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Urinary incontinence is a common complication in stroke survivors for whom new interventions are needed. This study investigated the therapeutic effect of low-frequency (LF) repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (M1) in patients with poststroke urinary incontinence (PSI). A total of 100 patients were randomly assigned to the rTMS group or sham-rTMS group on basis of the intervention they received. Both groups underwent five treatment sessions per week for 4 weeks. Data from the urodynamic examination were used as the primary outcome. The secondary outcome measures were questionnaires and pelvic floor surface electromyography. After 4 weeks of intervention, the maximum cystometric capacity (MCC), maximum detrusor pressure (Pdet.max), residual urine output, overactive bladder score (OABSS) (including frequency, urgency, and urgency urinary incontinence), and the ICIQ-UI SF improved significantly in the rTMS group compared with those in the sham-rTMS group (P < 0.05). However, no changes in pelvic floor muscle EMG were detected in patients with PSI (both P > 0.05). Our data confirmed that 4 weeks of LF-rTMS stimulation on the contralateral M1 positively affects poststroke urinary incontinence in several aspects, such as frequency, urgency urinary incontinence, MCC, end-filling Pdet, OABSS, and ICIQ-UI SF scores.
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Eletromiografia , Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Bexiga Urinaria Neurogênica , Humanos , Estimulação Magnética Transcraniana/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Bexiga Urinaria Neurogênica/terapia , Bexiga Urinaria Neurogênica/etiologia , Bexiga Urinaria Neurogênica/fisiopatologia , Resultado do Tratamento , Incontinência Urinária/terapia , Incontinência Urinária/etiologia , Incontinência Urinária/fisiopatologia , Urodinâmica , Diafragma da Pelve/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos , Córtex Motor/fisiopatologiaRESUMO
Gallbladder cancer (GBC) is characterized by a high degree of malignancy and a poor prognosis. This study revealed that circEZH2 was frequently upregulated in GBC tissues and correlated with advanced tumor-node-metastasis (TNM) stage in GBC patients. In vitro and in vivo experiments confirmed that circEZH2 promoted the proliferation and inhibited the ferroptosis of GBC. Besides, this study discovered that circEZH2 regulated lipid metabolism reprogramming in GBC cells. Mechanistically, circEZH2 promotes SCD1 expression by sponging miR-556-5p in GBC cells. In addition, IGF2BP2 enhances the stability of circEZH2 in an m6A-dependent manner, while circEZH2 suppresses the ubiquitination and degradation of IGF2BP2 by binding to IGF2BP2. Taken together, our findings indicated that circEZH2, upregulated via a positive feedback loop between circEZH2 and IGF2BP2, promotes GBC progression and lipid metabolism reprogramming through the miR-556-5p/SCD1 axis in GBC. circEZH2 may serve as a potential therapeutic target for GBC.
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AIM: To evaluate the effectiveness and safety of nutritional interventions (i.e. nutritional support, dietary patterns and dietary supplements) on cognitive function in cancer survivors. DESIGN: Systematic review. METHODS: A systematic and comprehensive search of PubMed, Web of Science, the Cochrane Library, Embase, and CINAHL was conducted from the inception until March 10, 2023. The last search was conducted on December 10, 2023. REPORTING METHOD: PRISMA. RESULTS: A total of 59 randomized controlled trials were included for analysis. Nutritional support, dietary patterns and dietary supplements improved cognitive function in cancer survivors with no apparent safety concerns. The anti-inflammatory diet, the fasting-mimicking diet and the web-based diet significantly improved cognitive function. Whereas the ketogenic diet or dietary advice to consume more soluble dietary fibres and less insoluble dietary fibres and lactose could not. There was evidence from dietary supplements to support the beneficial effects of polyunsaturated fatty acid supplements, traditional herbal medicines and other supplements. CONCLUSIONS: Nutritional interventions have great promise for improving cognitive function in adult cancer survivors. Further validation of the nutritional interventions supported in this study in other survivors and exploration of more effective nutritional interventions are needed. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This work can support the construction of nutritional support interventions and dietary guidance programs to prevent cancer-related cognitive decline. IMPACT: This work filled a gap in preventive strategies for cancer-related cognitive decline from a nutritional perspective. Nutritional support, dietary patterns, and dietary supplements can prevent cancer-related cognitive decline without serious safety concerns. This work highlighted nutritional interventions that have the potential to improve cognitive function in cancer survivors, benefiting the further construction of evidence-based nutritional intervention programs. PROTOCOL REGISTRATION: PROSPERO. