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1.
J Immunol ; 212(11): 1782-1790, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629901

RESUMO

Enterovirus 71 (EV71) is a significant causative agent of hand, foot, and mouth disease, with potential serious neurologic complications or fatal outcomes. The lack of effective treatments for EV71 infection is attributed to its elusive pathogenicity. Our study reveals that human plasmacytoid dendritic cells (pDCs), the main type I IFN-producing cells, selectively express scavenger receptor class B, member 2 (SCARB2) and P-selectin glycoprotein ligand 1 (PSGL-1), crucial cellular receptors for EV71. Some strains of EV71 can replicate within pDCs and stimulate IFN-α production. The activation of pDCs by EV71 is hindered by Abs to PSGL-1 and soluble PSGL-1, whereas Abs to SCARB2 and soluble SCARB2 have a less pronounced effect. Our data suggest that only strains binding to PSGL-1, more commonly found in severe cases, can replicate in pDCs and induce IFN-α secretion, highlighting the importance of PSGL-1 in these processes. Furthermore, IFN-α secretion by pDCs can be triggered by EV71 or UV-inactivated EV71 virions, indicating that productive infection is not necessary for pDC activation. These findings provide new insights into the interaction between EV71 and pDCs, suggesting that pDC activation could potentially mitigate the severity of EV71-related diseases.


Assuntos
Células Dendríticas , Enterovirus Humano A , Interferon-alfa , Proteínas de Membrana Lisossomal , Glicoproteínas de Membrana , Células Dendríticas/imunologia , Células Dendríticas/virologia , Humanos , Enterovirus Humano A/imunologia , Enterovirus Humano A/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Lisossomal/metabolismo , Proteínas de Membrana Lisossomal/imunologia , Interferon-alfa/metabolismo , Interferon-alfa/imunologia , Receptores Depuradores/metabolismo , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/virologia , Replicação Viral
2.
Nano Lett ; 24(3): 958-965, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38207219

RESUMO

Photoelectrochemical (PEC) water splitting in acidic media holds promise as an efficient approach to renewable hydrogen production. However, the development of highly active and stable photoanodes under acidic conditions remains a significant challenge. Herein, we demonstrate the remarkable water oxidation performance of Ru single atom decorated hematite (Fe2O3) photoanodes, resulting in a high photocurrent of 1.42 mA cm-2 at 1.23 VRHE under acidic conditions. Comprehensive experimental and theoretical investigations shed light on the mechanisms underlying the superior activity of the Ru-decorated photoanode. The presence of single Ru atoms enhances the separation and transfer of photogenerated carriers, facilitating efficient water oxidation kinetics on the Fe2O3 surface. This is achieved by creating additional energy levels within the Fe2O3 bandgap and optimizing the free adsorption energy of intermediates. These modifications effectively lower the energy barrier of the rate-determining step for water splitting, thereby promoting efficient PEC hydrogen production.

3.
J Am Chem Soc ; 146(10): 6846-6855, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38424010

RESUMO

This investigation probes the intricate interplay of catalyst dynamics and reaction pathways during the oxygen evolution reaction (OER), highlighting the significance of atomic-level and local ligand structure insights in crafting highly active electrocatalysts. Leveraging a tailored ion exchange reaction followed by electrochemical dynamic reconstruction, we engineered a novel catalytic structure featuring single Ir atoms anchored to NiOOH (Ir1@NiOOH). This novel approach involved the strategic replacement of Fe with Ir, facilitating the transition of selenide precatalysts into active (oxy)hydroxides. This elemental substitution promoted an upward shift in the O 2p band and intensified the metal-oxygen covalency, thereby altering the OER mechanism toward enhanced activity. The shift from a single-metal site mechanism (SMSM) in NiOOH to a dual-metal-site mechanism (DMSM) in Ir1@NiOOH was substantiated by in situ differential electrochemical mass spectrometry (DEMS) and supported by theoretical insights. Remarkably, the Ir1@NiOOH electrode exhibited exceptional electrocatalytic performance, achieving overpotentials as low as 142 and 308 mV at current densities of 10 and 1000 mA cm-2, respectively, setting a new benchmark for the electrocatalysis of OER.

