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Growing evidence suggests prevalence of transcriptional condensates on chromatin, yet their mechanisms of formation and functional significance remain largely unclear. In human cancer, a series of mutations in the histone acetylation reader ENL create gain-of-function mutants with increased transcriptional activation ability. Here, we show that these mutations, clustered in ENL's structured acetyl-reading YEATS domain, trigger aberrant condensates at native genomic targets through multivalent homotypic and heterotypic interactions. Mechanistically, mutation-induced structural changes in the YEATS domain, ENL's two disordered regions of opposing charges, and the incorporation of extrinsic elongation factors are all required for ENL condensate formation. Extensive mutagenesis establishes condensate formation as a driver of oncogenic gene activation. Furthermore, expression of ENL mutants beyond the endogenous level leads to non-functional condensates. Our findings provide new mechanistic and functional insights into cancer-associated condensates and support condensate dysregulation as an oncogenic mechanism.
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Neoplasias , Cuerpos Nucleares , Humanos , Dominios Proteicos , Cromatina/genética , Mutación , Neoplasias/genéticaRESUMEN
Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions from patients with cutaneous Candida granulomas. Second, we showed that dermal Candida albicans (C. albicans) infection in mice robustly triggered the dermal reactive adipogenesis response and induced cathelicidin expression, and inhibition of adipogenesis with pharmacological inhibitors of peroxisome proliferator-activated receptor γ (PPARγ) impaired skin resistance to C. albicans. In vitro, C. albicans products induced cathelicidin expression in pAds, and differentiating pAds markedly suppressed the growth of C. albicans by producing cathelicidin. Finally, we showed that C. albicans induced an antimicrobial response in pAds through the FGFR-MEK-ERK pathway. Together, our data reveal a previously unknown role of dFBs in the defense against skin infection caused by C. albicans.
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Candida albicans , Candidiasis , Humanos , Ratones , Animales , Candida albicans/metabolismo , Catelicidinas , Sistema de Señalización de MAP Quinasas , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos AntimicrobianosRESUMEN
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Up to 40% of patients with DLBCL display refractory disease or relapse after standard chemotherapy treatment (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]), leading to significant morbidity and mortality. The molecular mechanisms of chemoresistance in DLBCL remain incompletely understood. Using a cullin-really interesting new gene (RING) ligase-based CRISPR-Cas9 library, we identify that inactivation of the E3 ubiquitin ligase KLHL6 promotes DLBCL chemoresistance. Furthermore, proteomic approaches helped identify KLHL6 as a novel master regulator of plasma membrane-associated NOTCH2 via proteasome-dependent degradation. In CHOP-resistant DLBCL tumors, mutations of NOTCH2 result in a protein that escapes the mechanism of ubiquitin-dependent proteolysis, leading to protein stabilization and activation of the oncogenic RAS signaling pathway. Targeting CHOP-resistant DLBCL tumors with the phase 3 clinical trial molecules nirogacestat, a selective γ-secretase inhibitor, and ipatasertib, a pan-AKT inhibitor, synergistically promotes DLBCL destruction. These findings establish the rationale for therapeutic strategies aimed at targeting the oncogenic pathway activated in KLHL6- or NOTCH2-mutated DLBCL.
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Resistencia a Antineoplásicos , Linfoma de Células B Grandes Difuso , Humanos , Resistencia a Antineoplásicos/genética , Ubiquitina , Proteómica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Rituximab/uso terapéutico , Vincristina , Ciclofosfamida , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Prednisona , Mutación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor Notch2/genéticaRESUMEN
Cobalt-nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.
