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Arsenic (As) pollution in soils is a pervasive environmental issue. Biochar immobilization offers a promising solution for addressing soil As contamination. The efficiency of biochar in immobilizing As in soils primarily hinges on the characteristics of both the soil and the biochar. However, the influence of a specific property on As immobilization varies among different studies, and the development and application of arsenic passivation materials based on biochar often rely on empirical knowledge. To enhance immobilization efficiency and reduce labor and time costs, a machine learning (ML) model was employed to predict As immobilization efficiency before biochar application. In this study, we collected a dataset comprising 182 data points on As immobilization efficiency from 17 publications to construct three ML models. The results demonstrated that the random forest (RF) model outperformed gradient boost regression tree and support vector regression models in predictive performance. Relative importance analysis and partial dependence plots based on the RF model were conducted to identify the most crucial factors influencing As immobilization. These findings highlighted the significant roles of biochar application time and biochar pH in As immobilization efficiency in soils. Furthermore, the study revealed that Fe-modified biochar exhibited a substantial improvement in As immobilization. These insights can facilitate targeted biochar property design and optimization of biochar application conditions to enhance As immobilization efficiency.
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Arsênio , Carvão Vegetal , Aprendizado de Máquina , Poluentes do Solo , Solo , Carvão Vegetal/química , Arsênio/química , Poluentes do Solo/química , Poluentes do Solo/análise , Solo/química , Modelos QuímicosRESUMO
BACKGROUND: Rheumatoid arthritis (RA) remains a devastating autoimmune disease characterized by joint damage, inflammation, and disability. This study investigates the function of lymphocyte antigen 96 (LY96) in the inflammatory response in RA and explores its regulatory mechanism. METHODS: A mouse model of RA was developed using type II collagen, and the LY96 expression in the ankle joint tissue was determined. Upstream regulators targeting LY96 were investigated using bioinformatics, followed by chromatin immunoprecipitation and luciferase reporter assays for validation. Gain- or loss-of-functions of LY96 and forkhead box A2 (FOXA2) were performed to analyze their roles in arthritis score, pathological changes, and inflammatory responses in mice. The effects of FOXA2 and LY96 on pro-inflammatory activation of macrophages were additionally investigated in vitro using a mouse RAW264.7 macrophage model with lipopolysaccharide treatment. RESULTS: LY96 mRNA and protein (MD-2) levels were increased in the RA mice. Knockdown of LY96 alleviated arthritis severity, joint deformities, inflammation, and cartilage destruction in mice. In vitro, the LY96 knockdown reduced the pro-inflammatory activation of RAW264.7 macrophages by inhibiting the TLR4/NF-κB inflammatory signaling transduction. FOXA2 was identified as a transcriptional repressor of LP96 poorly expressed in RA. Overexpression of FOXA2 similarly alleviated inflammation and reduced M1-type macrophages in vivo and in vitro. However, these changes were reversed by the additional LY96 upregulation. CONCLUSION: This study suggests that FOXA2 represses LY96 transcription to inhibit the TLR4/NF-κB signaling transduction, thus reducing pro-inflammatory activation of macrophages in the context of RA.
