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PURPOSE: Recently, the detrimental effect of cigarette smoking on muscle metabolism has attracted much attention, but the relationship between cigarette smoking and muscle mass is poorly understood. Thus, this study investigated the association between exposure to cigarette smoke, defined based on serum cotinine, and muscle mass in the US population. METHODS: We utilized National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2018 for analysis. Data on serum cotinine, muscle mass (quantified by appendicular skeletal muscle mass index, ASMI), and covariates were extracted and analyzed. Weighted multivariate linear regression analyses and smooth curve fittings were performed to investigate the association between serum cotinine and ASMI. Subgroup analyses were stratified by gender, race and smoking status. When nonlinearity was detected, the threshold effects were analyzed using a two-piecewise linear regression model. RESULTS: In total, 8004 participants were included for analysis. The serum level of cotinine was negatively associated with ASMI in the fully adjusted model. Furthermore, comparing participants in the highest vs. the lowest tertile of serum cotinine, we found that ASMI decreased by 0.135 Kg/m2. In subgroup analysis stratified by gender and race, the association between serum cotinine and ASMI remained significant in all genders and races. In addition, the association remained significant among current and former smokers, but not among those who never smoked. Smooth curve fittings showed nonlinear relationships between serum cotinine and ASMI, with the inflection points identified at 356 ng/mL. CONCLUSIONS: Our study revealed that serum cotinine was negatively related to muscle mass. This finding improves our understanding of the deleterious effects of cigarette smoking on muscle mass and highlights the importance of smoking cessation for muscle health.
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Cotinina , Músculo Esquelético , Encuestas Nutricionales , Humanos , Cotinina/sangre , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Estudios Transversales , Adulto Joven , Fumar Cigarrillos/sangre , Fumar Cigarrillos/epidemiología , AncianoRESUMEN
BACKGROUND: Alzheimer's disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. METHODS: The differentiated human neural cells were induced by Aß1-42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aß1-42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. RESULTS: The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. CONCLUSIONS: Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aß-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Modelos Animales de Enfermedad , Complejo I de Transporte de Electrón , Terapia Genética , Mitocondrias , Animales , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/genética , Complejo I de Transporte de Electrón/metabolismo , Complejo I de Transporte de Electrón/genética , Humanos , Péptidos beta-Amiloides/metabolismo , Mitocondrias/metabolismo , Dependovirus/genética , Hipocampo/patología , Hipocampo/metabolismo , Ratones , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Neuronas/metabolismo , Neuronas/patología , Fragmentos de Péptidos , MasculinoRESUMEN
In the age of information explosion, the exponential growth of digital data far exceeds the capacity of current mainstream storage media. DNA is emerging as a promising alternative due to its higher storage density, longer retention time, and lower power consumption. To date, commercially mature DNA synthesis and sequencing technologies allow for writing and reading of information on DNA with customization and convenience at the research level. However, under the disconnected and nonspecialized mode, DNA data storage encounters practical challenges, including susceptibility to errors, long storage latency, resource-intensive requirements, and elevated information security risks. Herein, we introduce a platform named DNA-DISK that seamlessly streamlined DNA synthesis, storage, and sequencing on digital microfluidics coupled with a tabletop device for automated end-to-end information storage. The single-nucleotide enzymatic DNA synthesis with biocapping strategy is utilized, offering an ecofriendly and cost-effective approach for data writing. A DNA encapsulation using thermo-responsive agarose is developed for on-chip solidification, not only eliminating data clutter but also preventing DNA degradation. Pyrosequencing is employed for in situ and accurate data reading. As a proof of concept, DNA-DISK successfully stored and retrieved a musical sheet file (228 bits) with lower write-to-read latency (4.4 min of latency per bit) as well as superior automation compared to other platforms, demonstrating its potential to evolve into a DNA Hard Disk Drive in the future.
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ADN , Microfluídica , ADN/biosíntesis , Microfluídica/métodos , Microfluídica/instrumentación , Análisis de Secuencia de ADN/métodos , Almacenamiento y Recuperación de la Información/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodosRESUMEN
PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.
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The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3-/- (Shn3-/-) mice with augmented osteoblast activity, we show Shn3-/-mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3-/-mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome.
