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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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Aiming to address soft sensing model degradation under changing working conditions, and to accommodate dynamic, nonlinear, and multimodal data characteristics, this paper proposes a nonlinear dynamic transfer soft sensor algorithm. The approach leverages time-delay data augmentation to capture dynamics and projects the augmented data into a latent space for constructing a nonlinear regression model. Two regular terms, distribution alignment regularity and first-order difference regularity, are introduced during data projection to address data distribution disparities. Laplace regularity is incorporated into the nonlinear regression model to ensure geometric structure preservation. The final optimization objective is formulated within the framework of partial least squares, and hyperparameters are determined using Bayesian optimization. The effectiveness of the proposed algorithm is demonstrated through experiments on three public datasets.
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Hérnias Diafragmáticas Congênitas , Imagem Multimodal , Pericárdio , Humanos , Imagem Multimodal/métodos , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/patologia , Pericárdio/diagnóstico por imagem , Pericárdio/anormalidades , Pericárdio/patologia , Tomografia Computadorizada por Raios X , Masculino , Feminino , EcocardiografiaRESUMO
Deubiquitinating enzymes (DUBs) play a pivotal role in regulating the antiviral immune response by targeting members of the RLR signaling pathway. As a pivotal member of the RLR pathway, TRAF3 is essential for activating the MAVS/TBK-1/IRF3 signaling pathway in response to viral infection. Despite its importance, the function of DUBs in the TRAF3-mediated antiviral response is poorly understood. Ubiquitin-specific protease 26 (USP26) regulates the RLR signaling pathway to modulate the antiviral immune response. The results demonstrate that EV71 infection upregulates the expression of USP26. Knockdown of USP26 significantly enhances EV71-induced expression of IFN-ß and downstream interferon-stimulated genes (ISGs). Deficiency of USP26 not only inhibits EV71 replication but also weakens the host's resistance to EV71 infection. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. USP26 physically interacts with TRAF3 and reduces the K63-linked polyubiquitination of TRAF3, thereby promoting pIRF3-mediated antiviral signaling. Conversely, knockdown of USP26 leads to an increase in the K63-linked polyubiquitination of TRAF3. These findings unequivocally establish the essential role of USP26 in RLR signaling and significantly contribute to the understanding of deubiquitination-mediated regulation of innate antiviral responses.
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Transdução de Sinais , Fator 3 Associado a Receptor de TNF , Ubiquitinação , Fator 3 Associado a Receptor de TNF/metabolismo , Fator 3 Associado a Receptor de TNF/genética , Humanos , Interferon Tipo I/metabolismo , Enterovirus Humano A/fisiologia , Células HEK293 , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Interferon beta/metabolismo , Interferon beta/genética , Replicação ViralRESUMO
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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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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BACKGROUND AND PURPOSE: Epigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats. METHODS AND MATERIALS: PE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50â¯mg/kg (High, H) from gestational day (GD) 6-17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured. RESULTS: EGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG. CONCLUSION: EGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.
