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Inflammatory response and oxidative stress are considered to be important mechanisms of lung injury induced by lunar dust. However, the pulmonary toxicological mechanism remains unclear. In the present study, Wistar rats were exposed to CLDS-i 7 days/week, 4 h/day, for 4 weeks in the mouth and nose. Lung tissue samples were collected for histopathological analysis and ultra-performance liquid chromatography-mass spectrometry analysis. Enzyme activities and expression levels of key metabolic enzymes were detected by biochemical analysis and real-time PCR. The pathological features of lung tissue showed that CLDS-i caused congestion and inflammation in the lungs, and the lung structure was severely damaged. Metabolomics analysis showed that 141 metabolites were significantly changed in the lung tissue of the CLDS-i group compared with the control group. Combined with Kegg pathway analysis, it was found that the changes of amino acid metabolites were involved in these pathways, indicating that the simulated lunar dust exposure had the most obvious effect on amino acid metabolism in the lung tissue of rats. Real-time PCR analysis showed that the mRNA expression of six key enzymes related to amino acid metabolism was changed, and the enzyme activities of these key enzymes were also changed, which were consistent with the results of qPCR. These results suggest that changes in amino acid metabolism may be closely related to the pathogenesis of lung injury induced by lunar dust, and amino acid metabolism may be a potential biomarker of lung diseases related to lunar dust exposure.
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Pneumopatias , Lesão Pulmonar , Ratos , Animais , Poeira/análise , Lesão Pulmonar/metabolismo , Ratos Wistar , Pulmão , Pneumopatias/metabolismo , Metabolômica , Aminoácidos/toxicidade , Aminoácidos/metabolismoRESUMO
Inspired by many living creatures with adjustment of shape and color in an ever-changing environment, color changeable shape memory hydrogels are designed and expected to be potential candidates in the fields spanning from anti-counterfeiting to biomedical devices. However, they normally require complex synthesis, and more importantly, the cooling-induced shape recovery hydrogel is still rare and in its infancy so far. Herein, a unique color changeable shape memory hydrogel by simply incorporating polyvinylalcohol and copper acetate into covalent polyacrylamide network is developed. As core functional element, copper ions serve as reversible crosslinks after heating to achieve excellent cooling-triggered shape memory effect, color shifting and self-healing behavior, showing significant potential in diverse applications like grabbing, information encryption, and biomimetic designs. This work may guide the development of cooling-triggered smart hydrogels for practical applications.
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Hidrogéis , Álcool de Polivinil , Cobre , Íons , AcetatosRESUMO
We present a unified exact tensor network approach to compute the ground state energy, identify the optimal configuration, and count the number of solutions for spin glasses. The method is based on tensor networks with the tropical algebra defined on the semiring of (Râª{-∞},â,â). Contracting the tropical tensor network gives the ground state energy; differentiating through the tensor network contraction gives the ground state configuration; mixing the tropical algebra and the ordinary algebra counts the ground state degeneracy. The approach brings together the concepts from graphical models, tensor networks, differentiable programming, and quantum circuit simulation, and easily utilizes the computational power of graphical processing units (GPUs). For applications, we compute the exact ground state energy of Ising spin glasses on square lattice up to 1024 spins, on cubic lattice up to 216 spins, and on three regular random graphs up to 220 spins, on a single GPU; we obtain exact ground state energy of ±J Ising spin glass on the chimera graph of D-Wave quantum annealer of 512 qubits in less than 100 s and investigate the exact value of the residual entropy of ±J spin glasses on the chimera graph; finally, we investigate ground-state energy and entropy of three-state Potts glasses on square lattices up to size 18×18. Our approach provides baselines and benchmarks for exact algorithms for spin glasses and combinatorial optimization problems, and for evaluating heuristic algorithms and mean-field theories.
