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1.
Plant Physiol ; 194(3): 1906-1922, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-37987562

RESUMO

Salinity is a severe abiotic stress that limits plant survival, growth, and development. 14-3-3 proteins are phosphopeptide-binding proteins that are involved in numerous signaling pathways, such as metabolism, development, and stress responses. However, their roles in salt tolerance are unclear in woody plants. Here, we characterized an apple (Malus domestica) 14-3-3 gene, GENERAL REGULATORY FACTOR 8 (MdGRF8), the product of which promotes salinity tolerance. MdGRF8 overexpression improved salt tolerance in apple plants, whereas MdGRF8-RNA interference (RNAi) weakened it. Yeast 2-hybrid, bimolecular fluorescence complementation, pull-down, and coimmunoprecipitation assays revealed that MdGRF8 interacts with the transcription factor MdWRKY18. As with MdGRF8, overexpressing MdWRKY18 enhanced salt tolerance in apple plants, whereas silencing MdWRKY18 had the opposite effect. We also determined that MdWRKY18 binds to the promoters of the salt-related genes SALT OVERLY SENSITIVE 2 (MdSOS2) and MdSOS3. Moreover, we showed that the 14-3-3 protein MdGRF8 binds to the phosphorylated form of MdWRKY18, enhancing its stability and transcriptional activation activity. Our findings reveal a regulatory mechanism by the MdGRF8-MdWRKY18 module for promoting the salinity stress response in apple.


Assuntos
Malus , Tolerância ao Sal , Tolerância ao Sal/genética , Malus/metabolismo , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética
2.
Small ; 20(1): e2305119, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37653595

RESUMO

Rampant dendrite growth, electrode passivation and severe corrosion originate from the uncontrolled ions migration behavior of Zn2+ , SO4 2- , and H+ , which are largely compromising the aqueous zinc ion batteries (AZIBs) performance. Exploring the ultimate strategy to eliminate all the Zn anode issues is challenging but urgent at present. Herein, a fluorinated separator interface (PVDF@GF) is constructed simply by grafting the polyvinylidene difluoride (PVDF) on the GF surface to realize high-performance AZIBs. Experimental and theoretical studies reveal that the strong interaction between C─F bonds in the PVDF and Zn2+ ions enables evenly redistributed Zn2+ ions concentration at the electrode interface and accelerates the Zn transportation kinetics, leading to homogeneous and fast Zn deposition. Furthermore, the electronegative separator interface can spontaneously repel the SO4 2- and anchor H+ ions to alleviate the passivation and corrosion. Accordingly, the Zn|Zn symmetric cell with PVDF@GF harvests a superior cycling stability of 500 h at 10 mAh cm-2 , and the Zn|VOX full cell delivers 76.8% capacity retention after 1000 cycles at 2 A g-1 . This work offers an all-round solution and provides new insights for the design of advanced separators with ionic sieve function toward stable and reversible Zn metal anode chemistry.

3.
J Sep Sci ; 47(2): e2300624, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38286726

RESUMO

The comprehensive and efficient characterization of components in traditional Chinese medicine is crucial for elucidating its active constituents and uncovering its mechanism. Identifying the compounds of the Bushen Huoxue Prescription (BHP) is difficult because of its complex composition and the large difference in concentration among its compounds. In this study, a hydrophilic interaction liquid chromatography coupled with reversed-phase LC (HILIC × RPLC) offline 2D-LC tandem high-resolution mass spectrometry method was established to analyze the total compounds of the BHP. Database screening and molecular networking were performed to identify the compounds. In contrast to conventional 1D chromatography, 2D chromatography increased peak capacity, enriched trace ingredients, and prevented the masking of high-abundance compounds. A total of 165 compounds were identified, and 14 potential compounds needed to be further identified. This study provided an effective method for comprehensively analyzing the complex system of traditional Chinese medicine compounds.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas , Cromatografia Líquida , Tecnologia , Cromatografia de Fase Reversa
4.
Sensors (Basel) ; 24(4)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38400309

