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1.
J Hazard Mater ; 470: 134237, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38593662

RESUMO

Ti-based MOFs exhibit ultra-high stability in radioactive waste gases containing nitrogen oxides (NOX) and are effective in capturing radioactive iodine. In this study, NH2-MIL-125 was synthesized via a one-pot solvothermal method and its adsorption performance for iodine was investigated using batch adsorption experiments, the stability of materials was tested by simulating post-processing conditions. The results indicated that NH2-MIL-125 had a maximum iodine adsorption capacity of 1.61 g/g at 75 â„ƒ and reached adsorption equilibrium within 60 min, and the adsorption capacity of methyl iodine reached 776.9 mg/g. The material also exhibited excellent stability and iodine adsorption performance in the presence of NOX. After soaking in NO2 for 24 h, its structure remained stable and the adsorption capacity for iodine remained at 231.5 mg/g. The excellent co-adsorption performance of NH2-MIL-125 on iodine and NOX was attributed to the synergistic effects of Ti-OH groups and amino functional groups. These findings provide a reference for the capture of radioactive iodine and also demonstrate the potential of NH2-MIL-125 for iodine capture during spent fuel reprocessing.

2.
Chemistry ; 29(72): e202302445, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-37803818

RESUMO

Efficient adsorption of palladium ions from acid nuclear waste solution is crucial for ensuring the safety of vitrification process for radioactive waste. However, the limited stability and selectivity of most current adsorbents hinder their practical applications under strong acid and intense radiation conditions. Herein, to address these limitations, we designed and synthesized an aryl-ether-linked covalent organic framework (COF-316-DM) grafted dimethylthiocarbamoyl groups on the pore walls. This unique structure endows COF-316-DM with high stability and exceptional palladium capture capacity. The robust polyarylether linkage enables COF-316-DM to withstand irradiation doses of 200 or 400 kGy of ß/γ ray. Furthermore, COF-316-DM demonstrates fast adsorption kinetics, high adsorption capacity (147 mg g-1 ), and excellent reusability in 4 M nitric acid. Moreover, COF-316-DM exhibits remarkable selectivity for palladium ions in the presence of 17 interference ions, simulating high level liquid waste scenario. The superior adsorption performance can be attributed to the strong binding affinity between the thioamide groups and Pd2+ ions, as confirmed by the comprehensive analysis of FT-IR and XPS spectra. Our findings highlight the potential of COFs with robust linkers and tailored functional groups for efficient and selective capture of metal ions, even in harsh environmental conditions.

3.
Eur J Med Res ; 28(1): 277, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559150

RESUMO

BACKGROUND: Preeclampsia is a unique multisystem disorder that affects 5-8% of pregnancies. A high level of soluble fms-like tyrosine kinase-1 (sFlt-1) is a hallmark of preeclampsia that causes endothelial dysfunction. Exosomes derived from mesenchymal stem cells (MSCs) have been indicated to improve endothelial performances by transporting signals to target cells. We hypothesized that exosomes derived from MSCs have potential effects against preeclampsia. METHODS: We collected human umbilical cord MSC-derived exosomes (HUCMSC-exos) by ultracentrifugation. The size and morphology of the exosomes were examined using a transmission electron microscope and nanoparticle tracking analysis. Pregnant mice were injected with murine sFlt-1 adenovirus to build the preeclampsia-like mouse model and then treated with HUCMSC-exos. Human umbilical vein endothelial cells (HUVECs) were infected with lentiviruses expressing tet-on-sFlt-1 to obtain cells overexpressing sFlt-1. Cell proliferation and migration assays were used to measure the endothelial functions. The exosomes enriched proteins underlying mechanisms were explored by proteomic analysis. RESULTS: In the current study, we successfully collected the cup-shaped HUCMSC-exos with diameters of 30-150 nm. In the sFlt-1-induced preeclampsia mouse model, HUCMSC-exos exhibited beneficial effects on adverse birth events by decreasing blood pressure and improving fetal birth weight. In addition, preeclamptic dams that were injected with HUCMSC-exos had rebuilt dense placental vascular networks. Furthermore, we observed that HUCMSC-exos partially rescued sFlt-1-induced HUVECs dysfunction in vitro. Proteomics analysis of HUCMSC-exos displayed functional enrichment in biological processes related to vesicle-mediated transport, cell communication, cell migration, and angiogenesis. CONCLUSION: We propose that exosomes derived from HUCMSCs contain abundant Versican and play beneficial roles in the birth outcomes of sFlt-1-induced preeclamptic mice by promoting angiogenesis.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Pré-Eclâmpsia , Humanos , Camundongos , Feminino , Gravidez , Animais , Pré-Eclâmpsia/terapia , Pré-Eclâmpsia/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Exossomos/genética , Exossomos/metabolismo , Proteômica , Placenta/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Cordão Umbilical
4.
Acta Biomater ; 167: 205-218, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37331615