4.
Plant Physiol ; 192(4): 2838-2854, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37204807

RESUMO

Somatic embryogenesis (SE) is a key regeneration pathway in various biotechnology approaches to crop improvement, especially for economically important perennial woody crops like citrus. However, maintenance of SE capability has long been a challenge and becomes a bottleneck in biotechnology-facilitated plant improvement. In the embryogenic callus (EC) of citrus, we identified 2 csi-miR171c-targeted SCARECROW-LIKE genes CsSCL2 and CsSCL3 (CsSCL2/3), which exert positive feedback regulation on csi-miR171c expression. Suppression of CsSCL2 expression by RNA interference (RNAi) enhanced SE in citrus callus. A thioredoxin superfamily protein CsClot was identified as an interactive protein of CsSCL2/3. Overexpression of CsClot disturbed reactive oxygen species (ROS) homeostasis in EC and enhanced SE. Chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA-Seq identified 660 genes directly suppressed by CsSCL2 that were enriched in biological processes including development-related processes, auxin signaling pathway, and cell wall organization. CsSCL2/3 bound to the promoters of regeneration-related genes, such as WUSCHEL-RELATED HOMEOBOX 2 (CsWOX2), CsWOX13, and Lateral Organ Boundaries Domain 40 (LBD40), and repressed their expression. Overall, CsSCL2/3 modulate ROS homeostasis through the interactive protein CsClot and directly suppress the expression of regeneration-related genes, thus regulating SE in citrus. We uncovered a regulatory pathway of miR171c-targeted CsSCL2/3 in SE, which shed light on the mechanism of SE and regeneration capability maintenance in citrus.


Assuntos
Citrus , Citrus/genética , Citrus/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biotecnologia , RNA-Seq , Regeneração , Técnicas de Embriogênese Somática de Plantas , Regulação da Expressão Gênica de Plantas
5.
Stem Cells ; 41(9): 877-891, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37317862

RESUMO

Preeclampsia (PE) is a common complication of pregnancy characterized by new-onset hypertension, albuminuria, or end-stage organ dysfunction, which is seriously harmful to maternal and infant health. Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from extraembryonic mesoderm. They have the potential for self-renewal, multidirectional differentiation, immunomodulation, and tissue regeneration. Several in vivo and in vitro experiments have confirmed that MSCs can delay the pathological progression of PE and improve maternal and fetal outcomes. However, the major limitations in the application of MSCs are their low-survival rates in ischemic and hypoxic disease areas after transplantation and their low rate of successful migration to the diseased regions. Therefore, enhancing cell viability and migration ability of MSCs in both ischemic and anoxic environments is important. This study aimed to investigate the effects of hypoxic preconditioning on the viability and migration ability of placental mesenchymal stem cells (PMSCs) and their underlying mechanisms. In this study, we found that hypoxic preconditioning enhanced the viability and migration ability of PMSCs, increased the expression of DANCR and hypoxia-inducible factor-1α (HIF-1α), and decreased the expression of miR-656-3p in PMSCs. Inhibiting the expression of HIF-1α and DACNR in PMSCs under hypoxia can inhibit the promotive effect of hypoxic preconditioning on viability and migration ability. In addition, RNA pull down and double luciferase assays confirmed that miR-656-3p could directly bind to DANCR and HIF-1α. In conclusion, our study showed that hypoxia could promote the viability and migration ability of PMSCs through the DANCR/miR-656-3p/HIF-1α axis.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Humanos , Feminino , Gravidez , Sobrevivência Celular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Placenta/metabolismo , Hipóxia/metabolismo , Hipóxia Celular , Isquemia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo
6.
BMC Health Serv Res ; 24(1): 387, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539184

