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In response to the environmental implications of the massive quantities of excavation soil generated by global urbanization and infrastructure development, recent research efforts have explored the repurposing of calcined excavation soils as sustainable supplementary cementitious materials (SCMs). As it is still at an early stage, current research lacks systematic analysis across diverse soil deposits regarding their reactivity and mechanical properties within cementitious binders, despite recognized geographical variability in kaolinite content. Through comprehensive experimentation with soils sourced from four major southern Chinese cities, this study presents a pioneering assessment of the compressive strength, pozzolanic reactivity (X-ray diffraction, Fourier-transform infrared spectroscopy, solid-state nuclear magnetic resonance), and microstructural development (mercury intrusion porosimetry, scanning electron microscopy) of mortars modified by various calcined excavation soils (up to 28 days curing). The experimental data suggest that soils with a kaolinite content above 53.39% produce mortars of equal or superior quality to plain cement mixes, primarily due to their refined pore structures, microstructural densification, and enhanced hydration reactions. The findings highlight kaolinite-specifically, aluminum content-as the principal indicator of excavation soil viability for SCM application, suggesting a promising avenue for sustainable construction practices.
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Rapid urbanization in many cities has produced massive amounts of problematic excavation soil. The direct disposal of untreated excavation soil often leads to significant land use and severe environmental concerns. A sustainable solution is to transform the soil waste into high-quality nano-calcined excavation soil (NCES) for application as a substitute for cement in construction. However, research in this area is very limited. This study presents a systematic investigation of the nano-sized calcined soil materials from preparation to application in cementitious material. The influence of milling parameters, including the rotational speed, milling duration, ball diameter, and milling strategy, was investigated to produce NCES with various specific surface areas. The effect of NCES substitution (15 wt% of Portland cement) in cementitious materials was then examined for mechanical performance, hydration dynamics, hydration products, and microstructure. A cement mix with very fine NCES (specific surface area of 108.76 m2/g) showed a 29.7% enhancement in mechanical strength and refined pore structure while a cement mix with un-grounded calcined soil showed a mechanical loss in comparison to the Control specimen. Delayed and reduced heat release at an early age was observed in a cement paste mixed with NCES. The underlying mechanism was investigated. The results of this work will contribute to the high-quality application of excavation soil waste.
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Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming "cold" tumors into "hot" tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias , Receptor de Muerte Celular Programada 1 , Inmunoterapia , Sistemas de Liberación de Medicamentos , Linfocitos T CD8-positivos , Neoplasias/tratamiento farmacológicoRESUMEN
Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.
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Proteína HMGB1 , Melanoma , Humanos , Ratones , Animales , Interleucina-12 , Linfocitos T CD8-positivos , Melanoma/terapia , Melanoma/metabolismo , Proteína HMGB1/metabolismo , Muerte Celular Inmunogénica , Ratones Endogámicos C57BL , Proliferación Celular , Linfocitos T CD4-Positivos , Adenosina Trifosfato/metabolismoRESUMEN
Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.
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Adenina , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , Adenina/análogos & derivados , Autofagia/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Antígeno CD47/genética , Línea Celular Tumoral , Proliferación Celular/genética , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Pulmonares/patología , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Fagocitosis , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Nonobstructive azoospermia (NOA), the most severe manifestation of male infertility, lacks a comprehensive understanding of its genetic etiology. Here, a bi-allelic loss-of-function variant in REC114 (c.568C > T: p.Gln190*) were identified through whole exome sequencing (WES) in a Chinese NOA patient. Testicular histopathological analysis and meiotic chromosomal spread analysis were conducted to assess the stage of spermatogenesis arrested. Co-immunoprecipitation (Co-IP) and Western blot (WB) were used to investigate the influence of variant in vitro. In addition, our results revealed that the variant resulted in truncated REC114 protein and impaired interaction with MEI4, which was essential for meiotic DNA double-strand break (DSB) formation. As far as we know, this study presents the first report that identifies REC114 as the causative gene for male infertility. Furthermore, our study demonstrated indispensability of the REC114-MEI4 complex in maintaining DSB homoeostasis, and highlighted that the disruption of the complex due to the REC114 variant may underline the mechanism of NOA.