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BACKGROUND: Childhood hypertension is a growing health concern in China. Accurate estimation of prevalence is essential but challenging due to the variability of blood pressure and the need for multiple occasions for confirmation. This study aimed to estimate the national, regional, and provincial prevalence of childhood hypertension in China in 2020. METHODS: For this systematic review and modelling study, we did a comprehensive literature search of epidemiological studies reporting the prevalence of elevated blood pressure (EBP) or hypertension among Chinese children (aged 18 years or younger) that were published between Jan 1, 1990 and June 20, 2024 in PubMed, Embase, MEDLINE, China National Knowledge Infrastructure, Wanfang Data, and Chinese Science and Technology Journal Database. EBP was defined as blood pressure greater than or equal to the 95th percentile on a single occasion, and childhood hypertension as blood pressure greater than or equal to the 95th percentile consistently across three occasions. First, we estimated the prevalence of childhood EBP using a multi-level mixed-effects meta-regression and the pooled odds ratios (ORs) for factors associated with childhood EBP through random-effects meta-analysis. Second, the ratio of childhood EBP to childhood hypertension was calculated via random-effects meta-analysis, based on which the national and regional prevalence of childhood hypertension was imputed. Finally, we derived the provincial prevalence of childhood hypertension using an associated factor-based model. The review protocol was registered in PROSPERO (CRD42024537570). FINDINGS: We identified 8872 records, of which 134 articles covering 22 431 861 children were included. In 2020, the overall prevalence of hypertension among Chinese children aged 6-18 years was 3·11% (95% CI 2·35-4·04), equivalent to 6·80 million (5·13-8·83) affected children. The prevalence of childhood hypertension ranged from 2·25% (1·54-2·75) for children aged 6 years to 2·01% (1·36-3·37) for those aged 18 years, peaking at 3·84% (2·97-4·94) for those aged 14 years. The overall prevalence was higher in boys (3·34% [2·53-4·35]) than in girls (2·85% [2·13-3·69]). Associations between four factors (overweight, obesity, salted food intake, and family history of hypertension) and childhood EBP were graded as highly suggestive evidence. INTERPRETATION: This study reveals substantial regional and provincial variations in the prevalence of childhood hypertension in China. Our findings could inform targeted public health initiatives and optimise resource allocation to address this public health concern. FUNDING: This study was supported by the National Natural Science Foundation of China (72104211 and 82273654) and the Chao Kuang Piu High-tech Development Fund (2022RC019). TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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OBJECTIVES: To investigate the prevalence of tension-type headache (TTH) in children and adolescents aged 0-19 years globally in 1990-2021, and to provide a basis for the prevention and treatment of TTH. METHODS: Based on the Global Burden of Disease Study data, the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years, with different sexes, age groups, sociodemographic index (SDI) regions and countries/territories. RESULTS: The age-standardized prevalence rate (ASPR) of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000, which was increased by 1.73% since 1990. The ASPR in females was slightly higher than that in males (1990: 17 707.65/100 000 vs 16 403.78/100 000; 2021: 17 946.29/100 000 vs 16 763.09/100 000). The ASPR in adolescence was significantly higher than that in school-aged and preschool periods (1990: 27 672.04/100 000 vs 10 134.16/100 000; 2021: 28 239.04/100 000 vs 10 059.39/100 000). Regions with high SDI exhibited a higher ASPR than the other regions, with significant differences in prevalence rates across different countries. From 1990 to 2021, there was a slight increase in global ASPR, with an average annual percentage change (AAPC) of 0.06%. Females experienced a smaller increase than males based on AAPC (0.04% vs 0.07%). There was reduction in ASPR in preschool and school-aged groups, with an AAPC of -0.02%, while there was a significant increase in ASPR in adolescence, with an AAPC of 0.07%. ASPR decreased in regions with low-middle and low levels of SDI, with an AAPC of -0.02% and -0.04%, respectively, while it increased in regions with middle SDI, with an AAPC of 0.24%. CONCLUSIONS: There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally, with significant differences across sexes, age groups, SDI regions and countries/territories.
