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Synthetic aromatic esters, widely employed in agriculture, food, and chemical industries, have become emerging environmental pollutants due to their strong hydrophobicity and poor bioavailability. This study attempted to address this issue by extracellularly expressing the promiscuous aminopeptidase (Aps) from Pseudomonas aeruginosa GF31 in B. subtilis, achieving an impressive enzyme activity of 13.7 U/mg. Notably, we have demonstrated, for the first time, the Aps-mediated degradation of diverse aromatic esters, including but not limited to pyrethroids, phthalates, and parabens. A biochemical characterization of Aps reveals its esterase properties and a broader spectrum of substrate profiles. The degradation rates of p-nitrobenzene esters (p-NB) with different side chain structures vary under the action of Aps, showing a preference for substrates with relatively longer alkyl side chains. The structure-dependent degradability aligns well with the binding energies between Aps and p-NB. Molecular docking and enzyme-substrate interaction elucidate that hydrogen bonding, hydrophobic interactions, and π-π stacking collectively stabilize the enzyme-substrate conformation, promoting substrate hydrolysis. These findings provide new insights into the enzymatic degradation of aromatic ester pollutants, laying a foundation for the further development and modification of promiscuous enzymes.
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Aminopeptidasas , Proteínas Bacterianas , Ésteres , Simulación del Acoplamiento Molecular , Pseudomonas aeruginosa , Hidrólisis , Ésteres/metabolismo , Ésteres/química , Aminopeptidasas/metabolismo , Aminopeptidasas/química , Aminopeptidasas/genética , Especificidad por Sustrato , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Pseudomonas aeruginosa/enzimología , Biodegradación Ambiental , Cinética , Bacillus subtilis/enzimología , Ácidos Ftálicos/química , Ácidos Ftálicos/metabolismoRESUMEN
BACKGROUND: Our study aimed to assess the clinical and hemodynamic characteristics of pulmonary hypertension (PH) in patients with overlapping obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to OSA-COPD overlap syndrome (OS). METHODS: We enrolled a total of 116 patients with OS, COPD, or OSA who underwent right heart catheterization (RHC) due to suspected PH. We conducted a retrospective analysis of the clinical and hemodynamic characteristics of these patients. RESULTS: Among the three groups (OS group, n = 26; COPD group, n = 36; OSA group, n = 54), the prevalence of PH was higher in the OS group (n = 17, 65.4%)compared to OSA group (n = 26,48.1%) and COPD group (n = 20,55.6 %). Among three groups with PH, the superior vena cava pressure (CVP) and right ventricular pressure (RAP) were higher in the OS group than in the OSA group (P < 0.05). Patients in the OS and COPD groups had higher pulmonary artery wedge pressure (PAWP) than in the OSA group (14.88 ± 4.79 mmHg, 13.45 ± 3.68 mmHg vs. 11.00 ± 3.51 mmHg, respectively, P < 0.05). OS patients with PH exhibited higher respiratory event index (REI), time spent with SpO2 <90%, oxygen desaturation index (ODI), minimal SpO2 (MinSpO2) and mean SpO2 (MSpO2) compared to OS patients without PH. After adjusting for potential covariates, we found that MinSpO2 (OR 0.937, 95 % CI 0.882-0.994, P = 0.032), MSpO2 (OR 0.805, 95% CI 0.682-0.949, P = 0.010), time spent with SpO2 <90% (OR 1.422, 95% CI 1.137-1.780, P = 0.002), and FEV1 % pred (OR 0.977, 95 % CI 0.962-0.993, P = 0.005) were related to the development of PH. CONCLUSIONS: Patients with OS showed higher prevalence of PH, along with higher PAWP, CVP and RAP. Worse nocturnal hypoxemia was found in OS patients with PH.
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Hemodinámica , Hipertensión Pulmonar , Enfermedad Pulmonar Obstructiva Crónica , Apnea Obstructiva del Sueño , Humanos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/etiología , Masculino , Femenino , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Estudios Retrospectivos , Anciano , Cateterismo CardíacoRESUMEN
Strong molecular photooxidants are important in many disciplines including organic synthesis and renewable energy. In these fields, strongly oxidizing chromophores are employed to drive various transformations from challenging bond formations to energy storage systems. A range of photooxidant strengths are needed to drive these processes. A series of 8 symmetrically bisarylated 5,6-dicyano[2,1,3]benzothiadiazole (DCBT) dyes were studied for their tunability toward breadth of light absorption and photooxidant strength. The dye oxidation strength and light absorption tunability is the result of appending various aryl substituents on the periphery of the DCBT core which shows remarkable tunability of the final chromophore. The dyes are studied via steady-state absorption and emission, time-correlated single photon counting, computational analysis, and cyclic voltammetry. In changing the peripheral aryl substituents via electronics, sterics, and π-conjugation length, a series of dyes are arrived at with a dramatic 1.5 eV range in oxidizing strength and >200 nm (0.95 eV) absorption maxima tunability. Furthermore, two dyes in the series exhibit strong oxidizing strength while still approaching red light absorbance (>650 nm onset) which provides unique opportunities for the use of lower energy light to affect chemical transformations. Ultimately, this series provides options for photooxidations that allow for energetic tuning and selectivity for a given chemical transformation.