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Azoospermia , Infertilidad Masculina , Humanos , Masculino , Azoospermia/genética , Azoospermia/patología , Pérdida de Heterocigocidad , Infertilidad Masculina/genética , Infertilidad Masculina/patología , Testículo/patología , Meiosis/genética , Proteínas de Ciclo Celular/genéticaRESUMEN
ABSTRACT: The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis. The single-cell RNA sequencing (scRNA-seq) analysis of the testis was performed to identify genes upregulated in spermatogonia. Using scRNA-seq analysis, we identified the spermatogonia upregulated gene origin recognition complex subunit 6 (Orc6), which is involved in DNA replication and cell cycle regulation; its protein expression in the human and mouse testis was detected by western blot and immunofluorescence. To explore the potential function of Orc6 in spermatogonia, the C18-4 cell line was transfected with control or Orc6 siRNA. Subsequently, 5-ethynyl-2-deoxyuridine (EdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, flow cytometry, and western blot were used to evaluate its effects on proliferation and apoptosis. It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells. Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated (Wnt)/ ß-catenin signaling. Western blot revealed that the expression of ß-catenin protein and its phosphorylation (Ser675) were significantly decreased when silencing the expression of ORC6. Our findings indicated that Orc6 was upregulated in spermatogonia, whereby it regulated proliferation and apoptosis by activating Wnt/ß-catenin signaling.
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Leukemia cells prevent immune system from clearing tumor cells by inducing the immunosuppression of the bone marrow (BM) microenvironment. In recent years, further understanding of the BM microenvironment and immune landscape of leukemia has resulted in the introduction of several immunotherapies, including checkpoint inhibitors, T-cell engager, antibody drug conjugates, and cellular therapies in clinical trials. Among them, the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis is a significant checkpoint for controlling immune responses, the PD-1 receptor on tumor-infiltrating T cells is bound by PD-L1 on leukemia cells. Consequently, the activation of tumor reactive T cells is inhibited and their apoptosis is promoted, preventing the rejection of the tumor by immune system and thus resulting in the occurrence of immune tolerance. The PD-1/PD-L1 axis serves as a significant mechanism by which tumor cells evade immune surveillance, and PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of lymphomas and varieties of solid tumors. However, the development of drugs targeting PD-1/PD-L1 in leukemia remains in the clinical-trial stage. In this review, we tally up the basic research and clinical trials on PD-1/PD-L1 inhibitors in leukemia, as well as discuss the relevant toxicity and impacts of PD-1/PD-L1 on other immunotherapies such as hematopoietic stem cell transplantation, bi-specific T-cell engager, chimeric antigen receptor T-cell immunotherapy.
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Antígeno B7-H1 , Leucemia , Humanos , Antígeno B7-H1/metabolismo , Tolerancia Inmunológica , Inmunoterapia/métodos , Leucemia/terapia , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente TumoralRESUMEN
Introduction: As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies. Methods: In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core. Results: In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities. Conclusion: In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.
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Micelas , Nanopartículas , Muerte Celular Inmunogénica , Indoles/química , Fototerapia/métodos , Nanopartículas/química , Mitocondrias , Línea Celular TumoralRESUMEN
The electrochemical recycling nanoarchitectonics of graphene oxide from carbon fiber reinforced polymers (CFRPs) is a promising approach due to its economic and environmental benefits. However, the rapid degradation of the CFRP anode during the recycling process reduces its overall efficiency. Although previous studies have investigated the electrochemical oxidation of carbon fibers (CFs) and bonding of CFs to the matrix, few researchers have explicitly studied the electrochemical activity of CFs and the possible fracture caused by strong electrochemical reactions. To address this gap, this study investigates the degradation mechanism of CF anodes by analyzing changes in overall mechanical properties, hardness, elastic modulus, functional groups, and elemental composition of individual fibers. The experimental results demonstrate that the three-phase boundary region experiences the most severe degradation, primarily due to the number of oxygen-containing functional groups, which is the most important factor affecting the degree of degradation. This continuous decrease in the hardness and elastic modulus of individual fibers eventually leads to the fracture of CF anodes.
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Imatinib resistance in chronic myelogenous leukemia (CML) is a clinical problem. The present study examined the role of NMyc downstream regulatory gene 3 (NDRG3) in imatinib resistance in CML. Quantitative PCR demonstrated that NDRG3 was highly expressed in patients with CML. Cell Counting Kit (CCK)8 experiments proved that NDRG3 promoted the proliferation of K562 CML cells and enhanced imatinib resistance. Dualluciferase assay showed that microRNA (miR)2045p inhibited expression of NDRG3 and immunofluorescence experiments showed that NDRG3 promoted accumulation of ßcatenin in the nucleus, thereby increasing the expression of downstream drug resistance and cell cycleassociated factors (cMyc and MDR1). At the same time, cell proliferation experiments showed that ßcatenin played a role in cell proliferation and drug resistance. Cotransfection with small interfering (si)ßcatenin partially reversed the effect of NDRG3. This finding indicated that NDRG3 plays an important role in imatinib resistance and miR2045p and ßcatenin are involved in the biological behavior of NDRG3. The present results provide theoretical support for overcoming drug resistance in CML.
