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While Ru-catalyzed hydrogenolysis holds significant promise in converting waste polyolefins into value-added alkane fuels, a major constraint is the high cost of noble metal catalysts. In this work, we propose, for the first time, that Co-based catalysts derived from CoAl-layered double hydroxide (LDH) are alternatives for efficient polyolefin hydrogenolysis. Leveraging the chemical flexibility of the LDH platform, we reveal that metallic Co species serve as highly efficient active sites for polyolefin hydrogenolysis. Furthermore, we introduced Ni into the Co framework to tackle the issue of restricted hydrogenation ability associated with contiguous Co-Co sites. In-situ analysis indicates that the integration of Ni induces electron transfer and facilitates hydrogen spillover. This dual effect synergistically enhances the hydrogenation/desorption of olefin intermediates, resulting in a significant reduction in the yield of low-value CH4 from 27.1 to 12.6%. Through leveraging the unique properties of LDH, we have developed efficient and cost-effective catalysts for the sustainable recycling and valorization of waste polyolefin materials.
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Schistosomiasis is caused by parasitic flatworms known as schistosomes and affects over 200 million people worldwide. Prevention of T cell exhaustion by blockade of PD-1 results in clinical benefits to cancer patients and clearance of viral infections, however it remains largely unknown whether loss of PD-1 could prevent or cure schistosomiasis in susceptible mice. In this study, we found that S. japonicum infection dramatically induced PD-1 expression in T cells of the liver where the parasites chronically inhabit and elicit deadly inflammation. Even in mice infected by non-egg-producing unisex parasites, we still observed potent induction of PD-1 in liver T cells of C57BL/6 mice following S. japonicum infection. To determine the function of PD-1 in schistosomiasis, we generated PD-1-deficient mice by CRISPR/Cas9 and found that loss of PD-1 markedly increased T cell count in the liver and spleen of infected mice. IL-4 secreting Th2 cells were significantly decreased in the infected PD-1-deficient mice whereas IFN-γ secreting CD4+ and CD8+ T cells were markedly increased. Surprisingly, such beneficial changes of T cell response did not result in eradication of parasites or in lowering the pathogen burden. In further experiments, we found that loss of PD-1 resulted in both beneficial T cell responses and amplification of regulatory T cells that prevented PD-1-deficient T cells from unleashing anti-parasite activity. Moreover, such PD-1-deficient Tregs exert excessive immunosuppression and express larger amounts of adenosine receptors CD39 and CD73 that are crucial for Treg-mediated immunosuppression. Our experimental results have elucidated the function of PD-1 in schistosomiasis and provide novel insights into prevention and treatment of schistosomiasis on the basis of modulating host adaptive immunity.
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Schistosoma japonicum , Esquistossomose Japônica , Animais , Humanos , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/genética , Linfócitos T ReguladoresRESUMO
Phosphorus (P) is a crucial macronutrient for plant growth, development, and reproduction. The effects of low P (LP) stress on leaf senescence and the role of PHR1 in LP-induced leaf senescence are still unknown. Here, we report that PHR1 plays a crucial role in LP-induced leaf senescence, showing delayed leaf senescence in phr1 mutant and accelerated leaf senescence in 35S:PHR1 transgenic Arabidopsis under LP stress. The transcriptional profiles indicate that 763 differentially expressed SAGs (DE-SAGs) were upregulated and 134 DE-SAGs were downregulated by LP stress. Of the 405 DE-SAGs regulated by PHR1, 27 DE-SAGs were involved in P metabolism and transport. PHR1 could bind to the promoters of six DE-SAGs (RNS1, PAP17, SAG113, NPC5, PLDζ2, and Pht1;5), and modulate them in LP-induced senescing leaves. The analysis of RNA content, phospholipase activity, acid phosphatase activity, total P and phosphate content also revealed that PHR1 promotes P liberation from senescing leaves and transport to young tissues under LP stress. Our results indicated that PHR1 is one of the crucial modulators for P recycling and redistribution under LP stress, and the drastic decline of P level is at least one of the causes of early senescence in P-deficient leaves.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Fósforo/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Senescência Vegetal , Fatores de Transcrição/metabolismo , Fosfatos/metabolismo , Folhas de Planta/metabolismo , Homeostase , Regulação da Expressão Gênica de PlantasRESUMO
Cladding-pumped multicore erbium-doped fiber is an important element for future spatial division multiplexing (SDM) amplification. We propose an M-type erbium-doped multicore fiber to achieve high-efficiency SDM amplification. The performance of cladding-pumped erbium-doped fiber with a central refractive index depression has been investigated, and the M-type fiber has better amplification performance than conventional fibers by reducing the signal mode overlap with the doped region. The experiment results show that the M-type 4-core erbium-doped fiber has a gain improvement of 2.8â dB compared with conventional 4-core fiber. The pump conversion efficiency (PCE) has been enhanced from 4.47% to 8.01%. For a 7.0 W pump power at 976â nm, the M-type fiber exhibits an average gain of 20.0â dB and an average noise fiber of 6.8â dB at the L-band. The core-to-core gain variation is less than 1.6â dB.
