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Skin infections are a major threat to human health. Early diagnosis of bacterial infections is of great significance for implementing protective measures on the skin. Therefore, in this study, we designed an electrospun membrane (PPBT) for visual monitoring of colonized bacteria and responsive antibacterial ability. Specifically, the acidity of the microenvironment caused by bacterial metabolism was applied to drive the color change of bromothymol blue (BTB) on the PPBT membrane from green to yellow, thereby facilitating the early warning of infection and timely treatment. Within 4 h, different concentrations of Staphylococcus aureus (â¼105 CFU mL-1), Escherichia coli (â¼105 CFU mL-1), Pseudomonas aeruginosa (â¼105 CFU mL-1) and Candida albicans (â¼104 CFU mL-1) were visually monitored. Moreover, as the local acidity was enhanced via microbial metabolism, ZIF-8 nanoparticles loaded with TCS (TCS@ZIF-8) on the PPBT membrane could release TCS in an acid-responsive manner. At the same time, ROS were generated under 405 nm irradiation to achieve synergistic antibacterial ability. Experiments confirmed that the PPBT membrane has ideal and controllable antibacterial features based on acid responsive release and a synergistic photocatalytic antibacterial mechanism after monitoring. Therefore, the PPBT membrane developed in this work provides a feasible solution for bacterial monitoring and inactivation devices. More importantly, it can be beneficial for meeting the needs of clinical diagnosis and timely treatment of bacterial infection.
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Background: Metabolic remodeling is a hallmark of the failing heart. Oncometabolic stress during cancer increases the activity and abundance of the ATP-dependent citrate lyase (ACL, Acly ), which promotes histone acetylation and cardiac adaptation. ACL is critical for the de novo synthesis of lipids, but how these metabolic alterations contribute to cardiac structural and functional changes remains unclear. Methods: We utilized human heart tissue samples from healthy donor hearts and patients with hypertrophic cardiomyopathy. Further, we used CRISPR/Cas9 gene editing to inactivate Acly in cardiomyocytes of MyH6-Cas9 mice. In vivo, positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to the loss of ACL. We conducted a multi-omics analysis using RNA-sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. Results: Here, we show that in mice, ACL drives metabolic adaptation in the heart to sustain contractile function, histone acetylation, and lipid modulation. Notably, we show that loss of ACL increases glucose oxidation while maintaining fatty acid oxidation. Ex vivo isotope tracing experiments revealed a reduced efflux of glucose-derived citrate from the mitochondria into the cytosol, confirming that citrate is required for reductive metabolism in the heart. We demonstrate that YAP inactivation facilitates ACL deficiency. Computational flux analysis and integrative multi-omics analysis indicate that loss of ACL induces alternative isocitrate dehydrogenase 1 flux to compensate. Conclusions: This study mechanistically delineates how cardiac metabolism compensates for suppressed citrate metabolism in response to ACL loss and uncovers metabolic vulnerabilities in the heart.
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Introduction: The effects of continuous cropping and rotation cropping, two important tobacco cultivation practices, on soil microbial communities at different stages remain unclear. Different planting patterns have been shown to influence soil physical and chemical properties, which in turn can affect the composition and diversity of soil microbial communities. Methods: In order to investigate the impact of different planting methods on soil microbial community structure, we selected two representative planting methods: continuous cropping (tobacco) and rotational cropping (tobacco-maize). These methods were chosen as the focal points of our research to explore the potential effects on soil microbial communities. High-throughput sequencing technology was employed to investigate the structure of soil microbial communities, as well as their relationships with soil environmental factors, by utilizing the 16S rRNA, ITS, and 18S genes. Furthermore, the interaction among microorganisms was explored through the application of the Random Matrix Theory (RMT) molecular ecological network approach. Results: There was no significant difference in α diversity, but significant difference in ß diversity based on Jaccard distance test. Compared to continuous cropping, crop rotation significantly increased the abundance of beneficial prokaryotes Verrucomicrobia and Rhodanobacter. These findings indicate that crop rotation promotes the enrichment of Verrucomicrobia and Rhodanobacter in the soil microbial community. AP and NH4-N had a greater effect on the community structure of prokaryotes and fungi in tobacco soil, while only AP had a greater effect on the community structure of protist. Molecular ecological network analysis showed that the network robustness and Cohesion of rotation were significantly higher than that of continuous cropping, indicating that the complexity and stability of molecular ecological networks were higher in the rotational, and the microbial communities cooperated more effectively, and the community structure was more stable. Discussion: From this point of view, rotational cropping is more conducive to changing the composition of soil microbial community, enhancing the stability of microbial network structure, and enhancing the potential ecological functions in soil.
