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Fascin actin-bundling protein 1 (Fascin) is highly expressed in a variety of cancers, including esophageal squamous cell carcinoma (ESCC), working as an important oncogenic protein and promoting the migration and invasion of cancer cells by bundling F-actin to facilitate the formation of filopodia and invadopodia. However, it is not clear how exactly the function of Fascin is regulated by acetylation in cancer cells. Here, in ESCC cells, the histone acetyltransferase KAT8 catalyzed Fascin lysine 41 (K41) acetylation, to inhibit Fascin-mediated F-actin bundling and the formation of filopodia and invadopodia. Furthermore, NAD-dependent protein deacetylase sirtuin (SIRT) 7-mediated deacetylation of Fascin-K41 enhances the formation of filopodia and invadopodia, which promotes the migration and invasion of ESCC cells. Clinically, the analysis of cancer and adjacent tissue samples from patients with ESCC showed that Fascin-K41 acetylation was lower in the cancer tissue of patients with lymph node metastasis than in that of patients without lymph node metastasis, and low levels of Fascin-K41 acetylation were associated with a poorer prognosis in patients with ESCC. Importantly, K41 acetylation significantly blocked NP-G2-044, one of the Fascin inhibitors currently being clinically evaluated, suggesting that NP-G2-044 may be more suitable for patients with low levels of Fascin-K41 acetylation, but not suitable for patients with high levels of Fascin-K41 acetylation. © 2024 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Proteínas de Transporte , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteínas dos Microfilamentos , Sirtuínas , Humanos , Acetilação , Actinas/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Histona Acetiltransferases/metabolismo , Metástase Linfática , Sirtuínas/metabolismoRESUMO
Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high-dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcγRIIb. In mice, the antibody rapidly eliminated total serum IgE to baseline levels and caused lower free IgE levels than omalizumab. At low dosages, the antibody also exhibited favorable IgE elimination effects. In addition, the antibody can degrade the corresponding allergen with the removal of IgE, addressing the allergy from its source. Introduction of the M252Y/S254T/T256E (YTE) mutation into this antibody prolongs its serum half-life without reducing potency. Thus, this engineered antibody holds a promising therapeutic option for allergy patients. Mechanistic insights are also included in this study.
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Alérgenos , Imunoglobulina E , Omalizumab , Receptores de IgG , Imunoglobulina E/imunologia , Imunoglobulina E/metabolismo , Receptores de IgG/metabolismo , Receptores de IgG/imunologia , Animais , Camundongos , Omalizumab/farmacologia , Humanos , Alérgenos/imunologia , Concentração de Íons de Hidrogênio , Hipersensibilidade/imunologia , Hipersensibilidade/tratamento farmacológico , Ligação Proteica , Antialérgicos/farmacologiaRESUMO
BACKGROUND: There has been limited data regarding the incidence of anaphylaxis in Asia. We aim to describe patterns in patient characteristics, triggers and clinical presentation of childhood anaphylaxis in Singapore. METHODS: This was a retrospective review of emergency electronic medical records of children with anaphylaxis. Patients with the allergy-related diagnoses of anaphylaxis, angioedema, allergy and urticaria based on ICD-9 codes were screened. Cases fulfilling the World Allergy Organization criteria for anaphylaxis were included. RESULTS: A total of 1188 cases of anaphylaxis were identified with a median age of 6.3 years. Extrapolating data from the study sites, from 2015 to 2022, the incidence rate of childhood anaphylaxis emergency visits in Singapore doubled from 18.9 to 38.8 per 100,000 person-years, with an incidence rate ratio (IRR) of 2.06 (95% confidence interval [CI] 1.70-2.49). In 2022, the incidence rate of food anaphylaxis was 30.1 per 100,000 person-years, IRR 2.39 (95% CI 1.90-3.01) and drug anaphylaxis was 4.6 per 100,000 person-years, IRR 1.89 (95% CI 1.11-3.25). The incidence rate in children aged 0-4 years quadrupled during the study period. Common triggers were egg (10.4%), peanut (9.3%), tree nut (8.8%), milk (8%), shellfish (7.8%) and non-steroidal anti-inflammatory drug (4.4%). The majority (88.6%) of patients were treated with intramuscular adrenaline. Total number of allergy-related visits did not increase over time between 2015 and 2019. Rates of severe anaphylaxis, namely anaphylactic shock and admission to high-dependency and intensive care, did not increase over time, with a mean incidence of 1.6, IRR 0.85 (95% CI 0.40-1.83) and 0.7, IRR 1.77 (95% CI 0.54-5.76) per 100,000 person-years, respectively. CONCLUSION: While the number of emergency visits due to childhood anaphylaxis has increased, the number of cases of allergy-related visits, anaphylactic shock and anaphylaxis requiring high-dependency and intensive care did not rise.
