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As social entities, individuals' perception and behaviors are susceptible to the influence of their social groups. Previous research has consistently shown that the group context in which individuals are situated significantly influences their perceptual processing. We aim to investigate whether the group context in which another individual is situated alters our understanding of their visual perception, which holds profound implications for interpersonal interactions. To address this inquiry, we conducted three experiments. In Experiment 1, participants were presented with a visual scene depicting multiple avatars seated around a table, all facing an arrow positioned at the center of the table. They were instructed to adopt the visual perspective of a specific avatar within the group to perceive the arrow's orientation, and then reproduce its orientation from their own perspectives. We found that participants exhibited a bias towards the group's average perspective when reproducing the arrow's orientation. Experiment 2 further demonstrated that reinforced group processing could elicit an earlier appearance of this bias. In Experiment 3, we investigated an alternative explanation positing that the aforementioned bias originated from visual ensemble perception rather than group influence by instructing participants to reproduce the target avatar's position relative to the arrow's orientation. If the bias indeed originated from ensemble perception, it should also manifest in this task. However, the absence of any reproduction bias refuted this possibility. Through these experiments, we demonstrate that our understanding of an individual's perceptual experiences is influenced by the social context in which they are situated, which manifests as a convergence phenomenon.
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Accurate comprehension of others' thoughts and intentions is crucial for smooth social interactions, wherein understanding their perceptual experiences serves as a fundamental basis for this high-level social cognition. However, previous research has predominantly focused on the visual modality when investigating perceptual processing from others' perspectives, leaving the exploration of multisensory inputs during this process largely unexplored. By incorporating auditory stimuli into visual perspective-taking (VPT) tasks, we have designed a novel experimental paradigm in which the spatial correspondence between visual and auditory stimuli was limited to the altercentric rather than the egocentric reference frame. Overall, we found that when individuals engaged in explicit or implicit VPT to process visual stimuli from an avatar's viewpoint, the concomitantly presented auditory stimuli were also processed within this avatar-centered reference frame, revealing altercentric cross-modal interactions.
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Background: We explored the feasibility of a large-scale UK ambulance services trial of optimal defibrillation shock energy for out-of-hospital cardiac arrest. The primary objective of this feasibility study was to establish the number of eligible patients and the number recruited. Secondary outcomes were adherence to allocated treatment and data completeness. Methods: We conducted a three-arm parallel group cluster randomised controlled feasibility study in a single ambulance service in southern England. Adult patients in out-of-hospital cardiac arrest treated for a shockable rhythm were included. Zoll X series defibrillators (clusters) were randomised to deliver 120-150-200 J, 150-200-200 J, or 200-200-200 J shock strategies. Results: Between March 2022 and February 2023, we randomised 38 eligible patients (120-150-200 J (n = 12), 150-200-200 J (n = 10), 200-200-200 J (n = 16)) to the study. The recruitment rate per cluster was 0.07 per month. The median patient age was 71 years (IQR 59-81 years); 79% were male. Twenty-eight cardiac arrests (74%) occurred in a private residence, 29 (76%) were witnessed and 32 (84%) patients received bystander CPR. Treatment adherence was 93% and completeness of clinical and electrical outcomes was 86%. At 30 days, 3/36 (8.3%) patients survived; we were unable to collect survival outcomes for two patients. Defibrillation data collection became difficult when defibrillators became separated from their allocated vehicles. Conclusion: We have demonstrated the feasibility of a cluster randomised controlled trial of optimal shock energy for defibrillation in a UK ambulance service. We have identified possible solutions to issues relating to trial design.
