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This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.
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Aspartato-Amônia Ligase , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Aspartato-Amônia Ligase/genética , Aspartato-Amônia Ligase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Prognóstico , Animais , Camundongos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-AmidaRESUMO
Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery.
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Endosperma , Oryza , Edição de RNA , Oryza/genética , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Endosperma/metabolismo , Endosperma/genética , Endosperma/crescimento & desenvolvimento , RNA de Plantas/genética , RNA de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/genéticaRESUMO
OBJECTIVES: This study aims to develop an innovative approach for monitoring and assessing labor pain through ECG waveform analysis, utilizing machine learning techniques to monitor pain resulting from uterine contractions. METHODS: The study was conducted at National Taiwan University Hospital between January and July 2020. We collected a dataset of 6010 ECG samples from women preparing for natural spontaneous delivery (NSD). The ECG data was used to develop an ECG waveform-based Nociception Monitoring Index (NoM). The dataset was divided into training (80%) and validation (20%) sets. Multiple machine learning models, including LightGBM, XGBoost, SnapLogisticRegression, and SnapDecisionTree, were developed and evaluated. Hyperparameter optimization was performed using grid search and five-fold cross-validation to enhance model performance. RESULTS: The LightGBM model demonstrated superior performance with an AUC of 0.96 and an accuracy of 90%, making it the optimal model for monitoring labor pain based on ECG data. Other models, such as XGBoost and SnapLogisticRegression, also showed strong performance, with AUC values ranging from 0.88 to 0.95. CONCLUSIONS: This study demonstrates that the integration of machine learning algorithms with ECG data significantly enhances the accuracy and reliability of labor pain monitoring. Specifically, the LightGBM model exhibits exceptional precision and robustness in continuous pain monitoring during labor, with potential applicability extending to broader healthcare settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04461704.
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Background: Amidst the expansion of student enrollment in higher education, the well-being and retention rates of students have emerged as important concerns. Resilience, especially academic resilience, a multidimensional construct that can lead to academic success in adversity, is pivotal in enabling students to successfully cope with academic challenges. While the Academic Resilience Scale-30 (ARS-30) has been validated as an effective instrument in various languages, its applicability for Chinese students in higher education remains unexplored. Objective: This study aims to translate and validate the ARS-30 in Chinese, assessing its reliability and validity among Chinese college students in higher education. Methods: A convenience sample of 1,542 students participated in this study. The inventory included the demographic form, Chinese version of ARS-30 (C-ARS-30), 10-item Connor Davidson Resilience Scale (CD-RISC-10), and General Self-Efficacy Scale (GSES). The assessment of validity was conducted by analyzing content validity, construct validity, convergent and discriminant validity, as well as criterion-related validity. Construct validity was evaluated through Confirmatory Factor Analysis (CFA), Exploratory Factor Analysis (EFA) and Exploratory Structural Equation Modeling (ESEM). Reliability analysis was performed using Cronbach's alpha and test-retest reliability. Results: The C-ARS-30 demonstrated commendable content validity, with the CVI value of items ranging from 0.833 to 1.000, and a total scale CVI of 0.986. ESEM analysis revealed a solid four-factor structure, maintaining the scale's 30 items with excellent fit indices (χ2/df = 2.647, CFI = 0.937, TLI = 0.915, RMSEA = 0.057, SRMR = 0.027). The total score of C-ARS-30 exhibited positive correlations with the CD-RISC-10 (r = 0.542) and the GSES (r = 0.488). The scale demonstrated high internal consistency (Cronbach's α = 0.930) and test-retest reliability (0.794, p < 0.01). Conclusion: The C-ARS-30 is a reliable and valid instrument for assessing academic resilience among Chinese college students, offering a valuable tool for educational and psychological evaluations.
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Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.
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AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P<0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio (P<0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy (P<0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy (P>0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.
