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Background: Gut microbiota is closely related to the occurrence and development of sepsis. However, the causal effects between the gut microbiota and sepsis, and whether circulating inflammatory proteins act as mediators, remain unclear. Methods: Gut microbiota, circulating inflammatory proteins, and four sepsis-related outcomes were identified from large-scale genome wide association studies (GWAS) summary data. Inverse Variance Weighted (IVW) was the primary statistical method. Additionally, we investigated whether circulating inflammatory proteins play a mediating role in the pathway from gut microbiota to the four sepsis-related outcomes. Results: There were 14 positive and 15 negative causal effects between genetic liability in the gut microbiota and four sepsis-related outcomes. Additionally, eight positive and four negative causal effects were observed between circulating inflammatory proteins and the four sepsis-related outcomes. Circulating inflammatory proteins do not act as mediators. Conclusions: Gut microbiota and circulating inflammatory proteins were causally associated with the four sepsis-related outcomes. However, circulating inflammatory proteins did not appear to mediate the pathway from gut microbiota to the four sepsis-related outcomes.
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Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Sepse , Sepse/microbiologia , Sepse/sangue , Humanos , Microbioma Gastrointestinal/genética , Inflamação/sangue , Polimorfismo de Nucleotídeo ÚnicoRESUMO
A 79-year-old man underwent operative drainage and 2-week cephalosporin treatment due to a maxillofacial space infection (bilateral submaxillaris, submentum, and left face). However, he experienced anorexia, nausea, vomiting, and emaciation in the following 2 months. It was initially considered that a malignancy might be present, thus a series of examinations were performed. Laboratory investigations showed increases in inflammatory markers and a significant eosinophilia, which seemed to be a hematological system disease. Combined with the gastrointestinal endoscopes and histology examination, the patient was diagnosed with eosinophilic gastroenteritis (EGE). After cessation of antibiotic treatment and administration of corticosteroid, our patient experienced a rapid progress in his clinical condition. Despite the low incidence, EGE should be considered in patients with unknown cause of gastrointestinal disorder, elevated eosinophilia, and so on.
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Background: Following COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated. Methods: Summary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn's disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA). Results: The evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00-1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01-1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03-1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD. Conclusion: This MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.
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Oligomerization is one of the important mechanisms for G protein-coupled receptors (GPCRs) to modulate their activity in signal transduction. However, details of how and why the oligomerization of GPCRs regulates their functions under physiological conditions remain largely unknown. Here, using single-molecule photobleaching technology, we show that chemokine ligand 5 (CCL5) and chemokine ligand 8 (CCL8) are similar to the previously reported chemokine ligand 11 (CCL11) and chemokine ligand 24 (CCL24), which can regulate the oligomerization of chemokine receptor 3 (CCR3). Our results further demonstrate that downstream proteins, ß-arrestin 2 and Gi protein complex, on the CCR3 signal transduction pathway, can inversely regulate the oligomeric states of CCR3 induced by its binding ligands. This unexpected discovery suggests complex relationships between the oligomeric behaviors of CCR3 and the components of ligands-CCR3-downstream proteins, reflecting the potentially functional impact of the oligomerization on the multiple activation pathways of GPCR, such as biased activation.