RESUMO

A lack of available information on heating, ventilation, and air-conditioning (HVAC) systems can affect the performance of data-driven fault-tolerant control (FTC) models. This study proposed an in situ selective incremental calibration (ISIC) strategy. Faults were introduced into the indoor air (Ttz1) thermostat and supply air temperature (Tsa) and chilled water supply air temperature (Tchws) sensors of a central air-conditioning system. The changes in the system performance after FTC were evaluated. Then, we considered the effects of the data quality, data volume, and variable number on the FTC results. For the Ttz1 thermostat and Tsa sensor, the system energy consumption was reduced by 2.98% and 3.72% with ISIC, respectively, and the predicted percentage dissatisfaction was reduced by 0.67% and 0.63%, respectively. Better FTC results were obtained using ISIC when the Ttz1 thermostat had low noise, a 7-day data volume, or sufficient variables and when the Tsa and Tchws sensors had low noise, a 14-day data volume, or limited variables.

5.
Small ; 19(20): e2300130, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36794300

RESUMO

Uncontrollable dendrite growth and sluggish ion-transport kinetics are considered as the main obstacles for the further development of high-performance aqueous zinc ion batteries (AZIBs). Here, a nature-inspired separator (ZnHAP/BC) is developed to tackle these issues via the hybridization of the biomass-derived bacterial cellulose (BC) network and nano-hydroxyapatite particles (HAP). The as-prepared ZnHAP/BC separator not only regulates the desolvation process of the hydrated Zn2+ ions (Zn(H2 O)6 2+ ) by suppressing the water reactivity through the surface functional groups, alleviating the water-induced side-reactions, but also boosts the ion-transport kinetics and homogenize the Zn2+ flux, resulting in a fast and uniform Zn deposition. Remarkably, the Zn|Zn symmetric cell with ZnHAP/BC separator harvests a long-term stability over 1600 h at 1 mA cm-2 , 1 mAh cm-2 and endures stable cycling over 1025 and 611 h even at a high depth of discharge (DOD) of 50% and 80%, respectively. The Zn|V2 O5 full cell with a low negative/positive (N/P) capacity ratio of 2.7 achieves a superior capacity retention of 82% after 2500 cycles at 10 A g-1 . Furthermore, the Zn/HAP separator can be totally degraded within 2 weeks. This work develops a novel nature-derived separator and provides insights in constructing functional separators toward sustainable and advanced AZIBs.

6.
Mol Carcinog ; 62(12): 1974-1989, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37792308

RESUMO

Testis expression 10 (Tex10) is reported to be associated with tumorigenesis in several types of cancer types, but its role in hepatocellular carcinoma (HCC) metastasis has not been investigated. In this study, the expression of Tex10 in the HCC cell line and tissue microarray was determined by Western blot and immunohistochemistry (IHC), respectively. RNA sequencing-based transcriptome analysis was performed to identify the Tex10-mediated biological process. Cell Counting Kit-8, colony formation, transwell assays, xenograft tumor growth, and lung metastasis experiments in nude mice were applied to assess the effects of Tex10 on cell proliferation, migration, invasion, and metastasis. The underlying mechanisms were further investigated using dual-luciferase reporter, co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. We found that Tex10 was upregulated in HCC tumor tissues compared to adjacent normal tissues, with its expression correlated with a poor prognosis. Gene ontology function enrichment analysis revealed alterations in several biological processes in response to Tex10 knockdown, especially cell motility and cell migration. Functional studies demonstrated that Tex10 promotes HCC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Moreover, Tex10 was shown to regulate invasion and epithelial-mesenchymal transition via signal transducer and activator of transcription 3 (STAT3) signaling. Mechanistically, Tex10 was found to interact with STAT3 and promote its transcriptional activity. In addition, we found that Tex10 promotes p300-mediated STAT3 acetylation, while p300 silencing abolishes Tex10-enhanced STAT3 transcriptional activity. Together, these findings indicate that Tex10 functions as an oncogene by upregulating STAT3 activity, thus suggesting that Tex10 may serve as a prognostic biomarker and/or therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica
7.
Int J Mol Sci ; 24(19)2023 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-37834443

