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Circadian gene transcription is fundamental to metabolic physiology. Here we report that the nuclear receptor REV-ERBα, a repressive component of the molecular clock, forms circadian condensates in the nuclei of mouse liver. These condensates are dictated by an intrinsically disordered region (IDR) located in the protein's hinge region which specifically concentrates nuclear receptor corepressor 1 (NCOR1) at the genome. IDR deletion diminishes the recruitment of NCOR1 and disrupts rhythmic gene transcription in vivo. REV-ERBα condensates are located at high-order transcriptional repressive hubs in the liver genome that are highly correlated with circadian gene repression. Deletion of the IDR disrupts transcriptional repressive hubs and diminishes silencing of target genes by REV-ERBα. This work demonstrates physiological circadian protein condensates containing REV-ERBα whose IDR is required for hub formation and the control of rhythmic gene expression.
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Relógios Circadianos , Camundongos , Animais , Relógios Circadianos/genética , Ritmo Circadiano/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Fígado/metabolismo , Expressão GênicaRESUMO
BACKGROUND: Quantitative myocardial tissue characterization with T1 and T2 parametric mapping can provide an accurate and complete assessment of tissue abnormalities across a broad range of cardiomyopathies. However, current clinical T1 and T2 mapping tools rely predominantly on two-dimensional (2D) breath-hold sequences. Clinical adoption of three-dimensional (3D) techniques is limited by long scan duration. The aim of this study is to develop and validate a time-efficient 3D free-breathing simultaneous T1 and T2 mapping sequence using multi-parametric SAturation-recovery and Variable-flip-Angle (mSAVA). METHODS: mSAVA acquires four volumes for simultaneous whole-heart T1 and T2 mapping. We validated mSAVA using simulations, phantoms, and in-vivo experiments at 3T in 11 healthy subjects and 11 patients with diverse cardiomyopathies. T1 and T2 values by mSAVA were compared with modified Look-Locker inversion recovery (MOLLI) and gradient and spin echo (GraSE), respectively. The clinical performance of mSAVA was evaluated against late gadolinium enhancement (LGE) imaging in patients. RESULTS: Phantom T1 and T2 by mSAVA showed a strong correlation to reference sequences (R2 = 0.98 and 0.99). In-vivo imaging with an imaging resolution of 1.5 × 1.5 × 8 mm3 could be achieved. Myocardial T1 and T2 of healthy subjects by mSAVA were 1310 ± 46 and 44.6 ± 2.0 ms, respectively, with T1 standard deviation higher than MOLLI (105 ± 12 vs 60 ± 16 ms) and T2 standard deviation lower than GraSE (4.5 ± 0.8 vs 5.5 ± 1.0 ms). mSAVA T1 and T2 maps presented consistent findings in patients undergoing LGE. Myocardial T1 and T2 of all patients by mSAVA were 1421 ± 79 and 47.2 ± 3.3 ms, respectively. CONCLUSION: mSAVA is a fast 3D technique promising for clinical whole-heart T1 and T2 mapping.
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Due to the unique chemical and biomedical properties of carbon dots (CDs), they have increasingly obtained the attention in many research fields, for example, bioimaging, fluorescence sensing, and drug delivery, etc. Recently, it was found that, under light excitation, CDs can also be exploited as a novel photosensitizer to prepare reactive oxygen species (ROS), which expand their applications in the field of photodynamic therapy for cancer treatment. Nevertheless, the high cost and complex fabrication approach of CDs significantly limit their applications. To address this issue, bottom-up routes usually utilize sustainable and inexpensive carbon precursor as starting materials, employed N,N-dimethylformamide (DMF) or ethanol as an environmental-friendly solvent. Bottom-up approach was energy efficient, and the purification process was relatively simple by dialysis. Therefore, carbon dots (CDs) were facilely fabricated in a one-pot solvothermal process using 1-aminoanthraquinone as a precursor, and their application as photosensitizers for in vitro antitumor cells, especially photodynamic therapy (PDT) was established. Then the photophysical and nanoscale dimensions properties of the fabricated CDs were characterized via TEM, UV-visible, fluorescence, and FT-IR spectroscopy. The synthesized N-doped CDs can easily dissolve in water, possess very low biotoxicity, yellow-light emission (maximum peak at 587 nm). More importantly, PDT studies demonstrated that the obtained CDs possess a high singlet oxygen yield of 35%, and exhibit significant phototoxicity to cancer cells upon 635 nm laser irradiation. These studies highlight that N-doped CDs can be facilely synthesized from only one precursor, and are a potentially novel theranostic agent for in vivo PDT.
