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Optical path length (OPL) noise resulting from stray light significantly constrains interferometry displacement measurements in the low-frequency band. This paper presents an analytical model considering the presence of stray light in heterodyne laser interferometers. Due to the cyclic nonlinear coupling effect, there will be some special OPLs of stray light, minimizing the frequency-mixing impact to zero. Consequently, we propose a noise suppression scheme that locks the OPL of stray light at the zero coupling point. Therefore, we significantly enhanced the interference displacement measurement noise within the low-frequency band. Experimental results show that the interferometer achieves a displacement noise level lower than 6 pm/Hz1/2 covering 1 mHz.
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A novel photoredox-catalyzed direct hydroacylation of benzylidenemalononitriles is described. In this method, aroyl chlorides are employed as a readily available and affordable source of acyl groups, while commercially available tris(trimethylsilyl)silane acts as both the hydrogen atom donor and electron donor. By eliminating the requirement for complex synthesis of acyl precursors and hydrogen atom-transfer (HAT) reagents, this approach offers a convenient and efficient strategy for the hydroacylation of benzylidenemalononitriles.
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OBJECTIVES: We determined the common clinical characteristics of patients infected with Helicobacter pylori (H. pylori) and investigated the relationship between H. pylori infection, and clinical symptoms, and gastroscopic manifestations. Our focus was specifically on the clinical manifestations in asymptomatic patients. METHODS: We obtained the physical examination data of patients who underwent the 14C urea breath test between January 2018 and December 2020 at our Hospital. Basic demographic data, questionnaire data on clinical symptoms, and clinical examination data of the patients were also collected, and the correlation analysis was performed. RESULTS: A total of 2863 participants were included in the study. The overall H. pylori infection rate was 26.30%. The clinical symptoms between H. pylori-positive patients and H. pylori-negative patients did not differ significantly (P > .05). However, H. pylori-positive patients exhibited more severe gastroscopic manifestations (P < .001). The 14C urea breath test disintegrations per minute (DPM) values in H. pylori-positive patients correlated with their serum pepsinogen and gastrin-17 levels. With an increase in the DPM value, more combinations of clinical symptoms appeared in the patients. Among H. pylori-positive patients, DPM levels in asymptomatic patients were lower than those in symptomatic patients (P < .001). However, gastroscopic manifestations did not vary significantly between asymptomatic and symptomatic patients (P > .05). CONCLUSION: Patients infected with H. pylori showed no specific gastrointestinal symptoms. Patients with asymptomatic infection showed lower DPM levels, but their gastroscopic manifestations were similar to those of patients with symptomatic infection, and their lesions were more severe than H. pylori-negative people.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones Asintomáticas/epidemiología , Urea/análisis , Gastroscopía , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Radioisótopos de CarbonoRESUMEN
Extracellular vesicles (EVs) are lipid-bilayer particles secreted from cells that primarily assist in cell-to-cell communication through the content of their cargo, such as proteins and RNA. EVs have been implicated in the pathogenesis of various autoimmune diseases, including dermatomyositis (DM), an inflammatory autoimmune disease characterized by distinct cutaneous manifestations, myopathy, and lung disease. We sought to review the role of EVs in DM and understand how they contribute to the pathogenesis and clinical characterization of the disease. We summarized the research progress on EVs in dermatomyositis based on recent publications. EV cargoes, such as double-stranded DNA, microRNA, and proteins, contribute to DM pathogenesis and mediate the proinflammatory response and cytokine release through signaling pathways such as the stimulator of interferon genes (STING) pathway. These nucleic acids and proteins have been proposed as disease-specific, stable biomarkers to monitor disease activity and responses to therapy. They also correlate with clinical parameters, inflammatory markers, and disease severity scores. Furthermore, some markers show an association with morbidities of DM, such as muscle weakness and interstitial lung disease. The continued study of EVs will help us to further elucidate our understanding of dermatomyositis.