RESUMO

The P301L mutation in tau protein is a prevalent pathogenic mutation associated with neurodegenerative frontotemporal dementia, FTD. The mechanism by which P301L triggers or facilitates neurodegeneration at the molecular level remains unclear. In this work, we examined the effect of the P301L mutation on the biochemical and biological characteristics of pathologically relevant hyperphosphorylated tau. Hyperphosphorylated P301L tau forms cytotoxic aggregates more efficiently than hyperphosphorylated wildtype tau or unphosphorylated P301L tau in vitro. Mechanistic studies establish that hyperphosphorylated P301L tau exacerbates endoplasmic reticulum (ER) stress-associated gene upregulation in a neuroblastoma cell line when compared to wildtype hyperphosphorylated tau treatment. Furthermore, the microtubule cytoskeleton is severely disrupted following hyperphosphorylated P301L tau treatment. A hyperphosphorylated tau aggregation inhibitor, apomorphine, also inhibits the harmful effects caused by P301L hyperphosphorylated tau. In short, the P301L single mutation within the core repeat domain of tau renders the underlying hyperphosphorylated tau more potent in eliciting ER stress and cytoskeleton damage. However, the P301L mutation alone, without hyperphosphorylation, is not sufficient to cause these phenotypes. Understanding the conditions and mechanisms whereby selective mutations aggravate the pathogenic activities of tau can provide pivotal clues on novel strategies for drug development for frontotemporal dementia and other related neurodegenerative tauopathies, including Alzheimer's disease.


Assuntos
Demência Frontotemporal , Doença de Pick , Tauopatias , Camundongos , Animais , Humanos , Proteínas tau/genética , Proteínas tau/metabolismo , Demência Frontotemporal/genética , Camundongos Transgênicos , Tauopatias/metabolismo , Mutação , Citoesqueleto/metabolismo
8.
J Med Virol ; 94(8): 3613-3624, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35365888

RESUMO

The Delta variant has gradually replaced the Alpha variant as the major strain of SARS-COV-2 infection worldwide. We extracted the clinical characteristics and outcomes information about 381 hospitalized patients infected with Delta variant and compared them with 856 patients diagnosed with Alpha variant infection in Zhejiang Province. The majority (85.3%) of patients infected with the Delta variant had received inactivated vaccine. The patients' condition was generally mild. Most of them were mild (35.7%) and common (62.7%) types. Only six patients (1.5%) were severe/critical types. During the follow-up period, patients infected with the Delta variant had longer hospital stays than the Alpha variant (24 [21-26] vs. 18 [14-24], p < 0.001). In addition, the unvaccinated patients infected with the Delta variant had a higher proportion of severe/critical cases than vaccinated patients (11.11% vs. 0.92%, p = 0.024) and a higher usage rate of glucocorticoids (38.89 vs. 14.77%, p = 0.017) and antibiotics (55.56% vs. 32.31%, p = 0.042) during hospitalization. The vaccine's efficacy against severe COVID-19 did not diminish over time for patients who received two doses of the inactivated vaccine. The disease types and clinical manifestations were generally mild in patients infected with the Delta variant, possibly associated with widespread vaccination with inactivated vaccines in China.


