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Thermal quenching (TQ) is still a critical challenge for lanthanide (Ln3+)-doped luminescent materials. Herein, we report the novel negative thermal expansion nonhygroscopic phosphor ZrSc(WO4)2PO4:Yb3+/Er3+. Upon excitation with a 980 nm laser, a simultaneous thermal enhancement is realized on upconversion (UC) and downshifting (DS) emissions from room temperature to 573 K. In situ temperature-dependent X-ray diffraction and photoluminescence dynamics are used to reveal the luminescence mechanism in detail. The coexistence of the high energy transfer efficiency and the promoted radiative transition probability can be responsible for the thermally enhanced luminescence. On the basis of the luminescence intensity ratio of thermally coupled energy levels 2H11/2 and 4S3/2 at different temperatures, the relative and absolute sensitivities of the targeted samples reach 1.10% K-1 and 1.21% K-1, respectively, and the low-temperature uncertainty is approximately 0.1-0.4 K on the whole temperature with a high repeatability (98%). Our findings highlight a general approach for designing a hygro-stable, thermostable, and highly efficient Ln3+-doped phosphor with UC and DS luminescence.
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AIMS: Bidirectional and durable block of mitral isthmus (MI) is essential for catheter ablation of persistent atrial fibrillation (PeAF) and perimitral flutter (PMF), but it remains a challenge. The aim of this study was to create a simple anatomical ablation strategy with minimal fluoroscopy that would yield a high success rate for MI block. METHODS AND RESULTS: Patients with PeAF or PMF were included. Mitral isthmus was ablated in a stepwise strategy. In Step 1, endocardial MI linear ablation was performed; in Step 2, ablation was targeted to the posterolateral portion of the left atrium along the MI line; in Step 3, epicardial ablation within the coronary sinus (CS) was performed across the MI line to the ostium of the vein of Marshall (VOM) or performed within the VOM if available; in Step 4, the catheter was rotated and ablated in the CS to isolate the CS; and in Step 5, the early activation site with complex component potential above the MI line during distal CS pacing was considered as the ablation target. All patients were followed up. A total of 178 (17 patients with mechanical prosthetic mitral valve) were included. One hundred and sixty-six patients achieved a confirmed MI bidirectional conduction block (93%). One patient had cardiac tamponade. Four patients showed re-conduction across the MI line during a repeated ablation. In the latest follow-up [12 (7, 16) months], 161 of 178 (90%) patients maintained their sinus rhythm. CONCLUSION: A simple stepwise anatomical ablation strategy for MI shows a high success rate with low fluoroscopy exposure.
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Fibrilación Atrial , Ablación por Catéter , Seno Coronario , Humanos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Frecuencia Cardíaca , Atrios Cardíacos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Resultado del TratamientoRESUMEN
Chromium (Cr), one of the prime hazardous trace elements in coals, may engender adverse effects on eco-environment and threaten human health during utilization of coal. Based on the samples obtained in our laboratory and published literature, the abundance and modes of occurrence of Cr in Chinese coals, and the environmental impacts associated with coal-fired power plants (CFPPs) were elucidated in this study. With a total of 1397 sets of data, the mean concentration of Cr in Chinese coals was calculated as 21.33 µg/g by the "reserve-concentration" weighted calculation method. Spatially, the average Cr contents increased gradually from North China to South China. Temporally, coals from T3, E-N and P2 were relatively enriched in Cr compared to the other geological time. The Cr concentration in coal varied with different coal ranks. The geological factors accounted for Cr enrichment in coals could be divided into the primary, secondary and epigenetic processes. Higher percentages of organically Cr occurred in low-rank coals, while inorganically associated Cr was mainly found in clay minerals. After coal combustion, most of Cr was enriched in solid wastes (e.g., fly ash and bottom ash). The leaching of Cr from solid wastes in the rainy season (especially acid rain) needs to be a concern for CFPPs. It was estimated that the atmospheric emission of Cr from CFPPs increased annually from 2015 to 2019 and reached approximately 159 tons in 2019.