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Cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1) are immune checkpoint proteins expressed in T cells. Although CTLA4 expression was found in multiple tumours including non-small cell lung cancer (NSCLC) tissues and cells, its function in tumour cells is unknown. Recently, PD-1 was found to be expressed in melanoma cells and to promote tumorigenesis. We found that CTLA4 was expressed in a subset of NSCLC cell lines and in a subgroup of cancer cells within the lung cancer tissues. We further found that in NSCLC cells, anti-CTLA4 antibody can induce PD-L1 expression, which is mediated by CTLA4 and the EGFR pathway involving phosphorylation of MEK and ERK. In CTLA4 knockout cells, EGFR knockout cells or in the presence of an EGFR tyrosine kinase inhibitor, anti-CTLA4 antibody was not able to induce PD-L1 expression in NSCLC cells. Moreover, anti-CTLA4 antibody promoted NSCLC cell proliferation in vitro and tumour growth in vivo in the absence of adaptive immunity. These results suggest that tumour cell-intrinsic CTLA4 can regulate PD-L1 expression and cell proliferation, and that anti-CTLA4 antibody, by binding to the tumour cell-intrinsic CTLA4, may result in the activation of the EGFR pathway in cancer cells.
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Antígeno B7-H1/metabolismo , Antígeno CTLA-4/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Células A549 , Animais , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Camundongos , Camundongos Nus , Fosforilação/fisiologia , Transdução de Sinais/fisiologia , Linfócitos T/metabolismoRESUMO
In this work, two amphiphilic gluconamide-tailored anthracene gelators 1 and 2 have been synthesized, and found to form stable hydrogels with fibril structures. The stimuli-responsive behaviors of hydrogel 1 and 2 were investigated thoroughly by temperature-dependent 1H NMR, UV-Vis, rheometry, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The results showed that hydrogel 1 exhibited multiple responsive behaviours upon exposure to stimuli including temperature, anions, light, electron-deficient chemicals and external stress; conversely, hydrogel 2 showed a distinct responsive phenomenon attributed to a subtle structural difference in the linker. This work demonstrates that gluconamide-tailored anthracene gelators could be a potential soft material and highlights the importance of a precisely designed structure.
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Lunar dust is one of the biggest risk factors in the future manned exploration mission. Much is not known about the pulmonary toxicity of lunar dust. The aim of this study was to evaluate the lung inflammation and oxidative stress induced by subacute exposure to lunar dust stimulant (LDS) in rats. Wistar rats were intratracheally administered LDS, twice a week for 3 weeks. Inflammatory cell counting and cytokine assays using bronchoalveolar lavage fluid (BALF) were performed. Lung tissues were processed for histopathological examination and immunohistochemical staining. Biomarkers of oxidative stress and genes and proteins related to inflammation and fibrosis in lung tissue were also determined. The neutrophil count in the BALF of LDS-exposed groups was higher than that in controls (P < .05). LDS caused a significant increase in some of biochemical indicators and proinflammatory factors levels in BALF compared with control group. The normal balance between oxidation and antioxidation was broken by LDS. Pathological characteristics of lung tissue and immunohistochemical results for α-smooth muscle actin (α-SMA) indicated that inflammatory response was an extremely important passage to pulmonary fibrosis. Real-time PCR analysis showed elevated levels of nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) mRNA in the lungs (P < .05). Western blotting results were consistent with immunohistochemistry and qPCR results. These results indicate that inhalation of lunar dust may cause inflammatory pulmonary fibrosis. NOX4 may be a key potential therapeutic target for inflammatory injury and fibrosis in the lung.