Assuntos
COVID-19 , Vacinas Virais , COVID-19/prevenção & controle , China/epidemiologia , Humanos , SARS-CoV-2/genética , Vacinas de Produtos Inativados
9.
J Med Virol ; 94(11): 5475-5483, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35836102

RESUMO

Hepatitis B surface antigen (HBsAg) loss or seroconversion is an ideal treatment endpoint for patients with chronic hepatitis B but is rarely achievable in  hepatitis B e-antigen (HBeAg)-positive patients using existing treatment strategies. In this study, the effect of pegylated interferon (peg-IFN) alfa-2b plus tenofovir disoproxil fumarate (TDF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and hepatitis B vaccine was evaluated. This randomized controlled trial was conducted at nine liver centers in Chinese university hospitals from May 2018 to July 2020. Patients (n = 303) enrolled were randomly administered peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine (experimental group); peg-IFN-α-2b plus TDF (control group 2); or interferon-α-2b alone (control group 1). The primary efficacy endpoint was HBsAg seroconversion at 48 weeks and the secondary endpoint included safety. No differences in baseline HBsAg levels were observed among the groups. The primary endpoint was achieved in three (3.0%), one (1.03%), and one (1.19%) patient in the experimental group, control group 2, and control group 1, respectively. The incidence of HBsAg seroconversion at week 48 was not significantly different among the three groups (p = 0.629). However, the decrease in serum levels of HBsAg at week 48 was significantly higher in the experimental and control group 2 compared with that in control group 1 (p = 0.008 and 0.006, respectively). No significant difference between the experimental and control group 2 was observed (p = 0.619). Adverse events were not significantly different among the groups except for the lower incidence of neutropenia in the experimental group. Peg-IFN-α-2b combined with TDF, GM-CSF, and hepatitis B vaccine is not superior to peg-IFN-α-2b combined with TDF in HBeAg-positive naïve patients. Clinical Trials Registration: ChiCTR1800016173.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos , Vacinas contra Hepatite B , Hepatite B Crônica , Tenofovir , Antivirais , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Antígenos de Superfície da Hepatite B , Vacinas contra Hepatite B/efeitos adversos , Antígenos E da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Polietilenoglicóis , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Resultado do Tratamento
10.
Cell Mol Neurobiol ; 42(4): 1065-1077, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33161527

RESUMO

Glioma is the most common malignant brain tumor and long non-coding RNAs (lncRNAs) have been reported to play an important role in the growth and angiogenesis of glioma. However, the potential mechanisms of lncRNA H19 in glioma remain unclear. In the present study, the effects of lncRNA H19 on glioma cell proliferation, migration, and angiogenesis were evaluated. The expression levels of H19, miR-342, and Wnt5a in glioma tissues and cells were detected by RT-qPCR or Western blotting. Dual luciferase reporter assay confirmed the interaction between H19, miR-342, and Wnt5a. Cell proliferation, migration, and angiogenesis were analyzed by colony formation, transwell, and tube formation assays, respectively. IHC was performed to test the angiogenesis-related factor CD31. H19 and Wnt5a expression were remarkably upregulated in glioma tissues and cells, whereas miR-342 expression was downregulated. Moreover, functional analysis confirmed that knockdown of H19 or overexpression of miR-342 suppressed glioma cell proliferation, migration, and angiogenesis in vitro. Besides, H19 was found to directly target miR-342 to promote Wnt5a expression and activate ß-catenin pathway in glioma cells. Moreover, suppression of miR-342 or overexpression of Wnt5a reversed the inhibitory effect of sh-H19 on glioma growth and metastasis. Additionally, we verified that H19 promoted glioma cell proliferation, migration, and angiogenesis via miR-342/Wnt5a/ß-catenin axis in vivo. H19 regulates glioma cell growth and metastasis through miR-342 to mediate Wnt5a/ß-catenin signaling pathway, which provides new therapeutic targets for glioma treatment.