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Cromo , Carbón Mineral , China , Cromo/toxicidad , Carbón Mineral/análisis , Ceniza del Carbón/análisis , Centrales Eléctricas , Residuos SólidosRESUMEN
Galactolipids are characteristic lipids of the photosynthetic membranes. They are highly enriched in the chloroplast and are present in photosystem structures. There are two major types of galactolipids, i.e., monogalactosyldiacylglycerol and digalactosyldiacylglycerol (DGDG) in chloroplastic membranes, which amount to â¼50 and â¼20 mol % of the total chloroplast lipids, respectively. Under phosphate-limiting conditions, the amount of DGDG increases dramatically for rescuing phosphate from phospholipids. In Arabidopsis thaliana, the gene digalactosyldiacylglycerol synthase 2 (DGD2) encodes a membrane-associated glycosyltransferase. The gene expression is highly responsive to phosphate starvation and is significantly upregulated in this case. To understand the molecular mechanism of DGD2, we established a protocol for DGD2 expression and purification in an Escherichia coli-based system. The work involved optimization of the expression condition and the purification protocol and a careful selection of buffer additives. It was found that a removal of around 70 C-terminal residues was necessary to produce a homogeneous monomeric protein sample with high purity, which was highly active. The purified sample was characterized by an activity assay for enzyme kinetics in which a range of membrane mimetics with different lipid compositions were used. The results demonstrate that DGD2 activity is stimulated by the presence of negatively charged lipids, which highlight the importance of the membrane environment in modulating the enzyme's activity. The study also paves way for future biophysical and structural studies of the enzyme.
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Proteínas de Cloroplastos/química , Galactolípidos/síntesis química , Proteínas de la Membrana/química , Secuencia de Aminoácidos , Arabidopsis/química , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/aislamiento & purificación , Proteínas de Cloroplastos/genética , Proteínas de Cloroplastos/aislamiento & purificación , Galactosiltransferasas/química , Galactosiltransferasas/genética , Galactosiltransferasas/aislamiento & purificación , Cinética , Membrana Dobles de Lípidos/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/aislamiento & purificación , Alineación de Secuencia , Eliminación de Secuencia , Liposomas Unilamelares/químicaRESUMEN
Siglec-15 is an immunoreceptor that binds to its ligand to exert diverse functions in osteoclast development, bone resorption, and even tumor-associated macrophage-mediated T cell immunity. Siglec-15 is a highly conserved member of the Siglec family and is constitutively expressed in osteoclasts, macrophages and dendritic cells. The activation domain in Siglec-15 can transmit a positive signal to regulate osteoclastogenesis via the formation of a complex with DAP12. In tumors, Siglec-15 is negatively regulated by IFN-γ, thus influencing effector T cell-mediated antitumor immunity. Importantly, this tumor-associated function of Siglec-15 is similar to that identified for PD-L1/PD-1 in normalization cancer immunotherapy. Cell-directed therapies are increasingly urgent and of clinical interest for their potential for reduced side effects and increased safety. Therefore, targeting Siglec15 might lead to novel discoveries for the clinical treatment of bone and tumor diseases or related diseases.
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Remodelación Ósea , Inmunoglobulinas/inmunología , Proteínas de la Membrana/inmunología , Neoplasias/inmunología , Animales , HumanosRESUMEN
BACKGROUND: Nowadays, microbial infections have caused increasing economic losses in aquaculture industry and deteriorated worldwide environments. Many of these infections are caused by opportunistic pathogens through cell-density mediated quorum sensing (QS). The disruption of QS, known as quorum quenching (QQ), is an effective and promising way to prevent and control pathogens, driving it be the potential bio-control agents. In our previous studies, AHL lactonase AiiK was identified with many characteristics, and constitutive expression vector pELX1 was constructed to express heterologous proteins in Lactobacillus casei MCJΔ1 (L. casei MCJΔ1). In this study, recombinant strain pELCW-aiiK/L. casei MCJΔ1 (LcAiiK) and wild-type Aeromonas hydrophila (A. hydrophila) were co-cultured to test the QQ ability of LcAiiK against A. hydrophila. RESULTS: A cell wall-associated expression vector pELCW for L. casei MCJΔ1 was constructed. Localization assays revealed that the expressed AiiK was anchored at the surface layer of LcAiiK via vector pELCW-aiiK. LcAiiK (OD600 = 0.5) degraded 24.13 µM of C6-HSL at 2 h, 40.99 µM of C6-HSL at 12 h, and 46.63 µM of C6-HSL at 24 h. Over 50% LcAiiK cells maintained the pELCW-aiiK plasmid after 15 generations of cultivation without erythromycin. Furthermore, LcAiiK inhibited the swimming motility, extracellular proteolytic activity, haemolytic activity and biofilm formation of A. hydrophila AH-1 and AH-4. CONCLUSION: The AHL lactonase AiiK is firstly and constitutively expressed at the surface layer of L. casei MCJΔ1. LcAiiK displayed considerable AHL lactonase activity and great QQ abilities against A. hydrophila AH-1 and AH-4 by attenuating their QS processes instead of killing them. Therefore, the LcAiiK can be exploited as an anti-pathogenic drug or a bio-control agent to control the AHL-mediated QS of pathogenic bacteria.