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Bismuth-doped germanosilicate fiber (BGSF), the active media of fiber amplifiers, has attracted widespread attention. Here, we report a BGSF with a high bismuth concentration of 0.075â wt. % and achieve high-efficiency E + S-band amplification, which was prepared by the modified chemical vapor deposition (MCVD) process. The small signal absorption (SSA) and unsaturated loss (UL) of BGSF at 1310â nm are 1.32 and 0.11â dB/m, respectively. The results show a record with only 45 m BGSF was created, to the best of our knowledge, which provides a maximum gain of 39.24â dB with an NF of 6.2â dB at 1430â nm under -20â dBm input signal power.
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Extending the gain bandwidth of L-band optical fiber amplifier has provoked a widespread interest. To date, achieving a high-efficiency extended L-band amplification remains a challenge. Here, we report a cladding-pumped Er/Yb co-doped alumino-phosphosilicate fiber, prepared by the modified chemical vapor deposition process. We demonstrate the efficiency of alumino-phosphosilicate glass for cladding-pumped Er/Yb co-doped fiber, with a gain per unit fiber length of 0.45â dB/m at 1625â nm and a gain ripple of â¼9.4â dB. For 0.8â W pump power, the fiber exhibits a 20â dB gain bandwidth covering 1575-1625â nm and 6.9â dB noise figure at 1625â nm. Additionally, the utilization of multi-mode laser diode enables further significant power savings and cost reduction. To the best of our knowledge, Er/Yb co-doped fiber in alumino-phosphosilicate glass is first proposed, with a cladding-pumped scheme for enhancing an extended L-band performance.
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Heart failure (HF) is a complex clinical syndrome associated with significant morbidity and mortality. Dysregulation of long non-coding RNA (lncRNA) has been implicated in the pathogenesis of HF. The present study aims to investigate the role of lncRNA HOX transcript antisense RNA (HOTAIR) in cardiomyocyte pyroptosis in a murine HF model. A murine HF model was established through transverse aortic contraction surgery, and an in vitro HF cell model was developed by treating HL-1 cells with H2O2. HOTAIR was overexpressed in TAC mice and HL-1 cells via pcDNA3.1-HOTAIR transfection. Cardiac function was assessed in TAC mice, and myocardial changes were evaluated using HE staining. The expression of NLRP3 was examined by immunohistochemistry. Myocardial injury markers and pyroptosis-related inflammatory cytokines were quantified using ELISA. Protein levels of NLRP3, cleaved-caspase-1, and GSDMD-N were analyzed by Western blot. Dual-luciferase assays and RNA immunoprecipitation were employed to confirm the binding interactions between HOTAIR and miR-17-5p, miR-17-5p and RORA. Functional rescue experiments were conducted by overexpressing miR-17-5p or silencing RORA in HL-1 cells. HOTAIR exhibited reduced expression in TAC mice and H2O2-induced cardiomyocytes. Overexpression of HOTAIR ameliorated cardiac dysfunction, reduced myocardial pathological injury, enhanced cardiomyocyte viability, and decreased myocardial injury and pyroptosis. HOTAIR interacted with miR-17-5p to repress RORA transcription. Overexpression of miR-17-5p or silencing of RORA abolished the inhibitory effect of HOTAIR overexpression on cardiomyocyte pyroptosis. In conclusion, HOTAIR competitively bound to miR-17-5p, relieving its inhibition of RORA transcription and leading to increased RORA expression and suppressed cardiomyocyte pyroptosis in HF models.