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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Proteins and peptides play vital roles in different biological processes in vivo. As a dynamic hydrolysis system, milk is rich in proteins and proteases and provides a constant supply of endogenous bioactive peptides to newborn mammals. Previous studies have primarily focused on researching bioactive peptides by adding exogenous enzymes to milk samples. However, such an approach overlooks the significance of endogenous peptides and parent proteins that naturally exist in milk. Herein, we analyzed and compared parent proteins and their releasing peptides in human colostrum (HC), bovine colostrum (BC), and donkey colostrum (DC). The predominant proteins and hydrolyzed peptides in the three types of milk were identified. Among them, peptides were found to possess common bioactivities, including ACE inhibitory, antioxidant, antibacterial and immunomodulatory properties in HC, BC, and DC. Furthermore, the biological functions of these parent proteins were clarified using bioinformatics. These insights offer a novel perspective on natural bioactive peptides and the potential utilization of specific parent proteins and peptides to develop infant formulae derived from diverse milk sources.
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Colostro , Equidae , Proteínas do Leite , Peptídeos , Proteólise , Colostro/química , Animais , Humanos , Bovinos , Proteínas do Leite/metabolismo , Proteínas do Leite/química , Peptídeos/metabolismo , Peptídeos/análise , Feminino , Leite Humano/químicaRESUMO
The traditional Chinese medicine (TCM) industry in China exhibits significant regional disparities in health service utilization, the underlying reasons for which are yet to be fully explored. This study employs Geodetector models to analyze the factors affecting TCM service utilization, providing the first examination of spatial distribution patterns and influencing factors for both TCM outpatient (TCMOSU) and inpatient services (TCMISU). The findings of this study reveal spatial disparities across China's provinces, showing a prevalence of TCMOSU in the east and TCMISU decreasing from southwest to northeast. Global Moran's I autocorrelation analysis revealed a positive spatial correlation between TCMOSU and TCMISU across Chinese provinces, suggesting spatial clustering and the potential for interregional collaboration in the development of TCM services. Local Moran's I autocorrelation analysis revealed clusters of TCMOSU in wealthier eastern provinces, such as Jiangsu and Tianjin, and clusters of TCMISU in the southwest. Factor detector analysis revealed that disposable income per capita was the most significant factor linking higher incomes with increased TCMOSU. In contrast, TCMISU was primarily influenced by demographic factors, such as the illiteracy rate and population urbanization rate, emphasizing traditional practices in lower education regions. Interaction detector analysis revealed the joint effects of these factors, demonstrating how regional economic status, health status, and healthcare resource indicators interact with other factors for TCMOSU and how demographic factors significantly influence the prevalence of TCMISU. This study highlights the importance of considering health status together with regional economic, demographic, and healthcare resources when formulating TCM healthcare policies and allocating such resources in China. Promoting the balanced and coordinated regional development of TCM services across the country requires the development of strategies that account for these varied regional characteristics.
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Medicina Tradicional Chinesa , Fatores Socioeconômicos , Análise Espacial , Humanos , China/epidemiologia , Medicina Tradicional Chinesa/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
Perovskite solar cells (PSCs) have garnered significant attention owing to their highly power conversion efficiency (PCE) and cost-effectiveness. Traditionally, screening for PSCs with superior photovoltaic parameters relies on resource-intensive trial-and-error experiments. Nowadays, time-saving machine learning (ML) techniques serve as an artificial intelligence approach to expedite the prediction of photovoltaic parameters using accumulated research datasets. In this study, we employ seven supervised ML methods to forecast key photovoltaic parameters for PSCs such as PCE, short-circuit current density (Jsc), open-circuit voltage (Voc), and fill factor (FF). Particularly, we design an artificial neural network (ANN) architecture that incorporates residual connectivity and layer normalization after the linear layers to enhance the scope and adaptability of the network. For PCE andJsc, ANN demonstrates superior prediction accuracy, yielding root mean square errors of 2.632% and 2.244 mA cm-2, respectively. The Random Forest (RF) model exhibits exceptional prediction performance forVocand FF. Additionally, an interpretability analysis of the model is conducted to elucidate the impact of features on PCE prediction, offering a novel approach for accurate and interpretable ML methods in the context of PSCs.