RESUMO

PURPOSE: To gain an in-depth and comprehensive understanding of Chinese organ transplant recipients' perceptions, expectations, and suggestions of pharmacy services to hospital pharmacists. METHODS: This qualitative study was conducted in central China, from February to December 2020. Participants were collected with a purposive and snowball sampling method. Focus group discussions were conducted with organ transplant recipients and content analysis was applied to identify themes and subthemes. RESULTS: 21 recipients participated in the qualitative study. Four themes and thirteen subthemes were identified: (1) perceptions of clinical pharmacists and pharmacy services; (2) expectations for pharmacy service content; (3) expectations for pharmacy service form; and (4) difficulties as a special group. CONCLUSION: The pharmacy services provided by Chinese healthcare institutions are inadequate to meet the needs of organ transplant recipients. However, the acceptance and expectation of pharmacy services by transplant recipients are high. Therefore, China should learn from the experience of developed countries and focus on the actual needs of patients to establish a better pharmacy service system for organ transplantation.


Assuntos
Serviços Comunitários de Farmácia , Motivação , Humanos , Transplantados , Pesquisa Qualitativa , Grupos Focais , Farmacêuticos
7.
Int J Biometeorol ; 68(4): 625-635, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38147118

RESUMO

Particulate matter (PM10) changes have been confirmed as one of the contributory factors affecting human health, the association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease (COPD) with comorbidity diseases was rarely reported. The same inpatient more than twice times admissions with COPD illness from January 1, 2016 to December 31, 2021 were identified from hospitals in the 17 cities of Henan, Central China. City-specific associations were firstly estimated using the case time series (CTS) model and then combined to obtain the regional average association. The multivariate meta-analytic model produces pooled estimates of the set of coefficients representing the PM10-COPD hospitalizations association across the 17 cities. Cause-specific hospitalization analyses were performed by COPD patients with different comorbidity combinations. A total of 34,348 elderly (age ≥ 65) subjects were analyzed and with a total of 35,122.35 person-years. These coefficients can be used to compute the linear exposure-response curve expressed as relative risk (RR) in per 10 µg/m3 increase in PM10 at lag03, which was 1.0091 (95% CI 1.0070-1.0112) for COPD with comorbidity, 1.0089 (95% CI 1.0067-1.0110) for COPD with circulatory system diseases, 1.0079 (95% CI 1.0052-1.0105) for COPD with respiratory system diseases, 1.0076 (95% CI 1.0032-1.0121) for COPD with endocrine system diseases, and 1.0087 (95% CI 1.0013-1.0162) for COPD with genitourinary system diseases, respectively. Some heterogeneity was found across cities, with estimates ranging from 1.0227 in the Puyang and Jiaozuo to 1.0053 in Henan Provance, China. The effect of higher PM10, on average, was higher in studies for northern cities, with a steeper raise in risk: per 10 µg/m3 increase in PM10, the RR from 1.0062 (95% CI 1.0030-1.0093) for the 10th percentile of latitude to 1.0124 (95% CI 1.0089-1.0160) for the 90th percentile. Our findings indicated that PM10 exposure may increase the risk of hospitalizations for COPD with comorbidity. Moreover, there might be a higher morbidity risk associated with PM10 in northern latitudes, indicating that stricter air quality standards could potentially reduce PM10-related morbidity among individuals with COPD. These findings have implications for the implementation of effective clean air interventions aligned with national climate policies.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Poluentes Atmosféricos/análise , Cidades/epidemiologia , Poluição do Ar/análise , Material Particulado/análise , Hospitalização , Doença Pulmonar Obstrutiva Crônica/epidemiologia , China/epidemiologia , Comorbidade , Exposição Ambiental/análise
8.
Plant Dis ; : PDIS07231369RE, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37822099