Assuntos
Glioma , MicroRNAs , RNA Longo não Codificante , Proliferação de Células/genética , Glioma/genética , Glioma/patologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Wnt-5a/genética , beta Catenina
11.
BMC Musculoskelet Disord ; 23(1): 1047, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36457082

RESUMO

PURPOSE: In soft tissue reconstructive surgery, perforator localization and flap harvesting have always been critical challenges, but augmented reality (AR) has become a dominant technology to help map perforators. METHODS: The lateral circumflex femoral artery (LCFA) and its perforators were reconstructed by CTA in consecutive patients (N = 14). Then, the anterolateral thigh perforators and the points from which the perforators emerged from the deep fascia were marked and projected onto the skin surface. As the virtual images were projected onto patients according to bony markers, the courses of the LCFA and its perforators were depicted on the skin surface for intraoperative guidance. Finally, the locations of the emergence points were verified by intraoperative findings and compared to those determined by handheld Doppler ultrasound. RESULTS: The sources, locations, and numbers of perforators were determined by CTA. The perforators and their emergence points were accurately mapped on the skin surface by a portable projector to harvest the anterolateral thigh perforator flap. During the operation, the accuracy of the CTA & AR method was 90.2% (37/41), and the sensitivity reached 97.4% (37/38), which were much higher than the corresponding values of Doppler ultrasound. Additionally, the differences between the AR-marked points and the intraoperative findings were much smaller than those seen with Doppler ultrasound (P < 0.001). Consequently, all of the flaps were well designed and survived, and only one complication occurred. CONCLUSION: Augmented reality, namely, CTA combined with projection in this study, plays a vital and reliable role in locating the perforator emergence points and guiding the procedure to harvest flaps and has fewer potential risks.


Assuntos
Realidade Aumentada , Humanos , Coxa da Perna/diagnóstico por imagem , Coxa da Perna/cirurgia , Veias , Retalhos Cirúrgicos , Angiografia
12.
J Mol Struct ; 12672022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36310922

RESUMO

In contrast to Aß plaques, the spatiotemporal distribution of neurofibrillary tangles of hyperphosphorylated tau (p-tau) predicts cognitive impairment in Alzheimer's disease (AD), underscoring the key pathological role of p-tau and the utmost need to develop AD therapeutics centering upon the control of p-tau aggregation and cytotoxicity. Our drug discovery program is focused on compounds that prevent the aggregation and cytotoxicity of p-tau moieties of the tau isoform 1N4R due to its prevalence (1 N) and long-distance trans-synaptic propagation (4R). We prepared and tested twenty-four newly synthesized small molecules representing the urea (1, 2, 3), sulfonylurea (4), and sulfonamide (5-24) series and evaluated their anti-aggregation effects with biophysical methods (thioflavin T and S fluorescence assays, transmission electron microscopy) and intracellular inclusion cell-based assays. Pre-evaluation was performed on alpha-synuclein (α-syn) to identify molecules to be challenged with p-tau. The sulfonamide derivatives 18 and 20 exhibited an anti-fribrillization activity on α-syn and p-tau. Sulfonamide compounds 18 and 20 reduced inclusion formation in M17D neuroblastoma cells that express inclusion-prone αSynuclein3K::YFP. This project advances new concepts in targeting prone-to-aggregate proteins such as α-syn and p-tau, and provides a molecular scaffold for further optimization and pre-clinical studies focused on AD drug development.

13.
Sensors (Basel) ; 22(12)2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35746253

RESUMO

Low-power wide-area networks (LPWANs), such as LoRaWAN, play an essential role and are expanding quickly in miscellaneous intelligent applications. However, the collision problem is also expanding significantly with the mass promotion of LPWAN nodes and providing collision-resilient techniques that are urgently needed for these applications. This paper proposes BackLoRa, a lightweight method that enables collision-resilient LoRa transmission with extra propagation information provided by backscatter tags. BackLoRa uses several backscatter tags to create multipath propagation features related to the LoRa nodes' positions and offers a lightweight algorithm to extract the feature and correctly distinguish each LoRa node. Further, BackLoRa proposes a quick-phase acquisition algorithm with low time complexity that can carry out the iterative recovery of symbols for robust signal reconstructions in low-SNR conditions. Finally, comprehensive experiments were conducted in this study to evaluate the performance of BackLoRa systems. The experimental results show th compared with the existing scheme, our scheme can reduce the symbol error rate from 65.3% to 5.5% on average and improve throughput by 15× when SNR is -20 dB.