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Aeromonas hydrophila/metabolismo , Hidrolasas de Éster Carboxílico/genética , Lacticaseibacillus casei/genética , Percepción de Quorum , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas , Agentes de Control Biológico , Hidrolasas de Éster Carboxílico/metabolismo , Lacticaseibacillus casei/metabolismoRESUMEN
OBJECTIVE: To observe the clinical effect of priligy (dapoxetine hydrochloride) combined with behavioral therapy and psychological counseling in the treatment of primary premature ejaculation (PPE). METHODS: A total of 202 PPE patients diagnosed from 2017 to 2018 were randomized into a control (n = 100) and an experimental group (n = 102), the former treated with oral priligy at 30 mg 1ï¼3 hours before anticipated sexual activity, and the latter by the same medication combined with 30-minute behavioral therapy and psychological counseling once a month for two times. The therapeutic effects were evaluated according to the Premature Ejaculation Profile (PEP) scores of the patients at 1 and 2 months of treatment. RESULTS: After 1 month of treatment, both groups of the patients showed significant improvement, as compared with the baseline, in the PEP scores on personal distress related to ejaculation (P < 0 05), interpersonal difficulty related to ejaculation (P < 0.05) and satisfaction with sexual intercourse (P < 0.05) but not on perceived control over ejaculation (P > 0.05). At 2 months, however, the patients' scores on all the four PEP items were dramatically improved, even more significantly in the experimental than in the control group, as on perceived control over ejaculation (2.73 ± 0.95 vs 2.22 ± 0.68, P < 0.05), personal distress related to ejaculation (2.97 ± 1.07 vs 2.57 ± 0.69, P < 0.05), interpersonal difficulty related to ejaculation (3.19 ± 1.03 vs 2.77 ± 0.69, P < 0 05) and satisfaction with sexual intercourse (2.85 ± 0.99 vs 2.35 ± 0.63, P < 0.05). There was no statistically significant difference in the incidence rate of adverse events between the experimental and control groups (21.6% vs 20.0%, P > 0.05), and all the symptoms were relieved within 24 hours. CONCLUSIONS: Priligy combined with behavioral therapy and psychological counseling is more effective than priligy alone in improving the sexual function of PPE patients, raise their interest in sexual life and increase the intimacy between the partners, and can even achieve clinical cure in some patients.
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Bencilaminas/uso terapéutico , Terapia Cognitivo-Conductual , Naftalenos/uso terapéutico , Eyaculación Prematura , Psicoterapia , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Humanos , Masculino , Eyaculación Prematura/terapia , Resultado del TratamientoRESUMEN
Our aim was to study the regulatory molecule networks involved in the epithelial-to-mesenchymal transition and thus promoting the early onset of metastasis in triple-negative breast cancer (TNBC). Forty pairs of human TNBC and their adjacent normal breast tissues were analyzed by real-time PCR and immunochemistry to demonstrate the correlation between the miR-205 expression and clinicopathological characteristics. In vitro, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, cell migration, and invasion assay were used to detect the cell growth and invasive ability of TNBC cells after upregulation or downregulation of miR-205 expression. Luciferase reporter assay was used to confirm the potential target directly influenced by miR-205. Our results showed that miR-205 abnormal expression may be involved and associated with the biological traits of TNBC. Ectopic expression of miR-205 not only inhibited cell growth, but also suppressed migration and invasion of mesenchymal-like TNBC cells. In addition, we found that overexpression of miR-205 significantly suppressed HMGB1 by binding its 3'-untranslated region, and that miR-205 was inversely correlated with the expression of HMGB1 and RAGE in cell lines and clinical samples. Our study illustrated that miR-205 was a tumor suppressor in TNBC, which attenuated the viability and the acquisition of the epithelial-to-mesenchymal transition phenotype TNBC cells at least partially exerted through targeting of HMGB1-RAGE signaling pathway.