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Dermatomiositis , Exosomas , Vesículas Extracelulares , Enfermedades Pulmonares Intersticiales , MicroARNs , Ácidos Nucleicos , Humanos , Dermatomiositis/diagnóstico , Dermatomiositis/terapia , Dermatomiositis/metabolismo , Vesículas Extracelulares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/terapia , Ácidos Nucleicos/metabolismo , Proteínas/metabolismo , Exosomas/metabolismoRESUMEN
OBJECTIVE: To perform a systematic review of the literature exploring magnetic resonance imaging (MRI) methods for measuring natural brain tissue pulsations (BTPs) in humans. METHODS: A prospective systematic search of MEDLINE, SCOPUS and OpenGrey databases was conducted by two independent reviewers using a pre-determined strategy. The search focused on identifying reported measurements of naturally occurring BTP motion in humans. Studies involving non-human participants, MRI in combination with other modalities, MRI during invasive procedures and MRI studies involving externally applied tests were excluded. Data from the retrieved records were combined to create Forest plots comparing brain tissue displacement between Chiari-malformation type 1 (CM-I) patients and healthy controls using an independent samples t-test. RESULTS: The search retrieved 22 eligible articles. Articles described 5 main MRI techniques for visualisation or quantification of intrinsic brain motion. MRI techniques generally agreed that the amplitude of BTPs varies regionally from 0.04 mm to ~ 0.80 mm, with larger tissue displacements occurring closer to the centre and base of the brain compared to peripheral regions. Studies of brain pathology using MRI BTP measurements are currently limited to tumour characterisation, idiopathic intracranial hypertension (IIH), and CM-I. A pooled analysis confirmed that displacement of tissue in the cerebellar tonsillar region of CM-I patients was + 0.31 mm [95% CI 0.23, 0.38, p < 0.0001] higher than in healthy controls. DISCUSSION: MRI techniques used for measurements of brain motion are at an early stage of development with high heterogeneity across the methods used. Further work is required to provide normative data to support systematic BTPs characterisation in health and disease.
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Encéfalo , Imagen por Resonancia Magnética , Humanos , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Frecuencia Cardíaca , Movimiento (Física)RESUMEN
Chloroquine phosphate (CQP) has been suggested as an important and effective clinical reliever medication for the 2019 coronavirus (COVID-19). Nevertheless, its excessive use will inevitably cause irreparable damage to the entire ecosystem, thereby posing a considerable environmental safety concern. Hence, the development of highly-efficient methods of removing CQP from water pollution sources, e.g., effluents from hospitals and pharmaceutical factories is significant. This study reported the fabrication of novel C-N bond linked conjugated microporous polymers (CMPs) (BPT-DMB-CMP) with multiple nitrogen-rich anchoring sites for the quick and efficient removal of CQP from aqueous solutions. The irreversible covalent C-N bond linked in the internal framework of BPT-DMB-CMP endowed it with good chemical stability and excellent adsorbent regeneration. With its predesigned functional groups (i.e., rich N-H bonds, triazine rings, and benzene rings) and large area surface (1,019.89 m2·g-1), BPT-DMB-CMP demonstrated rapid adsorption kinetics (25 min) and an extraordinary adsorption capacity (334.70 mg·g-1) for CQP, which is relatively higher than that of other adsorbents. The adsorption behavior of CQP on BPT-DMB-CMP corresponded with Liu model and mixed-order model. Based on the density functional theory (DFT) calculations, X-ray photoelectron spectroscopy (XPS), and adsorption comparisons test, the halogen bonding, and hydrogen bonding cooperates with π - π, C - H···π interactions and size-matching effect in the CQP adsorption system on BPT-DMB-CMP. The excellent practicability for the removal of CQP from real wastewater samples verified the prospect of practical application of BPT-DMB-CMP. BPT-DMB-CMP exhibited the application potentials for the adsorption of other antiviral drugs. This work opens up an efficient, simple, and high adsorption capacity way for removal CQP.