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Hemochromatosis, also known as siderosis, is a disease caused by excessive iron deposition in human organs and tissues, resulting from iron metabolism disorders. It is clinically characterized by skin pigmentation (bronze color), liver cirrhosis, diabetes, weakness, and fatigue. Additional symptoms may include arthritis, hypothyroidism, heart failure, and sexual hypofunction. Clinical manifestations can vary from person to person, with a few patients showing no clinical manifestations, which makes the diagnosis difficult for clinicians. In this case report, we described hereditary hemochromatosis related to a mutation in the HAMP gene in Fuyang City, China, as a reference for clinicians. Hereditary hemochromatosis is rarely reported in China. Clinicians in China have relatively insufficient knowledge of this disease, which leads to frequent misdiagnosis. In this case report, we describe hereditary hemochromatosis related to HAMP gene mutation in Fuyang City, China, for the clinician's reference.
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Tooth attachment and replacement play significant roles in the feeding ecology of polyphyodont vertebrates, yet these aspects have remained largely unexplored in non-avialan paravians including troodontids. Here, we describe a new troodontid species, Urbacodon norelli sp.n., recovered from the Upper Cretaceous Iren Dabasu Formation of Inner Mongolia, China, based on an incomplete right dentary and 12 associated replacement teeth. Urbacodon norelli is distinguished from all other known troodontids, including its relative U. itemirensis from Uzbekistan, by several features: the presence of paired dentary symphyseal foramina, the presence of a relatively steep anterior margin of the dentary, the absence of a dentary chin, the presence of a common groove hosting the anterior 12 dentary teeth, and the presence of relatively larger dentary teeth. Phylogenetic analysis places both species of Urbacodon as sister taxa to Zanabazar junior, confirming their status as later-diverging troodontids. Radiographs revealed an alternating tooth replacement pattern in U. norelli, with a maximum Zahnreihen-spacing estimated to be 3. During tooth replacement, the anteriorly inclined interdental septa, which wedge between anterior dentary teeth, underwent frequent remodelling as the developing tooth moved upwards, particularly anterolabially. This rapid turnover left insufficient time for an interdental plate to form, resulting in the absence of such structures in this specimen. The frequent remodelling of periodontal tissues accompanying tooth replacement is likely to account for the absence of interdental plates. The discovery of this new troodontid expands our understanding of paravian theropods from the Upper Cretaceous Iren Dabasu Formation and provides valuable insights into troodontid tooth biology.
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Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aß-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aß toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aß deposition in Aß1-42-injured mice. Mechanistically, the compound regulated APP processing by promoting the ADAM10-associated nonamyloidogenic signaling and inhibiting the BACE1-mediated amyloidogenic pathway. Moreover, it suppressed intracellular AChE activity and tau phosphorylation. Therefore, compound 4j may be a promising multitargeted active molecule against AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Cinamatos , Triazoles , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Animales , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Cinamatos/química , Cinamatos/farmacología , Cinamatos/síntesis química , Humanos , Ratones , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/antagonistas & inhibidores , Relación Estructura-Actividad , Estructura Molecular , Ésteres/química , Ésteres/farmacología , Ésteres/síntesis química , Relación Dosis-Respuesta a Droga , Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/síntesis química , Descubrimiento de Drogas , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/síntesis química , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/antagonistas & inhibidores , MasculinoRESUMEN
[This corrects the article DOI: 10.3389/fcvm.2023.1109946.].
