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BACKGROUND: Patients with severe community-acquired pneumonia (sCAP) admitted to the intensive care unit (ICU) often exhibit muscle catabolism, muscle weakness, and/or atrophy, all related to an increased morbidity and mortality. However, the relationship between thoracic skeletal muscle mass and sCAP-related mortality has not been well-studied. Early recognition of sarcopenia in ICU patients with sCAP would benefit their prognosis. METHODS: A retrospective study was conducted in Taizhou Hospital of Zhejiang Province, involving 101 patients with sCAP admitted in the ICU between December 2022 and February 2023. We measured the cross-sectional aera of the pectoralis, intercostal, paraspinal, serratus, and latissimus muscles at the T4 vertebral level (T4CSA) using chest computed tomography. Discriminatory thresholds were established by performing receiver operating characteristic curve analysis, with a designated cutoff value of 96.75 cm2 for male patients. This cohort was classified into mortality and survival groups based on a 6-month post-admission outcome. Univariate and multifactorial logistic regression analyses were performed to validate the correlation between low thoracic skeletal muscle area and prognostic outcomes. RESULTS: The mean age of the patients was 75.39 ± 12.09 years, with an overall 6-month mortality of 73.27%. T4CSA of the 6-month survival group was significantly larger than that in the mortality group for overall cohort. The T4CSA in the survival group was significantly larger than that in the mortality group (104.29 ± 23.98cm2 vs. 87.44 ± 23.0cm2, p = 0.008). T4CSA predicted the 6-month mortality from sCAP in males with an AUC of 0.722 (95% confidence interval (CI), 0.582-0.861). The specificity and sensitivity were 71.4% and 71.1%, respectively, (p < 0.05). No significant difference was observed between the two groups in terms of T4CSA. CONCLUSIONS: This study revealed that low thoracic skeletal muscle mass increased the risk of all-cause 6-month mortality in ICU patients with sCAP, particularly among male patients.
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Infecções Comunitárias Adquiridas , Unidades de Terapia Intensiva , Músculo Esquelético , Pneumonia , Sarcopenia , Humanos , Masculino , Infecções Comunitárias Adquiridas/mortalidade , Idoso , Estudos Retrospectivos , Unidades de Terapia Intensiva/estatística & dados numéricos , Sarcopenia/mortalidade , Sarcopenia/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Fatores de Risco , Idoso de 80 Anos ou mais , Pneumonia/mortalidade , Tomografia Computadorizada por Raios X , China/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Curva ROCRESUMO
Phosphorus (P) plays a crucial role in plant growth, which can provide nutrients for plants. Nonetheless, excessive phosphate can cause eutrophication of water, deterioration of aquatic environment, and even harm for human health. Therefore, adopting feasible adsorption technology to remove phosphate from water is necessary. Biochar (BC) has received wide attention for its low cost and environment-friendly properties. However, undeveloped pore structure and limited surface groups of primary BC result in poor uptake performance. Consequently, this work introduced the synthesis of pristine BC, parameters influencing phosphate removal, and corresponding mechanisms. Moreover, multifarious metal-doped BCs were summarized with related design principles. Meanwhile, mechanisms of selective phosphate adsorption by metal-doped BC were investigated deeply, and the recovery of phosphate from water, and the utilization of phosphate-loaded adsorbents in soil were critically presented. Finally, challenges and prospects for widespread applications of selective phosphate adsorption were proposed in the future.
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Carvão Vegetal , Fosfatos , Poluentes Químicos da Água , Purificação da Água , Carvão Vegetal/química , Fosfatos/química , Adsorção , Purificação da Água/métodos , Metais/química , Água/química , ReciclagemRESUMO
Development of luminescent segmented heterostructures featuring multiple spatial-responsive blocks is important to achieve miniaturized photonic barcodes toward anti-counterfeit applications. Unfortunately, dynamic manipulation of the spatial color at micro/nanoscale still remains a formidable challenge. Here, a straightforward strategy is proposed to construct spatially varied heterostructures through amplifying the conformation-driven response in flexible lanthanide-metal-organic frameworks (Ln-MOFs), where the thermally induced minor conformational changes in organic donors dramatically modulate the photoluminescence of Ln acceptors. Notably, compositionally and structurally distinct heterostructures (1D and 2D) are further constructed through epitaxial growth of multiple responsive MOF blocks benefiting from the isomorphous Ln-MOF structures. The thermally controlled emissive colors with distinguishable spectra carry the fingerprint information of a specific heterostructure, thus allowing for the effective construction of smart photonic barcodes with spatially responsive characteristics. The results will deepen the understanding of the conformation-driven responsive mechanism and also provide guidance to fabricate complex stimuli-responsive hierarchical microstructures for advanced optical recording and high-security labels.
