Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Plant Pathol J ; 40(1): 73-82, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326960

RESUMO

Gardenia (Gardenia jasminoides) is a popular and economically vital plant known for its ornamental and medicinal properties. Despite its widespread cultivation, there has been no documentation of plant viruses on gardenia yet. In the present study, gardenia leaves exhibiting symptoms of plant viral diseases were sampled and sequenced by both metatranscriptome and small RNA sequencing. As a consequence, bean common mosaic virus (BCMV) was identified in gardenia for the first time and named BCMV-gardenia. The full genome sequence of BCMV-gardenia is 10,054 nucleotides (nt) in length (excluding the poly (A) at the 3' termini), encoding a large polyprotein of 3,222 amino acids. Sequence analysis showed that the N-termini of the polyprotein encoded by BCMV-gardenia is less conserved when compared to other BCMV isolates, whereas the C-termini is the most conserved. Maximum likelihood phylogenetic analysis showed that BCMV-gardenia was clustered closely with other BCMV isolates identified outside the leguminous plants. Our results indicated that the majority of BCMV-gardenia virus-derived small interfering RNAs (vsiRNAs) were 21 nt and 22 nt, with 21 nt being more abundant. The first nucleotide at the 5' termini of vsiRNAs derived from BCMV-gardenia preferred U and A. The ratio of vsiRNAs derived from sense (51.1%) and antisense (48.9%) strands is approaching, and the distribution of vsiRNAs along the viral genome is generally even, with some hot spots forming in local regions. Our findings could provide new insights into the diversity, evolution, and host expansion of BCMV and contribute to the prevention and treatment of this virus.

2.
Arch Virol ; 169(1): 19, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38180588

RESUMO

The complete genomic sequence of a novel robigovirus, provisionally named "Mentha arvensis robigovirus 1" (MARV1), was determined by combining next-generation sequencing (NGS), reverse transcription polymerase chain reaction (RT-PCR), and rapid amplification of cDNA ends (RACE) PCR. The complete genomic sequence of this new virus is 7617 nucleotides in length, excluding the 3' poly(A) tail. The MARV1 genome encodes a putative replicase, "triple gene block" proteins, and a coat protein. Phylogenetic analysis demonstrated that MARV1 is a member of the genus Robigovirus, with closest relationships to African oil palm ringspot virus (AOPRV). Furthermore, MARV1-derived small interfering RNAs (siRNAs) showed typical patterns of plant-virus-derived siRNAs produced by the host antiviral RNA interference pathway. This is the first report of a plant virus of the genus Robigovirus in M. arvensis.


Assuntos
Flexiviridae , Mentha , Filogenia , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro , RNA Interferente Pequeno/genética
3.
J Vasc Surg ; 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38122857

