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High-performance transferable and integratable microlasers hold great promise to construct the integrated photonics and optoelectronics. However, the qualified candidates are still being pursued. Herein, a mass-production of low-threshold and wavelength-tunable microlasers that is readily integratable with the optical fiber platform is realized by a two-step solution-phase approach. The demonstration is enabled by the formation of a novel semiconductor heterostructure from halide perovskites featuring the quasi-free-standing and highly emissive properties. Corroborated by the in-situ optical characterization, we reveal that the lateral perovskite heterostructures are constructed through a sequential reaction driven by the surface energy contrast. These perovskite heterostructures exhibit low-threshold and broadband tunable lasing action thanks to the efficient spatial light conversion nature and the facile composition tunability. Taking the merits together, the heterostructure microlasers can be the competitive applicants for photonic integration as demonstrated by the laser-on-fiber configuration.
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The exponential growth of encrypted network traffic poses significant challenges for detecting malicious activities online. The scale of emerging malicious traffic is significantly smaller than that of normal traffic, and the imbalanced data distribution poses challenges for detection. However, most existing methods rely on single-category features for classification, which struggle to detect covert malicious traffic behaviors. In this paper, we introduce a novel semi-supervised approach to identify malicious traffic by leveraging multimodal traffic characteristics. By integrating the sequence and topological information inherent in the traffic, we achieve a multifaceted representation of encrypted traffic. We design two independent neural networks to learn the corresponding sequence and topological features from the traffic. This dual-feature extraction enhances the model's robustness in detecting anomalies within encrypted traffic. The model is trained using a joint strategy that minimizes both the reconstruction error from the autoencoder and the classification loss, allowing it to effectively utilize limited labeled data alongside a large amount of unlabeled data. A confidence-estimation module enhances the classifier's ability to detect unknown attacks. Finally, our method is evaluated on two benchmark datasets, UNSW-NB15 and CICIDS2017, under various scenarios, including different training set label ratios and the presence of unknown attacks. Our model outperforms other models by 3.49% and 5.69% in F1 score at labeling rates of 1% and 0.1%, respectively.
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An essential intervention for patients with end-stage renal disease is kidney transplantation. Nonetheless, patient outcomes are substantially affected by complications associated with postoperative wounds. The purpose of this research was to determine the prevalence, risk factors and repercussions of wound-related complications among kidney transplant recipients. A cross-sectional observational study was undertaken at Qilu Hospital of Shandong University Department of Organ Transplantation, China. Included in the study were 118 patients who had undergone kidney transplantation during the specified time period. Medical record evaluations, questionnaires and patient interviews were utilized to collect data, with an emphasis on demographics, transplant information, postoperative care and wound complications. Infection, dehiscence, lymphocoele, delayed wound healing, seroma formation and haematoma were classified as complications. The presence of comorbidities, age over 50 and living donor transplants were identified as significant risk factors for postoperative complications. The most prevalent complications observed were delayed wound healing (21.2%) and infections (16.9%) (p < 0.05). Antibiotics were found to be effective in managing infections, while prolonged conservative management was necessary for delayed wound healing. Prominent complications that recurred were infections and wound healing delays. No statistically significant correlation was observed between gender, BMI and prior transplants with the occurrence of complications (p > 0.05). The research highlighted the significance of taking into account patient-specific variables, including age and concurrent medical conditions, when conducting post-kidney transplantation treatment. The results supported the use of individualized strategies in postoperative care, particularly for populations at high risk, in order to reduce the incidence and severity of complications associated with wounds in pursuit to enhancing clinical practices and formulating focused intervention strategies to improve patient outcomes following transplantation.
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Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Estudos Transversais , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Fatores de Risco , Cicatrização , Estudos RetrospectivosRESUMO
The precision, minimal invasiveness, and integration of diagnosis and treatment are critical factors for tumor treatment at the present. Although nanomedicine has shown the potential in tumor precision treatment, nanocarriers with high efficiency, excellent targeting, controlled release, and good biocompatibility still need to be further explored. Hollow mesoporous manganese oxides nanomaterials (HM-MONs), as an efficient drug delivery carrier, have attracted substantial attention in applications of tumor diagnosis and therapy due to their unique properties, such as tumor microenvironment stimuli-responsiveness, prominent catalytic activity, excellent biodegradation, and outstanding magnetic resonance imaging ability. The HM-MONs can not only enhance the therapeutic efficiency but also realize multimodal diagnosis of tumors. Consequently, it is necessary to introduce applications based on HM-MONs in cancer diagnosis and therapy. In this review, the representative progress of HM-MONs in synthesis is discussed. Then, several promising applications in drug delivery, bio-imaging, and bio-detection are highlighted. Finally, the challenges and perspectives of the anticancer applications are summarized, which is expected to provide meaningful guidance on further research.