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Lychnophora pinaster, known as arnica-mineira, is endemic to campos rupestres, at risk of extinction. The present study aimed to characterize the ecogeography and phenolic constituents of 11 L. pinaster populations collected in the mesoregions North, Jequitinhonha, Metropolitan of Belo Horizonte and Campos das Vertentes in the state of Minas Gerais, Brazil. Phenolic constituents were identified and quantified by Ultra-high performance liquid chromatography- mass spectrometry. Lychnophora pinaster occurs in sites at high altitude (700 and 1498 m), annual rainfall of up to 1455 m, soils with low fertility and predominantly loamy texture. Therefore, it can be considered tolerant to acidic soils, with low availability of nutrient. The most abundant substances in all populations were vitexin (18 - 1345 ng/g) and chlorogenic acid (60 - 767 ng/g). The 11 populations formed four groups in relation to the phenolic constituents, with group 1 consisting of the populations of the North Mesoregion (GM, OD) and Jetiquinhonha (DIMa), group 2, the Metropolitan of Belo Horizonte (SRM, NLSC, SM, RPS, CTRA), group 3, the North Mesoregion (ODMa and DI), and group 4, the Campos das Vertentes (CC). Among the populations, only those from the Metropolitan of Belo Horizonte showed correlation of soil properties with phenolic constituents.
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Arnica , Asteraceae , Brasil/epidemiología , Extractos Vegetales , SueloRESUMEN
The nuclear lamina is essential for the structural integration of the nuclear envelope. Nuclear envelope rupture and chromatin externalization is a hallmark of the formation of neutrophil extracellular traps (NETs). NET release was described as a cellular lysis process; however, this notion has been questioned recently. Here, we report that during NET formation, nuclear lamin B is not fragmented by destructive proteolysis, but rather disassembled into intact full-length molecules. Furthermore, we demonstrate that nuclear translocation of PKCα, which serves as the kinase to induce lamin B phosphorylation and disassembly, results in nuclear envelope rupture. Decreasing lamin B phosphorylation by PKCα inhibition, genetic deletion, or by mutating the PKCα consensus sites on lamin B attenuates extracellular trap formation. In addition, strengthening the nuclear envelope by lamin B overexpression attenuates NET release in vivo and reduces levels of NET-associated inflammatory cytokines in UVB-irradiated skin of lamin B transgenic mice. Our findings advance the mechanistic understanding of NET formation by showing that PKCα-mediated lamin B phosphorylation drives nuclear envelope rupture for chromatin release in neutrophils.
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Lamina Tipo B , Membrana Nuclear , Animales , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Lamina Tipo B/genética , Lamina Tipo B/metabolismo , Ratones , Membrana Nuclear/metabolismo , Lámina Nuclear/metabolismo , Fosforilación , Proteína Quinasa C-alfa/genética , Proteína Quinasa C-alfa/metabolismoRESUMEN
In idiopathic (primary) membranous glomerulopathy (MGN), there is a phenomenon of subepithelial deposits (stages 1 and 2) transitioned to intramembranous deposits, with lucent resolving features (stages 3 and 4). This phenomenon has not been described in other types of immune complex mediated glomerulonephritis with either subendothelial or mesangial deposits. The goal of this study was to evaluate what unique immunostaining pattern could occur in primary MGNs with intramembranous resolving features. PLA2R and IgG4 immunostains were performed in 50 primary MGNs, and 39 secondary MGNs after the clinical history was reviewed. Primary MGNs with resolving features were further evaluated in detail. A total of 84% (42/50) of primary MGN cases had diffuse positive immunostaining for IgG4 in the glomeruli, and most of them were also positive for PLA2R staining. Eight of the remaining primary MGN cases (8/50) with positive PLA2R but negative IgG4 staining in the glomeruli had diffuse resolving features as observed by electron microscopy. All secondary MGNs were stained negatively for both IgG4 and PLA2R except for one case with positive IgG4 staining but negative staining for PLA2R. Our data indicate that IgG4 staining on paraffin tissue is a very reliable screening tool to confirm the presence of primary MGN. Primary MGN with PLA2R+/IgG4- stains were seen in those with intramembranous resolving features. This finding is consistent with the known weak-binding capacity of IgG4 to the glomerular basement membranes. The transitional phenomenon from PLA2R+/IgG4+ subepithelial deposits to PLA2R+/IgG4- intramembranous resolving deposits in primary MGN implies that there may be a continuous metabolic activity from podocyte to glomerular basement membrane.