RESUMO

BACKGROUND: At present, open surgical aortic arch repair (OAR) and debranching hybrid surgical aortic arch repair (HAR) serve as significant therapeutic approaches for aortic arch aneurysm or dissection. It remains unclear which technique is preferable. Our study aimed to compare the short-term and long-term outcomes of these two procedures. METHODS: To identify comparison studies of debranching HAR and OAR, a systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases was performed from January 2002 to April 2022. This study was registered on PROSPERO (CRD42020218080). RESULTS: Sixteen publications (1316 patients), including six propensity score-matching (PSM) analysis papers, were included in this study. Compared with the HAR group, the patients who underwent OAR were younger (OAR vs HAR: 67.53 ± 12.81 vs 71.29 ± 11.0; P < .00001), had less coronary artery disease (OAR vs HAR: 22.45% vs 32.6%; P = .007), less chronic obstructive pulmonary disease (OAR vs HAR: 16.16% vs 23.92%; P = .001), lower rates of previous stroke (OAR vs HAR: 12.46% vs 18.02%; P = .05), and a lower EuroSCORE (European System for Cardiac Operative Risk Evaluation) score (OAR vs HAR: 6.27 ± 1.04 vs 6.9 ± 3.76; P < .00001). HAR was associated with less postoperative blood transfusion (OAR vs HAR: 12.23% vs 7.91%; P = .04), shorter length of intensive care unit stays (OAR vs HAR: 5.92 ± 7.58 days vs 4.02 ± 6.60 days; P < .00001) and hospital stays (OAR vs HAR: 21.59 ± 17.54 days vs 16.49 ± 18.45 days; P < .0001), lower incidence of reoperation for bleeding complications (OAR vs HAR: 8.07% vs 3.96%; P = .01), fewer postoperative pulmonary complication (OAR vs HAR: 14.75% vs 5.02%; P < .0001), and acute renal failure (OAR vs HAR: 7.54% vs 5.17%; P = .03). In the PSM subgroup, the rates of spinal cord ischemic (OAR vs HAR: 5.75% vs 11.49%; P = .02), stroke (OAR vs HAR: 5.1% vs 17.35%; P = .01), and permanent paraplegia (OAR vs HAR: 2.79% vs 6.08%; P = .006) were lower in the OAR group than that in the HAR group. Although there was no statistically significant difference in 1-year survival rates (HAR vs OAR: hazard ratio [HR]: 1.54; P = .10), the 3-year and 5-year survivals were significantly higher in the OAR group than that in the HAR group (HAR vs OAR: HR: 1.69; P = .01; HAR vs OAR: HR: 1.68; P = .01). In the PSM subgroup, the OAR group was also significantly superior to the HAR group in terms of 3-year and 5-year survivals (HAR vs OAR: HR: 1.73; P = .04; HAR vs OAR: HR: 1.67; P = .04). The reintervention rate in the HAR group was significantly higher than that in the OAR group (OAR vs HAR: 8.24% vs 16.01%; P = .01). The most common reintervention was postoperative bleeding (8.07%) in the OAR group and endoleak (9.67%) in the HAR group. CONCLUSIONS: Our meta-analysis revealed that debranching HAR was associated with fewer perioperative complications than the OAR group, except for postoperative permanent paraplegia, reintervention, and stroke events. The OAR group demonstrated better 3-year and 5-year survivals than the debranching HAR group. However, patients in the OAR group had fewer comorbid factors and were younger than those in the HAR group. High-quality studies and well-powered randomized trials are needed to further evaluate this evolving field.

4.
Nat Commun ; 14(1): 7264, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945658

RESUMO

Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed throughout the genomes of eukaryotes. Although nrEVEs are known to be involved in host antiviral immunity, it remains an open question whether they can be domesticated as functional proteins to serve cellular innovations in arthropods. In this study, we found that endogenous toti-like viral elements (ToEVEs) are ubiquitously integrated into the genomes of three planthopper species, with highly variable distributions and polymorphism levels in planthopper populations. Three ToEVEs display exon‒intron structures and active transcription, suggesting that they might have been domesticated by planthoppers. CRISPR/Cas9 experiments revealed that one ToEVE in Nilaparvata lugens, NlToEVE14, has been co-opted by its host and plays essential roles in planthopper development and fecundity. Large-scale analysis of ToEVEs in arthropod genomes indicated that the number of arthropod nrEVEs is currently underestimated and that they may contribute to the functional diversity of arthropod genes.


Assuntos
Artrópodes , Hemípteros , Animais , Artrópodes/genética , Hemípteros/genética , Retroviridae
5.
EMBO Rep ; 24(1): e55387, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36394357

RESUMO

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.


