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Sequence alignment is an essential method in bioinformatics and the basis of many analyses, including phylogenetic inference, ancestral sequence reconstruction, and gene annotation. Sequencing artifacts and errors made during genome assembly, such as abiological frameshifts and incorrect early stop codons, can impact downstream analyses leading to erroneous conclusions in comparative and functional genomic studies. More significantly, while indels can occur both within and between codons in natural sequences, most amino-acid- and codon-based aligners assume that indels only occur between codons. This mismatch between biology and alignment algorithms produces suboptimal alignments and errors in downstream analyses. To address these issues, we present COATi, a statistical, codon-aware pairwise aligner that supports complex insertion-deletion models and can handle artifacts present in genomic data. COATi allows users to reduce the amount of discarded data while generating more accurate sequence alignments. COATi can infer indels both within and between codons, leading to improved sequence alignments. We applied COATi to a dataset containing orthologous protein-coding sequences from humans and gorillas and conclude that 41% of indels occurred between codons, agreeing with previous work in other species. We also applied COATi to semiempirical benchmark alignments and find that it outperforms several popular alignment programs on several measures of alignment quality and accuracy.
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Mutação INDEL , Alinhamento de Sequência , Alinhamento de Sequência/métodos , Humanos , Animais , Software , Algoritmos , Códon , Gorilla gorilla/genética , Biologia Computacional/métodos , Fases de Leitura Aberta , FilogeniaRESUMO
Organic polyradicals with a high-spin ground state and quantum magnetic properties suitable for spin manipulation are valuable materials for diverse innovative technologies, including quantum devices. However, the typically high reactivity and low stability of conventional polyradicals present a major obstacle to such applications. In this study, a highly stable carbon-centered triradical TR with a quartet ground state and excellent stability (τ1/2 of â¼90 days in air-saturated toluene at room temperature) is achieved, which shows apposite magnetic anisotropy and Zeeman splitting partition with favorable addressability. By virtue of the optimal stability, thorough structural and magnetic characterizations are realized. With X-ray crystallography unambiguously proving the molecular structure, the quartet ground state (ΔED-Q = 0.78 kcal/mol) is confirmed by the SQUID measurements, while the cw- and pulsed EPR techniques offer additional supportive evidence for the high-spin nature. Remarkably, owing to the easily attained magnetic anisotropy, selective excitations between different Zeeman splitting levels are successfully demonstrated with TR in its frozen toluene solution without the requirement for special alignment, which is unprecedented for organic polyradicals. Along with the millisecond spin-lattice relaxation and microsecond coherence time manifested by TR, this triradical is promising for potential coherent spin manipulation applications as a multienergy-level quantum information carrier.
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Soil minerals influence the biogeochemical cycles of fluoride (F) and phosphorus (P), impacting soil quality and bioavailability to plants. However, the cooperative mechanisms of soil minerals in governing F and P in the soil environment remain a grand challenge. Here, we reveal the essential role of a typical soil mineral, montmorillonite (Mt), in the cycling and fate of F and P. The results show that the enrichment of metal sites on the Mt surface promotes the mineralization of F to the fluorapatite (FAP) phase, thereby remaining stable in the environment, simultaneously promoting P release. This differential behavior leads to a reduction in the level of F pollution and an enhancement of P availability. Moreover, solid-state NMR and HRTEM observations confirm the existence of metastable F-Ca-F intermediates, emphasizing the pivotal role of Mt surface sites in regulating crystallization pathways and crystal growth of FAP. Furthermore, the in situ atomic force microscopy and theoretical calculations reveal molecular fractionation mechanisms and adsorption processes. It is observed that a competitive relationship exists between F and P at the Mt interface, highlighting the thermodynamically advantageous pathway of forming metastable intermediates, thereby governing the activity of F and P in the soil environment at a molecular level. This work paves the way to reveal the important role of clay minerals as a mineralization matrix for soil quality management and offers new strategies for modulating F and P dynamics in soil ecosystems.