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Anafilaxia , Humanos , Anafilaxia/epidemiologia , Singapura/epidemiologia , Criança , Masculino , Feminino , Pré-Escolar , Lactente , Estudos Retrospectivos , Incidência , Adolescente , Recém-Nascido , Hipersensibilidade Alimentar/epidemiologiaRESUMO
Due to incommensurability between initial thickness and interdomain distance, thermal annealing inevitably produces relief surface terraces (islands and holes) of various morphologies in thin films of block copolymers. We have demonstrated three kinds of surface terraces in blend films: polygrain terraces with diffuse edges, polygrain terraces with step edges, and pseudo-monograin terraces with island coarsening. The three morphologies were obtained by three different thermal histories, respectively. The thermal histories were imposed on blend films, which were prepared by mixing a homopolystyrene (hPS, 6.1 kg/mol) with a weakly segregated, symmetry polystyrene-block poly(methyl methacrylate) (PS-b-PMMA, 42 kg/mol) followed by spin coating. At a given weight-fraction ratio of PS-b-PMMA/hPS = 75/25, the interior of the blend films forms parallel cylinders. Nevertheless, the surface of the blend films is always dominated by a skin layer of perforations, which epitaxially grow on top of parallel cylinders. By oxygen plasma etching at various time intervals to probe interior nanodomains, the epitaxial relationship between surface perforations and parallel cylinders has been identified by a scanning electron microscope.
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BACKGROUND: Vascular smooth muscle cells (VSMCs) are commonly used as seed cells in tissue-engineered vascular constructions. However, their variable phenotypes and difficult to control functions pose challenges. This study aimed to overcome these obstacles using a three-dimensional culture system. METHODS: Calf VSMCs were administered tumor necrosis factor-alpha (TNF-α) before culturing in two- and three-dimensional well plates and polyglycolic acid (PGA) scaffolds, respectively. The phenotypic markers of VSMCs were detected by immunofluorescence staining and western blotting, and the proliferation and migration abilities of VSMCs were detected by CCK-8, EDU, cell counting, scratch, and Transwell assays. RESULTS: TNF-α rapidly decreased the contractile phenotypic markers and elevated the synthetic phenotypic markers of VSMCs, as well as markedly increasing the proliferation and migration ability of VSMCs under two- and three-dimensional culture conditions. CONCLUSIONS: TNF-α can rapidly induce a phenotypic shift in VSMCs and change their viability on PGA scaffolds.
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Movimento Celular , Proliferação de Células , Sobrevivência Celular , Músculo Liso Vascular , Miócitos de Músculo Liso , Fenótipo , Alicerces Teciduais , Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Alicerces Teciduais/química , Bovinos , Células Cultivadas , Engenharia Tecidual/métodos , Técnicas de Cultura de Células em Três Dimensões/métodosRESUMO
PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.