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PURPOSE: To investigate the causality between periodontitis and non-alcoholic fatty liver disease (NAFLD) using a two-sample bidirectional Mendelian randomisation (MR) analysis. MATERIALS AND METHODS: Genetic variations in periodontitis and NAFLD were acquired from genome-wide association studies (GWAS) using the Gene-Lifestyle Interaction in Dental Endpoints, a large-scale meta-analysis, and FinnGen consortia. Data from the first two databases were used to explore the causal relationship between periodontitis and NAFLD ("discovery stage"), and the data from FinnGen was used to validate our results ("validation stage"). We initially performed MR analysis using 5 single nucleotide polymorphisms (SNPs) in the discovery samples and 18 in the replicate samples as genetic instruments for periodontitis to investigate the causative impact of periodontitis on NAFLD. We then conducted a reverse MR analysis using 6 SNPs in the discovery samples and 4 in the replicate samples as genetic instruments for NAFLD to assess the causative impact of NAFLD on periodontitis. We further implemented heterogeneity and sensitivity analyses to assess the reliability of the MR results. RESULTS: Periodontitis was not causally related to NAFLD (odds ratio [OR] = 1.036, 95% CI: 0.914-1.175, p = 0.578 in the discovery stage; OR = 1.070, 95% CI: 0.935-1.224, p = 0.327 in the validation stage), and NAFLD was not causally linked with periodontitis (OR = 1.059, 95% CI: 0.916-1.225, p = 0.439 in the discovery stage; OR = 0.993, 95% CI: 0.896-1.102, p = 0.901 in the validation stage). No heterogeneity was observed among the selected SNPs. Sensitivity analyses demonstrated the absence of pleiotropy and the reliability of our MR results. CONCLUSION: The present MR analysis showed no genetic evidence for a cause-and-effect relationship between periodontitis and NAFLD. Periodontitis may not directly influence the development of NAFLD and vice versa.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hepatopatia Gordurosa não Alcoólica , Periodontite , Polimorfismo de Nucleotídeo Único , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/complicações , Periodontite/genética , CausalidadeRESUMO
The bacterial flagellum is an elongated filament that protrudes from the cell and is responsible for bacterial motility. It can also be a pathogen-associated molecular pattern (PAMP) that regulates the host immune response and is involved in bacterial pathogenicity. In contrast to motile bacteria, the Brucella flagellum does not serve a motile purpose. Instead, it plays a role in regulating Brucella virulence and the host's immune response, similar to other non-motile bacteria. The flagellin protein, FliK, plays a key role in assembly of the flagellum and also as a potential virulence factor involved in the regulation of bacterial virulence and pathogenicity. In this study, we generated a Brucella suis S2 flik gene deletion strain and its complemented strain and found that deletion of the flik gene has no significant effect on the main biological properties of Brucella, but significantly enhanced the inflammatory response induced by Brucella infection of RAW264.7 macrophages. Further experiments demonstrated that the FliK protein was able to inhibit LPS-induced cellular inflammatory responses by down-regulating the expression of MyD88 and NF-κB, and by decreasing p65 phosphorylation in the NF-κB pathway; it also inhibited the expression of NLRP3 and caspase-1 in the NLRP3 inflammasome pathway. In conclusion, our study suggests that Brucella FliK may act as a virulence factor involved in the regulation of Brucella pathogenicity and modulation of the host immune response.