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Glomerulonefritis Membranosa , Glomerulonefritis , Epitelio , Membrana Basal Glomerular , Humanos , Redes y Vías MetabólicasRESUMEN
BACKGROUND/PURPOSE: Previously we had identified concurrent genes, which highlighted the interplay between copy number variation (CNV) and differential gene expression (GE) for Han Chinese breast cancers. The merit of the approach is to discovery biomarkers not identifiable by conventional GE only data, for which phenotype-correlation or gene variability is the criteria of gene selection. MATERIALS AND METHODS: Thirty-one comparative genomic hybridization (CGH) and 83 GE microarrays were performed, with 29 breast cancers assayed from both platforms. Potential targets were revealed by Genomic Identification of Significant Targets in Cancer (GISTIC) from CGH arrays. Concurrent genes and genes with significant GISTIC scores were used to derive the extended concurrent genes signature, which was consensus from leading edge analysis across all studies and a supervised partial least square (PLS) regression predictive model of disease-free survival was constructed. RESULTS: There were 1584 concurrent genes from 29 samples with both CGH and GE microarrays. Enriched concurrent genes sets for disease-free survival were identified independently from 83 GE arrays and another one with Han Chinese origin as well as three studies of Western origin. For five studies with disease-free survival follow up, prognostic discrepancy was observed between predicted high-risk and low-risk group patients. CONCLUSION: We concluded that through parallel analyses of CGH and GE microarrays, the proposed extended concurrent gene expression signature can identify biomarkers with prognostic values.
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Variaciones en el Número de Copia de ADN , Neoplasias , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Hibridación Genómica Comparativa , Supervivencia sin Enfermedad , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , PronósticoRESUMEN
The kidney is a complicated and important internal organ receiving approximately 20% of the cardiac output and mediates numerous pathophysiologic actions. These include selectively filtering macromolecules of the blood, exquisite reclaimation of electrolyctes, urine concentration via an elegant osmotic mechanism, and excretion of an acid load. In addition, the renal tubules carry out secretory functions and produce hormones and cytokines. The kidney receives innervation and hormonal regulation. Therefore, dysfunction of the kidney leads to retention of metabolic waste products, and/or significant proteinuria and hematuria. In the past several decades, the role of extracellular vesicles (EVs) in intercellular communications, and the uptake of EVs by recipient cells through phagocytosis and endocytosis have been elucidated. The new knowledge on EVs expands over the classical mechanisms of cellular interaction, and may change our way of thinking of renal pathophysiology in the subcellular scale. Based on some ultrastructural discoveries in the kidney, this review will focus on the role of EVs in intercellular communications, their internalization by recipient cells, and their relationship to renal pathology.
