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Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.
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Mapeo Encefálico , Indoles , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Adulto Joven , Odorantes , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Percepción Olfatoria/fisiología , Emociones/fisiología , Olfato/fisiologíaRESUMEN
Sensing of environmental challenges, such as mechanical injury, by a single plant tissue results in the activation of systemic signaling, which attunes the plant's physiology and morphology for better survival and reproduction. As key signals, both calcium ions (Ca2+ ) and hydrogen peroxide (H2 O2 ) interplay with each other to mediate plant systemic signaling. However, the mechanisms underlying Ca2+ -H2 O2 crosstalk are not fully revealed. Our previous study showed that the interaction between glycolate oxidase and catalase, key enzymes of photorespiration, serves as a molecular switch (GC switch) to dynamically modulate photorespiratory H2 O2 fluctuations via metabolic channeling. In this study, we further demonstrate that local wounding induces a rapid shift of the GC switch to a more interactive state in systemic leaves, resulting in a sharp decrease in peroxisomal H2 O2 levels, in contrast to a simultaneous outburst of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived apoplastic H2 O2 . Moreover, the systemic response of the two processes depends on the transmission of Ca2+ signaling, mediated by glutamate-receptor-like Ca2+ channels 3.3 and 3.6. Mechanistically, by direct binding and/or indirect mediation by some potential biochemical sensors, peroxisomal Ca2+ regulates the GC switch states in situ, leading to changes in H2 O2 levels. Our findings provide new insights into the functions of photorespiratory H2 O2 in plant systemic acclimation and an optimized systemic H2 O2 signaling via spatiotemporal interplay between the GC switch and NADPH oxidases.
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Oxidorreductasas de Alcohol , Plantas , Catalasa/metabolismo , Plantas/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Receptores de Glutamato , Peróxido de Hidrógeno/metabolismoRESUMEN
In this multicentre, real-world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in T-lymphoblastic lymphoma (T-LBL). A total of 130 Ann Arbor stage III or IV T-LBL patients (>16 years) treated with allo-HSCT across five transplant centres were enrolled. The 2-year cumulative incidence of disease progression, the probabilities of progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM) after allo-HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo-HSCT in NR were associated with disease progression. Thus, our real-world data suggested that allo-HSCT appeared to be an effective therapy for adult T-LBL patients with Ann Arbor stage III or IV disease.
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Trasplante de Células Madre Hematopoyéticas , Humanos , Adulto , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Adolescente , Adulto Joven , Trasplante Homólogo , Acondicionamiento Pretrasplante/métodos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Supervivencia sin EnfermedadRESUMEN
An ultrahigh-speed phase demodulation system was designed for the Fabry-Perot (F-P) interferometric sensor based on fiber array parallel spectral detection. A high-power amplified spontaneous emission (ASE) source served as the broadband detection light. The spectrum generated by the dispersion of the F-P interference light through an arrayed waveguide grating (AWG) was incident into the fiber array and was detected in parallel by 48 photodiodes. The 48-channel signals were acquired synchronously and processed in real time to achieve a phase demodulation for the F-P cavity at 200â kHz. As a result, a low-resolution spectral detection and demodulation system was constructed with high speed. The length demodulation range of the F-P cavity was 60-700â µm, and the demodulation resolution was as high as 0.22â nm. The designed high-sensitivity demodulator is expected to be used for ultrasonic and high-frequency vibration detection.