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Brucelose , Flagelina , Macrófagos , Fatores de Virulência , Animais , Camundongos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Brucella suis/patogenicidade , Brucella suis/imunologia , Brucelose/imunologia , Brucelose/microbiologia , Caspase 1/metabolismo , Flagelina/metabolismo , Inflamassomos/metabolismo , Inflamassomos/imunologia , Inflamação/imunologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Células RAW 264.7 , Virulência , Fatores de Virulência/metabolismo , Fatores de Virulência/genéticaRESUMO
China faces challenges in meeting the World Health Organization (WHO)'s target of reducing hepatitis B virus (HBV) infections by 95% using 2015 as the baseline. Using Global Burden of Disease (GBD) 2019 data, joinpoint regression models were used to analyse the temporal trends in the crude incidence rates (CIRs) and age-standardized incidence rates (ASIRs) of acute HBV (AHBV) infections in China from 1990 to 2019. The age-period-cohort model was used to estimate the effects of age, period, and birth cohort on AHBV infection risk, while the Bayesian age-period-cohort (BAPC) model was applied to predict the annual number and ASIRs of AHBV infections in China through 2030. The joinpoint regression model revealed that CIRs and ASIRs decreased from 1990 to 2019, with a faster decline occurring among males and females younger than 20 years. According to the age-period-cohort model, age effects showed a steep increase followed by a gradual decline, whereas period effects showed a linear decline, and cohort effects showed a gradual rise followed by a rapid decline. The number of cases of AHBV infections in China was predicted to decline until 2030, but it is unlikely to meet the WHO's target. These findings provide scientific support and guidance for hepatitis B prevention and control.
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Hepatite B , Masculino , Feminino , Humanos , Teorema de Bayes , Hepatite B/epidemiologia , Vírus da Hepatite B , Incidência , China/epidemiologiaRESUMO
Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.
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Carcinoma Neuroendócrino , Inibidores de Checkpoint Imunológico , Humanos , Imunoterapia/efeitos adversos , Anticorpos Monoclonais , Retratamento , Progressão da Doença , DNA Helicases , Proteínas Nucleares , Fatores de TranscriçãoRESUMO
Rechargeable aqueous zinc batteries are promising but hindered by unfavorable dendrite growth and side reactions on zinc anodes. In this study, we demonstrate a fast melting-solidification approach for effectively converting commercial Zn foils into single (002)-textured Zn featuring millimeter-sized grains. The melting process eliminates initial texture, residual stress, and grain size variations in diverse commercial Zn foils, guaranteeing the uniformity of commercial Zn foils into single (002)-textured Zn. The single (002)-texture ensures large-scale epitaxial and dense Zn deposition, while the reduction in grain boundaries significantly minimizes intergranular reactions. These features enable large grain single (002)-textured Zn shows planar and dense Zn deposition under harsh conditions (100â mA cm-2, 100â mAh cm-2), impressive reversibility in Zn||Zn symmetric cell (3280â h under 1â mA cm-2, 830â h under 10â mAh cm-2), and long cycling stability over 180â h with a high depth of discharge value of 75 %. This study successfully addresses the issue of uncontrollable texture formation in Zn foils following routine annealing treatments with temperatures below the Zn melting point. The findings of this study establish a highly efficient strategy for fabricating highly reversible single (002)-textured Zn anodes.
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This ecological study examined the individual and joint impacts of natural-human factors on the spatial patterns of maternal and child health status in China at the provincial scale in 2020. We considered natural factors (forest coverage, average temperature, and total sulfur dioxide and particulate matter emissions) and human factors (economic development, urbanization, healthcare access, and education level). We combined maternal, infant, and under-five mortality rates into a composite maternal and child health index using the entropy method. The spatial autocorrelation analysis of this index highlighted distinct health patterns across provinces, whereas the geodetector method assessed the effects of natural-human factors on the patterns. A notable east-central-west stepwise decline in health status was observed. Global Moran's I showed positive spatial clustering, with high-high clustering areas in the Yangtze River Delta and low-low clustering areas in western regions. Factor detection identified eight significant natural-human factors impacting maternal and child health, with total sulfur dioxide emission density having the greatest impact. The interaction between average schooling years and total sulfur dioxide emission notably affected maternal and child health patterns. The study concludes that natural-human factors critically affect the spatial distribution of maternal and child health.