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Nanotubos de Carbono , Peróxidos , Benzodiazepinas , Carbamazepina , Cobalto , Nitrógeno , AguaRESUMEN
BACKGROUND & AIMS: We aimed to identify long noncoding RNAs (lncRNAs) that are up-regulated in gastric cancer tissues from patients and study their function in gastric tumor metastasis. METHODS: We collected gastric tumor and nontumor tissues from patients in China and analyzed levels of lncRNAs by microarray analysis, proteins by immunohistochemistry, and RNAs by quantitative reverse-transcription polymerase chain reaction; we compared these with survival times of patients and tumor progression. RNA levels were knocked down or knocked out in BGC-823, SGC-7901, and MKN45 cell lines using small interfering or short hairpin RNAs or clustered regularly interspaced short palindromic repeats (ie, CRISPR)/CRISPR associated protein 9 (ie, Cas9) vectors. Genes were overexpressed from transfected plasmids in HGC-27 cells. Cells were analyzed by Northern blot and immunoblot, polysome profiling assay, and cell invasion assay. Cells were injected into the tail veins or spleens of nude mice or SCID mice; lung and liver tissues were collected, and metastases were counted. lncRNAs were cloned by using rapid amplification of complementary DNA ends. Their interactions with other genes were determined by RNA pulldown and mapping assays. RESULTS: In microarray analyses, we identified 151 lncRNAs expressed at significantly higher levels in gastric tumor vs nontumor tissues. Levels of an lncRNA that we called gastric cancer metastasis associated long noncoding RNA (GMAN) were increased in gastric tumor tissues, compared with nontumor tissues; its up-regulation was associated with tumor metastasis and shorter survival times of patients. The GMAN gene overlaps with the ephrin A1 gene (EFNA1) and was highly expressed in BGC-823 and MKN45 cells. Knockdown of GMAN in these cells did not affect proliferation, colony formation, or adhesion but did reduce their invasive activity in Transwell assays. Ectopic expression of GMAN increased the invasive activity of HGC-27 cells. BGC-823 and MKN45 cells with knockdown of GMAN formed fewer metastases after injection into tail veins of nude mice. Knockdown or knockout of GMAN also reduced levels of ephrin A1 protein in cells. We found that GMAN promoted translation of ephrin A1 messenger RNA into protein by binding to the antisense GMAN RNA (GMAN-AS)-this antisense sequence is also complementary to that of ephrin A1 mRNA. Levels of ephrin A1 protein were also increased in gastric tumors from patients with metastases than in those without metastases. Knockout of ephrin A1 in BGC-823 cells reduced their invasive activity in Transwell assays and ability to form metastases after injection into SCID mice. Ectopic expression of ephrin A1 in BGC-823 cells with knockdown or knockout of GMAN restored their invasive activities and ability form metastases in nude or SCID mice. A CRISPR/Cas9-based strategy to disrupt the GMAN gene significantly reduced the numbers of metastases formed from SGC-7901 cells in mice. CONCLUSIONS: We identified an lncRNA, which we call GMAN, that is increased in gastric tumors from patients and associated with survival and formation of metastases. It regulates translation of ephrin A1 mRNA by binding competitively to GMAN-AS. Knockdown or knockout of GMAN or ephrin A1 in gastric cancer cell lines reduces their invasive activity and ability to form metastases after injection into mice. These genes might be targeted to prevent or reduce gastric cancer metastasis.
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Biomarcadores de Tumor/genética , Efrina-A1/genética , Regulación Neoplásica de la Expresión Génica/genética , ARN Largo no Codificante/genética , Neoplasias Gástricas/genética , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Noqueados , Ratones Desnudos , Ratones SCID , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/patología , Interferencia de ARN , ARN Mensajero/genética , Distribución Aleatoria , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias Gástricas/patología , Análisis de Matrices Tisulares , Técnicas de Cultivo de Tejidos , Activación Transcripcional , Regulación hacia ArribaRESUMEN
In order to improve the practicality of the rapid biochemical oxygen demand (BOD) method, a highly sensitive rapid detection method for BOD that is based on establishing the correlation between current and dissolved oxygen (DO) was developed. In this experiment, Bacillus subtilis was used as the test microorganism, and the embedding method was used to achieve quantitative fixation of microorganisms, which could increase the content of microorganisms and prolong the service life of the biological element. The conductivity (COND) probe is used as a sensing element, so that the testing value can be read every second. In the program, the moving average method is used to process the collected data so that the value can be read every minute. National standard samples were detected to test the accuracy and stability of the method. The results showed that relative error and analytical standard deviations were less than 5%. Different polluted water was tested to evaluate its application range. The results showed that relative error was less than 5%. The results of the method are consistent with the results of the wastewater sample obtained by the BOD5 standard method. The proposed rapid BOD current sensing biosensor method should be promising in practical application of wastewater monitoring.