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Leucemia Mielógena Crónica BCR-ABL Positiva , MicroARNs , Humanos , Mesilato de Imatinib/farmacología , Mesilato de Imatinib/uso terapéutico , beta Catenina/genética , MicroARNs/genética , MicroARNs/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Células K562 , Péptidos y Proteínas de Señalización IntracelularRESUMEN
Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-ß signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.
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BACKGROUND: MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR-138-5p in lung cancer progression and the value of miR-138-5p in lung cancer diagnosis. METHODS: Quantitative real-time PCR was performed to examine the expressions of miR-138-5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR-138-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR-138-5p on cell proliferation and metastasis by CCK-8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay. RESULTS: MiR-138-5p was decreased in the serum of patients with non-small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR-138-5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR-138-5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR-138-5p directly binds to the 3'-untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c-Myc. Moreover, overexpression of SNIP1 rescues the miR-138-5p-mediated inhibition in NSCLC cells. CONCLUSIONS: The results suggested that miR-138-5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR-138-5p is a novel and valuable biomarker for NSCLC diagnosis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Neoplasias Pulmonares/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , MicroARNs/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al ARN/genéticaRESUMEN
Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O2-producing liposome with NAG/R8-dual-ligand and stimuli-responsive dePEGylation was developed to address the abovementioned issues simultaneously. The designed C-NAG-R8-PTXL/MnO2-lip could also achieve magnetic resonance imaging (MRI)-guided synergistic chemodynamic/chemotherapy (CDT/CT). In vitro and in vivo studies showed that C-NAG-R8-PTXL/MnO2-lip enhanced circulation time by PEG and targeted the tumor site. After tumor accumulation, endogenous l-cysteine was administered, and the PEG-attached disulfide bond was broken, resulting in the dissociation of PEG shells. The previously hidden positively charged R8 by different lengths of PEG chains was exposed and mediated efficient internalization. In addition, the oxygen (O2) generated by C-NAG-R8-PTXL/MnO2-lip relieved the hypoxic environment within the tumor, thus reducing the efflux of chemotherapeutic drug. O2 was able to burst liposomes and triggered the release of PTXL. The toxic hydroxyl radical (·OH), which was produced by H2O2 and Mn2+, strengthened CDT/CT. C-NAG-R8-PTXL/MnO2-lip was also used as MRI contrast agent, which blazed the trail to rationally design theranostic agents for tumor imaging.
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Liposomas , Neoplasias , Humanos , Liposomas/química , Compuestos de Manganeso/química , Línea Celular Tumoral , Peróxido de Hidrógeno , Óxidos/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Resistencia a Múltiples Medicamentos , Oxígeno , Imagen por Resonancia Magnética , Microambiente Tumoral , Nanomedicina TeranósticaRESUMEN
Long non-coding RNAs (lncRNAs) modulate cell proliferation, cycle, and apoptosis. However, the role of lncRNA-WFDC21P in the tumorigenesis of triple-negative breast cancer (TNBC) remains unclear. Results of this study demonstrated that WFDC21P levels significantly increased in TNBC, which was associated with the poor survival of patients. WFDC21P overexpression significantly promoted TNBC cell proliferation and metastasis. WFDC21P interacted with miR-628-5p, which further suppressed cell proliferation and metastasis by negatively regulating Smad3-related gene expression. Recovery of miR-628-5p weakened the roles of WFDC21P in promoting the growth and metastasis of TNBC cells. Moreover,N6-methyladenosine (m6A) modification upregulated WFDC21P expression in the TNBC cells. WFDC21P and its m6A levels were increased after methyltransferase like 3 (METTL3) overexpression but reduced after METTL3 silencing. The proliferation and metastasis of TNBC cells were promoted by METTL3 overexpression but suppressed by METTL3 silencing. This study demonstrated the vital roles of WFDC21P and its m6A in regulating the proliferation and metastasis of TNBC cells via the WFDC21P/miR-628/SMAD3 axis.
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In this paper, an electrochemical method was proposed to recycle nanoarchitectonics of graphene oxide (GO) from carbon fiber reinforced polymer (CFRP). In the recycling process, NaCl solution with varied concentrations (3% and 10%) and tap water were used as electrolyte, while the impressed current density varied from 2.67 A/m2 to 20.63 A/m2. The results indicated that in NaCl electrolyte, the obtained nanoarchitectonics of GO contained a large amount of nano-carbon onions (NCO) produced by etching CFRP, while high purity GO was produced when tap water was used as electrolyte. The higher current density improved the production efficiency and resulted in a finer GO particle size. The proposed recycling method of GO is economical and simple to operate. It also provides an alternate approach to handle discarded CFRP.