RESUMO

Black point, a severe global wheat disease, necessitates deploying resistant cultivars for effective control. However, susceptibility remains prevalent among most wheat cultivars. Identifying new sources of resistance and understanding their mechanisms are crucial for breeding resistant cultivars. This study pinpointed black point resistance in an ethyl methane sulfonate (EMS)-mutagenized wheat population of Wanyuanbai 1 (WYB) and analyzed resistant mutants using RNA-Seq. The findings revealed the following: (i) wyb-18, among 10,008 EMS-mutagenized lines, exhibited robust resistance with significantly lower black point incidence under artificial Bipolaris sorokiniana inoculation in 2020 and 2021 (average incidence of 5.2% over 2 years), markedly reduced compared with WYB (50.9%). (ii) wyb-18 kernels displayed black point symptoms at 12 days after inoculation (dai), 3 days later than WYB. At 15 dai, wyb-18 kernels had isolated black spots, unlike WYB kernels, where the entire embryo turned black. (iii) wyb-18 showed heightened antioxidant enzyme activity, including peroxidase, catalase, and superoxide dismutase. (iv) Analysis of 543 differentially expressed genes between wyb-18 and WYB at 9 dai identified enrichment in the MAPK signaling pathway through KEGG analysis. Ten genes in this pathway exhibited upregulated expression, while one was downregulated in wyb-18. Among these genes, PR1, WRKY11, SAPK5, and TraesCS1A02G326800 (chitin recognition protein) consistently showed upregulation in wyb-18, making them potential candidates for black point resistance. These results offer valuable germplasm resources for breeding and novel insights into the mechanisms of black point resistance.

9.
Plant Dis ; 108(2): 426-433, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37578361

RESUMO

Crown rot caused by Fusarium pseudograminearum is a devastating wheat disease worldwide. In addition to yield losses, the fungi causing Fusarium crown rot (FCR) also deteriorate the quality and safety of food because of the production of mycotoxins. Planting resistant cultivars is an effective way to control FCR. However, most wheat cultivars are susceptible to FCR. Therefore, development of new sources and detection of loci for FCR resistance are necessary. In the present study, a resistant mutant, fcrZ22, was identified from an ethyl methane sulfonate (EMS)-mutagenized population of the cultivar Zhoumai 22, and then fcrZ22 was crossed with the wild type to produce an F2 population. Genetic analysis of the F2 population was carried out by the mixed inheritance model of major genes plus polygenes, and 20 resistant and 20 susceptible plants were selected to assemble mixed pools. Combining 660K SNP arrays, the resistance loci were detected by bulked segregant analysis. The resistance to FCR caused by F. pseudograminearum in the F2 population was in accordance with the "mixed model with two major genes of additive-epistasis effect + additive-dominant polygenes," and the heritability of the major gene was 0.92. Twenty-one loci were detected, which were located on 10 chromosomes, namely, 1B (1), 1D (1), 2A (3), 1B (1), 3A (3), 3B (3), 4A (2), 5A (2), 7A (3), and 7B (2). Among the 21 loci, eight were new loci for FCR resistance. This is the first report of detecting loci for FCR resistance from a mutant. The results of the present study provided excellent germplasm resources for breeding wheat cultivars with FCR resistance and laid the foundation for fine mapping of FCR resistance loci.


Assuntos
Fusarium , Locos de Características Quantitativas , Fusarium/genética , Resistência à Doença/genética , Melhoramento Vegetal
10.
BMC Med Educ ; 24(1): 69, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233919

RESUMO

OBJECTIVE: The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. METHODS: This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. RESULTS: Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs' perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. CONCLUSION: This study found that from the HPPs' perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.