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Análisis de la Demanda Biológica de Oxígeno/métodos , Técnicas Biosensibles/métodos , Oxígeno/química , Aguas Residuales/químicaRESUMEN
As emerging alternatives of legacy perfluoroalkyl substances, perfluorophosphinates (PFPiAs) and perfluorophosphonates (PFPAs) are widely applied in industrial and agricultural fields and are supposed to be large partitioned to soil and highly persistent. It is of particular interest to understand their transfer from roots to shoots and transformation in plants, such as wheat. The results of hydroponic experiments indicated that C6/C6 PFPiA, C8/C8 PFPiA, perfluorooctanophosphonic acid (PFOPA), and perfluorohexaphosphonic acid (PFHxPA) were quickly adsorbed on the epidermis of wheat root (Triticum aestivum L.), which was driven by their hydrophobicity. A small fraction of the accumulated PFPiAs and PFPAs in the wheat root was subjected to absorption via an active process dependent on H+-ATPase. PFHxPA, which has the smallest molecular weight and medium hydrophilicity (logâ¯Kow < 4), displayed the strongest absorption efficiency via the water and anion channels and had the highest translocation potential from roots to shoots in wheat. C6/C6 and C8/C8 PFPiAs experienced phase I metabolism in wheat, although at a low rate, to form more persistent PFHxPA and PFOPA, respectively, as well as 1H-perfluorohexane (1H-PFHx) and 1H-perfluorooctane (1H-PFO), which were regulated by cytochrome P450 in wheat root. As a result, exposure to PFPiAs in roots ultimately caused the accumulation of more persistent PFPAs in the above-ground parts of plants, raising concerns on their potential risks on human health.
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Contaminantes del Suelo , Triticum , Transporte Biológico , Humanos , Hidroponía , Raíces de Plantas , SueloRESUMEN
Shape-transformable liquid metal (LM) micromachines have attracted the attention of the scientific community over the past 5 years, but the inconvenience of transfer routes and the use of corrosive fuels have limited their potential applications. In this work, a shape-transformable LM micromotor that is fabricated by a simple, versatile ice-assisted transfer printing method is demonstrated, in which an ice layer is employed as a "sacrificial" substrate that can enable the direct transfer of LM micromotors to arbitrary target substrates conveniently. The resulting LM microswimmers display efficient propulsion of over 60 µm s-1 (≈3 bodylength s-1 ) under elliptically polarized magnetic fields, comparable to that of the common magnetic micro/nanomotors with rigid bodies. Moreover, these LM micromotors can undergo dramatic morphological transformation in an aqueous environment under the irradiation of an alternating magnetic field. The ability to transform the shape and efficiently propel LM microswimmers holds great promise for chemical sensing, controlled cargo transport, materials science, and even artificial intelligence in ways that are not possible with rigid-bodies microrobots.
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A bioinspired magnetically powered microswimmer is designed and experimentally demonstrated by mimicking the morphology of annelid worms. The structural parameters of the microswimmer, such as the surface wrinkling, can be controlled by applying prestrain on substrate for the precise fabrication and consistent performance of the microswimmers. The resulting annelid-worm-like microswimmers display efficient propulsion under an oscillating magnetic field, reaching a peak speed of ≈100 µm s-1 . The speed and directionality of the microswimmer can be readily controlled by changing the parameters of the field inputs. Additionally, it is demonstrated that the microswimmers are able to transport microparticles toward a predefined destination, although the translation velocity is inevitably reduced due to the additional hydrodynamic resistance of the microparticles. These annelid-worm-like microswimmers have excellent mobility, good maneuverability, and strong transport capacity, and they hold considerable promise for diverse biomedical, chemical sensing, and environmental applications.
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Materiales Biomiméticos/química , Animales , Biotecnología , MicrotecnologíaRESUMEN
Sacred lotus (Nelumbo nucifera) is an ornamental plant that is also used for food and medicine. This basal eudicot species is especially important from an evolutionary perspective, as it occupies a critical phylogenetic position in flowering plants. Here we report the draft genome of a wild strain of sacred lotus. The assembled genome is 792 Mb, which is approximately 85-90% of genome size estimates. We annotated 392 Mb of repeat sequences and 36,385 protein-coding genes within the genome. Using these sequence data, we constructed a phylogenetic tree and confirmed the basal location of sacred lotus within eudicots. Importantly, we found evidence for a relatively recent whole-genome duplication event; any indication of the ancient paleo-hexaploid event was, however, absent. Genomic analysis revealed evidence of positive selection within 28 embryo-defective genes and one annexin gene that may be related to the long-term viability of sacred lotus seed. We also identified a significant expansion of starch synthase genes, which probably elevated starch levels within the rhizome of sacred lotus. Sequencing this strain of sacred lotus thus provided important insights into the evolution of flowering plant and revealed genetic mechanisms that influence seed dormancy and starch synthesis.