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Introduction: To assess the performance of the European Thyroid Association Thyroid Imaging and Reporting Data System (EU-TIRADS) and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), which combine risk stratification systems for thyroid nodules (TN-RSS) and cervical lymph nodes (LN-RSS) in diagnosing malignant and metastatic thyroid cancer in a single referral center. Methods: We retrospectively analyzed 2,055 consecutive patients who underwent thyroidectomy or fine-needle aspiration (FNA) from January 2021 to December 2022. TNs and LNs were categorized according to the ultrasonography (US) features of EU-TIRADS and K-TIRADS, respectively. The diagnostic performance and postponed malignancy rate (PMR) were compared with those of EU-TIRADS and K-TIRADS. PMR was defined as the number of patients with malignant nodules not recommended for biopsy among patients with cervical LN metastasis. Results: According to the EU-TIRADS and K-TIRADS, for TN-RSS alone, there were no significant differences in sensitivity, specificity, accuracy, unnecessary FNA rate (UFR), missed malignancy rate (MMR), and PMR between the two TIRADSs (29.0% vs. 28.8%, 50.5% vs. 51.1%, 32.3% vs. 32.2%, 23.6% vs. 23.5%, 88.6% vs. 88.5%, and 54.2% vs. 54.5%, P > 0.05 for all). Combining the LN-RSS increased the diagnostic accuracy (42.7% vs. 32.3% in EU-TIRADS; 38.8% vs. 32.2% in K-TIRADS) and decreased the PMR (54.2% vs. 33.9% in EU-TIRADS; 54.5% vs. 39.3% in K-TIRADS). EU-TIRADS had higher sensitivity and accuracy and lower PMR than K-TIRADS (41.3% vs. 36.7%, 42.7% vs. 38.8%,33.9% vs. 39.3%, P < 0.05 for all). Conclusions: A combination of TN-RSS and LN-RSS for the management of thyroid nodules may be associated with a reduction in PMR, with enhanced sensitivity and accuracy for thyroid cancers in EU-TIRADS and K-TIRADS. These results may offer a new direction for the detection of aggressive thyroid cancers.
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Mutations in the transcription factors encoded by PHOX2B or LBX1 correlate with congenital central hypoventilation disorders. These conditions are typically characterized by pronounced hypoventilation, central apnea, and diminished chemoreflexes, particularly to abnormally high levels of arterial PCO2. The dysfunctional neurons causing these respiratory disorders are largely unknown. Here, we show that distinct, and previously undescribed, sets of medullary neurons coexpressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in congenital hypoventilation. By combining intersectional chemogenetics, intersectional labeling, lineage tracing, and conditional mutagenesis, we uncovered subgroups of dB2 neurons with key functions in (i) respiratory tidal volumes, (ii) the hypercarbic reflex, (iii) neonatal respiratory stability, and (iv) neonatal survival. These data provide functional evidence for the critical role of distinct medullary dB2 neurons in neonatal respiratory physiology. In summary, our work identifies distinct subgroups of dB2 neurons regulating breathing homeostasis, dysfunction of which causes respiratory phenotypes associated with congenital hypoventilation.
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Proteínas de Homeodomínio , Hipoventilação , Bulbo , Neurônios , Fatores de Transcrição , Hipoventilação/congênito , Hipoventilação/genética , Animais , Neurônios/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Bulbo/metabolismo , Apneia do Sono Tipo Central/genética , Fenótipo , HumanosRESUMO
BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.