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Investigation of the reactivity of heteronuclear metal oxide clusters is an important way to uncover the molecular-level mechanisms of the doping effect. Herein, we performed a comparative study on the reactions of CH4 with NiAl3O6+ and Al4O6+ cluster cations at room temperature to understand the role of Ni during the activation and transformation of methane. Mass spectrometric experiments identify that both NiAl3O6+ and Al4O6+ could bring about hydrogen atom abstraction reaction to generate CH3⢠radical; however, only NiAl3O6+ has the potential to stabilize [CH3] moiety and then transform [CH3] to CH2O. Density functional theory calculations demonstrate that the terminal oxygen radicals (Ot-â¢) bound to Al act as the reactive sites for the two clusters to activate the first C-H bond. Although the Ni atom cannot directly participate in methane activation, it can manipulate the electronic environment of the surrounding bridging oxygen atoms (Ob) and enable such Ob to function as an electron reservoir to help Ot-⢠oxidize CH4 to [H-O-CH3]. The facile reduction of Ni3+ to Ni+ also facilitates the subsequent step of activating the second C-H bond by the bridging "lattice oxygen" (Ob2-), finally enabling the oxidation of methane into formaldehyde. The important role of the dopant Ni played in improving the product selectivity of CH2O for methane conversion discovered in this study allows us to have a possible molecule-level understanding of the excellent performance of the catalysts doping with nickel.
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While networking integration has been regarded as a significant driver in technology development, it remains unknown which and how situations influence the online business innovation process. This study used survey data from 466 smart city Internet firms in China to examine how three network embeddedness dimensions-structural embeddedness, relational embeddedness, and cognitive embeddedness-affect product innovation from the perspective of value network embeddedness, drawing on network embeddedness, intergrowth, and knowledge absorptive capacity theory. This paper also looked at the mediating variable of intergrowth and information knowledge transfer. According to our findings, intellectual, social, or architectural inclusion, all contribute to the enhancement of product innovativeness. Such beneficial connections are mediated to some extent by the resources provided. The association among networking involvement as well as technology innovation is moderated by information absorbent ability. Our findings add to the body of research in the areas of innovative technology, networking inclusion, and information absorbent ability.
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A large number of transcriptome studies generate important data and information for the study of pathogenic mechanisms of pathogens, including Vibrio cholerae. V. cholerae transcriptome data include RNA-seq and microarray: microarray data mainly include clinical human and environmental samples, and RNA-seq data mainly focus on laboratory processing conditions, including different stresses and experimental animals in vivo. In this study, we integrated the data sets of both platforms using Rank-in and the Limma R package normalized Between Arrays function, achieving the first cross-platform transcriptome data integration of V. cholerae. By integrating the entire transcriptome data, we obtained the profiles of the most active or silent genes. By transferring the integrated expression profiles into the weighted correlation network analysis (WGCNA) pipeline, we identified the important functional modules of V. cholerae in vitro stress treatment, gene manipulation, and in vitro culture as DNA transposon, chemotaxis and signaling, signal transduction, and secondary metabolic pathways, respectively. The analysis of functional module hub genes revealed the uniqueness of clinical human samples; however, under specific expression patterning, the Δhns, ΔoxyR1 strains, and tobramycin treatment group showed high expression profile similarity with human samples. By constructing a protein-protein interaction (PPI) interaction network, we discovered several unreported novel protein interactions within transposon functional modules. IMPORTANCE We used two techniques to integrate RNA-seq data for laboratory studies with clinical microarray data for the first time. The interactions between V. cholerae genes were obtained from a global perspective, as well as comparing the similarity between clinical human samples and the current experimental conditions, and uncovering the functional modules that play a major role under different conditions. We believe that this data integration can provide us with some insight and basis for elucidating the pathogenesis and clinical control of V. cholerae.