Assuntos
Educação em Farmácia , Assistência Farmacêutica , Residências em Farmácia , Estudantes de Farmácia , Succinimidas , Humanos , Capacidades de Enfrentamento , Hospitais Gerais , Preceptoria , Pesquisa Qualitativa
11.
Funct Integr Genomics ; 23(1): 53, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36717477

RESUMO

Olverembatinib represents the third-generation breakpoint cluster region protein-Abelson-murine leukemia 1 (BCR-ABL1) tyrosine kinase inhibitor with oral bioavailability, which can be used to overcome the T315I mutation in Philadelphia chromosome-positive (Ph +) leukemia. BCR-ABL-independent resistance to olverembatinib has been reported among patients in various clinical cases. However, the mechanism of olverembatinib resistance has rarely been reported. This study has illustrated bone marrow cell transcriptome and metabolome profiles among Ph + acute lymphoblastic leukemias (ALL) cases pre- and post-olverembatinib resistance. The transcriptome studies demonstrated that PI3K/AKT, purine metabolism, and other signaling pathways could play a vital role in olverembatinib resistance. As suggested by metabolomics, olverembatinib resistance in Ph + ALL was associated with purine metabolism alterations. Subsequently, high-performance liquid chromatography along with real-time quantitative PCR was utilized to measure purine metabolism-related mRNA levels and metabolism expression levels between olverembatinib resistance and sensitive cell lines. Our results elucidate the mechanism of olverembatinib resistance in Ph + ALL at transcriptome and metabolome levels, which facilitate a better understanding of olverembatinib resistance and hence may prove crucial in identifying novel drugs to tackle this conundrum.


Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metaboloma , Mutação , Fosfatidilinositol 3-Quinases/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/farmacologia , Purinas , Transcriptoma
12.
BMC Public Health ; 23(1): 1409, 2023 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481576

RESUMO

BACKGROUND: This study aimed to examine the bidirectional relationship between social isolation and cognitive performance among Chinese middle-aged and older adults. METHODS: We used four waves of data from the China Health and Retirement Longitudinal Study. A latent growth model (LGM) was applied to examine the association between social isolation and cognitive performance across different characteristics. RESULTS: In the analysis, we ultimately included 9,367 participants after excluding respondents with missing key variables. Social isolation and cognitive performance showed significant differences across time. After adjusting for the confounders, there was a significant association between higher social isolation and poor cognitive performance (ß = -1.38, p < 0.001), and higher levels of social isolation resulted in a more pronounced decline in cognition over time (ß = 0.17, p < 0.001). Additionally, the path coefficient between the initial level of cognition at baseline and the slope of social isolation was - 0.07 (p < 0.001) and 0.01 (p = 0.021), respectively. For the correlation between slopes, our study found that females' cognition scores were more susceptible to social isolation (ß = - 2.78, p < 0.001). Similarly, regarding cognition scores, the influence of social isolation was greater among people with education below the primary level (ß = - 2.89, p = 0.002) or a greater number of chronic diseases (ß = - 2.56, p = 0.001). CONCLUSION: Our findings support the bidirectional association between social isolation and cognition. Specifically, higher baseline social isolation and its rate of increase over time contribute to an intensification of cognitive decline at follow-up. Besides, poorer cognitive performance predicted higher social isolation.


Assuntos
Cognição , Disfunção Cognitiva , Isolamento Social , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Povo Asiático , Estudos Longitudinais , China
13.
Molecules ; 28(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36677570

RESUMO

Glochidpurnoids A and B (1 and 2), two new coumaroyl or feruloyl oleananes, along with 17 known triterpenoids (3-19) were obtained from the stems and twigs of Glochidion puberum. Their structures were elucidated by extensive spectroscopic data analyses, chemical methods, and single crystal X-ray diffraction. All compounds were screened for cytotoxicity against the colorectal cancer cell line HCT-116, and 2, 3, 5, 6, 11, and 17 showed remarkable inhibitory activities (IC50: 0.80-2.99 µM), being more active than the positive control 5-fluorouracil (5-FU). The mechanistic study of 2, the most potent compound, showed that it could induce endoplasmic reticulum (ER) stress-mediated apoptosis and improve the sensitivity of HCT-116 cells to 5-FU.