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Tejido Adiposo Blanco , Huesos , Dieta Alta en Grasa , Péptidos y Proteínas de Señalización Intercelular , Ratones Noqueados , Obesidad , Osteoblastos , Animales , Obesidad/metabolismo , Obesidad/genética , Obesidad/etiología , Tejido Adiposo Blanco/metabolismo , Osteoblastos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Dieta Alta en Grasa/efectos adversos , Huesos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Masculino , Tejido Adiposo Pardo/metabolismo , Ratones Endogámicos C57BL , Adipocitos/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.
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Insuficiencia Cardíaca , Modelos de Riesgos Proporcionales , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Femenino , Masculino , Anciano , Reproducibilidad de los Resultados , Pronóstico , Análisis de Supervivencia , Persona de Mediana Edad , Curva ROC , Algoritmos , Área Bajo la Curva , Bases de Datos Factuales , Aprendizaje Profundo , Índice de Severidad de la EnfermedadRESUMEN
Background: Aminoacylase 1 (ACY-1) has been found to be a tumor suppressor gene in neuroblastoma (NB). This study aimed to identify and verify the microRNAs (miRNAs) that may regulate ACY-1 through database prediction analysis, and verify the mutual regulatory effect of miRNA and ACY-1 in NB through cell experiments. Methods: The miRNAs that might bind ACY-1 were predicted and selected by TargetScan, miRTarBase and four other databases, the expression of the predicted miRNAs and ACY-1 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in four groups of clinical samples, and the differentially expressed miRNAs were screened. Then, luciferase vector was constructed according to the ACY-1 gene sequence to detect whether ACY-1 binds to the selected miRNA. Then, miR-1271-5p expression was silenced to detect miR-1271-5p function in the growth and migration of NB. Finally, ACY-1 and miR-1271-5p were silenced to change ACY-1 expression, and ACY-1 function in NB and the regulatory role of miR-1271-5p were explored. Results: ACY-1 was downregulated in NB, miR-1271-5p was upregulated in NB, and miR-1271-5p could be targeted to ACY-1. Silencing miR-1271-5p expression can reduce cell viability and inhibit tumor progression. After interfering with ACY-1 expression in cells, cell viability was enhanced, apoptosis was significantly decreased, and migration and invasion were enhanced. After partially restoring ACY-1 expression, the effect of si-ACY-1 on cells was weakened. In SK-N-SH and SH-SY-5Y cells, the miR-1271-5p inhibitor restored ACY-1 expression and improved ACY-1 function. Conclusions: MiR-1271-5p can promote the growth and migration of tumor cells by inhibiting ACY-1 expression in NB.
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In this issue of Cell Host & Microbe, Huang et al. determine that an oncogenic bacterium contributes to colorectal cancer progression and resistance to receptor tyrosine kinase inhibitors. These findings highlight the need for an integrative approach for cancer treatment that considers the influence of the microbiome.
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Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Microbiota/efectos de los fármacos , Inhibidores de Proteínas Quinasas/uso terapéutico , AnimalesRESUMEN
The improper storage of seeds can potentially compromise agricultural productivity, leading to reduced crop yields. Therefore, assessing seed viability before sowing is of paramount importance. Although numerous techniques exist for evaluating seed conditions, this research leveraged hyperspectral imaging (HSI) technology as an innovative, rapid, clean, and precise nondestructive testing method. The study aimed to determine the most effective classification model for watermelon seeds. Initially, purchased watermelon seeds were segregated into two groups: One underwent sterilization in a dehydrator machine at 40°C for 36 h, whereas the other batch was stored under favorable conditions. Watermelon seeds' spectral images were captured using an HSI with a charge-coupled device camera ranging from 400 to 1000 nm, and the segmented regions of all samples were measured. Preprocessing techniques and wavelength selection methods were applied to manage spectral data workload, followed by the implementation of a support vector machine (SVM) model. The initial hybrid-SVM model achieved a predictive accuracy rate of 100%, with a test set accuracy of 92.33%. Subsequently, an artificial bee colony (ABC) optimization was introduced to enhance model precision. The results indicated that, with kernel parameters (c, g) set at 13.17 and 0.01, respectively, and a runtime of 4.19328 s, the training and evaluation of the dataset achieved an accuracy rate of 100%. Hence, it was practical to utilize HSI technology combined with the PCA-ABC-SVM model to detect different watermelon seeds. As a result, these findings introduce a novel technique for accurately forecasting seed viability, intended for use in agricultural industrial multispectral imaging. PRACTICAL APPLICATION: The traditional methods for determining the condition of seeds primarily emphasize aesthetics, rely on subjective assessment, are time-consuming, and require a lot of labor. On the other hand, HSI technology as green technology was employed to alleviate the aforementioned problems. This work significantly contributes to the field of industrial multispectral imaging by enhancing the capacity to discern various types of seeds and agricultural crop products.