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BACKGROUND: Ultra-high field 7T MRI can provide excellent tissue contrast and anatomical details, but is often cost prohibitive, and is not widely accessible in clinical practice. PURPOSE: To generate synthetic 7T images from widely acquired 3T images with deep learning and to evaluate the feasibility of this approach for brain imaging. STUDY TYPE: Prospective. POPULATION: 33 healthy volunteers and 89 patients with brain diseases, divided into training, and evaluation datasets in the ratio 4:1. SEQUENCE AND FIELD STRENGTH: T1-weighted nonenhanced or contrast-enhanced magnetization-prepared rapid acquisition gradient-echo sequence at both 3T and 7T. ASSESSMENT: A generative adversarial network (SynGAN) was developed to produce synthetic 7T images from 3T images as input. SynGAN training and evaluation were performed separately for nonenhanced and contrast-enhanced paired acquisitions. Qualitative image quality of acquired 3T and 7T images and of synthesized 7T images was evaluated by three radiologists in terms of overall image quality, artifacts, sharpness, contrast, and visualization of vessel using 5-point Likert scales. STATISTICAL TESTS: Wilcoxon signed rank tests to compare synthetic 7T images with acquired 7T and 3T images and intraclass correlation coefficients to evaluate interobserver variability. P < 0.05 was considered significant. RESULTS: Of the 122 paired 3T and 7T MRI scans, 66 were acquired without contrast agent and 56 with contrast agent. The average time to generate synthetic images was ~11.4 msec per slice (2.95 sec per participant). The synthetic 7T images achieved significantly improved tissue contrast and sharpness in comparison to 3T images in both nonenhanced and contrast-enhanced subgroups. Meanwhile, there was no significant difference between acquired 7T and synthetic 7T images in terms of all the evaluation criteria for both nonenhanced and contrast-enhanced subgroups (P ≥ 0.180). DATA CONCLUSION: The deep learning model has potential to generate synthetic 7T images with similar image quality to acquired 7T images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.
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Medios de Contraste , Imagen por Resonancia Magnética , Humanos , Estudios de Factibilidad , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear. PURPOSE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy. STUDY TYPE: Retrospective. SUBJECTS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison. FIELD STRENGTH/SEQUENCE: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence. ASSESSMENT: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05. RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement. DATA CONCLUSION: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.
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Temblor Esencial , Sustancia Blanca , Masculino , Humanos , Imagen de Difusión Tensora , Temblor Esencial/diagnóstico por imagen , Temblor Esencial/cirugía , Estudios Retrospectivos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/cirugía , Temblor , Tálamo/diagnóstico por imagen , Tálamo/cirugía , Imagen por Resonancia Magnética/métodos , Resultado del TratamientoRESUMEN
OBJECTIVES: We aim to investigate whether cerebral small vessel disease (cSVD) imaging markers correlate with deep medullary vein (DMV) damage in small vessel occlusion acute ischemic stroke (SVO-AIS) patients. METHODS: The DMV was divided into six segments according to the regional anatomy. The total DMV score (0-18) was calculated based on segmental continuity and visibility. The damage of DMV was grouped according to the quartiles of the total DMV score. Neuroimaging biomarkers of cSVD including white matter hyperintensity (WMH), cerebral microbleed (CMB), perivascular space (PVS), and lacune were identified. The cSVD score were further analyzed. RESULTS: We included 229 SVO-AIS patients, the mean age was 63.7 ± 23.1 years, the median NIHSS score was 3 (IQR, 2-6). In the severe DMV burden group (the 4th quartile), the NIHSS score grade (6 (3-9)) was significantly higher than other groups (p < 0.01). The grade scores for basal ganglia PVS (BG-PVS) were positively correlated with the degree of DMV (R = 0.67, p < 0.01), rather than centrum semivole PVS (CS-PVS) (R = 0.17, p = 0.1). In multivariate analysis, high CMB burden (adjusted odds ratio [aOR], 25.38; 95% confidence interval [CI], 1.87-345.23) was associated with severe DMV scores. In addition, BG-PVS was related to severe DMV burden in a dose-dependent manner: when BG-PVS score was 3 and 4, the aORs of severe DMV burden were 18.5 and 12.19, respectively. CONCLUSION: The DMV impairment was associated with the severity of cSVD, which suggests that DMV burden may be used for risk stratification in SVO-AIS patients. CLINICAL RELEVANCE STATEMENT: The DMV damage score, based on the association between small vessel disease and the deep medullary veins impairment, is a potential new imaging biomarker for the prognosis of small vessel occlusion acute ischemic stroke, with clinical management implications. KEY POINTS: ⢠The damage to the deep medullary vein may be one mechanism of cerebral small vessel disease. ⢠Severe burden of the basal ganglia perivascular space and cerebral microbleed is closely associated with significant impairment to the deep medullary vein. ⢠The deep medullary vein damage score may reflect a risk of added vascular damage in small vessel occlusion acute ischemic stroke patients.