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Cefaleia do Tipo Tensional , Humanos , Adolescente , Criança , Feminino , Masculino , Prevalência , Pré-Escolar , Cefaleia do Tipo Tensional/epidemiologia , Lactente , Adulto Jovem , Recém-Nascido , Fatores de TempoRESUMO
Non-uniform zinc plating/stripping in aqueous zinc-ion batteries (ZIBs) often leads to dendrites formation and low Coulombic efficiency (CE), limiting their large-scale application. In this study, a pre-corroded Zn (PC-Zn) anode with 3D ridge-like structure is constructed by a facile solution etching in sodium hypophosphite (NaH2PO2) solution. The surface preparation process can significantly remove impurities from the passivation layer of bare Zn anode, thus exposing a great quantity of active sites for easy plating/stripping. Moreover, the pre-corroded structure enables a uniform-distributed electric field to promote the 3D Zn2+ diffusion process and accelerate the transfer kinetics, thereby suppressing the zinc dendrites and interfacial side reactions. Consequently, symmetric cells with PC-Zn electrodes demonstrate remarkable stability, maintaining cycles for over 3200 h under 1 mA cm-2. The PC-Zn/VO2 full cell maintains a specific capacity of 361 mAh g-1 at 0.1 A g-1, and a capacity retention rate of ≈80% over 1000 cycles at 4 A g-1. Notably, no obvious dendrites and side reactions are detected after extended cycling. Leveraging the cost-effectiveness, environmentally friendly nature, and easy fabrication of the PC-Zn electrode, this Zn protection strategy holds promise for advancing the industrial application of ZIBs.
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RATIONALE AND OBJECTIVES: Non-muscle-invasive bladder cancer (NMIBC) is highly recurrent, with each recurrence potentially progressing to muscle-invasive cancer, affecting patient prognosis. Intratumoral heterogeneity plays a crucial role in NMIBC recurrence. This study investigated a novel habitat-based radiomic analysis for stratifying NMIBC recurrence risk. MATERIALS AND METHODS: A retrospective collection of 382 NMIBC patients between 2015 and 2021 from two medical institutions was carried out. Patients' CT images were collected across three phases, with tumor sites delineated within the bladder. Intratumoral habitats were identified using K-means clustering on 19 texture features of the tumor sites, followed by the extraction of 107 radiomic features per habitat with PyRadiomics. These features were integrated into machine learning algorithms to develop a habitat-based model (HBM) for predicting two-year recurrence of NMIBC patients. The clinical and multiphase radiomic models were also constructed for comparison, with the Delong test comparing their diagnostic efficiency. The impact of HMB on patients' recurrence-free survival and the correlation between HBM and tumor-stroma ratio were further analyzed. RESULTS: Three distinct habitats were identified within NMIBC. The HBM showed an AUC of 0.932 (95% CI: 0.906 - 0.958) in the training cohort and 0.782 (95% CI: 0.674 - 0.890) in the validation cohort for predicting two-year recurrence. With comparison between different models, The HBM is demonstrated to possess superior diagnostic efficacy to the clinical model (p < 0.001) in the training cohort. However, no significant difference was noted between the multiphase and clinical models (p = 0.130) in the training cohort. The HBM score effectively distinguished the recurrence-free survival of NIMBC patients and demonstrated a significant correlation with the tumor-stroma ratio. CONCLUSIONS: Habitat-based radiomics, coupled with machine learning, efficiently predicts NMIBC recurrence. Further research on habitat-based radiomics offers potential improvement in clinical management of NMIBC.
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In recent years, organic semiconductor (OSC) ultrathin films and their solution-processed organic field-effect transistors (OFETs) have garnered attention for their high flexibility, light weight, solution processability, and tunable optoelectronic properties. These features make them promising candidates for next-generation optoelectronic applications. An ultrathin film typically refers to a film thickness of less than 10 nm, i.e., several molecular layers, which poses challenges for OSC materials and solution-processed methods. In this paper, first we introduce the carrier-transport regulation mechanism under ultrathin limits. Second, we summarize various solution-processed techniques for OSC ultrathin films and elucidate advances in their OFETs performance, such as enhanced or maintained mobilities, improved switching ratios, reduced threshold voltages, and minimized contact resistance. The relationship between the ultrathin-film thickness, microstructure of various OSCs (small molecules and polymers), and device performance is discussed. Third, we explore the recent application of OSC ultrathin-film-based OFETs, such as gas sensors, biosensors, photodetectors, and ferroelectric OFETs (Fe-OFETs). Finally, the conclusion is drawn, and the challenges and prospects of ultrathin OSC transistors are presented. Nowadays, research on ultrathin films is still in its early stages; further experience in precise film deposition control is crucial to advancing research and broadening the scope of applications for OSC ultrathin devices.