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Insuficiência Cardíaca , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Insuficiência Cardíaca/genética , Peróxido de Hidrogênio , MicroRNAs/genética , Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Piroptose/genética , RNA Longo não Codificante/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismoRESUMO
Glomalin-related soil protein (GRSP) is a significant component in the sequestration of heavy metal in soils, but its mechanisms for metal adsorption are poorly known. This study combined spectroscopic data with molecular docking simulations to reveal metal adsorption onto GRSP's surface functional groups at the molecular level. The EXAFS combined with FTIR and XPS analyses indicated that the adsorption of Cd(II), Sr(II), and Ni(II) by GRSP occurred mainly through the coordination of -OH and -COOH groups with the metal. The -COOH and -OH groups bound to the metal as electron donors and the electron density of the oxygen atom decreased, suggesting that electrostatic attraction might be involved in the adsorption process. Two-dimensional correlation spectroscopy revealed that preferential adsorption occurred on GRSP for the metal in sequential order of -COOH groups followed by -OH groups. The presence of the Ni-C shell in the Ni EXAFS spectrum suggested that Ni formed organometallic complexes with the GRSP surface. However, Sr-C and Cd-C were absent in the second shell of the Sr and Cd spectra, which was attributed to the adsorption of Sr and Cd ions with large hydration ion radius by GRSP to form outer-sphere complexes. Through molecular docking simulations, negatively charged residues such as ASP151 and ASP472 in GRSP were found to provide electrostatic attraction and ligand combination for the metal adsorption, which was consistent with the spectroscopic analyses. Overall, these findings provided new insights into the interaction mechanisms between GRSP and metals, which will help deepen our understanding of the ecological functions of GRSP in metal sequestration.
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Simulação de Acoplamento Molecular , Níquel , Níquel/química , Adsorção , Cádmio/química , Sedimentos Geológicos/química , Proteínas Fúngicas/química , Metais Pesados/química , Áreas Alagadas , Poluentes do Solo/química , GlicoproteínasRESUMO
Microplastics (MPs), emerging as significant pollutants, have been consistently detected in aquatic environments, with the Yangtze River experiencing a particularly severe level of microplastic pollution, exceeding all other watersheds in China. Polypropylene (PP), the plastic most abundantly found in the middle and lower reaches of the Yangtze River Basin, has less comprehensive research results into its toxic effects. Consequently, the present investigation employed zebrafish as a model organism to delve into the toxicological impacts of polypropylene microplastics (PP-MPs) with a diameter of 5 µm across varying concentrations (300â¯mg/L and 600â¯mg/L). Using histopathological, microbiota profiling, and transcriptomic approaches, we systematically evaluated the impact of PP-MPs exposure on the intestine and liver of zebrafish. Histopathological analysis revealed that exposure to PP-MPs resulted in thinner intestinal walls, damaged intestinal mucosa, and hepatic cellular damage. Intestinal microbiota profiling demonstrated that, the richness, uniformity, diversity, and homogeneity of gut microbes significantly increased after the PP-MPs exposure at high concentration. These alterations were accompanied by shifts in the relative abundance of microbiota associated with intestinal pathologies, suggesting a profound impact on the intestinal microbial community structure. Concurrently, hepatic transcriptome analysis and RT-qPCR indicated that the downregulation of pathways and genes associated with cell proliferation regulation and DNA damage repair mechanisms contributed to hepatic cellular damage, ultimately exerting adverse effects on the liver. Correlation analysis between the intestinal microbiota and liver transcriptome profiles further highlighted significant associations between intestinal microbiota and the downregulated hepatic pathways. Collectively, these results provide novel insights into the subacute toxicological mechanisms of PP-MPs in aquatic organisms and highlight the need for further research on the ecological and health risks associated with PP-MPs pollution.
