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CD19-targeted chimeric antigen receptor (CAR) T cell therapies have driven a paradigm shift in the treatment of relapsed/refractory B-cell malignancies. However, >50% of CD19-CAR-T-treated patients experience progressive disease mainly due to antigen escape and low persistence. Clinical prognosis is heavily influenced by CAR-T cell function and systemic cytokine toxicities. Furthermore, it remains a challenge to efficiently, cost-effectively, and consistently manufacture clinically relevant numbers of virally engineered CAR-T cells. Using a highly efficient piggyBac transposon-based vector, Quantum pBac™ (qPB), we developed a virus-free cell-engineering system for development and production of multiplex CAR-T therapies. Here, we demonstrate in vitro and in vivo that consistent, robust and functional CD20/CD19 dual-targeted CAR-T stem cell memory (CAR-TSCM) cells can be efficiently produced for clinical application using qPB™. In particular, we showed that qPB™-manufactured CAR-T cells from cancer patients expanded efficiently, rapidly eradicated tumors, and can be safely controlled via an iCasp9 suicide gene-inducing drug. Therefore, the simplicity of manufacturing multiplex CAR-T cells using the qPB™ system has the potential to improve efficacy and broaden the accessibility of CAR-T therapies.
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Antígenos CD19 , Antígenos CD20 , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Antígenos CD19/imunologia , Humanos , Antígenos CD20/imunologia , Antígenos CD20/genética , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Animais , Camundongos , Engenharia Celular/métodos , Linfócitos T/imunologia , Linhagem Celular TumoralRESUMO
INTRODUCTION: Sharing mental models is essential for high-performance teams, and speaking up is key for exchanging critical insights, especially during medical errors. Understanding how health providers and trainees voice their concerns is crucial for improving speaking-up behavior. This study aims to fill a gap in the literature by examining how medical students speak up when they encounter medical errors and assessing the impact of training on their speaking-up patterns. METHOD: A quasi-experimental study involving 146 students, who were divided into two groups, was conducted in Northern Taiwan. One group of students encountered life-threatening scenario before intervention, followed by a faculty-led personalized debriefing session, then a non-life-threatening scenario after the intervention. Another group of students underwent these sessions in the reverse order. Students' Speaking-up patterns, including expression style, form and attitude, and their speaking-up confidence were assessed at pre- and post-intervention scenarios. RESULTS: During pre-intervention scenario, in expression style, 50 students (34.5%) addressed their concerns to medical errors with direct expression and 14 students (9.7%) utilized indirect hint to express their concerns. In expression form, 31 students (21.4%) addressed their concerns to medical errors with affirmative sentences and 33 students (22.8%) asked questions to express their concerns. In speaking-up attitude, 47 students (32.4%) used unoffensive words, while 17 students (11.7%) used offensive words. After intervention, significantly change of speaking-up styles, forms, and attitude were observed along with their speaking-up confidence (p < 0.001). DISCUSSION: Medical students are inclined to speak up in the event of medical errors using more direct expression and affirmative sentences, along with increased speaking-up confidence after simulation scenario learning and faculty-led personalized debriefing. Healthcare educators can focus more on discussing with students the advantages and disadvantages of various approaches of speaking-up in medical errors, helping them to develop effective speaking-up behaviors in a variety of medical contexts.
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This study investigated the influence of photoaging on a nanoscale metal-organic framework (MOF), truncated rhombic dodecahedron nano-zeolitic imidazolate framework-8 (nZIF-8), focusing on its oxidative stress, inflammation, and implications for pulmonary diseases. We observed significant photodegradation-induced transformations in nZIF-8, characterized by a reduction in particle size from 200.5 to 101.4 nm and notable structural disintegration after prolonged exposure to simulated solar radiation. This alteration resulted in a marked decrease in oxidative cytotoxicity in BEAS-2B cells, which was attributed to changes in surface properties and reduced reactive oxygen species (ROS) production. Gene expression analysis further revealed a decrease in cytotoxic and inflammatory responses, which potentially lowers the risk of chronic obstructive pulmonary disease (COPD). Aged nZIF-8 also showed diminished capacity to induce pro-inflammatory cytokines and influence COPD-related gene expression, reducing its potential to exacerbate COPD pathogenesis. Our findings highlight the critical need for comprehensive safety evaluations of these materials, while considering their long-term environmental and biological impacts. The diminished cytotoxicity and inflammatory potential of aged nZIF-8 highlighted its enhanced suitability for broader applications, indicating that photoaging may lead to safer and more sustainable material utilization.