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Relativistic exact two-component coupled-cluster calculations of molecular sensitivity factors for nuclear Schiff moments (NSMs) are reported. We focus on molecules containing heavy nuclei, especially octupole-deformed nuclei. Analytic relativistic coupled-cluster gradient techniques are used and serve as useful tools for identifying candidate molecules that sensitively probe for physics beyond the Standard Model in the hadronic sector. Notably, these tools enable straightforward "black-box" calculations. Two competing chemical mechanisms that contribute to the NSM are analyzed, illuminating the physics of ligand effects on NSM sensitivity factors.
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A new computational framework for spinor-based relativistic exact two-component (X2C) calculations is developed using contracted basis sets with a spin-orbit contraction scheme. Generally contracted, j-adapted basis sets of p-block elements using primitive functions in the correlation-consistent basis sets are constructed for the X2C Hamiltonian with atomic mean-field spin-orbit integrals (the X2CAMF scheme). The contraction coefficients are taken from atomic X2CAMF Hartree-Fock spinors, thereby following the simple concept of a linear combination of atomic orbitals. Benchmark calculations of spin-orbit splittings, equilibrium bond lengths, and harmonic vibrational frequencies demonstrate the accuracy and efficacy of the j-adapted spin-orbit contraction scheme.
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The objective of this research is to assess how salvianolate impacts inflammation and oxidative stress in a laboratory setting, as well as to investigate the underlying mechanisms. HK-2 cells were subjected to different treatments, including normal glucose, mannitol, high glucose and high glucose plus salvianolate. Cell proliferation, death, MDA levels, IL-1ß, IL-6, TNF-α, MCP-1 concentrations, ROS levels, MMP, MPTP and ATP levels were assessed using various kits. The protein expressions of NOX4, TGF-ß1, P-Smad2, P-Smad3, Smad4 and Smad7 were ascertained through western blot analysis. Our results indicated salvianolate could reduce the release of IL-1ß, IL-6, TNF-α, as well as MCP-1, alleviate the levels of oxidative stress markers NOX4 and MDA, and improve mitochondrial function by increasing MMP and ATP levels while reducing ROS and MPTP opening. Furthermore, salvianolate inhibited the TGF-ß1/Smad2, Smad3 signaling pathway, suppressed Smad4 expression and increased Smad7 expression. Salvianolate seems to mitigate inflammation and oxidative stress through a variety of mechanisms. These discoveries offer valuable understanding into the possible mechanisms by which salvianolate may be employed in the treatment of diabetic nephropathy.
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Glucose , Inflamação , Estresse Oxidativo , Transdução de Sinais , Humanos , Anti-Inflamatórios/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Glucose/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Seed size and weight are important factors that influence soybean yield. Combining the weighted gene co-expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ-type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc-finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean. The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32-bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds. Our study reveals a novel module of GmPLATZ-GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits.
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Glycine max , Transcriptoma , Glycine max/genética , Transcriptoma/genética , Melhoramento Vegetal , Locos de Características Quantitativas , Sementes/genéticaRESUMO
The purpose of the current study was to develop and evaluate a three-dimensional single Breath-hOLd cardiac T2 mapping sequence (3D BOLT) with low-rank plus sparse (L + S) reconstruction for rapid whole-heart T2 measurement. 3D BOLT collects three highly accelerated electrocardiogram-triggered volumes with whole-heart coverage, all within a single 12-heartbeat breath-hold. Saturation pulses are performed every heartbeat to prepare longitudinal magnetization before T2 preparation (T2 -prep) or readout, and the echo time of T2 -prep is varied per volume for variable T2 weighting. Accelerated volumes are reconstructed jointly by an L + S algorithm. 3D BOLT was optimized and validated against gradient spin echo (GraSE) and a previously published approach (three-dimensional free-breathing cardiac T2 mapping [3DFBT2]) in both phantoms and human subjects (11 healthy subjects and 10 patients). The repeatability of 3D BOLT was validated on healthy subjects. Retrospective experiments indicated that 3D BOLT with 4.2-fold acceleration achieved T2 measurements comparable with those obtained with fully sampled data. T2 measured in phantoms using 3D BOLT demonstrated good accuracy and precision compared with the reference (R2 > 0.99). All in vivo imaging was successful and the average left ventricle T2 s measured by GraSE, 3DFBT2, and 3D BOLT were comparable and consistent for all healthy subjects (47.0 ± 2.3 vs. 47.7 ± 2.7 vs. 48.4 ± 1.8 ms) and patients (50.8 ± 3.0 vs. 48.6 ± 3.9 vs. 49.1 ± 3.7 ms), respectively. Myocardial T2 measured by 3D BOLT had excellent agreement with 3DFBT2 and there was no significant difference in mean, standard deviation, and coefficient of variation. 3D BOLT showed excellent repeatability (intraclass correlation coefficient: 0.938). The proposed 3D BOLT achieved whole-heart T2 mapping in a single breath-hold with good accuracy, precision, and repeatability on T2 measurements.
