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Osteocytes perceive and process mechanical stimuli in the lacuno-canalicular network in bone. As a result, they secrete signaling molecules that mediate bone formation and resorption. To date, few three-dimensional (3D) models exist to study the response of mature osteocytes to biophysical stimuli that mimic fluid shear stress and substrate strain in a mineralized, biomimetic bone-like environment. Here we established a biomimetic 3D bone model by utilizing a state-of-art perfusion bioreactor platform where immortomouse/Dmp1-GFP-derived osteoblastic IDG-SW3 cells were differentiated into mature osteocytes. We evaluated proliferation and differentiation properties of the cells on 3D microporous scaffolds of decellularized bone (dBone), poly(L-lactide-co-trimethylene carbonate) lactide (LTMC), and beta-tricalcium phosphate (ß-TCP) under physiological fluid flow conditions over 21 days. Osteocyte viability and proliferation were similar on the scaffolds with equal distribution of IDG-SW3 cells on dBone and LTMC scaffolds. After seven days, the differentiation marker alkaline phosphatase (Alpl), dentin matrix acidic phosphoprotein 1 (Dmp1), and sclerostin (Sost) were significantly upregulated in IDG-SW3 cells (p = 0.05) on LTMC scaffolds under fluid flow conditions at 1.7 ml/min, indicating rapid and efficient maturation into osteocytes. Osteocytes responded by inducing the mechanoresponsive genes FBJ osteosarcoma oncogene (Fos) and prostaglandin-endoperoxide synthase 2 (Ptgs2) under perfusion and dynamic compressive loading at 1 Hz with 5 % strain. Together, we successfully created a 3D biomimetic platform as a robust tool to evaluate osteocyte differentiation and mechanobiology in vitro while recapitulating in vivo mechanical cues such as fluid flow within the lacuno-canalicular network. STATEMENT OF SIGNIFICANCE: This study highlights the importance of creating a three-dimensional (3D) in vitro model to study osteocyte differentiation and mechanobiology, as cellular functions are limited in two-dimensional (2D) models lacking in vivo tissue organization. By using a perfusion bioreactor platform, physiological conditions of fluid flow and compressive loading were mimicked to which osteocytes are exposed in vivo. Microporous poly(L-lactide-co-trimethylene carbonate) lactide (LTMC) scaffolds in 3D are identified as a valuable tool to create a favorable environment for osteocyte differentiation and to enable mechanical stimulation of osteocytes by perfusion and compressive loading. The LTMC platform imitates the mechanical bone environment of osteocytes, allowing the analysis of the interaction with other cell types in bone under in vivo biophysical stimuli.
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Reatores Biológicos , Diferenciação Celular , Osteócitos , Osteócitos/citologia , Osteócitos/metabolismo , Animais , Alicerces Teciduais/química , Camundongos , Perfusão , Estresse Mecânico , Linhagem Celular , Proliferação de Células , Força Compressiva , Modelos BiológicosRESUMO
A ratiometric sensor with ultralow background is highly desired due to its low environmental influence and high sensitivity. Herein, inspired by the solubility difference of carboxylate in aqueous and organic solvents, we prepared a core-shell structure porous zirconia-covalent organic framework (COF) composite through thermal hydrolysis of UiO-66-COF precursors in organic alkali solution. The ligand 2-aminoterephthalic acids (H2BDC-NH2) of UiO-66 were transformed into 2-aminoterephthalate salts (ATA salts) that existed in zirconium-oxo clusters building units. The composites emitted only yellow emission (597 nm) from the COF in organic solvent due to the insolubility of ATA salts that induce aggregation-caused quenching (ACQ) and the protection of the COF shell. Contrarily, when water was added into mixture, the ATA salts were released into solution and its fluorescence recovered at 446 nm, while the fluorescence of COF was quenched due to the blockage of the intramolecular charge transfer (ICT) process by water. Thus, a high-sensitivity ratiometric fluorescence method is obtained with ultralow background signal and fast response (less than 1 min) for sensing water in organic solvent. We believe that the proposed ratiometric fluorescence sensor based on the zirconia-COF composite will provide the guidance for detection with wide applications.
