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OBJECTIVE: To investigate the effects of silencing the semenogelin 1 (SEMG1) protein on the cycle and apoptosis of the spermatogonia germ cell line (GC-1 spg). METHODS: SEMG1-specific siRNA was transfected into GC-1 spg cells by lipofectamine 2000 (the siRNA-SEMG1 group), the relative expression levels of the SEMG1 protein in the GC-1 spg cells of the siRNA-SEMG1, blank control and negative control groups were detected by Western blot, and the apoptosis and cycle of the cells in different groups were determined by flow cytometry. RESULTS: The expression of the SEMG1 protein in the GC-1 spg cells was dramatically decreased in the siRNA-SEMG1 group compared with those in the blank and negative control groups (1.80±0.05 vs 2.51±0.13 and 2.50±0.12ï¼ P < 0.01), but the apoptosis rate was remarkably higher in the former than in the latter two groups (ï¼»6.77 ± 0.15ï¼½% vs ï¼»0.70 ± 0.06ï¼½% and ï¼»0.8 ± 0.06ï¼½%, P < 0.01). No statistically significant difference was observed in the cell cycles among the three groups (P > 0.05). In addition, Western blot showed that the expression of the caspase-3 protein was significantly higher and that of the BCL2 protein markedly lower in the siRNA-SEMG1 than in the blank and negative control groups (P < 0.05). CONCLUSIONS: SEMG1-specific siRNA can effectively silence the expression of the SEMG1 protein in GC-1 spg cells and promote their apoptosis.
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Apoptosis , Ciclo Celular , Silenciador del Gen , Proteínas de Secreción de la Vesícula Seminal/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Masculino , Ratones , ARN Interferente Pequeño/genética , TransfecciónRESUMEN
There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system. The short-term effects of primary tumor and lymph node after radiotherapy were assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) of WHO. And acute radiation-induced toxic reactions were evaluated according to the Radiation Therapy Oncology Group or European Organization for Research and Treatment of Cancer (RTOG/EORTC). The effects of gene polymorphisms on clinical outcomes of chemoradiotherapy were assessed by chi-square test, univariate and multivariate logistic regression analyses. We found that CT and CT+CC genotypes of CANX rs7566 was significantly correlated with primary tumor treatment efficacy at 3 months after chemoradiotherapy and with occurrence of radiation-induced myelosuppression in Chinese NPC patients. CT and CT+CC genotypes of CALCR rs2528521 were significantly correlated with cervical lymph node efficacy at 3 months after chemoradiotherapy. And CC and CT+CC genotypes of VCP rs2074549 were significantly associated with occurrence of myelosuppression. In conclusion, SNPs of VCP rs2074549, CANX rs7566 and CALCR rs2528521 in ER stress pathway genes may serve as predictors for clinical outcomes of chemoradiotherapy in Chinese NPC patients.
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Carcinoma/terapia , Estrés del Retículo Endoplásmico/genética , Neoplasias Nasofaríngeas/terapia , Adenosina Trifosfatasas/genética , Adulto , Pueblo Asiatico , Calnexina/genética , Carcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Quimioradioterapia , Chaperón BiP del Retículo Endoplásmico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/metabolismo , Polimorfismo Genético , Receptores de Calcitonina/genética , Transducción de Señal , Proteína que Contiene ValosinaRESUMEN
AIM: To investigate the molecular targets of DCLAK11, a novel compound discovered from a series of substituted pyridin-3-amine derivatives, and to characterize its anti-tumor properties in vitro. METHODS: Kinase inhibition was measured by an ELISA assay. Cell viability was assessed with an SRB or a CCK8 assay. The alterations induced by kinase signaling proteins in cancer cells were detected by Western blot. Apoptosis was determined by an Annexin V-PI assay. The following assays were used to evaluate the impact on angiogenesis: wound-healing, Transwell, tube formation and microvessel outgrowth from rat aortic rings. RESULTS: DCLAK11 was a multi-targeted kinase inhibitor that primarily inhibited the EGFR, HER2, and VEGFR2 tyrosine kinases with IC50 value of 6.5, 18, and 31 nmol/L, respectively. DCLAK11 potently inhibited the proliferation of EGFR- and HER2-driven cancer cells: its IC50 value was 12 and 22 nmol/L, respectively, in HCC827 and HCC4006 cells with EGFR exon deletions, and 19 and 81 nmol/L, respectively, in NCI-N87 and BT474 cells with HER2 amplification. Consistently, DCLAK11 blocked the EGFR and HER2 signaling in cancer cells with either an EGFR or a HER2 aberration. Furthermore, DCLAK11 effectively induced EGFR/HER2-driven cell apoptosis. Moreover, DCLAK11 exhibited anti-angiogenic activity, as shown by its inhibitory effect on the proliferation, migration and tube formation of human umbilical vascular endothelial cells and the microvessel outgrowth of rat aortic rings. CONCLUSIONS: DCLAK11 is a multi-targeted kinase inhibitor with remarkable potency against tyrosine kinases EGFR, HER2 and VEGFR2, which confirms its potent anti-cancer activity in EGFR- and HER2-addicted cancers and its anti-angiogenic activity.
