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Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus consisting of both latent and lytic life cycles. Primary effusion lymphoma (PEL) is an aggressive B-cell lineage lymphoma, dominantly latently infected by KSHV. The latent infection of KSHV is persistent and poses an obstacle to killing tumor cells. Like the "shock and kill" strategy designed to eliminate latent HIV reservoir, methods that induce viral lytic reactivation in tumor latently infected by viruses represent a unique antineoplastic strategy, as it could potentially increase the specificity of cytotoxicity in cancer. Inspired by this conception, we proposed that the induction of KSHV lytic reactivation from latency could be a potential therapeutic stratagem for KSHV-associated cancers. Oxidative stress, the clinical hallmark of PEL, is one of the most prominent inducers for KSHV reactivation. Paradoxically, we found that hydrogen peroxide (H2O2) triggers robust cytotoxic effects on KSHV-negative rather than KSHV-positive B lymphoma cells in a dose-dependent manner. Mechanistically, we identified forkhead box protein O1 (FoxO1) and FoxO3 as irrevocable antioxidant defense genes and both of them are upregulated by KSHV latent infection, which is essential for the promoted ROS scavenging in KSHV-positive B lymphoma cells. Pharmacological inhibition or functional knockdown of either FoxO1 or FoxO3 is sufficient to ablate the antioxidant ability and therefore increases the intracellular ROS level that further reverses KSHV from latency to active lytic replication in PEL cells, resulting in tremendous cell death both in vitro and in vivo. Additionally, the elevated level of ROS by inhibiting FoxO proteins further sensitizes PEL cells to ROS-induced apoptosis. Our study therefore demonstrated that the lytic reactivation of KSHV by inhibiting FoxO proteins is a promising therapeutic approach for PEL, which could be further extended to other virus-associated diseases.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , HIV-1 , Herpesviridae , Herpesvirus Humano 8 , Linfoma de Efusão Primária , Humanos , Antioxidantes , Peróxido de Hidrogênio , Espécies Reativas de Oxigênio , Latência ViralRESUMO
BACKGROUND: Balloon pulmonary angioplasty (BPA) improves the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH). Right ventricle (RV) is an important predictor of prognosis in CTEPH patients. 2D-speckle tracking echocardiography (2D-STE) can evaluate RV function. This study aimed to evaluate the effectiveness of BPA in CTEPH patients and to assess the value of 2D-STE in predicting outcomes of BPA. METHODS: A total of 76 patients with CTEPH underwent 354 BPA sessions from January 2017 to October 2022. Responders were defined as those with mean pulmonary artery pressure (mPAP) ≤ 30 mmHg or those showing ≥ 30% decrease in pulmonary vascular resistance (PVR) after the last BPA session, compared to baseline. Logistic regression analysis was performed to identify predictors of BPA efficacy. RESULTS: BPA resulted in a significant decrease in mPAP (from 50.8 ± 10.4 mmHg to 35.5 ± 11.9 mmHg, p < 0.001), PVR (from 888.7 ± 363.5 dyn·s·cm-5 to 545.5 ± 383.8 dyn·s·cm-5, p < 0.001), and eccentricity index (from 1.3 to 1.1, p < 0.001), and a significant increase in RV free wall longitudinal strain (RVFWLS: from 15.7% to 21.0%, p < 0.001). Significant improvement was also observed in the 6-min walking distance (from 385.5 m to 454.5 m, p < 0.001). After adjusting for confounders, multivariate analysis showed that RVFWLS was the only independent predictor of BPA efficacy. The optimal RVFWLS cutoff value for predicting BPA responders was 12%. CONCLUSIONS: BPA was found to reduce pulmonary artery pressure, reverse RV remodeling, and improve exercise capacity. RVFWLS obtained by 2D-STE was an independent predictor of BPA outcomes. Our study may provide a meaningful reference for interventional therapy of CTEPH.