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The electrochemical reduction of carbon dioxide (CO2) to ethylene creates a carbon-neutral approach to converting carbon dioxide into intermittent renewable electricity. Exploring efficient electrocatalysts with potentially high ethylene selectivity is extremely desirable, but still challenging. In this report, a laboratory-designed catalyst HKUST-1@Cu2O/PTFE-1 is prepared, in which the high specific surface area of the composites with improved CO2 adsorption and the abundance of active sites contribute to the increased electrocatalytic activity. Furthermore, the hydrophobic interface constructed by the hydrophobic material polytetrafluoroethylene (PTFE) effectively inhibits the occurrence of hydrogen evolution reactions, providing a significant improvement in the efficiency of CO2 electroreduction. The distinctive structures result in the remarkable hydrocarbon fuels generation with high Faraday efficiency (FE) of 67.41%, particularly for ethylene with FE of 46.08% (-1.0 V vs RHE). The superior performance of the catalyst is verified by DFT calculation with lower Gibbs free energy of the intermediate interactions with improved proton migration and selectivity to emerge the polycarbonï¼C2+ï¼ product. In this work, a promising and effective strategy is presented to configure MOF-based materials with tailored hydrophobic interface, high adsorption selectivity and more exposed active sites for enhancing the efficiency of the electroreduction of CO2 to C2+ products with high added value.
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Breast cancer is a common cancer in which patients are highly susceptible to different sleep disturbances. However, current evidence lacked consistency in methodologies in investigating the prevalence of sleep disturbances among breast cancer survivors. The review aims to (1) investigate the global prevalence of sleep disturbances among breast cancer survivors; and (2) investigate the factors influencing the prevalence estimates. A comprehensive search was conducted in 8 databases using a 3-step approach, up to January 2022. The Newcastle-Ottawa Scale and Cochrane risk of bias tool were used to evaluate the quality of individual studies. Meta-analysis, meta-regression, and subgroup analysis were performed using R software. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations criteria. A total of 51 studies were selected involving 28,036 breast cancer survivors across 17 countries. The global prevalence of poor sleep quality was 62%, different severities of insomnia were 3%-32%, and excessive daytime sleepiness was 24%. Subgroup analyses showed that a significantly higher prevalence of poor sleep quality was found in breast cancer survivors during treatment compared with pre- or post-treatment. No significant covariates were found in a series of meta-regression analyses. The majority (73.5%) of individual studies were high quality but the certainty of the evidence was low or very low according to Grading of Recommendations, Assessment, Development, and Evaluations criteria. More than half of breast cancer survivors have sleep disturbances, so developing a strategic intervention is warranted. Given the low or very low certainty of the evidence, a robust design for large-scale research is crucial in the future.
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Excitons in two-dimensional transition metal dichalcogenides have a valley degree of freedom that can be optically manipulated for quantum information processing. Here, we integrate MoS2 monolayers with achiral silicon disk array metasurfaces to enhance and control valley-specific absorption and emission. Through the coupling to the metasurface electric and magnetic Mie modes, the intensity and lifetime of the emission of neutral excitons, trions, and defect bound excitons can be enhanced and shortened, respectively, while the spectral shape can be modified. Additionally, the degree of polarization (DOP) of exciton and trion emission from the valley can be symmetrically enhanced at 100 K. The DOP increase is attributed to both the metasurface-enhanced chiral absorption of light and the metasurface-enhanced exciton emission from the Purcell effect. Combining Si-compatible photonic design with large-scale 2D materials integration, our work makes an important step toward on-chip valleytronic applications approaching room-temperature operation.