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Citrullus , Imágenes Hiperespectrales , Aprendizaje Automático , Semillas , Espectroscopía Infrarroja Corta , Citrullus/química , Semillas/química , Imágenes Hiperespectrales/métodos , Espectroscopía Infrarroja Corta/métodos , Máquina de Vectores de Soporte , AlgoritmosRESUMEN
OBJECTIVE: In this study, we investigated the efficacy of percutaneous poking reduction and Kirschner wire fixation in older children with irreducible supracondylar flexion-type fractures of the humerus. METHODS: This retrospective investigation included 27 children, comprising 15 males and 12 females, aged between 10 years and 3 months to 14 years and 11 months, all diagnosed with a flexion-type supracondylar fracture of the humerus within one week of trauma. All patients underwent surgery under general anesthesia. Following unsuccessful manual reduction, percutaneous poking reduction with Kirschner wires was performed under C-arm fluoroscopy to achieve fracture reduction. Following successful reduction, three 2.0 mm Kirschner wires were inserted in a cross pattern to secure the fracture ends. Postoperatively, the elbow joint was immobilized in a functional position with a plaster cast for four weeks. RESULTS: Follow-up in the outpatient department ranged from 9 to 36 months. Clinical functional assessment using Flynn's criteria rated 24 cases as excellent, 2 as good, and 1 as fair, yielding an overall efficacy of 96.3%. No cases of fracture re-displacement, fracture fragment necrosis, or other complications such as nonunion, iatrogenic nerve injury, myositis ossificans, or long-term elbow joint dysfunction were observed during the postoperative follow-up. CONCLUSION: The percutaneous poking reduction and Kirschner wire fixation technique is a simple and reliable procedure for treating irreducible flexion-type supracondylar fractures of the humerus in older children, with minimal trauma. This technique offers substantial stability for the fracture and results in excellent long-term recovery of joint function.
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Hilos Ortopédicos , Fracturas del Húmero , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Femenino , Masculino , Niño , Fracturas del Húmero/cirugía , Fracturas del Húmero/diagnóstico por imagen , Estudios Retrospectivos , Adolescente , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Fijación Interna de Fracturas/métodos , Rango del Movimiento Articular , Resultado del Tratamiento , Estudios de Seguimiento , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagenRESUMEN
Rapid identification of soybean seed varieties is crucial for agricultural production and seed quality. Identifying varieties of soybean seed using conventional chemical methods is time-consuming, destructive, and inappropriate for seed quality evaluation. This study utilized hyperspectral imaging technology (HSI) to identify four varieties of soybean seeds. The hyperspectral images of soybean seeds were collected in the spectral range of 400-1000 nm. A multi-level data fusion strategy based on spectral and image information was proposed to improve the accuracy of model. Subsequently, the multi-level data fusion strategy based on partial least squares discriminant analysis (PLS-DA) was used to establish the classification models of soybean seeds. Compared with the models using individual analytical sources, the results demonstrated that the models with multi-level data fusion strategy obtained better prediction performance. The high-level data fusion (HLDF) based on Bayesian consensus provided the optimal results with an accuracy (Acc) and F1-score of 93.13 % and 93.70 % in the prediction phase, respectively. Therefore, the multi-level data fusion strategy can be used as an identification method for soybean seed varieties and an effective approach to enhance the discriminatory capability of models.