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Saúde da Criança , Dióxido de Enxofre , Lactente , Criança , Humanos , Análise Espacial , Florestas , Fatores Socioeconômicos , ChinaRESUMO
BACKGROUND: Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. METHODS: Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. RESULTS: FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan-Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role. CONCLUSION: Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Metástase Linfática/patologia , Proliferação de Células , Linhagem Celular Tumoral , Fatores de Transcrição/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismoRESUMO
Transition state (TS) on the potential energy surface (PES) plays a key role in determining the kinetics and thermodynamics of chemical reactions. Inspired by the fact that the dynamics of complex systems are always driven by rare but significant transition events, we herein propose a TS search method in accordance with the Q-learning algorithm. Appropriate reward functions are set for a given PES to optimize the reaction pathway through continuous trial and error, and then the TS can be obtained from the optimized reaction pathway. The validity of this Q-learning method with reasonable settings of Q-value table including actions, states, learning rate, greedy rate, discount rate, and so on, is exemplified in 2 two-dimensional potential functions. In the applications of the Q-learning method to two chemical reactions, it is demonstrated that the Q-learning method can predict consistent TS and reaction pathway with those by ab initio calculations. Notably, the PES must be well prepared before using the Q-learning method, and a coarse-to-fine PES scanning scheme is thus introduced to save the computational time while maintaining the accuracy of the Q-learning prediction. This work offers a simple and reliable Q-learning method to search for all possible TS and reaction pathway of a chemical reaction, which may be a new option for effectively exploring the PES in an extensive search manner.
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OBJECTIVE: Drawing on the control value theory, this study aims to identify the pertinent factors of self-regulated learning in the online learning environment for college students. The analysis will inductively examine how these factors impact self-regulated learning, thereby furnishing a reference for educators and online learning platform developers to create more efficacious online learning and teaching modes. DESIGN: Systematic review. DATA SOURCES: In March 2023, electronic databases of PubMed, Web of Science, Embase, EBSCO, Cochrane and Scopus were searched, and there was no time limit for publication. REVIEW METHODS: The inclusion criteria were: (1) Includes both online learning environment and self-regulated learning variables. (2) The research object is college students. (3) The research focuses on online teaching. Assessment of risk of bias for all included studies using a mixed-methods assessment tool. RESULTS: After screening, 31 articles were finally included. Including 24 quantitative studies, 2 qualitative study and 5 mixed studies. According to the control value theory, the factors affecting self-regulated learning in online learning environment are divided into seven aspects, namely cognitive quality, motivational quality, autonomy support, goal structures and social expectations, feedback and considerations of achievement, perceived control and perceived value. CONCLUSIONS: Teachers should exercise reasonable management over the number of assignments and provide timely and supportive feedback, as well as actively create interactive learning environments to facilitate peer-to-peer communication. Developers of online learning platforms should improve the functions of the platforms according to students' needs, and provide training for teachers and students when necessary. Learners should adapt their learning status in a timely manner to realise efficient learning and improve learning outcomes.
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Educação a Distância , Humanos , Comunicação , Retroalimentação , Aprendizagem , Estudantes , Educação/métodosRESUMO
A new green pathway of in situ electro-leaching coupled with electrochemically switched ion exchange (EL-ESIX) technology was developed for the separation and recovery of valuable metal ions from waste lithium batteries. By using the in situ electro-leaching, the leaching rates of Li+ and Co2+ from the prepared LiCoO2 film electrodes reached 100 % and 93.30 %, respectively, under the combined effect of the acidic microenvironment formed by the anodic electrolytic water and electrostatic repulsion. Subsequently, the Li+ in the electrolyte was further extracted by an electrochemically switched ion exchange (ESIX) process using LiMn2O4 as the film electrode, and Li+ was further enriched in the eluate by a cyclic adsorption and desorption process. The results indicate that the in situ electro-leaching has significant advantages over powder leaching, and for the recycling of waste lithium batteries, the final lithium recovery rate reached 94.51 % by using this in situ EL-ESIX technology.