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Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Proteína HMGB1/metabolismo , MicroARNs/antagonistas & inhibidores , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Antígenos de Neoplasias/genética , Apoptosis , Biomarcadores de Tumor/genética , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Femenino , Proteína HMGB1/genética , Humanos , MicroARNs/genética , Proteínas Quinasas Activadas por Mitógenos/genética , Invasividad Neoplásica , Pronóstico , Transducción de Señal , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Células Tumorales CultivadasAsunto(s)
Resección Endoscópica de la Mucosa , Fundus Gástrico , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Fundus Gástrico/cirugía , Fundus Gástrico/patología , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/instrumentación , Tracción/métodos , Masculino , Femenino , Gastroscopía/métodos , Persona de Mediana EdadRESUMEN
A series of new biochar-supported composite based on the combination of biochar and metallic nanoparticles (NPs) were produced through single-step pyrolysis of FeCl3-Ti(OBu)4 laden agar biomass under NH3 environment. The physiochemical properties of composites were characterized thoroughly. It has found that heating temperature and N-doping through NH3-ambiance pyrolysis significantly influence the visible-light sensitivity and bandgap energy of composites. The catalytic activities of composites were measured by degradation of Methylene Blue (MB) in the presence or absence of H2O2 and visible-light irradiation. Our best catalyst (N-TiO2-Fe3O4-biochar) exhibits rapid and high MB removal competency (99.99%) via synergism of adsorption, photodegradation, and Fenton-like reaction. Continuous production of O2- and OH radicles performs MB degradation and mineralization, confirmed by scavenging experiments and degradation product analysis. The local trap state Ti3+, Fe3O4, and N-carbon of the catalyst acted as active sites. It has suggested that the Ti3+ and N-doped dense carbon layer improve charge separation and shuttle that prolonged photo-Fenton like reaction. Moreover, the catalyst is highly stable, collectible, and recyclable up to 5â¯cycles with high MB degradation efficiency. This work provides a new insight into the synthesis of highly visible-light sensitized biochar-supported photocatalyst through NH3-ambiance pyrolysis of NPs-laden biomass.
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Amoníaco/química , Carbón Orgánico/química , Azul de Metileno/química , Modelos Químicos , Pirólisis , Contaminantes Químicos del Agua/química , Adsorción , Catálisis , Peróxido de Hidrógeno/química , Titanio/químicaRESUMEN
Monotopic glycosyltransferases (GTs) interact with membranes via electrostatic interactions. The N-terminal domain is permanently anchored to the membrane while the membrane interaction of the C-terminal domain is believed to be weaker so that it undergoes a functionally relevant conformational change upon donor or acceptor binding. Here, we studied the applicability of this model to the glycosyltransferase WaaG. WaaG is involved in the synthesis of lipopolysaccharides (LPS) in Gram-negative bacteria and was previously categorized as a monotopic GT. We analyzed the binding of WaaG to membranes by stopped-flow fluorescence and NMR diffusion experiments. We find that electrostatic interactions are required to bind WaaG to membranes while mere hydrophobic interactions are not sufficient. WaaG senses the membrane's surface charge density but there is no preferential binding to specific anionic lipids. However, the binding is weaker than expected for monotopic GTs but similar to peripheral GTs. Therefore, WaaG may be a peripheral GT and this could be of functional relevance in vivo since LPS synthesis occurs only when WaaG is membrane-bound. We could not observe a C-terminal domain movement under our experimental conditions.
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Proteínas de Escherichia coli/metabolismo , Glucosiltransferasas/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Sustitución de Aminoácidos , Catálisis , Difusión , Proteínas de Escherichia coli/genética , Glucosiltransferasas/genética , Membrana Dobles de Lípidos , Modelos Moleculares , Mutación Puntual , Unión Proteica , Conformación Proteica , Dominios Proteicos , Proteínas Recombinantes de Fusión/metabolismo , Electricidad EstáticaRESUMEN
BACKGROUND: The expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients' prognosis and chemoresistance remains unclear. METHODS: The expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA). RESULTS: B7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p < 0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression. CONCLUSIONS: Our data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.
