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Although leucine zipper tumour suppressor 1 (LZTS1) has been considered a potential tumour suppressor, accumulating evidence suggests that LZTS1 is highly expressed in many cancer types. To unravel the exact role of LZTS1 in colorectal carcinogenesis, we performed the bioinformatic analysis of LZTS1, including expression differences, correlations between expression levels and survival, methylation status of LZTS1 promoter and related cellular pathways based on TCGA dataset, GEO databases and our own CRC patient cohort. Furthermore, we confirmed the oncogenic function of LZTS1 in human mammalian cells by employing a series of assays including tissue microarray, immunoblotting, cell proliferation and migration assay. We found that the expression of LZTS1 is higher in tumour samples compared to paired normal tissue in CRC cancer and its different clinical subtypes, which is, at least in part, due to the low methylation status of LZTS1 promoter in CRC tumour samples. Functional analysis identified the close relationship between high expression of LZTS1 and PI3K-AKT pathway and the epithelial-mesenchymal transition (EMT) process. Consistently, we found that the expression of LZTS1 positively correlated with the expression PIK3CD, N-cadherin in CRC tumour samples, while the expression of LZTS1 negatively correlated with the expression of E-cadherin and PTEN in CRC tumour samples. Experimental data further confirmed that overexpression of LZTS1 upregulated activity of AKT and promoted EMT process. Furthermore, depletion of LZTS1 repressed the proliferation and migration rate of CRC cells. Thus, this study indicates that LZTS1 plays an oncogenic role in colorectal carcinogenesis.
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Neoplasias Colorrectales , Metilación de ADN , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Regiones Promotoras Genéticas , Humanos , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Metilación de ADN/genética , Transición Epitelial-Mesenquimal/genética , Oncogenes/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Transducción de Señal , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.
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Antibody-drug conjugates (ADCs) represent a promising cancer therapy modality which specifically delivers highly toxic payloads to cancer cells through antigen-specific monoclonal antibodies (mAbs). To date, 15 ADCs have been approved and more than 100 ADC candidates have advanced to clinical trials for the treatment of various cancers. Among these ADCs, microtubule-targeting and DNA-damaging agents are at the forefront of payload development. However, several challenges including toxicity and drug resistance limit the potential of this modality. To tackle these issues, multiple innovative payloads such as immunomodulators and proteolysis targeting chimeras (PROTACs) are incorporated into ADCs to enable multimodal cancer therapy. In this review, we describe the mechanism of ADCs, highlight the importance of ADC payloads and summarize recent progresses of conventional and unconventional ADC payloads, trying to provide an insight into payload diversification as a key step in future ADC development.
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Inmunoconjugados , Neoplasias , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Inmunoconjugados/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , AnimalesRESUMEN
BACKGROUND: The posterior auricular flap has long been favored for repairing skin defects on the ear's surface. However, achieving optimal esthetic outcomes in ear reconstruction requires a flexible approach to flap transfer methods. While bipedicle advancement flaps are commonly used for body wound coverage, they are rarely used in auricular defect repair. OBJECTIVE: To propose a modified flap transfer approach based on the orientation of the auricular defect's long axis and assess the postoperative esthetic outcomes. METHODS: The authors reported 12 patients treated using 2 distinct flap transfer techniques. Mild to moderate helix soft tissue defects remained after excision of the masses. A direct island flap was created for patients with longitudinal defects to cover the defect. For patients with transverse defects, a combination of bipedicle and island flaps was used for repair. Scar quality and esthetic outcomes were assessed at least 6 months postsurgery using the Scar Cosmesis Assessment and Rating scale. RESULTS: All patients experienced no serious complications and achieved excellent cosmetic results. Patients undergoing combined flap transfer exhibited relatively more favorable esthetic outcomes. CONCLUSION: The authors propose a novel concept for repairing helix soft tissue defects by designing local flaps based on the direction of the defect's long axis. For repairing helix soft tissue defects with a long axis parallel to the auricular edge, the combined utilization of bipedicle advancement flap and island rotation flap transfer should be consideration more.
