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Zearalenone, a prominent mycotoxin produced by Fusarium spp., ubiquitously contaminates cereal grains and animal feedstuffs. The thermal stability of zearalenone creates serious obstacles for traditional removal methods, which may introduce new safety issues, or reducing nutritional quality. In contrast, biological technologies provide appealing benefits such as easy to apply and effective, with low toxicity byproducts. Thus, this review aims to describe the occurrence of zearalenone in cereals and cereal-based feedstuffs in the recent 5 years, outline the rules and regulations regarding zearalenone in the major countries, and discuss the recent developments of biological methods for controlling zearalenone in cereals and cereal-based feedstuffs. In addition, this article also reviews the application and the development trend of biological strategies for removal zearalenone in cereals and cereal-based feedstuffs.
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Advanced glycation end products (AGEs), heterocyclic aromatic amines (HAAs), acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and polycyclic aromatic hydrocarbons (PAHs) are toxic substances that are produced in certain foods during thermal processing by using common high-temperature unit operations such as frying, baking, roasting, grill cooking, extrusion, among others. Understanding the formation pathways of these potential risk factors, which can cause cancer or contribute to the development of many chronic diseases in humans, is crucial for reducing their occurrence in thermally processed foods. During thermal processing, food rich in carbohydrates, proteins, and lipids undergoes a crucial Maillard reaction, leading to the production of highly active carbonyl compounds. These compounds then react with other substances to form harmful substances, which ultimately affect negatively the health of the human body. Although these toxic compounds differ in various forms of formation, they all partake in the common Maillard pathway. This review primarily summarizes the occurrence, formation pathways, and reduction measures of common toxic compounds during thermal processing of food, based on independent studies for each specific contaminant in its corresponding food matrix. Finally, it provides several approaches for the simultaneous reduction of multiple toxic compounds.
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Al x CoCrFeNi (x = 0.1, 0.5 and 1) high-entropy alloys (HEAs) were prepared using a spark plasma sintering (SPS) technique combined with aerosol powder. Their microstructure and phase constituents were characterized using an X-ray diffractometer and SEM, and their tensile properties, hardness and compactness were tested. The results show that the crystal structure of the Al x CoCrFeNi HEAs changed significantly with the Al content, from the original single face-centered cubic FCC phase (Al0.1CoCrFeNi) to an FCC + BCC structure (Al0.5CoCrFeNi), and then to FCC + BCC + sigma (σ) phase structures (AlCoCrFeNi). Chemical composition analysis showed that the crystal structure transformation was related to the segregation caused by the increased Al content. The hardness of the Al x CoCrFeNi HEAs increases with increasing Al content, and the hardness of AlCoCrFeNi reaches a maximum of 507.3 HV. The tensile properties of the alloy show a trend of first increasing and then decreasing with increasing Al content, and the yield strength, ultimate tensile strength and elongation of the Al0.5CoCrFeNi alloy reach maximum values of 527.4 MP, 943.3 MPa and 28.2%, respectively. The fracture mechanism of the Al0.1CoCrFeNi and Al0.5CoCrFeNi alloys is typical ductile fracture, while that of the AlCoCrFeNi alloy is cleavage fracture. The compactness of the alloy increases with the Al content. The samples were also subjected to high-temperature water vapour corrosion, and corrosion products such as Al3Fe5O12, CoCr2O4 and NiCr2O4 were found in the Al0.1 and Al0.5 alloys, whereas no oxide peaks were detected using XRD for the Al1 alloy. It was also presumed that a very thin alumina film was generated on the surface of the Al1 alloy, preventing the oxidation of the sample, in combination with the analysis of SEM, EDS and XPS behaviour.
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Background and purpose: Nutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury. Methods: This cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA). Results: The CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40-0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35-0.64)] in the multivariate logistic model. A positive association between "Organ meat, poultry, and vegetable oil" dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42-6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09-3.05)] was observed. Conclusion: In conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the "Organ meat, poultry, and vegetable oil" dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.