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Fluoretos , Fósforo , Fluoretos/química , Fósforo/química , Solo/química , Argila/química , Apatitas/química , Bentonita/química , Adsorção , Minerais/química , Silicatos de Alumínio/químicaRESUMO
OBJECTIVES: Due to the government's liberalization of epidemic control, the current 2019 novel coronavirus disease (COVID-19) has started to spread widely within China. This study aimed to use the fetal heart quantification (fetal HQ) technique to assess the cardiac function and morphology of the fetuses of pregnant women diagnosed with COVID-19 in the early stages of pregnancy. METHODS: Exactly 86 pregnant women diagnosed with COVID-19 infection in early pregnancy (COVID-19 group) and 90 healthy pregnant women (control group) who underwent fetal echocardiography were prospectively included in this study. The fetal HQ technique was applied to compare the differences in the global sphericity index (GSI), global strain values (GS), fractional area change (FAC), and 24-segment fractional shortening (FS) of the left and right ventricles, between the COVID-19 group and the control group. RESULTS: Compared with the control group, the differences in GS and 24-segment FS of the left ventricle in the COVID-19 group were not statistically significant. However, the COVID-19 group showed lower GSI values compared with the control group (1.24 vs 1.28). FAC (48.12%) of the left ventricle and GS (-23.55%), FAC (41.74%) of the right ventricle in the COVID-19 group were reduced compared with FAC (50.50%) of the left ventricle and GS (-27.63%), FAC (46.01%) of the right ventricle in the control group. Segmental analysis revealed reduced FS in segments 20-24 in the COVID-19 group compared with the control group. Right ventricular GS was an independent predictor of adverse pregnancy outcome with an optimal cutoff value of -18.66%. CONCLUSIONS: The results suggest that COVID-19 infection in early pregnancy may have a negative impact on fetal cardiac morphology and function. Fetal HQ may offer a new assessment method for the early identification of fetal cardiac alterations in pregnant women infected with COVID-19.
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COVID-19 , Ecocardiografia , Coração Fetal , Complicações Infecciosas na Gravidez , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , COVID-19/diagnóstico por imagem , COVID-19/fisiopatologia , COVID-19/complicações , Coração Fetal/diagnóstico por imagem , Coração Fetal/fisiopatologia , Adulto , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Complicações Infecciosas na Gravidez/fisiopatologia , Ultrassonografia Pré-Natal/métodos , Estudos Prospectivos , Ecocardiografia/métodos , SARS-CoV-2 , Sístole , China/epidemiologiaRESUMO
Recent increases in vegetation greenness over much of the world reflect increasing CO2 globally and warming in cold areas. However, the strength of the response to both CO2 and warming in those areas appears to be declining for unclear reasons, contributing to large uncertainties in predicting how vegetation will respond to future global changes. Here, we investigated the changes of satellite-observed peak season absorbed photosynthetically active radiation (Fmax ) on the Tibetan Plateau between 1982 and 2016. Although climate trends are similar across the Plateau, we identified robust divergent responses (a greening of 0.31 ± 0.14% year-1 in drier regions and a browning of 0.12 ± 0.08% year-1 in wetter regions). Using an eco-evolutionary optimality (EEO) concept of plant acclimation/adaptation, we propose a parsimonious modelling framework that quantitatively explains these changes in terms of water and energy limitations. Our model captured the variations in Fmax with a correlation coefficient (r) of .76 and a root mean squared error of .12 and predicted the divergent trends of greening (0.32 ± 0.19% year-1 ) and browning (0.07 ± 0.06% year-1 ). We also predicted the observed reduced sensitivities of Fmax to precipitation and temperature. The model allows us to explain these changes: Enhanced growing season cumulative radiation has opposite effects on water use and energy uptake. Increased precipitation has an overwhelmingly positive effect in drier regions, whereas warming reduces Fmax in wetter regions by increasing the cost of building and maintaining leaf area. Rising CO2 stimulates vegetation growth by enhancing water-use efficiency, but its effect on photosynthesis saturates. The large decrease in the sensitivity of vegetation to climate reflects a shift from water to energy limitation. Our study demonstrates the potential of EEO approaches to reveal the mechanisms underlying recent trends in vegetation greenness and provides further insight into the response of alpine ecosystems to ongoing climate change.