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Vibrio cholerae , Animales , Humanos , Vibrio cholerae/genética , Vibrio cholerae/metabolismo , Transcriptoma , Perfilación de la Expresión Génica , RNA-Seq , Elementos Transponibles de ADNRESUMEN
Understanding the active sites and reaction mechanisms of Ni-based catalysts, such as Ni/Al2O3, toward methane is a prerequisite for improving their rational design. Here, the gas-phase reactivity of NiAlO3+ cations toward CH4 is studied using mass spectrometry combined with density functional theory. Similar to our previous study on NiAl2O4+, we find evidence for the formation of both the methyl radical (CH3â¢) and formaldehyde (CH2O). The first step for methane activation is hydrogen atom abstraction by the terminal oxygen radical Ni(O)2AlO⢠from methane forming a [Ni(O)2AlOH+, â¢CH3] complex and leaving the Ni-oxidation state unchanged. The second C-H bond is subsequently activated by the association of a bridged Ni-O2--Al. The oxidation state of the Ni atom is reduced from +3 to +1 during the formation of formaldehyde. Compared to Al2O3+/CH4 and YAlO3+/CH4 systems, the Ni-atom substitution increases the overall reaction rate by roughly an order of magnitude and yields a CH3â¢/CH2O branching ratio of 0.62/0.38. The present study provides molecular-level insights into the highly efficient gas-phase reaction mechanism contributing to an improved understanding of methane conversion by Ni/Al2O3 catalysts.
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Intracellular movement is an important step for the initial spread of virus in plants during infection. This process requires virus-encoded movement proteins (MPs) and their interaction with host factors. Despite the large number of known host factors involved in the movement of different viruses, little is known about host proteins that interact with one of the MPs encoded by potexviruses, the triple-gene-block protein 3 (TGBp3). The main obstacle lies in the relatively low expression level of potexviral TGBp3 in hosts and the weak or transient nature of interactions. Here, we used TurboID-based proximity labeling to identify the network of proteins directly or indirectly interacting with the TGBp3 of a potexvirus, Bamboo mosaic virus (BaMV). Endoplasmic reticulum (ER) luminal-binding protein 4 and calreticulin 3 of Nicotiana benthamiana (NbBiP4 and NbCRT3, respectively) associated with the functional TGBp3-containing BaMV movement complexes, but not the movement-defective mutant, TGBp3M. Fluorescent microscopy revealed that TGBp3 colocalizes with NbBiP4 or NbCRT3 and the complexes move together along ER networks to cell periphery in N. benthamiana. Loss- and gain-of-function experiments revealed that NbBiP4 or NbCRT3 is required for the efficient spread and accumulation of BaMV in infected leaves. In addition, overexpression of NbBiP4 or NbCRT3 enhanced the targeting of BaMV TGBp1 to plasmodesmata (PD), indicating that NbBiP4 and NbCRT3 interact with TGBp3 to promote the intracellular transport of virion cargo to PD that facilitates virus cell-to-cell movement. Our findings revealed additional roles for NbBiP4 and NbCRT3 in BaMV intracellular movement through ER networks or ER-derived vesicles to PD, which enhances the spread of BaMV in N. benthamiana.
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Potexvirus , Proteínas Virales , Proteínas Virales/metabolismo , Proteínas Portadoras/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Plantas/metabolismo , Nicotiana/metabolismo , Retículo Endoplásmico/metabolismoRESUMEN
PURPOSE: Oxaliplatin-based chemotherapy is a standard treatment for advanced colorectal cancer (CRC) patients. However, chemoresistance-induced resistance is an essential cause for mortality. Therefore, it is necessary to study the mechanism of drug resistance in CRC. METHODS: Here, we established two strains of patient-derived organoids (PDOs) selected from oxaliplatin-resistant and treatment-naïve CRC patients. To dissect the drug-resistant mechanisms, these CRC-PDOs were subjected to single-cell RNA sequencing (scRNA-Seq). RESULTS: We found that the drug sensitivity test outcome from these organoids subjected to oxaliplatin and 5-FU exposure was consistent with the clinic readout. CRC-PDOs well recapitulated the morphology and histology of their parental biopsies based on HE and IHC staining of pathological biomarkers. The scRNA-Seq data filtered drug-resistant cell populations and related signaling pathways (e.g. oxidative phosphorylation and ATP metabolic process). The data also revealed several putative drug resistant-driven genes (STMN1, VEGFA and NDRG1) and transcription factors (E2F1, BRCA1, MYBL2, CDX2 and CDX1). CONCLUSION: We generated an oxaliplatin-resistant CRC organoid model that was employed to provide potential therapeutic targets for treating CRC patients exhibiting oxaliplatin-resistance.