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This study explores the factors influencing unsafe behaviors among decorators. The study begins with a literature review on unsafe behaviors among construction workers, compiling a checklist of factors specific to decorators. Utilizing exploratory factor analysis (EFA), a measurement scale for these factors is developed. Subsequently, stepwise regression analysis (SRA) is conducted to validate relationships and identify crucial factors. Results categorize influencing factors into three dimensions: personal, organizational and environmental. Non-compliance with safety procedures and protocols is found to correlate directly with increased unsafe behavior at an individual level. Additionally, internal safety regulations within companies are identified as having a direct negative impact on unsafe behaviors at the organizational level. This study enhances our understanding of unsafe behaviors among decorators and offers recommendations for mitigation.
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Background: Cytochrome P450 2E1 (CYP2E1) converts isoniazid (INH) to toxic metabolites and is critical in INH-induced liver injury. The aim is to investigate the effect of folic acid (FA) on CYP2E1 and INH-induced liver injury. Methods: Male Balb/c mice were used. The mice in the control group only received an AIN-93M diet. The AIN-93M diet was supplemented with 0.66 g INH/kg diet for the mice in the INH and FA groups. The mice in the FA group were treated with additional 0.01 g FA/kg diet. The one-carbon cycle metabolites, the expressions of CYP2E1 and the DNA and RNA methylation levels were detected to reveal the potential mechanism. Results: FA treatment significantly reduced the alanine aminotransferase level and alleviated the liver necrosis. The mRNA and protein expressions of CYP2E1 were significantly lower in the FA group than those in the INH group. The N6-methyladenosine RNA methylation level of Cyp2e1 significantly increased in the FA group compared with the INH group, while the DNA methylation levels of Cyp2e1 were similar between groups. Additionally, the liver S-adenosyl methionine (SAM)/S-adenosyl homocysteine (SAH) was elevated in the FA group and tended to be positively correlated with the RNA methylation level of Cyp2e1. Conclusion: FA alleviated INH-induced liver injury which was potentially attributed to its inhibitory effect on CYP2E1 expressions through enhancing liver SAM/SAH and RNA methylation.
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BACKGROUND AND AIMS: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in hepatocellular carcinoma (HCC) patients is increasing, yet its association with postoperative complications of HCC remains unclear. The aim of this study was to investigate the impact of MAFLD on complications after radical resection in HCC patients. METHODS: Patients with HCC who underwent radical resection were included. Patients were stratified into MAFLD group and non-MAFLD group. Clinical features and post-hepatectomy complications were compared between the two groups, and logistic regression analysis was used to determine independent risk factors associated with post-hepatectomy complications. RESULTS: Among the 936 eligible patients with HCC who underwent radical resection, concurrent MAFLD was diagnosed in 201 (21.5%) patients. Compared to the non-MAFLD group, the MAFLD group exhibited a higher incidence of complications, including infectious and major complications after radical resection in HCC patients. The logistic regression analysis found that MAFLD was an independent risk factor for complications, including infectious and major complications in HCC patients following radical resection (OR 1.565, 95%CI 1.109-2.343, P = 0.012; OR 2.092, 95%CI 1.386-3.156, P < 0.001; OR 1.859, 95% CI 1.106-3.124, P = 0.019; respectively). Subgroup analysis of HBV-related HCC patients yielded similar findings, and MAFLD patients with type 2 diabetes mellitus (T2DM) exhibited a higher incidence of postoperative complications compared to those without T2DM (all P < 0.05). CONCLUSIONS: Concurrent MAFLD was associated with an increased incidence of complications after radical resection in patients with HCC, especially MAFLD with T2DM.