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Poluentes Atmosféricos/toxicidade , Poeira Cósmica/efeitos adversos , Poeira/análise , Pulmão/efeitos dos fármacos , Pneumonia/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Poluentes Atmosféricos/química , Animais , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Citocinas/imunologia , Exposição por Inalação , Pulmão/metabolismo , Pulmão/patologia , Masculino , Tamanho da Partícula , Pneumonia/metabolismo , Pneumonia/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Epidemiological studies have shown that urban particulate matter (PM) increases the risk of respiratory infection. However, the underlying mechanisms are poorly understood. PM has been postulated to suppress the activation of airway epithelial innate defence in response to infection. METHODS: The effects of PM on antibacterial defence were studied using an in vitro infection model. The levels of antimicrobial peptides were measured using RT-PCR and ELISA. In addition to performing colony-forming unit counts and flow cytometry, confocal microscopy was performed to directly observe bacterial invasion upon PM exposure. RESULTS: We found that PM PM increased bacterial invasion by impairing the induction of ß-defensin-2 (hBD-2), but not the other antimicrobial peptides (APMs) secreted by airway epithelium. PM further increases bacteria-induced ROS production, which is accompanied by an accelerated cell senescence and a decrease in bacteria-induced hBD-2 production, and the antioxidant NAC treatment attenuates these effects. The PM exposure further upregulated the expression of IL-8 but downregulated the expression of IL-13 upon infection. CONCLUSIONS: PM promotes bacterial invasion of airway epithelial cells by attenuating the induction of hBD-2 via an oxidative burst. These findings associate PM with an increased susceptibility to infection. These findings provide insight into the underlying mechanisms regarding the pathogenesis of particulate matter.
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Peptídeos Catiônicos Antimicrobianos/antagonistas & inibidores , Peptídeos Catiônicos Antimicrobianos/metabolismo , Material Particulado/efeitos adversos , Pseudomonas aeruginosa , Mucosa Respiratória/metabolismo , Mucosa Respiratória/microbiologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Mucosa Respiratória/efeitos dos fármacos , beta-Defensinas/antagonistas & inibidores , beta-Defensinas/metabolismoRESUMO
BACKGROUND: C-type lectin receptors (CLRs), Toll-like receptors (TLRs), and Nod-like receptors (NLRs) have the ability to recognize Aspergillus fumigatus (A. fumigates) and induce innate immune response. Dectin-1 is a well-described CLR, while interleukin-1 receptor-associated kinase 1 (Irak1) and receptor-interacting protein 2 (Rip2) are pivotal adaptor proteins of TLRs and NLRs signaling pathways, respectively. OBJECTIVES: Our primary aim is to elucidate whether Dectin-1 regulates the expression of Irak1 and Rip2, and confirm that CLRs, TLRs, and NLRs pathways act synergistically in response to A. fumigatus infection. METHODS: Pulmonary infection mouse models were established. Myeloid cells were differentiated in cell culture and examined by inverted microscopy, flow cytometry, and scanning electron microscopy. The relative mRNA levels were determined by qRT-PCR. The protein expression levels were determined by immunohistochemistry and Western blot. RESULTS: The expression of Dectin-1, Irak1, Rip2, and phosphorylation level of nuclear factor (NF)-κB p65 were induced by conidia in immunocompetent mice, while their expression and phosphorylation level were inhibited in immunocompromised mice after the administration of conidia. Conidia increased the expression of Dectin-1, Irak1, and Rip2 in myeloid cells, while Dectin-1 silencing significantly reduced their expression. CONCLUSION: Our findings demonstrate that Dectin-1, Irak1, and Rip2 are involved in response to A. fumigatus infection. Dectin-1 modulates the expression of Irak1 and Rip2. Additionally, these three signaling pathways are interconnected, and CLRs pathway plays a dominant role against A. fumigatus invasion.