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Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/terapia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/terapia , Remodelação Ventricular , Ecocardiografia , Doença Crônica , Artéria Pulmonar/diagnóstico por imagemRESUMO
PURPOSE: This study aimed to explore the role of atorvastatin (ATO) in the prevention and treatment of the scarring of filtration channels after glaucoma surgery. METHODS: Human Tenon's capsule fibroblasts (HTFs) were co-cultured with various concentrations of ATO. First, Cell Counting Kit-8 assay was performed to evaluate the effects of various concentrations of ATO on the viability of HTFs. Then, after the ATO stimulated the HTFs for 24 h, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate the apoptosis of HTFs. Transwell assay was also performed to evaluate the migration of HTFs. Moreover, enzyme-linked immunosorbent assay (ELISA) was performed to detect the protein expression levels of transforming growth factor-ß1 (TGF-ß1) and TGF-ß2 in the cell culture supernatant of HTFs. Western blot was carried out to detect the protein expression levels of smooth muscle actin (SMA), p38, Smad3, fibronectin, collagen I and collagen III in different groups. RESULTS: The results revealed that ATO could inhibit the proliferation and migration of HTFs. Based on the TUNEL assay, 100 µM and 150 µM ATO could induce cell apoptosis. The ELISA results indicated that ATO could down-regulate the expression level of TGF-ß2, and western blot analysis revealed that the protein expression levels of SMA, p38, Smad3, fibronectin, collagen I and collagen III in the TGF-ß2 group were all up-regulated compared with the control group, whereas the addition of ATO could reverse this up-regulation. CONCLUSIONS: ATO could inhibit the proliferation and migration of HTFs and induce their apoptosis. It was preliminary proven that ATO could inhibit the signaling pathway induced by TGF-ß. It is suggested that ATO could be a basis for the treatment of the scarring of filtration channels after glaucoma surgery.
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Glaucoma , Cápsula de Tenon , Humanos , Cápsula de Tenon/patologia , Fator de Crescimento Transformador beta2/farmacologia , Fator de Crescimento Transformador beta2/metabolismo , Fibronectinas/metabolismo , Fibronectinas/farmacologia , Atorvastatina/farmacologia , Atorvastatina/metabolismo , Glaucoma/metabolismo , Cicatriz/patologia , Células Cultivadas , Fibroblastos , Colágeno/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo I/farmacologia , Proliferação de CélulasRESUMO
ConspectusLoading metal nanoparticles on the surface of solid supports has emerged as an efficient route for the preparation of heterogeneous catalysts. Notably, most of these supported metal nanoparticles still have shortcomings such as dissatisfactory activity and low product selectivity in catalysis. In addition, these metal nanoparticles also suffer from deactivation because of nanoparticle sintering, leaching, and coke formation under harsh conditions. The fixation of metal nanoparticles within zeolite crystals should have advantages of high activities for metal nanoparticles and excellent shape selectivity for zeolite micropores as well as extraordinary stability of metal nanoparticles immobilized with a stable zeolite framework, which is a good solution for the shortcomings of supported metal nanoparticles.Materials with metal nanostructures within the zeolite crystals are normally denoted as metal@zeolite, where the metal nanoparticles with diameters similar to those of industrial catalysts are usually larger than the micropore size. These metal nanoparticles are enveloped with the zeolite rigid framework to prevent migration under harsh reaction conditions, which is described as a fixed structure. The zeolite micropores allow the diffusion of reactants to the metal nanoparticles. As a result, metal@zeolite catalysts combine the features of both metal nanoparticles (high activity) and zeolites (shape selectivity and thermal stability), compared with the supported metal nanoparticles.In this Account, we describe how the zeolite micropore and metal nanoparticle synergistically work to improve the catalytic performance by the preparation of a variety of metal@zeolite catalysts. Multiple functions of zeolites with respect to the metal nanoparticles are highlighted, including control of the reactant/product diffusion in the micropores, the adjustment of reactant adsorption on the metal nanoparticles, and sieving the reactants and products with zeolite micropores. Furthermore, by optimizing the wettability of the zeolite external surface, the zeolite crystals could form a nanoreactor to efficiently enrich the crucial intermediates, thus boosting the performance in low-temperature methane oxidation. Also, the microporous confinement weakens the adsorption of C1 intermediates on the metal sites, accelerating the C-C coupling to improve C2 oxygenate productivity in syngas conversion. In particular, the zeolite framework efficiently stabilizes the metal nanoparticles against sintering and leaching to give durable catalysts. Clearly, this strategy not only guides the rational design of efficient heterogeneous catalysts for potential applications in a variety of industrial chemical reactions but also accelerates the fundamental understanding of the catalytic mechanisms by providing new model catalysts.