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BACKGROUND: Increasing data has indicated an association between increased soluble B7-H3 (sB7-H3) levels and unfavorable prognosis in patients with malignancies. However, the level of sB7-H3 and its clinical significance in osteosarcoma (OS) are not well known. In this present study, we investigated whether sB7-H3 levels in serum could be as a tool for differential diagnosis of OS patients. METHODS: Peripheral blood samples from healthy controls, benign bone tumors, and OS patients were collected. Levels of sB7-H3 in serum samples were measured by enzyme-linked immunosorbent assays. The correlation between OS-derived sB7-H3 and clinical features was analyzed, and prognostic significance of the sB7-H3 concentrations and tumor expressions of the biomarkers was then evaluated. RESULTS: sB7-H3 concentrations were significantly increased in patients with OS than in osteochondroma patients, bone fibrous dysplasia patients and healthy people (p < 0.05, respectively). Using 60.94 ng/mL as a cutoff value, the sensitivity and specificity of sB7-H3 was to differentiate between OS patients and other bone benign tumor patients were 75.7% and 83.8%, respectively. In addition, upregulated serum sB7-H3 in patients with OS associated with tumor differentiation, tumor stage, and metastasis status (p < 0.05, respectively). The area under the curve value for sB7-H3 (0.868) was markedly higher than those for ALP (0.713) and CA125 (0.789) for differentiating between OS patients and other begin bone tumor patients. CONCLUSIONS: We demonstrated that enhanced sB7-H3 levels correlated with the clinical characteristics of OS patients, and B7-H3 might be a potential biomarker and associated with the pathogenesis of OS.
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Our previous studies have shown that the expression level of B7 homolog 3 (B7-H3) was correlated with clinical staging and prognosis of osteosarcoma (OS) patients, and its silencing inhibited the proliferation and invasion of OS cells in vitro. However, its overexpression mechanism behind was far from elucidated. On the basis of bioinformatics and the preliminary screening data, we hypothesized that miR-124 might play an important role in OS development and as a lead candidate for modulating B7-H3 expression. In this study, we found that miR-124 was downregulated significantly in OS tumor tissue, compared to normal adjacent tissues (NATs). Lower miR-124 expression levels were associated with advanced Ennecking stage, lower tumor differentiation, and common pulmonary metastasis. The 5-year overall survival rate in the miR-124 upregulated group was 61.5 %, while with low miR-124 expression, only 11.8 % survived. Further studies in vitro showed that B7-H3 was a direct target of miR-124. Overexpression of miR-124 decreased B7-H3 mRNA and protein level and inhibited B7-H3 3'-UTR reporter activity. Treatment of OS cells with miR-124 mimics induced the inhibition of cell growth and invasion in vitro, which could be abrogated by transfected by B7-H3 expression vector. Our findings highlight the potential application of miR-124 as a novel onco-miRNA in OS, and its oncogenic effects are mediated chiefly through downregulation of B7-H3, thus suggesting a model for identifying miR-124 that can be exploited to improve the therapeutic potential efficacy of mAb targeting to B7-H3.
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Antígenos B7/biosíntesis , Neoplasias Óseas/patología , Movimiento Celular/genética , Proliferación Celular/genética , MicroARNs/genética , Osteosarcoma/patología , Adulto , Antígenos B7/genética , Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/secundario , Masculino , Invasividad Neoplásica/genética , Oncogenes/genética , Osteosarcoma/genética , Osteosarcoma/mortalidad , Adulto JovenRESUMEN
BACKGROUND: B7-homologue 3 (B7-H3), a recently identified immunoregulatory protein, has been shown to be overexpressed in human hepatocellular carcinoma (HCC). However, whether the dynamic expression pattern of B7-H3 contributes to early invasion of HCC is largely unknown. In addition, the biological roles of B7-H3 in HCC are still unclear. Herein, we are going to examine B7-H3 expression profile and its clinicopathological significance in primary and metastatic HCC, and further determine whether B7-H3 knockdown simulates different pathological states of HCC progression and metastasis. METHODS: Using immunohistochemistry, B7-H3 expression was studied on 116 HCC containing primary and metastatic HCCs. Survival curves and log-rank tests were used to test the association of B7-H3 expression with survival. HCC cells with B7-H3 depletion were established by RNA interference to investigate the effect of B7-H3 on cell proliferation, apoptosis, migration and invasion in vitro. RESULTS: Statistical analysis of clinical cases revealed that B7-H3 high expression group had inclinations towards late TNM stage, the presence of vascular invasion, lymph metastasis, and the formation of microsatellite tumors. Increased intensity of tumor B7-H3 staining was detected more significantly in metastatic HCC tumors. Consistently in experiments performed in vitro, B7-H3 was able to stimulate the wound healing, metastasis and invasion of hepatoma cells by targeting epithelial-to-mesenchymal transition (EMT) via JAK2/Stat3/Slug signaling pathway, while no obvious influence on cell growth and apoptosis. CONCLUSION: B7-H3 in the regulation of the metastatic capacity of HCC cells makes itself a promising therapeutic target for anti-metastasis therapy.