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BACKGROUND: While the world's population ages, social isolation has continued to increase globally. However, no review exists on the prevalence of social isolation among community-dwelling older adults, and the global prevalence remains uncertain. This study aims to estimate the global prevalence of social isolation among community-dwelling older adults and to identify potential covariates including study characteristics (methodological diversity) or populations (clinical diversity) that contribute to the heterogeneity. METHODS: This review searched through seven search engines and databases. The meta-analysis was conducted using the metafor package in the R software. The random-effects model was used to calculate the prevalence rates. Cochran's Q statistics and I2 statistics were used to assess the statistical heterogeneity of prevalence estimates. Studies were appraised using the Newcastle-Ottawa Scale and the Grading of Recommendations, Assessment, Development, and Evaluations criteria for the quality of individual articles and the certainty of the evidence, respectively. RESULTS: A total of 41 studies were selected from databases and reference lists. The pooled prevalence rate was 25% (95% CI: 21.0-30.0). The sample size was found to be a significant covariate of the prevalence estimate in the subgroup analysis. CONCLUSIONS: We found 13 high-quality studies, but the overall quality of evidence very low. This study provides the prevalence of social isolation in community-dwelling older adults, identifying vulnerable groups for targeted intervention. Well-designed observational research with standard measures is recommended for future studies.
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Vida Independente , Isolamento Social , Humanos , Idoso , PrevalênciaRESUMO
Aging, an irreversible and unavoidable physiological process in all organisms, is often accompanied by obesity, diabetes, cardiovascular diseases, sleep disorders, and fatigue. Thus, older adults are more likely to experience metabolic symptoms and sleep disturbances than are younger adults. Restricted feeding (RF) is a dietary regimen aimed at improving metabolic health and extending longevity, as well as reorganizing sleep-wake cycles. However, the potential of RF to improve metabolic health and sleep quality in older adults who are known to show a tendency toward increased weight gain and decreased sleep is unknown. To elucidate this issue, aged mice were assigned to an RF protocol during the active phase for 2 h per day for 2 weeks. Sleep-wake cycles were recorded during the RF regime in RF group and control mice. At the end of this period, body weight and blood biochemistry profiles, including blood glucose, cholesterol, and enzyme activity, in addition to dopamine concentrations in the brain, were measured in the RF group and age-matched controls. RF for 2 weeks improved the metabolic health of aged mice by reducing their body weights and blood glucose and cholesterol levels. At the beginning of the RF regime, sleep decreased in the dark period but not in the light period. After stable food entrainment was achieved (7 days post-RF commencement), the amount of time spent in wakefulness during the light period dramatically increased for 2 h before food availability, thereby increasing the mean duration of awake episodes and decreasing the number of wakefulness episodes. There was no significant difference in the sleep-wake time during the dark period in the RF group, with similar total amounts of wakefulness and sleep in a 24-h period to those of the controls. During the RF regime, dopamine levels in the midbrain increased in the RF group, pointing to its potential as the mechanism mediating metabolic symptoms and sleep-wake regulation during RF. In conclusion, our study suggested that RF during aging might prohibit or delay the onset of age-related diseases by improving metabolic health, without having a severe deleterious effect on sleep.
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Capture and conversion of CO2 from oceanwater can lead to net-negative emissions and can provide carbon source for synthetic fuels and chemical feedstocks at the gigaton per year scale. Here, we report a direct coupled, proof-of-concept electrochemical system that uses a bipolar membrane electrodialysis (BPMED) cell and a vapor-fed CO2 reduction (CO2R) cell to capture and convert CO2 from oceanwater. The BPMED cell replaces the commonly used water-splitting reaction with one-electron, reversible redox couples at the electrodes and demonstrates the ability to capture CO2 at an electrochemical energy consumption of 155.4 kJ mol-1 or 0.98 kWh kg-1 of CO2 and a CO2 capture efficiency of 71%. The direct coupled, vapor-fed CO2R cell yields a total Faradaic efficiency of up to 95% for electrochemical CO2 reduction to CO. The proof-of-concept system provides a unique technological pathway for CO2 capture and conversion from oceanwater with only electrochemical processes.