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BACKGROUND: This study aimed to translate and culturally adapt the Assessment of Quality of Life (AQoL)-6D into Malay (Malay-AQoL-6D), and assesses the instrument's acceptability, reliability, and validity among Malaysians living with chronic heart failure (HF). METHODS: The translation and cross-cultural adaptation process adhered to international guidelines. The Malay-AQoL-6D underwent content and face validity assessments via expert review, and pretesting among healthy individuals and patients with chronic conditions. Subsequent psychometric validation utilised clinico-sociodemographic data and paired AQoL-6D and EQ-5D-5L data from a health-related quality-of-life (HRQoL) survey involving Malay-speaking patients with HF, which encompassed assessments of Malay-AQoL-6D acceptability, internal consistency and test-retest reliability, as well as its construct, concurrent, convergent and divergent, and known-group validity. RESULTS: The Malay-AQoL-6D was deemed acceptable among clinicians and local patients, achieving a 90.8% completion rate among 314 patients surveyed. The instrument demonstrated strong content validity (item-level content validity index [CVI]: 0.83-1.00, average CVI: 0.98), internal consistency (Cronbach's alpha: 0.72-0.89; MacDonald's omega: 0.82-0.90, excluding the Senses dimension), and test-retest reliability (average intraclass correlation coefficients: 0.79-0.95). Confirmatory factor analysis confirmed the instrument's two-level, six-factor structure (Satorra-Bentler [SB]-scaled χ2(df: 164): 283.67, p-value < 0.001; root mean square error of approximation [RMSEA]: 0.051; comparative fix index [CFI]: 0.945, Tucker-Lewis index [TLI]: 0.937; standardised root mean-squared error [SRMR]: 0.058). The Malay-AQoL-6D's concurrent validity was evident through its good agreement with EQ-5D-5L. Multiple hypothesis tests further affirmed its construct and known-group validity. The Malay-AQoL-6D's psychometric properties remained consistent across different missing data techniques. CONCLUSION: The findings suggest that Malay-AQoL-6D could be a culturally acceptable, reliable, and valid HRQoL measure for quantifying HRQoL among the local HF population. Future studies are necessary to further validate the instrument against other measures and confirm the instrument's test-retest reliability and responsiveness, which are possible with the availability of the Malay-AQoL-6D.
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Comparación Transcultural , Insuficiencia Cardíaca , Psicometría , Calidad de Vida , Humanos , Calidad de Vida/psicología , Psicometría/instrumentación , Psicometría/métodos , Psicometría/normas , Malasia , Masculino , Femenino , Insuficiencia Cardíaca/psicología , Insuficiencia Cardíaca/etnología , Reproducibilidad de los Resultados , Persona de Mediana Edad , Anciano , Enfermedad Crónica , Encuestas y Cuestionarios , Traducciones , Adulto , Pueblos del Sudeste AsiáticoRESUMEN
Lynch syndrome (LS) is defined by inherited mutations in DNA mismatch repair genes, including MSH2, and carries 60% lifetime risk of developing endometrial cancer (EC). Beyond hypermutability, specific mechanisms for LS-associated endometrial carcinogenesis are not well understood. Here, we assessed the effects of MSH2 loss on EC pathogenesis using a novel mouse model (PR-Cre Msh2 flox/flox , abbreviated Msh2KO), primary cell lines established from this model, human tissues, and human EC cell lines with isogenic MSH2 knockdown. Beginning at eight months of age, 30% of Msh2KO mice exhibited endometrial atypical hyperplasia (AH), a precancerous lesion. At 12 to 16 months of age, 47% of Msh2KO mice exhibited either AH or ECs with histologic features similar to human LS-related ECs. Transcriptomic profiling of EC from Msh2KO mice revealed a transcriptomic signature for mitochondrial dysfunction. Studies in vitro and in vivo revealed mitochondrial dysfunction based upon two mechanisms: marked mitochondrial content reduction, along with pronounced disruptions to the integrity of retained mitochondria. Human LS-related ECs also exhibited mitochondrial content reduction compared with non-LS-related ECs. Functional studies revealed metabolic reprogramming of MSH2-deficient EC cells in vitro , including reduced oxidative phosphorylation and increased susceptibility to glycolysis suppression. We are the first to identify mitochondrial dysfunction and metabolic disruption as a consequence of MSH2 deficiency-related EC. Mitochondrial and metabolic aberrations should be evaluated as novel biomarkers for endometrial carcinogenesis or risk stratification and could serve as targets for cancer interception in women with LS. Significance: This is the first study to report mitochondrial dysfunction contributing to MSH2-deficient endometrial cancer development, identifying a noncanonical pathway for MSH2 deficient carcinogenesis, which also imparts vulnerability to metabolic targeting.