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Nomogramas , Tromboembolia Venosa , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Procedimentos Neurocirúrgicos , Pescoço , Fatores de RiscoRESUMO
Objective: Network pharmacology is an emerging discipline that applies computational methods to understand drug actions and interactions with multiple molecular targets. Xiao'ai Jiedu is a valued traditional Chinese medicine preparation for which the mechanism of action is not yet established. This study aims to explore the mechanism of Xiao'ai Jiedu in treating lung cancer through network pharmacology. Methods: First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) data platform was used to analyze the target treatment results of different medicinal materials in Mr. Zhou's cancer prescriptions. Then, functional enrichment analysis was performed to conduct a secondary analysis of the dissemination of cancer biological and pharmacological information in the human body. The Cancer Genome Atlas (TCGA) was used to obtain several cancer-aggressive target groups, and their transcription RNA was extracted for collection. The CIBERSORT evaluation method was used to conduct a Spearman correlation analysis on the data processing results. Then the matching degree between the experimental cells and the principle of drug treatment was analyzed to improve the statistical analysis. Results: Pharmacology research results showed that the network can accurately eliminate cancer detoxification targeted target correlation set, and through the data interpretation found that four different gene transcription have significant influence on lung cancer. The findings also confirmed that the degree of immune cell infiltration has a key role in lung cancer The study summarizes the active ingredients and their targets and mechanisms of action of the elimination of Xiao'ai Jiedu formula for the treatment of lung cancer. Conclusion: Network pharmacology can carry on the processing of the data, find the key to conform to the goal of research data, and the corresponding results are obtained, and the development of network pharmacology is not limited to, the study of lung cancer.
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BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.
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Tigres , Animais , Feminino , Masculino , Tigres/genética , Metagenômica , Genoma , Genômica , China , Conservação dos Recursos NaturaisRESUMO
Sarcolemmal ATP-sensitive potassium (KATP) channels play a vital role in cardioprotection. Cardiac KATP channels are enriched in caveolae and physically interact with the caveolae structural protein caveolin-3 (Cav3). Disrupting caveolae impairs the regulation of KATP channels through several signaling pathways. However, the direct functional effect of Cav3 on KATP channels is still poorly understood. Here, we used the cardiac KATP channel subtype, Kir6.2/SUR2A, and showed that Cav3 greatly reduced KATP channel surface density and current amplitude in a caveolae-independent manner. A screen of Cav3 functional domains revealed that a 25 amino acid region in the membrane attachment domain of Cav3 is the minimal effective segment (MAD1). The peptide corresponding to the MAD1 segment decreased KATP channel current in a concentration-dependent manner with an IC50 of â¼5 µM. The MAD1 segment prevented KATP channel recycling, thus decreasing KATP channel surface density and abolishing the cardioprotective effect of ischemic preconditioning. Our research identified the Cav3 MAD1 segment as a novel negative regulator of KATP channel recycling, providing pharmacological potential in the treatment of diseases with KATP channel trafficking defects.NEW & NOTEWORTHY Cardiac KATP channels physically interact with caveolin-3 in caveolae. In this study, we investigated the functional effect of caveolin-3 on KATP channel activity and identified a novel segment (MAD1) in the C-terminus domain of Caveolin-3 that negatively regulates KATP channel surface density and current amplitude by impairing KATP channel recycling. The peptide corresponding to the MAD1 segment abolished the cardioprotective effect of ischemic preconditioning.
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Sirtuins are NAD+-dependent deacetylases with beneficial roles in conditions relevant to human health, including metabolic disease, type II diabetes, obesity, cancer, aging, neurodegenerative diseases, and cardiac ischemia. Since ATP-sensitive K+ (KATP) channels have cardioprotective roles, we investigated whether they are regulated by sirtuins. Nicotinamide mononucleotide (NMN) was used to increase cytosolic NAD+ levels and to activate sirtuins in cell lines, isolated rat and mouse cardiomyocytes or insulin-secreting INS-1 cells. KATP channels were studied with patch clamping, biochemistry techniques, and antibody uptake experiments. NMN led to an increase in intracellular NAD+ levels and an increase in the KATP channel current, without significant changes in the unitary current amplitude or open probability. An increased surface expression was confirmed using surface biotinylation approaches. The rate of KATP channel internalization was diminished by NMN, which may be a partial explanation for the increased surface expression. We show that NMN acts via sirtuins since the increased KATP channel surface expression was prevented by blockers of SIRT1 and SIRT2 (Ex527 and AGK2) and mimicked by SIRT1 activation (SRT1720). The pathophysiological relevance of this finding was studied using a cardioprotection assay with isolated ventricular myocytes, in which NMN protected against simulated ischemia or hypoxia in a KATP channel-dependent manner. Overall, our data draw a link between intracellular NAD+, sirtuin activation, KATP channel surface expression, and cardiac protection against ischemic damage.