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Intrinsically disordered proteins (IDPs) are involved in a wide range of essential biological processes, including in particular signalling and regulation. We are only beginning, however, to develop a detailed knowledge of the structure and dynamics of these proteins. It is becoming increasingly clear that, as IDPs populate highly heterogeneous states, they should be described in terms of conformational ensembles rather than as individual structures, as is instead most often the case for the native states of globular proteins. Within this context, in this chapter we describe the conceptual tools and methodological aspects associated with the description of the structure and dynamics of IDPs in terms of conformational ensembles. A major emphasis is given to methods in which molecular simulations are used in combination with experimental nuclear magnetic resonance (NMR) measurements, as they are emerging as a powerful route to achieve an accurate determination of the conformational properties of IDPs.
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Proteínas Intrínsecamente Desordenadas/química , Resonancia Magnética Nuclear Biomolecular , Conformación ProteicaRESUMEN
Restrictive fluid intake is recommended, in addition to standard pharmacologic treatment, in the treatment of patients with chronic heart failure (CHF). However, this recommendation lacks firm scientific evidence. We conducted a systematic review and meta-analysis of published randomized controlled trials to estimate the effect of fluid restriction in patients with heart failure.Randomized controlled trials were identified in the MEDLINE, EMBASE, and Cochrane databases using the search-keywords "fluid" and "heart failure". Outcomes were compared in heart failure patients with liberal and restricted fluid intake. Pooled risk ratios (RR) and weighted mean differences (WMD) were calculated using random effects models. Studies focusing on decompensated heart failure were analyzed separately.Six small randomized trials comparing liberal and restricted fluid intake met the inclusion criteria. Significant heterogeneity was noted in the reported studies for several outcomes. There were no differences in readmission rate (5 studies, pooled RR = 1.32; 95% CI: 0.86 to 2.01; P = 0.2), mortality rate (5 studies, pooled RR = 1.50; 95% CI: 0.87 to 2.57; P = 0.14), perceived thirst (4 studies, WMD = -0.7; 95% CI: -2.58 to 1.17; P = 0.46), duration of intravenous diuretics (2 studies, WMD = 0.17; 95% CI: -1.26 to 1.6; P = 0.81) or serum sodium levels (WMD = -1.61; 95% CI: -3.28 to 0.07; P = 0.06) between the liberal fluid intake group and the restrictive fluid intake group. Mean serum creatinine and BNP levels were significantly higher in the liberal fluid group: WMD 0.20 (95% CI: 0.15 to 0.25; P < 0.00001) and 172.59 (95% CI: 67.38 to 277.8; P = 0.001), respectively. There was no difference in any of the outcomes after correcting for heterogeneity.While studies to date are limited by heterogeneity and small sample sizes, the combined data suggest similar clinical outcomes in patients with CHF managed with liberal and restrictive fluid intake. Larger studies are needed to confirm our findings.
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Fluidoterapia/métodos , Insuficiencia Cardíaca/terapia , Diuréticos/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To investigate the protective effect of lycopene against cryopreservation injury of post-thawing human sperm and its mechanism. METHODS: Semen samples were collected from 25 volunteers, each sample equally divided into four parts to be cryopreserved with cryoprotectant only (Ly0 control) or cryoprotectant + lycopene at the concentrations of 2 (Ly2), 5 (Ly5), and 10 µmol/L (Ly10), respectively. Before and after thawing, the semen samples were subjected to computer-assisted semen analysis ( CASA) for sperm kinematics, flow cytometry for sperm apoptosis, thiobarbituric acid assay for malondialdehyde (MDA) concentration, and JC-1 fluorescent staining for the sperm mitochondrial membrane potential (MMP). RESULTS: After cryopreservation, sperm motility was markedly decreased in all the groups (P < 0.01). The rate of sperm apoptosis was significantly lower in the Ly5 group than in the Ly0 control ([25.68 ± 4.36]% vs [33.26 ± 4.78]%, P < 0.05), while sperm MMP remarkably higher in the former than in the latter ([66.18 ± 14.23]% vs [55.24 ± 12.31]%, P < 0.05). The Ly2, Ly5 and Ly10 groups showed no statistically significance differences in the MDA level from the Ly0 control (P > 0.05). CONCLUSION: Addition of lycopene at a proper concentration to cryoprotectant may reduce oxidative damage to sperm mitochondria in the freezing-thawing process, attenuate oxidative stress injury induced by reactive oxygen species to sperm plasma membrane, and improve the anti-apoptosis ability of sperm.