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Plant environmental stress response has become a global research hotspot, yet there is a lack of clear understanding regarding the mechanisms that maintain microbial diversity and their ecosystem services under environmental stress. In our research, we examined the effects of moderate elevation on the rhizosphere soil characteristics, microbial community composition, and ecosystem multifunctionality (EMF) within agricultural systems. Our findings revealed a notable negative correlation between EMF and elevation, indicating a decline in multifunctionality at higher elevations. Additionally, our analysis across bacterial and protistan communities showed a general decrease in microbial richness with increasing elevation. Using random forest models, pH was identified as the key environmental stressor influencing microbial communities. Furthermore, we found that microbial community diversity is negatively correlated with stability by mediating complexity. Interestingly, while pH was found to affect the complexity within bacterial networks, it did not significantly impact the ecosystem stability along the elevation gradients. Using a Binary-State Speciation and Extinction (BiSSE) model to explore the evolutionary dynamics, we found that Generalists had higher speciation rates and lower extinction rates compared to specialists, resulting in a skewed distribution towards higher net diversification for generalists under increasing environmental stress. Moreover, structural equation modeling (SEM) analysis highlighted a negative correlation between environmental stress and community diversity, but showed a positive correlation between environmental stress and degree of cooperation & competition. These interactions under environmental stress indirectly increased community stability and decreased multifunctionality. Our comprehensive study offers valuable insights into the intricate relationship among environmental factors, microbial communities, and ecosystem functions, especially in the context of varying elevation gradients. These findings contribute significantly to our understanding of how environmental stressors affect microbial diversity and ecosystem services, providing a foundation for future ecological research and management strategies in similar contexts.
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Ecosistema , Microbiota , Microbiología del Suelo , Suelo , Concentración de Iones de Hidrógeno , Suelo/química , Altitud , BiodiversidadRESUMEN
A microwave-assisted synthesis of 7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazine-2-propanamides was developed using a three-component, catalyst-free reaction of cyanamide and trimethyl orthoformate with 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides (3). The reaction tolerated structurally diverse substrates and proceeded chemo- and regio-selectively, affording the target compounds in high purity in 5-10â minutes. The convenient chromatography-free isolation and purification of the products add practicality to this method. The structural features of the prepared compounds were investigated using dynamic NMR spectroscopy, X-ray crystallography and computational chemistry calculations. X-ray crystallography performed on a representative compound, 3-(7-amino-1,2,4-triazolo[1,5-a][1,3,5]triazin-2-yl)-N-(4-benzyl)propanamide (4 l), showed the overall molecular conformation to adopt the shape of the letter C. Notable localisation of π-electron density is found within the 1,2,4-triazolo[1,5-a][1,3,5]triazine system; a relatively short C-NH2 bond is consistent with restricted rotation about this bond. This study also presents a detailed analysis of the molecular interactions in 4 l using DFT and QTAIM methods with a focus on the hydrogen-bonding and π-stacking interactions that influence the molecular packing of 4 l. The findings reveal the significant roles of N-Hâ O, N-Hâ N and C-Hâ N interactions, along with electrostatically enhanced πâ π contacts. A broad screening for insecticidal, fungicidal and herbicidal properties identified several compounds with potent herbicidal activity against Matricaria inodora.
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OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss. METHODS: We quantified genomic, metabolomic, and proteomic changes in cultured skeletal muscle cells and mouse models of IDH-mutant leukemia using RNA sequencing, mass spectrometry, and computational modeling. RESULTS: D2-HG impairs NADH redox homeostasis in myotubes. Increased NAD+ levels drive activation of nuclear deacetylase Sirt1, which causes deacetylation and activation of LC3, a key regulator of autophagy. Using LC3 mutants, we confirm that deacetylation of LC3 by Sirt1 shifts its distribution from the nucleus into the cytosol, where it can undergo lipidation at pre-autophagic membranes. Sirt1 silencing or p300 overexpression attenuated autophagy activation in myotubes. In vivo, we identified increased muscle atrophy and reduced grip strength in response to D2-HG in male vs. female mice. In male mice, glycolytic intermediates accumulated, and protein expression of oxidative phosphorylation machinery was reduced. In contrast, female animals upregulated the same proteins, attenuating the phenotype in vivo. Network modeling and machine learning algorithms allowed us to identify candidate proteins essential for regulating oncometabolic adaptation in mouse skeletal muscle. CONCLUSIONS: Our multi-omics approach exposes new metabolic vulnerabilities in response to D2-HG in skeletal muscle and provides a conceptual framework for identifying therapeutic targets in cachexia.