Assuntos
Interferon Tipo I , Viroses , Camundongos , Animais , Viroses/genética , Antivirais , Imunidade Inata , Ubiquitinação , Fator Regulador 7 de Interferon/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(6): 988-992, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36443039

RESUMO

Objective: To summarize our hospital's single-center experience of and reflections on the treatment of chronic limb-threatening ischemia (CLTI) of lower limbs combined with diabetes in the past 5 years. Methods: We retrospectively analyzed cases of lower limb CLTI combined with diabetes diagnosed at our hospital from March 2017 to June 2021. The baseline data, surgical information, and follow-up results of the patients were collected. The primary outcome indicator was the patency rate of lower limb target artery within 1 year post-op, and the secondary indicators were the reoperation rate within 1 year post-op and the amputation rate within 1 year post-op. Results: A total of 89 patients with lower limb CLTI combined with diabetes were included in the study. A total of 85 patients underwent percutaneous transluminal angioplasty and the operation of 7 patients ended in failure, with the operation success rate reaching 91.76% (78/85). Three patients underwent femoral popliteal artery bypass grafting with artificial blood vessels and one patient underwent iliac femoral artery bypass grafting with artificial blood vessels, with the success rate of the operations reachign 100% (4/4). Among 78 patients who successfully underwent percutaneous transluminal angioplasty, the median follow-up time was 33 months (13, 64). Two patients died within one year after operation, with the post-op one-year survival rate being 97.44% (76/78). The post-op 1-year reoperation rate was 19.23% (15/78), the 1-year target vascular patency rate (deaths not included) was 85.53% (65/76), and the 1-year amputation rate was 3.85% (3/78). Among the patients who underwent bypass surgery, the follow-up period was 13-48 months. No thrombosis in or re-occlusion of the artificial blood vessels were observed during the follow-up period, and the artificial blood vessels remained unoccluded. Conclusion: Transluminal angioplasty has a relatively ideal rate of postoperative vascular patency. In addition, it is a minimally invasive procedure involving low perioperative risks and is performed under local anesthesia. Therefore, it can be used as the preferred treatment for patients with CLTI. On the other hand, bypass surgery has good long-term patency rate, but it involves higher perioperative risks and the procedure is more invasive. Therefore, bypass surgery can be used as an alternative when transluminal angioplasty ends in failure.


Assuntos
Substitutos Sanguíneos , Diabetes Mellitus , Humanos , Isquemia Crônica Crítica de Membro , Estudos Retrospectivos , Extremidade Inferior
7.
J R Soc Interface ; 19(188): 20210783, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35317652

RESUMO

Human beings often explore and perceive the characteristics of objects by touching with their fingers. During this process, the contact pressure and shear stress acting on the skin also modulate the tactile sensation. The external environment is an important factor that influences tactile perception as well as the finger friction characteristics. The purpose of this study was to investigate the effects of fluid environments, such as air, deionized water (DW) and thickened water (TW), on perceived roughness and relevant friction behaviour during finger movement. Two studies were performed to analyse the effect of fluid environment as well as the influence of lubricant viscosity on finger tactile friction behaviour. Participants conducted perception and sliding friction tests with their index finger in air and submerged in DW and TW, respectively. Perception tests were performed using a pairwise comparison, scoring the perceived roughness difference between a reference sample and the test sample. The statistical analysis showed that there was no significant difference in the roughness perception between air and DW, while the sensitivity of perception reduced with increasing lubricant viscosity. An approximate calculation of the film thickness was combined with classical lubrication theory to investigate the relationship between perception and friction. In TW, the thick film formed between the finger and the polytetrafluoroethylene plate changed the contact of the asperities with the skin, thus changing the subjective judgement and friction.


Assuntos
Percepção do Tato , Dedos , Fricção , Humanos , Pele , Tato
8.
Immunity ; 54(8): 1728-1744.e7, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34343498

RESUMO

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.