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Comunicación Celular/fisiología , Vesículas Extracelulares/metabolismo , Túbulos Renales/patología , Riñón/patología , Citocinas/metabolismo , Humanos , Riñón/metabolismo , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Túbulos Renales/metabolismoRESUMEN
BACKGROUND: To compare the efficacy of three different fixation methods of fibula combined with external fixation of tibia for the treatment of extra-articular open fractures of distal tibia and fibula. METHODS: From January 2017 to July 2019, 91 cases of open fractures of distal tibia and fibula were treated with external fixator, and the fibula was fixed with non-fixation (group A, n = 35), plate-screw (group B, n = 30) and Kirschner wire (group C, n = 26). The operation time, intraoperative blood loss, surgical and implants costs, fracture healing time, postoperative complications, and American Orthopaedic Foot and Ankle surgery (AOFAS) scores were compared among the groups. RESULTS: Four patients were lost to follow-up, and 87 patients were followed up for 5-35 months (average, 14.2 months). The operation time of group C (114.92 ± 36.09 min) was shorter than that of group A (142.27 ± 47.05 min) and group B (184.00 ± 48.56 min) (P < 0.05). There was no difference in intraoperative blood loss among the three groups (P > 0.05). The surgical and implants costs in group C (5.24 ± 1.21, thousand dollars) is lower than that in group A (6.48 ± 1.11, thousand dollars) and group B (9.37 ± 2.16, thousand dollars) (P < 0.05). The fracture healing time of group C (5.67 ± 1.42 months) was significantly less than that of group A (6.90 ± 1.33 months) and group B (6.70 ± 1.12 months) (P < 0.05). The postoperative complications such as fractures delayed union and nonunion in group C (2 cases, 8.00%) is less than that in group A (13 cases, 39.39%) and group B (11cases, 37.93%) (P < 0.05). The wound infection and needle-tract infection did not differ among the three groups (P > 0.05). The excellent or good rate of ankle function was 69.70% in group A, 72.41% in group B and 84.00% in group C, with no statistical difference among the three groups (P > 0.05). CONCLUSION: Compared with simple external fixator fixation and external fixator combined with plate-screw osteosynthesis, external fixator combined with K-wire intramedullary fixation shortens the operative time and fracture healing time, reduced costs and complications of fracture healing, while the blood loss, infection complications and ankle function recovery showed no difference with the other two groups. External fixator combined with plate-screw osteosynthesis had no advantage in treating extra-articular open fractures of distal tibia and fibula when compared with simple external fixation.
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Fracturas Abiertas , Fracturas de la Tibia , Fijadores Externos , Peroné/diagnóstico por imagen , Peroné/cirugía , Fijación Interna de Fracturas , Curación de Fractura , Fracturas Abiertas/diagnóstico por imagen , Fracturas Abiertas/cirugía , Humanos , Estudios Retrospectivos , Tibia , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/cirugía , Resultado del TratamientoRESUMEN
Objectives: Long-term volunteering has been associated with better physical, mental, and cognitive health in correlational studies. Few studies, however, have examined the longitudinal benefits of volunteering with randomized experimental designs (e.g., intervention studies). Even fewer studies have examined whether such benefits can be shown after short-term volunteering. To fill this gap, we conducted four 1-hour volunteering intervention sessions to promote volunteering among a group of older adults with limited volunteering experience and examined the impact of volunteering on depressive symptoms, meaning in life, general self-efficacy, and perceived autonomy.Methods: A total of 384 participants aged 50-96 years were assigned at random to either an intervention group to promote volunteering behaviors or an active control group to promote physical activity. The participants' monthly volunteering minutes, depressive symptoms, meaning in life, general self-efficacy and perceived autonomy were measured at baseline and six weeks, three months, and six months after the intervention.Results: Being in the volunteering intervention condition was not directly associated with depressive symptoms, meaning in life, general self-efficacy, or perceived autonomy at the 6-week, 3-month, or 6-month follow-ups after the intervention. However, there was an indirect effect of the intervention on depressive symptoms: participants in the intervention group, who had increased their volunteering at the 3-month follow-up, reported fewer depressive symptoms at the 6-month follow-up.Discussion: Our randomized controlled trial suggests that short-term volunteering does not reliably lead to short-term changes in psychosocial health measures as correlational studies would suggest. Efforts need to be made to encourage older adults to maintain long-term volunteering.