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A vast amount of energy can be extracted from the untapped low-grade heat from sources below 100 °C and the Gibbs free energy from salinity gradients. Therefore, a process for simultaneous and direct conversion of these energies into electricity using permselective membranes was developed in this study. These membranes screen charges of ion flux driven by the combined salinity and temperature gradients to achieve thermo-osmotic energy conversion. Increasing the charge density in the pore channels enhanced the permselectivity and ion conductance, leading to a larger osmotic voltage and current. A 14-fold increase in power density was achieved by adjusting the ionic site population of covalent organic framework (COF) membranes. The optimal COF membrane was operated under simulated estuary conditions at a temperature difference of 60â K, which yielded a power density of ≈231â W m-2 , placing it among the best performing upscaled membranes. The developed system can pave the way to the utilization of the enormous supply of untapped osmotic power and low-grade heat energy, indicating the tremendous potential of using COF membranes for energy conversion applications.
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A method for the solidification of metallic alloys involving spiral self-organization is presented as a new strategy for producing large-area chiral patterns with emergent structural and optical properties, with attention to the underlying mechanism and dynamics. This study reports the discovery of a new growth mode for metastable, two-phase spiral patterns from a liquid metal. Crystallization proceeds via a non-classical, two-step pathway consisting of the initial formation of a polytetrahedral seed crystal, followed by ordering of two solid phases that nucleate heterogeneously on the seed and grow in a strongly coupled fashion. Crystallographic defects within the seed provide a template for spiral self-organization. These observations demonstrate the ubiquity of defect-mediated growth in multi-phase materials and establish a pathway toward bottom-up synthesis of chiral materials with an inter-phase spacing comparable to the wavelength of infrared light. Given that liquids often possess polytetrahedral short-range order, our results are applicable to many systems undergoing multi-step crystallization.
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BACKGROUND: Conjunctival filtering bleb scar formation is the main reason for the failure of glaucoma filtration surgery. Cytoglobin (Cygb) has been reported to play an important role in extracellular matrix (ECM) remodeling, fibrosis and tissue damage repairing. This study aimed to investigate the role of Cygb in anti-scarring during excessive conjunctival wound healing after glaucoma filtration surgery. METHODS: Cygb was overexpressed in human tenon fibroblasts (hTFs) by transfecting hTFs with lentiviral particles encoding pLenti6.2-FLAG-Cygb. Changes in the mRNA and protein levels of fibronectin, collagen I, collagen III, TGF-ß1, and HIF1α were determined by RT-PCR and western blotting respectively. RESULTS: After Cygb overexpression, hTFs displayed no significant changes in visual appearance and cell counts compared to controls. Whereas, Cygb overexpression significantly decreased the mRNA and protein expression levels of collagen I, collagen III and fibronectin compared with control (p < 0.01). There was also a statistically significant decrease in the mRNA and protein levels of TGF-ß1 and HIF-1α in hTFs with overexpressed Cygb compared with control group (p < 0.05). CONCLUSION: Our study provided evidence that overexpression of Cygb decreased the expression levels of fibronectin, collagen I, collagen III, TGF-ß1 and HIF-1α in hTFs. Therefore, therapies targeting Cygb expression in hTFs may pave a new way for clinicians to solve the problem of post-glaucoma surgery scarring.
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Citoglobina/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Cápsula de Tenon/metabolismo , Colágeno/análise , Citoglobina/farmacologia , Matriz Extracelular/efeitos dos fármacos , Fibronectinas/análise , Humanos , RNA Mensageiro/análise , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Oxidative stress can cause injury in retinal endothelial cells. Carboxymethyl cellulose modified with collagen peptide (CMCC) is of a distinct antioxidant capacity and potentially a good drug carrier. In this study, the protective effects of CMCC against H2 O2 -induced injury of primary retinal endothelial cells were investigated. In vitro, we demonstrated that CMCC significantly promoted viability of H2 O2 -treated cells, efficiently restrained cellular reactive oxygen species (ROS) production and cell apoptosis. Then, the CMCC was employed as both drug and anti-inflammatory drug carrier for treatment of retinal ischaemia/reperfusion (I/R) in rats. Animals were treated with CMCC or interleukin-10-loaded CMCC (IL-10@CMCC), respectively. In comparisons, the IL-10@CMCC treatment exhibited superior therapeutic effects, including better restoration of retinal structural thickness and less retinal apoptosis. Also, chemiluminescence demonstrated that transplantation of IL-10@CMCC markedly reduced the retinal oxidative stress level compared with CMCC alone and potently recovered the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that CMCC provides a promising platform to enhance the drug-based therapy for I/R-related retinal injury.