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Microbioma Gastrointestinal , Fígado , Microplásticos , Polipropilenos , Poluentes Químicos da Água , Peixe-Zebra , Animais , Microplásticos/toxicidade , Polipropilenos/toxicidade , Poluentes Químicos da Água/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , China , Intestinos/efeitos dos fármacos , Intestinos/patologia , Transcriptoma/efeitos dos fármacos , Rios/química , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologiaRESUMO
AIM: To examine the level and influencing factors of discharge readiness among patients with oesophageal cancer following oesophagectomy and to explore its association with post-discharge outcomes (post-discharge coping difficulty and unplanned readmission). BACKGROUND: Oesophageal cancer is common and usually treated via oesophagectomy in China. The assessment of patient's discharge readiness gradually attracts attention as patients tend to be discharged more quickly. DESIGN: Prospective observational study. The STROBE statement was followed. METHODS: In total, 154 participants with oesophageal cancer after oesophagectomy were recruited in a tertiary cancer centre in Southern China from July 2019 to January 2020. The participants completed a demographic and disease-related questionnaire, the Quality of Discharge Teaching Scale and Readiness for Hospital Discharge Scale before discharge. Post-discharge outcomes were investigated on the 21st day (post-discharge coping difficulty) and 30th day (unplanned readmission) after discharge separately. Multiple linear regressions were used for statistical analysis. RESULTS: The mean scores of discharge readiness and quality of discharge teaching were (154.02 ± 31.58) and (138.20 ± 24.20) respectively. The quality of discharge teaching, self-care ability, dysphagia and primary caregiver mainly influenced patient's discharge readiness and explained 63.0% of the variance. The low discharge readiness could predict more risk of post-discharge coping difficulty (r = -0.729, p < 0.01) and unplanned readmission (t = -2.721, p < 0.01). CONCLUSIONS: Discharge readiness among patients with oesophageal cancer following oesophagectomy is influenced by various factors, especially the quality of discharge teaching. A high discharge readiness corresponds to good post-discharge outcomes. IMPLICATIONS FOR THE PROFESSION AND PATIENT CARE: Healthcare professionals should improve the discharge readiness by constructing high-quality discharge teaching, cultivating patients' self-care ability, mobilizing family participation and alleviating dysphagia to decrease adverse post-discharge outcomes among patients with oesophageal cancer. PATIENTS OR PUBLIC CONTRIBUTION: Patients with oesophageal cancer after oesophagectomy who met the inclusion criteria were recruited.
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BACKGROUND: Microsurgical training should be implemented with consideration of operative difficulties that occur in actual clinical situations. We evaluated the effectiveness of a novel clinical scenario simulator for step-by-step microsurgical training that progressed from conventional training to escalated training with additional obstacles. METHODS: A training device was designed according to multiple and intricate clinical microsurgery scenarios. Twenty surgical residents with no experience in microsurgery were randomly assigned to either the control group (conventional training curricula, n = 10) or the experimental group (step-by-step training courses, n = 10). After 4 weeks of laboratory practice, the participants were scheduled to perform their first microvascular anastomoses on patients in an operating room. The Global Rating Scale (GRS) scores and operative duration were used to compare microsurgical skills between the two groups. RESULTS: There were no significant differences in the participants' baseline characteristics before microsurgical training between the groups with respect to age, sex, postgraduate year, surgical specialty, or mean GRS score (p < 0.05). There were also no significant differences in recipient sites between the two groups (p = 0.735). After training, the GRS scores in both groups were significantly improved (p = 0.000). However, in the actual microsurgical situations, the GRS scores were significantly higher in the experimental than control group (p < 0.05). There was no significant difference in the operative duration between the two groups (p < 0.13). CONCLUSION: Compared with a traditional training program, this step-by-step microsurgical curriculum based on our clinical scenario simulator results in significant improvement in acquisition of microsurgical skills.
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Competência Clínica , Internato e Residência , Microcirurgia , Treinamento por Simulação , Microcirurgia/educação , Humanos , Treinamento por Simulação/métodos , Masculino , Feminino , Adulto , Educação de Pós-Graduação em Medicina/métodos , Currículo , Duração da Cirurgia , Anastomose Cirúrgica/educaçãoRESUMO
Erectile dysfunction (ED) is one of the most common sexual disorders in males, which seriously affects the health of the patient and well-being of the family. The therapeutic strategy of ED is an individualized comprehensive treatment based on phosphodiesterase inhibitors. At present, as a new option for the treatment of ED, micro-energy medicine has attracted more and more attention in its therapeutic effects and advantages. This article presents an overview of the progress in the studies of micro-energy medicine in the treatment of ED.