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Aspergillus fumigatus/crescimento & desenvolvimento , Interações Hospedeiro-Patógeno , Quinases Associadas a Receptores de Interleucina-1/análise , Lectinas Tipo C/análise , Aspergilose Pulmonar/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/análise , Animais , Células Cultivadas , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo Real , Proteína Serina-Treonina Quinase 2 de Interação com ReceptorRESUMO
OBJECTIVE: To detect the presence of ROS1 fusion gene in pulmonary adenocarcinoma and its clinicopathologic parameters. METHODS: Fluorescence RT-PCR was used to detect the presence of ROS1 fusion gene in 369 surgical resection samples of pulmonary adenocarcinoma with known EGFR mutation status. The presence of ROS1 fusion gene in correlation with clinicopathologic features was analyzed. Sixteen positive and 20 negative samples by RT-PCR were further confirmed by direct sequencing. RESULTS: ROS1 fusion gene was detected in 16 of 369 lung adenocarcinoma samples (4.3%). The presence of ROS1 fusion gene was not correlated to gender, age, smoking history, tumor site, size, histological subtype, tumor differentiation, T staging, lymph node metastasis, TNM staging and EGFR mutation (P > 0.05). The frequency of ROS1 fusion gene was similar in female and male patients, 4.4% (8/183) vs 4.3% (8/186), P > 0.05. The presence of ROS1 fusion gene in patients of ≤ 60 years of age was higher than that in patients of > 60 years, 5.1% (10/195) vs 3.4% (6/174), P > 0.05. The rate of ROS1 fusion gene of non-smokers was a slight higher than that of smokers, 4.4% (14/318) vs 3.9% (2/51), P > 0.05. Both positive and negative cases were confirmed by direct sequencing in all cases. CONCLUSIONS: ROS1 fusion gene occurs more frequently in younger and non-smoking patients of pulmonary adenocarcinoma, and may coexist with EGFR mutations. ROS1 fusion gene seems to define a distinct subset of pulmonary adenocarcinoma.
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Adenocarcinoma/genética , Neoplasias Pulmonares/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Fatores Etários , Feminino , Genes erbB-1 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , FumarRESUMO
The generation of images from electroencephalography (EEG) signals has become a popular research topic in recent research because it can bridge the gap between brain signals and visual stimuli and has wide application prospects in neuroscience and computer vision. However, due to the high complexity of EEG signals, the reconstruction of visual stimuli through EEG signals continues to pose a challenge. In this work, we propose an EEG-ConDiffusion framework that involves three stages: feature extraction, fine-tuning of the pretrained model, and image generation. In the EEG-ConDiffusion framework, classification features of EEG signals are first obtained through the feature extraction block. Then, the classification features are taken as conditions to fine-tune the stable diffusion model in the image generation block to generate images with corresponding semantics. This framework combines EEG classification and image generation means to enhance the quality of generated images. Our proposed framework was tested on an EEG-based visual classification dataset. The performance of our framework is measured by classification accuracy, 50-way top-k accuracy, and inception score. The results indicate that the proposed EEG-Condiffusion framework can extract effective classification features and generate high-quality images from EEG signals to realize EEG-to-image conversion.
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Duodenal neuroendocrine tumors (NETs), comprising 2-3% of all gastrointestinal NETs and 1-3% of all duodenal tumors, are remarkably uncommon. In this report, we described a patient diagnosed with two submucosal tumors in the duodenal bulb. We used two distinct endoscopic resection methods, including endoscopic submucosal dissection (ESD) and submucosal tunneling endoscopic resection (STER), to achieve en bloc resection of the lesions without complications. Pathological evaluation, involving hematoxylin-eosin staining and immunohistochemistry, confirmed the diagnosis of NET. Given the limited operative field and space in the duodenal bulb, STER proved to be a viable endoscopic resection technique.