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Ferroelectric catalysts are known for altering surface catalytic activities by changing the direction of their electric polarizations. This study demonstrates polarization-switchable electrochemistry using layered bismuth oxyselenide (L-Bi2O2Se) bifunctional microreactors through ferroelectric modulation. A selective-area ionic liquid gating is developed with precise control over the spatial distribution of the dipole orientation of L-Bi2O2Se. On-chip microreactors with upward polarization favor the oxygen evolution reaction, whereas those with downward polarization prefer the hydrogen evolution reaction. The microscopic origin behind polarization-switchable electrochemistry primarily stems from enhanced surface adsorption and reduced energy barriers for reactions, as examined by nanoscale scanning electrochemical cell microscopy. Integrating a pair of L-Bi2O2Se microreactors consisting of upward or downward polarizations demonstrates overall water splitting in a full-cell configuration based on a bifunctional catalyst. The ability to modulate surface polarizations on a single catalyst via ferroelectric polarization switching offers a pathway for designing catalysts for water splitting.
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BACKGROUND: In Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan. METHODS: The incidence of candidemia and fluconazole susceptibility of Candida species before (2015-2019) and during COVID-19 pandemic (2020-2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136). RESULTS: Age (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01-1.03), ICU stay (AOR = 1.84, 95% CI: 1.29-2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03-1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04-2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29-0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38-0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar. CONCLUSION: While the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.
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PURPOSE: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. METHODS: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. RESULTS: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. CONCLUSION: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients.
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Autoanticorpos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Nocardiose , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Nocardiose/imunologia , Nocardiose/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Proteinose Alveolar Pulmonar/imunologia , Proteinose Alveolar Pulmonar/diagnóstico , Cryptococcus gattii/imunologiaRESUMO
Context: Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). Objective: To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Methods: Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. Results: RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. Conclusion: This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.
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Manipulating electronic polarizations such as ferroelectric or spin polarizations has recently emerged as an effective strategy for enhancing the efficiency of photocatalytic reactions. This study demonstrates the control of electronic polarizations modulated by ferroelectric and magnetic approaches within a two-dimensional (2D) layered crystal of copper indium thiophosphate (CuInP2S6) to boost the photocatalytic reduction of CO2. We investigate the substantial influence of ferroelectric polarization on the photocatalytic CO2 reduction efficiency, utilizing the ferroelectric-paraelectric phase transition and polarization alignment through electrical poling. Additionally, we explore enhancing the CO2 reduction efficiency by harnessing spin electrons through the synergistic introduction of sulfur vacancies and applying a magnetic field. Several advanced characterization techniques, including piezoresponse force microscopy, ultrafast pump-probe spectroscopy, in situ X-ray absorption spectroscopy, and in situ diffuse reflectance infrared Fourier transformed spectroscopy, are performed to unveil the underlying mechanism of the enhanced photocatalytic CO2 reduction. These findings pave the way for manipulating electronic polarizations regulated through ferroelectric or magnetic modulations in 2D layered materials to advance the efficiency of photocatalytic CO2 reduction.
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In situ spectral reflectance initially captured at high spatial resolution with underwater hyperspectral imaging (UHI) is effective for classification and quantification in oceanic biogeochemical studies; however, the measured spectral radiance is rarely used as an absolute quantity due to challenges in calibration of UHI instruments. In this paper, a commercial UHI instrument was calibrated for radiometric flat field response and pixelwise immersion effect to support in situ measurement of absolute spectral radiance. The radiometric and immersion factor calibrations of the UHI instrument were evaluated quantitatively through comparative experiments with a spectroradiometer and a spectrometer. Results show that the immersion factor of the center pixel of the tested UHI instrument was 1.763 in pure water at 600 nm, and the averaged difference in immersion factor between the center and edge pixel of the UHI instrument in the visible light band was only 1â¼3% across its half angle field of view of 35° in air. The new calibration coefficients were further used to calculate the spectral radiance of transmitted sunlight through ice algae clusters in sea ice measured by the UHI instrument during an Arctic under-ice bio-optical survey.