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Disfunção Erétil , Disfunção Erétil/terapia , Humanos , Masculino , Tratamento por Ondas de Choque Extracorpóreas/métodos , Inibidores de Fosfodiesterase/uso terapêuticoRESUMO
The adsorbate-mediated strong metal-support interaction (A-SMSI) offers a reversible means of altering the selectivity of supported metal catalysts, thereby providing a powerful tool for facile modulation of catalytic performance. However, the fundamental understanding of A-SMSI remains inadequate and methods for tuning A-SMSI are still in their nascent stages, impeding its stabilization under reaction conditions. Here, we report that the initial concentration of oxygen vacancy in oxide supports plays a key role in tuning the A-SMSI between Ru nanoparticles and defected titania (TiO2-x). Based on this new understanding, we demonstrate the in situ formation of A-SMSI under reaction conditions, obviating the typically required CO2-rich pretreatment. The as-formed A-SMSI layer exhibits remarkable stability at various temperatures, enabling excellent activity, selectivity and long-term stability in catalyzing the reverse water gas-shift reaction. This study deepens the understanding of the A-SMSI and the ability to stabilize A-SMSI under reaction conditions represents a key step for practical catalytic applications.
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Insect pathogenic fungi, also known as entomopathogenic fungi, are one of the largest insect pathogenic microorganism communities, represented by Beauveria spp. and Metarhizium spp. Entomopathogenic fungi have been proved to be a great substitute for chemical pesticide in agriculture. In fact, a lot of functional genes were also already characterized in entomopathogenic fungi, but more depth of exploration is still needed to reveal their complicated pathogenic mechanism to insects. Metarhizium rileyi (Nomuraea rileyi) is a great potential biocontrol fungus that can parasitize more than 40 distinct species (mainly Lepidoptera: Noctuidae) to cause large-scale infectious diseases within insect population. In this study, a comparative analysis of transcriptome profile was performed with topical inoculation and hemolymph injection to character the infectious pattern of M. rileyi. Appressorium and multiple hydrolases are indispensable constituents to break the insect host primary cuticle defense in entomopathogenic fungi. Within our transcriptome data, numerous transcripts related to destruction of insect cuticle rather growth regulations were obtained. Most importantly, some unreported ribosomal protein genes and novel unannotated protein (hypothetical protein) genes were proved to participate in the course of pathogenic regulation. Our current data provide a higher efficiency gene library for virulence factors screen in M. rileyi, and this library may be also useful for furnishing valuable information on entomopathogenic fungal pathogenic mechanisms to host.
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Metarhizium , Animais , Metarhizium/genética , Transcriptoma , Insetos/genética , Insetos/microbiologia , Perfilação da Expressão GênicaRESUMO
INTRODUCTION: The anatomical substrate for idiopathic left ventricular tachycardia (ILVT) remains speculative. Purkinje networks surrounding false tendons (FTs) might be involved in the reentrant circuit of ILVT. The objective was to evaluate the anatomical and electrophysiological features of false tendons FTs in relation to ILVT. METHODS: Intracardiac echocardiography (ICE) was conducted on patients with ILVT. The relationship of the FTs with ILVT was determined using electro-anatomical mapping. RESULTS: Electrophysiological evaluation and radiofrequency ablation were conducted in 23 consecutive patients with ILVT. FTs were identified in 19/23 cases (82.6%) with P1 potentials during VT recorded at the FT in 14 of these patients (73.7%). Three FT types were identified. In type 1, the FT attached the septum to the base of the posteromedial papillary muscle (PPM) (4/19); type 2 FTs ran between the septum and the PPM apex (3/19), while in type 3, the connection occurred between the septum and apex (11/19) or between the septum and the LV free wall (1/19). The effective ILVT ablation sites were situated at the FT-PPM (3/19) and the FT-septum (16/19) attachment sites. CONCLUSIONS: This series demonstrates the association between Purkinje fibers and FTs during catheter ablation of ILVT and verifies that left ventricular FTs are an important substrate in this type of tachycardia.