Assuntos
Antioxidantes/farmacologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Selênio/farmacologia , Selenoproteína W/metabolismo , Células Th1/citologia , Diferenciação Celular/imunologia , Polaridade Celular , Colo/imunologia , Colo/patologia , Glicina Hidroximetiltransferase/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Ribonucleoproteínas/metabolismo , Células Th1/imunologia , Ubiquitina-Proteína Ligases/metabolismo
9.
J Exp Med ; 218(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33616624

RESUMO

Frequent outbreaks of viruses have caused a serious threat to public health. Previous evidence has revealed that DNA methylation is correlated with viral infections, but its role in innate immunity remains poorly investigated. Additionally, DNA methylation inhibitors promote IFN-I by upregulating endogenous retrovirus; however, studies of intrinsically demethylated tumors do not support this conclusion. This study found that Uhrf1 deficiency in myeloid cells significantly upregulated Ifnb expression, increasing resistance to viral infection. We performed whole-genome bisulfite sequencing and found that a single-nucleotide methylation site in the Ifnb promoter region disrupted IRF3 recruitment. We used site-specific mutant knock-in mice and a region-specific demethylation tool to confirm that this methylated site plays a critical role in regulating Ifnb expression and antiviral responses. These findings provide essential insight into DNA methylation in the regulation of the innate antiviral immune response.


Assuntos
Antivirais/metabolismo , Metilação de DNA/genética , Imunidade Inata/genética , Interferon Tipo I/metabolismo , Nucleotídeos/genética , Animais , Sequência de Bases , Proteínas Estimuladoras de Ligação a CCAAT/deficiência , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Cromatina/metabolismo , Ilhas de CpG/genética , Citocinas/metabolismo , Células HEK293 , Homeostase , Humanos , Sistema Imunitário/metabolismo , Vacinas contra Influenza/imunologia , Camundongos , Células Mieloides/metabolismo , Orthomyxoviridae/fisiologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Regiões Promotoras Genéticas/genética , Transdução de Sinais , Receptores Toll-Like/agonistas , Receptores Toll-Like/metabolismo , Transcrição Gênica , Transcriptoma/genética , Ubiquitina-Proteína Ligases/deficiência , Ubiquitina-Proteína Ligases/metabolismo
10.
Sci Adv ; 7(3)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33523871

RESUMO

The classic NF-κB pathway plays crucial roles in various immune responses and inflammatory diseases. Its key kinase, IKKß, participates in a variety of pathological and physiological processes by selectively recognizing its downstream substrates, including p105, p65, and IκBα, but the specific mechanisms of these substrates are unclear. Hyperactivation of one of the substrates, p105, is closely related to the onset of inflammatory bowel disease (IBD) in Nfkb1-deficient mice. In this study, we found that IKKß ubiquitination on lysine-238 was substantially increased during inflammation. Using mass spectrometry, we identified USP16 as an essential regulator of the IKKß ubiquitination level that selectively affected p105 phosphorylation without directly affecting p65 or IκBα phosphorylation. Furthermore, USP16 was highly expressed in colon macrophages in patients with IBD, and myeloid-conditional USP16-knockout mice exhibited reduced IBD severity. Our study provides a new theoretical basis for IBD pathogenesis and targeted precision intervention therapy.

11.
Signal Transduct Target Ther ; 6(1): 79, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33612829

RESUMO

The response of immune cells in cardiac injury is divided into three continuous phases: inflammation, proliferation and maturation. The kinetics of the inflammatory and proliferation phases directly influence the tissue repair. In cardiac homeostasis, cardiac tissue resident macrophages (cTMs) phagocytose bacteria and apoptotic cells. Meanwhile, NK cells prevent the maturation and transport of inflammatory cells. After cardiac injury, cTMs phagocytose the dead cardiomyocytes (CMs), regulate the proliferation and angiogenesis of cardiac progenitor cells. NK cells prevent the cardiac fibrosis, and promote vascularization and angiogenesis. Type 1 macrophages trigger the cardioprotective responses and promote tissue fibrosis in the early stage. Reversely, type 2 macrophages promote cardiac remodeling and angiogenesis in the late stage. Circulating macrophages and neutrophils firstly lead to chronic inflammation by secreting proinflammatory cytokines, and then release anti-inflammatory cytokines and growth factors, which regulate cardiac remodeling. In this process, dendritic cells (DCs) mediate the regulation of monocyte and macrophage recruitment. Recruited eosinophils and Mast cells (MCs) release some mediators which contribute to coronary vasoconstriction, leukocyte recruitment, formation of new blood vessels, scar formation. In adaptive immunity, effector T cells, especially Th17 cells, lead to the pathogenesis of cardiac fibrosis, including the distal fibrosis and scar formation. CMs protectors, Treg cells, inhibit reduce the inflammatory response, then directly trigger the regeneration of local progenitor cell via IL-10. B cells reduce myocardial injury by preserving cardiac function during the resolution of inflammation.