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In thermoelectric, phase interface engineering proves effective in reducing the lattice thermal conductivity via interface scattering and amplifying the density-of-states effective mass by energy filtering. However, the indiscriminate introduction of phase interfaces inevitably leads to diminished carrier mobility. Moreover, relying on a singular energy barrier is insufficient for comprehensive filtration of low-energy carriers throughout the entire temperature range. Addressing these challenges, we advocate the establishment of a composite phase interface using atomic layer deposition (ALD) technology. This design aims to effectively decouple the interrelated thermoelectric parameters in ZrNiSn. The engineered coherent dual-interface energy barriers substantially enhance the density-of-states effective mass across the entire temperature spectrum while preser carrier mobility. Simultaneously, the strong interface scattering on phonons is crucial for curtailing lattice thermal conductivity. Consequently, a 40-cycles TiO2 coating on ZrNi1.03Sn0.99Sb0.01 achieves an unprecedented zT value of 1.3 at 873 K. These findings deepen the understanding of coherent composite-phase interface engineering.
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Diabetic kidney disease (DKD) is the primary cause of chronic kidney and end-stage renal disease. Glomerular podocyte loss and death are pathological hallmarks of DKD, and programmed cell death (PCD) in podocytes is crucial in DKD progression. PCD involves apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis. During DKD, PCD in podocytes is severely impacted and primarily characterized by accelerated podocyte apoptosis and suppressed autophagy. These changes lead to a gradual decrease in podocyte numbers, impairing the glomerular filtration barrier function and accelerating DKD progression. However, research on the interactions between the different types of PCD in podocytes is lacking. This review focuses on the novel roles and mechanisms of PCD in the podocytes of patients with DKD. Additionally, we summarize clinical drugs capable of regulating podocyte PCD, present challenges and prospects faced in developing drugs related to podocyte PCD and suggest that future research should further explore the detailed mechanisms of podocyte PCD and interactions among different types of PCD.
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Apoptosis , Nefropatías Diabéticas , Podocitos , Podocitos/patología , Podocitos/metabolismo , Humanos , Nefropatías Diabéticas/patología , Nefropatías Diabéticas/metabolismo , Animales , Autofagia/fisiologíaRESUMEN
The posterolateral tibial plateau is crucial for maintaining knee stability during flexion, and fractures in this area often involve ligament and meniscus injuries, necessitating effective management. However, treating posterolateral tibial plateau fractures (PLF) poses significant challenges due to the complex anatomy. Therefore, this review aims to explore contemporary concepts of PLF, from identification to fixation, and proposes a comprehensive treatment strategy. In this article, the authors detail the injury mechanisms, fracture morphology, PLF classification systems, surgical approaches, and techniques for open reduction and internal fixation (ORIF) as well as arthroscopic-assisted internal fixation (ARIF). The findings indicate that PLF is typically caused by flexion-valgus forces, resulting in depression or split-depression patterns. For isolated PLF, the supra-fibular head approach is often preferable, whereas posterior approaches are more suitable for combined fractures. Additionally, innovative plates, particularly the horizontal belt plate, have shown satisfactory outcomes in treating PLF. Currently, the 'bicondylar four-quadrant' concept is widely used for assessing and managing the tibial plateau fractures involving PLF, forming the cornerstone of the comprehensive treatment strategy. Despite challenges in surgical exposure and implant placement, ORIF remains the mainstream treatment for PLF, benefiting significantly from the supra-fibular head approach and the horizontal belt plate. Furthermore, ARIF has proven effective by providing enhanced visualization and surgical precision in managing PLF, emerging as a promising technique.