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Lítio , Metais , Troca Iônica , Reciclagem/métodos , Fontes de Energia Elétrica , Íons , EletrodosRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5. METHODS: In this study, we investigated the association between the spatial localization of epithelial cells and TAMs by combining scRNA-seq analysis with multiplex immunofluorescence analysis. Through bulk sequencing analysis and spatial analysis, lipid metabolism genes closely related to TAM infiltration were screened. In vitro co-culture model was constructed to verify that ALOX5 and its downstream metabolite LTB4 promote M2 macrophage migration. Bulk sequencing after co-culture combined with single-cell analysis was performed to identify key pathways for up-regulation of M2 macrophage migration. Finally, the effect of CSF1R inhibitor (PLX3397) combined with ALOX5 inhibitor (Zileuton) in vivo was investigated by by xenograft tumor formation experiment in nude mice. RESULTS: ALOX5 in ICC cells was a key lipid metabolism gene affecting the infiltration of M2 macrophages in TME. Mechanically, LTB4, a metabolite downstream of ALOX5, recruited M2 macrophages to migrate around tumor cells by binding to BLT1/BLT2 and activating the PI3K pathway, which ultimately lead to the promotion of ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor effectively reduced tumor volume and M2 macrophage infiltration abundance. CONCLUSION: In ICC, LTB4, a metabolite secreted by ALOX5 of epithelial cells, binded to BLT1/BLT2 on TAM surface to activate PI3K pathway and promote TAM migration, thus promoting ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor for ICC is a promising combination therapy modality.
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Colangiocarcinoma , Fosfatidilinositol 3-Quinases , Animais , Camundongos , Humanos , Macrófagos Associados a Tumor , Camundongos Nus , Leucotrieno B4 , Colangiocarcinoma/genética , Microambiente Tumoral , Linhagem Celular Tumoral , Araquidonato 5-LipoxigenaseRESUMO
BACKGROUND: Sexually transmitted and blood-borne infections (STBBIs) is a major public health concern in China. This study assessed the overall trends in STBBIs to improve the comprehensive understanding of the burden of STBBIs and provide evidence for their prevention and control. METHODS: Data for the period from 2005 to 2021 were analyzed across China on infections with hepatitis B or C; syphilis; gonorrhea; and HIV infection. Trends, annual percent change (APC), and average annual percent change (AAPC) in diagnosis rate was analyzed using joinpoint regression models for the five STBBIs together or individually. RESULTS: From 2005 to 2021, the overall diagnosis rate of all five STBBIs increased, with an AAPC of 1.3% [95% confidence interval (CI) -0.5% to 3.1%]. Diagnosis rates of HIV, syphilis and hepatitis C increased individually, but it decreased for infections of hepatitis B and gonorrhea. Joinpoint analysis identified four phases in diagnosis rate of hepatitis C; three phases in diagnosis rate of hepatitis B, HIV infection, and syphilis; two in diagnosis rate of gonorrhea infection. CONCLUSION: Despite national efforts to prevent and control STBBIs, their overall diagnosis rate has continued to rise in China, and they remain an important public health challenge. Further efforts should be made to educate the general population about STBBIs, particularly HIV. Interventions targeting vulnerable groups should be adopted and their efficacy monitored through regular analysis of trends.
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Gonorreia , Infecções por HIV , Hepatite B , Hepatite C , Infecções Sexualmente Transmissíveis , Sífilis , Humanos , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Sífilis/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Infecções Transmitidas por Sangue , Hepatite B/epidemiologia , Hepatite C/epidemiologia , China/epidemiologiaRESUMO
Medical image segmentation is crucial for accurate diagnosis and treatment in the medical field. In recent years, convolutional neural networks (CNNs) and Transformers have been frequently adopted as network architectures in medical image segmentation. The convolution operation is limited in modeling long-range dependencies because it can only extract local information through the limited receptive field. In comparison, Transformers demonstrate excellent capability in modeling long-range dependencies but are less effective in capturing local information. Hence, effectively modeling long-range dependencies while preserving local information is essential for accurate medical image segmentation. In this paper, we propose a four-axis fusion framework called FAFuse, which can exploit the advantages of CNN and Transformer. As the core component of our FAFuse, a Four-Axis Fusion module (FAF) is proposed to efficiently fuse global and local information. FAF combines Four-Axis attention (height, width, main diagonal, and counter diagonal axial attention), a multi-scale convolution, and a residual structure with a depth-separable convolution and a Hadamard product. Furthermore, we also introduce deep supervision to enhance gradient flow and improve overall performance. Our approach achieves state-of-the-art segmentation accuracy on three publicly available medical image segmentation datasets. The code is available at https://github.com/cczu-xiao/FAFuse.