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Autofagia , Glutaratos , Músculo Esquelético , Transducción de Señal , Animales , Ratones , Músculo Esquelético/metabolismo , Masculino , Glutaratos/metabolismo , Isocitrato Deshidrogenasa/metabolismo , Isocitrato Deshidrogenasa/genética , Caquexia/metabolismo , Femenino , Sirtuina 1/metabolismo , Sirtuina 1/genética , Ratones Endogámicos C57BLRESUMEN
PURPOSE: Health-related quality-of-life (HRQoL) data for the chronic heart failure (HF) population in Malaysia are lacking. Using EQ-5D-5L, this study intended to describe their HRQoL, identify predictors of worse HRQoL, and derive EQ-5D-5L index scores for use in economic evaluations. METHODS: A cross-sectional survey was conducted between April and September 2023 to collect EQ-5D-5L, sociodemographic, and clinical data from outpatients with HF across seven public specialist hospitals in Malaysia. Multivariable logistic and linear regression models were used to identify independent predictors of reported problems in the EQ-5D-5L dimensions, and predictors of index scores and EQ-VAS, respectively. RESULTS: EQ-5D-5L data from 424 outpatients of multi-ethnic background (mean age: 57.1 years, 23.8% female, mean left ventricular ejection fraction: 35.7%, 89.7% NYHA class I-II) were collected using either Malay, English, or Chinese, achieving a 99.8% completion rate. Nearly half of the respondents reported issues in the Mobility, Usual Activities, and Pain/Discomfort dimensions. Mean EQ-5D-5L index was 0.820, lower than the general population, and significantly lower with NYHA class III-IV (0.747) versus NYHA class I (0.846) and NYHA class II (0.805). Besides NYHA class, independent predictors of worse HRQoL included Indian ethnicity, living alone, lower education, unemployment due to ill-health, and proxy-reported HRQoL, largely aligning with existing literature. CONCLUSION: Community-dwelling Malaysians with HF reported poorer HRQoL compared to the general population. The observed disparities in HRQoL among HF patients may be linked to specific patient characteristics, suggesting potential areas for targeted interventions. HRQoL assessment using EQ-5D-5L proves feasible and should be considered for routine implementation in local clinics.
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Insuficiencia Cardíaca , Calidad de Vida , Humanos , Femenino , Masculino , Insuficiencia Cardíaca/psicología , Malasia , Estudios Transversales , Persona de Mediana Edad , Anciano , Encuestas y Cuestionarios , Enfermedad Crónica , Adulto , Pacientes Ambulatorios/psicología , Estado de Salud , PsicometríaRESUMEN
The impact of general anesthetics on brain function development is one of the top frontier issues of public concern. However, little bibliometric analysis has investigated this territory systematically. Our study aimed to visualize the publications between 2000 and 2023 to inspire the trends and hotspots in anesthetic neurodevelopmental toxicity research. Publications from 2000 to 2023 were collected from the Web of Science Core Collection. CiteSpace was utilized to plot and analyze the network maps of countries, institutions, authors, journals, and keywords associated with these publications. A total of 864 publications, consisting of 786 original articles and 78 reviews, were extracted from 2000 to 2023. The annual publications have increased constantly over the past two decades. The USA and the People's Republic of China were the leading driving forces in this field. Harvard University was the most productive institution. Zhang Y published the most related articles, and Jevtovic-Todorovic V was mostly cited in this field. The most prolific journal was Pediatric Anesthesia, and the most frequently co-cited journal was Anesthesiology. Keywords were divided into nine clusters: "apoptosis", "propofol", "developing brain", "cognitive dysfunction", "neuronal cell degeneration", "brain", "neuroinflammation", "local anesthesia", and "oxygen therapy". The strongest citation bursts in earlier years were "learning disability", "cell death", and "cognitive function". The emerging trends in the coming years were "awake regional anesthesia", "behavioral outcome", and "infancy general anesthesia compared to spinal anesthesia". We conclude that anesthetic-induced neurotoxicity has received growing attention in the past two decades. Our findings evaluated the present status and research trends in this area, which may provide help for exploring further potential prospects on hot topics and frontiers.
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Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.