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Multimerização Proteica , Receptores CCR3 , Transdução de Sinais , Receptores CCR3/metabolismo , Receptores CCR3/química , Humanos , Ligantes , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/química , beta-Arrestina 2/metabolismo , beta-Arrestina 2/químicaRESUMO
Purpose: To evaluate the performance of calcium quantification on photon-counting detector CT (PCD-CT) with high-pitch at low radiation doses compared to third-generation dual-source energy-integrating detector CT (EID-CT). Materials and methods: The phantom with three calcium inserts (50, 100, and 300 mg of calcium per milliliter), with and without the elliptical outer layer, was evaluated using high-pitch (3.2) and standard pitch (0.8) on PCD-CT, and standard pitch on EID-CT. Scans were performed with different tube voltages (PCD-CT: 120 and 140 kilo-voltage peak [kVp]; EID-CT: 70/Sn150 and 100/Sn150 kVp) and four radiation doses (1, 3, 5, and, 10 milli-Gray [mGy]). Utilizing the true calcium concentrations (CCtrue) of the phantom as the gold standard references, regression equations for each kVp setting were formulated to convert CT attenuations (CaCT) into measured calcium concentrations (CCm). The correlation analysis between CaCT and CCtrue was performed. The percentage absolute bias (PAB) was calculated from the differences between CCm and CCtrue and used to analyze the effects of scanning parameters on calcium quantification accuracy. Results: A strong correlation was found between CaCT and CCtrue on PCD-CT (r > 0.99) and EID-CT (r > 0.98). For high- and standard-pitch scans on PCD-CT, the accuracy of calcium quantification is comparable (p = 0.615): the median (interquartile range [IQR]) of PAB was 5.59% (2.79%-8.31%) and 4.87 % (2.62%-8.01%), respectively. The PAB median (IQR) was 7.43% (3.77%-11.75%) for EID-CT. The calcium quantification accuracy of PCD-CT is superior to EID-CT at the large phantom (5.46% [2.68%-9.55%] versus 9.01% [6.22%-12.74%]), and at the radiation dose of 1 mGy (4.43% [2.08%-8.59%] versus 13.89% [8.93%-23.09%]) and 3 mGy (4.61% [2.75%-6.51%] versus 9.97% [5.17%-14.41%]), all p < 0.001. Conclusions: Calcium quantification using low-dose PCD-CT with high-pitch scanning is feasible and accurate, and superior to EID-CT.
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Thanks to the line-scanning camera, the measurement method based on line-scanning stereo vision has high optical accuracy, data transmission efficiency, and a wide field of vision. It is more suitable for continuous operation and high-speed transmission of industrial product detection sites. However, the one-dimensional imaging characteristics of the line-scanning camera cause motion distortion during image data acquisition, which directly affects the accuracy of detection. Effectively reducing the influence of motion distortion is the primary problem to ensure detection accuracy. To obtain the two-dimensional color image and three-dimensional contour data of the heavy rail surface at the same time, a binocular color line-scanning stereo vision system is designed to collect the heavy rail surface data combined with the bright field illumination of the symmetrical linear light source. Aiming at the image motion distortion caused by system installation error and collaborative acquisition frame rate mismatch, this paper uses the checkerboard target and two-step cubature Kalman filter algorithm to solve the nonlinear parameters in the motion distortion model, estimate the real motion, and correct the image information. The experiments show that the accuracy of the data contained in the image is improved by 57.3% after correction.
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Background: Long COVID is a major challenge facing the public. Gut microbiota is closely related to Long COVID. However, the causal effects between gut microbiota and Long COVID remains unclear. Methods: Using summary statistics from Genome-Wide Association Studies (GWAS), Mendelian randomization (MR) analyses were performed to investigate the relationship between gut microbiota and Long COVID. The primary statistical method employed was Inverse Variance Weighted (IVW). Sensitivity analyses were then conducted to evaluate the reliability of the findings and account for potential confounding variables. Finally, a reverse MR analysis was conducted to examine potential associations between Long COVID and genetically predicted gut microbiota compositions. Results: There were 2 positive and 1 negative causal effect between gut microbiota and Long COVID. Meta-analysis results show that genus Parasutterella (OR = 1.145, 95%CI = 1.035 â¼ 1.266, P = 0.008) and genus Oscillospira (OR = 1.425, 95%CI = 1.235 â¼ 1.645, P < 0.001) significantly increased the risk of Long COVID. And genus Eisenbergiella (OR = 0.861, 95%CI = 0.785 â¼ 0.943, P = 0.001) significantly decreased the risk of Long COVID. Neither the pleiotropy nor the heterogeneity was observed. Reverse causal effect does not hold. Conclusion: Our research has provided genetic evidence that establishes multiple causal relationships between the gut microbiota and Long COVID, supporting the role of the gut microbiota in Long COVID. It is possible that different taxa play a role in the development of Long COVID. The causal relationships identified in this study require further investigation.
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Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure.