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BACKGROUND: The Omicron wave of Coronavirus disease 2019 (COVID-19) remains the dominant strain worldwide. The studies of nutritional status in geriatric people with COVID-19 Omicron variant are limited. Thus, the aim of this study was to investigate the incidence of poor nutritional status among Omicron infected older patients, and to explore the correlation between the nutritional status and the severity of Omicron infection in older patients. METHODS: This is a retrospective cross-sectional study. According to the clinical symptoms, patients were divided into two groups: mild and moderate to severe. Mini Nutritional Assessment short-form (MNA-SF) was conducted when patients were admitted and poor nutritional status was defined as MNA-SF score of 0-11. The inflammatory markers including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic inflammatory index (SII) were calculated and compared between two groups. RESULTS: Total of 324 patients were enrolled, with median [interquartile range (IQR)] age of 73 (17) years. Overall, 241 cases were mild, 83 cases were moderate to severe at the time of diagnosis and that 54.3% of patients had poor nutritional status. Patients with poor nutritional status were found to be older (P < 0.001) and less vaccinated (P < 0.001), with a longer virus shedding duration (P = 0.022), more comorbidities (≥ 2) (P = 0.004) and higher value of NLR (P < 0.001), PLR (P < 0.001) and SII (P = 0.012). Vaccination, cycle threshold value in ORF1ab gene (OR CT value) and female, higher MNA-SF score was negatively connected with probability of moderate to severe infection. For every 1 score increase in MNA-SF, the odds ratio of moderate to severe infection decreased by 14.8% [adjusted odds ratio (aOR), 0.852; 95% confidence interval (CI): 0.734-0.988; P = 0.034]. CONCLUSIONS: Older patients with poor nutritional status are more likely to develop moderate to severe Omicron infection.
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COVID-19 , Desnutrición , Humanos , Femenino , Anciano , Estado Nutricional , Estudios Retrospectivos , Estudios Transversales , Desnutrición/epidemiología , Evaluación Nutricional , COVID-19/epidemiologíaRESUMEN
Clinical studies had found that hydrogen/oxygen mixed inhalation was beneficial to ameliorate the respiratory symptoms in the adjuvant treatment of patients with COVID-19. We aimed to explore the efficacy of hydrogen/oxygen therapy in favoring the recovery of Omicron SARS-CoV-2 variant infection. There were 64 patients who randomly assigned to receive hydrogen/oxygen inhalation (32 patients) and oxygen inhalation (32 patients). The average shedding duration of Omicron in hydrogen/oxygen group was shorter than oxygen group. The trend of cumulative negative conversion rate of Omicron increased gradually after the third day. The IL-6 levels in hydrogen/oxygen group decreased by 22.8% compared with the baseline. After hydrogen/oxygen mixed gas inhalation, the lymphocyte count increased to 61.1% of the baseline on the 3rd day in the hydrogen/oxygen group. More patients in the hydrogen/oxygen group had resolution of pulmonary lesions. Our study showed the beneficial trends of molecular hydrogen in treating patients with COVID-19, which may offer a prospective solution to adjuvant therapy for COVID-19 Patients.
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This review aims to provide a summary of the clinical characteristics and outcomes of lung cancer during pregnancy. A comprehensive literature search yielded 93 cases of lung cancer during pregnancy from 1953 to 2022, with an average maternal age of â¼34 years old. The initial symptoms reported were often nonspecific, such as cough, dyspnea, and chest pain. Cancer-related treatments, including surgery, radiotherapy, chemotherapy, and tyrosine kinase inhibitors, have shown beneficial effects on maternal outcomes. A majority of the newborns were born without malformation or diseases, but extended follow-up remains necessary. Early diagnosis of lung cancer is imperative for reducing the risks of placental and fetal metastasis and enhancing overall survival.