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The characteristics of dissolved organic matter (DOM) in the influent and secondary effluent from 6 municipal wastewater treatment plants (WWTPs) were investigated with a size exclusion chromatogram (SEC) coupled with multiple detectors to simultaneously detect ultraviolet absorbance, fluorescence, dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) as a function of molecular weight (MW). The SEC chromatograms showed that biopolymers (>6 kDa) and humic substances (0.5-6 kDa) comprised the significant fraction in the influent, while humic substances became the abundant proportion in the secondary effluent. Direct linkages between MW distribution and hydrophobicity of DOM in the secondary effluent were further explored via SEC analysis of XAD resin fractions. DON and DOC with different hydrophobicity exhibited significantly distinct MW distribution, indicating that it was improper to consider DOC as a surrogate for DON. Different from DOC, the order of averaged MW in terms of DON was hydrophobic neutral ≈ transphilic neutral > hydrophobic acid > transphilic acid > hydrophilic fraction. Fluorescence spectral properties exhibited a significant semi-quantitative correlation with MW and hydrophobicity of DOC, with Pearson's coefficients of -0.834 and 0.754 (p < 0.01) for biopolymer and humic substances. Meanwhile, regional fluorescence proportion was demonstrated to indicate the MW and hydrophobicity properties of DON at the semi-quantitative level. The fluorescence excitation-emission matrix (EEM) could be explored to provide a rapid estimation of MW distribution and hydrophobic/hydrophilic proportion of DOC and DON in WWTPs.
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Aguas Residuales , Contaminantes Químicos del Agua , Materia Orgánica Disuelta , Sustancias Húmicas/análisis , Interacciones Hidrofóbicas e Hidrofílicas , Peso Molecular , Espectrometría de Fluorescencia , Aguas Residuales/química , Contaminantes Químicos del Agua/análisisRESUMEN
This paper proposes a new chemical combustion method for the synthesis of nano-low-carbon belite cement via a simple one-step process without using any oxidizers, and related mechanisms are briefly introduced. The starting materials used, including micro-silica (silica fume) as a byproduct of the metallurgic industry and CaCO3 powders, are of great abundance, and the processing parameters involved were optimized using a series of systematic experiments based on X-ray diffraction (XRD) and the Rietveld fitting method. Besides, the properties of the synthesized belite cement were characterized by the Brunauer-Emmett-Teller (BET) technique and scanning electron microscopy (SEM). Experimental results revealed that the optimized fuel agent was urea with a dosage of 4.902 times that of the starting materials by mass, and the corresponding holding temperature and time were 1150 °C and 2 h, respectively. In addition, the CaO/(SiO2 + CaO) for the starting materials should be set at 62.5% by mass ratio. BET and SEM results showed that the obtained belite cement had a specific surface area of 11.17 m2/g and a size of around 500 nm or even smaller in spherical shapes, suggesting that this method was successfully implemented. Thus, it can be a promising approach for the synthesis of nano-belite particles as a low-carbon construction material, which could be used more in the near future, such as for low-carbon concrete productions.
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PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a "pseudokinase", contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a "pseudokinase", has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2-/- mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.
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The determination of trace-level pharmaceuticals in water is generally performed using liquid chromatography combined with mass spectrometry, which is susceptible to interference from non-target substances, such as natural organic matter (NOM). In this study, the interference of NOM on the determination of 20 typical pharmaceuticals using solid-phase extraction followed by ultra-performance liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (UPLC-ESI-tqMS) was investigated with a combined consideration of recoveries, matrix effects, and process efficiencies. The results showed that the recoveries of most pharmaceuticals were not significantly affected by NOM concentrations of 1-50 mg/L. The matrix effects and process efficiencies decreased linearly with increasing logarithmic NOM concentrations, and the changes in matrix effects and process efficiencies both exhibited negative linear correlations with the pharmaceuticals' hydrophobicity (logKow). This result indicated that the determination of hydrophilic pharmaceuticals suffered from more severe NOM interference, as NOM entered the ESI source together with hydrophilic pharmaceuticals after UPLC separation and subsequently weakened the ionization efficiency of these pharmaceuticals. According to the correlations between logKow and the changes in matrix effects and process efficiencies, the pharmaceutical determination in positive/negative ESI modes with logKow ≤ 3.80/4.27 is considered to be significantly affected by NOM, accompanied by > 20% changes in matrix effects and process efficiencies.