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Antineoplásicos , Neoplasias Colorrectales , Humanos , Oxaliplatino/farmacología , Resistencia a Antineoplásicos/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Organoides/patología , Línea Celular TumoralRESUMEN
China Internet plus agriculture was first put forward in 2015 by the Chinese government's work report, laying the foundation for the development of Internet plus agriculture and promoting the rapid growth of e-commerce marketing of agricultural products. The combination of agricultural product marketing and e-commerce effectively reduces the intermediate links of agricultural product sales. Many e-commerce professional villages have sprung up in some rural areas across the country, and the number of rural e-commerce stores has continued to grow. At this stage, rural e-commerce has become a new way of agricultural trade, and rural e-commerce has formed a unique rural e-store. At present, the e-commerce market share of agricultural products in rural stores is very large, and its advantages are favored by the government, scientific research institutions, and agricultural products processing enterprises. However, with the gradual development of rural e-commerce, it has also encountered many difficulties. Based on this point, this study applies deep learning and data mining to optimize e-commerce marketing. First, with the growth of the online scale of agricultural product transaction data, the creation of traditional shallow model cannot meet the needs of online data processing. Therefore, this study decides to use the deep learning theory for optimization. It has excellent performance in the technical fields of big data processing and image and voice processing and has strong construction ability, which can effectively represent the characteristics of the model. Combined with the characteristics of e-commerce agricultural products processing and consumer practice, this study designs and develops a new customer value evaluation model based on data mining and e-commerce agricultural products value characteristics in the field of e-commerce. By combining deep learning and data mining technology, this study applies it to the field of e-commerce, so as to promote the transformation of marketing optimization.
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Aprendizaje Profundo , Agricultura , Comercio , Minería de Datos , MercadotecníaRESUMEN
BACKGROUND: Magnesium (Mg) alloy have biodegradation and mechanical properties that are similar to those of human bone, making it a promising candidate material for inclusion in implantable medical devices. OBJECTIVE: The osteointegration effect of Mg alloy scaffolds with different corrosion rates were studied and evaluated in large bone defect models. METHOD: Mg-Sr and Mg-Ca alloy scaffolds with a 20-µm Micro-arc oxidation (MAO) coating were used to repair critical bone defects for subsequent assessment of each alloy's degradation and osteointegration by X-ray, Micro-CT, fluorescence and histological examination. RESULTS: At 12 weeks post-implantation, each defect was found to be effectively reconstructed by either of the Mg alloys based on X-ray and Micro-CT images. The corrosion rate (CR) of each Mg alloy - as calculated based on micro-computed tomography information - demonstrated that the MAO coating could provide effective protection for only 4 weeks post-surgery. From weeks 8 to 12, the CR of the Mg-Ca alloy scaffold increased from 1.34 ± 0.23 mm/y to 1.57 ± 0.16 mm/y. In contrast, the CR of the Mg-Sr alloy scaffold decreased from 0.58 ± 0.14 mm/y to 0.54 ± 0.16 mm/y. However, fluorescence and histological examination revealed more mature, closely and regularly arranged newborn osteocytes at the Mg-Ca scaffold-fracture interface e from weeks 8 to 12 after surgery. CONCLUSION: The Mg-Sr scaffold was more corrosion resistant and the Mg-Ca scaffold yielded a better overall repair, which indicates that the CR of magnesium alloys matches the rate of new bone formation and is the key to repair bone defects as a bone substitute.
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Aleaciones , Materiales Biocompatibles Revestidos , Magnesio , Osteocitos , Corrosión , Humanos , Osteocitos/citología , Osteogénesis , Microtomografía por Rayos XRESUMEN
Objectives@#. Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. @*Methods@#. This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. @*Results@#. Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). @*Conclusion@#. We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.