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Osteoarthritis (OA) is a prevalent articular disorder characterized by joint degeneration and persistent pain; it imposes a significant burden on both individuals and society. While OA has traditionally been viewed as a localized peripheral disorder, recent preclinical and clinical studies have revealed the crucial interconnections between the bone and the brain, highlighting the systemic nature of OA. The neuronal pathway, molecular signaling, circadian rhythms, and genetic underpinnings within the bone-brain axis play vital roles in the complex interplay that contributes to OA initiation and progression. This review explores emerging evidence of the crosstalk between the bone and brain in OA progression, and discusses the potential contributions of the bone-brain axis to the development of effective interventions for managing OA.
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Background: Chronic obstructive pulmonary disease (COPD) is one of the primary causes of significant morbidity and mortality worldwide. This study aimed to explore the cross-country inequalities by age, sex, and region in COPD's burden and care quality from 1990 to 2021. Methods: We obtained data from the Global Burden of Disease 2021. Using age-standardised disability-adjusted life years rate (ASDR) per 100 000 population and quality of care index (QCI), we quantified the COPD burden and care quality, respectively. Applying the principal component analysis method, we calculated QCI scores, ranging from 0 to 100, where higher values indicate better care quality. We quantified temporal trends from 1990 to 2021 for ASDR and QCI by estimated annual percentage change (EAPC). Finally, we assessed the absolute and relative disparities in ASDR and QCI across countries using the slope index of inequality (SII) and concentration index. Results: Between 1990 and 2021, there was a notable decline in ASDR of COPD globally (1990 = 1492.64; 2021 = 940.66; EAPC = -1.71), accompanied by an increase in QCI (1990 = 58.42; 2021 = 73.86; EAPC = 0.89). Regions with middle sociodemographic index (SDI) consistently demonstrated the highest ASDR and the lowest QCI in 1990 (ASDR = 2332.91; QCI = 31.70), whereas by 2021, low-middle SDI regions exhibited similar trends (ASDR = 1707.90; QCI = 57.50). In 2021, the highest ASDR was among individuals aged 95 years and above (16251.22), while the lowest QCI was among people aged 70-74 years (72.18). Papua New Guinea recorded the highest ASDR and the lowest QCI in 2021 (ASDR = 3004.36; QCI = 19.18). Compared to 1990, where the SII for ASDR was -612.44 and for QCI was 21.78, with concentration indices of -0.14 for ASDR and 0.11 for QCI, the absolute values of both SII and concentration index were smaller in 2021, with ASDR's SII at -555.90, QCI's at 16.72, ASDR's concentration index at -0.13, and QCI's at 0.04. Conclusions: The global burden of COPD decreases and care quality increases over time, with notable variations across ages, sexes and SDI regions. Countries with lower SDI had disproportionately higher burden and poorer care quality for COPD.
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Carga Global da Doença , Doença Pulmonar Obstrutiva Crônica , Qualidade da Assistência à Saúde , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Adulto , Disparidades em Assistência à Saúde , Efeitos Psicossociais da Doença , Idoso de 80 Anos ou mais , Saúde Global , Disparidades nos Níveis de Saúde , Anos de Vida Ajustados por Deficiência , Fatores Socioeconômicos , Adulto JovemRESUMO
Despite the widespread adoption of Zn anodes for aqueous energy storage, the presence of an inherent passivation layer and the polycrystalline interface of commercial Zn foil consistently lead to non-uniform electrodeposition, undermining stability and practicality. Herein, the study introduces a chemically polished Zn metal anode (CP-Zn) fabricated via a simple immersion method. This "chemically polishing" process can effectively remove the interfacial passivation layer (de-passivation), providing ample active sites for plating/stripping and ensuring the uniformly distributed electric field and Zn2+ ion flux. Additionally, selective etching during chemical polishing exposes more (002) crystal planes, promoting homogeneous and smooth zinc deposition while suppressing related side reactions. Demonstrated by CP-Zn anode, the symmetric cell exhibits stable cycling over 4600 h at 1 mA cm-2 and 240 h at 50% depth of discharge (DOD), with a CP-Zn||VO2 full cell maintaining ≈75.3% capacity retention over 1000 cycles at 3 A g-1. This chemically polishing strategy presents a promising avenue for advancing the commercialization of aqueous zinc-ion batteries.