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Catequina , Fator 2 Relacionado a NF-E2 , Óxido Nítrico Sintase Tipo III , Pré-Eclâmpsia , Animais , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/administração & dosagem , Gravidez , Feminino , Fator 2 Relacionado a NF-E2/metabolismo , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/imunologia , Pré-Eclâmpsia/patologia , Ratos , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Modelos Animais de Doenças , Placenta/efeitos dos fármacos , Placenta/patologia , Placenta/metabolismo , Resultado da Gravidez , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Ratos Sprague-Dawley , Heme Oxigenase (Desciclizante)/metabolismoRESUMO
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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COVID-19 vaccination is vital in reducing illness, hospitalization, and mortality in the face of this global pandemic. However, COVID-19 vaccination rates worldwide remain below WHO public health targets, and persistent structural inequities reduce vaccine uptake likelihood among populations of low socioeconomic status. We conducted a cross-sectional study based on publicly available data from the Our World in Data project. We included all 124 countries with available open epidemic data and a population of more than 5 million. We used a Cox Regression Model, with population, population density, median age, human development index, GDP per capita, gender inequality index, healthcare access and quality index, hospital beds per thousand people, completion rate of primary education, infection cases of COVID-19 by the end of 2022, and death rate due to COVID-19 by the end of 2022 as predictors for model hazard rates of completion of 50% population vaccination. According to our study, countries with higher populations, higher population density, higher human development index, lower gender inequality index, and lower hospital beds per 1000 people had a higher hazard rate, which means they were more likely to achieve 50% population vaccination faster. By utilizing the time to achieve vaccination rate goals as our primary endpoint, we evaluated inequity from a dual perspective, considering both the differences in vaccination rates and the duration required to attain them. Consequently, this study employed survival analysis approaches to gain a comprehensive understanding of vaccine drivers and population-level trends nationally and inform all communities from a statistical perspective to prepare for health emergencies. Development-level standing modified the effects of equal access to COVID-19 vaccination on cumulative cases and mortality, for which countries of low or medium human development tended to fare worse in outcomes than high human development countries. As COVID-19 vaccination efforts evolve, healthcare professionals, scholars, and policymakers need to identify the structural impediments to equitable vaccination awareness, access, and uptake so that future vaccination campaigns are not impeded by these barriers to immunization. Recognizing the complex nature of this significant barrier, it is evident that no single statistical analysis method can comprehensively address all intricacies.
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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
High spinal cord injury (SCI) leads to persistent and debilitating compromise in respiratory function. Cervical SCI not only causes the death of phrenic motor neurons (PhMNs) that innervate the diaphragm, but also damages descending respiratory pathways originating in the rostral ventral respiratory group (rVRG) located in the brainstem, resulting in denervation and consequent silencing of spared PhMNs located caudal to injury. It is imperative to determine whether interventions targeting rVRG axon growth and respiratory neural circuit reconnection are efficacious in chronic cervical contusion SCI, given that the vast majority of individuals are chronically-injured and most cases of SCI involve contusion-type damage to the cervical region. We therefore employed a rat model of chronic cervical hemicontusion to test therapeutic manipulations aimed at reconstructing damaged rVRG-PhMN-diaphragm circuitry to achieve recovery of respiratory function. At a chronic time point post-injury, we systemically administered: an antagonist peptide directed against phosphatase and tensin homolog (PTEN), a central inhibitor of neuron-intrinsic axon growth potential; an antagonist peptide directed against receptor-type protein tyrosine phosphatase sigma (PTPσ), another important negative regulator of axon growth capacity; or a combination of these two peptides. PTEN antagonist peptide (PAP4) promoted partial recovery of diaphragm motor activity out to nine months post-injury (though this effect depended on the anesthetic regimen used during recording), while PTPσ peptide did not impact diaphragm function after cervical SCI. Furthermore, PAP4 promoted robust growth of descending bulbospinal rVRG axons caudal to the injury within the denervated portion of the PhMN pool, while PTPσ peptide did not affect rVRG axon growth at this location that is critical to control of diaphragmatic respiratory function. In conclusion, we find that, when PTEN inhibition is targeted at a chronic time point following cervical contusion, our non-invasive PAP4 strategy can successfully promote significant regrowth of damaged respiratory neural circuitry and also partial recovery of diaphragm motor function.