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Antioxidantes/administração & dosagem , Inflamação/tratamento farmacológico , Interleucina-10/administração & dosagem , Traumatismo por Reperfusão/tratamento farmacológico , Retina/efeitos dos fármacos , Animais , Antioxidantes/química , Apoptose/efeitos dos fármacos , Carboximetilcelulose Sódica/administração & dosagem , Carboximetilcelulose Sódica/química , Catalase/genética , Colágeno/administração & dosagem , Colágeno/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Humanos , Peróxido de Hidrogênio/toxicidade , Inflamação/patologia , Interleucina-10/química , Estresse Oxidativo , Peptídeos/administração & dosagem , Peptídeos/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/patologia , Retina/patologiaRESUMO
Zeolites with intricate micropores have been widely studied for a long time as an important class of porous materials in different areas of industrial processes such as gas adsorption and separation, ion exchange, and shape-selective catalysis. However, their industrial syntheses are not sustainable, and normally require the presence of expensive organic templates and a large amount of solvents such as water. The presence of organic templates not only increases zeolite cost but also produces harmful gases during the removal of these templates by calcination, while the use of solvents significantly increases the amount of polluted water. This Personal Account briefly summarizes recent sustainable routes for the synthesis of zeolites in our group according to our understanding of the synthetic mechanism, and mainly focuses on the organotemplate-free synthesis of zeolites in the presence of zeolite seeds, the design of environmentally friendly templates, and solvent-free synthesis of zeolites.
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PURPOSE: There is increasing evidence that suggests stromal cell-derived factor-1 (SDF-1) can induce a protective response against ischemic injury in various organs. In this study, we examined the expression of SDF-1 in a rat model of retinal ischemia-reperfusion (IR) injury. Further, we explored the effect of estrogen 17ß-estradiol (E2), and the role of estrogen receptor (ER) in regulating SDF-1 expression. METHODS: Retinal IR injury was established in Sprague-Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 mins. Relative expression levels of SDF-1 mRNA and protein in the retina at 6 h, 12 h, and 24 h after reperfusion were determined by RT-PCR and western blot respectively. To investigate the influence of estrogen and ER on SDF-1 expression, E2 was administered intraperitoneally 30 mins before induction of ischemia, and the estrogen receptor antagonist ICI 182-780 was administered 1 h before E2 injection. RESULTS: SDF-1 expression in IR-injured retina is upregulated at 6 h, 12 h, and 24 h after injury, with maximum expression at 12 h. As expected, pretreatment of retinal IR rats with E2 enhanced the upregulation in SDF-1 expression after injury, through activation of the estrogen receptor. We proved this hypothesis by demonstrating that pretreatment of retinal IR rats with ICI 182-780 led to a partial decrease in E2-induced SDF-1 expression. CONCLUSIONS: Our findings suggest that 17ß-estradiol offers protection against retinal ischemic injury by inducing an upregulation in SDF-1 expression through activation of the estrogen receptor.
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Quimiocina CXCL12/genética , Estradiol/farmacologia , Estrogênios/farmacologia , Regulação da Expressão Gênica/fisiologia , Receptores de Estrogênio/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Retina/efeitos dos fármacos , Animais , Western Blotting , Quimiocina CXCL12/metabolismo , Modelos Animais de Doenças , Estradiol/análogos & derivados , Antagonistas do Receptor de Estrogênio/farmacologia , Fulvestranto , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Retina/metabolismo , Regulação para CimaRESUMO
In this paper, actively Q-switched laser operation with an acousto-optic switch has been demonstrated by using Yb:Ca3La2(BO3)4 crystals cut along the a, b, and c crystallographic axes. The most efficient Q-switched laser operation was obtained by using b-cut Yb:Ca3La2(BO3)4 crystal with 1 kHz pulse repetition frequency, generating laser pulses of 0.5 mJ, 42.56 KW peak power and 9 ns pulse width, when the output couplings were 3%, 5%, and 5%, respectively. Pulse performances and output laser spectra of the a-, b-, and c-cut Yb:Ca3La2(BO3)4 crystals were compared under similar experimental conditions.