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Enfermedades de los Pequeños Vasos Cerebrales , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Anciano , Venas Cerebrales/diagnóstico por imagen , Venas Cerebrales/patología , Imagen por Resonancia Magnética/métodos , Bulbo Raquídeo/diagnóstico por imagen , Bulbo Raquídeo/irrigación sanguínea , Bulbo Raquídeo/patología , Estudios RetrospectivosRESUMEN
Geometric phase (GP) effects in chemical reactions are subtle quantum phenomena that are challenging to identify. In this work, we report a joint experimental and theoretical study of the H + HD â H2 + D reaction at a collision energy of 2.07 eV, which is far below the energy of the conical intersection of 2.53 eV. The rotationally state-resolved differential cross sections were measured by a crossed-beam experiment with the scheme of D-atom Rydberg tagging time-of-flight detection. Experimental angular distributions of three rotational states of H2 products exhibit notable variation near the backward scattering direction. Time-dependent quantum mechanics calculations (TDQMs) were carried out at the same collision energy, with and without the inclusion of GP. The experimental angular distributions are in good agreement with TDQM results with the inclusion of GP but do not agree with TDQM results without the inclusion of GP. This work demonstrates the existence of GP effects at energy far below the conical intersection.
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The comprehension of metaphor, a vivid and figurative language, is a complex endeavor requiring cooperation among multiple cognitive systems. There are still many important questions regarding neural mechanisms implicated in specific types of metaphor. To address these questions, we conducted activation likelihood estimation meta-analyses on 30 studies (containing data of 480 participants) and meta-analytic connectivity modeling analyses. First, the results showed that metaphor comprehension engaged the inferior frontal gyrus, middle temporal gyrus, fusiform gyrus, lingual gyrus, and middle occipital gyrus-all in the left hemisphere. In addition to the commonly reported networks of language and attention, metaphor comprehension engaged networks of visual. Second, sub-analysis showed that the contextual complexity can modulate figurativeness, with the convergence on the left fusiform gyrus during metaphor comprehension at discourse-level. Especially, right hemisphere only showed convergence in studies of novel metaphors, suggesting that the right hemisphere is more associated with difficulty than metaphorical. The work here extends knowledge of the neural mechanisms underlying metaphor comprehension in individual brain regions and neural networks.
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Comprensión , Metáfora , Humanos , Comprensión/fisiología , Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Rectal temperature (RT) is an important index of core temperature, which has guiding significance for the diagnosis and treatment of pet diseases. OBJECTIVES: Development and evaluation of an alternative method based on machine learning to determine the core temperatures of cats and dogs using surface temperatures. ANIMALS: 200 cats and 200 dogs treated between March 2022 and May 2022. METHODS: A group of cats and dogs were included in this study. The core temperatures and surface body temperatures were measured. Multiple machine learning methods were trained using a cross-validation approach and evaluated in one retrospective testing set and one prospective testing set. RESULTS: The machine learning models could achieve promising performance in predicting the core temperatures of cats and dogs using surface temperatures. The root mean square errors (RMSE) were 0.25 and 0.15 for cats and dogs in the retrospective testing set, and 0.15 and 0.14 in the prospective testing set. CONCLUSION: The machine learning model could accurately predict core temperatures for companion animals of cats and dogs using easily obtained body surface temperatures.
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Temperatura Corporal , Aprendizaje Automático , Animales , Gatos/fisiología , Perros/fisiología , Estudios Retrospectivos , Masculino , Femenino , Estudios ProspectivosRESUMEN
Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.