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Introduction: Several studies of MADS-box transcription factors in flowering plants have been conducted, and these studies have indicated that they have conserved functions in floral organ development; MIKC-type MADS-box genes has been proved to be expanded in ferns, however, few systematic studies of these transcription factors have been conducted in non-seed plants. Although ferns and seed plants are sister groups, they exhibit substantial morphological differences. Methods: Here, we clarified the evolution of MADS-box genes across 71 extant fern species using available transcriptome, genome, and gene expression data. Results: We obtained a total of 2,512 MADS-box sequences, ranging from 9 to 89 per species. The most recent common ancestor (MRCA) of ferns contained approximately three type I genes and at least 5-6 type II MADS-box genes. The domains, motifs, expression of type I and type II proteins, and the structure of the both type genes were conserved in ferns as to other land plants. Within type II genes, MIKC*-type proteins are involved in gametophyte development in ferns; MIKCC-type proteins have broader expression patterns in ferns than in seed plants, and these protein sequences are likely conserved in extant seed plants and ferns because of their diverse roles in diploid sporophyte development. More than 90% of MADS-box genes are type II genes, and MIKCC genes, especially CRM1 and CRM6-like genes, have undergone a large expansion in leptosporangiate ferns; the diverse expression patterns of these genes might be related to the fuctional diversification and increased complexity of the plant body plan. Tandem duplication of CRM1 and CRM6-like genes has contributed to the expansion of MIKCC genes. Conclusion or Discussion: This study provides new insights into the diversity, evolution, and functions of MADS-box genes in extant ferns.
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This study aims to explore the link between retinal vein occlusion (RVO), a blinding ocular condition, and alterations in gut microbiota composition, to offer insights into the pathogenesis of RVO. Fecal samples from 25 RVO patients and 11 non-RVO individuals were analyzed using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). Significant differences in the abundance of gut microbial species were noted between RVO and non-RVO groups. At the phylum level, the RVO group showed an elevation in the ratio of Firmicutes to Bacteroidetes. At the genus level, the RVO group showed higher abundance in Escherichia_Shigella (P < 0.05) and less abundance in Parabacteroides (P < 0.01) than the non-RVO group. Functional predictions indicated reduced folate synthesis, biotin metabolism, and oxidative phosphorylation, with an increase in butyric acid metabolism in the RVO group. LC-MS analysis showed significant differences in purine metabolism, ABC transporters, and naphthalene degradation pathways, especially purine metabolism. Pearson correlation analysis revealed significant associations between bacterial genera and fecal metabolites. Enrichment analysis highlighted connections between specific metabolites and bacterial genera. The findings showed that the dysregulation of gut microbiota was observed in RVO patients, suggesting the gut microbiota as a potential therapeutic target. Modulating the gut microbiota could be a novel strategy for managing RVO and improving patient outcomes. Furthermore, the study findings suggest the involvement of gut microbial dysbiosis in RVO development, underscoring the significance of understanding its pathogenesis for effective treatment development. IMPORTANCE: Retinal vein occlusion (RVO) is a blinding ocular condition, and understanding its pathogenesis is crucial for developing effective treatments. This study demonstrates significant differences in gut microbiota composition between RVO patients and non-RVO individuals, implicating the involvement of gut microbial dysbiosis in RVO development. Functional predictions and metabolic profiling provide insights into the underlying mechanisms, highlighting potential pathways for therapeutic intervention. These findings suggest that modulating the gut microbiota might be a promising strategy for managing RVO and improving patient outcomes.
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Bacterias , Heces , Microbioma Gastrointestinal , Metabolómica , ARN Ribosómico 16S , Oclusión de la Vena Retiniana , Humanos , Oclusión de la Vena Retiniana/metabolismo , Oclusión de la Vena Retiniana/microbiología , Heces/microbiología , Masculino , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Persona de Mediana Edad , Femenino , ARN Ribosómico 16S/genética , Anciano , Adulto , Cromatografía LiquidaRESUMEN
It has been shown that the formation of filopodia is a key step in tumor cell metastasis, but there is limited research regarding its mechanism. In this study, we demonstrated that fatty acid synthase (FASN) promoted filopodia formation in liver cancer cells by regulating fascin actin-bundling protein 1 (FSCN1), a marker protein for filopodia. Mechanistically, on the one hand, the accumulation of FASN is caused by the enhanced deubiquitination of FASN mediated by UCHL5 (ubiquitin c-terminal hydrolase L5). In this pathway, low expression of SIAH1 (Seven in absentia homolog 1) can decrease the ubiquitination and degradation of ADRM1 (adhesion regulating molecule 1) thereby increasing its protein level, which will recruit and activate the deubiquitination enzyme UCHL5, leading to FASN undergo deubiquitination and escape from proteasomal degradation. On the other hand, the accumulation of FASN is related to its weakened ubiquitination, where SIAH1 directly acts as a ubiquitin ligase toward FASN, and low expression of SIAH1 reduces the ubiquitination and degradation of FASN. Both the two pathways are involved in the regulation of FASN in liver cancer. Our results reveal a novel mechanism for FASN accumulation due to the low expression of SIAH1 in human liver cancer and suggest an important role of FASN in filopodia formation in liver cancer cells.