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Estética , Procedimientos de Cirugía Plástica , Colgajos Quirúrgicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Adulto , Resultado del Tratamiento , Anciano , Neoplasias del Oído/cirugía , Oído Externo/cirugía , Pabellón Auricular/cirugía , Cicatriz/cirugíaRESUMEN
Background and Objective: Previous research suggested a relationship between the Systemic Immune-Inflammation Index (SII) and multiple adverse health conditions. However, the role of SII in prediabetes and insulin resistance (IR) remains poorly understood. Therefore, this study aims to explore the potential relationship between SII and prediabetes and IR, providing data support for effective diabetes prevention by reducing systemic inflammation. Methods: Linear regression models were used to assess the correlation between continuous SII and risk markers for type 2 diabetes (T2D). Subsequently, multivariate logistic regression models and subgroup analyses were employed to evaluate the association between SII tertiles and prediabetes and IR, controlling for various confounding factors. Finally, restricted cubic spline graphs were used to analyze the nonlinear relationship between SII and IR and prediabetes. Results: After controlling for multiple potential confounders, SII was positively correlated with fasting blood glucose (FBG) (ß: 0.100; 95% CI: 0.040 to 0.160), fasting serum insulin (FSI) (ß: 1.042; 95% CI: 0.200 to 1.885), and homeostasis model assessment of insulin resistance (HOMA-IR) (ß: 0.273; 95% CI: 0.022 to 0.523). Compared to participants with lower SII, those in the highest tertile had increased odds of prediabetes (OR: 1.17; 95% CI: 1.02-1.34; p for trend < 0.05) and IR (OR: 1.35; 95% CI: 1.18 to 1.51; p for trend<0.001). Conclusions: Our study results demonstrate an elevated association between SII levels and both IR and prediabetes, indicating SII as a straightforward and cost-effective method identifying individuals with IR and prediabetes.
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Glucemia , Inflamación , Resistencia a la Insulina , Estado Prediabético , Humanos , Estado Prediabético/inmunología , Estado Prediabético/sangre , Estado Prediabético/epidemiología , Masculino , Estudios Transversales , Femenino , Persona de Mediana Edad , Inflamación/sangre , Inflamación/inmunología , Glucemia/análisis , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/epidemiología , Adulto , Anciano , Biomarcadores/sangre , Insulina/sangreRESUMEN
BACKGROUND: Previous studies on maternal parenting styles and children's callous-unemotional behavior (CU behavior) have focused on the West, and few studies have examined the longitudinal relationship between maternal parenting styles and CU behavior using Chinese preschoolers as subjects. OBJECTIVE: Through a 1.5-year longitudinal lens, this study probed the relations between maternal parenting styles and CU behavior in the Chinese cultural setting. PARTICIPANTS: Participants were N = 492 Chinese young children (Mage = 52.44 months, SD = 5.00, 48 % girls). METHODS: At Time 1 (T1), mothers reported their use of authoritative parenting styles (i.e., warmth, reasoning, and autonomy), authoritarian parenting styles (i.e., physical coercion, verbal hostility, and nonreasoning) and children's CU behavior. At Time 2 (T2; approximately 1.5 years later), mothers again reported the above variables. RESULTS: Cross-lagged models indicated that maternal warmth, reasoning, autonomy, and nonreasoning at T1 predicted CU behavior at T2. However, not only did maternal physical coercion and verbal hostility at T1 predict CU behavior at T2, but CU behavior at T1 also predicted maternal physical coercion and verbal hostility at T2. Additionally, there were no gender differences in the relationship between dimensions of maternal parenting styles and CU behavior. CONCLUSIONS: It underscores the influence of authoritative parenting in potentially mitigating CU behavior, while authoritarian approaches may exacerbate CU behavior. The absence of gender differences suggests these dynamics are broadly applicable across genders. These findings have significant implications for parenting strategies aimed at addressing CU behavior in children, emphasizing the need for warmth, reasoning, and autonomy in parenting practices.