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A fundamental understanding of hot-carrier dynamics in photo-excited metal nanostructures is needed to unlock their potential for photodetection and photocatalysis. Despite numerous studies on the ultrafast dynamics of hot electrons, so far, the temporal evolution of hot holes in metal-semiconductor heterostructures remains unknown. Here, we report ultrafast (t < 200 fs) hot-hole injection from Au nanoparticles into the valence band of p-type GaN. The removal of hot holes from below the Au Fermi level is observed to substantially alter the thermalization dynamics of hot electrons, reducing the peak electronic temperature and the electron-phonon coupling time of the Au nanoparticles. First-principles calculations reveal that hot-hole injection modifies the relaxation dynamics of hot electrons in Au nanoparticles by modulating the electronic structure of the metal on timescales commensurate with electron-electron scattering. These results advance our understanding of hot-hole dynamics in metal-semiconductor heterostructures and offer additional strategies for manipulating the dynamics of hot carriers on ultrafast timescales.
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We report the light-induced modification of catalytic selectivity for photoelectrochemical CO2 reduction in aqueous media using copper (Cu) nanoparticles dispersed onto p-type nickel oxide (p-NiO) photocathodes. Optical excitation of Cu nanoparticles generates hot electrons available for driving CO2 reduction on the Cu surface, while charge separation is accomplished by hot-hole injection from the Cu nanoparticles into the underlying p-NiO support. Photoelectrochemical studies demonstrate that optical excitation of plasmonic Cu/p-NiO photocathodes imparts increased selectivity for CO2 reduction over hydrogen evolution in aqueous electrolytes. Specifically, we observed that plasmon-driven CO2 reduction increased the production of carbon monoxide and formate, while simultaneously reducing the evolution of hydrogen. Our results demonstrate an optical route toward steering the selectivity of artificial photosynthetic systems with plasmon-driven photocathodes for photoelectrochemical CO2 reduction in aqueous media.
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We describe the fabrication and use of arrays of TiO2 nanocones to yield high optical transmission into semiconductor photoelectrodes covered with high surface loadings of light-absorbing electrocatalysts. Covering over 50% of the surface of a light absorber with an array of high-refractive-index TiO2 nanocones imparted antireflective behavior (<5% reflectance) to the surface and allowed >85% transmission of broadband light to the underlying Si, even when thick metal contacts or opaque catalyst coatings were deposited on areas of the light-facing surface that were not directly beneath a nanocone. Three-dimensional full-field electromagnetic simulations for the 400-1100 nm spectral range showed that incident broadband illumination couples to multiple waveguide modes in the TiO2 nanocones, reducing interactions of the light with the metal layer. A proof-of-concept experimental demonstration of light-driven water oxidation was performed using a p+n-Si photoanode decorated with an array of TiO2 nanocones additionally having a Ni catalyst layer electrodeposited onto the areas of the p+n-Si surface left uncovered by the TiO2 nanocones. This photoanode produced a light-limited photocurrent density of â¼28 mA cm-2 under 100 mW cm-2 of simulated air mass 1.5 illumination, equivalent to the photocurrent density expected for a bare planar Si surface even though 54% of the front surface of the Si was covered by an â¼70 nm thick Ni metal layer.
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Photoelectrochemical deposition of Se-Te on isolated Au islands using an unstructured, incoherent beam of light produces growth of Se-Te alloy toward the direction of the incident light beam. Full-wave electromagnetic simulations of light absorption indicated that the induced spatial growth anisotropy was a function of asymmetric absorption in the evolving deposit. Inorganic phototropic growth is analogous to biological systems such as palm trees that exhibit phototropic growth wherein physical extension of the plant guides the crown toward the time-averaged position of the sun, to maximize solar harvesting.