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Neoplasias Hepáticas , Proteínas de Microfilamentos , Proteínas Nucleares , Seudópodos , Ubiquitina-Proteína Ligasas , Ubiquitinación , Humanos , Seudópodos/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Animales , Línea Celular Tumoral , Ratones Desnudos , Acido Graso Sintasa Tipo I/metabolismo , Acido Graso Sintasa Tipo I/genética , Células Hep G2 , RatonesRESUMEN
At present, a clear dependency of the dynamics upon temperature and pH has not been established for many heavy metals (HMs), so making it difficult to project and quantify the impact of ocean warming and acidification on metal biogeochemistry in future scenarios. To understand the responses of HMs to future ocean warming and acidification, we estimated the spatial-temporal variations and pollution status of six dissolved HMs (i.e., Cu, Zn, Pb, Cd, Hg, and As) in surface seawater throughout the Bohai Sea during 2012-2014. The results showed that the average concentrations of Cu, Zn, Pb, Cd, Hg, and As in seawater of the Bohai Sea were between 2.01-3.18, 10.47-15.58, 0.85-2.31, 0.25-0.55, 0.05-0.13, and 1.24-1.98 µg L-1, respectively. Spatially, the average concentrations of the studied HMs generally decreased from the three bays towards the central area, except for Hg which was relatively high in the central Bohai Sea in some cases. This implied that, in addition to continental inputs, there may be other processes affecting the distribution pattern of Hg, such as cyclonic or anticyclonic gyres, benthic fluxes between surface and bottom layers, and some marine planktonic and microbial activities. The pollution assessments of six HMs in seawater revealed that the major risk pollutants were Pb and Hg across the Bohai Sea. Analyses of the local and interactive effects of temperature and pH on HMs showed that the interactive effect of changing temperature and pH on HMs is much more complex than a direct temperature/pH relationship with HMs. Altogether, the results suggested that future ocean warming and acidification will significantly influence the concentrations of dissolved HMs in seawater of the Bohai Sea, but with different relationships.
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This study explored the feasibility of employing hyperspectral imaging (HSI) technology to quantitatively assess the effect of silicon (Si) on lead (Pb) content in oilseed rape leaves. Aiming at the defects of hyperspectral data with high dimension and redundant information, this paper proposed two improved feature wavelength extraction algorithms, repetitive interval combination optimization (RICO) and interval combination optimization (ICO) combined with stepwise regression (ICO-SR). The entire oilseed rape leaves were taken as the region of interest (ROI) to extract the visible near-infrared hyperspectral data within the 400.89-1002.19 nm range. In data processing, Savitzky-Golay (SG) smoothing, detrending (DT), and multiple scatter correction (MSC) were utilized for spectral data preprocessing, while recursive feature elimination (RFE), iteratively variable subset optimization (IVSO), ICO, and the two enhanced algorithms were employed to identify characteristic wavelengths. Subsequently, based on the spectral data of preprocessing and feature extraction, partial least squares regression (PLSR) and support vector regression (SVR) methods were used to construct various Pb content prediction models in oilseed rape leaves, with a comparison and analysis of each model performance. The results indicated that the two improved algorithms were more efficient in extracting representative spectral information than conventional methods, and the performance of SVR models was better than PLSR models. Finally, to further improve the prediction accuracy and robustness of the SVR models, the whale optimization algorithm (WOA) was introduced to optimize their parameters. The findings demonstrated that the MSC-RICO-WOA-SVR model achieved the best comprehensive performance, with Rp2 of 0.9436, RMSEP of 0.0501 mg/kg, and RPD of 3.4651. The results further confirmed the great potential of HSI combined with feature extraction algorithms to evaluate the effectiveness of Si in alleviating Pb stress in oilseed rape and provided a theoretical basis for determining the appropriate amount of Si application to alleviate Pb pollution in oilseed rape.