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Background and objective: Bleeding following endoscopic variceal ligation (EVL) may occur as a result of numerous factors, including a diameter of esophageal varices (EV) that is too large to be completely ligated. The present study aimed to develop an artificial intelligence-based endoscopic virtual ruler (EVR) to measure the diameter of EV with a view to finding more suitable cases for EVL. Methods: The present study was a multicenter retrospective study that included a total of 1,062 EVLs in 727 patients with liver cirrhosis with EV, who underwent EVL from April 2016 to March 2023. Patients were divided into early rebleeding (n = 80) and non-rebleeding groups (n = 982) according to whether postoperative bleeding occurred at 6 weeks. The characteristics of patient baseline data, the status of rebleeding at 6 weeks after surgery and the survival status at 6 weeks after rebleeding were analyzed. Results: The early rebleeding rate following 1,062 EVL procedures was 7.5%, and the mortality rate at 6 weeks after bleeding was 16.5%. Results of the one-way binary logistic regression analysis demonstrated that the risk factors for early rebleeding following EVL included: high TB (P = 0.009), low Alb (P = 0.001), high PT (P = 0.004), PVT (P = 0.026), HCC (P = 0.018), high Child-Pugh score (P < 0.001), Child-Pugh grade C(P < 0.001), high MELD score(P = 0.004), Japanese variceal grade F3 (P < 0.001), diameter of EV (P < 0.001), and number of ligature rings (P = 0.029). Results of the multifactorial binary logistic regression analysis demonstrated that Child-Pugh grade C (P = 0.007), Japanese variceal grade F3 (P = 0.009), and diameter of EV (P < 0.001) may exhibit potential in predicting early rebleeding following EVL. ROC analysis demonstrated that the area under curve (AUC) for EV diameter was 0.848, and the AUC for Japanese variceal grade was 0.635, which was statistically significant (P < 0.001). Thus, results of the present study demonstrated that EV diameter was more optimal in predicting early rebleeding following EVL than Japanese variceal grade criteria. The cut-off value of EV diameter was calculated to be 1.35 cm (sensitivity, 70.0%; specificity, 89.2%). Conclusion: If the diameter of EV is ≥1.4 cm, there may be a high risk of early rebleeding following EVL surgery; thus, we recommend caution with EVL.
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Doença Diverticular do Colo , Humanos , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/cirurgia , Doença Aguda , Masculino , Abscesso/cirurgia , Abscesso/terapia , Colonoscopia/métodos , Abscesso Abdominal/cirurgia , Abscesso Abdominal/etiologia , Abscesso Abdominal/terapia , Pessoa de Meia-Idade , Drenagem/métodosRESUMO
Capsule endoscopy (CE) is non-invasive and painless during gastrointestinal examination. However, capsule endoscopy can increase the workload of image reviewing for clinicians, making it prone to missed and misdiagnosed diagnoses. Current researches primarily concentrated on binary classifiers, multiple classifiers targeting fewer than four abnormality types and detectors within a specific segment of the digestive tract, and segmenters for a single type of anomaly. Due to intra-class variations, the task of creating a unified scheme for detecting multiple gastrointestinal diseases is particularly challenging. A cascade neural network designed in this study, Cascade-EC, can automatically identify and localize four types of gastrointestinal lesions in CE images: angiectasis, bleeding, erosion, and polyp. Cascade-EC consists of EfficientNet for image classification and CA_stm_Retinanet for lesion detection and location. As the first layer of Cascade-EC, the EfficientNet network classifies CE images. CA_stm_Retinanet, as the second layer, performs the target detection and location task on the classified image. CA_stm_Retinanet adopts the general architecture of Retinanet. Its feature extraction module is the CA_stm_Backbone from the stack of CA_stm Block. CA_stm Block adopts the split-transform-merge strategy and introduces the coordinate attention. The dataset in this study is from Shanghai East Hospital, collected by PillCam SB3 and AnKon capsule endoscopes, which contains a total of 7936 images of 317 patients from the years 2017 to 2021. In the testing set, the average precision of Cascade-EC in the multi-lesions classification task was 94.55%, the average recall was 90.60%, and the average F1 score was 92.26%. The mean mAP@ 0.5 of Cascade-EC for detecting the four types of diseases is 85.88%. The experimental results show that compared with a single target detection network, Cascade-EC has better performance and can effectively assist clinicians to classify and detect multiple lesions in CE images.