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Galvanoplastia , Selênio/química , Telúrio/química , Eletroquímica , Processos FotoquímicosRESUMO
Tunable metasurfaces enable dynamical control of the key constitutive properties of light at a subwavelength scale. To date, electrically tunable metasurfaces at near-infrared wavelengths have been realized using free carrier modulation, and switching of thermo-optical, liquid crystal and phase change media. However, the highest performance and lowest loss discrete optoelectronic modulators exploit the electro-optic effect in multiple-quantum-well heterostructures. Here, we report an all-dielectric active metasurface based on electro-optically tunable III-V multiple-quantum-wells patterned into subwavelength elements that each supports a hybrid Mie-guided mode resonance. The quantum-confined Stark effect actively modulates this volumetric hybrid resonance, and we observe a relative reflectance modulation of 270% and a phase shift from 0° to ~70°. Additionally, we demonstrate beam steering by applying an electrical bias to each element to actively change the metasurface period, an approach that can also realize tunable metalenses, active polarizers, and flat spatial light modulators.
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Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200â»300 µm) and large (200â»500 µm) pores by salt leaching to stimulate chondrocyte differentiation, cartilage formation, and endochondral ossification. The scaffold surface was treated with tyramine to promote scaffold integration into native tissue. Porcine chondrocytes retained a round shape during differentiation when grown on the small pore size scaffold, and had a fibroblast-like morphology during transdifferentiation in the large pore size scaffold after five days of culture. Tyramine-treated scaffolds with mixed pore sizes seeded with chondrocytes were pressed into three-mm porcine osteochondral defects; tyramine treatment enhanced the adhesion of the small pore size scaffold to osteochondral tissue and increased glycosaminoglycan and collagen type II (Col II) contents, while reducing collagen type X (Col X) production in the cartilage layer. Col X content was higher for scaffolds with a large pore size, which was accompanied by the enhanced generation of subchondral bone. Thus, chondrocytes seeded in tyramine-treated bilayered scaffolds with small and large pores in the upper and lower parts, respectively, can promote osteochondral regeneration and integration for articular cartilage repair.
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Cartilagem Articular/citologia , Condrócitos/citologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Regeneração , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Tiramina/química , Animais , Materiais Biocompatíveis/química , Colágeno/metabolismo , Força Compressiva , Modelos Animais , Espectroscopia Fotoeletrônica , Porosidade , Propriedades de Superfície , Suínos , Água/químicaRESUMO
Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6-/-), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH) cell differentiation and T cell metabolism. In vitro, DUSP6-/- CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6-/- mice and in transgenic OTII-DUSP6-/- mice at steady state. After immunization, DUSP6-/- and OTII-DUSP6-/- mice generated more TFH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6-/- T cells showed enhanced JNK and p38 phosphorylation but impaired glycolysis. JNK or p38 inhibitors significantly reduced IL-21 production but did not restore glycolysis. TCR-stimulated DUSP6-/- T cells could not induce phosphofructokinase activity and relied on glucose-independent fueling of mitochondrial respiration. Upon CD28 costimulation, activated DUSP6-/- T cells did not undergo the metabolic commitment to glycolysis pathway to maintain viability. Unexpectedly, inhibition of fatty acid oxidation drastically lowered IL-21 production in DUSP6-/- TFH cells. Our findings suggest that DUSP6 connects TCR signaling to activation-induced metabolic commitment toward glycolysis and restrains TFH cell differentiation via inhibiting IL-21 production.