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PURPOSE: To compare preoperative and postoperative clinical and radiologic outcomes between patients undergoing high tibial osteotomy (HTO) with medial meniscal posterior root tear (MMPRT) reconstruction using gracilis tendon graft and those undergoing HTO without MMPRT reconstruction. METHODS: Patients with MMPRTs who underwent HTO between January 2018 and December 2021 with minimum 2-year follow-up were included. All patients were divided into 2 groups based on whether they underwent meniscal root reconstruction with tendon graft: HTO alone (33 cases) and HTO with MMPRT reconstruction (21 cases). Clinical evaluation included the Lysholm score, International Knee Documentation Committee (IKDC) score, and visual analog scale (VAS) score. Functional recovery and radiologic outcomes of the knees were evaluated at the latest follow-up. Meniscal root healing rates and medial meniscal extrusion according to a second magnetic resonance imaging reading were compared between the 2 groups at the latest follow-up. RESULTS: The results showed statistically significant improvements in the postoperative Lysholm score, IKDC score, and VAS score in both groups at the latest follow-up (P < .001). Analysis of the minimal clinically important difference for postoperative outcomes revealed that the percentage of patients who reached the minimal clinically important difference threshold was 100% for the Lysholm score, 100% for the IKDC score, and 100% for the VAS score in the HTO-MMPRT reconstruction group. In comparison, the percentages were 87.9% for the Lysholm score, 90.9% for the IKDC score, and 100% for the VAS score in the HTO-alone group. Additionally, compared with the HTO-alone group, the HTO-MMPRT reconstruction group using gracilis tendon graft showed significantly improved meniscal root healing rates (complete healing, 85.7% vs 45.4% [95% confidence interval, 0.003-0.007]; P = .001) and functional recovery (P < .005) at the final follow-up. Additionally, the HTO-MMPRT reconstruction group showed significantly more improvement in the Kellgren-Lawrence grade (10 of 21 knees vs 6 of 33 knees with improved Kellgren-Lawrence grade, P = .033) and medial meniscal extrusion (2.1 ± 1.0 mm vs 3.1 ± 1.6 mm [95% confidence interval, 0.3-1.7 mm]; P = .007) compared with the HTO-alone group. CONCLUSIONS: HTO with reconstruction of the meniscal root using a tendon graft resulted in improved radiographic and patient-reported outcomes, as well as improved healing rates, compared with HTO alone. LEVEL OF EVIDENCE: Level III, retrospective case-series comparison.
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BACKGROUND: Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. METHODS: Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. RESULTS: 379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. CONCLUSIONS: Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. TRIAL REGISTRATION: ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.
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Metilación de ADN , Cardiopatías Congénitas , Recién Nacido , Humanos , Gemelos Monocigóticos/genética , Cardiopatías Congénitas/genética , Secuenciación Completa del Genoma , Epigénesis GenéticaRESUMEN
The homeostasis of hydrogen peroxide (H2 O2 ), a key regulator of basic biological processes, is a result of the cooperation between its generation and scavenging. However, the mechanistic basis of this balance is not fully understood. We previously proposed that the interaction between glycolate oxidase (GLO) and catalase (CAT) may serve as a molecular switch that modulates H2 O2 levels in plants. In this study, we demonstrate that the GLO-CAT complex in plants exists in different states, which are dynamically interchangeable in response to various stimuli, typically salicylic acid (SA), at the whole-plant level. More crucially, changes in the state of the complex were found to be closely linked to peroxisomal H2 O2 fluctuations, which were independent of the membrane-associated NADPH oxidase. Furthermore, evidence suggested that H2 O2 channeling occurred even in vitro when GLO and CAT worked cooperatively. These results demonstrate that dynamic changes in H2 O2 levels are physically created via photorespiratory metabolic channeling in plants, and that such H2 O2 fluctuations may serve as signals that are mechanistically involved in the known functions of photorespiratory H2 O2 . In addition, our study also revealed a new way for SA to communicate with H2 O2 in plants.