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Iron-nitrogen-carbon single-atom catalysts derived from zeolitic-imidazolate-framework-8 (ZIF-8) have presented its great potential for the oxygen reduction reaction (ORR) in Zn-air batteries (ZABs). However, due to insufficient active Fe-N sites, its ORR activity is inferior to Pt-based catalysts. Herein, a carboxylate (OAc) linker strategy is proposed to design a ZIF-8-derived FeNCOAc catalyst with abundant accessible Fe-N4 single-atom sites. Except that imidazole groups can coordinate with Fe ions, the OAc linker on the unsaturated coordination Zn nodes can anchor and coordinate with more Fe ions, resulting in a significant increase in Fe-N4 site density. Meanwhile, the corrosion of carbon skeleton by OAc oxidation during heat-treatment leads to improved porosity of catalyst. Benefitting from the highly dense Fe-N4 sites and hierarchical pores, the FeNCOAc endows superior performance in alkaline medium (E1/2 = 0.906 V), which is confirmed by density functional theory calculation results. Meanwhile, the assembled liquid ZAB delivers a favorable peak power density of 173.9 mW cm-2, and a high specific capacity of 770.9 mAh g-1 as well as outstanding durability. Besides, the solid-state ZAB also shows outstanding discharge performance.
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AIM: This study aimed to investigate the heterogeneity of academic resilience among nursing students using latent profile analysis and its associated influencing factors. BACKGROUND: Nursing students experience higher levels of stress compared to their peers in other professions, and the cultivation of academic resilience plays a pivotal role in their ability to effectively cope with this stress. Academic resilience not only facilitates success in the face of academic adversity but also contributes to the promotion of mental well-being among nursing students. However, the current research on the academic resilience of nursing students has predominantly focused on a scale-centered total score approach, disregarding individual variability, and hindering the development to inform personalized interventions for enhancing academic resilience. DESIGN: A cross-sectional study. METHODS: A convenience sampling method was used to collect a total of 644 nursing students from two medical schools in Guangzhou City. The participants were recruited through an online survey conducted from January to March 2023. The questionnaires consisted of a general information form, the Chinese version of the Academic Resilience Scale-30 (C-ARS-30), the 10-item Connor Davidson Resilience Scale (CD-RISC-10), and the General Self-Efficacy Scale (GSES). Latent profile analysis was used to identify distinct categories of academic resilience among nursing students, and influencing factors were examined through ordinal logistic regression analysis. RESULTS: The academic resilience levels of nursing students can be divided into three potential categories: 'low academic resilience' (13.0%), 'moderate academic resilience' (70.0%), and 'high academic resilience' (17.0%). Level of grade, GPA, self-reported physical health level, resilience and self-efficacy were significantly influenced the different categories of academic resilience of nursing students (P<0.05). CONCLUSIONS: The majority of undergraduate nursing students were placed in the moderate academic resilience group, however, educational institutions should pay special attention to nursing students demonstrating low levels. Regular assessments of academic resilience are recommended, and personalized interventions should be tailored to address specific academic resilience characteristics across different grades of nursing students. Strategies aimed at enhancing academic resilience among nursing students may include improvements in GPA performance, attention to physical health, and the reinforcement of resilience and self-efficacy.