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Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Retículo Endoplasmático , Proteínas de Membrana , ATPases do Tipo-P , Dobramento de Proteína , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/química , Retículo Endoplasmático/metabolismo , Células HEK293 , Interações Hidrofóbicas e Hidrofílicas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/química , Domínios Proteicos , Processamento de Proteína Pós-Traducional , ATPases Translocadoras de Prótons/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/química , ATPases do Tipo-P/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismoRESUMO
In order to explore the effect of sub-freezing storage on water holding capacity and tenderness of beef, four treatments were compared in this study: sub-freezing (-7 °C) fast sub-freezing (-38 °C until the core temperature achieved to -7 °C), superchilling (-1 °C) and fast frozen (-38 °C until the core temperature achieved to -18 °C) with the latter two treatments serving as the controls. The differences in muscle fiber structure, water distribution, protein oxidation and cytoskeletal protein degradation were studied. The results demonstrated that compared with other treatments, the fast sub-freezing treatment resulted in less structural damage to the muscle fibers and had better water holding capacity. Both sub-freezing and fast sub-freezing treatments inhibited protein oxidation compared with superchilling, but the former treatment's level of protein oxidation was higher than that in fast sub-freezing treatment during long-term storage (42 weeks). In addition, the structural proteins in the sub-freezing and fast sub-freezing treatments underwent faster degradation during long-term storage and therefore the meat was more tender compared with the fast frozen treatment. The results indicate that the fast sub-freezing treatment can be potentially applied in beef storage.
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Armazenamento de Alimentos , Congelamento , Oxirredução , Carne Vermelha , Água , Bovinos , Animais , Carne Vermelha/análise , Armazenamento de Alimentos/métodos , Músculo Esquelético/química , Fibras Musculares Esqueléticas/química , Proteínas MuscularesRESUMO
PURPOSE: We aimed to evaluate the reproducibility of computed tomography (CT) radiomic features (RFs) about Epicardial Adipose Tissue (EAT). The features derived from coronary photon-counting computed tomography (PCCT) angiography datasets using the PureCalcium (VNCPC) and conventional virtual non-contrast (VNCConv) algorithm were compared with true non-contrast (TNC) series. METHODS: RFs of EAT from 52 patients who underwent PCCT were quantified using VNCPC, VNCConv, and TNC series. The agreement of EAT volume (EATV) and EAT density (EATD) was evaluated using Pearson's correlation coefficient and Bland-Altman analysis. A total of 1530 RFs were included. They are divided into 17 feature categories, each containing 90 RFs. The intraclass correlation coefficients (ICCs) and concordance correlation coefficients (CCCs) were calculated to assess the reproducibility of RFs. The cutoff value considered indicative of reproducible features was > 0.75. RESULTS: the VNCPC and VNCConv tended to underestimate EATVs and overestimate EATDs. Both EATV and EATD of VNCPC series showed higher correlation and agreement with TNC than VNCConv series. All types of RFs from VNCPC series showed greater reproducibility than VNCConv series. Across all image filters, the Square filter exhibited the highest level of reproducibility (ICC = 67/90, 74.4%; CCC = 67/90, 74.4%). GLDM_GrayLevelNonUniformity feature had the highest reproducibility in the original image (ICC = 0.957, CCC = 0.958), exhibiting a high degree of reproducibility across all image filters. CONCLUSION: The accuracy evaluation of EATV and EATD and the reproducibility of RFs from VNCPC series make it an excellent substitute for TNC series exceeding VNCConv series.