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Relaciones Madre-Hijo , Responsabilidad Parental , Humanos , Femenino , Responsabilidad Parental/psicología , Masculino , Preescolar , Estudios Longitudinales , Relaciones Madre-Hijo/psicología , China , Conducta Infantil/psicología , Autoritarismo , Hostilidad , Adulto , Pueblos del Este de AsiaRESUMEN
Purpose Tinnitus is a phantom perception of sound in the absence of acoustic source. Previous evidence has indicated that miR-375-3p is downregulated in rats with tinnitus in comparison to the controls. Nevertheless, its molecular mechanism underlying tinnitus pathogenesis is unclarified. Methods SH-SY5Y cells were differentiated into neuronlike cells and stimulated with salicylate to mimic tinnitus in vitro. Immunofluorescence staining was utilized for measuring expression of NR2B (glutamate ionotropic receptor NMDA type subunit 2B). Intracellular reactive oxygen species (ROS) level was determined using DCFH-DA assay kit. Real-time quantitative polymerase chain reaction as well as western blotting was utilized for examining RNA and protein levels. Luciferase reporter assay was implemented for verifying the interaction between miR-375-3p and ELAVL4 (ELAV-like RNA-binding protein 4). Results Salicylate treatment enhanced levels of NR2B and the early immediate gene ARC as well as ROS production. miR-375-3p was downregulated in salicylate-treated group. Overexpressing miR-375-3p attenuated the effects induced by salicylate in SH-SY5Y cells. miR-375-3p targeted ELAVL4 and upregulating ELAVL4 reversed miR-375-3p upregulation-triggered effects on SH-SY5Y cells under salicylate treatment. Conclusion miR-375-3p mitigates salicylate-triggered neuronal injury in SH-SY5Y cells by regulating ELAVL4 expression.
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Introduction: Conduct problems in children are related to callous-unemotional (CU) behaviors. However, results of the relationships between CU behaviors and conduct problems among preschoolers mainly focused on Western countries, no studies have examined whether CU behaviors predict conduct problem in Chinese preschoolers. The primary objective of the current study therefore was to examine the associations between CU behaviors and conduct problems as well as the moderating effects of surgency and child gender in Chinese preschool children. Methods: The present study randomly selected 2,154 children (1,043 boys, Mage = 56 months, SD = 10.47) from six kindergartens in Shanghai, People's Republic of China. Mothers rated children's surgency and teachers reported children's CU behaviors and conduct problems. Results: Results demonstrated that CU behaviors were positively associated with conduct problems. Surgency and child gender significantly moderated these associations. Specifically, CU behaviors were positively associated with conduct problems, with a stronger effect found for high levels of surgency. CU behaviors had a positive association with conduct problems, with a stronger effect found for boys. Discussion: This study indicate that temperament and gender characteristics influence conduct problems in preschoolers who exhibit high levels of CU behaviors. As well, the findings emphasize the significance of considering the meaning and implication of CU behaviors in Chinese culture.
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AIMS: To estimate the association between long-term changes in frailty and the risk of incident type 2 diabetes (T2DM) and to evaluate the effect of preventing the worsening of frailty on the risk of T2DM. METHODS: We included 348 205 participants free of baseline T2DM and with frailty phenotype (FP) data from the UK Biobank; among them, 36 175 had at least one follow-up assessment. According to their FP score, participants were grouped into nonfrailty, prefrailty and frailty groups. Frailty assessed at baseline and at follow-up was used to derive the trajectory of frailty (ΔFP). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with those in the nonfrailty group at baseline, the HRs of T2DM for the prefrailty and frailty groups were 1.38 (95% CI 1.33-1.43) and 1.69 (95% CI 1.59-1.79), respectively (both p < 0.001), in the multivariable-adjusted model. During a median follow-up of 5.4 years after the final assessment, data for 472 T2DM patients were recorded. A 1-point increase in the final FP was associated with a 25% (95% CI 1.14-1.38; p < 0.001) increased risk of T2DM. For the trajectory of frailty, each 0.5-point/year increase in ΔFP was associated with a 52% (95% CI 1.18-1.97; p < 0.001) greater risk of T2DM, independent of the FP score at baseline. Compared with those that remained in the nonfrailty group, the greatest risk of T2DM over time was prefrailty aggravation (HR 3.03, 95% CI 2.00-4.58; p < 0.001). Using the frailty index did not materially change the results. CONCLUSIONS: Long-term changes in frailty were associated with the risk of incident T2DM, irrespective of baseline frailty status. Preventing the worsening of frailty may reduce T2DM risk.