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Fibrosis characterized by intestinal strictures is a common complication of Crohn's disease (CD), without specific antifibrotic drugs, which usually relies on surgical intervention. The transcription factor XBP1, a key component of endoplasmic reticulum (ER) stress, is required for degranulation of mast cells and linked to PAR2 activation and fibrosis. Many studies have confirmed that naringin (NAR) can inhibit ER stress and reduce organ fibrosis. We hypothesized that ER stress activated the PAR2-induced epithelial-mesenchymal transition process by stimulating mast cell degranulation to release tryptase and led to intestinal fibrosis in CD patients; NAR might play an antifibrotic role by inhibiting ER stress-induced PAR2 activation. We report that the expression levels of XBP1, mast cell tryptase, and PAR2 are upregulated in fibrotic strictures of CD patients. Molecular docking simulates the interaction of NAR and spliced XBP1. ER stress stimulates degranulation of mast cells to secrete tryptase, activates PAR2-induced epithelial-mesenchymal transition process, and promotes intestinal fibrosis in vitro and vivo experiments, which is inhibited by NAR. Moreover, F2rl1 (the coding gene of PAR2) deletion in intestinal epithelial cells decreases the antifibrotic effect of NAR. Hence, the ER stress-mast cell tryptase-PAR2 axis can promote intestinal fibrosis, and NAR administration can alleviate intestinal fibrosis by inhibiting ER stress-induced PAR2 activation.
Fibrosis characterized by intestinal strictures is a common complication of Crohn's disease. The endoplasmic reticulum stressmast cell tryptasePAR2 axis promotes intestinal fibrosis, and naringin administration alleviates intestinal fibrosis by inhibiting endoplasmic reticulum stressinduced PAR2 activation.
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The aging process significantly impacts the gastrointestinal tract and various bodily systems, exacerbating age-related diseases. Research suggests a correlation between an imbalance in intestinal flora and gut aging, yet the precise mechanism remains incompletely elucidated. Epigenetic modifications, particularly m6A methylation, play a pivotal role in driving aging and are closely associated with gut aging. Maintaining a healthy balance of intestinal microbes is contingent upon m6A methylation, which is believed to be crucial in the vicious cycle of gut aging and intestinal flora. This article highlights the importance of m6A methylation in the nexus between gut aging and flora. It proposes the potential for targeted m6A methylation to break the vicious cycle of gut aging and flora imbalance, offering novel perspectives on attenuating or reversing gut aging.
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Envelhecimento , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Envelhecimento/genética , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Animais , Metilação , Epigênese Genética , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologiaRESUMO
Lunar dust particles are an environmental threat to lunar astronauts, and inhalation of lunar dust can cause lung damage. The current study explored the mechanism of lunar dust simulant (CLDS-i) inducing inflammatory pulmonary injury. Wistar rats were exposed to CLDS-i for 4 h/d and 7d/week for 4 weeks. Pathological results showed that a large number of inflammatory cells gathered and infiltrated in the lung tissues of the simulated lunar dust group, and the alveolar structures were destroyed. Transcriptome analysis confirmed that CLDS-i was mainly involved in the regulation of activation and differentiation of immune inflammatory cells, activated signaling pathways related to inflammatory diseases, and promoted the occurrence and development of inflammatory injury in the lung. Combined with metabolomics analysis, the results of joint analysis of omics were found that the genes Kmo, Kynu, Nos3, Arg1 and Adh7 were involved in the regulation of amino acid metabolism in rat lung tissues, and these genes might be the key targets for the treatment of amino acid metabolic diseases. In addition, the imbalance of amino acid metabolism might be related to the activation of nuclear factor kappaB (NF-κB) signaling pathway. The results of quantitative real-time polymerase chain reaction and Western blot further confirmed that CLDS-i may promote the occurrence and development of lung inflammation and lead to abnormal amino acid metabolism by activating the B cell activation factor (BAFF)/ B cell activation factor receptor (BAFFR)-mediated NF-κB signaling pathway.
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Colorectal cancer (CRC) is one of the common malignancies with a global trend of increasing incidence and mortality. There is an urgent need to identify new predictive markers and therapeutic targets for the treatment of CRC. Protease-activated receptors (PARs) are a class of G-protein-coupled receptors, with currently identified subtypes including PAR1, PAR2, PAR3 and PAR4. Increasingly, studies suggest that PARs play an important role in the growth and metastasis of CRC. By targeting multiple signaling pathways may contribute to the pathogenesis of CRC. In this review, we first describe recent studies on the role of PARs in CRC inflammation-cancer transformation, focusing on the important role of PARs in signaling pathways associated with inflammation-cancer transformation, and summarize the progress of research on PARs-targeted drugs.