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Many positive-strand (+) RNA viruses produce subgenomic RNAs (sgRNAs) in the infection cycle through the combined activities of viral replicase and host proteins. However, knowledge about host proteins involved in direct sgRNA promoter recognition is limited. Here, in the partially purified replicase complexes from Bamboo mosaic virus (BaMV)-infected tissue, we have identified the Nicotiana benthamiana photosystem II oxygen-evolving complex protein, NbPsbO1, which specifically interacted with the promoter of sgRNA but not that of genomic RNA (gRNA). Silencing of NbPsbO1 expression suppressed BaMV accumulation in N. benthamiana protoplasts without affecting viral gRNA replication. Overexpression of wild-type NbPsbO1 stimulated BaMV sgRNA accumulation. Fluorescent microscopy examination revealed that the fluorescence associated with NbPsbO1 was redistributed from chloroplast granal thylakoids to stroma in BaMV-infected cells. Overexpression of a mislocalized mutant of NbPsbO1, dTPPsbO1-T7, inhibited BaMV RNA accumulation in N. benthamiana, whereas overexpression of an NbPsbO1 derivative, sPsbO1-T7, designed to be targeted to chloroplast stroma, upregulated the sgRNA level. Furthermore, depletion of NbPsbO1 in BaMV RdRp preparation significantly inhibited sgRNA synthesis in vitro but exerted no effect on (+) or (-) gRNA synthesis, which indicates that NbPsbO1 is required for efficient sgRNA synthesis. These results reveal a novel role for NbPsbO1 in the selective enhancement of BaMV sgRNA transcription, most likely via direct interaction with the sgRNA promoter. IMPORTANCE Production of subgenomic RNAs (sgRNAs) for efficient translation of downstream viral proteins is one of the major strategies adapted for viruses that contain a multicistronic RNA genome. Both viral genomic RNA (gRNA) replication and sgRNA transcription rely on the combined activities of viral replicase and host proteins, which recognize promoter regions for the initiation of RNA synthesis. However, compared to the cis-acting elements involved in the regulation of sgRNA synthesis, the host factors involved in sgRNA promoter recognition mostly remain to be elucidated. Here, we found a chloroplast protein, NbPsbO1, which specifically interacts with Bamboo mosaic virus (BaMV) sgRNA promoter. We showed that NbPsbO1 is relocated to the BaMV replication site in BaMV-infected cells and demonstrated that NbPsbO1 is required for efficient BaMV sgRNA transcription but exerts no effect on gRNA replication. This study provides a new insight into the regulating mechanism of viral gRNA and sgRNA synthesis.
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Nicotiana/metabolismo , Complejo de Proteína del Fotosistema II/metabolismo , Potexvirus/metabolismo , Regiones no Traducidas 3' , Cloroplastos/metabolismo , Proteínas de Plantas/genética , Potexvirus/genética , Regiones Promotoras Genéticas/genética , Unión Proteica , ARN/genética , ARN/metabolismo , ARN Viral/genética , ARN Polimerasa Dependiente del ARN , Nicotiana/genética , Nicotiana/virología , Proteínas Virales/metabolismo , Proteinas del Complejo de Replicasa Viral/genética , Proteinas del Complejo de Replicasa Viral/metabolismo , Replicación Viral/fisiologíaRESUMEN
Sand and dust storms in arid and semiarid regions deteriorate regional air quality and threaten public health security. To quantify the negative effects of river dust on regional air quality, this study selected the estuary areas located in central Taiwan as a case study and proposed an integrated framework to measure the fugitive emission of dust from riverbeds with the aid of satellite remote sensing and wind tunnel test, together with the concentrations of particulate matter with a diameter of <10 µm (PM10) around the river system by using The Air Pollution Model. Additionally, the effects of 25 types of meteorological conditions on the health risk due to exposure to dust were evaluated near the estuary areas. The results reveal landscape changes in the downstream areas of Da'an and Dajia rivers, with an increase of 370,820 m2 and 1,554,850 m2 of bare land areas in the dry season compared with the wet season in Da'an and Dajia rivers, respectively. On the basis of the maximum emission of river dust, PM10 concentration increases considerably during both wet and dry seasons near the two rivers. Among 25 different types of weather conditions, frontal surface transit, outer-region circulation from tropical depression system, weak northeast monsoons, and anticyclonic outflow have considerable influence on PM10 diffusion. In particular, weak northeast monsoons cause the highest health risk in the areas between Da'an and Dajia rivers, which is the densely populated Taichung City. Future studies should attempt to elucidate the environmental impact of dust in different weather conditions and understand the spatial risks to human health due to PM10 concentration. Facing the increasing threat of climate and landscape changes, governments are strongly encouraged to begin multimedia assessments in environmental management and propose a long-term and systematic framework in resources planning.