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Bancos de Muestras Biológicas , Diabetes Mellitus Tipo 2 , Fragilidad , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Fragilidad/epidemiología , Femenino , Masculino , Reino Unido/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Bancos de Muestras Biológicas/estadística & datos numéricos , Incidencia , Factores de Riesgo , Estudios de Seguimiento , Adulto , Modelos de Riesgos Proporcionales , Anciano Frágil/estadística & datos numéricos , Estudios de Cohortes , Biobanco del Reino UnidoRESUMEN
Peer relationships play an indispensable role in the social, emotional, and cognitive development of children. However, children exhibiting social withdrawal, such as unsociability, may face challenges in social adjustment. In collectivistic cultures like China, unsociability may be perceived negatively, aligning poorly with collective norms. The objective of the present investigation was to examine the associations between unsociability, receptive vocabulary, and indicators of social adjustment in a cohort of young migrant children residing in urban regions of mainland China. The study mainly aimed to investigate the potential moderating influence of receptive language on these associations. The study involved 148 young children (82 boys, 66 girls, Mage = 62.32 months, SD = 6.76) enrolled in preschools or kindergartens in Shanghai, People's Republic of China. Multiple sources of assessment were utilized, encompassing evaluations from mothers (about child unsociability), teacher (assessing social adjustment), and standardized tests (measuring receptive vocabulary). The results indicated that the relations between unsociability and peer exclusion were more positive among children with lower levels of receptive vocabulary but not significant for children with higher levels of receptive vocabulary. Similarly, the relations between unsociability and peer exclusion were more negative among children with lower levels of receptive vocabulary but not significant for children with higher levels of receptive vocabulary. Thus, this study informs us about how receptive vocabulary is jointly associated with unsociable children's development. As well, the findings highlight the importance of considering the meaning and implication of unsociability in Chinese culture.
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Litter input triggers the secretion of soil extracellular enzymes and facilitates the release of carbon (C), nitrogen (N), and phosphorus (P) from decomposing litter. However, how soil extracellular enzyme activities were controlled by litter input with various substrates is not fully understood. We examined the activities and stoichiometry of five enzymes including ß-1,4-glucosidase, ß-D-cellobiosidase, ß-1,4-N-acetyl-glucosaminidase, leucine aminopeptidase and acidic phosphatase (AP) with and without litter input in 10-year-old Castanopsis carlesii and Cunninghamia lanceolata plantations monthly during April to August, in October, and in December 2021 by using an in situ microcosm experiment. The results showed that: 1) There was no significant effect of short-term litter input on soil enzyme activity, stoichiometry, and vector properties in C. carlesii plantation. In contrast, short-term litter input significantly increased the AP activity by 1.7% in May and decreased the enzymatic C/N ratio by 3.8% in August, and decreased enzymatic C/P and N/P ratios by 11.7% and 10.3%, respectively, in October in C. lanceolata plantation. Meanwhile, litter input increased the soil enzymatic vector angle to 53.8° in October in C. lanceolata plantations, suggesting a significant P limitation for soil microorganisms. 2) Results from partial least squares regression analyses showed that soil dissolved organic matter and microbial biomass C and N were the primary factors in explaining the responses of soil enzymatic activity to short-term litter input in both plantations. Overall, input of low-quality (high C/N) litter stimulates the secretion of soil extracellular enzymes and accelerates litter decomposition. There is a P limitation for soil microorganisms in the study area.