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Neoplasias , Receptores Ativados por Proteinase , Humanos , Receptores Ativados por Proteinase/metabolismo , Receptores de Trombina/metabolismo , Transdução de Sinais , InflamaçãoRESUMO
The distributed resilient tracking problem for multiagent systems (MASs) is investigated in the presence of actuator/sensor faults over directed topology. Both actuator fault and sensor fault are taken into account. Meanwhile, using the local information, the fault compensators are introduced. Then, based on the fuzzy-logic systems (FLSs) and modification technique of adaptive law, a novel distributed adaptive resilient control protocol is developed, which can compensate the effect of faults on the actuator and sensor. It turns out that all signals of MASs are bounded, while the tracking errors enter an adjustable bounded region around the origin. Toward the end, two simulations are provided to validate the effectiveness of the theoretical results.
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Background: To assess the efficacy and safety of different endoscopic resection methods for colorectal laterally spreading tumors (LSTs) in East Asian countries. Methods: A literature search was performed in PubMed, Embase, Cochrane Library and Web of Science databases. Colorectal LSTs of the included studies were resected with endoscopic mucosal resection (EMR) and/or endoscopic submucosal dissection (ESD). The main outcomes involved rates of en bloc resection, R0 resection, adverse events and recurrence. Results: A total of 20 studies were finally included in the present study. The total number of lesions were 3,903 (EMR: 1,230, ESD: 2,673). EMR-en bloc resection was obtained in 395/591 (66.8%), with ESD-en bloc resection reported in 2,020/2,265 (89.2%) [odds ratio (OR) 0.244, P<0.0001, 95% confidence interval (CI): 0.197-0.304]. EMR-R0 resection was achieved in 409/547 (74.8%), which was lower than that of ESD (1,895/2,241, 84.6%) (OR 0.541, P<0.0001, 95% CI: 0.432-0.677). Bleedings occurred more frequently in EMR than in ESD group (10.4% vs. 3.1%, OR 3.559, P<0.0001, 95% CI: 2.618-4.836). Rates of perforations in EMR and ESD were 0.4% and 4.1% (OR 0.099, P<0.0001, 95% CI: 0.036-0.27). Recurrence of EMR was higher than ESD group (6.3% vs. 1.0%, OR 6.732, P<0.0001, 95% CI: 3.751-12.082). Discussion: Endoscopic resections of colorectal LSTs are safe and effective. ESD leads to higher rates of en bloc and R0 resection, as well as lower rates of bleeding and recurrence, but it has a high risk of perforation, compared with EMR.
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Purpose: To explore pharmacological mechanisms of Pulsatilla decoction (PD) against Crohn's disease (CD) via network pharmacology analysis followed by experimental validation. Methods: Public databases were searched to identify bioactive compounds and related targets of PD as well as related genes in patients with CD. Analyses using the drug-compound-target-disease network, the protein-protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the core targets and pathways of PD against CD. Colon tissue resected from patients with CD and tissue samples from a mouse model of CD fibrosis treated with PD were assessed to verify the major targets of PD in CD predicted by network pharmacologic analysis. Results: A search of the targets of bioactive compounds in PD and targets in CD identified 134 intersection targets. The target HSP90AA1, which was common to the drug-compound-target-disease and PPI networks, was used to simulate molecular docking with the corresponding bioactive compound. GO and KEGG enrichment analyses showed that multiple targets in the antifibrotic pathway were enriched and could be experimentally validated in CD patients and in a mouse model of CD fibrosis. Assays of colon tissues from CD patients showed that intestinal fibrosis was greater in stenoses than in nonstenoses, with upregulation of p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, p-PKC, and PKC targets. Treatment of CD fibrosis mice with PD reduced the degree of fibrosis, with downregulation of the p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, and PKC targets. Conclusion: Network pharmacology analysis was able to predict bioactive compounds in PD and their potential targets in CD. Several of these targets were validated experimentally, providing insight into the pharmacological mechanisms underlying the biological activities of PD in patients with CD.