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Tecido Adiposo , Algoritmos , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Pericárdio , Valor Preditivo dos Testes , Interpretação de Imagem Radiográfica Assistida por Computador , Humanos , Reprodutibilidade dos Testes , Tecido Adiposo/diagnóstico por imagem , Pericárdio/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Adiposidade , Tecido Adiposo Epicárdico , RadiômicaRESUMO
OBJECTIVES: This study aimed to compare the image quality and diagnostic performance of standard-resolution (SR) and ultra-high-resolution (UHR) coronary CT angiography (CCTA) based on photon-counting detector CT (PCD-CT) of coronary stents and explore the best reconstruction kernel for stent imaging. METHODS: From July 2023 to September 2023, patients were enrolled to undergo CCTA using a dual-source PCD-CT system after coronary angioplasty with stent placement. SR images with a slice thickness/increment of 0.6/0.4 mm were reconstructed using a vascular kernel (Bv48), while UHR images with a slice thickness/increment of 0.2/0.2 mm were reconstructed using vascular kernels of six sharpness levels (Bv48, Bv56, Bv60, Bv64, Bv72, and Bv76). The in-stent lumen diameters were evaluated. Subjective image quality was also evaluated by a 5-point Likert scale. Invasive coronary angiography was conducted in 12 patients (25 stents). RESULTS: Sixty-nine patients (68.0 [61.0, 73.0] years, 46 males) with 131 stents were included. All UHR images had significantly larger in-stent lumen diameter than SR images (p < 0.001). Specifically, UHR-Bv72 and UHR-Bv76 for in-stent lumen diameter (2.17 [1.93, 2.63] mm versus 2.20 [1.93, 2.59] mm) ranked the two best kernels. The subjective analysis demonstrated that UHR-Bv72 images had the most pronounced effect on reducing blooming artifacts, showcasing in-stent lumen and stent demonstration, and diagnostic confidence (p < 0.001). Furthermore, SR and UHR-Bv72 images showed a diagnostic accuracy of 78.3% (95% confidence interval [CI]: 56.3%-92.5%) and 88.0% (95%CI: 68.8%-97.5%), respectively. CONCLUSION: UHR CCTA by PCD-CT leads to significantly improved visualization and diagnostic performance of coronary stents, and Bv72 is the optimal reconstruction kernel showing the stent struts and in-stent lumen. CLINICAL RELEVANCE STATEMENT: The significantly improved visualization of coronary stents using ultra-high resolution CCTA could increase the diagnostic accuracy for in-stent restenosis and avoid unnecessary invasive quantitative coronary angiography, thus changing the clinical management for patients after percutaneous coronary intervention. KEY POINTS: Coronary stent imaging is challenging with energy-integrating detector CT due to "blooming artifacts." UHR images using a PCD-CT enhanced coronary stent visualization. UHR coronary stent imaging demonstrated improved diagnostic accuracy in clinical settings.
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The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.
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Neoplasias de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Microambiente Tumoral/genética , Prognóstico , Ritmo Circadiano/genética , Neoplasias de Cabeça e Pescoço/genéticaRESUMO
The urgency to mitigate greenhouse gas emissions from maritime vessels has intensified due to the increasingly stringent directives set forth by the International Maritime Organization (IMO). These directives specifically address energy efficiency enhancements and emissions reduction within the shipping industry. In this context, hydrogen is the much sought after fuel for all the global economies and its applications, for transportation and propulsion in particular, is crucial for cutting down carbon emissions. Nevertheless, the realization of hydrogen-powered vessels is confronted by substantial technical hurdles that necessitate thorough examination. This study undertakes a comprehensive analysis encompassing diverse facets, including distinct variations of hydrogen fuel cells, hydrogen internal combustion engines, safety protocols associated with energy storage, as well as the array of policies and commercialization endeavors undertaken globally for the advancement of hydrogen-propelled ships. By amalgamating insights from these multifaceted dimensions, this paper adeptly encapsulates the myriad challenges intrinsic to the evolution of hydrogen-fueled maritime vessels, while concurrently casting a forward-looking gaze on their prospective trajectory.
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BACKGROUND: Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. METHODS: Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). RESULTS: Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. CONCLUSIONS: This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.