14.
J Prosthet Dent ; 128(4): 618-624, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34521506

RESUMO

STATEMENT OF PROBLEM: Clinical studies comparing the occurrence and quality of residual cement between custom zirconia and custom titanium abutments with subgingival margins are scarce. PURPOSE: The purpose of this clinical study was to assess the difference in the amount of residual cement between custom zirconia and titanium abutments with a 1-mm subgingival margin. MATERIAL AND METHODS: Eighty participants were randomized to receive either a custom zirconia abutment with a bonded titanium insert or a custom titanium abutment with a 1-mm subgingival margin on a posterior bone-level implant. Monolithic lithium disilicate crowns with a screw-access hole were cemented to abutments randomly with either a resin-modified glass ionomer cement or a resin cement. After cementation, the crown-abutment assemblies were removed and photographed from the mesial, buccal, distal, and lingual of the specimen to record the residual cement. The length along the abutment margin of each aspect of the assembly was measured. The surface area of the residual cement (SA) and the surface area of the residual cement per unit length of margin (SA_P) were calculated. Results for the groups were compared with the Fisher exact test, the Friedman test, and the Mann-Whitney U test (α=.05). RESULTS: The median (lower quartile, upper quartile) of SA and SA_P for the custom zirconia abutment with a bonded titanium insert was 1.9 (0.5, 3.9) mm2 and 0.086 (0.032, 0.02) mm2, respectively, and for the custom titanium abutment, the values were 2.9 (1.3, 5.1) mm2 and 0.138 (0.062, 0.239) mm2, respectively. No significant difference was found between the custom zirconia abutments with bonded titanium inserts and titanium abutments for SA (P=.075) and SA_P (P=.083) with the Mann-Whitney U test. No significant difference was found in residual cement between the 4 aspects of the abutment (SA: P=.852; SA_P: P=.954) with the Friedman test and between the 2 types of cement (SA: P=.447; SA_P: P=.878) with the Mann-Whitney U test. CONCLUSIONS: A similar amount of subgingival residual cement was recorded around the abutment-crown assembly, regardless of the abutment material or cement type used.


Assuntos
Dente Suporte , Titânio , Humanos , Projeto do Implante Dentário-Pivô , Estudos de Coortes , Zircônio , Cimentos Dentários/uso terapêutico , Coroas , Desenho Assistido por Computador , Materiais Dentários , Cimentos de Ionômeros de Vidro , Teste de Materiais , Análise do Estresse Dentário
15.
N Engl J Med ; 378(15): 1396-1407, 2018 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-29641966

RESUMO

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell-like [ABC], germinal-center B-cell-like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. METHODS: We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. RESULTS: We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B mutations), BN2 (based on BCL6 fusions and NOTCH2 mutations), N1 (based on NOTCH1 mutations), and EZB (based on EZH2 mutations and BCL2 translocations). Genetic aberrations in multiple genes distinguished each genetic subtype from other DLBCLs. These subtypes differed phenotypically, as judged by differences in gene-expression signatures and responses to immunochemotherapy, with favorable survival in the BN2 and EZB subtypes and inferior outcomes in the MCD and N1 subtypes. Analysis of genetic pathways suggested that MCD and BN2 DLBCLs rely on "chronic active" B-cell receptor signaling that is amenable to therapeutic inhibition. CONCLUSIONS: We uncovered genetic subtypes of DLBCL with distinct genotypic, epigenetic, and clinical characteristics, providing a potential nosology for precision-medicine strategies in DLBCL. (Funded by the Intramural Research Program of the National Institutes of Health and others.).