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Nanopartículas , Neoplasias , Doxorrubicina/uso terapêutico , Portadores de Fármacos , Humanos , Manganês , Compostos de Manganês , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Óxidos , Microambiente TumoralRESUMO
In this work, we present a simple and active mechanism for manipulating the photonic spin Hall effect (SHE) of an InP-based layered structure by taking advantage of the alterable refractive index of InP via bias-assisted carrier injection. The photonic SHE of transmitted light for both H- and V-polarized beams is quite sensitive to the intensity of the bias-assisted light. The spin shift can reach its giant value under the optimal intensity of bias light, which corresponds to the proper refractive index of InP induced by the photon-induced carrier injection. Except for the modulation of the bias light intensity, there is another method to manipulate the photonic SHE by adjusting the wavelength of bias light. We found that this method of tuning the bias light wavelength is more effective for H-polarized light than for the V-polarized light.
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Albendazole (ABZ), a clinical antiparasitic drug, has shown potential antitumor effects in various tumors. Herein, we prepared dimeric cRGD [(cRGD)2] modified human serum albumin (HSA) nanosystem to co-delivery of albendazole (ABZ) and iodine-131 (131I) for chemoradiotherapy of triple-negative breast cancer (TNBC). HSA@ABZ NPs were synthesized by the self-assembly method. 131I-(cRGD)2/HSA@ABZ NPs were fabricated through covalently binding HSA@ABZ NPs with (cRGD)2 peptides, followed by chloramine T direct labeling with 131I. In vitro therapeutic effects on TNBC (MDA-MB-231 and 4T1 cells) were determined using MTT assay, crystal violet assay, wound-healing assay and western blotting analysis. In vivo treatment was performed using 4T1-bearing mice, and the tumor-targeting efficacy was assessed by gamma imaging. The distribution of NPs was quantitatively analyzed by detecting the gamma counts in tumor and main organs. The nanoparticles possessed negative charge, moderate size and good polydispersity index. Dual responding to pH and redox, the in vitro release rate of ABZ was more than 80% in 72 h. In vitro, NPs inhibited the proliferation of TNBC cells in a concentration-dependent manner and decreased cell migration. Western blotting analysis showed that the NPs, as well as free ABZ, cell-dependently induced autophagy and apoptosis by restraining or promoting the expression of p-p38 and p-JNK MAPK. In vivo, gamma imaging exhibited an earlier and denser radioactivity accumulation in tumor of 131I-(cRGD)2/HSA@ABZ NPs compared to NPs free of (cRGD)2 conjugating. Furthermore, 131I-(cRGD)2/HSA@ABZ NPs significantly suppressed tumor growth by restraining proliferation and promoting apoptosis in vivo. Our study suggested that the nanoparticles we developed enhanced tumor-targeting of ABZ and increased antitumor effects by combination of chemotherapy and radiotherapy.
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Albendazol/farmacologia , Quimiorradioterapia/métodos , Radioisótopos do Iodo/farmacologia , Nanopartículas/química , Peptídeos Cíclicos/química , Neoplasias de Mama Triplo Negativas/patologia , Albendazol/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Radioisótopos do Iodo/administração & dosagem , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Albumina Sérica , Propriedades de Superfície , Temperatura , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Invasive pulmonary aspergillosis often occurs in patients with poor immune function, who abuse steroids or broad-spectrum antibiotics, or who use intravenous drugs. Among the Aspergillus genus of pulmonary infection, Aspergillus fumigatus is the most important pathogen, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Inhalation injury complicated by Aspergillus infection has atypical clinical manifestations. Diagnosis is difficult, and it is easy to make mistakes in treatment. Moreover, there are few cases of burn inhalation injury complicated with pulmonary Aspergillus. CASE PRESENTATION: We report a case of severe burns combined with severe inhalation injury, early pulmonary aspergillosis, and severe respiratory failure due to treatment discontinuation. Through analyzing the processes of diagnosis and treatment in the present case and performing a literature review, we explore feasible diagnosis and treatment plans. CONCLUSIONS: Early application of a variety of diagnostic measures can be used to identify Aspergillus infection, and targeted anti-infection treatment is likely to reverse a severe adverse prognosis.