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Diabetes Mellitus Tipo 2 , Sirtuínas , Ratos , Camundongos , Humanos , Animais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , NAD/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Miócitos Cardíacos/metabolismo , Trifosfato de Adenosina/metabolismo , Canais KATP/genética , Canais KATP/metabolismoRESUMO
Loss of the histone H3.3-specific chaperone component ATRX or its partner DAXX frequently occurs in human cancers that employ alternative lengthening of telomeres (ALT) for chromosomal end protection, yet the underlying mechanism remains unclear. Here, we report that ATRX/DAXX does not serve as an immediate repressive switch for ALT. Instead, ATRX or DAXX depletion gradually induces telomere DNA replication dysfunction that activates not only homology-directed DNA repair responses but also cell cycle checkpoint control. Mechanistically, we demonstrate that this process is contingent on ATRX/DAXX histone chaperone function, independently of telomere length. Combined ATAC-seq and telomere chromatin immunoprecipitation studies reveal that ATRX loss provokes progressive telomere decondensation that culminates in the inception of persistent telomere replication dysfunction. We further show that endogenous telomerase activity cannot overcome telomere dysfunction induced by ATRX loss, leaving telomere repair-based ALT as the only viable mechanism for telomere maintenance during immortalization. Together, these findings implicate ALT activation as an adaptive response to ATRX/DAXX loss-induced telomere replication dysfunction.
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Proteínas Correpressoras/genética , Chaperonas Moleculares/genética , Homeostase do Telômero , Telômero/metabolismo , Proteína Nuclear Ligada ao X/genética , Linhagem Celular , Reparo do DNA , Deleção de Genes , Células HEK293 , Humanos , Telomerase/metabolismoRESUMO
Fiber-optic sensors are an indispensable element of modern sensing technologies by virtue of their low cost, excellent electromagnetic immunity, and remote sensing capability. Optical Vernier effect is widely used to enhance sensitivity of fiber-optic sensors but requires bulky and complex cascaded interferometers. Here we propose and experimentally demonstrate an ultracompact (â¼2 mm by â¼2 mm) Vernier-effect-improved sensor by only using a single microfiber-knot resonator. With the Vernier effect achieved by controlling the optical beating with the spectral ripple of a super light emitting diode (SLED), we show â¼20x sensitivity enhancement for quantitative temperature monitoring. Our sensor creates a new practical method to realize Vernier effect in fiber-optic sensors and beyond.
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This study has demonstrated how oxygen plasma etching carves surface structures for thin films of polystyrene-block-poly(methyl methacrylate)/homopolystyrene blends. By tuning the weight-fraction ratio, blend films form perforations and cylinders on the SiOx/Si substrate. Since perforations exist only on the free surface and substrate interface, short exposure to oxygen plasma to quickly etch the PMMA component produces distorted hexagonal arrays of nanodots on the free surface. The interior of the blend films forms polygrain micro-structures composed of parallel cylinders with an in-plane random orientation. Oxygen plasma etching imposed on the fractured surfaces results in five morphologies: (i) distorted hexagonal arrays of nanoholes, (ii) layer-by-layer stacks, (iii) zigzag-like arrays, (iv) intertwined rectangular arrays of nanodots and nanoholes, and (v) intertwined parallelogram arrays of nanodots and nanoholes. The morphologies suggest synergic effects of grain orientations, stresses, spatial confinement, local segregation of chains, and etching kinetics on the terraced films with oxygen plasma etching.
