac remodeling compared with PBS-treated control animals. To understand the underlying molecular mechanism, microfluidic single-cell profiling of harvested iPSC-CMs, laser capture microdissection of host myocardium, and in vitro ischemia stimulation were used to demonstrate that the iPSC-CMs could release significant levels of proangiogenic and antiapoptotic factors in the ischemic microenvironment. CONCLUSIONS: Transplantation of human iPSC-CMs into an acute mouse myocardial infarction model can improve left ventricular function and attenuate cardiac remodeling. Because of limited engraftment, most of the effects are possibly explained by paracrine activity of these cells.


Asunto(s)
Células Madre Pluripotentes Inducidas/fisiología , Microfluídica/métodos , Infarto del Miocardio/terapia , Miocitos Cardíacos/fisiología , Análisis de la Célula Individual/métodos , Trasplante de Células Madre , Animales , Línea Celular , Femenino , Humanos , Células Madre Pluripotentes Inducidas/trasplante , Ratones , Ratones Endogámicos NOD , Ratones SCID , Infarto del Miocardio/patología , Distribución Aleatoria
19.
Qual Life Res ; 24(3): 685-91, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25150709

RESUMEN

PURPOSE: The purpose of this study was to determine the factors affecting institutionalized older peoples' self-perceived dry mouth. METHODS: This cross-sectional study was conducted on elderly residents at 22 long-term care facilities. A total of 165 questionnaires were returned from 13 senior citizen welfare institutions (SCWIs) and nine nursing homes. Multiple logistic regression analysis was used to analyze the data obtained. RESULTS: The results showed that the type of long-term care (LTC) facility, regular oral examinations, wearing dentures, and the ability to chew sticky foods affected self-perceived dry mouth. This study determined an association between the type of LTC facility where the participants lived and self-perceived dry mouth. CONCLUSIONS: The results indicated the importance of providing oral care in order to improve and prevent dry mouth among institutionalized older people living in SCWIs who do not undergo regular oral examinations, wear dentures, and have difficulty chewing sticky foods.


Asunto(s)
Estado de Salud , Casas de Salud , Autocuidado , Autoinforme , Xerostomía/etiología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Dentaduras , Diagnóstico Bucal , Femenino , Humanos , Cuidados a Largo Plazo , Masculino , Masticación , Calidad de Vida , Encuestas y Cuestionarios
20.
Nucleic Acids Res ; 40(10): 4666-80, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22298511

RESUMEN

RNase P, which catalyzes tRNA 5'-maturation, typically comprises a catalytic RNase P RNA (RPR) and a varying number of RNase P proteins (RPPs): 1 in bacteria, at least 4 in archaea and 9 in eukarya. The four archaeal RPPs have eukaryotic homologs and function as heterodimers (POP5•RPP30 and RPP21•RPP29). By studying the archaeal Methanocaldococcus jannaschii RPR's cis cleavage of precursor tRNA(Gln) (pre-tRNA(Gln)), which lacks certain consensus structures/sequences needed for substrate recognition, we demonstrate that RPP21•RPP29 and POP5•RPP30 can rescue the RPR's mis-cleavage tendency independently by 4-fold and together by 25-fold, suggesting that they operate by distinct mechanisms. This synergistic and preferential shift toward correct cleavage results from the ability of archaeal RPPs to selectively increase the RPR's apparent rate of correct cleavage by 11,140-fold, compared to only 480-fold for mis-cleavage. Moreover, POP5•RPP30, like the bacterial RPP, helps normalize the RPR's rates of cleavage of non-consensus and consensus pre-tRNAs. We also show that archaeal and eukaryal RNase P, compared to their bacterial relatives, exhibit higher fidelity of 5'-maturation of pre-tRNA(Gln) and some of its mutant derivatives. Our results suggest that protein-rich RNase P variants might have evolved to support flexibility in substrate recognition while catalyzing efficient, high-fidelity 5'-processing.


Asunto(s)
Archaea/enzimología , Proteínas Arqueales/metabolismo , Procesamiento Postranscripcional del ARN , ARN de Transferencia de Glutamina/metabolismo , Ribonucleasa P/metabolismo , Bacterias/enzimología , Eucariontes/enzimología , Conformación de Ácido Nucleico , División del ARN , Precursores del ARN/química , Precursores del ARN/metabolismo , ARN de Archaea/química , ARN de Archaea/metabolismo , ARN de Transferencia de Glutamina/química
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