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Axônios , Diafragma , PTEN Fosfo-Hidrolase , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Animais , Feminino , Ratos , Axônios/efeitos dos fármacos , Medula Cervical/lesões , Doença Crônica , Diafragma/inervação , Modelos Animais de Doenças , PTEN Fosfo-Hidrolase/antagonistas & inibidores , PTEN Fosfo-Hidrolase/metabolismo , Ratos Sprague-Dawley , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/antagonistas & inibidores , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Recuperação de Função Fisiológica/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/patologiaRESUMO
BACKGROUND: To assess the predictive capabilities of serum exosomal levels of micro-RNA-520a-5p (miR-520a-5p) concerning the occurrence of severe preeclampsia (sPE) and fetal growth restriction (FGR) during the first trimester of pregnancy. METHODS: During the period spanning from October 2020 to October 2021, serum samples were procured from the first trimester and subsequently preserved by freezing at -80 â. These samples were obtained from 105 pregnant women in a nested case-control study. This cohort consisted of individuals who later developed sPE (sPE group, n = 35) and FGR (FGR group, n = 35) during the third trimester. Additionally, 35 women with normal blood pressure were denoted as normal pregnancy group. Serum samples from the first trimester were retrieved from all groups for further analysis after thawing. Exosomes were extracted from the serum samples collected during the first trimester and examined using transmission electron microscopy, western blot, and nanoparticle tracking analysis. Additionally, the determination of their placental origin was also established during the course of the study. Exosome miR-520a-5p levels were measured using real-time quantitative polymerase chain reaction assays, primarily involving quantitative reverse transcription polymerase chain reactions. Fetal placental tissues from the 3 groups were collected shortly after birth, and miR-520a-5p expression was measured using real-time quantitative polymerase chain reaction. Serum placental exosomes and fetal placental tissues were compared for miR-520a-5p levels. Placental trophoblasts were identified as the source of serum exosomes in all 3 groups. RESULTS: It was found that serum placental exosomes exhibited lower levels of miR-520a-5p in both the sPE and FGR groups when compared to the normal pregnancy group. This finding was consistent with observations made in postpartum placental tissues. The predictive accuracy for sPE using miR-520a-5p levels in serum placental exosomes during the first trimester was notably higher (area under the receiver operating characteristic curve = 0.806, P <.05) compared to the prediction of FGR (area under the receiver operating characteristic curve = 0.628, P <.05). CONCLUSION: Placenta-derived exosomes can be extracted from maternal serum during the first trimester of pregnancy and miR-520a-5p detected from the exosomes. The downregulation of miR-520a-5p serves as a more predictive indicator for the subsequent development of sPE compared to predicting FGR.
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Exossomos , Retardo do Crescimento Fetal , MicroRNAs , Placenta , Pré-Eclâmpsia , Primeiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Retardo do Crescimento Fetal/sangue , MicroRNAs/sangue , Exossomos/metabolismo , Adulto , Estudos de Casos e Controles , Primeiro Trimestre da Gravidez/sangue , Placenta/metabolismo , Biomarcadores/sangue , Valor Preditivo dos TestesRESUMO
The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.
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Adipócitos Bege , Adipogenia , Envelhecimento , Temperatura Baixa , Animais , Adipogenia/genética , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Camundongos , Adipócitos Bege/metabolismo , Camundongos Endogâmicos C57BL , Masculino , Adipócitos/metabolismo , Diferenciação Celular , Reprogramação Celular , Reprogramação MetabólicaRESUMO
Small RNA (sRNA)-mediated RNA silencing (also known as RNA interference, or RNAi) is a conserved mechanism in eukaryotes that includes RNA degradation, DNA methylation, heterochromatin formation and protein translation repression. In plants, sRNAs can move either cell-to-cell or systemically, thereby acting as mobile silencing signals to trigger noncell autonomous silencing. However, whether and what proteins are also involved in noncell autonomous silencing have not been elucidated. In this study, we utilized a previously reported inducible RNAi plant, PDSi, which can induce systemic silencing of the endogenous PDS gene, and we demonstrated that DCL3 is involved in systemic PDS silencing through its RNA binding activity. We confirmed that the C-terminus of DCL3, including the predicted RNA-binding domain, is capable of binding short RNAs. Mutations affecting RNA binding, but not processing activity, reduced systemic PDS silencing, indicating that DCL3 binding to RNAs is required for the induction of systemic silencing. Cucumber mosaic virus infection assays showed that the RNA-binding activity of DCL3 is required for antiviral RNAi in systemically noninoculated leaves. Our findings demonstrate that DCL3 acts as a signaling agent involved in noncell autonomous silencing and an antiviral effect in addition to its previously known function in the generation of 24-nucleotide sRNAs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00124-6.