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Ablação por Cateter , Cardiopatias Congênitas , Taquicardia Ventricular , Humanos , Eletrocardiografia , Ramos Subendocárdicos , Ventrículos do CoraçãoRESUMO
We propose a scheme to realize robust optical entanglement in cavity optomagnonics, where two optical whispering gallery modes (WGMs) couple to a magnon mode in a yttrium iron garnet (YIG) sphere. The beam-splitter-like and two-mode squeezing magnon-photon interactions can be realized simultaneously when the two optical WGMs are driven by external fields. Entanglement between the two optical modes is then generated via their coupling with magnons. By exploiting the destructive quantum interference between the bright modes of the interface, the effects of initial thermal occupations of magnons can be eliminated. Moreover, the excitation of the Bogoliubov dark mode is capable of protecting the optical entanglement from thermal heating effects. Therefore, the generated optical entanglement is robust against thermal noise and the requirement of cooling the magnon mode is relaxed. Our scheme may find applications in the study of magnon-based quantum information processing.
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The extended L-band 4-core Er/Yb co-doped fiber and amplifier (MC-EYDFA) is first proposed and demonstrated, to the best of our knowledge, for space division multiplexing combined with wavelength division multiplexing application. The fiber core co-doped with Er/Yb/P is adopted for bandwidth expansion, and the long wavelength extends to 1625â nm. Numerical simulations further show that efficient amplification and higher saturation power are achieved with the 1018â nm cladding pumping. Based on the integrated 4-core fiber amplifier, an average gain of â¼22â dB covering 1575-1625â nm is experimentally obtained with a 4 W pump power and a 3 dBm total signal power, and the max core-dependent gain (CDG) variation is measured to be 1.7â dB.
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The 1.5-µm fiber laser is widely used in the fields of laser lidar, remote sensing, and gas monitoring because of its advantages of being eye-safe and exhibiting low atmospheric transmission loss. However, due to the â¼1-µm amplified spontaneous emission (ASE) of the Er/Yb co-doped fiber (EYDF), it is difficult to improve the laser power. Here, we simulated the effect of the Er3+ concentration and the seed power on â¼1-µm ASE, and fabricated a large mode area EYDF by the modified chemical vapor deposition process. Additionally, a piece of ytterbium-doped fiber was introduced into the master oscillator power amplifier (MOPA) configuration to absorb the generated â¼1-µm ASE simultaneously. Experimental results show that an output power of 345 W with a slope efficiency of 43% at 1535â nm is obtained in an all-fiber configuration, profiting from effective suppression of â¼ 1-µm ASE. To the best of our knowledge, this is the highest output power available with an Er/Yb co-doped fiber from an all-fiber MOPA configuration.
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T and B cells continually recirculate between blood and secondary lymphoid organs. To promote their trans-endothelial migration (TEM), chemokine receptors control the activity of RHO family small GTPases in part via GTPase-activating proteins (GAPs). T and B cells express several RHO-GAPs, the function of most of which remains unknown. The ARHGAP45 GAP is predominantly expressed in hematopoietic cells. To define its in vivo function, we describe two mouse models where ARHGAP45 is ablated systemically or selectively in T cells. We combine their analysis with affinity purification coupled to mass spectrometry to determine the ARHGAP45 interactome in T cells and with time-lapse and reflection interference contrast microscopy to assess the role of ARGHAP45 in T-cell polarization and motility. We demonstrate that ARHGAP45 regulates naïve T-cell deformability and motility. Under physiological conditions, ARHGAP45 controls the entry of naïve T and B cells into lymph nodes whereas under competitive repopulation it further regulates hematopoietic progenitor cell engraftment in the bone marrow, and T-cell progenitor thymus seeding. Therefore, the ARGHAP45 GAP controls multiple key steps in the life of T and B cells.
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Linfócitos T , Internalização do Vírus , Animais , Linfócitos B , Movimento Celular , Proteínas Ativadoras de GTPase/genética , Linfonodos , Camundongos , TimoRESUMO
Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.