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BACKGROUND: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). METHODS: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. RESULTS: We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10-6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). CONCLUSIONS: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.
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Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Proteoma , Locos de Características Quantitativas , Humanos , Proteoma/efeitos dos fármacos , Transtornos de Enxaqueca/genética , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/sangue , Mapas de Interação de Proteínas/genética , Enxaqueca com Aura/genética , Enxaqueca com Aura/tratamento farmacológico , Enxaqueca com Aura/sangue , Enxaqueca sem Aura/genética , Enxaqueca sem Aura/tratamento farmacológico , Enxaqueca sem Aura/sangue , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismoRESUMO
PURPOSE: To propose and validate a CT radiomics model utilizing radiomic features from lymph nodes (LNs) with maximum short axis diameter (MSAD) < 1 cm for predicting small metastatic LN (sMLN) in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 196 resectable patients with ESCC undergoing surgery were retrospectively enrolled, among whom 25% had sMLN. 146 out of 196 patients (from hospital 1) were randomly divided into the training (n = 116) and testing cohorts (n = 30) at an 8:2 ratio, while the remaining 50 patients from hospital 2 constituted the external validation cohort. Least absolute shrinkage and selection operator binary logistic regression was employed for radiomics feature dimensionality reduction and selection, and multivariable logistic regression analysis was used to construct the radiomics prediction model. The clinical features were statistically selected to develop the clinical model. And both the selected radiomics and clinical features were used to develop the combined model. The predictive value of models was assessed using the area under the receiver operating characteristic curves (AUC). RESULTS: The LN radiomics model was constructed with 9 radiomics features, the clinical model was developed with 3 clinical features, and the combined model was developed using both the LN radiomics and clinical features. However, no statistical radiomics features from ESCC were extracted in dimensionality reduction. Compared to the clinical model, the combined model exhibited superior predictive ability (AUC: 0.893 vs. 0.766, P = 0.003), and the LN radiomics model showed slightly better predictive ability (AUC: 0.860 vs. 0.766, P = 0.153). It was validated in the test and external validation cohorts. CONCLUSION: The combined model could assist in preoperatively identifying sMLN in resectable ESCC. It is beneficial for more accurate N staging and clinical comprehensive staging of ESCC, thereby facilitating the clinical physician to make more personalized and standardized treatment strategies.