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Inhibidores de la Angiogénesis/farmacología , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/farmacología , Piridinas/farmacología , Receptor ErbB-2/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Angiogénesis/química , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptores ErbB/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Inhibidores de Proteínas Quinasas/química , Piridinas/química , Ratas Sprague-Dawley , Receptor ErbB-2/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Resistive random-access memory (RRAM) is a promising candidate for next-generation non-volatile memory. However, due to the random formation and rupture of conductive filaments, RRMS still has disadvantages, such as small storage windows and poor stability. Therefore, the performance of RRAM can be improved by optimizing the formation and rupture of conductive filaments. In this study, a hafnium oxide-/aluminum-doped zinc oxide/hafnium oxide (HfO2/Al-ZnO/HfO2) tri-layer structure device was prepared using the sol-gel method. The oxygen-rich vacancy Al-ZnO layer was inserted into the HfO2 layers. The device had excellent RS properties, such as an excellent switch ratio of 104, retention of 104 s, and multi-level storage capability of six resistance states (one low-resistance state and five high-resistance states) and four resistance states (three low-resistance states and one high-resistance state) which were obtained by controlling stop voltage and compliance current, respectively. Mechanism analysis revealed that the device is dominated by ohmic conduction and space-charge-limited current (SCLC). We believe that the oxygen-rich vacancy concentration of the Al-ZnO insertion layer can improve the formation and rupture behaviors of conductive filaments, thereby enhancing the resistive switching (RS) performance of the device.
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Sulfate and water management can be respectively applied to control Cd accumulation in rice, but the interaction mechanisms remain unclear. Three water management coupled with five sulfate application concentrations were employed to investigate rice Cd uptake. Results showed there was a significant interaction between sulfate application and soil redox state, and the highest sulfate treatments reduced rice grain Cd by 63.2, 53.5, and 59.4% under the flooding, flooding-moist alternate (FM), and moist irrigation (M) conditions, respectively. It could be explained by the reduction in rhizosphere soil available Cd and lower transport coefficient from root to aboveground. The Desulfovibrio was demonstrated to participate in CdS precipitation, and its abundance was promoted by sulfate especially under flooding. Additionaly, sulfate application facilitated Cd bounded to FeMn oxides, as rhizosphere soil pH raising under flooding. Under FM and M treatments, sulfate application reduced the abundance of Fe-reducing bacteria Geobacter, and correspondingly reduced Fe and Cd availability in rhizosphere soil. Summarily, Cd transfer from soil to rice can be reduced by applying sulfate fertilizer; which is favored by higher soil moisture because of the higher abundance of Desulfovibrio and lower abundance of Geobacter.