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Dióxido de Carbono , Ecossistema , Mudança Climática , Temperatura , Água , TibetRESUMO
OBJECTIVE: To develop and investigate a deep learning model with data integration of ultrasound contrast-enhanced micro-flow (CEMF) cines, B-mode images, and patients' clinical parameters to improve the diagnosis of significant liver fibrosis (≥ F2) in patients with chronic hepatitis B (CHB). METHODS: Of 682 CHB patients who underwent ultrasound and histopathological examinations between October 2016 and May 2020, 218 subjects were included in this retrospective study. We devised a data integration-based deep learning (DIDL) model for assessing ≥ F2 in CHB patients. The model contained three convolutional neural network branches to automatically extract features from ultrasound CEMF cines, B-mode images, and clinical data. The extracted features were fused at the backend of the model for decision-making. The diagnostic performance was evaluated across fivefold cross-validation and compared against the other methods in terms of the area under the receiver operating characteristic curve (AUC), with histopathological results as the reference standard. RESULTS: The mean AUC achieved by the DIDL model was 0.901 [95% CI, 0.857-0.939], which was significantly higher than those of the comparative methods, including the models trained by using only CEMF cines (0.850 [0.794-0.893]), B-mode images (0.813 [0.754-0.862]), or clinical data (0.757 [0.694-0.812]), as well as the conventional TIC method (0.752 [0.689-0.808]), APRI (0.792 [0.734-0.845]), FIB-4 (0.776 [0.714-0.829]), and visual assessments of two radiologists (0.812 [0.754-0.862], and 0.800 [0.739-0.849]), all ps < 0.01, DeLong test. CONCLUSION: The DIDL model with data integration of ultrasound CEMF cines, B-mode images, and clinical parameters showed promising performance in diagnosing significant liver fibrosis for CHB patients. KEY POINTS: ⢠The combined use of ultrasound contrast-enhanced micro-flow cines, B-mode images, and clinical data in a deep learning model has potential to improve the diagnosis of significant liver fibrosis. ⢠The deep learning model with the fusion of features extracted from multimodality data outperformed the conventional methods including mono-modality data-based models, the time-intensity curve-based recognizer, fibrosis biomarkers, and visual assessments by experienced radiologists. ⢠The interpretation of the feature attention maps in the deep learning model may help radiologists get better understanding of liver fibrosis-related features and hence potentially enhancing their diagnostic capacities.
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Aprendizado Profundo , Hepatite B Crônica , Humanos , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Estudos Retrospectivos , Cirrose Hepática/patologia , Ultrassonografia , Meios de Contraste , Fígado/diagnóstico por imagemRESUMO
The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.
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Proteínas de Arabidopsis , Arabidopsis , Malus , Malus/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Filogenia , Secas , Proteínas de Arabidopsis/metabolismoRESUMO
Stable carbon-based polyradicals exhibiting strong spin-spin coupling and slow depolarization processes are particularly attractive functional materials. A new molecular motif synthesized by a convenient method that allows the integration of stable, high-spin radicals to (hetero)aromatic polycycles has been developed, as illustrated by a non-Kekulé diradical showing a triplet ground state with long persistency (τ1/2 ≈31â h) in air. Compared to the widely used 1,3-phenylene, the newly designed (diaza)pyrene-4,10-diyl moiety is for the first time demonstrated to confer ferromagnetic (FM) spin coupling, allowing delocalized non-disjoint SOMOs. With the X-ray crystallography unambiguously proving the diradical structure, the triplet ground state was thoroughly characterized. A large ΔES-T of 1.1â kcal/mol, proving the strong FM coupling effect, was revealed consistently by superconducting quantum interference device (SQUID) measurements and variable-temperature electron paramagnetic resonance (EPR) spectroscopy, while the zero-field splitting and triplet nutation characters were examined by continuous-wave and pulsed EPR spectroscopy. A millisecond spin-lattice relaxation time was also detected. The current study not only offers a new molecular motif enabling FM coupling between carbon-based spins, but more importantly presents a general method for installing stable polyradicals into functional π-systems.