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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Complicaciones Posoperatorias , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Femenino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Persona de Mediana Edad , Hepatectomía/efectos adversos , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Estudios Retrospectivos , Hígado Graso/etiología , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Hígado Graso/metabolismo , Hígado Graso/patología , Anciano , IncidenciaRESUMEN
Chronic pancreatitis (CP) is a progressive inflammatory disease with an increasing global prevalence. In recent years, a strong association between CP and metabolic bone diseases (MBDs), especially osteoporosis, has been identified, attracting significant attention in the research field. Epidemiological data suggest a rising trend in the incidence of MBDs among CP patients. Notably, recent studies have highlighted a profound interplay between CP and altered nutritional and immune profiles, offering insights into its linkage with MBDs. At the molecular level, CP introduces a series of biochemical disturbances that compromise bone homeostasis. One critical observation is the disrupted metabolism of vitamin D and vitamin K, both essential micronutrients for maintaining bone integrity, in CP patients. In this review, we provide physio-pathological perspectives on the development and mechanisms of CP-related MBDs. We also outline some of the latest therapeutic strategies for treating patients with CP-associated MBDs, including stem cell transplantation, monoclonal antibodies, and probiotic therapy. In summary, CP-associated MBDs represent a rising medical challenge, involving multiple tissues and organs, complex disease mechanisms, and diverse treatment approaches. More in-depth studies are required to understand the complex interplay between CP and MBDs to facilitate the development of more specific and effective therapeutic approaches.
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Enfermedades Óseas Metabólicas , Pancreatitis Crónica , Humanos , Pancreatitis Crónica/epidemiología , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/complicaciones , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/etiología , Enfermedades Óseas Metabólicas/metabolismo , Vitamina D/metabolismo , Vitamina D/uso terapéutico , Vitamina K/metabolismo , AnimalesRESUMEN
BACKGROUND: The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. METHODS: A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. RESULTS: We defined three new microglial subtypes at cellular level, including two M1 types (Egr2+ M1 and Egr2- M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. CONCLUSIONS: We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR.
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Liver injury is a main adverse effect of first-line tuberculosis drugs. Current management of tuberculosis-drug-induced liver injury (TBLI) mainly relies on withdrawing tuberculosis drugs when necessary. No effective treatment exists. Various nutrients and functional food ingredients may play a protective role in TBLI. However, a comprehensive review has not been conducted to compare the effects of these nutrients and functional food ingredients. We searched Pubmed and Web of Science databases from the earliest date of the database to March 2023. All available in-vitro, animal and clinical studies that examined the effects of nutritional intervention on TBLI were included. The underlying mechanism was briefly reviewed. Folic acid, quercetin, curcumin, Lactobacillus casei, spirulina and Moringa oleifera possessed moderate evidence to have a beneficial effect on alleviating TBLI mostly based on animal studies. The evidence of other nutritional interventions on TBLI was weak. Alleviating oxidative stress and apoptosis were the leading mechanisms for the beneficial effects of nutritional intervention on TBLI. In conclusion, a few nutritional interventions are promising for alleviating TBLI including folic acid, quercetin, curcumin, L. casei, spirulina and M. oleifera, the effectiveness and safety of which need further confirmation by well-designed randomized controlled trials. The mechanisms for the protective role of these nutritional interventions on TBLI warrant further study, particularly by establishing the animal model of TBLI using the tuberculosis drugs separately.
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A series of five-element CoCrFeNi-Nbx (x = 0, 1, 3, 5, 7, and 9 wt%) high-entropy alloys were prepared using high-energy ball milling and discharge plasma sintering methods. Then, the effects of doping with Nb elements on the organization and properties of the CoCrFeNi HEAs were systematically investigated by tensile testing, hardness testing, and examining their micro-morphologies. The results show that with the addition of the Nb element, the lattice distortion of the alloy due to the large size of the Nb atoms causes the microstructure of CoCrFeNi HEAs to change from a single-phase FCC structure to a dual-phase structure of FCC and Laves. With the increase in the Nb content, the increase in the volume fraction of the hard and brittle Laves phase leads to the enhancement of the HEA's tensile strength, yield strength, and hardness, and a decrease in plasticity. The Nb5 alloy showed the most excellent comprehensive performance, with a tensile strength, yield strength, and plasticity of 879.1 MPa, 491.8 MPa, and 39.8%, respectively, and all the properties were improved compared with those of the HEAs obtained by the arc melting method. The increase in the hardness of the HEAs was nearly proportional to the increase in the volume fraction of the Laves phase, which was the direct cause of the increase in the hardness of the HEA. Therefore, since the Laves phase is the direct cause of the increase in HEA hardness, the doping of CoCrFeNi HEAs with Nb can significantly improve the properties of HEAs.