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Bacharelado em Enfermagem , Resiliência Psicológica , Autoeficácia , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , Estudos Transversais , Feminino , Masculino , Inquéritos e Questionários , China , Adulto Jovem , Adaptação Psicológica , Adulto , Estresse Psicológico/psicologiaRESUMO
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is an aggressive disease with a poor prognosis, caused by the inactivation of critical cell growth regulators that lead to uncontrolled proliferation and increased malignancy. Although Serine/Threonine Kinase 3 (STK3), also known as Mammalian STE20-like protein kinase 2 (MST2), is a highly conserved kinase of the Hippo pathway, plays a critical role in immunomodulation, organ development, cellular differentiation, and cancer suppression, its phenotype and function in ESCC require further investigation. In this study, we report for the first time on the role of STK3 kinase and its activation condition in ESCC, as well as the mechanism and mediators of kinase activation. METHODS: In this study, we investigated the expression and clinical significance of STK3 in ESCC. We first used bioinformatics databases and immunohistochemistry to analyze STK3 expression in the ESCC patient cohort and conducted survival analysis. In vivo, we conducted a tumorigenicity assay using nude mouse models to demonstrate the phenotypes of STK3 kinase. In vitro, we conducted Western blot analysis, qPCR analysis, CO-IP, and immunofluorescence (IF) staining analysis to detect molecule expression, interaction, and distribution. We measured proliferation, migration, and apoptosis abilities in ESCC cells in the experimental groups using CCK-8 and transwell assays, flow cytometry, and EdU staining. We used RNA-seq to identify genes that were differentially expressed in ESCC cells with silenced STK3 or FOXO1. We demonstrated the regulatory relationship of the TP53INP1/P21 gene medicated by the STK3-FOXO1 axis using Western blotting and ChIP in vitro. RESULTS: We demonstrate high STK3 expression in ESCC tissue and cell lines compared to esophageal epithelium. Cellular ROS induces STK3 autophosphorylation in ESCC cells, resulting in upregulated p-STK3/4. STK3 activation inhibits ESCC cell proliferation and migration by triggering apoptosis and suppressing the cell cycle. STK3 kinase activation phosphorylates FOXO1Ser212, promoting nuclear translocation, enhancing transcriptional activity, and upregulating TP53INP1 and P21. We also investigated TP53INP1 and P21's phenotypic effects in ESCC, finding that their knockdown significantly increases tumor proliferation, highlighting their crucial role in ESCC tumorigenesis. CONCLUSION: STK3 kinase has a high expression level in ESCC and can be activated by cellular ROS, inhibiting cell proliferation and migration. Additionally, STK3 activation-mediated FOXO1 regulates ESCC cell apoptosis and cell cycle arrest by targeting TP53INP1/P21. Our research underscores the anti-tumor function of STK3 in ESCC and elucidates the mechanism underlying its anti-tumor effect on ESCC.
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Proliferação de Células , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína Forkhead Box O1 , Proteínas de Choque Térmico , Camundongos Nus , Serina-Treonina Quinase 3 , Transdução de Sinais , Humanos , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Proliferação de Células/genética , Animais , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Linhagem Celular Tumoral , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Transdução de Sinais/genética , Feminino , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Camundongos , Masculino , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Apoptose/genética , Movimento Celular/genética , Camundongos Endogâmicos BALB CRESUMO
As one of the most promising energy storage devices, supercapacitors exhibit a higher power density than batteries. However, its low energy density usually requires high-performance electrode materials. Although the RuO2 material shows desirable properties, its high cost and toxicity significantly limit its application in supercapacitors. Recent developments demonstrated that Co-based materials have emerged as a promising alternative to RuO2 for supercapacitors due to their low cost, favorable redox reversibility and environmental friendliness. In this paper, the morphological control and performance engineering of Co-based materials are systematically reviewed. Firstly, the principle of supercapacitors is briefly introduced, and the characteristics and advantages of pseudocapacitors are emphasized. The special forms of cobalt-based materials are introduced, including 1D, 2D and 3D nanomaterials. After that, the ways to enhance the properties of cobalt-based materials are discussed, including adding conductive materials, constructing heterostructures and doping heteroatoms. Particularly, the influence of morphological control and modification methods on the electrochemical performances of materials is highlighted. Finally, the application prospect and development direction of Co-based materials are proposed.