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Background: Stroke remains a significant global health challenge, with persistent disparities in burden across different countries and regions. This study aimed to assess the temporal trends in cross-country inequalities of stroke and its subtypes burden from 1990 to 2021. Methods: We conducted a secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The age-standardised disability-adjusted life years (DALYs) rate (ASDR) was used to assess the burden of stroke and its subtypes (ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) across 21 GBD regions and 204 countries. The slope index of inequality (SII) and the concentration index were calculated to quantify the absolute and relative cross-country inequalities in the burden of stroke and its subtypes, with negative values indicating a higher burden in lower socio-demographic index (SDI) countries, and positive values indicating a higher burden in higher SDI countries. Estimated annual percentage change (EAPC) was used to illustrate temporal trends at global and regional levels from 1990 to 2021. The inequality changing patterns from 1990 to 2021 were classified as worsening, improving, and shifting to higher burdens among higher or lower SDI countries. Findings: From 1990 to 2021, the ASDR of total stroke decreased from 3078.95 (95% uncertainty interval [UI]: 2893.58, 3237.34) to 1886.20 (95% UI: 1738.99, 2017.90) per 100,000 population globally. While both absolute and relative inequalities increased, with a disproportionately higher burden shouldered by countries with lower SDI. The SII of total stroke exhibited a worsening inequality among lower SDI countries, increasing by 286.97 units from -2329.47 (95% confidence interval [CI]: -2857.50, -1801.43) in 1990 to -2616.44 (95% CI: -2987.33, -2245.56) in 2021. Similarly, the concentration index of total stroke increased by 0.03 from -0.0819 (95% CI: -0.1143, -0.0495) in 1990 to -0.1119 (95% CI: -0.1478, -0.0759) in 2021. The changing patterns from 1990 to 2021 were diverse across regions, yet most regions exhibited a worsening inequality among lower SDI countries in both SII and concentration index. Southern Sub-Saharan Africa showed the largest worsening inequality in SII (EAPC: -2.15, 95% CI: -2.71, -1.57) while Central Europe showed the largest worsening inequality in concentration index (EAPC: -0.51, 95% CI: -0.58, -0.44). In 2021, the highest negative SII was observed in Oceania and the highest negative concentration index was in the Caribbean. In terms of subtypes, ischemic stroke reported a worsening inequality among lower SDI countries in SII (EAPC: -2.13, 95% CI: -2.20, -2.05) while intracerebral haemorrhage showed an improving inequality in SII (EAPC: 0.44, 95% CI: 0.40, 0.47). SII in subarachnoid haemorrhage (EAPC: -0.18, 95% CI: -0.19, -0.17) and concentration index in ischemic stroke (EAPC: -0.25, 95% CI: -0.27, -0.23) presented a shift to higher burden among lower SDI countries from 1990 to 2021. Interpretation: Although the burden of stroke and its subtypes decreased from 1990 to 2021, inequalities have persisted and even widened in some regions. Timely and effective prevention and management strategies for stroke and its subtypes are needed in specific areas to reduce the stroke burden and achieve equity in health outcomes. Funding: None.
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Doxorubicin (Dox) has been limited in clinical application due to its cardiac toxicity that varies with the dose. This study aimed to explore how Rhein modulates Dox-induced myocardial toxicity. The general condition and echocardiographic changes of mice were observed to evaluate cardiac function and structure, with myocardial cell injury and apoptosis checked by TUNEL and HE staining. The ELISA assessed markers of myocardial damage and inflammation. The TCMSP and SwissTargetPrediction databases were used to retrieve Rhein's targets while GeneCards was used to find genes related to Dox-induced myocardial injury. Intersection genes were analyzed by Protein-Protein Interaction Networks. The core network genes underwent GO and KEGG enrichment analysis using R software. Western blot was used to detect protein expression. Compared to the Dox group, there was no remarkable difference in heart mass /body mass ratio in the Rhein+Dox group. However, heart mass/tibia length increased. Mice in the Rhein+Dox group had significantly increased LVEF, LVPWs, and LVFS compared to those in the Dox group. Myocardial cell damage, inflammation, and apoptosis significantly reduced in the Rhein+Dox group compared to the model group. Eleven core network genes were selected. Further, Rhein+Dox group showed significantly downregulated expression of p38/p-p38, HSP90AA1, c-Jun/p-c-Jun, c-Fos/p-c-Fos, Bax, and cleaved-caspase-3/caspase-3 while Bcl-2 expression significantly upregulated compared to the Dox group. The study suggests that Rhein mediates cardioprotection against Dox-induced myocardial injury, at least partly, by influencing multiple core genes in the MAPK signaling pathway to inhibit myocardial cell apoptosis.