Assuntos
Traumatismos Cardíacos/imunologia , Infarto do Miocárdio/imunologia , Traumatismo por Reperfusão Miocárdica/imunologia , Miocárdio/imunologia , Traumatismos Cardíacos/patologia , Traumatismos Cardíacos/terapia , Homeostase/imunologia , Humanos , Células Matadoras Naturais/imunologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Miócitos Cardíacos/imunologia , Neutrófilos/imunologia , Regeneração/imunologia
12.
Sci China Life Sci ; 64(6): 957-965, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33141302

RESUMO

Interferon regulatory factors (IRFs) play pivotal and critical roles in innate and adaptive immune responses; thus, precise and stringent regulation of the stability and activation of IRFs in physiological processes is necessary. The stability and activities of IRFs are directly or indirectly targeted by endogenous and exogenous proteins in an ubiquitin-dependent manner. However, few reviews have summarized how host E3 ligases/DUBs or viral proteins regulate IRF stability and activity. Additionally, with recent technological developments, details about the ubiquitination of IRFs have been continuously revealed. As knowledge of how these proteins function and interact with IRFs may facilitate a better understanding of the regulation of IRFs in immune responses or other biological processes, we summarized current studies on the direct ubiquitination of IRFs, with an emphasis on how these proteins interact with IRFs and affect their activities, which may provide exciting targets for drug development by regulating the functions of specific E3 ligases.


Assuntos
Imunidade , Fatores Reguladores de Interferon/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina/metabolismo , Ubiquitinação , Proteínas Virais/metabolismo , Humanos
13.
Cell Mol Immunol ; 17(7): 712-721, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32523116

RESUMO

Mitochondria are highly mobile organelles due to fission, fusion, transport, and mitophagy, and these processes are known as mitochondrial dynamics. Mitochondrial dynamics play an important role in energy production, cell division, cell differentiation, and cell death. In the past decade, numerous studies have revealed the importance of mitochondrial metabolism in immunity, and mitochondrial dynamics are essential for immune responses mediated by various cell types. In this review, we mainly discuss the role of mitochondrial dynamics in activation, differentiation, cytokine production, and the activity of related pathways in immune cells, particularly T cells, B cells, and other cells involved in the innate immune response.


Assuntos
Linfócitos/imunologia , Dinâmica Mitocondrial/imunologia , Animais , Autofagia , Células Dendríticas/imunologia , Humanos , Macrófagos/imunologia , Modelos Biológicos
14.
Cell ; 179(4): 864-879.e19, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31675497

RESUMO

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.


Assuntos
Ansiedade/metabolismo , Comportamento Animal/fisiologia , Encefalopatias Metabólicas/metabolismo , Estresse Psicológico/metabolismo , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/patologia , Animais , Ansiedade/genética , Ansiedade/imunologia , Ansiedade/fisiopatologia , Encefalopatias Metabólicas/genética , Encefalopatias Metabólicas/fisiopatologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Dinâmica Mitocondrial/genética , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Análise de Célula Única , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Transcriptoma/genética , Xantina/metabolismo
15.
Proc Math Phys Eng Sci ; 475(2228): 20190232, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31534426