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Understanding the mechanisms underlying perfluoroalkyl acids (PFAAs) translocation, distribution, and accumulation in wheat-soil ecosystems is essential for agricultural soil pollution control and crop ecological risk assessment. This study systematically investigated the translocation of 13 PFAAs under different iron and nitrogen fertilization conditions in a wheat-soil ecosystem. Short-chain PFAAs including PFBA, PFPeA, PFHxA, and PFBS mostly accumulated in soil solution (10.43-55.33%) and soluble extracellular polymeric substances (S-EPS) (11.39-14.77%) by the adsorption to amino- (-NH2) and hydroxyl (-OH) groups in dissolved organic matter (DOM). Other PFAAs with longer carbon chain lengths were mostly distributed on the soil particle surface by hydrophobic actions (74.63-94.24%). Iron-nitrogen amendments triggered (p < 0.05) soil iron-nitrogen cycling, rhizospheric reactive oxygen species fluctuations, and the concentration increases of -NH2 and -OH in the DOM structure. Thus, the accumulation capacity of PFAAs in soil solution and root EPS was increased. In sum, PFAAs' translocation from soil particles to wheat root was synergistically reduced by iron and nitrogen fertilization through increased adsorption of soil particles (p < 0.05) and the retention of soil solution and root EPSs. This study highlights the potential of iron-nitrogen amendments in decreasing the crop ecological risks to PFAAs' pollution.
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Fluorocarbonos , Solo , Matéria Orgânica Dissolvida , Triticum , Ecossistema , Matriz Extracelular de Substâncias Poliméricas/química , Nitrogênio , Fluorocarbonos/análiseRESUMO
BACKGROUND: The Chinese monal (Lophophorus lhuysii, Galliformes) is a vulnerable and endemic bird from southwestern China. To better protect this species and increase its population size, genetic markers are urgently needed for investigation and conservation of both wild and captive populations. METHODS AND RESULTS: By using next-generation sequencing, we developed and characterized markers for seven microsatellite loci of the Chinese monal. PCR examination and statistical analysis indicated that these microsatellites exhibited moderate to high levels of polymorphism, with the expected heterozygosity and polymorphic information content ranging from 0.578 to 0.858 and from 0.540 to 0.841, respectively. Cross-species genome comparison further suggests that these microsatellites are a feature of certain galliform species rather than being specific to the Chinese monal. CONCLUSION: A combination of the seven highly polymorphic loci may provide a fundamental genetic toolkit to assess genetic backgrounds and will contribute to design conservation plan, breeding management and other possible studies of the Chinese monal and other evolutionarily related species in the future.
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Galliformes , Animais , Galliformes/genética , Sequenciamento de Nucleotídeos em Larga Escala , Repetições de Microssatélites , Polimorfismo GenéticoRESUMO
BACKGROUND: The existing ex vivo models of endoscopic submucosal dissection (ESD) cannot simulate intraoperative hemorrhage well. We aimed to establish an ESD training method by applying an ex vivo training model with continuous perfusion (ETM-CP). METHODS: Four training sessions were conducted for 25 novices under the guidance of 2 experts. Eventually, 10 novices completed ESD operations on a total of 89 patients after the training. The resection effectiveness, resection speed, complication rate, and novice performance before and after the training were compared. The data regarding the effects of the training and the model were gathered through a questionnaire survey. RESULTS: In terms of the simulation effect of the model, ETM-CP was evaluated as similar to the live pig in all aspects (P > 0.05). The questionnaire analysis revealed that the ESD theoretical knowledge, skill operation, and self-confidence of novices were improved after the training (P < 0.05). The resection time per unit area had a correlation with the number of training periods (rs = - 0.232). For novice performance, the resection time per unit area was shortened (P < 0.05). There was no difference in patient performance between the novice group and the expert group after the training in terms of en bloc resection, R0 resection, complication rate, endoscopic resection bleeding (ERB) score, muscularis propria injury (MPI) score, and resection time per unit area (P > 0.05). CONCLUSION: The ETM-CP is effective for ESD training.
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Ressecção Endoscópica de Mucosa , Suínos , Animais , Ressecção Endoscópica de Mucosa/métodos , Perda Sanguínea Cirúrgica , China , PerfusãoRESUMO
The offset linear canonical transform (OLCT) is an important research topic in many fields, and it has a more universal and elastic performance due to its extra parameters. However, although much work has been done concerning the OLCT, its fast algorithms are rarely addressed. In this paper, an O(N logâ¡N) fast OLCT (FOLCT) algorithm that can significantly reduce the amount of calculation and improve accuracy is proposed. First, the discrete form of the OLCT is provided, and several important properties of its kernel are advanced. Next, the FOLCT based on the fast Fourier transform (FT) is derived for its numerical implementation. Then, the numerical results indicate that the FOLCT is a serviceable tool for signal analysis; additionally, the FOLCT algorithm can be used for the FT, fractional FT, linear canonical transform, and other transforms. Finally, its application to the detection of linear frequency modulated signals and optical image encryption, which is a basic case in signal processing, is discussed. The FOLCT can be effectively applied for the fast numerical calculation of the OLCT with valid and accurate results.