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Ensuring food safety is a critical concern for the development and well-being of humanity, as foodborne illnesses caused by foodborne bacteria have increasingly become a major public health concern worldwide. Traditional food safety monitoring systems are expensive and time-consuming, relying heavily on specialized equipment and operations. Therefore, there is an urgent need to develop low-cost, user-friendly and highly sensitive biosensors for detecting foodborne bacteria. In recent years, the combination of nanomaterials with optical biosensors has provided a prospective future platform for the detection of foodborne bacteria. By harnessing the unique properties of nanomaterials, such as their high surface area-to-volume ratio and exceptional sensitivity, in tandem with the precision of optical biosensing techniques, a new prospect has opened up for the rapid and accurate identification of potential bacterial contaminants in food. This review focuses on recent advances and new trends of nanomaterial-based biosensors for the detection of foodborne pathogens, which mainly include noble metal nanoparticles (NMPs), metal organic frameworks (MOFs), graphene nanomaterials, quantum dot (QD) nanomaterials, upconversion fluorescent nanomaterials (UCNPs) and carbon dots (CDs). Additionally, we summarized the research progress of color indicators, nanozymes, natural enzyme vectors and fluorescent dye biosensors, focusing on the advantages and disadvantages of nanomaterial-based biosensors and their development prospects. This review provides an outlook on future technological directions and potential applications to help identify the most promising areas of development in this field.
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Técnicas Biosensibles , Enfermedades Transmitidas por los Alimentos , Nanoestructuras , Humanos , Inocuidad de los Alimentos , Técnicas Biosensibles/métodos , BacteriasRESUMEN
PURPOSE: The abnormal polarisation of microglial cells (MGs) following retinal ischemia/reperfusion (RIR) initiates neuroinflammation and progressive death of retinal ganglion cells (RGCs), causing increasingly severe and irreversible visual dysfunction. Roflumilast (Roflu) is a promising candidate for treating neuroinflammatory diseases. This study aimed to explore whether Roflu displayed a cytoprotective effect against RIR-induced neuroinflammation and to characterise the underlying signalling pathway. METHODS: The effects and mechanism of Roflu against RIR injury were investigated in C57BL/6J mice and the BV2 cell line. We used quantitative real-time PCR and enzyme-linked immunosorbent assay to examine the levels of inflammatory factors. Furthermore, haematoxylin and eosin and immunofluorescence (IF) stainings were used to assess the morphology of the retina and the states of MGs and RGCs. Reactive oxygen species (ROS) levels were examined using a ROS assay kit, while whole-genome sequencing analysis was conducted to identify altered pathways and molecules. Western blotting and IF staining were used to quantify the proteins associated with the nuclear factor erythroid 2-related factor 2 (Nrf2)/stimulator of interferon gene (STING)/nuclear factor kappa beta (NF-κB) pathway. RESULTS: MG polarisation includes the pro-inflammatory and neurotoxic M1 phenotype as well as the anti-inflammatory and neuroprotective M2 phenotype. Roflu significantly attenuated MG activation and contributed to a shift in the MG phenotype from M1 to M2. Moreover, Roflu decreased ROS release and increased heme oxygenase 1 and NAD(P)H quinone oxidoreductase 1 expression. In vitro and in vivo experiments validated that Roflu exerted its neuroprotective effects primarily by upregulating the Nrf2/STING/NF-κB pathway. However, these effects were abrogated when the Nrf2 expression was inhibited by pharmacological or genetic manipulation. CONCLUSIONS: Roflu suppressed RIR-induced neuroinflammation by driving the shift of MG polarisation from M1 to M2 phenotype, which was mediated by the upregulation of the Nrf2/STING/NK-κB pathway.