Assuntos
Perfilação da Expressão Gênica , Heterogeneidade Genética , Linfoma Difuso de Grandes Células B/genética , Mutação , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Epigênese Genética , Exoma , Genótipo , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Prognóstico , Análise de Sequência de DNA , Transcriptoma
16.
Psychol Med ; : 1-9, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33618792

RESUMO

BACKGROUND: Although poverty associated with severe mental illness (SMI) has been documented in many studies, little long-term evidence of social drift exists. This study aimed to unravel the poverty transitions among persons with SMI in a fast change community in China. METHODS: Two mental health surveys, using the International Classification of Disease (ICD-10), were conducted in the same six townships of Xinjin county, Chengdu, China in 1994 and 2015. A total of 308 persons with SMI identified in 1994 were followed up in 2015. The profiles of poverty transitions were identified and regression modelling methods were applied to determine the predictive factors of poverty transitions. RESULTS: The poverty rate of persons with SMI increased from 39.9% to 49.4% in 1994 and 2015. A larger proportion of them had fallen into poverty (27.3%) rather than moved out of it (17.8%). Those persons with SMI who had lost work ability, had physical illness and more severe mental disabilities in 1994, as well as those who had experienced negative changes on these factors were more likely to live in persistent poverty or fall into poverty. Higher education level and medical treatment were major protective factors of falling into poverty. CONCLUSIONS: This study shows long-term evidence on the social drift of persons with SMI during the period of rapid social development in China. Further targeted poverty alleviation interventions should be crucial for improving treatment and mental recovery and alleviating poverty related to SMI.

17.
Mediators Inflamm ; 2021: 8086253, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688304

RESUMO

Patients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NLRP3-inflammasome inhibitors (INF39 and CP-456773) or NLRP3 siRNA. Histopathological changes that occurred in liver tissue were examined by H&E staining. Additionally, the levels IL-33, IL-18, IL-1ß, NLRP3, ASC, and cleaved-caspase 1 expression in the liver tissues were also determined. NAT2 and CYP2E1 expression were identified by QRT-PCR analysis. Finally, in vitro assays were performed to examine the effects of siRNA targeting NLRP3. Treatment with the antituberculosis drugs caused significant liver injuries, induced inflammatory responses and oxidative stress (OS), activated NLRP3 inflammasomes, reduced the activity of drug-metabolizing enzymes, and altered the antioxidant defense system in rats and hepatic cells. The NLRP3 inflammasome was required for INH- and RIF-induced liver injuries that were produced by inflammatory responses, OS, the antioxidant defense system, and drug-metabolizing enzymes. This study indicated that the NLRP3 inflammasome is involved in antituberculosis drug-induced liver injuries (ATLIs) and suggests NLRP3 as a potential target for attenuating the inflammation response in ATLIs.


Assuntos
Antituberculosos/efeitos adversos , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Isoniazida/efeitos adversos , Fígado/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Rifampina/efeitos adversos , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Ratos
18.
J Prosthet Dent ; 125(6): 877-882, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487349

RESUMO

STATEMENT OF PROBLEM: Clinical studies comparing compatible computer-aided design and computer-aided manufacturing (CAD-CAM) titanium abutments (CAs) and original prefabricated 1-piece titanium abutments (PAs) for posterior fixed dental prostheses (FDPs) on Straumann Tissue Level (STL) implants are sparse. PURPOSE: The purpose of this retrospective clinical study was to compare the performance of posterior FDPs supported by CAs and PAs on STL implants after a mean observation period of 7.2 years. MATERIAL AND METHODS: Patients who received STL implants and posterior FDPs by using CAs or PAs between January 2002 and December 2012 and returned for follow-up between January 2017 and September 2018 were included in this study. Technical and biological complications of FDPs were examined and recorded. Radiographs were used for the measurement of marginal bone loss (MBL) of each implant. Variables, complication rates, and MBL of the 2 groups were analyzed by using a generalized estimating equation and multivariable linear mixed model. RESULTS: Ninety-nine patients with 195 implants in the CA group and 75 patients with 143 implants in the PA group were included. The mean functional time of FDPs was 6.5 ±1.1 years for the CA group and 8.1 ±2.6 years for the PA group. No implant failure was noted in either group. The technical complication rate was 20.8% in the CA group and 26.3% in the PA group. Abutment screw loosening (ASL) was noted in the CA group (8.5%). The decementation rate was significantly higher in the PA group (14.1%) than that in the CA group (3.1%) (adjusted odds ratio=4.40, confidence interval=1.41 to 13.69, P=.011). No significant differences were found between the 2 groups in terms of the rates of ceramic chipping, peri-implantitis, peri-implant mucositis, or mean MBL. CONCLUSIONS: Using CAs or PAs to support posterior FDPs on STL implants has no significant effect on the incidence rate of biological complications. However, a higher ASL rate and a lower decementation rate were noted with CAs than with PAs.