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Peróxido de Hidrógeno , Plantas , Peróxido de Hidrógeno/metabolismo , Plantas/metabolismo , HomeostasisRESUMEN
We designed and implemented a photoacoustic (PA) sensor for H2S detection in SF6 background gas based on a multi-pass differential photoacoustic cell (MDPC) and a near-infrared distributed feedback (DFB) laser. In the MDPC apparatus, two resonators with identical geometric parameters were vertically and symmetrically embedded. The differential processing algorithm of two phase-reversed signals realized the effective enhancement of the PA signal and suppressed the flow noise in the dynamic sampling process. In addition, the λ/4 buffer chamber in the MDPC was utilized as a muffler to further reduce the flow noise and realize the dynamic detection of H2S. The collimated excitation light was reflected 30 times in a multi-pass structure constituted of two gold-plated concave mirrors, and an absorption path length of 4.92 m was achieved. Due to the high gas density of SF6, the relationship between the signal-to-noise ratio (SNR) and the gas flow was different between SF6 and N2 background gases. The maximum flow rate of the characteristic gas components detected in the SF6 background is 150 standard cubic centimeters per minute (SCCM), which is lower than 350 SCCM in N2. The linearity property was analyzed, and the results show that the sensitivity of the sensor to H2S in the SF6 background was 27.3 µV/ppm. With the structure, parameters, temperature, gas flow, and natural frequency of the MDPC been optimized, a minimum detection limit (MDL) of 11 ppb was reached with an averaging time of 1000 s, which furnished an effective preventive implement for the safe operation of gas insulation equipment.
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Background Iodinated contrast agents (ICAs), which are widely used in CT angiography (CTA), may cause adverse effects in humans, and their use is time-consuming and costly. Purpose To develop an ICA-free deep learning imaging model for synthesizing CTA-like images and to assess quantitative and qualitative image quality as well as the diagnostic accuracy of synthetic CTA (Syn-CTA) images. Materials and Methods A generative adversarial network (GAN)-based CTA imaging model was trained, validated, and tested on retrospectively collected pairs of noncontrast CT and CTA images of the neck and abdomen from January 2017 to June 2022, and further validated on an external data set. Syn-CTA image quality was evaluated using quantitative metrics. In addition, two senior radiologists scored the visual quality on a three-point scale (3 = good) and determined the vascular diagnosis. The validity of Syn-CTA images was evaluated by comparing the visual quality scores and diagnostic accuracy of aortic and carotid artery disease between Syn-CTA and real CTA scans. Results CT scans from 1749 patients (median age, 60 years [IQR, 50-68 years]; 1057 male patients) were included in the internal data set: 1137 for training, 400 for validation, and 212 for testing. The external validation set comprised CT scans from 42 patients (median age, 67 years [IQR, 59-74 years]; 37 male patients). Syn-CTA images had high similarity to real CTA images (normalized mean absolute error, 0.011 and 0.013 for internal and external test set, respectively; peak signal-to-noise ratio, 32.07 dB and 31.58 dB; structural similarity, 0.919 and 0.906). The visual quality of Syn-CTA and real CTA images was comparable (internal test set, P = .35; external validation set, P > .99). Syn-CTA showed reasonable to good diagnostic accuracy for vascular diseases (internal test set: accuracy = 94%, macro F1 score = 91%; external validation set: accuracy = 86%, macro F1 score = 83%). Conclusion A GAN-based model that synthesizes neck and abdominal CTA-like images without the use of ICAs shows promise in vascular diagnosis compared with real CTA images. Clinical trial registration no. NCT05471869 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Zhang and Turkbey in this issue.
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Aorta , Angiografía por Tomografía Computarizada , Humanos , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Arterias CarótidasRESUMEN
Osteoarthritis (OA) is a common disease characterized by cartilage degradation. Growing evidence showed that glucose metabolism impacts joint homeostasis and an imbalance between glycolysis and oxidative phosphorylation (OXPHOS) may exacerbate OA progression, however, a definitive link is yet to be established. Here, we report that pyruvate metabolism and oxidative phosphorylation pathway is enriched in OA cartilage through gene set enrichment analysis (GSEA) and expression of Pyruvate Dehydrogenase Kinase 1 (PDK1), an enzyme that can phosphorylate Pyruvate Dehydrogenase (PDH), and inhibit pyruvate fluxes into the tricarboxylic acid (TCA) cycle and to OXPHOS, in articular cartilage is notably reduced through destabilization of medial meniscus (DMM). Moreover, by inhibiting PDK1, cartilage loss is markedly accelerated in DMM-induced OA through extracellular matrix (ECM) degradation and apoptosis of chondrocytes. These results indicate that PDK1 is involved in the progression of OA through accelerating cartilage matrix degradation and synovium inflammation to ameliorate cartilage degeneration.