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Evolución Biológica , Genoma de Planta , Nelumbo/genética , Secuencia de Aminoácidos , Datos de Secuencia Molecular , Nelumbo/crecimiento & desarrollo , Latencia en las Plantas/genética , Semillas/crecimiento & desarrollo , Selección Genética , Análisis de Secuencia de ADN , Almidón/biosíntesisRESUMEN
Precise gene expression, crucial for normal development and health, depends on the co-ordinated assembly and function of various factors within the crowded nucleus. Recent evidence suggests that this process is in part regulated by mesoscale compartmentalization and concentration of transcriptional components within condensates, offering a new perspective on gene regulation. Dysregulation of transcriptional condensates is increasingly associated with diseases, indicating a potential role in pathogenesis. In this mini-review, we provide a concise overview of the current understanding of the formation and function of transcriptional condensates, with a specific focus on recent advances in their dysregulation and implications in diseases, notably cancer. We also address limitations in the field and highlight open questions for future research.
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Regulación de la Expresión Génica , Neoplasias , Transcripción Genética , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Regulación de la Expresión Génica/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Cardiovascular and cerebrovascular diseases (CCVDs) significantly contribute to global mortality and morbidity due to their complex pathogenesis involving multiple biological processes. Ferroptosis is an important physiological process in CCVDs, manifested by an abnormal increase in intracellular iron concentration. MiRNAs, a key class of noncoding RNA molecules, are crucial in regulating CCVDs through pathways like glutathione-glutathione peroxidase 4, glutamate/cystine transport, iron metabolism, lipid metabolism, and other oxidative stress pathways. This article summarizes the progress of miRNAs' regulation on CCVDs, aiming to provide insights for the diagnosis and treatment of CCVDs.
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Enfermedades Cardiovasculares , Trastornos Cerebrovasculares , Ferroptosis , MicroARNs , Ferroptosis/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Trastornos Cerebrovasculares/genética , Trastornos Cerebrovasculares/metabolismo , Trastornos Cerebrovasculares/patología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Hierro/metabolismo , Estrés Oxidativo/genética , AnimalesRESUMEN
Refractory heart failure (RHF), or end-stage heart failure, has a poor prognosis and high case fatality rate, making it one of the therapeutic difficulties in the cardiovascular field. Despite the continuous abundance of methods and means for treating RHF in modern medicine, it still cannot meet the clinical needs of patients with RHF. How to further reduce the mortality rate and readmission rate of patients with RHF and improve their quality of life is still a difficult point in current research. In China, traditional Chinese medicine (TCM) has been widely used and has accumulated rich experience in the treatment of RHF due to its unique efficacy and safety advantages. Based on this, we comprehensively summarized and analyzed the clinical evidence and mechanism of action of TCM in the treatment of RHF and proposed urgent scientific issues and future research strategies for the treatment of RHF with TCM, to provide reference for the treatment of RHF.
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BACKGROUND AND PURPOSE: Colorectal cancer (CRC) ranks second in mortality worldwide and requires effective and affordable remedies. Cyclovirobuxine D (CVB-D) is the main effective component of Huangyangning tablet, an approved traditional patent medicine, which is mainly used for cardiovascular treatment. As a multibioactive natural compound, CVB-D possesses underlying anticancer activities. EXPERIMENTAL APPROACH: Cell viability and clone-forming ability were determined in human CRC lines. Western blot, immunofluorescence assay, transmission electron microscopy and senescence-associated ß-galactosidase (SA-ß-Gal) staining were utilized to investigate cell autophagy and senescence. The molecular mechanisms were explored by virtual prediction and experimental validation. Patient-derived xenograft (PDX), dextran sulfate sodium salt (DSS), and azomethane (AOM)/DSS mouse models were employed for in vivo studies. KEY RESULTS: CVB-D inhibited the growth and development of advanced CRC cells / mice by inducing autophagic and senescent activities through the chaperonin containing TCP1 subunit 3 (CCT3)/yes-associated protein (YAP) axis. CVB-D acted as a promising inhibitor of CCT3 by interacting with its ATP site. In PDX tumours, CVB-D showed potential therapeutic effects by targeting CCT3. Treatment with CVB-D alleviated the mouse model of colitis induced by DSS and attenuated AOM/DSS-induced formation of adenomatous polyps by its action on CCT3. CONCLUSIONS AND IMPLICATIONS: Our study has provided a scientific basis for the suggestion that CVB-D may be recognized as a prospective drug candidate for the therapy of CRC in patients.