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Autoeficacia , Voluntarios , Adulto , Anciano , Ejercicio Físico , Humanos , Proyectos de InvestigaciónRESUMEN
Recently, Toll-like receptors (TLRs), a family of pattern recognition receptors, are reported as potential modulators for neuropathic pain; however, the desired mechanism is still unexplained. Here, we operated on the sciatic nerve to establish a pre-clinical rodent model of chronic constriction injury (CCI) in Sprague-Dawley rats, which were assigned into CCI and Decompression groups randomly. In Decompression group, the rats were performed with nerve decompression at post-operative week 4. Mechanical hyperalgesia and mechanical allodynia were obviously attenuated after a month. Toll-like receptor 5 (TLR5)-immunoreactive (ir) expression increased in dorsal horn, particularly in the inner part of lamina II. Additionally, substance P (SP) and isolectin B4 (IB4)-ir expressions, rather than calcitonin-gene-related peptide (CGRP)-ir expression, increased in their distinct laminae. Double immunofluorescence proved that increased TLR5-ir expression was co-expressed mainly with IB4-ir expression. Through an intrathecal administration with FLA-ST Ultrapure (a TLR5 agonist, purified flagellin from Salmonella Typhimurium, only the CCI-induced mechanical hyperalgesia was attenuated dose-dependently. Moreover, we confirmed that mu-opioid receptor (MOR) and phospho-protein kinase Cα (pPKCα)-ir expressions but not phospho-protein kinase A RII (pPKA RII)-ir expression, increased in lamina II, where they mostly co-expressed with IB4-ir expression. Go 6976, a potent protein kinase C inhibitor, effectively reversed the FLA-ST Ultrapure- or DAMGO-mediated attenuated trend towards mechanical hyperalgesia by an intrathecal administration in CCI rats. In summary, our current findings suggest that nerve decompression improves CCI-induced mechanical hyperalgesia that might be through the cross-talk of TLR5 and MOR in a PKCα-dependent manner, which opens a novel opportunity for the development of analgesic therapeutics in neuropathic pain.
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Hiperalgesia/metabolismo , Proteína Quinasa C-alfa/metabolismo , Receptores Opioides mu/metabolismo , Receptor Toll-Like 5/metabolismo , Animales , Constricción , Activación Enzimática , Hiperalgesia/etiología , Hiperalgesia/fisiopatología , Masculino , Dimensión del Dolor/métodos , Ratas Sprague-Dawley , Receptor Cross-Talk , Nervio Ciático/fisiopatología , Transducción de Señal , Asta Dorsal de la Médula Espinal/metabolismoRESUMEN
The forkhead box A1 (FOXA1), one of the forkhead class of DNA-binding proteins, functions as a transcription factor and plays a vital role in cellular control of embryonic development and cancer progression. Downregulation of FOXA1 has reported in several types of cancer, which contributes to cancer cell survival and chemoresistance. However, the mechanism for FOXA1 downregulation in cancer remains unclear. Here, we report that the ubiquitination enzyme zinc finger protein 91 (ZFP91) ubiquitinates and destabilizes FOXA1, which promotes cancer cell growth. High level of ZFP91 expression correlates with low level of FOXA1 protein in human gastric cancer (GC) cell lines and patient samples. Furthermore, ZFP91 knockdown reduces FOXA1 polyubiquitination, which decreases FOXA1 turnover and enhances cellular sensitivity to chemotherapy. Taken together, our findings reveal ZFP91-FOXA1 axis plays an important role in promoting GC progression and provides us a potential therapeutic intervention in the treatment of GC.
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Resistencia a Antineoplásicos/genética , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Regulación hacia Abajo , Femenino , Mucosa Gástrica/patología , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Estabilidad Proteica , Proteolisis , ARN Interferente Pequeño/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation in process of FX activation by FIXa, for which deficiency results in the bleeding disorder hemophilia A. The gene of FVIII contains 26 exons that code for a 19 amino acid signal peptide and a 2332 amino acid polypeptide with a domain structure designated A1-A2-B-A3-C1-C2, of which the A domains are homologous with each other, as are the C domains. It has been well-documented that both the domains are the necessary elements for FVIII activities. The B domain is highly glycosylated and has a variable sequence, even among FVIIIs from different species. The B domain plays versatile roles in FVIII lifespan except for coagulation activity, but the functional characteristics of its specific regions remain still obscure. A series of recombinant FVIIIs (rFVIIIs) with B domain truncated were constructed and transiently expressed in hepatocyte cells. Media and cell lysates were collected after 72 h for the analyses of FVIII biosynthesis, secretion, activity and stability in ex vivo plasma relative to the full length wild-type FVIII. Unexpectedly, various regions in B domain exhibited different contribution to these functionalities. The discovery might facilitate the bioengineered rFVIIIs and gene therapeutics.