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Coração , Imageamento por Ressonância Magnética , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Coração/diagnóstico por imagem , Miocárdio , Suspensão da Respiração , Imageamento Tridimensional/métodos , Imagens de Fantasmas , Reprodutibilidade dos TestesRESUMO
We report optical trapping of a polyatomic molecule, calcium monohydroxide (CaOH). CaOH molecules from a magneto-optical trap are sub-Doppler laser cooled to 20(3) µK in free space and loaded into an optical dipole trap. We attain an in-trap molecule number density of 3(1)×10^{9} cm^{-3} at a temperature of 57(8) µK. Trapped CaOH molecules are optically pumped into an excited vibrational bending mode, whose â-type parity doublet structure is a potential resource for a wide range of proposed quantum science applications with polyatomic molecules. We measure the spontaneous, radiative lifetime of this bending mode state to be â¼0.7 s.
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BACKGROUND: Common genetic variation in close proximity to the ILRUN gene are significantly associated with coronary artery disease as well as with plasma lipid traits. We recently demonstrated that hepatic inflammation and lipid regulator with ubiquitin-associated domain-like and NBR1-like domains (ILRUN) regulates lipoprotein metabolism in vivo in mice. However, whether ILRUN, which is expressed in vascular cells, directly impacts atherogenesis remains unclear. We sought to determine the role of ILRUN in atherosclerosis development in mice. METHODS: For our study, we generated global Ilrun-deficient (IlrunKO) male and female mice on 2 hyperlipidemic backgrounds: low density lipoprotein receptor knockout (LdlrKO) and apolipoprotein E knockout (ApoeKO; double knockout [DKO]). RESULTS: Compared with littermate control mice (single LdlrKO or ApoeKO), deletion of Ilrun in DKO mice resulted in significantly attenuated both early and advanced atherosclerotic lesion development, as well as reduced necrotic area. DKO mice also had significantly decreased plasma cholesterol levels, primarily attributable to non-HDL (high-density lipoprotein) cholesterol. Hepatic-specific reconstitution of ILRUN in DKO mice on the ApoeKO background normalized plasma lipids, but atherosclerotic lesion area and necrotic area remained reduced in DKO mice. Further analysis showed that loss of Ilrun increased efferocytosis receptor MerTK expression in macrophages, enhanced in vitro efferocytosis, and significantly improved in situ efferocytosis in advanced lesions. CONCLUSIONS: Our results support ILRUN as an important novel regulator of atherogenesis that promotes lesion progression and necrosis. It influences atherosclerosis through both plasma lipid-dependent and lipid-independent mechanisms. These findings support ILRUN as the likely causal gene responsible for genetic association of variants with coronary artery disease at this locus and suggest that suppression of ILRUN activity might be expected to reduce atherosclerosis.