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Transtornos Cronobiológicos , Relógios Circadianos , Colite Ulcerativa , Humanos , Colite Ulcerativa/genética , Relógios Circadianos/genética , Análise da Randomização Mendeliana , Comorbidade , Estudo de Associação Genômica Ampla , Peptidase 7 Específica de Ubiquitina , Proteínas ArgonautasRESUMO
OBJECTIVE: Traditional observational research has suggested a connection between socioeconomic position, mental health, and sleep apnea (SA), but the specifics of this connection are still unclear. Using the Mendelian randomization approach, we intended to evaluate the potential causal link between mental health, socioeconomic status, and SA. METHODS: Our research employed summary statistics data from large-scale genome-wide association studies (GWAS) on mental health, socioeconomic status, and SA. In the main study, the connection between mental health, socioeconomic status, and SA was examined using the inverse variance weighted approach. In addition, as a supplement, we also used other Mendelian randomization methods, including MR Egger, weighted median, simple mode, and weighted mode. RESULTS: The primary analysis showed that educational attainment, including longer years of schooling, college or university degree, and higher intelligence was associated with a lower risk of SA (OR = 0.750, 95%CI = 0.653-0.862; OR = 0.558, 95%CI = 0.423-0.735; OR = 0.871, 95%CI = 0.760-0.999, respectively), while social deprivation was associated with a higher risk of SA (OR = 1.821, 95%CI = 1.075-3.085). And the income was not associated with the risk of sleep apnea (OR = 0.877, 95%CI = 0.682-1.129). In mental health exposure, major depressive disorder was associated with a higher risk of sleep apnea (OR = 1.196, 95%CI = 1.015-1.409), while attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia were not associated with the risk of sleep apnea (OR = 1.064, 95%CI = 0.958-1.181; OR = 1.030, 95%CI = 0.942-1.127; OR = 0.990, 95%CI = 0.957-1.025, respectively). Reverse MR analysis failed to find a causal effect from SA on mental health and socioeconomic status. CONCLUSIONS: This MR investigation offers proof of a possible causal relationship between SA, socioeconomic level, and mental health.
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Transtorno Depressivo Maior , Síndromes da Apneia do Sono , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Saúde Mental , Classe SocialRESUMO
This paper investigates the adaptive neural event-triggered control for an underactuated surface vessel (USV), considering constraints of the obstacle's vicious maneuvering and the limited communication channel. In the algorithm, a novel logical phantom virtual ship (LPVS) guidance principle is developed to generate the global path following reference and the obstacle avoidance order in the simulation results, where the corresponding operation comply to the suggestion in international regulations for prevention collision at sea (COLREGs). The improved design of velocity obstacle (VO) method can guarantee its predictive capability to prevent the obstacle's vicious maneuvering. As for the control module, the adaptive event-triggered control algorithm is proposed by employing the robust neural damping technique and the input event-triggered mechanism. And the derived adaptive law can effectively solve perturbations from the gain uncertainty and the external disturbances. Through the theoretical analysis, all signals of the closed-loop control system are with the semi-globally uniform ultimate bounded (SGUUB) stability. The simulation experiments have been presented to verify the obstacle avoidance effectiveness and the burden-some superiority of the algorithm.
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BACKGROUND: Acute lung injury (ALI) is distinguished by rapid and severe respiratory distress and prolonged hypoxemia. A traditional Chinese medicine (TCM), known as the Fuzhengjiedu formula (FZJDF), has been shown to have anti-inflammatory benefits in both clinical and experimental studies. The precise underlying processes, nevertheless, are yet unclear. PURPOSE: This study sought to enlighten the protective mechanism of FZJDF in ALI through the standpoint of the gut-lung crosstalk. METHODS: The impact of FZJDF on lipopolysaccharide (LPS)-induced ALI murine model were investigated, and the lung injury score, serum interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) expression were measured to confirm its anti-inflammatory effects. Additionally, gut microbiota analysis and serum and fecal samples metabolomics were performed using metagenomic sequencing and high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, respectively. RESULTS: FZJDF significantly induced histopathological changes caused by LPS-induced ALI as well as downregulated the serum concentration of IL-1ß and TNF-α. Furthermore, FZJDF had an effect in gut microbiota disturbances, and linear discriminant effect size analysis identified signal transduction, cell motility, and amino acid metabolism as the potential mechanisms of action in the FZJDF-treated group. Several metabolites in the LPS and FZJDF groups were distinguished by untargeted metabolomic analysis. Correlations were observed between the relative abundance of microbiota and metabolic products. Comprehensive network analysis revealed connections among lung damage, gut microbes, and metabolites. The expression of glycine, serine, glutamate, cysteine, and methionine in the lung and colon tissues was dysregulated in LPS-induced ALI, and FZJDF reversed these trends. CONCLUSION: This study revealed that FZJDF considerably protected against LPS-induced ALI in mice by regulating amino acid metabolism via the gut-microbiota-lung axis and offered thorough and in-depth knowledge of the multi-system linkages of systemic illnesses.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Pulmão/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Aminoácidos/metabolismo , NF-kappa B/metabolismoRESUMO