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Antraquinonas , Apoptose , Cardiotoxicidade , Modelos Animais de Doenças , Doxorrubicina , Proteínas de Choque Térmico HSP90 , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-fos , Proteínas Proto-Oncogênicas c-jun , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Apoptose/efeitos dos fármacos , Antraquinonas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Camundongos , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genética , Cardiopatias/induzido quimicamente , Cardiopatias/prevenção & controle , Cardiopatias/patologia , Cardiopatias/metabolismo , Mapas de Interação de ProteínasRESUMO
Pyroptosis, a pro-inflammatory form of programmed cell death, is crucial for host defense against pathogens and danger signals. Proteolytic cleavage of gasdermin proteins B-E (GSDMB-GSDME) is well established as a trigger for pyroptosis, but the intracellular activation mechanism of GSDMA remains elusive. Here, we demonstrate that severe starvation induces pyroptosis through phosphorylation-induced activation of GSDMA. Nutrient stresses stimulate GSDMA activation via phosphorylation mediated by Unc-51-like autophagy-activating kinase 1 (ULK1). Phosphorylation of Ser353 on human GSDMA by ULK1 or the phospho-mimetic Ser353Asp mutant of GSDMA liberates GSDMA from auto-inhibition, facilitating its membrane targeting and initiation of pyroptosis. To further validate the significance of GSDMA phosphorylation, we generated a constitutively active mutant Ser354Asp of mouse Gsdma, which induced skin inflammation and hyperplasia in mice, reminiscent of phenotypes with activated Gsdma. This study uncovers phosphorylation of GSDMA as a mechanism underlying pyroptosis initiation and cellular response to nutrient stress.
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Gasderminas , Piroptose , Animais , Humanos , Camundongos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Gasderminas/metabolismo , Células HEK293 , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Fosforilação , Inanição/metabolismoRESUMO
AIM: To explore the trend of burden and care quality of chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) and their cross-country inequalities from 1990 to 2021. MATERIALS AND METHODS: Data were from the Global Burden of Disease 2021 study. Disease burden and care quality were quantified using the disability-adjusted life years rate and the quality-of-care index (QCI). Trend analyses of the age-standardized disability-adjusted life years rate (ASDR) and age-standardized QCI from 1990 to 2021 were conducted using the estimated annual percentage change. The associations of disease burden and care quality with the socio-demographic index (SDI) were explored. Cross-country inequalities in disease burden and care quality were assessed using the slope index of inequality (SII) and concentration index. RESULTS: From 1990 to 2021, the global ASDR for CKD-T2DM increased, while the age-standardized QCI slightly decreased, with an estimated annual percentage change of 0.81 [95% confidence interval (CI): 0.75, 0.87] and -0.08 (95% CI: -0.09, -0.07). The ASDR escalated with increasing SDI, reaching a peak at mid-level SDI, followed by a decrease. The age-standardized QCI was higher with increasing SDI. Globally, ASDR concentrated on countries/territories with a lower SDI. The SII of ASDR was -96.64 (95% CI: -136.94, -56.35) in 1990 and -118.15 (95% CI: -166.36, -69.94) in 2021, with a concentration index of -0.1298 (95% CI: -0.1904, -0.0692) in 1990 and -0.1104 (95% CI: -0.1819, -0.0389) in 2021. In 1990 and 2021, countries/territories at higher SDI levels exhibited increased age-standardized QCI, indicated by an SII of 15.09 (95% CI: 10.74, 19.45) and 15.75 (95% CI: 10.92, 20.59), and a concentration index of 0.0393 (95% CI: 0.0283, 0.0503) and 0.0400 (95% CI: 0.0264, 0.0536). CONCLUSIONS: Our study highlights considerable disparities in the burden and care quality of CKD-T2DM. Regions experiencing an increasing burden and a declining care quality simultaneously underscore the need for further research and tailored health interventions.