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Citoesqueleto de Actina , Etanol , Hipocampo , Microtúbulos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Masculino , Etanol/farmacologia , Etanol/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Depressores do Sistema Nervoso Central/farmacologia , Depressores do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacosRESUMO
BACKGROUND: Acute kidney injury (AKI) is a common complication in patients admitted to intensive care unit (ICU) and mortality rates for this condition are high. To reduce the high incidence of short-term mortality, reliable prognostic indicators are required to facilitate early diagnosis and treatment of AKI. We assessed the ability of plasma proenkephalin (pPENK) and plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict 28-day mortality in AKI patients in intensive care. METHODS: This prospective study, carried out between January 2019 and December 2019, comprised 150 patients (100 male) diagnosed with AKI after excluding 20 patients discharged within 24 h and those with missing hospitalization data. Blood samples were collected to determine admission p-PENK and p-NGAL levels. The study outcome was 28day mortality. RESULTS: The mean patient age was 68 years (female, 33%). The average PPENK and pNGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. PPENK levels >0.36 ng/µL and pNGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28day mortality for patients with AKI (adjusted hazard ratios 0.785 [95% confidence interval 0.706-0.865, P<0.001] and 0.700 [95% confidence interval 0.611-0.789, P<0.001], respectively). This association was significant for mortality in patients in intensive care with AKI. Baseline p-PENK (0.36 ng/µL) and p-NGAL (230.30 ng/mL) levels and their respective cut-off values showed clinical value in predicting 28-day mortality. CONCLUSION: Serum PENK and NGAL levels, when used in conjunction, improved the accuracy of predicting 28-day mortality in patients with AKI while retaining sensitivity and specificity.
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Injúria Renal Aguda , Biomarcadores , Encefalinas , Unidades de Terapia Intensiva , Lipocalina-2 , Humanos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/diagnóstico , Masculino , Feminino , Lipocalina-2/sangue , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Encefalinas/sangue , Biomarcadores/sangue , Precursores de Proteínas/sangue , Prognóstico , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Mortalidade HospitalarRESUMO
Microcystin-leucine arginine (MC-LR) is a common cyantotoxin produced by hazardous cyanobacterial blooms, and eutrophication is increasing the contamination level of MC-LR in drinking water supplies and aquatic foods. MC-LR has been linked to colorectal cancer (CRC) progression associated with tumor microenvironment, however, the underlying mechanism is not clearly understood. In present study, by using GEO, KEGG, GESA and ImmPort database, MC-LR related differentially expressed genes (DEGs) and pathway- and gene set-enrichment analysis were performed. Of the three identified DEGs (CXCL1, GUCA2A and GDF15), CXCL1 was shown a positive association with tumor infiltration, and was validated to have a dominantly higher upregulation in MC-LR-treated tumor-associated macrophages (TAMs) rather than in MC-LR-treated CRC cells. Both CRC cell/macrophage co-culture and xenograft mouse models indicated that MC-LR stimulated TAMs to secrete CXCL1 resulting in promoted proliferation, migration, and invasion capability of CRC cells. Furtherly, IP-MS assay found that interaction between TAMs-derived CXCL1 and CRC cell-derived IGHG1 may enhance CRC cell proliferation and migration after MC-LR treatment, and this effect can be attenuated by silencing IGHG1 in CRC cell. In addition, molecular docking analysis, co-immunoprecipitation and immunofluorescence further proved the interactions between CXCL1 and IGHG1. In conclusion, CXCL1 secreted by TAMs can trigger IGHG1 expression in CRC cells, which provides a new clue in elucidating the mechanism of MC-LR-mediated CRC progression.
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Quimiocina CXCL1 , Neoplasias Colorretais , Transdução de Sinais , Macrófagos Associados a Tumor , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Humanos , Animais , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Camundongos , Macrófagos Associados a Tumor/metabolismo , Microcistinas/toxicidade , Toxinas Marinhas , Linhagem Celular Tumoral , Progressão da Doença , Proliferação de Células/efeitos dos fármacos , Microambiente TumoralRESUMO
Memory about food and eating is crucial in regulating appetite and eating behaviors. Successfully stopping vivid imagination of delicious food could help reduce food craving and thus reduce the possibility of further intake. Memory inhibition is a cognitive process that involves intentional suppression of certain memories coming to consciousness. Successful memory suppression derives from inhibitory control. Although considerable work has consistently observed the impairment in motor or response inhibitory control among individuals with obesity, there has been a lack of investigation into the influence of bodyweight status on memory inhibitory control. To fill this gap, current study investigated behavioral and neurophysiological correlates of memory suppression in young women. Using Think/No-Think task and event-related potentials among 47 females, we found that participants with higher visceral adipose tissue (VAT) showed a tendency towards decreased suppression ability for memories related to food but not memories related to nonfood items. In depth analysis showed that decrease in the differences in P2 amplitudes between suppression vs. retrieval of food-related memories mediated the impairment of suppression ability by high VAT. We then tested whether individual differences in memory suppression ability as well as ERP correlates predicted future BMI or VAT change over 1-year follow-up. Results showed that P2 amplitudes when retrieving food-related memory could predict VAT change at 1-year follow-up among participants with healthy BMI. These observations suggest a hypersensitivity inference hypothesis underlying memory control impairments. To be specific, deficits in memory suppression may be in part resulted from elevated sensitivity to the cues coupling with food-related memory. It extends previous studies of memory suppression with food rewards and provides the first evidence to help understand the relationship between inhibitory control on food-related memory and obesity.