RESUMO

Tuned mass dampers (TMDs), in which a reaction mass is attached to a structural system via a spring-parallel-damper connection, are commonly used in a wide range of applications to suppress deleterious vibrations. Recently, a mass-included absorber layout with an inerter element, termed the tuned mass damper inerter (TMDI), was introduced, showing significant performance benefits on vibration suppression. However, there are countless mass-included absorber layouts with springs, dampers and inerters, which could potentially provide more preferred dynamic properties. Currently, because there is no systematic methodology for accessing them, only an extremely limited number of mass-included absorber layouts have been investigated. This paper proposes an approach to identify optimum vibration absorbers with a reaction mass. Using this approach, a full class of absorber layouts with a reaction mass and a pre-determined number of inerters, dampers and springs connected in series and parallel, can be systematically investigated using generic Immittance-Function-Networks. The advan- tages of the proposed approach are demonstrated via a 3 d.f. structure example.

16.
J Clin Invest ; 129(7): 2856-2871, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31135381

RESUMO

Calcineurin acts as a calcium-activated phosphatase that dephosphorylates various substrates, including members of the nuclear factor of activated T cells (NFAT) family, to trigger their nuclear translocation and transcriptional activity. However, the detailed mechanism regulating the recruitment of NFATs to calcineurin remains poorly understood. Here, we report that calcineurin A (CNA), encoded by PPP3CB or PPP3CC, is constitutively ubiquitinated on lysine 327, and this polyubiquitin chain is rapidly removed by ubiquitin carboxyl-terminal hydrolase 16 (USP16) in response to intracellular calcium stimulation. The K29-linked ubiquitination of CNA impairs NFAT recruitment and transcription of NFAT-targeted genes. USP16 deficiency prevents calcium-triggered deubiquitination of CNA in a manner consistent with defective maintenance and proliferation of peripheral T cells. T cell-specific USP16 knockout mice exhibit reduced severity of experimental autoimmune encephalitis and inflammatory bowel disease. Our data reveal the physiological function of CNA ubiquitination and its deubiquitinase USP16 in peripheral T cells. Notably, our results highlight a critical mechanism for the regulation of calcineurin activity and a novel immunosuppressive drug target for the treatment of autoimmune diseases.


Assuntos
Doenças Autoimunes , Calcineurina , Linfócitos T , Ubiquitina Tiolesterase , Ubiquitinação , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Calcineurina/genética , Calcineurina/imunologia , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Linfócitos T/imunologia , Linfócitos T/patologia , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/imunologia , Ubiquitinação/genética , Ubiquitinação/imunologia
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-773647

RESUMO

To systemically evaluate the benefits and side effects of Shensong Yangxin Capsules( SYC) in the adjuvant treatment of stable angina pectoris( SAP). Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP,Wan Fang database) were retrieved to collect the randomized controlled trials( RCTs) about therapeutic efficacy of SYC combined with routine drug( trial group) vs routine drug( control group) in the treatment of SAP. The methodological quality of the RCTs was evaluated based on the cochrane risk of bias assessment tool. The data were extracted and Meta-analyzed by Reviewer Manager 5. 3. TSA 0. 9 software was used for trial sequential analysis( TSA) of the total effective rate of symptoms improvement. A total of 15 RCTs with 1 316 participants were included. RESULTS:: of Meta-analysis showed that the total effective rate of angina symptoms improvement( RR = 1. 15,95% CI[1. 09,1. 21],P<0. 001) of trial group were significantly higher than those of control group,with statistical significance,the total effective rate of electrocardiograms( ECG) improvement( RR = 1. 10,95% CI[0. 94,1. 29],P = 0. 25) of trial group were significantly higher than those of control group,but the difference was not statistically significant. After treatment,the improvement of the total time of 24 h general ischemia( SMD =-1. 21,95%CI[-1. 97,-0. 45],P = 0. 002),the ST-segment depression amplitude( SMD =-1. 30,95%CI [-1. 52,-1. 09],P<0. 001),the duration of angina pectoris attack( SMD =-1. 16,95% CI[-1. 36,-0. 95],P< 0. 001),the angina pectoris attack every week( SMD =-0. 80,95%CI[-1. 10,-0. 50],P<0. 001),the onsumption of nitroglycerin every week( SMD=-0. 72,95%CI[-1. 05,-0. 39],P<0. 001) in the trial group were better than that of the control group,and the difference was statistically significant. Besides,the improvement of the blood lipid and high sensitivity C reactive protein( hs-CRP) in the trial group were better than those of the control group after treatment,and the difference was statistically significant( P< 0. 001). Funnel plots and Egger's linear regression showed that there was no publication bias. By sensitivity analysis,it showed that the results of this study were stable and reliable. No obvious adverse drug reactions were observed in all studies. TSA analysis showed that the evidence of Meta-analysis was reliable. SYC combined with routine Western medicine treatment for SAP can improve the total effective rate of angina pectoris,reduce 24 h total ischemia time,ST segment depression amplitude,duration of angina pectoris attack,frequency of angina pectoris attack and nitroglycerin dosage,and also can improve blood lipid and hs-CRP levels.