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Oxidative stress-induced autophagy dysfunction is involved in the pathogenesis of intervertebral disc degeneration (IVDD). MicroRNAs (miRNAs) not only have been regarded as important regulators of IVDD but also reported to be related to autophagy. This research was aimed to explore the role of miR-130b-3p in IVDD and its regulation on autophagy mechanism. The miR-130b-3p expression in the patient's degenerative nucleus pulposus (NP) samples and rat NP tissues was detected by qRT-PCR and FISH assay. The miR-130b-3p was knocked down or overexpressed in the human NP cells by lentivirus transfection. TBHP was used to induce oxidative stress in the human NP cells. Apoptosis, senescence, and autophagy were evaluated by flow cytometry, ß-gal staining, immunofluorescence, electron microscopy, and Western blot in the miR-130b-3p knocked down human NP cells under TBHP treatment. The relationship between the miR-130b-3p and ATG14 or PRKAA1 was confirmed by luciferase assay. The siRNA transfection was used to knock down the ATG14 and PRKAA1 expression, and then the human NP cells functions were further determined. In the in vivo experiment, the IVDD rat model was constructed and an adeno-associated virus (AAV)-miR-130b-3p inhibitor was intradiscally injected. After that, MRI and histological staining were conducted to evaluate the role of miR-130b-3p inhibition in the IVDD rat model. We found that the miR-130b-3p was upregulated in the degenerative NP samples from humans and rats. Interestingly, the inhibition of miR-130b-3p rescued oxidative stress-induced dysfunction of the human NP cells, and miR-130b-3p inhibition upregulated autophagy. Mechanistically, we confirmed that the miR-130b-3p regulated the ATG14 and PRKAA1 directly and the knockdown of the ATG14 or PRKAA1 as well as the treatment of autophagy inhibitor blockaded the autophagic flux and reversed the protective effects of miR-130b-3p inhibition in the TBHP-induced human NP cells. Furthermore, the inhibition of the miR-130b-3p via AAV- miR-130b-3p injection ameliorated the IVDD in a rat model. These data demonstrated that the miR-130b-3p inhibition could upregulate the autophagic flux and alleviate the IVDD via targeting ATG14 and PRKAA1.The translational potential of this article: The suppression of miR-130b-3p may become an effective therapeutic strategy for IVDD.
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Degeneração do Disco Intervertebral , Disco Intervertebral , MicroRNAs , Núcleo Pulposo , Animais , Apoptose/genética , Autofagia/genética , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , MicroRNAs/metabolismo , Núcleo Pulposo/metabolismo , RatosRESUMO
Polycyclic aromatic hydrocarbon (PAH) structures with suitable electron-withdrawing groups are useful building blocks for developing optical and electron-transporting materials. Here, we report the application of a double benzannulation process to the syntheses of PAH diimides with enlarged π-frameworks featuring a central anthracene moiety. The preparations are realized by copper-catalyzed [4+2] cycloaddition of ethynyl-substituted aromatic dicarboximide to 2,5-bis(phenylethynyl)terephthalaldehyde, followed by intramolecular photocyclization or direct arylation via Heck cross coupling. A central symmetric benzo[1,2-k:4,5-k']-bis(fluoranthene)-3,4,12,13-tetracarboxyl diimide (BFDI) is acquired, with the single crystal structure revealing its completely planar polycyclic skeleton. Such a shape-persistent PAH expectedly exhibits a tendency to stack face-to-face and forms J-aggregates. Moreover, BFDI can be difunctionalized site-selectively at the reactive 9 and 10 positions of the anthracene unit and then applied to prepare conjugated polymers. When coupled with 1,4-diketopyrrolo[3,4-c]-pyrrole (DPP) via thiophene and dithiophene linkers, two polymers with significantly broadened absorption bands extended to the near-infrared regime are obtained, evidencing the effective π-conjugative extension ability of BFDI unit.