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Histoplasmosis is a global infection caused by the thermally dimorphic fungus, Histoplasma capsulatum complex. It is endemic in the United States, as well as in Central and South America. In Taiwan, histoplasmosis is rare, with the first reported case not occurring until 1977. We summarized a total of 17 cases reported in Taiwan over the past 40 years and provided detailed descriptions for four probable indigenous cases. Due to the lack of rapid diagnostic tools and clinical suspicion, histoplasmosis may be underdiagnosed in Taiwan. We recognize that a limitation of our review is the lack of data on the environmental surveillance for H. capsulatum complex in Taiwan. Conducting a further phylogenetic analysis on both environmental and clinical isolates would provide valuable evidence for the region.
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BACKGROUND: The inherent problems in the existence of electron equilibrium and steep dose fall-off pose difficulties for small- and narrow-field dosimetry. OBJECTIVE: To investigate the cutout factors for keloid electron radiotherapy using various dosimetry detectors for small and narrow fields. METHOD: The measurements were performed in a solid water phantom with nine different cutout shapes. Five dosimetry detectors were used in the study: pinpoint 3D ionization chamber, Farmer chamber, semiflex chamber, Classic Markus parallel plate chamber, and EBT3 film. RESULTS: The results demonstrated good agreement between the semiflex and pinpoint chambers. Furthermore, there was no difference between the Farmer and pinpoint chambers for large cutouts. For the EBT3 film, half of the cases had differences greater than 1%, and the maximum discrepancy compared with the reference chamber was greater than 2% for the narrow field. CONCLUSION: The parallel plate, semiflex chamber and EBT3 film are suitable dosimeters that are comparable with pinpoint 3D chambers in small and narrow electron fields. Notably, a semiflex chamber could be an alternative option to a pinpoint 3D chamber for cutout widths≥3âcm. It is very important to perform patient-specific cutout factor calibration with an appropriate dosimeter for keloid radiotherapy.
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Elétrons , Imagens de Fantasmas , Radiometria , Dosagem Radioterapêutica , Radiometria/métodos , Radiometria/instrumentação , Humanos , Queloide/radioterapiaRESUMO
Objectives: To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods: This prospective case-control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results: After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions: Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.
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The pursuit of high-performance electronic devices has driven the research focus toward 2D semiconductors with high electron mobility and suitable band gaps. Previous studies have demonstrated that quasi-2D Bi2O2Se (BOSe) has remarkable physical properties and is a promising candidate for further exploration. Building upon this foundation, the present work introduces a novel concept for achieving nonvolatile and reversible control of BOSe's electronic properties. The approach involves the epitaxial integration of a ferroelectric PbZr0.2Ti0.8O3 (PZT) layer to modify BOSe's band alignment. Within the BOSe/PZT heteroepitaxy, through two opposite ferroelectric polarization states of the PZT layer, we can tune the Fermi level in the BOSe layer. Consequently, this controlled modulation of the electronic structure provides a pathway to manipulate the electrical properties of the BOSe layer and the corresponding devices.
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Spin-to-charge conversion at the interface between magnetic materials and transition metal dichalcogenides has drawn great interest in the research efforts to develop fast and ultralow power consumption devices for spintronic applications. Here, we report room temperature observations of spin-to-charge conversion arising from the interface of Ni80Fe20 (Py) and molybdenum disulfide (MoS2). This phenomenon can be characterized by the inverse Edelstein effect length (λIEE), which is enhanced with decreasing MoS2 thicknesses, demonstrating the dominant role of spin-orbital coupling (SOC) in MoS2. The spin-to-charge conversion can be significantly improved by inserting a Cu interlayer between Py and MoS2, suggesting that the Cu interlayer can prevent magnetic proximity effect from the Py layer and protect the SOC on the MoS2 surface from exchange interactions with Py. Furthermore, the Cu-MoS2 interface can enhance the spin current and improve electronic transport. Our results suggest that tailoring the interface of magnetic heterostructures provides an alternative strategy for the development of spintronic devices to achieve higher spin-to-charge conversion efficiencies.