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Aspergilose , Aspergilose Pulmonar Invasiva , Aspergilose Pulmonar , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Aspergillus fumigatus , Aspergillus niger , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/tratamento farmacológicoRESUMO
The photonic spin Hall effect (SHE), manifesting itself as spin-dependent splitting of light, holds potential applications in nano-photonic devices and precision metrology. However, the photonic SHE is generally weak, and therefore its enhancement is of great significance. In this paper, we propose a simple method for enhancing the photonic SHE of reflected light by taking advantage of the gradient-refractive-index (GRIN) material. The transverse shifts for a normal (homogeneous) layer and linear GRIN structure with three different types (singly increasing, singly decreasing, and doubly linear ones) are theoretically investigated. We found that the doubly linear GRIN materials exhibit the prominent photonic SHE of reflected light, which is mainly due to the Fabry-Perot resonance. By optimizing the thickness and the lower (higher) refractive index of the doubly linear GRIN layer, the transverse shift for a horizontally polarized incident beam can nearly reach its upper limitation (i.e., half of the beam waist). These findings provide us a potential method to enhance the photonic SHE, and therefore establish a strong foundation for developing spin-based photonic devices in the future.
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Due to the lack of places to employ communication infrastructures, there are many coverage blind zones in maritime communication networks. Benefiting from the high flexibility and maneuverability, unmanned aerial vehicles (UAVs) have been proposed as a promising method to provide broadband maritime coverage for these blind zones. In this paper, a multi-UAV-enabled maritime communication model is proposed, where UAVs are deployed to provide the transmission service for maritime users. To improve the performance of the maritime communication systems, an optimization problem is formulated to maximize the minimum average throughput among all users by jointly optimizing the user association, power allocation, and UAV trajectory. To derive the solutions with a low computational complexity, we decompose this problem into three subproblems, namely user association optimization, power allocation optimization, and UAV trajectory optimization. Then, a joint iterative algorithm is developed to achieve the solutions based on the successive convex approximation and interior-point methods. Extensive simulation results validate the effectiveness of the proposed algorithm and demonstrate that UAVs can be used to enhance the maritime coverage.
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Severe acquired aplastic anaemia (AA) is a serious disease characterised by autoreactive T cells attacking haematopoietic stem cells, leading to marrow hypoplasia and pancytopenia. Immunosuppressive therapy combined with antithymocyte globulin and ciclosporin can rescue most patients with AA. However, the relapse after ciclosporin withdrawal and the severe side effects of long-term ciclosporin administration remain unresolved. As such, new strategies should be developed to supplement current therapeutics and treat AA. In this study, the possibility of all-trans-retinoic acid (ATRA) as an alternative AA treatment was tested by using an immune-mediated mouse model of AA. Results revealed that ATRA inhibited T-cell proliferation, activation and effector function. It also restrained the Fas/Fasl pathway, shifted Th1 towards Th2 cell development, rebalanced T-cell subsets at a relatively high level and corrected the Th1/Th2 ratio by targeting NFAT1 signalling. In addition, ATRA inhibited Th17 cell differentiation and promoted regulatory T-cell development. Therefore, ATRA was an effective agent to improve AA treatment outcomes.