Assuntos
Implantes Dentários , Titânio , Dente Suporte , Prótese Dentária Fixada por Implante , Falha de Restauração Dentária , Prótese Parcial Fixa , Humanos , Estudos Retrospectivos
19.
Mol Biol Evol ; 36(3): 487-499, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30481341

RESUMO

The origin and population history of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) remain largely unavailable and/or controversial. We here integrate analyses of multiple genomic markers, including mitochondrial (mt) genomes, Y-chromosomes, and autosomes of 54 golden monkey individuals from all three geographic populations (SG, QL, and SNJ). Our results reveal contrasting population structures. Mt analyses suggest a division of golden monkeys into five lineages: one in SNJ, two in SG, and two in QL. One of the SG lineages (a mixed SG/QL lineage) is basal to all other lineages. In contrast, autosomal analyses place SNJ as the most basal lineage and identify one QL and three SG lineages. Notably, Y-chromosome analyses bear features similar to mt analyses in placing the SG/QL-mixed lineage as the first diverging lineage and dividing SG into two lineages, while resembling autosomal analyses in identifying one QL lineage. We further find bidirectional gene flow among all three populations at autosomal loci, while asymmetric gene flow is suggested at mt genomes and Y-chromosomes. We propose that different population structures and gene flow scenarios are the result of sex-linked differences in the dispersal pattern of R. roxellana. Moreover, our demographic simulation analyses support an origin hypothesis suggesting that the ancestral R. roxellana population was once widespread and then divided into SNJ and non-SNJ (SG and QL) populations. This differs from previous mt-based "mono-origin (SG is the source population)" and "multiorigin (SG is a fusion of QL and SNJ)" hypotheses. We provide a detailed and refined scenario for the origin and population history of this endangered primate species, which has a broader significance for Chinese biogeography. In addition, this study highlights the importance to investigate multiple genomic markers with different modes of inheritance to trace the complete evolutionary history of a species, especially for those exhibiting differential or mixed patterns of sex dispersal.


Assuntos
Distribuição Animal , Cercopithecidae/genética , Espécies em Perigo de Extinção , Fluxo Gênico , Animais , China , Genoma Mitocondrial , Desequilíbrio de Ligação , Masculino , Filogenia , Filogeografia , Polimorfismo de Nucleotídeo Único , Cromossomo Y
20.
Nanotechnology ; 31(50): 505502, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021217

RESUMO

The NiO films were deposited on the surface of BaTiO3 (BTO) by atomic layer deposition (ALD). The thickness of NiO film was controlled by the number of ALD cycles, which the optimum number of ALD cycles were 400 cycles. The morphology of NiO-BTO nanocomposite was observed by x-ray diffraction, scanning electron microscope, and transmission electron microscopy. The sensor based on NiO-BTO nanocomposite displays good electrocatalytic activity and high sensitivity for serotonin (at 0.36 V vs. Ag/AgCl). In the range of 0.05-5 µM, the concentrations of serotonin are linearly related to current intensity and the detection limit is 0.03 µM (S/N = 3). The NiO-BTO/GCE was successfully applied in serum samples. It shows that the NiO-BTO nanocomposite prepared by ALD can serve as electrochemical sensor devices and applications in the fields of biosensors.

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