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Oryza , Contaminantes del Suelo , Cadmio/análisis , Fertilización , Oxidación-Reducción , Rizosfera , Suelo , Contaminantes del Suelo/análisis , Sulfatos , AzufreRESUMEN
BACKGROUND: Thrombocytopenia is a serious complication in the medical practice of numerous drugs. Vancomycin is frequently used for the prophylaxis and treatment of suspected or identified methicillin-resistant positive infections. Several cases with vancomycin-induced thrombocytopenia (VIT) have been reported. However, these have rarely been extensively reviewed. The present report describes a case of VIT in endocarditis, and reviews all VIT cases reported in the literature. CASE SUMMARY: A 26-year-old male diagnosed with infective endocarditis was admitted. The patient was treated with multiple drugs, including vancomycin, which was initially intravenously given at 1000 mg every 12 h and subsequently at 500 mg every 8 h on day 3. On day 11, the platelet count decreased to 51 × 109/L, vancomycin was switched to 500 mg every 12 h, and platelet transfusion was given. On day 17, the platelet count dropped to 27 × 109/L, and platelet transfusion was administered again. On day 23, vancomycin was adjusted to 500 mg every 8 h as the trough concentration dropped to the minimum effective concentration. On day 33, the platelet count declined to approximately 40 × 109/L. After platelet transfusion, the platelet count rebounded to 90 × 109/L on day 35 but dropped again to 42 × 109/L on day 43. Based on the time-to-platelet count curve and Naranjo's Adverse Drug Reaction Probability Scale score, VIT was suspected. After vancomycin discontinuation and platelet transfusion, the platelet count gradually normalized. CONCLUSION: The diagnosis of VIT can be achieved through the time-to-platelet count curve and Naranjo's Adverse Drug Reaction Probability Scale score. The platelet count cannot be normalized simply by platelet transfusion alone, and vancomycin discontinuation is essential.
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The Asian larch bark beetle, Ips subelongatus, is a severe pest of larches in Northeastern China. The gustatory and olfactory systems of I. subelongatus play important roles in host location, mating, and feeding. In this study, we examined the types, distributions, and abundances of various sensilla associated with the mouthparts and antennae of I. subelongatus using scanning electron microscopy (SEM). On the mouthparts, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-3), sensilla basiconica (S.b.1-2), sensilla twig basiconica (S.tb.1-3), and sensilla placodea (S.p). S.t.3 are the most abundant sensilla subtype on the mouthparts in both sexes, while S.b.1 are the least abundant. Most sensilla on the mouthparts are located on the maxillae and labium, and the apex of each maxillary and labial palp carry the same sensilla subtypes (S.b.2 and S.tb.1-3). However, the total number of sensilla on the apex of each maxillary palp is higher than that on the labial palp. On the antennae, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-2), sensilla basiconica (S.b.1-3), Böhm bristles (B.b), and sensilla coeloconica (S.co). Antennal sensilla are mostly situated on the anterior surface of the antennal club, particularly on the two dense sensory bands. S.b.1 are the most abundant sensilla subtype on the antennae in both sexes, while S.t.1 are the least abundant. No sexual dimorphism in sensilla type or distribution on the mouthparts or antennae is observed between the sexes of I. subelongatus. However, S.t.3 (on mouthparts) and S.c.1 (on antennae) were significantly more abundant in males than in females, while more S.t.1 (on mouthparts) were observed in females than in males. Finally, the putative functions of each kind of sensilla with respect to their fine structures, distributions, and abundances on the mouthparts and antennae are discussed.
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Antenas de Artrópodos/ultraestructura , Escarabajos/anatomía & histología , Larix , Microscopía Electrónica de Rastreo/métodos , Boca/anatomía & histología , Sensilos/ultraestructura , Animales , China , Escarabajos/ultraestructura , Femenino , Masculino , Boca/ultraestructura , Sensilos/fisiología , Caracteres SexualesRESUMEN
Spermatogenic dysfunction caused by cyclophosphamide (CP) chemotherapy has seriously influenced the life quality of patients. Unfortunately, treatments for CP-induced testicular spermatogenic dysfunction are limited, and the molecular mechanisms are not fully understood. For the first time, here, we explored the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) on CP-induced testicular spermatogenic dysfunction in vitro and in vivo. BMSC-exos could be taken up by spermatogonia (GC1-spg cells). CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses, and then, cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In addition, photophosphorylation of extracellular-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), and protein kinase B (AKT) proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry. Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells. Phosphorylated levels of ERK, AKT, and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos, indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. In experiments in vivo, CP-treated rats received BMSC-exos by injection into the tail vein, and testis morphology was compared between treated and control groups. Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes. Thus, BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.