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Anemia Aplástica/imunologia , Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição NFATC/imunologia , Transdução de Sinais/imunologia , Células Th1/imunologia , Células Th2/imunologia , Tretinoína/farmacologia , Anemia Aplástica/patologia , Animais , Diferenciação Celular/imunologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Células Th1/patologia , Células Th17/imunologia , Células Th17/patologia , Células Th2/patologiaRESUMO
The thermal stability of the phosphors in phosphor-converted light-emitting diodes (LEDs) plays an important role in the practical application of lighting. Herein, the Mn2+-based red-emitting phosphors of pure and Eu2+-doped Sr9MnLi(PO4)7 (SMPO) samples were prepared using the high temperature solid-state reaction method. The crystal field environment around the Mn2+ ions was analyzed by combining the results of photoluminescence excitation spectroscopy and Tanabe-Sugano diagrams. By comparing the results of X-ray photoelectron spectroscopy, two additional bands centered at about 129.8 eV and 130.7 eV were found in the Eu2+-doped sample, which corresponded to the chemical states of P 2p3/2 and P 2p1/2. Two different sets of emission spectra were observed for Sr9MnLi(PO4)7:5%Eu2+ (SMPO:Eu2+) on employing the time-resolved technique. The emission peaks centered at 615 nm and 661 nm were attributed to Mn2+ and Eu2+ ions, respectively. The thermal quenching behaviors of Eu2+ and Mn2+ were investigated in the temperature range of 300-620 K and the thermal quenching mechanisms are given in this work. Systematic research on the luminescent properties of Eu2+ and Mn2+ ions in the SMPO:Eu2+ phosphor contributes to the understanding of the thermal stability and aids in the development of Mn2+-based red-emitting phosphors.
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BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.
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Azepinas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Proteínas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Triazóis/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Células HEK293 , Humanos , Proteínas Nucleares/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Proteínas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição/metabolismoRESUMO
With the increasing application of hydraulic fracturing technology in exploration of tight oil and shale gas, the treatment of accompanying fracturing flowback fluids has become more urgent. Fe/Ni catalyst was successfully applied in the treatment of the flowback fluid for the first time in this paper. The effects of different oxidants and catalysts on the treatment of fracturing flowback were investigated. Electrolytic brine was an optimal oxidation gel breaker and molecular sieve loaded with Fe/Ni as catalyst for the treatment of fracturing flowback. Fe/Ni catalyst was characterized by SEM, EDS analysis, TEM and XRD, and the catalytic effect of the Fe/Ni proportion was explored. Fracturing flowback that dealt with catalytic oxidation was mixed with polyaluminum chloride (PAC) and polyacrylamide (PAM) for flocculation and sedimentation, through a filter, and was continuously treated for 20 days to simulate on-site operation. Finally, the suspended solids (SS) content of the fracturing flowback was steadily less than 15 mg/L, which meets the reinjection standard of fracturing flowback (SY/T 5329-2012 (China)). Hence, electrolytic brine-catalyzed oxidation treatment of high viscosity fracturing flowback possess broad application prospects.
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Águas Residuárias , Poluentes Químicos da Água , Catálise , China , Sais , Viscosidade , Poluentes Químicos da Água/análiseRESUMO
CONTEXT: Angelica sinensis (Oliv.) Diels (Apiaceae) (syn. Angelica polymorpha Maxim var. sinensis Oliver) processed with yellow rice wine (WAS) has a blood-supplementing effect. OBJECTIVE: To establish an optimal technology for preparing water decoction of WAS (WASD), and screen blood-supplementing fractions. MATERIALS AND METHODS: Ferulic acid and crude polysaccharide were used in optimizing the preparation technology for WASD through response surface methodology. The independent variables were liquid-solid ratio, soaking time, and extraction time. Eighty Kunming mice were randomly divided into normal control, model, and six intervention groups (n = 10). The intervention groups were given different WASD fractions by gavage (5 or 10 g/kg). The model intervention groups received acetylphenyl hydrazine (subcutaneous injection) and cyclophosphamide (intraperitoneal injection). Duration of study, 9 days. The components of blood-supplementing fractions were analyzed. RESULTS: The optimum extraction parameters were liquid-solid ratio, 7.69:1 mL/g; soaking time, 119.78 min; and extraction time, 143.35 min. The optimal OD value was 0.8437. RBC, WBC, and Hb in the water fraction (5, 10 g/kg) and n-butanol fraction (10 g/kg) intervention groups increased significantly compared with the model group (p < 0.05). Polysaccharide and caffeic acid contents of water fraction were 252.565 and 0.346 µg/mg, respectively; ferulic acid was not detected. Caffeic acid and ferulic acid contents of n-butanol fraction were 1.187 and 0.806 µg/mg, respectively, polysaccharide was not detected. CONCLUSIONS: The optimum preparation technology of WASD was obtained, and the water, n-butanol fractions were blood-supplementing fractions. This study provides a theoretical foundation for further application of WAS in the pharmaceutical industry.