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Microcystin-LR (MC-LR) affects bone health in adult mice via osteo-immunomodulation. However, its effect on osteoblasts and bone development is unclear. This study investigated the effect of MC-LR on bone osteoimmune and osteoblasts in the developing period. 18 Four-week-old male Sprague Dawley rats were divided into two groups (n = 9 per group) and exposed to 0 (control) and 1 µg/kg b.w. MC-LR (exposure) by intraperitoneal injection for four weeks. The heart blood was collected for serological examination, and the femur for morphological, histopathological, and biomechanical analysis. MC-LR exposure significantly weakened bone microstructures (bone volume, bone volume/total volume, bone trabecular number, connectivity density) and biomechanics (maximum loads and maximum deflection) (P < 0.05). Besides, MC-LR decreased serum procollagen type Ð car-boxy-terminal propeptide, osteocalcin, bone morphogenetic protein-2, osteoprotegerin, and receptor activator of nuclear factor κB ligand, while elevating osteoclasts number, matrix metalloproteinase-9, ß-catenin, Runt-related transcription factor 2, and osterix in bone, and bone alkaline phosphate, C-terminal cross-linked telopeptide of type-I collagen, tartrate-resistant acid phosphatase-5b in serum (P < 0.05). Moreover, MC-LR increased CD4+ T-cells, CD4+/CD8+, M1 and M2 macrophages, and cells apoptosis in the bone marrow, interleukin-6, interleukin-17, and tumor necrosis factor-α in serum, decreased serum interleukin-10 (P < 0.05). Overall, MC-LR can promote bone resorption by activating osteoclasts via osteoimmunology, which may involve macrophages besides lymphocytes. MC-LR may inhibit bone formation by stopping the osteoblasts at an immature stage. Thus, MC-LR weakened bone microstructure and biomechanics in developing period. Its risk on bone development needs further study.
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Microcistinas , Osteogênese , Ratos , Camundongos , Masculino , Animais , Leucina , Microcistinas/toxicidade , Arginina , Fenômenos Biomecânicos , Ratos Sprague-Dawley , OsteoblastosRESUMO
To achieve high spatial resolution of reconstructed images in positron emission tomography (PET), the size of the scintillation crystal element is set small in current PET systems, which greatly increases the inter-crystal scattering (ICS) frequency. The ICS is a type of Compton scattering of the gamma photons from one crystal element to its neighborhood element, which obscures the determination of the first interaction position. In this study, we propose a 1D U-Net convolutional neural network to predict the first interaction position, which provides a universal way to efficiently solve the ICS recovery problem. The network is trained using the dataset collected from the GATE Monte Carlo simulation. The 1D U-Net structure is applied due to its capability of synthesizing both low-level and high-level information, which shows superiority in solving the ICS recovery problem. After being well trained, the 1D U-Net can generate a prediction accuracy of 78.1%. Compared to the coincidence events only composed from two photoelectric gamma photons, the sensitivity is improved by 149%. The contrast-to-noise ratio of the reconstructed contrast phantom increases from 6.973 to 10.795 for the 16 mm hot sphere. Compared to the take-energy-centroid method, the spatial resolution of the reconstructed resolution phantom can obtain the best improvement of 33.46%. Compared with the previous deep learning method based on the fully connected network, the proposed 1D U-Net can work more stably with considerably fewer network parameters. The 1D U-Net network model shows good universality when predicting different phantoms, and the computation speed is fast.