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Cartílago Articular , Osteoartritis , Humanos , Animales , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Fosforilación Oxidativa , Condrocitos/metabolismo , Cartílago Articular/metabolismo , Osteoartritis/metabolismo , Modelos Animales de EnfermedadRESUMEN
Prostate cancer (PCa) is the most common malignant tumor in males, which frequently develops into castration-resistant prostate cancer (CRPC) with limited therapies. Gambogenic acid (GNA), a flavonoids compound isolated from Gamboge, exhibits anti-tumor capacity in various cancers. Our results showed that GNA revealed not only antiproliferative and pro-apoptotic activities but also the induction of autophagy in PCa cells. In addition, autophagy inhibitor chloroquine enhanced the pro-apoptosis effect of GNA. Moreover, the activation of JNK pathway and the induction of apoptosis and autophagy triggered by GNA were attenuated by JNK inhibitor SP600125. We also found that GNA significantly promoted reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress. Meanwhile, suppressing ER stress with 4-phenylbutyric acid (4-PBA) markedly blocked the activation of JNK pathway induced by GNA. Further research indicated that ROS scavenger N-acetyl-L-cysteine (NAC) effectively abrogated ER stress and JNK pathway activation induced by GNA. Furthermore, NAC and 4-PBA significantly reversed GNA-triggered apoptosis and autophagy. Finally, GNA remarkably suppressed prostate tumor growth with low toxicity in vivo. In conclusion, the present study revealed that GNA induced apoptosis and autophagy through ROS-mediated ER stress via JNK signaling pathway in PCa cells. Thus, GNA might be a promising therapeutic drug against PCa.
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Sistema de Señalización de MAP Quinasas , Neoplasias de la Próstata , Masculino , Humanos , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Estrés del Retículo Endoplásmico , Autofagia , Línea Celular Tumoral , Acetilcisteína/metabolismo , Acetilcisteína/farmacología , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
We propose an inferential procedure for additive hazards regression with high-dimensional survival data, where the covariates are prone to measurement errors. We develop a double bias correction method by first correcting the bias arising from measurement errors in covariates through an estimating function for the regression parameter. By adopting the convex relaxation technique, a regularized estimator for the regression parameter is obtained by elaborately designing a feasible loss based on the estimating function, which is solved via linear programming. Using the Neyman orthogonality, we propose an asymptotically unbiased estimator which further corrects the bias caused by the convex relaxation and regularization. We derive the convergence rate of the proposed estimator and establish the asymptotic normality for the low-dimensional parameter estimator and the linear combination thereof, accompanied with a consistent estimator for the variance. Numerical experiments are carried out on both simulated and real datasets to demonstrate the promising performance of the proposed double bias correction method.
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Sesgo , HumanosRESUMEN
Our previous studies have also demonstrated that AVP can significantly improve social interaction disorders and stereotypical behaviours in rats with VPA-induced autism model. To further explore the mechanisms of action of AVP, we compared the PFC transcriptome changes before and after AVP treatment in VPA-induced autism rat model. The autism model was induced by intraperitoneally injected with VPA at embryonic day 12.5 and randomly assigned to two groups: the VPA-induced autism model group and the AVP treatment group. The AVP treatment group were treated with intranasal AVP at postnatal day 21 and for 3 weeks. The gene expression levels and function changes on the prefrontal cortex were measured by RNA-seq and bioinformatics analysis at PND42 and the mRNA expression levels of synaptic and myelin development related genes were validated by qPCR. Our results confirmed that AVP could significantly improve synaptic and axon dysplasia and promote oligodendrocyte development in the prefrontal cortex in VPA-induced autism models by regulating multiple signalling pathways.