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Angelica sinensis/química , Sangue/efeitos dos fármacos , Oryza/química , Extratos Vegetais/farmacologia , Animais , Contagem de Células Sanguíneas , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Medicina Tradicional Chinesa , Camundongos , Raízes de Plantas/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Solventes , Espectrofotometria Ultravioleta , Timo/efeitos dos fármacos , Água , VinhoRESUMO
Aplastic anemia (AA) is a serious blood system disease that threatens human health. At present, the main cause of this disease is believed to be immune hyperfunction. However, the specific metabolic mode involved in the occurrence of lymphocytes in AA is still unknown. In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. We induced an AA mouse model through the classical immune-mediated pathway and simultaneously administered rapamycin intervention therapy. First, the AA-associated phenotypic changes and the efficacy of rapamycin in the treatment of AA were discussed. Second, the proliferation and metabolic pathway of bone marrow (BM) lymphocytes in AA and the effect of rapamycin on this process were determined. Finally, the expression levels of mTOR pathway-related proteins were analyzed. By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Moreover, we found that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and that rapamycin can inhibit this process. We confirmed that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. This viewpoint may provide a new therapeutic idea for clinical applications.
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Anemia Aplástica/tratamento farmacológico , Imunossupressores/farmacologia , Sirolimo/farmacologia , Linfócitos T/efeitos dos fármacos , Anemia Aplástica/imunologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Masculino , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a member of the rhodopsin-like 7-transmembrane domain receptor superfamily and has high homology to LGR4 and LGR5. LGR6 is highly expressed in osteoblastic progenitors, and LGR6-deficient mice show nail and bone regeneration defect. However, the effect of LGR6 on the osteogenic differentiation of osteoblastic progenitors and its underlying mechanisms are largely unknown. In this study, we overexpressed and knockdown LGR6 with lentivirus in the preosteoblastic cell MC3T3-E1 to observe the effect of LGR6 on osteogenic differentiation and explore its possible molecular mechanism. LGR6 overexpression promoted osteogenic differentiation and mineralization by stabilizing ß-catenin to potentiate the Wnt/ß-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing ß-catenin degradation to inactivate the Wnt/ß-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing ß-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation.
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Osteogênese , Receptores Acoplados a Proteínas G/metabolismo , Via de Sinalização Wnt , Animais , Calcificação Fisiológica , Diferenciação Celular , Linhagem Celular , Técnicas de Silenciamento de Genes , Camundongos , Estabilidade Proteica , Proteólise , beta Catenina/metabolismoRESUMO
BACKGROUND: The pathogenesis of the development of IgA nephropathy has not been clear up to now. At present, some studies revealed that the mTOR pathway may participate in IgA nephropathy; however, the mechanism has not been systematically studied. In this study, we established an IgAN rat model to investigate the protective effects of rapamycin as a new type of immunosuppressant, as well as its therapeutic mechanisms. METHODS: After the establishment of IgA nephropathy model, rats were treated with different concentrations of rapamycin, and the protective effect of different concentrations of rapamycin on renal function of the rats was observed. The deposition of IgA was observed by immunofluorescence. The kidney expression of Akt and p70S6k proteins in mTOR pathway was examined using the western blot assay after rapamycin treatment. RESULTS: Morphology and immunofluorescence confirmed that the rat model of IgA nephropathy was successfully established. In particular, the level of proteinuria decreased with the increase of the dose of rapamycin, as well as the deposition of IgA in glomeruli. Moreover, the western blot analysis indicated that the expression of p70S6K in the downstream of mTOR pathway decreased and the upstream protein AKT of the mTOR pathway was overexpressed in the rats model. CONCLUSION: We found that rapamycin has protective effects in the IgA nephropathy rat model in a dose-dependent manner. In addition, the result of western blot assay suggested that rapamycin may display its therapeutic effects through interfering the AKT-mTOR-p70S6K signaling pathway.