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Understanding the magnetic and ferroelectric ordering of magnetoelectric multiferroic materials at the nanoscale necessitates a versatile imaging method with high spatial resolution. Here, soft X-ray ptychography is employed to simultaneously image the ferroelectric and antiferromagnetic domains in an 80 nm thin freestanding film of the room-temperature multiferroic BiFeO3 (BFO). The antiferromagnetic spin cycloid of period 64 nm is resolved by reconstructing the corresponding resonant elastic X-ray scattering in real space and visualized together with mosaic-like ferroelectric domains in a linear dichroic contrast image at the Fe L3 edge. The measurements reveal a near perfect coupling between the antiferromagnetic and ferroelectric ordering by which the propagation direction of the spin cycloid is locked orthogonally to the ferroelectric polarization. In addition, the study evinces both a preference for in-plane propagation of the spin cycloid and changes of the ferroelectric polarization by 71° between multiferroic domains in the epitaxial strain-free, freestanding BFO film. The results provide a direct visualization of the strong magnetoelectric coupling in BFO and of its fine multiferroic domain structure, emphasizing the potential of ptychographic imaging for the study of multiferroics and non-collinear magnetic materials with soft X-rays.
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In patients with repaired tetralogy of Fallot (rTOF), the regurgitant fraction (RF) in left pulmonary artery (LPA) and right pulmonary artery (RPA) is usually unequal. The morphometrics may play a crucial role in this RF discrepancy. Cardiovascular MR of 79 rTOF patients and 20 healthy controls were retrospectively enrolled. Forty-four from the 79 patients were matched in age, sex and body surface area to the 20 controls and were investigated for: (1) phase-contrast flow of main pulmonary artery (MPA), LPA, and RPA; (2) vascular angles: the angles between the thoracic anterior-posterior line (TAPL) with MPA (θM-AP), MPA with RPA (θM-R), and MPA with LPA (θM-L); (3) cardiac angle, the angle between TAPL and the interventricular septum; (4) area ratio of bilateral lung and hemithorax regions. Compared with the 20 controls, the 44 rTOF patients exhibited wider θM-AP, sharper θM-L angle, and a smaller θM-L/θM-R ratio. In the 79 rTOF patients, LPA showed lower forward, backward, and net flow, and greater RF as compared with RPA. Multivariate analysis showed that the RF of LPA was negatively associated with the θM-L/θM-R ratio and the age at surgery (R2 = 0.255). Conversely, the RF of RPA was negatively associated with the left lung/left hemithorax area ratio and cross-sectional area (CSA) of LPA, and positively associated with CSA of RPA and MPA (R2 = 0.366). In rTOF patients, the RF of LPA is more severe than that of RPA, which may be related to the vascular morphometrics. Different morphometric parameters are independently associated with the RF of LPA or RPA, which may offer potential insights for surgical strategies.