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Aterosclerose , Doença da Artéria Coronariana , Animais , Feminino , Masculino , Camundongos , Aterosclerose/metabolismo , HDL-Colesterol/metabolismo , Doença da Artéria Coronariana/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Fluorene-9-bisphenol (BHPF), a bisphenol A (BPA) substitute, has been increasingly used as a material in syntheses of polymers that are widely used in road markings, artificial tracks, coating floors, building paints, etc., increasing the likelihood of BHPF contamination in the aquatic environment due to its release from the products. However, to date, it is unknown whether it may have actual impacts on fish in real environments. In this study, a 105-day exposure experiment of BHPF at various concentrations (0.01, 0.1, 1, and 10 µg/L) on Chinese medaka (Oryzias sinensis) was performed under laboratory conditions and found decreased fecundity, such as lower egg qualities and quantities, retarded oogenesis, and atretic follicles in the fish and deformed eyes and bodies in its F1 generation. Toxico-transcriptome analyses showed that estrogen-responsive genes were significantly suppressed by BHPF, indicating that antagonist properties of BHPF on estrogen receptors might be causes for the decreased fecundity. Field investigations (Beijing) demonstrated that BHPF was detectable in 60% surface waters, with a mean concentration of 10.49 ± 6.33 ng/L, by gas chromatography-mass spectrometry, and similar effects in wild Chinese medaka were also observed, some of which the parameters were found to be obviously correlated with the BHPF levels in corresponding waters.
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Oryzias , Poluentes Químicos da Água , Animais , Fluorenos/toxicidade , Fluorenos/química , Reprodução , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: T-box transcription factor 3(TBX3) is a transcription factor that can regulate cell proliferation, apoptosis, invasion, and migration in different tumor cells; however, its role in adenomyosis (ADM) has not been previously studied. Some of ADM's pathophysiological characteristics are similar to those of malignant tumors (e.g., abnormal proliferation, migration, and invasion). METHODS AND RESULTS: We hypothesized that TBX3 might have a role in ADM. We used tamoxifen-induced Institute of Cancer research (ICR) mice to establish ADM disease model. The study procedure included western blotting and immunohistochemistry to analyze protein levels; additionally, we used intraperitoneal injection of Wnt/ß-catenin pathway inhibitor XAV-939 to study the relationship between TBX3 and Wnt/ß-catenin pathway as well as Anti-proliferation cell nuclear antigen( PCNA) and TUNEL to detect cell proliferation and apoptosis, respectively. TBX3 overexpression and epithelial-to-mesenchymal transition (EMT) in ADM mice was found to be associated with activation of the Wnt3a/ß-catenin pathway. Treatment with XAV-939 in ADM mice led to the inhibition of both TBX3 and EMT; moreover, abnormal cell proliferation was suppressed, the depth of invasion of endometrium cells was limited. Thus, the use of XAV-939 effectively inhibited further invasion of endometrial cells. CONCLUSION: These findings suggest that TBX3 may play an important role in the development of ADM. The expression of TBX3 in ADM was regulated by the Wnt3a/ß-catenin pathway. The activation of the Wnt3a/ß-catenin pathway in ADM promoted TBX3 expression and induced the occurrence of EMT, thus promoting cell proliferation and inhibiting apoptosis, ultimately accelerating the development of ADM. The study provides a reference for the diagnosis of ADM.
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Adenomiose , beta Catenina , Animais , Feminino , Camundongos , Adenomiose/genética , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Proteínas com Domínio T/genética , Fator 3 de Transcrição/metabolismo , Via de Sinalização WntRESUMO
A relativistic coupled-cluster study of the low-lying electronic states in the radium monohydroxide molecule (RaOH), a radioactive polyatomic molecule of interest to laser cooling and to the search of new physics beyond the Standard Model, is reported. The level positions of the A2Π1/2 and C2Σ states have been computed with an accuracy of around 200 cm-1 to facilitate spectroscopic observation of RaOH using laser induced fluorescence spectroscopy, thereby exploiting the systematic convergence of electron-correlation and basis-set effects in relativistic coupled-cluster calculations. The energy level for the B2Δ3/2 state has also been calculated accurately to conclude that the B2Δ3/2 state lies above the A2Π1/2 state. This confirms X2Σ â A2Π1/2 as a promising optical cycling transition for laser cooling RaOH.