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Comprehending the spatial-temporal characteristics, contributions, and evolution of driving factors in agricultural non-CO2 greenhouse gas (GHG) emissions at a macro level is pivotal in pursuing temperature control objectives and achieving China's strategic goals related to carbon peak and carbon neutrality. This study employs the Intergovernmental Panel on Climate Change (IPCC) carbon emissions coefficient method to comprehensively evaluate agricultural non-CO2 GHG emissions at the provincial level. Subsequently, the contributions and spatial-temporal evolution of six driving factors derived from the Kaya identity were quantitatively explored using the Logarithmic Mean Divisia Index (LMDI) and Geographical and Temporal Weighted Regression (GTWR) methods. The results revealed that the distribution of agricultural non-CO2 GHG emissions is shifting from the central provinces to the northwest regions. Moreover, the dominant driving factors of agricultural non-CO2 GHG emissions were primarily economic factor (EDL) with positive impact (cumulative promotion is 2939.61 million metric tons (Mt)), alongside agricultural production efficiency factor (EI) with negative impact (cumulative reduction is 2208.98 Mt). Influence of EDL diminished in the eastern coastal regions but significantly impacted underdeveloped regions such as the northwest and southwest. In the eastern coastal regions, EI gradually became the absolute dominant driver, demonstrating a rapid reduction effect. Additionally, a declining birth rate and rural-to-urban population migration have significantly amplified the driving effects of the population factor (RP) at a national scale. These findings, in conjunction with the disparities in geographic and socioeconomic development among provinces, can serve as a guiding framework for the development of a region-specific roadmap aimed at reducing agricultural non-CO2 GHG emissions.
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Gases de Efeito Estufa , Agricultura , Dióxido de Carbono/análise , China , Carbono , Efeito EstufaRESUMO
Substantial evidence attests to the pivotal role of cancer stem cells (CSC) in both tumorigenesis and drug resistance. A member of the forkhead box (FOX) family, FOXC1, assumes significance in embryonic development and organogenesis. Furthermore, FOXC1 functions as an overexpressed transcription factor in various tumors, fostering proliferation, enhancing migratory capabilities, and promoting drug resistance, while maintaining stem-cell-like properties. Despite these implications, scant attention has been devoted to its role in esophageal squamous cell carcinoma. Our investigation revealed a pronounced upregulation of FOXC1 expression in ESCC, correlating with a poor prognosis. The downregulation of FOXC1 demonstrated inhibitory effects on ESCC tumorigenesis, proliferation, and tolerance to chemotherapeutic agents, concurrently reducing the levels of stemness-related markers CD133 and CD44. Further studies validated that FOXC1 induces ESCC stemness by transactivating CBX7 and IGF-1R. Additionally, IGF-1 activated the PI3K/AKT/NF-κB and MEK/ERK/NF-κB pathways through its binding to IGF-1R, thereby augmenting FOXC1 expression. Conversely, suppressing FOXC1 impeded ESCC stemness induced by IGF-1. The presence of a positive feedback loop, denoted by IGF-1-FOXC1-IGF-1R, suggests the potential of FOXC1 as a prognostic biomarker for ESCC. Taken together, targeting the IGF-1-FOXC1-IGF-1R axis emerges as a promising approach for anti-CSC therapy in ESCC.
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Unilateral absence of the pulmonary artery is a rare congenital cardiovascular anomaly that can lead to pulmonary hypertension and poor outcomes. We report the case of a 1-month-old infant with isolated unilateral absence of the pulmonary artery and severe pulmonary hypertension on the right and left sides, respectively. The patient was unresponsive to multiple medications for pulmonary hypertension, and surgical revascularisation was unfeasible. However, iloprost inhalation was effective.