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Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy's involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.
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Dye-sensitized solar cells (DSCs) can provide a clean energy solution to growing energy demands. In order to have devices of high performance, sensitizers that are able to absorb in the near-infrared region (NIR) are needed. Stronger electron donors are needed for intramolecular charge-transfer sensitizers to access longer wavelength photons. Thus, two novel organic dyes with a cross-conjugated dibenzosilin double donor design are studied herein. The double donor delocalizes multiple filled orbitals across both amine donors due to the fused design that planarizes the donor as observed computationally, which improves intramolecular charge-transfer strength. The dyes are studied via density functional theory (DFT), optical spectroscopy, electrochemistry, and in DSC devices. The studies indicate that the dye design can reduce recombination losses, allowing for improved DSC device performances relative to a single arylamine donor. The reduction in recombination losses is attributed to the six alkyl chains that are incorporated into the donor, which offer good surface protection.
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OBJECTIVE: To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters. METHODS: The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed. RESULTS: Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genesï¼P <0.001ï¼. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037). CONCLUSION: There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.
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Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Pronóstico , Leucemia Mieloide Aguda/genética , Mutación , Transducción de Señal , Receptores del Factor Estimulante de Colonias/genéticaRESUMEN
BACKGROUND: Anti-coagulation is the cornerstone management of acute pulmonary embolism (PE), which is a double-edged sword, as it increases the risk of bleeding. Thus, predicting bleeding risk is necessary. The liver produces most coagulation factors to maintain the coagulation balance. However, the association between liver dysfunction markers and bleeding risk has not been thoroughly investigated. METHODS: A single-center, retrospective analysis of patients with acute PE was performed. First, the authors studied the association between liver dysfunction indexes and the 1-month bleeding risk. Then, they investigated whether it is more effective to predict the bleeding risk using a new joint model, i.e., adding liver dysfunction indexes to the PE-SARD score, which is the first score to assess the bleeding risk of acute PE. RESULTS: Among 469 patients with acute PE, 34 patients (7.2%) had bleeding events within 1 month after the onset. The levels of aspartate aminotransferase (AST) were higher in the bleeding group compared with the non-bleeding group (36.0 [18.25-90.0] vs. 23.0 [18.0-31.0], p = 0.008). Compared with AST<40, the odds ratios of 80≤AST<120 and AST≥120 were significant (8.825 [2.449-31.804] and 8.023 [2.543-25.315] respectively, p<0.01), even when adjusted for nine confounding factors (p<0.05). The area under the curve of PE-SARD combined with AST was significantly higher than that of the PE-SARD score (p = 0.02). CONCLUSIONS: In PE patients, AST is an independent factor in predicting the 1-month bleeding risk, and a novel joint model that combines AST and PE-SARD score improved the predictive efficiency for the 1-month bleeding risk.
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Embolia Pulmonar , Humanos , Estudios Retrospectivos , Embolia Pulmonar/diagnóstico , Hemorragia/etiología , Aspartato AminotransferasasRESUMEN
Purpose: Sleep disturbance has been implicated in poor prognosis of coronavirus disease 2019 (COVID-19), but less is known about the influence of short sleep duration on COVID-19 outcomes. We aim to investigate whether short sleep duration is associated with prolonged virus shedding duration in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-infected patients. Patients and Methods: A total of 270 patients with a laboratory confirmed COVID-19 diagnosis during SARS-CoV-2 Omicron-predominant period were recruited. Self-reported sleep duration of the patients was collected. The two-way analysis of variance (ANOVA) was used to determine the interactions between sleep duration and variables, and multivariate logistic regression analysis was used to analyze the effect of independent variables on longer virus shedding duration. Results: The two-way ANOVA revealed a significant sleep duration × snoring interaction effect for virus shedding duration, and a sleep duration × sex interaction effect for virus shedding duration. Multivariate logistic regression model illustrated that patients sleeping <6 h were at greater risk of prolonged virus shedding duration compared to those sleeping ≥6 hours (OR = 1.80, 95% CI = 1.01-3.26), independent of age, sex, co-existing diseases, vaccination condition, and antiviral treatment. Conclusion: Short sleep duration (<6 h) was associated with increased virus shedding in SARS-CoV-2 Omicron-infected patients.