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Neoplasias Colorrectales , Reposicionamiento de Medicamentos , Animales , Humanos , Masculino , Ratones , Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ratones Desnudos , Proteínas Señalizadoras YAP/metabolismo , Chaperonina con TCP-1/metabolismoRESUMEN
Pomacea canaliculata (Lamarck 1822), a freshwater gastropod indigenous to lower Del Plata Basin of Argentina, has become the most destructive and invasive rice pests in south China since its introduction in the 1980s. In Guangdong, the main production areas for double rice, most of P. canaliculata overwinter in paddy field ditches after late-rice harvesting in mid-November and diapause to temporarily to avoid the damaging effects of extreme low temperatures. This pest aroused from diapause and migrated to the paddy field after early-rice reviving in next late March. Overwintering and cold tolerance of natural P. canaliculata have a non-negligible impact on population dynamics and distribution in the following year. We tested the supercooling capability, levels of cryoprotectant synthesis, activity of antioxidant defense system (antioxidant enzymes and reduced glutathione), and degree of oxidative damage (concentration of malondialdehyde as an index of lipid peroxidation) monthly, using natural P. canaliculata samples with a size-gender structure (i.e., juveniles, female, and male adults) from experimental ponds during the period of mid-November to the following April. P. canaliculata survived the winter with a monthly death rate of 7%-16.5% in coldest January. The supercooling point (SCP) of overwintering P. canaliculata decreased initially before increasing subsequently with monthly changes in water temperature. P. canaliculata accumulated a high glycogen content before December, which depleted towards the end of January, while lipid content reached peak in January and depleted since February. Activity of antioxidant defense system of P. canaliculata exhibited significant monthly differences and showed relatively higher size heterogeneity than monthly variations. The results contribute to the knowledge of adaptability in overwintering P. canaliculata and help to understand the mechanism of the invasive success of this species.
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Controlling the collective behavior of micro/nanomotors with ultrasound may enable new functionality in robotics, medicine, and other engineering disciplines. Currently, various collective behaviors of nanomotors, such as assembly, reconfiguration, and disassembly, have been explored by using acoustic fields with a fixed frequency, while regulating their collective behaviors by varying the ultrasound frequency still remains challenging. In this work, we designed an ultrasound manipulation methodology that allows nanomotors to exhibit different collective behaviors by regulating the applied ultrasound frequency. The experimental results and FEM simulations demonstrate that the secondary ultrasonic waves produced from the edge of the sample cell lead to the formation of complex acoustic pressure fields and microfluidic patterns, which causes these collective behaviors. This work has important implications for the design of artificial actuated nanomotors and optimize their performances.
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Objective.Accurate assessment of pleural line is crucial for the application of lung ultrasound (LUS) in monitoring lung diseases, thereby aim of this study is to develop a quantitative and qualitative analysis method for pleural line.Approach.The novel cascaded deep learning model based on convolution and multilayer perceptron was proposed to locate and segment the pleural line in LUS images, whose results were applied for quantitative analysis of textural and morphological features, respectively. By using gray-level co-occurrence matrix and self-designed statistical methods, eight textural and three morphological features were generated to characterize the pleural lines. Furthermore, the machine learning-based classifiers were employed to qualitatively evaluate the lesion degree of pleural line in LUS images.Main results.We prospectively evaluated 3770 LUS images acquired from 31 pneumonia patients. Experimental results demonstrated that the proposed pleural line extraction and evaluation methods all have good performance, with dice and accuracy of 0.87 and 94.47%, respectively, and the comparison with previous methods found statistical significance (P< 0.001 for all). Meanwhile, the generalization verification proved the feasibility of the proposed method in multiple data scenarios.Significance.The proposed method has great application potential for assessment of pleural line in LUS images and aiding lung disease diagnosis and treatment.