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A novel self-Q-switched and orthogonally polarized dual-wavelength laser has been investigated with Yb³âº-doped CGB disordered crystals. By slightly inclining output coupler to introduce the Fresnel loss, we realized simultaneously dual-wavelength laser operation at 1052.6 nm in E//b polarization and 1057.7 nm in E//c polarization with a frequency difference of 1.38 THz. Self-Q-switched pulse generation was observed in this free-running laser, originating from the nonlinear reabsorption effect of Yb:CGB as well as the strong storage of inversion population induced by the long excited-state lifetime (~1 ms). Pulse duration of 287 ns was obtained with an output average power of 416 mW and a repetition rate of 35 kHz. The self-Q-switching effect increased the peak power by 100 times the average power. This very simple laser, free from the complexity and high-cost of additional intracavity polarization modulator and Q-switcher, may be applied for constructing miniature, integrated and portable laser system.
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Lightning strike events pose significant challenges to the structural integrity and performance of composite materials, particularly in aerospace, wind turbine blade, and infrastructure applications. Through a meticulous examination of the state-of-the-art methodologies of laboratory testing and damage predictive modeling, this review elucidates the role of simulated lightning strike tests in providing inputs required for damage modeling and experimental data for model validations. In addition, this review provides a holistic understanding of what is there, what are current issues, and what is still missing in both lightning strike testing and modeling to enable a robust and high-fidelity predictive capability, and challenges and future recommendations are also presented. The insights gleaned from this review are poised to catalyze advancements in the safety, reliability, and durability of composite materials under lightning strike conditions, as well as to facilitate the development of innovative lightning damage mitigation strategies.
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Background: The relationship between obesity, sexual behavior, and prostate cancer (PCa) has been widely debated, contributing to a lack of understanding of its potential mechanisms and hindering the development of effective prevention measures. Purpose: The aim of this study was to examine the causal effect of body mass index (BMI), age at first sexual intercourse (AFS), and bioavailable testosterone levels on PCa while also quantifying the potential roles of mediators. Method: We conducted a Mendelian randomization (MR) study using summary statistics from genome-wide associations of BMI (152,893 European males), AFS (182,791 European males), bioavailable testosterone (184,205 European males), and PCa (79,148 cases, 61,106 controls, European ancestry). Inverse-variance weighted method, weighted median method, MR-Egger regression, Least Absolute Shrinkage and Selection Operator (LASSO), and outlier test were used for MR analyses. Reverse MR and mediation analysis were performed. Data analyses were conducted from December 2022 to July 2023. Results: The results showed that genetic liability to BMI was protective of PCa (OR, 0.82; 95% CI: 0.74-0.91; P = 3.29 × 10-4). Genetic liability to later AFS (OR, 1.28; 95% CI: 1.08-1.53; P = 5.64 × 10-3) and higher bioavailable testosterone levels (OR = 1.11, 95% CI: 1.01-1.24, P = 0.04) were associated with an increased risk of PCa. All of these potential causal effects could only be forwarded and were not affected by prostate specific antigen (PSA) screening. After controlling for bioavailable testosterone levels, the causal impact of BMI and AFS on PCa was no longer significant. The mediation analysis suggested that the causal influence of AFS/BMI on PCa relied on bioavailable testosterone levels. Conclusion: In conclusion, the difference between the univariable and multivariable MR results suggested that the causal influence of BMI and AFS on PCa relied on bioavailable testosterone levels. Further work is needed to identify other risk factors and to elucidate the specific mechanisms that underlie this causal pathway.
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Rhamnus leptacantha C.K.Schneid. (1914). is a rare shrub species of the genus Rhamnus. The complete plastid genome of Rhamnus leptacantha was sequenced for the first time in this study. The total length of this genome is 161,248 bp with a large single copy (LSC) region (89,386 bp), a small single copy (SSC) region (19,000 bp), and two inverted repeat regions (IRs, 26,431 bp). A total of 133 functional genes were annotated, including 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Plastome of R. leptacantha displayed a conservative structure and gene order. Phylogenetic analysis strongly supported R. leptacantha clustered with other members of genus Rhamnus. This study provides a foundation for further investigation of the complete chloroplast genome in inferring the evolution within the Rhamnaceae family.