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Factor VIII/metabolismo , Hepatocitos/metabolismo , Línea Celular , Exones , Factor VIII/química , Factor VIII/genética , Humanos , Mutación , Dominios Proteicos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
Lupus nephritis (LN) is a major cause for overall morbidity and mortality in patients with systemic lupus erythematosus (SLE), while its pathogenic mechanisms are still not well understood. Extracellular vesicles (EVs) are membrane vesicles that are released from almost all cell types. EVs can be subdivided into exosomes, microvesicles, and apoptotic bodies. Latest studies have shown that EVs can be released during several cellular events, including cell activation, autophagy, and several types of programed cell death, i.e. apoptosis, necroptosis, pyroptosis, and NETosis. Emerging evidence demonstrates that EVs harbor different bioactive molecules, including nucleic acids, proteins, lipids, cytokines, immune complexes (ICs), complements, and other molecules, some of which may contribute to pathogenesis of autoimmune diseases. EVs can serve as novel information shuttle to mediate local autocrine or paracrine signals to nearby cells, and distant endocrine signals to cells located far away. In LN, EVs may have pathogenic effects by transportation of autoantigens or complements, promotion of IC deposition or complement activation, and stimulation of inflammatory responses, renal tissue injury, or microthrombus formation. Additionally, EVs released from kidney cells may serve as specific biomarkers for diagnosis or monitoring of disease activity and therapeutic efficacy. In this review, we will summarize the latest progress about EV generation from basic research, their potential pathologic effects on LN, and their clinical implications. The cutting-edge knowledge about EV research provides insights into novel therapeutic strategy, new tools for diagnosis or prognosis, and evaluation approaches for treatment effectiveness in LN.
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Vesículas Extracelulares/inmunología , Riñón/patología , Nefritis Lúpica/inmunología , Comunicación Autocrina/inmunología , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Riñón/citología , Riñón/inmunología , Nefritis Lúpica/sangre , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/patología , Comunicación Paracrina/inmunología , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Objective- This study aims to determine whether and how the enriched metabolites of endothelial extracellular vesicles (eEVs) are critical for cigarette smoke-induced direct injury of endothelial cells and the development of pulmonary hypertension, rarely explored in contrast to long-investigated mechanisms secondary to chronic hypoxemia. Approach and Results- Metabonomic screen of eEVs from cigarette-smoking human subjects reveals prominent elevation of spermine-a polyamine metabolite with potent agonist activity for the extracellular CaSR (calcium-sensing receptor). CaSR inhibition with the negative allosteric modulator Calhex231 or CaSR knockdown attenuates cigarette smoke-induced pulmonary hypertension in rats without emphysematous changes in lungs or chronic hypoxemia. Cigarette smoke exposure increases the generation of spermine-positive eEVs and their spermine content. Immunocytochemical staining and immunogold electron microscopy recognize the spermine enrichment not only within the cytosol but also on the outer surface of eEV membrane. The repression of spermine synthesis, the inhibitory analog of spermine, N1-dansyl-spermine, Calhex231, or CaSR knockdown profoundly suppresses eEV exposure-mobilized cytosolic calcium signaling, pulmonary artery constriction, and smooth muscle cell proliferation. Confocal imaging of immunohistochemical staining demonstrates the migration of spermine-positive eEVs from endothelium into smooth muscle cells in pulmonary arteries of cigarette smoke-exposed rats. The repression of spermine synthesis or CaSR knockout results in attenuated development of pulmonary hypertension induced by an intravascular administration of eEVs. Conclusions- Cigarette smoke enhances eEV generation with spermine enrichment at their outer surface and cytosol, which activates CaSR and subsequently causes smooth muscle cell constriction and proliferation, therefore, directly leading to the development of pulmonary hypertension.