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Glomerulonefrite por IGA/prevenção & controle , Imunoglobulina A/sangue , Imunossupressores/administração & dosagem , Sirolimo/administração & dosagem , Animais , Modelos Animais de Doenças , Progressão da Doença , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/etiologia , Humanos , Imunoglobulina A/imunologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Resultado do TratamentoRESUMO
Sr2IrO4, known as the Jeff = 1/2 Mott insulator, was predicted to be an unconventional superconductor upon doping since it highly resembles the high-temperature cuprates. However, recent work pointed out an enhanced insulating behavior in the Ir-vacant Sr2Ir1-xO4 system. In this contribution, to investigate the microscopic mechanism of its enhanced insulating behavior, X-ray absorption spectroscopy was applied to study the electronic structure and local structure distortion of Sr2Ir1-xO4. Due to the presence of Ir5+ ions, the preconceived holes are barely doped in the Ir-vacant system. Nevertheless, Ir vacancies finely modulate the local atomic structure, i.e. the topology of IrO6 octahedra and the in-plane Ir-O1-Ir bond angle. Combined with theoretical calculations, it is demonstrated that both the more distorted IrO6 octahedra and decreased Ir-O1-Ir angle contribute to the increment of the band gap, and then result in the enhanced insulating state for Sr2Ir1-xO4.
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The food-borne trichothecene mycotoxins have been documented to cause human and animal food poisoning. Anorexia is a hallmark of the trichothecene mycotoxins-induced adverse effects. Type B trichothecenes have been previously demonstrated to elicit robust anorectic responses, and this response has been directly linked to secretion of the gut satiety hormones cholecystokinin (CCK) and glucagon-like peptide-17-36 amide (GLP-1). However, less is known about the anorectic effects and underlying mechanisms of the type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), neosolaniol (NEO). The purpose of this study was to relate type A trichothecenes T-2, HT-2, DAS and NEO-induced anorectic response to changes plasma concentrations of CCK and GLP-1. Following both oral gavage and intraperitoneal (IP) administration of 1mg/kg bw T-2, HT-2, DAS and NEO evoked robust anorectic response and secretion of CCK and GLP-1. Elevations of plasma CCK markedly corresponded to anorexia induction by T-2, HT-2, DAS and NEO. Following oral exposure, plasma CCK was peaked at 6h, 6h, 2h, 2h and lasted up to 24h, 24h, > 6h, > 6h for T-2, HT-2, DAS and NEO, respectively. IP exposed to four toxins all induced elevation of CCK with peak point and duration at 6h and >24h, respectively. In contrast to CCK, GLP-1 was moderately elevated by these toxins. Following both oral and IP exposure, T-2 and HT-2 evoked plasma GLP-1 elevation with peak point and duration at 2h and 6h, respectively. Plasma GLP-1 was peaked at 2h and still increased at 6h for IP and oral administration with DAS and NEO, respectively. In conclusion, CCK plays a contributory role in anorexia induction but GLP-1 might play a lesser role in this response.
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Anorexia/prevenção & controle , Regulação do Apetite , Comportamento Animal , Colecistocinina/sangue , Comportamento Alimentar , Peptídeo 1 Semelhante ao Glucagon/sangue , Fragmentos de Peptídeos/sangue , Resposta de Saciedade , Toxina T-2/análogos & derivados , Tricotecenos , Animais , Anorexia/sangue , Anorexia/induzido quimicamente , Anorexia/psicologia , Modelos Animais de Doenças , Feminino , Camundongos , Transdução de Sinais , Fatores de Tempo , Regulação para CimaRESUMO
OBJECTIVE: To investigate the relationship between 755 T>G polymorphisms in the CTNND1 gene, which is associated with the risk of pancreatic carcinoma in Chinese. METHODS: CTNND1 755 T>G genotypes were determined by PCR-RFLP in 122 pancreatic carcinoma patients and 180 healthy controls matched for age and sex, who did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed pancreatic carcinoma. RESULTS: In control subjects, the frequency of T/T and G/T genotypes, and T and G alleles was 79.4%, 17.2%, 88.1%, and 11.9%, respectively. The distribution of genotypes and allelotypes in the pancreatic carcinoma patients was significantly different from that in the controls (P = 0.007, P = 0.012). Combined GG and GT genotypes were found to have a higher OR in male pancreatic carcinoma patients and the group under the age of 70 years (males: OR, 1.409; 95%CI, 0.912~1.921; under 70 years: OR 1.626; 95% CI, 0.878~2.312). This study also showed a distinct difference in the distribution of P120ctn and single nucleotide polymorphisms (SNPs) between Chinese and Canadian (11.9% vs. 3.9%, P = 0.008). CONCLUSION: CTNND1 755 T>G polymorphism may be a stratification marker to predict the susceptibility to pancreatic carcinoma, at least in Chinese. CTNND1 promoter SNPs is diverse in ethnic populations.