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Diarrhea is the most common issue in sheep farms, typically due to pathogenic Escherichia coli (E. coli) infections, such as E. coli F17. microRNA, a primary type of non-coding RNA, has been shown to be involved in diarrhea caused by pathogenic E. coli. To elucidate the profound mechanisms of miRNA in E. coli F17 infections, methods such as E. coli F17 adhesion assay, colony counting assay, relative quantification of bacterial E. coli fimbriae gene expression, indirect immune fluorescence (IF), Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Western blotting (WB), and scratch assay were conducted to investigate the effect of miR-329b-5p overexpression/knock-down on E. coli F17 susceptibility of sheep intestinal epithelial cells (IECs). The findings indicated that miR-329b-5p enhances the E. coli F17 resistance of sheep IECs to E.coli F17 by promoting adhesion between E. coli F17 and IEC, as well as IEC proliferation and migration. In summary, miR-329b-5p plays a crucial role in the defense of sheep IECs against E. coli F17 infection, providing valuable insights into its mechanism of action.
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A promising mid-infrared (MIR) laser crystal with Er, Sm co-doped SrLaAlO4 (Er,Sm:SLA) crystal was successfully grown using the Czochralski (CZ) method. It was the first time that co-doped Sm3+ ion as deactivator for Er3+ activated â¼ 3.0 µm laser. The crystal structure, absorption spectra, emission spectra, and energy level lifetime were discussed in detail. The band structure and density of states were calculated by the density functional theory. The spectral parameters were calculated using Judd-Ofelt (J-O) theory and the deactivate effect of Sm3+ was systematically studied. The introduction of Sm3+ ions enhance the 2.7 µm mid infrared emission intensity by three times, and decrease the lifetime of 4I13/2 energy level of Er3+ ion from 4.35 ms to 0.98 ms. The lifetime ratio of upper and lower levels for 2.7 µm emission was calculated to be 0.63, which is 2.6 times of Er:SLA crystal and comparable to some commercial crystals. All the results indicate that the Sm3+ ion is an effective deactivator for â¼3 µm laser emission. The long upper level lifetime, as well as the large lifetime ratio, the broadening spectra characteristics and the appropriate emission cross-section show the Er,Sm:SLA crystal a good gain material for ultrafast and tunable lasers at â¼3.0 µm.
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Background: Balloon pulmonary angioplasty (BPA) is an established treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its efficacy in CTEPH patients with a pulmonary comorbidity has not been well-studied. Here, we compared post-BPA outcomes between CTEPH patients with and without chronic pulmonary disease at baseline and analyzed predictors of BPA success. Methods: From August 2017 to October 2022, 62 patients with inoperable CTEPH who underwent BPA were consecutively enrolled and grouped based on the presence of a pulmonary comorbidity at baseline. All patients underwent transthoracic echocardiography, pulmonary function tests, and right heart catheterization. Pre- and post-BPA data were evaluated to identify factors that influence the success of BPA. Results: Among the 62 CTEPH patients, BPA was considered successful in 50 patients and unsuccessful in 12 patients. Responders to BPA had better exercise capacity and right heart function at baseline, but no differences in hemodynamic or respiratory function were detected between the groups. In CTEPH patients with chronic pulmonary disease (n = 14), BPA significantly improved mean pulmonary arterial pressure, pulmonary vascular resistance and right heart function parameters. Only CTEPH patients without chronic pulmonary disease (n = 48) exhibited significant improvement in 6-minute walk distance and respiratory function. Multivariate logistic regression analysis showed that pulmonary comorbidity at baseline was independently associated with the efficacy of BPA. Conclusions: BPA provided significantly improvements in hemodynamics and right heart function in CTEPH patients, independent of pulmonary comorbidity at baseline. However, pulmonary comorbidity can negatively impact post-BPA outcomes.
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Major depressive disorder (MDD) is the most prevalent mental disorder characterized by anhedonia, loss of motivation, avolition, behavioral despair and cognitive abnormalities. Despite substantial advancements in the pathophysiology of MDD in recent years, the pathogenesis of this disorder is not fully understood. Meanwhile,the treatment of MDD with currently available antidepressants is inadequate, highlighting the urgent need for clarifying the pathophysiology of MDD and developing novel therapeutics. Extensive studies have demonstrated the involvement of nuclei such as the prefrontal cortex (PFC), hippocampus (HIP), nucleus accumbens (NAc), hypothalamus, etc., in MDD. NAc,a region critical for reward and motivation,dysregulation of its activity seems to be a hallmark of this mood disorder. In this paper, we present a review of NAc related circuits, cellular and molecular mechanisms underlying MDD and share an analysis of the gaps in current research and possible future research directions.