Assuntos
Neoplasias Colorretais , Malpighiales , Humanos , Apoptose , Fluoruracila/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Estresse do Retículo Endoplasmático
14.
Funct Integr Genomics ; 22(5): 1031-1041, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35794284

RESUMO

Recent studies have suggested the potency of berberine (BBR) for multiple cancer treatments, including multiple myeloma (MM). However, the direct target and underlying mechanism of BBR remain largely understood in MM. Here, we demonstrated that BBR inhibited cell proliferation and acted synergistically with bortezomib in MM.1S cells. BBR treatment induced MM cell cycle arrest by downregulating several cell cycle-related proteins. Murine double minute 2 (MDM2) as a BBR-binding protein was identified by surface plasmon resonance image (SPRi) analysis and molecular docking. Overexpression of MDM2 is associated with MM progression and a poor prognosis. Knockdown MDM2 by siRNA transfection can repress MM malignant progression and attenuate the BBR sensitivity to MM.1S cells. BBR treatment induced the degradation of MDM2 through the ubiquitin-proteasome system and reactivated P53/P21 in MM cells. Overall, our data has illustrated that MDM2, as a binding protein of BBR for the first time, may serve as a potential therapeutic option for MM.


Assuntos
Berberina , Mieloma Múltiplo , Animais , Apoptose , Berberina/farmacologia , Berberina/uso terapêutico , Bortezomib/metabolismo , Carcinogênese , Linhagem Celular Tumoral , Humanos , Camundongos , Simulação de Acoplamento Molecular , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , RNA Interferente Pequeno , Proteína Supressora de Tumor p53/genética , Ubiquitina
15.
J Transl Med ; 20(1): 441, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-36180856

RESUMO

OBJECTIVE: This study incorporates the results of subgroup analyses of currently published randomized controlled trials (RCTs) and real-world cohort studies to compare the effectiveness and safety of new direct oral anticoagulants (NOACs) and warfarin among nonvalvular atrial fibrillation patients with diabetes. METHODS: The PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched. Five retrospective cohort studies and four subgroup analyses of RCTs were included in this meta-analysis. RESULTS: A meta-analysis of the data of 26,7272 patients showed that for patients with nonvalvular atrial fibrillation and diabetes, NOACs can significantly reduce the incidence of stroke/systemic embolism (SSE), ischaemic stroke, and haemorrhagic stroke compared with warfarin, with no significant difference in major bleeding and all-cause mortality. Additionally, NOACs were superior to warfarin in the incidence of intracranial bleeding, gastrointestinal bleeding, myocardial infarction, and vascular death. CONCLUSIONS: Among nonvalvular atrial fibrillation patients with diabetes, NOACs were associated with a lower risk of SSE versus warfarin, with no significant difference in major bleeding. Therefore, NOACs may be a better clinical choice.


Assuntos
Fibrilação Atrial , Diabetes Mellitus , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento , Varfarina/efeitos adversos
16.
J Transl Med ; 20(1): 300, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35794565