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Trasplante de Médula Ósea/normas , Ciclofosfamida/efectos adversos , Factores Protectores , Trasplante de Médula Ósea/métodos , Trasplante de Médula Ósea/estadística & datos numéricos , Exosomas/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The spruce bark beetle (Ips typographus L.) is a destructive pest of Eurasian spruce forests. Although the gut bacteria of this insect are considered to play important roles in its lifecycle, the relationship between I. typographus and its gut bacterial community is poorly characterized. In this study, 16S rRNA gene sequencing was used to determine gut bacterial community composition across successive I. typographus life stages. Responses of the gut bacteria to α-pinene enantiomers were also explored. Ips typographus gut bacterial populations were dominated by the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, and the relative abundance of these phyla varied across different developmental stages of the beetle. Bacterial species diversity and richness indices increased with developmental stage progression. Relative abundances of the dominant genera, Erwinia (Enterobacteriales: Enterobacteriaceae), Pseudoxanthomonas (Xanthomonadales: Xanthomonadaceae), Serratia (Enterobacteriales: Enterobacteriaceae), and Romboutsia (Clostridiales: Peptostreptococcaceae), also varied across successive I. typographus life stages. Large disparities in the gut bacterial community of male adults were observed when the beetles were treated with S-(-)-α-pinene and R-(+)-α-pinene. The relative abundances of Lactococcus (Lactobacillales: Streptococcaceae) and Lelliottia (Enterobacteriales: Enterobacteriaceae) increased drastically with R-(+)-α-pinene and S-(-)-α-pinene treatment, respectively. This indicated a distinct enantiomer-specific effect of α-pinene on the I. typographus gut bacteria. This study demonstrated the plasticity of gut bacteria during I. typographus development, when α-pinene host monoterpenes are encountered. This study provides new insights into the relationship between 'I. typographus-gut bacteria' symbionts and host trees.
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Escarabajos , Microbioma Gastrointestinal , Gorgojos , Animales , Bacterias/genética , Monoterpenos Bicíclicos , Masculino , Monoterpenos , ARN Ribosómico 16S/genética , Características de la ResidenciaRESUMEN
A giant electrocaloric effect is reported in (Pb0.97La0.02)(Zr0.95Ti0.05)O3 anti-ferroelectric ceramics. These samples were fabricated by a solid-state mixed oxide technique. Dielectric analyses were employed to investigate the anti-ferroelectric (AFE) and ferroelectric (FE) phase transitions of the sample. During the heating process, the phase transition from the orthorhombic anti-ferroelectric phase (AFEO) to the tetragonal anti-ferroelectric phase (AFET) occurs at 155 °C, and the phase transition from AFET to PE occurs at 225 °C. Using the Maxwell relationship, the entropy change ΔS and adiabatic temperature change ΔT were obtained at different electric fields ranging from 40 to 65 kV/cm. The maximum adiabatic temperature change (ΔT max = -7.47 K) was obtained at 50 kV/cm, which was attributed to the field-induced phase transformation between the anti-ferroelectric and ferroelectric phases. These results showed that PLZT2/95/5 ceramics possess a large negative electrocaloric effect value, which could be applied in achieving cooling power as refrigerants.
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BACKGROUND: Most studies reported that high plasma endothelin-1 (ET-1), big ET-1, and C-terminal proET-1 (CT-proET-1) were correlated with poor prognosis of heart failure (HF). However, available evidence remains controversial. To help solve the debate, we collected all the available studies and performed a meta-analysis. METHODS: We searched the databases covering Embase, PubMed, Ovid, and Web of Science on June 28, 2017. The hazard ratio (HR) or risk ratio (RR) and its 95% confidence intervals (CIs) were collected and calculated by use of a random-effect model. Heterogeneity was assessed by Cochran's Q test, and publication bias was assessed by funnel plots with Egger's and Begg's linear regression test. RESULTS: Thirty-two studies with 18,497 patients were included in the analysis. Results showed that circulating ET-1, big ET-1, and CT-proET-1 were positively correlated with high risk of adverse outcomes, with pooled RRs (95% CIs) of 2.22 (1.82-2.71, Pâ<â.001), 2.47 (1.93-3.17, Pâ<â.001), and 2.27 (1.57-3.29, Pâ<â.001), respectively. In the subgroup of death as primary outcome, the pooled RRs (95% CIs) were 2.13 (1.68-2.70, Pâ<â.001), 2.55 (1.82-3.57, Pâ<â.001), and 2.02 (1.39-2.92, Pâ<â.001) for ET-1, big ET-1, and CT-proET-1, respectively. No significant publication bias was observed in this study. CONCLUSION: Our meta-analysis provided evidence that increased plasma levels of ET-1, big ET-1, and CT-proET-1 were associated with poor prognosis or mortality for HF populations.