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Antivirales , Subtipo H1N1 del Virus de la Influenza A , Compuestos Macrocíclicos , Oximas , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Oximas/farmacología , Oximas/química , Oximas/síntesis química , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Relación Estructura-Actividad , Humanos , Perros , Compuestos Macrocíclicos/farmacología , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/síntesis química , Animales , Células de Riñón Canino Madin Darby , Descubrimiento de Drogas , Biomimética , Oseltamivir/farmacología , Oseltamivir/químicaRESUMEN
In this study, a pyrite-based autotrophic denitrification (PAD) system, a polycaprolactone (PCL)-supported heterotrophic denitrification (PHD) system, and a pyrite+PCL-based split-mixotrophic denitrification (PPMD) system were constructed. The pyrite particle size was controlled in 1-3, 3-5, or 5-8 mm in both the PAD and PPMD systems to investigate the effect of pyrite particle size on the denitrification performance of autotrophic or split-mixotrophic bioreactors. It was found that the PAD system achieved the best denitrification efficiency with an average removal rate of 98.98% in the treatment of 1- to 3-mm particle size, whereas it was only 19.24% in the treatment of 5- to 8-mm particle size. At different phases of the whole experiment, the nitrate removal rates of both the PHD and PPMD systems remained stable at a high level (>94%). Compared with the PAD or PHD system, the PPMD system reduced the concentrations of sulfate and chemical oxygen demand in the final effluent efficiently. The interconnection network diagram explained the intrinsic metabolic pathways of nitrogen, sulfur, and carbon in the three denitrification systems at different phases. In addition, the microbial community analysis showed that the PPMD system was beneficial for the enrichment of Firmicutes. Finally, the impact mechanism of pyrite particle size on the performance of the PPMD system was proposed. PRACTITIONER POINTS: The reduction of pyrite particle size was beneficial for improving the efficiency of the PAD process. The change in particle size had an effect on NO2 --N accumulation in the PAD system. The accumulation of NH4 +-N in the PPMD system increased with the decrease in particle size. The reduction of pyrite particle size increased the production of SO4 2- in the PAD and PPMD systems. The correlations among the effluent indicators of the PAD and PPMD systems could be well explained.
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Reactores Biológicos , Desnitrificación , Hierro , Tamaño de la Partícula , Poliésteres , Sulfuros , Sulfuros/química , Sulfuros/metabolismo , Poliésteres/química , Poliésteres/metabolismo , Hierro/química , Hierro/metabolismo , Procesos Autotróficos , Nitratos/metabolismo , Nitratos/químicaRESUMEN
Herein, we present a patient who was undergoing chemotherapy for bilateral breast cancer and experienced delayed-onset skin toxicity reactions after rupture of a peripherally inserted central catheter (PICC) in the lower extremities. The objective of this case report is to provide the necessary nursing assessment for the risk awareness of the PICC internal rupture and the occurrence of central venous catheter extravasation, as well as to strengthen the judgment of delayed skin toxicity of chemotherapeutic drugs. Rupture of the PICC in the lower extremities was primarily attributed to the use of a silicone catheter and an excessive puncture angle. The nature of docetaxel and partial catheter rupture caused drug extravasation, leading to delayed skin toxicity. The use of a polyurethane catheter reduces the incidence of catheter rupture; hence, silicon catheters should be avoided. The central venous catheter is also at risk for the extravasation of chemotherapeutic agents. Moreover, docetaxel-induced delayed skin toxicity, which has a high incidence, should be treated as expected. Nurses and clinicians should be aware of PICC internal rupture and central venous catheter extravasation to strengthen the judgment of delayed skin toxicity of chemotherapeutic drugs.
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Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), omega-3 polyunsaturated fatty acids (ω-3 PUFAs) derived from fish oil, are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. However, studies investigating the effects of EPA and DHA on colorectal carcinogenesis (CRC) have yielded conflicting results. The factors that determine these discrepant results remain unknown. Resolvins, oxidative metabolites of EPA and DHA, inhibit key pro-tumorigenic cytokine and chemokine signaling of colorectal cancer (e.g., IL-6, IL-1ß, and CCL2). 15-lipoxygenase-1 (ALOX15), a critical enzyme for resolvin generation is commonly lost during human CRC. Whether ALOX15 expression, as a host factor, modulates the effects of EPA and DHA on CRC remains unknown. Therefore, we evaluated the effects of ALOX15 transgenic expression in colonic epithelial cells on resolvin generation by EPA and DHA and CRC in mouse models representative of human CRC. Our results revealed that 1) EPA and DHA effects on CRC were diverse, ranging from suppressive to promotive, and these effects were occasionally altered by the formulations of EPA and DHA (free fatty acid, ethyl ester, triglyceride); 2) EPA and DHA uniformly suppressed CRC in the presence of intestinal ALOX15 transgenic expression, which induced the production of resolvins, decreased colonic CCL3-5 and CXCL-5 expression and tumor associated macrophages while increasing CD8 T cell abundance in tumor microenvironment; and 3) RvD5, the predominant resolvin produced by ALOX15, inhibited macrophage generation of pro-tumorigenic cytokines. These findings demonstrate the significance of intestinal ALOX15 expression as a host factor in determining the effects of EPA and DHA on CRC. Significance: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely used as dietary supplements and FDA-approved treatments for hypertriglyceridemia. Studies of EPA and DHA effects on colorectal carcinogenesis (CRC) have revealed inconsistencies; factors determining the direction of their impact on CRC have remained unidentified. Our data show that EPA and DHA effects on CRC were divergent and occasionally influenced by their formulations. More importantly, intestinal 15-lipoxgenase-1 (ALOX15) expression modulated EPA and DHA effects on CRC, leading to their consistent suppression of CRC. ALOX15 promoted EPA and DHA oxidative metabolism to generate resolvins, which inhibited key pro-tumorigenic inflammatory cytokines and chemokines, including IL-6. IL-1ß, and CCL2. ALOX15 is therefore an important host factor in determining EPA and DHA effects on CRC.