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The current study evaluated the effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. 60 patients were randomized (1:1) to receive dapagliflozin 10 mg once daily, or placebo double blind for 1 year. Patients underwent transthoracic echocardiography and doppler evaluation prior to dapagliflozin initiation and at 1 year. At 1year, adjusted mean difference versus placebo in change from baseline in LVEF was 2.5% (95% CI: 1.00-4.06, P = 0.002). Adjusted mean difference versus placebo in change from baseline in LVED volume was - 6.0ml (95% CI: -8.07 --3.87, P<0.001). Adjusted mean difference versus placebo in change from baseline in LVES volume was - 8.1ml (95% CI: -11.07 --5.14, P<0.001). Similarly, adjusted mean difference versus placebo in change from baseline in LVED diameter was - 1.6 mm (95% CI: -2.67 --0.62, P = 0.002). Adjusted mean difference versus placebo in change from baseline in VTI was 0.20 cm (95% CI: 0.01-0.38, P = 0.036). Dapagliflozin was well tolerated. Dapagliflozin was associated with significant and clinically meaningful improvement in echocardiographic parameters versus placebo in patients with type 2 diabetes and HFrEF.Registration number and date: ChiCTR2300072707, 21/06/2023.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular , Método Duplo-CegoRESUMO
OBJECTIVES: Use of an AI system based on deep learning to investigate whether the system can aid in distinguishing malignant from benign calcifications on spot magnification mammograms, thus potentially reducing unnecessary biopsies. METHODS: In this retrospective study, we included public and in-house datasets with annotations for the calcifications on both craniocaudal and mediolateral oblique vies, or both craniocaudal and mediolateral views of each case of mammograms. All the lesions had pathological results for correlation. Our system comprised an algorithm based on You Only Look Once (YOLO) named adaptive multiscale decision fusion module. The algorithm was pre-trained on a public dataset, Curated Breast Imaging Subset of Digital Database for Screening Mammography (CBIS-DDSM), then re-trained and tested on the in-house dataset of spot magnification mammograms. The performance of the system was investigated by receiver operating characteristic (ROC) analysis. RESULTS: We included 1872 images from 753 calcification cases (414 benign and 339 malignant) from CBIS-DDSM. From the in-house dataset, 636 cases (432 benign and 204 malignant) with 1269 spot magnification mammograms were included, with all lesions being recommended for biopsy by radiologists. The area under the ROC curve for our system on the in-house testing dataset was 0.888 (95% CI 0.868-0.908), with a sensitivity of 88.4% (95% CI 86.9-8.99%), specificity of 80.8% (95% CI 77.6-84%), and an accuracy of 84.6% (95% CI 81.8-87.4%) at the optimal cutoff value. Using the system with two views of spot magnification mammograms, 80.8% benign biopsies could be avoided. CONCLUSION: The AI system showed good accuracy for classification of calcifications on spot magnification mammograms which were all categorized as suspicious by radiologists, thereby potentially reducing unnecessary biopsies.
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Neoplasias da Mama , Calcinose , Humanos , Feminino , Mamografia/métodos , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer , Calcinose/diagnóstico por imagem , Inteligência ArtificialRESUMO
A first implementation of analytic gradients for spinor-based relativistic equation-of-motion coupled-cluster singles and doubles method using an exact two-component Hamiltonian augmented with atomic mean-field spin-orbit integrals is reported. To demonstrate its applicability, we present calculations of equilibrium structures and harmonic vibrational frequencies for the electronic ground and excited states of the radium mono-amide molecule (RaNH2) and the radium mono-methoxide molecule (RaOCH3). Spin-orbit coupling is shown to quench Jahn-Teller effects in the first excited state of RaOCH3, resulting in a C3v equilibrium structure. The calculations also show that the radium atoms in these molecules serve as efficient optical cycling centers.
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Characterization of the inner-shell decay processes in molecules containing heavy elements is key to understanding x-ray damage of molecules and materials and for medical applications with Auger-electron-emitting radionuclides. The 1s hole states of heavy atoms can be produced by absorption of tunable x rays and the resulting vacancy decays characterized by recording emitted photons, electrons, and ions. The 1s hole states in heavy elements have large x-ray fluorescence yields that transfer the hole to intermediate electron shells that then decay by sequential Auger-electron transitions that increase the ion's charge state until the final state is reached. In molecules, the charge is spread across the atomic sites, resulting in dissociation to energetic atomic ions. We have used x-ray/ion coincidence spectroscopy to measure charge states and energies of Iq+ and Brq'+ atomic ions following 1s ionization at the I and Br K-edges of IBr. We present the charge states and kinetic energies of the two correlated fragment ions associated with core-excited states produced during the various steps of the cascades. To understand the dynamics leading to the ion data, we develop a computational model that combines Monte-Carlo/Molecular-Dynamics (MC/MD) simulations with a classical over-the-barrier model to track inner-shell cascades and redistribution of electrons in valence orbitals and nuclear motion of fragments.