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BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of disability with limited treatment strategies. A better understanding of the mechanism of IDD might enable less invasive and more targeted treatments. This study aimed to identify the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) regulatory mechanisms in IDD. METHODS : The GSE67567 microarray dataset was downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs, miRNAs and mRNAs between IDD and controls were identified. A ceRNA network was constructed on the basis of the interaction between circRNAs and miRNAs, and miRNAs and mRNAs. Pathway enrichment analysis was performed on the mRNAs in the ceRNA network. Then, with 'intervertebral disc degeneration' as keywords, IDD-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were searched for in the Comparative Toxicogenomics Database. RESULTS: A total of 105 differentially expressed circRNAs, 84 miRNAs and 967 mRNAs were identified. After analysis, 86 circRNA-miRNA, and 126 miRNA-mRNA regulatory relationship pairs were obtained to construct a ceRNA network. The mRNAs were enriched in six KEGG signalling pathways, and four were associated with IDD: the hsa04350: TGF-beta signalling pathway, hsa04068: FoxO signalling pathway, hsa05142: Chagas disease (American trypanosomiasis) and hsa04380: Osteoclast differentiation. An IDD-related ceRNA network was constructed involving four circRNAs, three miRNAs and 11 mRNAs. Auxiliary validation showed that the expression levels of miR-185-5p, miR-486-5p, ACVR1B, FOXO1, SMAD2 and TGFB1 were consistent in different databases. CONCLUSIONS: Our study identified some circRNA-miRNA-mRNA interaction axes potentially associated with the progression of IDD, viz.: circRNA_100086-miR-509-3p-MAPK1, circRNA_000200-miR-185-5p-TGFB1, circRNA_104308-miR-185-5p-TGFB1, circRNA_400090-miR-486-5p-FOXO1 and circRNA_400090-miR-486-5p-SMAD2.
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Degeneração do Disco Intervertebral , Disco Intervertebral , MicroRNAs , Biomarcadores , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
In mobile edge computing (MEC), mobile devices can choose to offload their tasks to edge servers for execution, thereby effectively reducing the completion time of tasks and energy consumption of mobile devices. However, most of the data transfer brought by offloading relies on wireless communication technology, making the private information of mobile devices vulnerable to eavesdropping and monitoring. Privacy leakage, especially the location and association privacies, can pose a significant risk to users of mobile devices. Therefore, protecting the privacy of mobile devices during task offloading is important and cannot be ignored. This paper considers both location privacy and association privacy of mobile devices during task offloading in MEC and targets to reduce the leakage of location and association privacy while minimizing the average completion time of tasks. To achieve these goals, we design a privacy-preserving task offloading scheme to protect location privacy and association privacy. The scheme is mainly divided into two parts. First, we adopt a proxy forwarding mechanism to protect the location privacy of mobile devices from being leaked. Second, we select the proxy server and edge server for each task that needs to be offloaded. In the proxy server selection policy, we make a choice based on the location information of proxy servers, to reduce the leakage risk of location privacy. In the edge server selection strategy, we consider the privacy conflict between tasks, the computing ability, and location of edge servers, to reduce the leakage risk of association privacy plus the average completion time of tasks as much as possible. Simulated experimental results demonstrate that our scheme is effective in protecting the location privacy and association privacy of mobile devices and reducing the average completion time of tasks compared with the-state-of-art techniques.
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Comunicação , Privacidade , Computadores de Mão , Tecnologia da Informação , PolíticasRESUMO
Stereo- and enantioselective cross-electrophile coupling involving C-F bond activation is reported. Treatment of gem-difluoroalkenes with racemic benzyl electrophiles in the presence of a chiral nickel complex using B2 pin2 as a stoichiometric reductant allows the construction of a C(sp2 )-C(sp3 ) bond under mild conditions, affording a broad range of monofluoroalkenes bearing stereogenic allylic centers. Initial mechanistic studies indicate that a radical chain pathway may be operating, wherein the ester group in the gem-difluoroalkene promotes C-F bond activation through oxidative addition to a Ni species.
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Enantioenriched alcohols comprise much of the framework of organic molecules. Here, we first report that chiral nickel complexes can catalyze the intermolecular enantioselective addition of aryl iodides across aldehydes to provide diverse optically active secondary alcohols using zinc metal as the reducing agent. This method shows a broad substrate scope under mild reaction conditions and precludes the traditional strategy through the pre-generation of organometallic reagents. Mechanistic studies indicate that an in situ formed arylnickel, instead of an arylzinc, adds efficiently to aldehydes, forming a new C-C bond and a chiral nickel alkoxide that may be turned over by zinc powder.