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Purpose@#The purpose of this study was to describe the meaning of incivility experienced by nursing students in relations with nurses during clinical practice. @*Methods@#This is a descriptive qualitative study that included thirty participants using convenience sampling in universities in S, J, Ch, and C provinces. Data saturation was achieved and methodological rigor was established. Qualitative content analysis was used to inductively determine categories. @*Results@#The four categories derived from analysis were ‘left alone at clinical field’, ‘treated as an assistant’, ‘not respected as a person’ and ‘ignored future dreams’. @*Conclusions@#Nursing students continue to carry out repetitive, low-risk tasks, for which they are not properly trained due to the lack of practical guidance in clinical practice. During clinical practice, they are not respected as persons by nurses and are negatively influenced by nurse professionals. A solution to this requires organic cooperation and policy preparation at universities and hospital sites to improve practical training of nursing students.
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OBJECTIVE: Watson for Oncology (WFO), an artificial intelligence from IBM Corporation, can provide a treatment plan by analyzing patient's disease characteristics. The present study was performed to examine the concordance between treatment recommendations proposed by WFO and the multidisciplinary tumor board at our center. The aim was to explore the feasibility of using WFO for breast cancer cases in China and to ascertain the ways to make WFO more suitable for Chinese patients with breast cancer. METHODS: Data from 302 breast cancer patients treated at the Second Affiliated Hospital of Xi'an Jiaotong University between October 2016 and February 2018 was retrieved and retrospectively analyzed by WFO. The recommendations were divided into 'recommended', 'considered' and 'not recommended' groups. Results were considered concordant when oncologists' recommendations were categorized as 'recommended' or 'for consideration' by WFO. RESULTS: The concordance rate of 200 subjects with postoperative adjuvant therapy was 77%. However, the rate was 27.5% in the remaining 102 cases with metastatic disease receiving either first-line or no treatment. Further analysis demonstrated that inconsistencies were mainly due to different choices of chemotherapy regimens. Subgroup study indicates that tumor stage, receptor status and age also had influences at the concordance rate. CONCLUSION: The results of this study suggest that WFO is a promising artificial intelligence system for the treatment of breast cancer. These findings can also serve as a reference framework for the inclusion of artificial intelligence in the ongoing medical reform in China.