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PURPOSE: To investigate the dosimetric impact of the calculation boundaries and dose calculation algorithms of radiotherapy in head and neck cancer patients with an opened oral cavity connected to the exterior by a hollow intraoral positioning stent. METHODS AND MATERIALS: A homemade silicone phantom with an opened oral cavity was placed in a CIRS head phantom to model head and neck cancer patients with a hollow intraoral positioning stent. 3D-CRT plans were designed on CT images of the phantom in Monaco and Pinnacle3 treatment planning systems (TPSs) with the same beam parameters. The default boundary and manually extrapolated boundary were both adopted in these two TPSs to explore the dosimetric impact on treatment plans. The nanoDot™ optically stimulated luminescence dosimeters (OSLDs) were chosen to measure the planned dose surrounding the oral cavity of the head phantom after calibration. RESULT: The doses in the air cavity and two measuring points at the joint area were dramatically changed from 0.0, 92.4 and 148.8 cGy to 177.8, 244.2 and 244.1 cGy in Monaco after adopting the extrapolated boundary. While the calculated doses at the same place were changed from 61.2, 143.7 and 198.3 cGy to 175.4, 234.7 and 233.2 cGy in Pinnacle3 with a similar calculation boundary. For the Monaco TPS, the relative errors compared to the OSLD measured doses were 2.94 ± 1.93%, 0.53 ± 8.64%, 2.65 ± 1.87% and 3.93 ± 1.69% at 4 measuring positions. In contrast, the relative errors 4.03 ± 1.93%, 4.85 ± 8.64%, 7.61 ± 1.87% and 5.61 ± 1.69% were observed in Pinnacle3 . CONCLUSION: The boundary setting of an opened oral cavity in TPSs has a significant dosimetric impact on head and neck cancer radiotherapy. An extrapolated boundary should be manually set up to include the whole oral cavity in the dose calculation domain to avoid major dose deviations.
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Neoplasias de Cabeça e Pescoço , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Radiometria/métodos , Imagens de Fantasmas , Radioterapia de Intensidade Modulada/métodosRESUMO
ABSTRACT: Limited treatments are available for alleviating heart remodeling in postmenopausal hypertension. The cardioprotective effect of naoxintong (NXT) has been widely accepted. This study aimed to explore the effects of NXT on pathological heart remodeling in a postmenopausal hypertension mouse model in vivo and H9c2 cardiomyocytes in vitro. In vivo, ovariectomy combined with chronic angiotensin II infusion was used to establish the postmenopausal hypertension animal model. NXT significantly ameliorated cardiac remodeling as indicated by a reduced ratio of heart weight/body weight and left ventricle weight/body weight, left ventricular wall thickness, diameter of cardiomyocytes, and collagen deposition in the heart. NXT also significantly increased the expression of estrogen receptors (ERs) and downregulated the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2). In vitro, NXT treatment greatly suppressed angiotensin II-induced cardiac hypertrophy, cardiac fibrosis, and excessive oxidative stress as proven by reducing the diameter of H9c2 cardiomyocytes, expression of hypertrophy and fibrosis markers, intracellular reactive oxygen species, and oxidative enzymes. Mechanistically, NXT significantly upregulated the expression of ERs, which activated the Nrf2/HO-1 signaling pathway and inhibited the phosphorylation of the p38α pathway. Collectively, the results indicated that NXT administration might attenuate cardiac remodeling through upregulating the expression of ERs, which activated the Nrf2/HO-1 signaling pathway, inhibited the phosphorylation of the p38α signaling pathway, and reduced oxidative stress.
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Hipertensão , Fator 2 Relacionado a NF-E2 , Angiotensina II/metabolismo , Animais , Peso Corporal , Medicamentos de Ervas Chinesas , Feminino , Fibrose , Heme Oxigenase-1/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Pós-Menopausa , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Remodelação VentricularRESUMO
Three pairs of chiral Ln-Ag(I) clusters d/l-Ln3Ag5 with C3 symmetry were prepared by d/l-penicillamine as multidentate ligand bridged Ln3+ and Ag(I) ions. The chiral ligand induced the molecular cluster to be chiral, and the CD spectra of the chiral compounds d/l-Ln3Ag5 were slightly blue-shifted due to the lanthanide contraction. The studies of optical properties indicated that tunable photoluminescence from {AgS}-to-Ln3+ was achieved by introducing Ln3+ ions with different emission bands or regulating various excitation light.