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To investigate the capability of π-π stacking motifs to enable spin-spin coupling, we designed and synthesized three pairs of regio-isomers featuring two radical moieties joined by a [2.2]paracyclophane (CP) unit. By fusing indeno units to CP, two partially stacked fluorene radicals are covalently linked, exhibiting evident antiferromagnetic (AFM) coupling regardless of the orientation of two spins. Remarkably, while possessing high diradical indices of 0.8 and 0.9, the two molecules demonstrate good air stability by virtue of their singlet ground state. Single crystals help unravel the structural basis of their AFM coupling behaviors. When two radical centers are arranged at the pseudometa-positions around CP, the face-to-face stacked phenylene rings intrinsically confer orbital interactions that promote AFM coupling. On the other hand, if two radicals are directed in the pseudopara-orientation, significant orbital overlapping is observed between the radical centers (i.e., C9 of fluorene) and the aromatic carbons laid on the side, rendering AFM coupling between the two spins. In contrast, when two fluorene radicals are tethered to CP via C9 through a single C-C bond, ferromagnetic (FM) coupling is manifested by both diradical isomers featuring pseudometa- and pseudopara-connectivity. With minimal spin distributed on CP and thus limited contribution from π-π stacking, their spin-spin coupling properties are more similar to a pair of nitroxide diradical analogues, in which the two spins are dominantly coupled via through-space interactions. From these results, important conclusions are elucidated such as that although through-space interactions may confer FM coupling, with weakened strength shown by PAH radicals due to their lower polarity, face-to-face stacked π-frameworks tend to induce AFM coupling, because favorable orbital interactions are readily achieved by PAH systems hosting delocalized spins that are capable of adopting varied stacking motifs.
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OBJECTIVES: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer. MATERIALS AND METHODS: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. RESULTS: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). CONCLUSIONS: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.
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Neoplasias Esofágicas/patologia , Esôfago/citologia , Células Gigantes/imunologia , Macrófagos/imunologia , Fagocitose/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , China , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/imunologia , Esôfago/imunologia , Esôfago/patologia , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de IgG/imunologiaRESUMO
The purpose of this study was to characterize the antimicrobial resistance produced by mobile genetic elements and integron gene cassettes in Escherichia coli isolated from the feces of captive giant pandas. We performed a standard disk diffusion antimicrobial susceptibility test with 84 E. coli isolates and further evaluated the mobile genetic elements and integron gene cassettes. The antimicrobial susceptibility test demonstrated that 43.37% (36/84) of the isolates showed multiple drug resistances. The E. coli isolates mainly showed resistance to aztreonam (86.90%, 73/84) and amoxicillin/clavulanic acid (80.95%, 68/84). The most frequently observed resistance patterns were ampicillin/amoxicillin-clavulanic acid (13.10%, n = 11), and doxycycline/amoxicillin-clavulanic acid (4.76%, n = 4). Further analyses detected 11 mobile genetic elements, of which merA (54/84, 64.30%) had the highest frequency. All isolates were negative for intI3, traA, tnpU, traF, tnp513, tnsA, ISkpn7, ISpa7, ISkpn6, and ISCR1. We further analyzed antimicrobial resistance-related integrons among 30 E. coli isolates (the 27 intI1-positive isolates and the 3 intI2-positive isolates); six gene cassette profiles (dfrA17+aadA5, aadA2, dfrA12+aadA2, dfrA1+aadA1, dfrA1, and aadA1) were identified in the 27 intI1-positive isolates, but not in the three intI2-positive ones. Our study sheds light on the prevalence of multiple drug resistances and the diversity of mobile genetic elements in E. coli isolates, and highlights the necessity to monitor antibiotic resistance in more E. coli strains from captive giant pandas.