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Inteligencia Artificial , Neoplasias de la Mama/terapia , Directrices para la Planificación en Salud , Investigación Interdisciplinaria , Oncología Médica , Adulto , Anciano , Neoplasias de la Mama/patología , China , Terapia Combinada , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios RetrospectivosRESUMEN
Mechanisms of cardiomyopathy caused by obesity/hyperlipidemia are complicated. Obesity is usually associated with chronic low-grade inflammation and may lead to the onset and progression of myocardial fibrosis and remodeling. TLR4/MyD88 signaling pathway, as a key regulator of inflammation, plays an important role in the pathogenesis of obesity-induced cardiomyopathy. We previously demonstrated that LM9, a novel MyD88 inhibitor, attenuated inflammatory responses and fibrosis in obesity-induced cardiomyopathy by inhibiting the formation of TLR4/MyD88 complex. In this study, we investigated the protective effects of LM9 on obesity-induced cardiomyopathy in vitro and in vivo. We showed that LM9 (5, 10 µM) significantly attenuates palmitic acid (PA)-induced inflammation in mouse peritoneal macrophages, evidenced by decreased expression of proinflammatory genes including TNF-α, IL-6, IL-1ß, and ICAM-1. In cardiac-derived H9C2 cells, LM9 treatment suppressed PA-induced inflammation, lipid accumulation, and fibrotic responses. In addition, LM9 treatment also inhibited PA-activated TLR4/MyD88/NF-κB signaling pathway. We further revealed in HEK293 cells that LM9 treatment blocked the TLR4/MyD88 binding and MyD88 homodimer formation. In HFD-fed mice, administration of LM9 (5, 10 mg/kg, ig, every other days for 8 weeks) dose-dependently alleviated inflammation and fibrosis in heart tissues and decreased serum lipid concentration. In conclusion, this study demonstrates that MyD88 inhibitor LM9 exerts protective effects against obesity-induced cardiomyopathy, suggesting LM9 to be a promising therapeutic candidate drug for the obesity-related cardiac complications.
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Antiinflamatorios/uso terapéutico , Cardiomiopatías/tratamiento farmacológico , Fibrosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Factor 88 de Diferenciación Mieloide/antagonistas & inhibidores , Piperazinas/uso terapéutico , Tiazoles/uso terapéutico , Animales , Cardiomiopatías/epidemiología , Cardiomiopatías/patología , Dieta Alta en Grasa , Relación Dosis-Respuesta a Droga , Fibrosis/patología , Células HEK293 , Humanos , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Miocardio/patología , FN-kappa B/metabolismo , Obesidad/complicaciones , Ratas , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismoRESUMEN
Phosphoglycerate kinase (Pgk), catalyzing the reversible conversions between glycerate-1.3-2P and glycerate-3P, plays an important role in carbohydrate metabolism. Here, we show that a Pgk-deficient mutant (NΔpgk) of Xanthomonas axonopodis pv. glycines (Xag) could grow in medium with glucose, galactose, fructose, mannose, or sucrose, as the sole carbon source, suggesting that Xag may employ Entner-Doudoroff (ED) and pentose phosphate pathway (PPP), but not glycolysis, to catabolize glucose. NΔpgk could not utilize pyruvate, suggesting that Pgk might be essential for gluconeogenesis. Mutation in pgk led to a reduction of extracellular polysaccharide (EPS) biosynthesis, cell motility, and intracellular ATP. As a result, the virulence of NΔpgk was significantly compromised in soybean. NΔpgk could be fully complemented by the wild-type pgk, but not by clp (encoding Crp-like protein). qRT-PCR analyses demonstrated that pgk is regulated by the HrpG/HrpX cascade, but not by Clp. These results suggest that Pgk is involved in carbohydrate utilization, EPS biosynthesis, and cell motility of Xag independent of Clp.
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A hydrothermal (HT) coating was applied to the biomedical Mg-Zn-Ca alloy surface by microarc oxidation (MAO) and heat treatment. Then, the corrosion resistance and biocompatibility of the coated alloy was evaluated in vitro and in vivo. The corrosion rate (CR) of HT-coated implants was significantly lower in experiment. In addition, this CR increased over time in vivo but was stable, albeit higher, in vitro. The proliferation, adhesion, and live activity of bone marrow stem cells (BMSCs) were significantly greater on the surface of the HT-coated Mg alloy in vitro. Serum Mg2+ was always within the normal range in rabbits with implants, although Ca2+ was higher than normal for both uncoated and coated scaffolds. There were no significant pathological effects on the main organs of alloy-implanted rabbits compared with healthy animals. Thus, the HT coating significantly improved the corrosion resistance and biocompatibility of the Mg-Zn-Ca alloy.