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BACKGROUND: N6-methyladenosine (m6A) methylation has been reported to participate in inflammatory bowel disease (including Crohn disease [CD]). However, the prognostic and therapeutic implication of m6A methylation modification in CD is still unclear. METHODS: Genomic information of CD patients was integrated to assess disease-related m6A regulators, and difference and correlation analyses of m6A regulators were explored by using the R packages. Next, CD patients were classified by the expression of differential and intersecting genes in m6A regulators, and difference and correlation analyses were conducted among immune infiltration and therapeutic responses. Finally, colon tissue resected from patients with CD were assessed to verify expression of Wilms tumor 1-associated protein (WTAP) and METTL14 from these m6A regulators. RESULTS: We identified 23 m6A regulators in CD patients. Difference analysis of these regulators showed that expression of METTL14, WTAP, RBM15 and YTHDF2/3 was upregulated in the treatment group compared with the control group, with expression of METTL3, YTHDF1, leucine-rich pentatricopeptide repeat motif-containing protein, HNRNPA2B1, IGF2BP1 and fat mass and obesity-associated protein downregulated. Moreover, RBM15, WTAP, leucine-rich pentatricopeptide repeat motif-containing protein, YTHDF1 and YTHDF3 were considered the characteristic genes of CD in m6A regulators. In addition, we identified 4 intersection genes of 3 m6A cluster patterns. Based on the expression of these intersection genes, difference analysis among m6A regulators indicated that the expression of 8 m6A regulators had statistical differences among the 3 geneCluster patterns. Assays of colon tissues from CD patients showed that expression of WTAP and METTL14 were higher in areas of stenosis than non-stenosis. CONCLUSION: m6A methylation modification might affect disease risk, immune infiltration and therapeutic responses in CD. Evaluating the expression of m6A regulators might provide insight into the prediction of disease prognosis and therapeutic responses.
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Doença de Crohn , Humanos , Prognóstico , Metilação , Doença de Crohn/genética , Leucina , Genes Reguladores , Metiltransferases/genéticaRESUMO
Hand detection is a crucial technology for space human-robot interaction (SHRI), and the awareness of hand identities is particularly critical. However, most advanced works have three limitations: 1) the low detection accuracy of small-size objects; 2) insufficient temporal feature modeling between frames in videos; and 3) the inability of real-time detection. In the article, a temporal detector (called TA-RSSD) is proposed based on the SSD and spatiotemporal long short-term memory (ST-LSTM) for real-time detection in SHRI applications. Next, based on the online tubelet analysis, a real-time identity-awareness module is designed for multiple hand object identification. Several notable properties are described as follows: 1) the hybrid structure of the Resnet-101 and the SSD improves the detection accuracy of small objects; 2) three-level feature pyramidal structure retains rich semantic information without losing detailed information; 3) a group of the redesigned temporal attentional LSTM (TA-LSTM) is utilized for three-level feature map modeling, which effectively achieves background suppression and scale suppression; 4) low-level attention maps are used to eliminate in-class similarity between hand objects, which improves the accuracy of identity awareness; and 5) a novel association training scheme enhances the temporal coherence between frames. The proposed model is evaluated on the SHRI-VID dataset (collected according to the task requirements), the AU-AIR dataset, and the ImageNet-VID benchmark. Extensive ablation studies and comparisons on detection and identity-awareness capacities show the superiority of the proposed model. Finally, a set of actual testing is conducted on a space robot, and the results show that the proposed model achieves a real-time speed and high accuracy.