RESUMO

BACKGROUND: Autophagy plays a critical role in drug resistance in acute myeloid leukemia (AML), including the subtype with FLT3-ITD mutation. Yet how autophagy is activated and mediates resistance to FLT3 inhibitors in FLT3-ITD-positive AML remains unsure. METHODS: We detected the expression of autophagy markers in FLT3-ITD-positive leukemic cells after vs. before acquired resistance to FLT3 inhibitors; tested the stimulative effect of acquired D835Y mutation and bone marrow micro-environment (BME) on autophagy; explored the mechanism of autophagy mediating FLT3 inhibitor resistance. RESULTS: Sorafenib-resistant cells markedly overpresented autophagy markers in comparison with sorafenib-sensitive cells or the cells before sorafenib treatment. Both acquired D835Y mutation and BME activated cytoprotective autophagy to mediate FLT3 inhibitor resistance. Autophagy activation decreased the suppression efficacy of FLT3 inhibitors on FLT3 downstream signaling and then weakened their anti-leukemia effect. Inhibition of autophagy with CQ significantly enhanced the suppressive effect of FLT3 inhibitor on FLT3 downstream signaling, in the end overcame resistance to FLT3 inhibitors. CONCLUSIONS: Autophagy might be stimulated by acquired mutation or BME, and bypass activate FLT3 downstream signaling to mediate FLT3 inhibitor resistance in FLT3-ITD-positive AML. Targeting autophagy could be a promising strategy to overcome resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Autofagia/genética , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Mutação/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Microambiente Tumoral , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/farmacologia , Tirosina Quinase 3 Semelhante a fms/uso terapêutico
17.
J Exp Bot ; 73(18): 6170-6185, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-35661206

RESUMO

Somatic embryogenesis (SE) is a major regeneration approach for in vitro cultured tissues of plants, including citrus. However, SE capability is difficult to maintain, and recalcitrance to SE has become a major obstacle to plant biotechnology. We previously reported that miR156-SPL modules regulate SE in citrus callus. However, the downstream regulatory pathway of the miR156-SPL module in SE remains unclear. In this study, we found that transcription factors CsAGL15 and CsFUS3 bind to the CsMIR156A promoter and activate its expression. Suppression of csi-miR156a function leads to up-regulation of four target genes, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (CsSPL) genes, and reduction of SE efficiency. In the short tandem target mimic (STTM)-miR156a overexpression callus (MIM156), the number of amyloplasts and starch content were significantly reduced, and genes involved in starch synthesis and transport were down-regulated. csi-miR172d was down-regulated, whereas the target genes, CsTOE1.1 and CsTOE1.2, which inhibit the expression of starch biosynthesis genes, were up-regulated. In our working model, CsAGL15 and CsFUS3 activate csi-miR156a, which represses CsSPLs and further regulates csi-miR172d and CsTOEs, thus altering starch accumulation in callus cells and regulating SE in citrus. This study elucidates the pathway of miR156-SPLs and miR172-TOEs-mediated regulation of SE, and provides new insights into enhancing SE capability in citrus.


Assuntos
Citrus , MicroRNAs , Regulação da Expressão Gênica de Plantas , Citrus/genética , Citrus/metabolismo , Amido/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Desenvolvimento Embrionário
18.
Artigo em Inglês | MEDLINE | ID: mdl-35100103

RESUMO

A nitrogen-fixing, endospore-forming, motile, rod-shaped, facultative aerobic bacterium, designated 81-11T, was isolated from rhizosphere soil of a peach tree collected from Handan, Hebei, PR China. From the comparison of 16S rRNA gene sequence, the strain is most closely related to Paenibacillus phoenicis DSM 27463T (96.9 %) and Paenibacillus faecis DSM 23593T (96.7 %). The genome size of strain 81-11T was 4.4 Mb, comprising 4879 predicted genes with a DNA G+C content of 50.0 mol%. The average nucleotide identity values of genome sequences between the novel isolate and the type strains of related species P. phoenicis DSM 27463T and P. faecis DSM 23593T were 71.8 and 72.1 %, respectively. The major cellular fatty acids were anteiso-C15 : 0(47.8 %), iso-C16 : 0 (15.5 %) and iso-C15 : 0 (13.0 %). Menaquinone-7 was the major respiratory quinone. The polar lipids contained phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid, aminoglycopid, unknown polar lipids and unidentified aminophosphoglycolipid. Based on phylogenetic, genomic and phenotypic characteristics, strain 81-11T was classified as a novel species within the genus Paenibacillus, for which the name Paenibacillus caui sp. nov. is proposed. The type strain of Paenibacillus caui is 81-11T (=JCM 34618T=CGMCC 1.18907T).