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Células Endoteliales/metabolismo , Vesículas Extracelulares/fisiología , Hipertensión Pulmonar/prevención & control , Receptores Sensibles al Calcio/fisiología , Espermina/fisiología , Contaminación por Humo de Tabaco/efectos adversos , Fumar Tabaco/efectos adversos , Animales , Benzamidas/farmacología , Transporte Biológico , Calcio/fisiología , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Ciclohexilaminas/farmacología , Endotelio Vascular/metabolismo , Vesículas Extracelulares/química , Técnicas de Silenciamiento del Gen , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/fisiopatología , Masculino , Miocitos del Músculo Liso/metabolismo , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Sensibles al Calcio/antagonistas & inhibidores , Receptores Sensibles al Calcio/deficiencia , Receptores Sensibles al Calcio/genética , Espermina/biosíntesisRESUMEN
BACKGROUND: Volunteering could be a win-win opportunity for older adults: Links between volunteering and societal improvements as well as older adults' own health and longevity are found in several observational studies. RCTs to increase volunteering in older adults are however sparse, leaving the question of causality unanswered. This study protocol describes a theory-based social-cognitive intervention with multiple behavior change techniques to increase volunteering among community-dwelling older adults in Hong Kong. METHODS: In a parallel group, two-arm, randomized controlled trial, an initial N = 360 are assigned to receive either the volunteering intervention or the active control intervention (parallel content targeting physical activity). The primarily outcome measure is self-reported volunteering minutes per month at baseline, six weeks, three months and six months after the intervention. Participants in the treatment group are expected to increase their weekly volunteering minutes over time as compared to participants in the control group. Possible active ingredients of the intervention as well as mental and physical health outcomes of increased volunteering are investigated by means of mediation analyses. DISCUSSION: Like many industrialized nations, Hong Kong faces a rapid demographic change. An effective psychological intervention to encourage retirees to engage in formal volunteering would alleviate some of the societal challenges a growing proportion of older adults entails. TRIAL REGISTRATION: Primary Registry and Trial Identifying Number ChiCTR-IIC-17010349 , secondary CCRB trial number CUHK_CCRB00543, registration date 2016/12/28.
Asunto(s)
Cognición , Autoeficacia , Conducta Social , Voluntarios/psicología , Anciano , Cognición/fisiología , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
A magnetic covalent organic framework (Fe3O4@COF) with core-shell structure was fabricated at room temperature and used as an adsorbent for magnetic solid-phase extraction of polar endocrine-disrupting phenols (4-n-nonylphenol, 4-n-octylphenol, bisphenol A and bisphenol AF). The sorbent was characterized by transmission electron microscopy, FTIR, powder X-ray diffraction and other techniques. The main parameters governing the extraction efficiency were optimized. The phenols were quantified by HPLC with fluorometric detection. The method has attractive features such as low limits of detection (0.08-0.21 ng.mL-1), wide linear ranges (0.5-1000 ng.mL-1), and good repeatability (intra-day: 0.39%-4.99%; inter-day: 1.57%-5.21%). Satisfactory results were obtained when the developed method was applied to determine the four target pollutants in real world drink samples with spiked recoveries over the range of 81.3~118.0%. This indicates that the method is a powerful tool for the enrichment and determination of endocrine-disrupting phenols in drink samples. Graphical abstract A magnetite based covalent organic framework (Fe3O4@COFs) was synthesized with TPAB, TPA and Fe3O4. It was used for magnetic solid-phase extraction of endocrine-disrupting phenols from plastic-packaged tea drink samples coupled with liquid chromatography (LC) for determination.