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FN-kappa B , Daño por Reperfusión , Ratones , Animales , FN-kappa B/metabolismo , Enfermedades Neuroinflamatorias , Factor 2 Relacionado con NF-E2/metabolismo , Microglía , Especies Reactivas de Oxígeno/metabolismo , Inflamación/metabolismo , Ratones Endogámicos C57BL , Fenotipo , Retina/metabolismo , Daño por Reperfusión/metabolismo , Isquemia/metabolismoRESUMEN
In this paper, the tensile mechanical behavior and progressive damage morphology of glass-fiber-reinforced magnesium alloy laminate for different numbers of holes in a temperature range of 25-180 °C were investigated. In addition, based on extensive tensile tests, the tensile mechanical behavior and microscopic damage morphology of porous-glass-fiber-reinforced magnesium alloy laminates at different temperatures were observed by finite element simulation and scanning electron microscopy (SEM). Finally, the numerical simulation and experimental results were in good accordance with the prediction of mechanical properties and fracture damage patterns of the laminates, the average difference between the residual strength values of the specimens at ambient temperature was 5.57%, and the stress-strain curves were in good agreement. The experimental and finite element analysis results showed that the damaged area of the bonded layer tended to expand with the increase in the number of holes, which has a lesser effect on the ultimate tensile strength. As the temperature increased, the specimens changed from obvious fiber breakage (pull-out) and the resin matrix damage mode to matrix softening damage and interfacial delamination fracture damage. As the testing temperature of the specimens increased from 25 °C to 180 °C, the tensile strength of the specimens decreased by an average of 51.59%, while the tensile strength of the specimens showed a nonlinear decreasing trend. The damage mechanism of porous-glass-fiber-reinforced magnesium alloy laminates at different temperatures is discussed in this paper, which can provide a reference for engineering applications and design.
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The global coronavirus disease 2019 (COVID-19) pandemic has had a massive impact on global social and economic development and human health. By combining traditional Chinese medicine (TCM) with modern medicine, the Chinese government has protected public health by supporting all phases of COVID-19 prevention and treatment, including community prevention, clinical treatment, control of disease progression, and promotion of recovery. Modern medicine focuses on viruses, while TCM focuses on differential diagnosis of patterns associated with viral infection of the body and recommends the use of TCM decoctions for differential treatment. This differential diagnosis and treatment approach, with its profoundly empirical nature and holistic view, endows TCM with an accessibility advantage and high application value for dealing with COVID-19. Here, we summarize the advantage of and evidence for TCM use in COVID-19 prevention and treatment to draw attention to the scientific value and accessibility advantage of TCM and to promote the use of TCM in response to public health emergencies. Please cite this article as: Huang M, Liu YY, Xiong K, Yang FW, Jin XY, Wang ZQ, Zhang JH, Zhang BL. The role and advantage of traditional Chinese medicine in the prevention and treatment of COVID-19. J Integr Med. 2023; 21(5): 407-412.
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COVID-19 , Medicina Tradicional China , Humanos , Pueblo Asiatico , COVID-19/prevención & control , Diagnóstico Diferencial , Medicina Tradicional China/métodos , Pandemias/prevención & controlRESUMEN
Metabolic reprogramming toward glycolysis is a hallmark of cancer malignancy. The molecular mechanisms by which the tumor glycolysis pathway promotes immune evasion remain to be elucidated. Here, by performing genome-wide CRISPR screens in murine tumor cells co-cultured with cytotoxic T cells (CTLs), we identified that deficiency of two important glycolysis enzymes, Glut1 (glucose transporter 1) and Gpi1 (glucose-6-phosphate isomerase 1), resulted in enhanced killing of tumor cells by CTLs. Mechanistically, Glut1 inactivation causes metabolic rewiring toward oxidative phosphorylation, which generates an excessive amount of reactive oxygen species (ROS). Accumulated ROS potentiate tumor cell death mediated by tumor necrosis factor alpha (TNF-α) in a caspase-8- and Fadd-dependent manner. Genetic and pharmacological inactivation of Glut1 sensitizes tumors to anti-tumor immunity and synergizes with anti-PD-1 therapy through the TNF-α pathway. The mechanistic interplay between tumor-intrinsic glycolysis and TNF-α-induced killing provides new therapeutic strategies to enhance anti-tumor immunity.