Assuntos
Humanos , Adjuvantes Farmacêuticos , Angina Estável , Tratamento Farmacológico , Proteína C-Reativa , Cápsulas , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Eletrocardiografia , Lipídeos , Sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-773218

RESUMO

To systemically evaluate the efficacy and safety of salvianolate intravenous drip in combination with hydration against contrast-induced nephropathy( CIN),and guide clinical medication. Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,VIP,Wan Fang database,CNKI) were retrieved to collect the randomized controlled trials( RCTs) about the efficacy of salvianolate intravenous drip in combination with hydration( trial group) vs routine hydration( control group) in the prevention of contrastinduced nephropathy. The methodological quality of the RCTs was evaluated by using the Cochrane 5. 1. 0 Bias Risks Assessment Tool.The data were extracted and Meta-analysis was conducted by Reviewer Manager 5. 3. Egger's test and non-parametric clipping method were used to evaluate publication bias. A total of 9 RCTs with 2 186 participants were included. RESULTS:: of Meta-analysis showed that the incidence of contrast-induced nephropathy of trial group was significantly higher than that of control group( RR = 0. 46,95% CI[0. 35,0. 59],P<0. 001). Subgroup analysis showed that the incidences of CIN in patients with acute coronary syndrome( ACS) undergoing PCI,in patients with the average age≥65 years,in patients who received mean contrast volume ≥200 m L,in patients with serum creatinine( Scr) ≥ 80 μmol,or in patients who received intraoperative administration of salvianolate or PCI were higher than those in control group,with statistically significant differences( P<0. 05). The experimental group was superior to the control group in improving the indexes of renal function after operation,and the difference was statistically significant( P<0. 05). No study reported the incidence of adverse reactions( ADRs). The funnel plots of the incidence of CIN showed potential publication bias. The results of Egger's linear regression showed that there was certain publication bias. Sensitivity analysis,funnel plot,and " trim and fill" showed that the results of this study were stable and reliable. Salvianolate combined with routine hydration showed definite clinical efficacy in the prevention of contrast-induced nephropathy. However,exact conclusion should be further verified by additional high-quality,multi-centre,and large-scale RCT studies.