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Pulmón , Neumonía , Humanos , Pulmón/diagnóstico por imagen , Tórax , Ultrasonografía/métodos , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pneumonia, the available treatment option is limited because the etiology and pathological process are not well understood. Although gut-lung axis reported with an emerging area of host-associated microbiota exist in many chronic lung diseases, the connection between gut-lung microbiota composition with in-site inflammation in IPF development is not yet established. PURPOSE: We aimed to address the microbiota and immunity connection, and make it clear how a listed drug, Xuanfei Baidu Decoction (XFBD) affect the lung-gut crosstalk for IPF amelioration, which was previously reported for restoring disrupted lung in IPF and protecting intestinal injury. METHODS: Firstly, Micro-CT (µCT) and histopathology were used to check for pathological changes in the lungs and intestines of bleomycin (BLM)-induced IPF mice. Then, Reverse Transcription and Quantitative Real-time PCR (RT-qPCR) and Western blot (WB) assays were employed to detect the integrity of the barrier of lungs and intestines in IPF mice. Subsequently, flow cytometry and 16S rRNA sequencing were used to evaluate the immune and microbial microenvironment of the lungs and intestines. We analyzed the lung-gut microbiota crosstalk for further mechanism exploration. RESULTS: Firstly, we revealed that XFBD protected the integrity of the lung and intestinal barriers in the IPF mice, as evidenced by the up-regulation of ZO-1, Claudin-1, Occludin, and VE Cadherin protein expression. Then, we analyzed the changing microbiota and T cell in the gut-lung axis in IPF, and with XFBD, six highly relevant microenvironments were demonstrated that crossing damaged lung-gut barriers and XFBD could reverse these chaotic bacterial and immunity micro-environment, among them Akkermansia was an essential bacteria affecting the expression of systemic IFN-γ downstream STAT1/STAT3 axis was also studied. XFBD prominently up-regulated the production of IFN-γ and p-STAT1 and down-regulated p-STAT3, consequently exerting effects on the lung barrier and gut barrier. Taken together, XFBD ameliorated BLM-induced IPF mice by regulating IFNγ/STAT1/STAT3 axis. CONCLUSION: Altogether, our results revealed that XFBD improved the BLM-elicited IPF mice by regulating gut-lung crosstalk via IFN-γ/STAT1/STAT3 axis and provided a new insight of gut-lung crosstalk in IPF, especially the dynamic changes of microorganisms in the damaged lungs needed to pay more attention during IPF therapy.
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High-performance photodetectors with the detection capability of linearly polarized light have broad applications in both military and civilian fields. Quasi-one-dimensional ZrS3 as an emerging anisotropic two-dimensional material has come under the spotlight owing to its intriguing properties. However, the performance of the ZrS3 photodetector is seriously restricted by its low responsivity. Herein, a novel high-performance photodetector based on the van der Waals ZrS3/MoS2 heterostructure is proposed. Attributed to the charge trapping-assisted photogating effect, interlayer carrier transitions, and fast spatial separation of the photogenerated electron-hole pairs, the device displays superior photoresponse characteristics ranging from the ultraviolet to the visible spectrum in terms of high responsivity up to 212 A/W, an extraordinary external quantum efficiency of 8.5 × 104%, and a prompt rise/decay time of 0.19/0.38 ms. In addition, owing to the profound birefringence and dichroism effects in ZrS3 together with strong light-matter interactions in the heterostructure, profound linear-polarization sensitivity is demonstrated with a dichroic ratio of about 2.8. Overall, this photodetector not only is integrated with the excellent properties of ZrS3 and monolayer MoS2 but also further enhances the advantages through interlayer couplings, which demonstrate the strong potential of the ZrS3-based devices for high-performance, ultrafast, and polarization-sensitive photodetection.
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Thoracic echocardiography (TTE) can provide sufficient cardiac structure information, evaluate hemodynamics and cardiac function, and is an effective method for atrial septal defect (ASD) examination. This paper aims to study a deep learning method based on cardiac ultrasound video to assist in ASD diagnosis. We chose four standard views in pediatric cardiac ultrasound to identify atrial septal defects; the four standard views were as follows: subcostal sagittal view of the atrium septum (subSAS), apical four-chamber view (A4C), the low parasternal four-chamber view (LPS4C), and parasternal short-axis view of large artery (PSAX). We enlist data from 300 children patients as part of a double-blind experiment for five-fold cross-validation to verify the performance of our model. In addition, data from 30 children patients (15 positives and 15 negatives) are collected for clinician testing and compared to our model test results (these 30 samples do not participate in model training). In our model, we present a block random selection, maximal agreement decision, and frame sampling strategy for training and testing respectively, resNet18 and r3D networks are used to extract the frame features and aggregate them to build a rich video-level representation. We validate our model using our private dataset by five cross-validation. For ASD detection, we achieve 89.33 ± 3.13 AUC, 84.95 ± 3.88 accuracy, 85.70 ± 4.91 sensitivity, 81.51 ± 8.15 specificity, and 81.99 ± 5.30 F1 score. The proposed model is a multiple instances learning-based deep learning model for video atrial septal defect detection which effectively improves ASD detection accuracy when compared to the performances of previous networks and clinical doctors.