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Neoplasias , Factor de Necrosis Tumoral alfa , Ratones , Animales , Humanos , Factor de Necrosis Tumoral alfa/metabolismo , Transportador de Glucosa de Tipo 1 , Evasión Inmune , Especies Reactivas de Oxígeno/metabolismo , Glucólisis , Linfocitos T/metabolismo , Línea Celular TumoralRESUMEN
Metal phosphonate frameworks (MPFs) consisting of tetravalent metal ions and aryl-phosphonate ligands feature a large affinity for actinides and excellent stabilities in harsh aqueous environments. However, it remains elusive how the crystallinity of MPFs influences their performance in actinide separation. To this end, we prepared a new category of porous, ultrastable MPF with different crystallinities for uranyl and transuranium separation. The results demonstrated that crystalline MPF was generally a better adsorbent for uranyl than the amorphous counterpart and ranked as the top-performing one for uranyl and plutonium in strong acidic solutions. A plausible uranyl sequestration mechanism was unveiled by using powder X-ray diffraction in tandem with vibrational spectroscopy, thermogravimetry, and elemental analysis.
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Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.
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Cisplatino , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Cisplatino/uso terapéutico , Gemcitabina , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/etiología , Neoplasias Nasofaríngeas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/uso terapéutico , Microambiente TumoralRESUMEN
To achieve osteogenesis, angiogenesis, and neurogenesis for repairing bone defects, we constructed an anisotropic microspheres-cryogel composite loaded with magnesium l-threonate (MgT). These composites were prepared by the photo-click reaction of norbornene-modified gelatin (GB) in the presence of MgT-loaded microspheres through the bidirectional freezing method. The composites possessed an anisotropic macroporous (around 100 µm) structure and sustained release of bioactive Mg2+, which facilitate vascular ingrowth. These composites could significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells, tubular formation of human umbilical vein vessel endothelial cells, and neuronal differentiation in vitro. Additionally, these composites significantly promoted early vascularization and neurogenesis as well as bone regeneration in the rat femoral condyle defects. In conclusion, owing to the anisotropic macroporous microstructure and bioactive MgT, these composites could simultaneously promote bone, blood vessel, and nerve regeneration, showing great potential for bone tissue engineering.
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Criogeles , Osteogénesis , Ratas , Humanos , Animales , Criogeles/química , Magnesio/farmacología , Microesferas , Regeneración Ósea , Diferenciación Celular , Neurogénesis , Células Endoteliales de la Vena Umbilical Humana , Andamios del Tejido/químicaRESUMEN
Methods for Pu determination in water samples has been longtime studied but they generally involved tedious manual operations. In this context, we proposed a novel strategy for accurate determination of ultra-trace Pu in water samples by the combination of fully automated separation with direct ICP-MS/MS measurement. A recently commercialized extraction resin TK200 was used for single-column separation due to its distinctive nature. Acidified waters up to 1 L were directly loaded to the resin at high flow rate (15 mL min-1) with omitting the frequently used co-precipitation process. Small volumes of dilute HNO3 were used for column washing, and Pu was efficiently eluted within only 2 mL 0.5 mol L-1 HCl-0.1 mol L-1 HF with a stable recovery (65%). This separation procedure was fully automated under the control of user program, meanwhile the final eluent was compatible for direct ICP-MS/MS measurement without extra sample treatment. In that way, both the labor intensity and reagent consumption were minimized compared with existing methods. With the high decontamination (104 to 105) of U in the chemical separation and the further elimination of uranium hydrides under oxygen reaction model during ICP-MS/MS measurement, the overall interference yields of UH+/U+ and UH2+/U+ were down to 10-15. The limits of detection (LODs) of this method reached 0.32 µBq L-1 for 239Pu and 2.00 µBq L-1 for 240Pu, which were much lower than those stipulated in the general guidelines for drinking water standards, suggesting this method was promising in routine or emergency radiation monitoring. Furthermore, the established method was successfully applied in a pilot study to determine global fallout derived Pu in surface glacier samples with extremely low concentrations of 239+240Pu, which suggested the method would also be feasible in glacial chronology studies in the future.