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Rationale: Craniofacial and pharyngeal morphology influences risk for obstructive sleep apnea (OSA). Quantitative photography provides phenotypic information about these anatomical factors and is feasible in large samples. However, whether associations between morphology and OSA severity differ among populations is unknown. Objectives: The aim of this study was to examine this question in a large sample encompassing people from different ancestral backgrounds. Methods: Participants in SAGIC (Sleep Apnea Global Interdisciplinary Consortium) with genotyping data were included (N = 2,393). Associations between photography-based measures and OSA severity were assessed using linear regression, controlling for age, sex, body mass index, and genetic ancestry. Subgroups (on the basis of 1000 Genomes reference populations) were identified: European (EUR), East Asian, American, South Asian, and African (AFR). Interaction tests were used to assess if genetically determined ancestry group modified these relationships. Results: Cluster analysis of genetic ancestry proportions identified four ancestrally defined groups: East Asia (48.3%), EUR (33.6%), admixed (11.7%; 46% EUR, 27% Americas, and 22% AFR), and AFR (6.4%). Multiple anatomical traits were associated with more severe OSA independent of ancestry, including larger cervicomental angle (standardized ß [95% confidence interval (CI)] = 0.11 [0.06-0.16]; P < 0.001), mandibular width (standardized ß [95% CI] = 0.15 [0.10-0.20]; P < 0.001), and tongue thickness (standardized ß [95% CI] = 0.06 [0.02-0.10]; P = 0.001) and smaller airway width (standardized ß [95% CI] = -0.08 [-0.15 to -0.002]; P = 0.043). Other traits, including maxillary and mandibular depth angles and lower face height, demonstrated different associations with OSA severity on the basis of ancestrally defined subgroups. Conclusions: We confirm that multiple facial and intraoral photographic measurements are associated with OSA severity independent of ancestral background, whereas others differ in their associations among the ancestrally defined subgroups.
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Cara , Apnea Obstructiva del Sueño , Humanos , Cefalometría , Cara/anatomía & histología , Apnea Obstructiva del Sueño/genética , Índice de Masa Corporal , FaringeRESUMEN
GOAL AND AIMS: To compare a bio-radar contact-free monitoring device in diagnosing obstructive sleep apnea (OSA) in older people with an established home sleep apnea testing system (HST). FOCUS METHOD/TECHNOLOGY: A bio-radar contact-free monitoring device (OrbSense+). REFERENCE METHOD/TECHNOLOGY: An established HST, Alice NightOne. SAMPLE: Fifty-three out of 63 recruited subjects were included in the final analysis. Seventy-two percent were male (age 72 ± 9 years; body mass index 31.05 ± 5.56 kg/m2). DESIGN: An observational, prospective study. CORE ANALYTICS: Intraclass correlation coefficient (ICC), Bland-Altman analysis, and receiver operating characteristic analysis. ADDITIONAL ANALYTICS AND EXPLORATORY ANALYSES: None. CORE OUTCOMES: Both 45 (84.91%) were diagnosed with OSA by Alice NightOne (average respiratory event index = 21.23 events/h) and by OrbSense+ (average respiratory event index = 25.98 events/h). Respiratory event index and oxygen desaturation index obtained by Alice NightOne and OrbSense+ were highly correlated, with ICC of 0.93 and 0.88, respectively. The Bland-Altman plot comparing the means showed good agreement between the 2 diagnostic techniques. With more than 5 respiratory events per hour as the standard for OSA diagnosis, OrbSense+ had a sensitivity of 100% and a specificity of 100% in diagnosis of OSA (P < .0001). With more than 15 respiratory events per hour as the standard for OSA diagnosis, OrbSense+ was found to have a sensitivity of 100% and a specificity of 86.96% in diagnosis of OSA (P < .0001). IMPORTANT ADDITIONAL OUTCOMES: None. CORE CONCLUSION: The bio-radar sleep monitoring device is a reasonably accurate home sleep apnea test for use in older patients.
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Radar , Apnea Obstructiva del Sueño , Humanos , Masculino , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Femenino , Estudios Prospectivos , Apnea Obstructiva del Sueño/diagnóstico , Sueño , Polisomnografía/métodosRESUMEN
Liposuction is not a risk-free procedure and potentially fatal complications may occur, especially liposuction-induced fat embolism syndrome (FES). Here we report the case of a 29-year-old woman who developed FES suddenly during a liposuction operation in a cosmetic medical clinic. She was transferred to the hospital and achieved complete recovery within 11 days by comprehensive therapeutic strategies, including noninvasive ventilation (NIV), corticosteroids, albumin, diuretics and anticoagulation. Liposuction-induced FES is a life-threatening condition, which can be treated with complate recovery by comprehensive therapeutic strategies according to its pathophysiologic mechanism.