Assuntos
Humanos , Meios de Contraste , Nefropatias , Intervenção Coronária Percutânea , Extratos Vegetais , Usos Terapêuticos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Exp Ther Med ; 15(1): 1081-1086, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29434698

RESUMO

The objective of the present study was to examine whether Clostridium butyricum supplementation has a role in the regulation of the intestinal flora and the development of the immune system of neonatal mice. A total of 30 pregnant BALB/c mice, including their offspring, were randomly divided into three groups: In the maternal intervention group (Ba), maternal mice were treated with Clostridium butyricum from birth until weaning at postnatal day 21 (PD21) followed by administration of saline to the offspring at PD21-28; in the offspring intervention group (Ab), breast-feeding maternal mice were supplemented with saline and offspring were directly supplemented with Clostridium butyricum from PD21-28; in the both maternal and offspring intervention group (Bb), both maternal mice and offspring were supplemented with Clostridium butyricum at PD 0-21 and at PD21-28. While mice in the control group were given the same volume of normal saline. Stool samples from the offspring were collected at PD14, -21 and -28 to observe the intestinal flora by colony counts of Enterococcus spp., Enterobacter spp., Bifidobacterium spp. and Lactobacillus spp. Detection of intestinal secreted immunoglobulin A (sIgA) levels and serum cytokine (interferon-γ, and interleukin-12, -4 and -10) levels in offspring was performed to evaluate the effect on their immune system. The results revealed that compared with the control group, offspring in the Ba group displayed significantly decreased stool colony counts of Enterococcus spp. (t=3.123, P<0.01) at PD14 and significantly decreased counts of Enterobacter spp. at PD14 and -21 (t=2.563, P<0.05 and t=2.292, P<0.05, respectively). Compared with the control group, the stool colony counts of Bifidobacterium spp. and Lactobacillus spp. were significantly increased in the Ba group at PD21 (t=3.085, P<0.01 and t=2.8508, P<0.05, respectively). The Ab group had significantly higher stool colony counts of Bifidobacterium spp. and Lactobacillus spp. at PD28, compared with the control group (Q=7.679, P<0.01 and Q=6.149, P<0.01, respectively). There were no significant differences identified in the sIgA levels of the intestinal fluid and serum cytokine levels between the control group and the intervention groups. In conclusion, Clostridium butyricum administered to breast-feeding maternal mice was able to regulate the intestinal flora balance in their offspring. However, due to insignificant effects on sIgA level and the associated cytokines, Clostridium butyricum had a limited influence on the balance of type 1 vs. type 2 T-helper cells. However, using Clostridium butyricum as an invention may be a safe method for improving the balance of intestinal flora and associated processes in offspring.

20.
Nature ; 526(7575): 696-9, 2015 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-26466566

RESUMO

The hominin record from southern Asia for the early Late Pleistocene epoch is scarce. Well-dated and well-preserved fossils older than ∼45,000 years that can be unequivocally attributed to Homo sapiens are lacking. Here we present evidence from the newly excavated Fuyan Cave in Daoxian (southern China). This site has provided 47 human teeth dated to more than 80,000 years old, and with an inferred maximum age of 120,000 years. The morphological and metric assessment of this sample supports its unequivocal assignment to H. sapiens. The Daoxian sample is more derived than any other anatomically modern humans, resembling middle-to-late Late Pleistocene specimens and even contemporary humans. Our study shows that fully modern morphologies were present in southern China 30,000-70,000 years earlier than in the Levant and Europe. Our data fill a chronological and geographical gap that is relevant for understanding when H. sapiens first appeared in southern Asia. The Daoxian teeth also support the hypothesis that during the same period, southern China was inhabited by more derived populations than central and northern China. This evidence is important for the study of dispersal routes of modern humans. Finally, our results are relevant to exploring the reasons for the relatively late entry of H. sapiens into Europe. Some studies have investigated how the competition with H. sapiens may have caused Neanderthals' extinction (see ref. 8 and references therein). Notably, although fully modern humans were already present in southern China at least as early as ∼80,000 years ago, there is no evidence that they entered Europe before ∼45,000 years ago. This could indicate that H. neanderthalensis was indeed an additional ecological barrier for modern humans, who could only enter Europe when the demise of Neanderthals had already started.


Assuntos
Fósseis , Migração Humana/história , Dente/anatomia & histologia , Animais , Cavernas , China , Europa (Continente) , História Antiga , Humanos , Homem de Neandertal , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...