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Carbono , Cunninghamia , Fagaceae , Nitrógeno , Fósforo , Microbiología del Suelo , Suelo , Suelo/química , Cunninghamia/crecimiento & desarrollo , Cunninghamia/metabolismo , Carbono/metabolismo , Carbono/análisis , Nitrógeno/metabolismo , Nitrógeno/análisis , Fósforo/metabolismo , Fósforo/análisis , Fagaceae/crecimiento & desarrollo , Fagaceae/metabolismo , Leucil Aminopeptidasa/metabolismo , Celulosa 1,4-beta-Celobiosidasa/metabolismo , Ecosistema , Hojas de la Planta/metabolismo , Hojas de la Planta/química , Acetilglucosaminidasa/metabolismo , Fosfatasa Ácida/metabolismo , beta-Glucosidasa/metabolismo , ChinaRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy, largely due to the paucity of reliable biomarkers for early detection and therapeutic targeting. Existing blood protein biomarkers for PDAC often suffer from replicability issues, arising from inherent limitations such as unmeasured confounding factors in conventional epidemiologic study designs. To circumvent these limitations, we use genetic instruments to identify proteins with genetically predicted levels to be associated with PDAC risk. Leveraging genome and plasma proteome data from the INTERVAL study, we established and validated models to predict protein levels using genetic variants. By examining 8,275 PDAC cases and 6,723 controls, we identified 40 associated proteins, of which 16 are novel. Functionally validating these candidates by focusing on 2 selected novel protein-encoding genes, GOLM1 and B4GALT1, we demonstrated their pivotal roles in driving PDAC cell proliferation, migration, and invasion. Furthermore, we also identified potential drug repurposing opportunities for treating PDAC. SIGNIFICANCE: PDAC is a notoriously difficult-to-treat malignancy, and our limited understanding of causal protein markers hampers progress in developing effective early detection strategies and treatments. Our study identifies novel causal proteins using genetic instruments and subsequently functionally validates selected novel proteins. This dual approach enhances our understanding of PDAC etiology and potentially opens new avenues for therapeutic interventions.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteoma , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Glicosiltransferasas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biomarcadores , Proteínas de la MembranaRESUMEN
Neoantigens have emerged as promising targets for cutting-edge immunotherapies, such as cancer vaccines and adoptive cell therapy. These neoantigens are unique to tumors and arise exclusively from somatic mutations or non-genomic aberrations in tumor proteins. They encompass a wide range of alterations, including genomic mutations, post-transcriptomic variants, and viral oncoproteins. With the advancements in technology, the identification of immunogenic neoantigens has seen rapid progress, raising new opportunities for enhancing their clinical significance. Prediction of neoantigens necessitates the acquisition of high-quality samples and sequencing data, followed by mutation calling. Subsequently, the pipeline involves integrating various tools that can predict the expression, processing, binding, and recognition potential of neoantigens. However, the continuous improvement of computational tools is constrained by the availability of datasets which contain validated immunogenic neoantigens. This review article aims to provide a comprehensive summary of the current knowledge as well as limitations in neoantigen prediction and validation. Additionally, it delves into the origin and biological role of neoantigens, offering a deeper understanding of their significance in the field of cancer immunotherapy. This article thus seeks to contribute to the ongoing efforts to harness neoantigens as powerful weapons in the fight against cancer.
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Antígenos de Neoplasias , Neoplasias , Humanos , Antígenos de Neoplasias/genética , Neoplasias/genética , Neoplasias/terapia , InmunoterapiaRESUMEN
Data mining by machine learning (ML) has recently come into application in heavy metals purification from wastewater, especially in exploring lead removal by biochar that prepared using tube furnace (TF-C) and fluidized bed (FB-C) pyrolysis methods. In this study, six ML models including Random Forest Regression (RFR), Gradient Boosting Regression (GBR), Support Vector Regression (SVR), Kernel Ridge Regression (KRR), Extreme Gradient Boosting (XGB), and Light Gradient Boosting Machine (LGBM) were employed to predict lead adsorption based on a dataset of 1012 adsorption experiments, comprising 422 TF-C groups from our experiments and 590 FB-C groups from literatures. The XGB model showed superior accuracy and predictive performance for adsorption, achieving R2 values for TF-C (0.992) and FB-C (0.981), respectively. Contrasting inferior results were observed in other models, including RF (0.962 and 0.961), GBR (0.987 and 0.975), SVR (0.839 and 0.763), KRR (0.817 and 0.881), and LGBM (0.975 and 0.868). Additionally, a hybrid dataset combining both biochars in Pb adsorption also indicated high accuracy (0.972) as obtained from XGB model. The investigation revealed that the influence of char characteristics and adsorption conditions on Pb adsorption differs between the two biochar. Specific char characteristics, particularly nitrogen content, significantly influence lead adsorption in both biochar. Interestingly, the influence of pyrolysis temperature (PT) on lead adsorption is found to be greater for TF-C than for FB-C. Consequently, careful consideration of PT is crucial when preparing TF-C biochar. These findings offer practical guidance for optimizing biochar preparation conditions during heavy metal removal from wastewater.