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Hipertensão Pulmonar , Artéria Pulmonar , Lactente , Humanos , Artéria Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/etiologia , Iloprosta/uso terapêuticoRESUMO
This paper describes the development of Health Level Seven Fast Healthcare Interoperability Resource (FHIR) profiles for pathology reports integrated with whole slide images and clinical data to create a pathology research database. A report template was designed to collect structured reports, enabling pathologists to select structured terms based on a checklist, allowing for the standardization of terms used to describe tumor features. We gathered and analyzed 190 non-small-cell lung cancer pathology reports in free text format, which were then structured by mapping the itemized vocabulary to FHIR observation resources, using international standard terminologies, such as the International Classification of Diseases, LOINC, and SNOMED CT. The resulting FHIR profiles were published as an implementation guide, which includes 25 profiles for essential data elements, value sets, and structured definitions for integrating clinical data and pathology images associated with the pathology report. These profiles enable the exchange of structured data between systems and facilitate the integration of pathology data into electronic health records, which can improve the quality of care for patients with cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Nível Sete de Saúde , Neoplasias Pulmonares/diagnóstico por imagem , Patologistas , Atenção à SaúdeRESUMO
Esophageal squamous cell carcinoma (ESCC) commonly has aggressive properties and a poor prognosis. Investigating the molecular mechanisms underlying the progression of ESCC is crucial for developing effective therapeutic strategies. Here, by performing transcriptome sequencing in ESCC and adjacent normal tissues, we find that E74-like transcription factor 4 (ELF4) is the main upregulated transcription factor in ESCC. The results of the immunohistochemistry show that ELF4 is overexpressed in ESCC tissues and is significantly correlated with cancer staging and prognosis. Furthermore, we demonstrate that ELF4 could promote cancer cell proliferation, migration, invasion, and stemness by in vivo assays. Through RNA-seq and ChIP assays, we find that the stemness-related gene fucosyltransferase 9 ( FUT9) is transcriptionally activated by ELF4. Meanwhile, ELF4 is verified to affect ESCC cancer stemness by regulating FUT9 expression. Overall, we first discover that the transcription factor ELF4 is overexpressed in ESCC and can promote ESCC progression by transcriptionally upregulating the stemness-related gene FUT9.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/metabolismo , Neoplasias Esofágicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismoRESUMO
OBJECTIVES: The elderly are disproportionately affected by age-related hearing loss (ARHL). Despite being a well-known tool for ARHL evaluation, the Hearing Handicap Inventory for the Elderly Screening version (HHIE-S) has only traditionally been used for direct screening using self-reported outcomes. This work uses a novel integration of machine learning approaches to improve the predicted accuracy of the HHIE-S tool for ARHL in older adults. METHODS: We employed a dataset that was gathered between 2016 and 2018 and included 1,526 senior citizens from several Taipei City Hospital branches. 80% of the data were used for training (n = 1220) and 20% were used for testing (n = 356). XGBoost, Gradient Boosting, and LightGBM were among the machine learning models that were only used and assessed on the training set. In order to prevent data leakage and overfitting, the Light Gradient Boosting Machine (LGBM) model-which had the greatest AUC of 0.83 (95% CI 0.81-0.85)-was then only used on the holdout testing data. RESULTS: On the testing set, the LGBM model showed a strong AUC of 0.82 (95% CI 0.79-0.86), far outperforming conventional techniques. Notably, several HHIE-S items and age were found to be significant characteristics. In contrast to traditional HHIE research, which concentrates on the psychological effects of hearing loss, this study combines cutting-edge machine learning techniques-specifically, the LGBM classifier-with the HHIE-S tool. The incorporation of SHAP values enhances the interpretability of the model's predictions and provides a more comprehensive comprehension of the significance of various aspects. CONCLUSIONS: Our methodology highlights the great potential that arises from combining machine learning with validated hearing evaluation instruments such as the HHIE-S. Healthcare practitioners can anticipate ARHL more accurately thanks to this integration, which makes it easier to intervene quickly and precisely.