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Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Simulação por Computador , Fótons , Método de Monte Carlo , Imagens de FantasmasRESUMO
Objective.Positron emission tomography (PET) is a functional imaging widely used in various applications such as tumour detection. PET image reconstruction is an ill-posed inverse problem, and the model-based iterative reconstruction methods commonly used in clinical practice have disadvantages such as long time consumption and low signal-to-noise ratio, especially at low doses.Approach.In this study, we propose a deep learning-based reconstruction method that is capable of reconstructing images directly from low-count sinograms. Our network consists of two parts, a truncated inverse radon layer for implementing domain transform and a U-shaped network for image enhancement.Main result.We validated our method on both simulation data and real data. Compared to ordered subset expectation maximization with a post-Guassian filter, the structural similarity can be improved from 0.9357 to 0.9613 and the peak signal-to-noise ratio can be improved by 5 dB.Significance.The proposed method can directly convert low-count sinograms into PET images, while obtaining improved image quality and having less time consumption than iterative reconstruction algorithms and the state-of-the-art convolutional neural network.
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Processamento de Imagem Assistida por Computador , Tomografia por Emissão de Pósitrons , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Algoritmos , Redes Neurais de Computação , Tomografia Computadorizada por Raios X/métodos , Imagens de FantasmasRESUMO
As a typical environmental endocrine disrupting chemical (EDC), di-(2-ethylhexyl) phthalate (DEHP) is thought to be related to reproductive disorders, especially in males. Growing evidence suggests that various EDCs may result in an impaired telomere structure and function, which is associated with male infertility. However, the adverse effect of DEHP on telomeres in male reproductive cells has rarely been studied, and the related mechanisms remain unclear. In this study, we tested the effects of mono-(2-ethylhexyl) phthalate (MEHP), the primary metabolite of DEHP, on telomere dysfunction in mouse spermatogonia-derived cells (GC-1) and the potential role of TERT and c-Myc in MEHP-induced spermatogenic cell damage. Results showed that MEHP induced cell viability inhibition, G0/G1 phase cell cycle arrest, and apoptosis in GC-1 cells in a dose-dependent manner. Shortened telomeres, reduced telomerase activity, and decreased expression of TERT, c-Myc, and upstream transcription factors of c-Myc were also observed in the MEHP-treated cells. In conclusion, it can be concluded that TERT-mediated telomere dysfunction may contribute to MEHP-induced G0/G1 phase cell cycle arrest and apoptosis in GC-1 cells through the impairment of c-Myc and its upstream transcription factors.
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Background: The aim of this study was to explore the diagnostic and therapeutic performances of the artificial intelligence (AI), American College of Radiology (ACR), and Kwak Thyroid Imaging Reporting and Data Systems (TIRADSs) using the size thresholds for fine needle aspiration (FNA) and follow-up defined in the ACR TIRADS. Methods: This retrospective study included 3,833 consecutive thyroid nodules identified in 2,590 patients from January 2010 to August 2017. Ultrasound (US) features were reviewed using the 2017 white paper of the ACR TIRADS. US categories were assigned according to the ACR/AI and Kwak TIRADS. We applied the thresholds for FNA and follow-up defined in the ACR TIRADS to the Kwak TIRADS. The diagnostic and therapeutic performances were calculated and compared using the McNemar or DeLong methods. Results: The AI TIRADS had higher specificity, accuracy, and area under the curve (AUC) than did the ACR and Kwak TIRADS (specificity: 64.6% vs. 57.4% and 52.69%; accuracy: 78.5% vs. 75.4% and 73.0%; AUC: 88.2% vs. 86.6% and 86.0%; all P values <0.05). Meanwhile, the AI TIRADS had a lower FNA rate (FNAR), unnecessary FNA rate (UFR), and follow-up rate (FUR) than did the ACR and Kwak TIRADS using the size thresholds of the ACR TIRADS (specificity: 30.9% vs. 34.4% and 36.9%; accuracy: 41.1% vs. 47.8% and 48.7%; AUC: 34.2% vs. 37.7% and 41.0%; all P values <0.05). In addition, the Kwak TIRADS incorporating the size thresholds of the ACR TIRADS was almost similar to the ACR TIRADS in diagnostic and therapeutical performance. Conclusions: The ACR TIRADS can be simplified, which potentially enhances its diagnostic and therapeutic performance. The method of score-based TIRADS (counting in the Kwak TIRADS and weighting in the ACR and AI TIRADS) might not determine the diagnostic and therapeutic performances of the TIRADS. Thus, we propose choosing a straightforward and practical TIRADS in daily practice.