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Carbón Orgánico , Plomo , Aprendizaje Automático , Carbón Orgánico/química , Plomo/química , Adsorción , Contaminantes Químicos del Agua/químicaRESUMEN
High temperatures affect grape yield and quality. Grapes can develop thermotolerance under extreme temperature stress. However, little is known about the changes in transcription that occur because of high-temperature stress. The heat resistance indices and transcriptome data of five grape cultivars, 'Xinyu' (XY), 'Miguang' (MG), 'Summer Black' (XH), 'Beihong' (BH), and 'Flame seedless' (FL), were compared in this study to evaluate the similarities and differences between the regulatory genes and to understand the mechanisms of heat stress resistance differences. High temperatures caused varying degrees of damage in five grape cultivars, with substantial changes observed in gene expression patterns and enriched pathway responses between natural environmental conditions (35 °C ± 2 °C) and extreme high temperature stress (40 °C ± 2 °C). Genes belonging to the HSPs, HSFs, WRKYs, MYBs, and NACs transcription factor families, and those involved in auxin (IAA) signaling, abscisic acid (ABA) signaling, starch and sucrose pathways, and protein processing in the endoplasmic reticulum pathway, were found to be differentially regulated and may play important roles in the response of grape plants to high-temperature stress. In conclusion, the comparison of transcriptional changes among the five grape cultivars revealed a significant variability in the activation of key pathways that influence grape response to high temperatures. This enhances our understanding of the molecular mechanisms underlying grape response to high-temperature stress.
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Skin wound healing often leads to scar formation, presenting physical and psychological challenges for patients. Advancements in messenger RNA (mRNA) modifications offer a potential solution for pulsatile cytokine delivery to create a favorable wound-healing microenvironment, thereby preventing cutaneous fibrosis. This study aimed to investigate the effectiveness of human adipose-derived stem cells (hADSCs) enriched with N 1-methylpseudouridine (m1ψ) modified transforming growth factor-ß3 (TGF-ß3) and interleukin-10 (IL-10) mRNA in promoting scar-free healing in preclinical models. The results demonstrated that the modified mRNA (modRNA)-loaded hADSCs efficiently and temporarily secreted TGF-ß3 and IL-10 proteins. In a dorsal injury model, hADSCs loaded with modRNA TGF-ß3 and IL-10 exhibited multidimensional therapeutic effects, including improved collagen deposition, extracellular matrix organization, and neovascularization. In vitro experiments confirmed the ability of these cells to markedly inhibit the proliferation and migration of keloid fibroblasts, and reverse the myofibroblast phenotype. Finally, collagen degradation mediated by matrix metalloproteinase upregulation was observed in an ex vivo keloid explant culture model. In conclusion, the synergistic effects of the modRNA TGF-ß3, IL-10, and hADSCs hold promise for establishing a scar-free wound-healing microenvironment, representing a robust foundation for the management of wounds in populations susceptible to scar formation.
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Introduction: Problem behaviors in preschoolers signals social adjustment challenges. This study investigates the mediating role of parenting stress in the relationship between co-parenting and these behaviors, and examines how family resilience impacts this dynamic. Methods: A detailed survey was conducted with 1279 mothers of 3-6-year-olds in Shanghai, China, focusing on co-parenting, family resilience, parenting stress, and children's behaviors. We employed SPSS 26 for initial tests and the Hayes PROCESS macro in SPSS 23.0 for advanced analysis, using bootstrap methods to assess mediation and moderation effects. Results: The analysis revealed that maternal parenting stress mediates the relationship between co-parenting and children's problem behaviors. Specifically, unsupportive co-parenting or low levels of supportive co-parenting heightened maternal stress, which in turn increased children's problem behaviors. Family resilience was found to moderate this relationship, buffering the impact of unsupportive co-parenting on maternal stress. High family resilience levels were associated with lower parenting stress, regardless of co-parenting quality. Conclusion: These findings highlight the importance of enhancing family resilience and supportive co-parenting to mitigate parenting stress and reduce problem behaviors in children. It has practical implications for developing family-centred interventions and policies to strengthen family resilience and co-parenting skills.
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Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children.