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Efeitos Psicossociais da Doença , Diabetes Mellitus Tipo 2 , Carga Global da Doença , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Feminino , Masculino , Qualidade da Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Saúde Global , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Idoso , Fatores Socioeconômicos , Anos de Vida Ajustados por Deficiência , AdultoRESUMO
The reconsideration of aqueous zinc-ion batteries (ZIBs) has been motivated by the attractive zinc metal, which stands out for its high theoretical capacity and cost efficiency. Nonetheless, detrimental side reactions triggered by the remarkable reactivity of H2O molecules and rampant dendrite growth significantly compromise the stability of the zinc metal anode. Herein, a novel approach was proposed by leveraging the unique properties of acrylamide (AM) molecules to increase the driving force for nucleation and parasitic reactions. Combined with experimental data and theoretical simulations, it is demonstrated that the incorporation of AM additive can reconstruct the solvation shell around Zn2+ and reduce the number of active H2O molecules, thereby effectively reducing the H2O molecule decomposition. Consequently, the Zn//Zn symmetric batteries with AM-containing ZnSO4 electrolytes can attain excellent long-term performances over 2000 h at 1 mA cm-2 and nearly 500 h at 10 mA cm-2. The Zn//VO2 full batteries still display improved cycling performances and a high initial discharging capacity of 227 mA h g-1 at 3 A g-1 compared to the ZnSO4 electrolyte. This electrolyte optimization strategy offers new insights for achieving long-term ZIBs and advances the progress of ZIBs in energy storage.
RESUMO
Hen egg low-density lipoprotein (heLDL), as alternative of serum-derived LDL, was used as drug delivery system of ceftiofur (CEF). The CEF-loaded hen egg low-density lipoprotein (CEF-heLDL) with complete apolipoprotein structure and high drug loading rate was synthesized, possesses suitable particle size. CEF-heLDL undergoes cellular uptake and colocalizes with lysosomes in vitro. An intracellular infection model of the bovine endometrial epithelial cells and a coeliac-induced inflammation model of mice by Staphylococcus aureus (S. aureus) were established, and significantly lower intracellular S. aureus levels of CEF-heLDL group than CEF-free group (P < 0.001) was observed. The antibacterial efficacy was sustained for 24 h. Up to 400 mg/kg of CEF-heLDL, 20 times the clinical practice, were intraperitoneally administrated, and no significant toxicity signs on mice were observed. HeLDLs is an effective, safe, and cheap drug carrier, and could also be used for transmembrane delivering other antibiotics.
Assuntos
Antibacterianos , Cefalosporinas , Galinhas , Lipoproteínas LDL , Staphylococcus aureus , Animais , Staphylococcus aureus/efeitos dos fármacos , Lipoproteínas LDL/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Cefalosporinas/farmacologia , Cefalosporinas/farmacocinética , Cefalosporinas/química , Bovinos , Feminino , Portadores de Fármacos/química , Infecções Estafilocócicas/tratamento farmacológico , OvosRESUMO
Oat products have gained widespread recognition as a health food due to their rich and balanced nutritional profile and convenience. However, the unique matrix composition of oats, which differs significantly from other cereals, presents specific challenges for mycotoxin analysis. This study presents an ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method enhanced with an innovative egg white gel pretreatment for the simultaneous analysis of 13 regulated and unregulated trichothecenes in oats. The method demonstrated excellent performance with high accuracy (> 87.5%), repeatability (< 5.7%), and reproducibility (< 8.1%). Analysis of 100 commercial oat products revealed a concerning detection rate (78%) for at least one of the 11 trichothecenes investigated. Notably, deoxynivalenol, exceeding the standard limit in 2% of samples, exhibited the highest detection rate (62%). Additionally, concerning co-occurrence patterns and positive correlations were observed, highlighting potential synergistic effects. The first-time detection of unregulated mycotoxins (T-2 triol, 4,15-diacetoxyscirpenol, 15-acetoxyscirpenol, and neosolaniol) underscores the need for comprehensive monitoring. This method, while developed for oats, shows potential for broader application to other cereals, though further investigation and confirmation are necessary. These findings suggest a potentially underestimated risk of trichothecenes in oats, necessitating continuous monitoring to ensure consumer safety.