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BACKGROUND: Giant Cell Arteritis (GCA) is a large vessel vasculitis that most commonly presents with headache, scalp tenderness, jaw claudication, and vision changes. Various other, less common, manifestations have been reported in the literature such as scalp and tongue necrosis. Though most patients respond to corticosteroids, some cases of GCA are refractory to the high doses of corticosteroids. CASE PRESENTATION: We present a 73-year-old female with GCA refractory to corticosteroids presenting with tongue necrosis. This patient significantly improved with a dose of tocilizumab, an IL-6 inhibitor. CONCLUSION: To the best of our knowledge, this is the first case report of a patient with refractory GCA presenting with tongue necrosis that had rapid improvement with tocilizumab. Prompt diagnosis and treatment can prevent severe outcomes such as tongue amputation in GCA patients with tongue necrosis, and tocilizumab may be effective for corticosteroid-refractory cases.
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Arterite de Células Gigantes , Feminino , Humanos , Idoso , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico por imagem , Arterite de Células Gigantes/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Língua , Necrose/tratamento farmacológicoRESUMO
Inner coastal wetland ecosystems are generally eutrophic and are often exposed to both salinity stress and Escherichia coli pollution. However, the effects of these stressors on nutrient-cycling and microbial communities are under-researched. Here, we established a vegetated wetland ecosystem in a saline environment to understand the effects of E. coli pollution on nutrient removal and benthic microorganisms. The results show that E. coli significantly inhibited nutrient removal, especially total nitrogen (TN) and ammonium (78.89-84.98 and 3.45-44.65% were removed from the non-E. coli-treated and the E. coli-treated water, respectively). Compared with non-vegetated systems, archaeal community variations at both compositional and phylogenetic levels were weakened in vegetated systems (p < 0.05). Among all the environmental factors, the ratios of PO43--P to total phosphorus and NO3--N to TN contributed the most to archaeal and bacterial community structural variations, respectively. E. coli pollution affected archaeal community succession more than bacteria (p < 0.05). E. coli also weakened the trophic transferring efficiencies between Cyanobacteria and Myxobacteria (p < 0.05). Metabolically, E. coli inhibited bacterial genetic metabolic pathways but made human infection more likely (p < 0.05). Our findings provide new insights into aquatic ecological conservation and environmental management.
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Ecossistema , Áreas Alagadas , Humanos , Salinidade , Filogenia , Bactérias/genética , Archaea/genética , Escherichia coli/genética , Nutrientes , NitrogênioRESUMO
Constructing photocatalyst systems to functionalize the inert C-H bonds has attracted extensive research interest. However, purposeful modulation of interfacial charge transfer in heterostructures remains a challenge, as it usually suffers from sluggish kinetics. Reported herein is an easy strategy to construct the heteroatom-induced interface for developing the titanium-organic frameworks (MOF-902) @ thiophene-based covalent triazine frameworks (CTF-Th) nanosheets S-scheme heterojunctions with controllable oxygen vacancies (OVs). Specifically, Ti atoms were first anchored onto the heteroatom site of CTF-Th nanosheets, and then grown into MOF-902 via an interfacial Ti-S linkage, generating OVs. Using in situ X-ray photoelectron spectroscopy (XPS), extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations, the enhanced interfacial charge separation and transfer induced by moderate OVs in the pre-designed S-scheme nanosheets was validated. The heterostructures exhibited an improved efficiency in photocatalytic C3-acylation of indoles under mild conditions with a yield 8.2â times larger than pristine CTF-Th or MOF-902 and enabled an extended scope of substrates (15â examples). This performance is superior to state-of-the-art photocatalyst and can be retained, without significant loss, after 12â consecutive cycles.