Assuntos
Fixação de Nitrogênio , Paenibacillus , Filogenia , Prunus persica , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Nitrogênio/metabolismo , Paenibacillus/classificação , Paenibacillus/isolamento & purificação , Fosfolipídeos/química , Prunus persica/microbiologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
19.
Transpl Infect Dis ; 24(2): e13776, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34941004

RESUMO

BACKGROUND: Cidofovir (CDV) is a nucleotide analogue with broad antiviral activities. It remains unclear about the CDV administration for anti-cytomegalovirus (CMV) treatment in patients with haploidentical hematopoietic stem cell transplantation (haplo-HSCT). PATIENTS AND METHODS: In this study, 31 out of 101 haplo-HSCT recipients who suffered CMV infection in the CT group (conventional treatment) were enrolled into the CDV-ST group (CDV second-line treatment). These patients were treated with CDV as they failed conventional treatment or they were unavailable to the preemptive antiviral therapy. Nine patients with CMV infection were enrolled into the CDV-FT group (CDV-frontline treatment) and received CDV preemptive therapy. RESULTS: In the CDV-ST group, 23 of 28 (82.1%) patients were observed treatment response with a median time of 9 (2-23) days, and 20 (71.8%) among these patients obtained complete response (CR). In the CDV-FT group, six of eight (75.0%) patients acquired CR with a median of 6 (4-25) days. The treatment response in CDV-treated groups was comparable with those in CT groups. Besides, there was no statistical difference in CMV-related mortality between the three groups (p > .05). During the follow-up period (median follow-up:10 [1-28] months), a total of 8 of 22 (36.4%) patients experienced CMV reactivation in the CDV-ST group versus 23 of 62 (37.1%) in the CT group (p > .05). CDV-related toxicities occurred in 13 of 40 (32.5%) patients, including six (15%) reversible nephrotoxicity. CONCLUSION: Our study suggests that CDV is potentially an option for the salvage treatment of CMV infection in the haplo-HSCT patients.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Antivirais , Cidofovir/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Terapia de Salvação
20.
Plant Cell Rep ; 41(6): 1403-1415, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35381869

RESUMO

KEY MESSAGE: Overexpression of miR171 restored SE competence in the recalcitrant citrus callus, and inhibition of miR171 function weakened SE competence in the strongly embryogenic citrus callus. Somatic embryogenesis (SE) is an important way of in vitro regeneration for plants. For perennial woody crops such as citrus, embryogenic callus is usually induced from unfertilized aborted ovules and widely used in biotechnology aided breeding. However, SE capacity always declines in callus during subculture, which makes regeneration difficult and hinders the application of biotechnology. We previously found that miR171 may be a regulator of SE in citrus, based on the abundant expression of csi-miR171c in the embryogenic callus and during SE of citrus. Here, we report that miR171 promotes SE and is required for SE in citrus. Overexpression of miR171 restored SE competence in the recalcitrant callus of 'Guoqing No.1' Satsuma mandarin (G1), whereas inhibition of miR171 function by Short Tandem Target Mimic (STTM) weakened SE competence in the strongly embryogenic callus of 'Valencia' sweet orange (V). The comparative transcriptomic analysis in miR171 overexpressed callus line (OE) and the wild type callus (WT) indicated that overexpression of miR171 decreased the expression level of its SCARECROW-LIKE (CsSCL) targets, and activated stress response related biological processes and metabolic processes that are required for cell differentiation. However, CsSCLs were up-regulated in the OE callus during SE induction process, which activated the cell division and developmental processes that are required for embryogenesis progress. Our results validate the function of miR171 in regulation of SE and reveal the biological responses provoked by miR171 in citrus that may promote SE.


Assuntos
Citrus sinensis , Citrus , Citrus/genética , Citrus sinensis/metabolismo , Desenvolvimento Embrionário , Regulação da Expressão Gênica de Plantas/genética , Melhoramento Vegetal
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