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Resistência a Múltiplos Medicamentos/genética , Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Ursidae/microbiologia , Animais , Farmacorresistência Bacteriana/genética , Fezes , Variação Genética , Integrons/genética , PrevalênciaRESUMO
Androgens such as testosterone and dihydrotestosterone are a critical driver of prostate cancer progression. Cancer resistance to androgen deprivation therapies ensues when tumors engage metabolic processes that produce sustained androgen levels in the tissue. However, the molecular mechanisms involved in this resistance process are unclear, and functional imaging modalities that predict impending resistance are lacking. Here, using the human LNCaP and C4-2 cell line models of prostate cancer, we show that castration treatment-sensitive prostate cancer cells that normally have an intact glucuronidation pathway that rapidly conjugates and inactivates dihydrotestosterone and thereby limits androgen signaling, become glucuronidation deficient and resistant to androgen deprivation. Mechanistically, using CRISPR/Cas9-mediated gene ablation, we found that loss of UDP glucuronosyltransferase family 2 member B15 (UGT2B15) and UGT2B17 is sufficient to restore free dihydrotestosterone, sustained androgen signaling, and development of castration resistance. Furthermore, loss of glucuronidation enzymatic activity was also detectable with a nonsteroid glucuronidation substrate. Of note, glucuronidation-incompetent cells and the resultant loss of intracellular conjugated dihydrotestosterone were detectable in vivo by 18F-dihydrotestosterone PET. Together, these findings couple a mechanism with a functional imaging modality to identify impending castration resistance in prostate cancers.
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Di-Hidrotestosterona/metabolismo , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/metabolismo , Testosterona/metabolismo , Animais , Linhagem Celular Tumoral , Di-Hidrotestosterona/química , Radioisótopos de Flúor , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Glicosilação , Humanos , Masculino , Camundongos , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Receptores Androgênicos/fisiologia , Transdução de Sinais , Testosterona/químicaRESUMO
Monitoring of wound pH is critical for interpreting wound status, because early identification of wound infection or nonhealing wounds is conducive to administion of therapies at the right time. Here, novel orange-emissive carbon quantum dots (O-CDs) are synthesized via microwave-assisted heating of 1,2,4-triaminobenzene and urea aqueous solution. The as-prepared O-CDs exhibit distinctive colorimetric response to pH changing, and also display pH-sensitive fluorescence. Benefiting from the response of O-CDs over a wound-relevant pH range (5-9), medical cotton cloth is selected to immobilize O-CDs through hydrogen bond interactions, the resultant O-CDs-coated cloth with emission at 560 nm shows a high response to pH variation in the range of 5-9 via both fluorescence and visible colorimetric changes. Moreover, the sensitivity of fluorescence to pH is capable of establishing an analytical mode for determining pH value. Further, the O-CDs-based pH indicator possesses not only superior biocompatibility and drug compatibility but also excellent resistance leachability and high reversibility. Importantly, the usage of O-CDs-coated cloth to detect pH is free from the interference of blood contamination and long-term storage, thus providing a valuable strategy for wound pH monitoring through visual response and quantitative determination.
Assuntos
Carbono/química , Colorimetria , Luz , Pontos Quânticos/química , Cicatrização , Animais , Morte Celular , Linhagem Celular , Concentração de Íons de Hidrogênio , Camundongos , Pontos Quânticos/ultraestrutura , Ratos , Soluções , Espectrometria de FluorescênciaRESUMO
PURPOSE: Low signal-to-noise-ratio and limited scan time of diffusion magnetic resonance imaging (dMRI) in current clinical settings impede obtaining images with high spatial and angular resolution (HSAR) for a reliable fiber reconstruction with fine anatomical details. To overcome this problem, we propose a joint space-angle regularization approach to reconstruct HSAR diffusion signals from a single 4D low resolution (LR) dMRI, which is down-sampled in both 3D-space and q-space. METHODS: Different from the existing works which combine multiple 4D LR diffusion images acquired using specific acquisition protocols, the proposed method reconstructs HSAR dMRI from only a single 4D dMRI by exploring and integrating two key priors, that is, the nonlocal self-similarity in the spatial domain as a prior to increase spatial resolution and ridgelet approximations in the diffusion domain as another prior to increase the angular resolution of dMRI. To more effectively capture nonlocal self-similarity in the spatial domain, a novel 3D block-based nonlocal means filter is imposed as the 3D image space regularization term which is accurate in measuring the similarity and fast for 3D reconstruction. To reduce computational complexity, we use the L2 -norm instead of sparsity constraint on the representation coefficients. RESULTS: Experimental results demonstrate that the proposed method can obtain the HSAR dMRI efficiently with approximately 2% per-voxel root-mean-square error between the actual and reconstructed HSAR dMRI. CONCLUSION: The proposed approach can effectively increase the spatial and angular resolution of the dMRI which is independent of the acquisition protocol, thus overcomes the inherent resolution limitation of imaging systems.