ABSTRACT BACKGROUND: The cardiopulmonary function of patients with obstructive sleep apnea (OSA) is significantly lower than that of patients with simple snoring and is significantly related to the severity of OSA. Currently, only a few studies have been conducted on cardiopulmonary exercise testing in overweight patients with OSA. OBJECTIVE: To analyze the correlation between cardiopulmonary exercise test (CPET) indices and the condition of overweight patients with OSA. DESIGN AND SETTING: Retrospective study in Guangdong Provincial Hospital of Chinese Medicine. METHODS: This study included 73 hospitalized overweight patients. The patients were divided into no, mild, moderate, and severe OSA groups. Differences in the CPET indices among the four groups were compared. The correlation between the CPET indices and conditions was analyzed. RESULTS: No, mild, moderate, and severe OSA groups had 18 men and 5 women, 11 men and 3 women, 12 men and 2 women, and 21 men and 1 woman, respectively (P > 0.05). No significant difference was observed in resting pulmonary function among the four groups (P > 0.05). In the CPET, the anaerobic threshold, maximum oxygen uptake, and oxygen pulse were significantly lower in the severe OSA group than those in the normal OSA group (P < 0.05). Moreover, CPET indices negatively correlated with the apnea-hypopnea index. CONCLUSION: Changes in CPET indices occurred earlier than changes in resting pulmonary function in patients with OSA. CPET might be a potential method for evaluating the severity of OSA combined with overweight status.
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This study investigated the relationship between tenderness and protein phosphorylation levels of normal ultimate pH (pHu, 5.4-5.8, NpHu), intermediate pHu (5.8-6.2, IpHu) and high pHu (≥6.2, HpHu) Longissimus lumborum from beef. During 21 d of ageing, the HpHu group had the lowest Warner-Bratzler shear force (WBSF) values, while the IpHu group showed the highest and even after 21 days of ageing still had high levels. In the late stage of the 24 h post-mortem period the faster degradation rate of troponin T and earlier activation of caspase 9 in the HpHu group were the key reasons for the lower WBSF compared with the NpHu and IpHu groups. The activity of caspase 3 cannot explain the tenderness differences between IpHu and HpHu groups, since their activities did not show any difference. At 24 h post-mortem, 17 common differential phosphorylated peptides were detected among pHu groups, of which nine were associated with pHu and WBSF. The higher phosphorylation level of glycogen synthase may have caused the delay of meat tenderization in the IpHu group.
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Carne , Músculo Esquelético , Animais , Bovinos , Fosforilação , Músculo Esquelético/metabolismo , Carne/análise , Autopsia , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: The cardiopulmonary function of patients with obstructive sleep apnea (OSA) is significantly lower than that of patients with simple snoring and is significantly related to the severity of OSA. Currently, only a few studies have been conducted on cardiopulmonary exercise testing in overweight patients with OSA. OBJECTIVE: To analyze the correlation between cardiopulmonary exercise test (CPET) indices and the condition of overweight patients with OSA. DESIGN AND SETTING: Retrospective study in Guangdong Provincial Hospital of Chinese Medicine. METHODS: This study included 73 hospitalized overweight patients. The patients were divided into no, mild, moderate, and severe OSA groups. Differences in the CPET indices among the four groups were compared. The correlation between the CPET indices and conditions was analyzed. RESULTS: No, mild, moderate, and severe OSA groups had 18 men and 5 women, 11 men and 3 women, 12 men and 2 women, and 21 men and 1 woman, respectively (P > 0.05). No significant difference was observed in resting pulmonary function among the four groups (P > 0.05). In the CPET, the anaerobic threshold, maximum oxygen uptake, and oxygen pulse were significantly lower in the severe OSA group than those in the normal OSA group (P < 0.05). Moreover, CPET indices negatively correlated with the apnea-hypopnea index. CONCLUSION: Changes in CPET indices occurred earlier than changes in resting pulmonary function in patients with OSA. CPET might be a potential method for evaluating the severity of OSA combined with overweight status.