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The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three-layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons.
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Cerebelo , Neurônios , Animais , Humanos , Cerebelo/anatomia & histologia , Cerebelo/citologia , Cerebelo/embriologia , Biologia do Desenvolvimento , Neurônios GABAérgicos/citologia , Homeostase , Neurônios/classificação , Neurônios/citologia , Neurônios/metabolismo , Neurociências , Análise de Célula ÚnicaRESUMO
Breathing (or respiration) is an unconscious and complex motor behavior which neuronal drive emerges from the brainstem. In simplistic terms, respiratory motor activity comprises two phases, inspiration (uptake of oxygen, O2) and expiration (release of carbon dioxide, CO2). Breathing is not rigid, but instead highly adaptable to external and internal physiological demands of the organism. The neurons that generate, monitor, and adjust breathing patterns locate to two major brainstem structures, the pons and medulla oblongata. Extensive research over the last three decades has begun to identify the developmental origins of most brainstem neurons that control different aspects of breathing. This research has also elucidated the transcriptional control that secures the specification of brainstem respiratory neurons. In this review, we aim to summarize our current knowledge on the transcriptional regulation that operates during the specification of respiratory neurons, and we will highlight the cell lineages that contribute to the central respiratory circuit. Lastly, we will discuss on genetic disturbances altering transcription factor regulation and their impact in hypoventilation disorders in humans.
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Gut microbiota plays a critical role in the healthy growth and development of young animals. However, there are few studies on the gut microbiota of young Hainan black goats. In this study, 12 three-month-old weaned lambs with the same birth date were selected and divided into the high body weight group (HW) and low body weight group (LW). The microbial diversity, composition, and predicted function in the feces of HW and LW groups were analyzed by collecting fecal samples and sequencing the 16S rRNA V3-V4 region. The results indicated that the HW group exhibited higher community diversity compared with the LW group, based on the Shannon index. The core phyla of the HW and LW groups were both Firmicutes and Bacteroidetes. Parabacteroides, UCG-005, and Bacteroides are the core genera of the HW group, and Bacteroides, Escherichia-Shigella, and Akkermansia are the core genera of the LW group. In addition, genera such as Ruminococcus and Anaerotruncus, which were positively correlated with body weight, were enriched in the HW group; those genera, such as Akkermansia and Christensenellaceae, which were negatively correlated with body weight, were enriched in the LW group. Differential analysis of the KEGG pathway showed that Amino Acid Metabolism, Energy Metabolism, Carbohydrate Metabolism, and Nucleotide Metabolism were enriched in the HW group, while Cellular Processes and Signaling, Lipid Metabolism, and Glycan Biosynthesis and Metabolism were enriched in the LW group. The results of this study revealed the gut microbial characteristics of Hainan black goats with different body weights at weaning age and identified the dominant flora that contributed to their growth.
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Cattle are raised around the world and are frequently exposed to heat stress, whether in tropical countries or in regions with temperate climates. It is universally acknowledged that compared to those in temperate areas, the cattle breeds developed in tropical and subtropical areas have better heat tolerance. However, the underlying mechanism of heat tolerance has not been fully studied, especially from the perspective of intestinal microbiomics. The present study collected fecal samples of cattle from four representative climatic regions of China, namely, the mesotemperate (HLJ), warm temperate (SD), subtropical (HK), and tropical (SS) regions. Then, the feces were analyzed using high-throughput 16S rRNA sequencing. The results showed that with increasing climatic temperature from HLJ to SS, the abundance of Firmicutes increased, accompanied by an increasing Firmicutes to Bacteroidota ratio. Proteobacteria showed a trend of reduction from HLJ to SS. Patescibacteria, Chloroflexi, and Actinobacteriota were particularly highest in SS for adapting to the tropical environment. The microbial phenotype in the tropics was characterized by an increase in Gram-positive bacteria and a decrease in Gram-negative bacteria, aerobic bacteria, and the forming of_biofilms. Consistently, the functional abundances of organismal systems and metabolism were decreased to reduce the material and energy demands in a hot environment. Genetic information processing and information storage and processing may be how gut flora deals with hot conditions. The present study revealed the differences in the structure and function of gut microbes of cattle from mesotemperate to tropical climates and provided an important reference for future research on the mechanism of heat tolerance regulated by the gut microbiota and a potential microbiota-based target to alleviate heat stress.