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[This corrects the article DOI: 10.1007/s42994-023-00124-6.].
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Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.
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Neoplasias Colorretais , Dieta , Fragilidade , Inflamação , Interleucina-10 , Interleucina-6 , Humanos , Neoplasias Colorretais/sangue , Estudos Transversais , Masculino , Feminino , Fragilidade/sangue , Inflamação/sangue , Idoso , Interleucina-6/sangue , Interleucina-10/sangue , Pessoa de Meia-Idade , Biomarcadores/sangueRESUMO
Automated classification of breast cancer subtypes from digital pathology images has been an extremely challenging task due to the complicated spatial patterns of cells in the tissue micro-environment. While newly proposed graph transformers are able to capture more long-range dependencies to enhance accuracy, they largely ignore the topological connectivity between graph nodes, which is nevertheless critical to extract more representative features to address this difficult task. In this paper, we propose a novel connectivity-aware graph transformer (CGT) for phenotyping the topology connectivity of the tissue graph constructed from digital pathology images for breast cancer classification. Our CGT seamlessly integrates connectivity embedding to node feature at every graph transformer layer by using local connectivity aggregation, in order to yield more comprehensive graph representations to distinguish different breast cancer subtypes. In light of the realistic intercellular communication mode, we then encode the spatial distance between two arbitrary nodes as connectivity bias in self-attention calculation, thereby allowing the CGT to distinctively harness the connectivity embedding based on the distance of two nodes. We extensively evaluate the proposed CGT on a large cohort of breast carcinoma digital pathology images stained by Haematoxylin & Eosin. Experimental results demonstrate the effectiveness of our CGT, which outperforms state-of-the-art methods by a large margin. Codes are released on https://github.com/wang-kang-6/CGT.
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Algoritmos , Neoplasias da Mama , Interpretação de Imagem Assistida por Computador , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/classificação , Feminino , Interpretação de Imagem Assistida por Computador/métodos , Mama/diagnóstico por imagem , Mama/patologiaRESUMO
A mild and effective strategy for the asymmetric synthesis of C2-quaternary indolin-3-ones from 2-alkynyl arylazides and ketones by gold/chiral amine relay catalysis is described. In this reaction, 2-alkynyl arylazides undergo gold-catalyzed cyclization, nucleophilic attack, and oxidation to form intermediate 2-phenyl-3H-indol-3-ones, followed by an l-proline-catalyzed asymmetric Mannich reaction with ketones, to afford corresponding products in satisfactory yields with excellent enantio- and diastereoselectivities.
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Increasing soil cadmium (Cd) contamination is a serious threat to human food health and safety. In order to reduce Cd uptake and Cd toxicity in silage maize, hydroponic tests were conducted to investigate the effect of exogenous Cd on the toxicity of silage maize in this study. In the study, a combination of Cd (5, 20, 50, 80, and 10 µM) treatments was applied in a hydroponic system. With increasing Cd concentration, Cd significantly inhibited the total root length (RL), root surface area (SA), root volume (RV), root tip number (RT), and branching number (RF) of maize seedlings, which were reduced by 28.1 to 71.3%, 20.2 to 64.9%, 11.2 to 56.5%, 43.7 to 63.4%, and 38.2 to 72.6%, respectively. The excessive Cd accumulation inhibited biomass accumulation and reduced silage maize growth, photosynthesis, and chlorophyll content and activated the antioxidant systems, including increasing lipid peroxidation and stimulating catalase (CAT) and peroxidase (POD), but reduced the activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX) in the root. Besides, selenium (Se) significantly decreased the Cd concentration of the shoot and root by 27.1% and 35.1% under Cd50, respectively. Our results reveal that exogenously applied Cd reduced silage maize growth and impaired photosynthesis. Whereas silage maize can tolerate Cd by increasing the concentration of ascorbate and glutathione and activating the antioxidant defense system, the application of exogenous selenium significantly reduced the content of Cd in silage maize.