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Diferenciação Celular/fisiologia , Fosfatase 6 de Especificidade Dupla , Glicólise/fisiologia , Receptores de Antígenos de Linfócitos T , Transdução de Sinais/fisiologia , Linfócitos T Auxiliares-Indutores , Animais , Formação de Anticorpos/fisiologia , Antígenos CD28/genética , Antígenos CD28/imunologia , Antígenos CD28/metabolismo , Fosfatase 6 de Especificidade Dupla/genética , Fosfatase 6 de Especificidade Dupla/imunologia , Fosfatase 6 de Especificidade Dupla/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Interleucinas/genética , Interleucinas/imunologia , Interleucinas/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/imunologia , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Consumo de Oxigênio/fisiologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Harvesting nonequilibrium hot carriers from plasmonic-metal nanostructures offers unique opportunities for driving photochemical reactions at the nanoscale. Despite numerous examples of hot electron-driven processes, the realization of plasmonic systems capable of harvesting hot holes from metal nanostructures has eluded the nascent field of plasmonic photocatalysis. Here, we fabricate gold/p-type gallium nitride (Au/p-GaN) Schottky junctions tailored for photoelectrochemical studies of plasmon-induced hot-hole capture and conversion. Despite the presence of an interfacial Schottky barrier to hot-hole injection of more than 1 eV across the Au/p-GaN heterojunction, plasmonic Au/p-GaN photocathodes exhibit photoelectrochemical properties consistent with the injection of hot holes from Au nanoparticles into p-GaN upon plasmon excitation. The photocurrent action spectrum of the plasmonic photocathodes faithfully follows the surface plasmon resonance absorption spectrum of the Au nanoparticles and open-circuit voltage studies demonstrate a sustained photovoltage during plasmon excitation. Comparison with Ohmic Au/p-NiO heterojunctions confirms that the vast majority of hot holes generated via interband transitions in Au are sufficiently hot to inject above the 1.1 eV interfacial Schottky barrier at the Au/p-GaN heterojunction. We further investigated plasmon-driven photoelectrochemical CO2 reduction with the Au/p-GaN photocathodes and observed improved selectivity for CO production over H2 evolution in aqueous electrolytes. Taken together, our results offer experimental validation of photoexcited hot holes more than 1 eV below the Au Fermi level and demonstrate a photoelectrochemical platform for harvesting hot carriers to drive solar-to-fuel energy conversion.
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Emission control of colloidal quantum dots (QDs) is a cornerstone of modern high-quality lighting and display technologies. Dynamic emission control of colloidal QDs in an optoelectronic device is usually achieved by changing the optical pump intensity or injection current density. Here we propose and demonstrate a distinctly different mechanism for the temporal modulation of QD emission intensity at constant optical pumping rate. Our mechanism is based on the electrically controlled modulation of the local density of optical states (LDOS) at the position of the QDs, resulting in the modulation of the QD spontaneous emission rate, far-field emission intensity, and quantum yield. We manipulate the LDOS via field effect-induced optical permittivity modulation of an ultrathin titanium nitride (TiN) film, which is incorporated in a gated TiN/SiO2/Ag plasmonic heterostructure. The demonstrated electrical control of the colloidal QD emission provides a new approach for modulating intensity of light in displays and other optoelectronics.
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Autoimmune hypophysitis (AH) is a chronic inflammatory disease characterized by infiltration of T and B lymphocytes in the pituitary gland. The mechanisms through which infiltrating lymphocytes cause disease remain unknown. Using a mouse model of AH we assessed whether T lymphocytes undergo activation in the pituitary gland. Infiltrating T cells co-localized with dendritic cells in the pituitary and produced increased levels of interferon-γ and interleukin-17 upon stimulation in vitro. Assessing proliferation of CD3- and B220-postive lymphocytes by double immunohistochemistry (PCNA-staining) and flow cytometry (BrdU incorporation) revealed that a discrete proportion of infiltrating T cells and B cells underwent proliferation within the pituitary parenchyma. This proliferation persisted into the late disease stage (day 56 post-immunization), indicating the presence of a continuous generation of autoreactive T and B cells within the pituitary gland. T cell proliferation in the pituitary was confirmed in patients affected by autoimmune hypophysitis. In conclusion, we show that pituitary-infiltrating lymphocytes proliferate in situ during AH, providing a previously unknown pathogenic mechanism and new avenues for treatment.