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Insuficiência da Valva Pulmonar , Tetralogia de Fallot , Septo Interventricular , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Estudos Retrospectivos , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/etiologia , Insuficiência da Valva Pulmonar/cirurgia , Valor Preditivo dos TestesRESUMO
An integrated, remotely sensed approach to assess land-use and land-cover change (LULCC) dynamics plays an important role in environmental monitoring, management, and policy development. In this study, we utilized the advantage of land-cover seasonality, canopy height, and spectral characteristics to develop a phenology-based classification model (PCM) for mapping the annual LULCC in our study areas. Monthly analysis of normalized difference vegetation index (NDVI) and near-infrared (NIR) values derived from SPOT images enabled the detection of temporal characteristics of each land type, serving as crucial indices for land type classification. The integration of normalized difference built-up index (NDBI) derived from Landsat images and airborne LiDAR canopy height into the PCM resulted in an overall performance of 0.85, slightly surpassing that of random forest analysis or principal component analysis. The development of PCM can reduce the time and effort required for manual classification and capture annual LULCC changes among five major land types: forests, built-up land, inland water, agriculture land, and grassland/shrubs. The gross change LULCC analysis for the Taoyuan Tableland demonstrated fluctuations in land types over the study period (2013 to 2022). A negative correlation (r = - 0.79) in area changes between grassland/shrubs and agricultural land and a positive correlation (r = 0.47) between irrigation ponds and agricultural land were found. Event-based LULCC analysis for Taipei City demonstrated a balance between urbanization and urban greening, with the number of urbanization events becoming comparable to urban greening events when the spatial extent of LULCC events exceeds 1000 m2. Besides, small-scale urban greening events are frequently discovered and distributed throughout the metropolitan area of Taipei City, emphasizing the localized nature of urban greening events.
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Monitoramento Ambiental , Tecnologia de Sensoriamento Remoto , Agricultura , Formulação de Políticas , LagoasRESUMO
Many insects have evolved the ability to manipulate plant growth to generate extraordinary structures called galls, in which insect larva can develop while being sheltered and feeding on the plant. In particular, cynipid (Hymenoptera: Cynipidae) wasps have evolved to form morphologically complex galls and generate an astonishing array of gall shapes, colors, and sizes. However, the biochemical basis underlying these remarkable cellular and developmental transformations remains poorly understood. A key determinant in plant cellular development is cell wall deposition that dictates the physical form and physiological function of newly developing cells, tissues, and organs. However, it is unclear to what degree cell walls are restructured to initiate and support the formation of new gall tissue. Here, we characterize the molecular alterations underlying gall development using a combination of metabolomic, histological, and biochemical techniques to elucidate how valley oak (Quercus lobata) leaf cells are reprogrammed to form galls. Strikingly, gall development involves an exceptionally coordinated spatial deposition of lignin and xylan to form de novo gall vasculature. Our results highlight how cynipid wasps can radically change the metabolite profile and restructure the cell wall to enable the formation of galls, providing insights into the mechanism of gall induction and the extent to which plants can be entirely reprogrammed to form unique structures and organs.
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Parede Celular , Interações Hospedeiro-Parasita , Tumores de Planta , Vespas , Animais , Parede Celular/metabolismo , Vespas/fisiologia , Tumores de Planta/parasitologia , Quercus/metabolismo , Quercus/parasitologia , Folhas de Planta/metabolismo , Folhas de Planta/parasitologia , Lignina/metabolismoRESUMO
Recently, carbon quantum dots (CQDs) have become popular because of their simple synthesis and potential applications. Although CQDs have high biocompatibility, their biotoxicity must be verified to reduce the possible risks associated with large-scale application. In this study, the hepatotoxicity of three CQD types, namely diammonium citrate (AC)-based (CQDs-AC), spermidine trihydrochloride (Spd)-based (CQDs-Spd), and AC- and Spd-based CQDs (CQDs-AC/Spd), were evaluated in vivo and in vitro. It was observed in vivo that CQDs-Spd and CQDs-AC/Spd, but not CQDs-AC, caused histopathological damage, including liver steatosis and mild mixed inflammatory cell infiltration; however, reduced liver function was only observed in CQD-Spd-treated mice. The in vitro results revealed that only CQDs-Spd significantly decreased the number of viable HepG2 cells (NADH depletion) and induced oxidative stress (heme oxygenase-1 activation) after 24 h of exposure, which promoted inflammatory factor secretion (NF-κB activation). Additionally, decreasing zonula occludens-2 and α1-antitrypsin protein expression in HepG2 cells suggested that CQD-Spd exposure increases the risk of liver diseases. Our results revealed that CQDs-Spd had greater hepatotoxic potential than CQDs-AC and CQDs-AC/Spd, which might be attributable to their high positive surface charge. Overall, the risk of CQD-induced hepatotoxic risk must be considered when applying positively charged CQDs.