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CRTAC1, one of the pyroptosis-related genes, has been identified as a protective factor in certain kinds of cancer, such as gastric adenocarcinoma and bladder cancer. The study aimed to investigate the role of CRTAC1 in lung adenocarcinoma (LUAD). LUAD datasets were obtained from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA), pyroptosis-related genes from GeneCard. Limma package used to find differentially expressed genes (DEGs), least absolute shrinkage and selection operator (LASSO) regression and weighted genes co-expression network analysis (WGCNA) to identify CRTAC1 as hub gene. CRTAC1 expression was confirmed in a real-world cohort using quantitative polymerase chain reaction (qPCR) and Western Blot (WB) analyses. Cellular experiments were conducted to investigate CRTAC1's potential oncogenic mechanisms. CRTAC1 mRNA expression was significantly lower in LUAD tissues (p < 0.05) and showed high accuracy in diagnosing LUAD. Reduced CRTAC1 expression was associated with a poor prognosis. Higher CRTAC1 expression correlated with increased immune cell infiltration. Individuals with high CRTAC1 expression showed increased drug sensitivity. Additionally, qPCR and WB analyses showed that CRTAC1 expression was lower in tumor tissue compared to adjacent normal tissue at both the RNA and protein levels. Upregulation of CRTAC1 significantly inhibited LUAD cell proliferation, invasion, and migration in cellular experiments. CRTAC1 has the potential to serve as a diagnostic and prognostic biomarker in LUAD.
Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Proteínas de Unión al Calcio , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Perfilación de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Pronóstico , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismoRESUMEN
INTRODUCTION: Lung cancer is a common malignant tumor, and different types of immune cells may have different effects on the occurrence and development of lung cancer subtypes, including lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). However, the causal relationship between immune phenotype and lung cancer is still unclear. METHODS: This study utilized a comprehensive dataset containing 731 immune phenotypes from the European Bioinformatics Institute (EBI) to evaluate the potential causal relationship between immune phenotypes and LUSC and LUAD using the inverse variance weighted (IVW) method in Mendelian randomization (MR). Sensitivity analyses, including MR-Egger intercept, Cochran Q test, and others, were conducted for the robustness of the results. The study results were further validated through meta-analysis using data from the Transdisciplinary Research Into Cancer of the Lung (TRICL) data. Additionally, confounding factors were excluded to ensure the robustness of the findings. RESULTS: Among the final selection of 729 immune cell phenotypes, three immune phenotypes exhibited statistically significant effects with LUSC. CD28 expression on resting CD4 regulatory T cells (OR 1.0980, 95% CI: 1.0627-1.1344, p < 0.0001) and CD45RA + CD28- CD8 + T cell %T cell (OR 1.0011, 95% CI: 1.0007; 1.0015, p < 0.0001) were associated with increased susceptibility to LUSC. Conversely, CCR2 expression on monocytes (OR 0.9399, 95% CI: 0.9177-0.9625, p < 0.0001) was correlated with a decreased risk of LUSC. However, no significant causal relationships were established between any immune cell phenotypes and LUAD. CONCLUSION: This study demonstrates that specific immune cell types are associated with the risk of LUSC but not with LUAD. While these findings are derived solely from European populations, they still provide clues for a deeper understanding of the immunological mechanisms underlying lung cancer and may offer new directions for future therapeutic strategies and preventive measures.