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Microcystin-LR (MC-LR) exists widely in polluted food and water in humid and warm areas, and facilitates the progression of colorectal cancer (CRC). However, the molecular mechanism associated with the MC-LR-induced CRC progression remains elusive. The purpose of this study is to explore the role of the hub genes associated with MC-LR-induced CRC development at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. By utilizing R, we screened and investigated the differentially expressed genes (DEGs) between the MC-LR and the control groups with the GEO, in which, HOXB4 highly expressed in MC-LR-treated group was identified and further explored as a hub gene. With the aid of TCGA, GEPIA, HPA, UALCAN, Cistrome, and TIMER, the increased mRNA and protein levels of HOXB4 in CRC tissue were found to be positively associated with high tumor stage and poor prognosis, and were linked to immune infiltration, especially tumor-associated macrophages and cancer-associated fibroblasts. Cox regression analysis and nomogram prediction model indicated that high HOXB4 expression was correlated to poor survival probability. To elucidate the mechanism of high HOXB4 expression induced by MC-LR, we overlapped the genes involved in the MC-LR-mediated CRC pathways and the HOXB4-correlated transcription genes. Importantly, C-myc instead of PPARG and RUNX1 promoted the high expression of HOXB4 through experiment validation, and was identified as a key target gene. Interestingly, C-myc was up-regulated by HOXB4 and maintained cell cycle progression. In addition, MC-LR was proved to up-regulate HOXB4 expression, thus promoting proliferation and migration of Caco2 cells and driving the cell cycle progression. In conclusion, MC-LR might accelerate CRC progression. In the process, MC-LR induced C-myc augmentation elevates the high expression of HOXB4 through increasing the S phase cell proportion to enhance Caco2 cell proliferation. Therefore, HOXB4 might be considered as a potential prognostic biomarker for CRC.
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Objective: To investigate the intervention effects and mechanism of interleukin-17A (IL-17A) on chronic obstructive pulmonary disease (COPD). Methods: C57BL/6 mice were randomly divided into wild type blank control group, wild type COPD group and IL-7A knockout COPD group. Mice in wild type blank control group received no treatment, and mice in the other two groups were exposed to cigarette smoke to induce COPD (Cigarette: 1 cigarette / time, 4 times/day, 45 minutes/time; interval time: 1 hour; total intervention time: 90 days). Lung function of mice was assessed using animal pulmonary function machine. Bronchoalveolar lavage fluid (BALF) of mice was collected and BALF cell count and classification were determined. The lung tissue of mice was collected, the expression level of IL-17A in airway epithelium was determined by flow cytometry, and the levels of inflammatory factors in lung tissue were determined by enzyme-linked immunosorbent assay. The expression level of JNK/AP1 signaling pathway protein in mouse lung tissue was determined by Western blot. Results: Compared with the wild type blank control group mice, the wild type COPD group mice had significantly higher expression level of IL-17A, significantly lower peak inspiratory flow rate (PIF) and peak expiratory flow rate (PEF), significantly higher number of BALF neutrophils, eosinophils, lymphocytes and macrophage, significantly higher expression levels of CXC chemokine 1(CXCL1), CXC chemokine 2 (CXCL2), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and significantly higher phosphorylation level of JNK, cJun and cFos and AP1 expression levels (Pï¼0.05). Compared with COPD mice, IL-17A expression level in airway epithelium of mice in IL-7A knockout COPD group was significantly lower, PIF and PEF were higher, the number of BALF neutrophils, eosinophils, lymphocytes and macrophage was significantly lower, the expression levels of CXCL1, CXCL2, IL-1ß and IL-6 in lung tissue were lower, and the phosphorylation levels of JNK, cJun and cFos and AP1 expression levels were significantly lower (Pï¼0.05). Conclusion: Cigarette smoke can induce the production of IL-17A and reduce (or inhibit) the production (or expression or secretion) of IL-17A in mouse airway epithelium, thus inhibiting the JNK/AP1 signaling pathway to reduce the airway inflammation and improve the lung function of COPD mice.