RESUMO

Intrauterine adhesions (IUA) caused by endometrial injury are one of the main causes of female infertility. The current treatments for endometrial injury offer limited clinical benefits and cannot improve endometrial receptivity and pregnancy outcomes. Tissue engineering and regenerative medicine are considered potential solutions to address this concern and may offer effective treatment methods for the regeneration of injured human endometrium. Herein, we prepared an injectable hydrogel based on oxidized hyaluronic acid (HA-CHO) and hydrazide-grafted gelatin (Gel-ADH). The injectable hydrogel showed satisfactory biocompatibility when mixed with human umbilical cord mesenchymal stem cells (hUCMSCs). In an endometrial injury rat model, the treatment with hUCMSCs-loaded injectable hydrogel significantly enhanced the thickness of the endometrium and increased the abundance of blood vessels and glands in the injured endometrium compared to the control group. The hUCMSCs-loaded injectable hydrogel treatment significantly reduced endometrial fibrosis, decreased the expression of the pro-inflammatory factors (IL-1ß and IL-6) and increased the expression of the anti-inflammatory factor (IL-10). This treatment induced endometrial VEGF expression by activating the MEK/ERK1/2 signaling pathway. Moreover, this treatment improved endometrial receptivity to the embryo and restored the embryo implantation rate similar to the sham group (48% in the sham group vs 46% in the treatment group), and this treatment achieved pregnancy and live birth in rats with endometrial injury. In addition, we also preliminarily validated the safety of this treatment in the maternal rats and fetuses. Collectively, our study showed that the hUCMSCs-loaded injectable hydrogel hold potential as an effective treatment strategy promoting rapid recovery of endometrial injury, and this hydrogel is a promising biomaterial for regenerative medicine applications. STATEMENT OF SIGNIFICANCE: 1. Oxidized hyaluronic acid (HA-CHO)/hydrazide-grafted gelatin (Gel-ADH) hydrogel combined with human umbilical cord mesenchymal stem cells (hUCMSCs) are effective in improving the regeneration of endometrium in the endometrial injury rat model. 2. The hUCMSCs-loaded hydrogel treatment promotes the expression of endometrial VEGF through MEK/ERK1/2 signaling pathway and regulates the balance of inflammatory factors. 3. The embryo implantation and live birth rates restore to normal level in the endometrial injury rat model, and the hydrogel has no adverse effects on maternal rats, fetuses, and offspring development after the treatments.


Assuntos
Hidrogéis , Células-Tronco Mesenquimais , Gravidez , Humanos , Ratos , Feminino , Animais , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Gelatina/farmacologia , Ácido Hialurônico/farmacologia , Ácido Hialurônico/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Endométrio/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical , Fertilidade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia
5.
Biol Reprod ; 108(3): 504-518, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36504380

RESUMO

The cause for at least 50% of recurrent miscarriages is unclear, which is defined as unexplained recurrent miscarriages. The B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in unexplained recurrent miscarriages. We found reduced levels of B7-H3 in the villus tissue of unexplained recurrent miscarriage patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts. Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through enzyme-linked immunosorbent assay after co-culturing with decidual natural killer cells and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from the decidual natural killer cells. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of unexplained recurrent miscarriages inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from the decidual natural killer cells. Furthermore, B7-H3 may be a promising new therapeutic target in unexplained recurrent miscarriage patients.


Assuntos
Aborto Habitual , Interleucina-8 , Animais , Feminino , Humanos , Camundongos , Gravidez , Aborto Habitual/metabolismo , Linhagem Celular Tumoral , Quimiocina CXCL10/metabolismo , Decídua/metabolismo , Interleucina-8/metabolismo , Células Matadoras Naturais/metabolismo , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Transdução de Sinais , Trofoblastos/metabolismo
6.
Adv Clin Exp Med ; 32(3): 357-367, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36330842

RESUMO

BACKGROUND: Hypertensive disorders complicating pregnancy (HDCP) are one of the most serious medical disorders during pregnancy. OBJECTIVES: To investigate the effects of hydrogen on the mitogen-activated protein kinase (MAPK) signaling pathway in preeclampsia (PE). MATERIAL AND METHODS: The N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced PE model with Sprague Dawley (SD) rats was employed. An inhibitor of MAPK signaling pathways (SB203580) was used as a p38 MAPK inhibitor. The SD rats were randomized into 5 groups: non-pregnant (NP); normal pregnancy (P); pregnancy + L-NAME (L); pregnancy + L-NAME + hydrogen-rich saline (LH); and pregnancy + L-NAME + hydrogen-rich saline + SB203580 (LHS). The pregnancies were terminated on day 22 of gestation, and the placentas and kidneys were microscopically inspected. Tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and malondialdehyde (MDA) levels were assessed. The mean systolic blood pressure (SBP) and level of proteinuria were recorded. The p38 MAPK mRNA expression and p-p38 MAPK protein levels were measured using real-time polymerase chain reaction (RT-PCR) and western blot, respectively. RESULTS: It was found that hydrogen-rich saline (LH group) decreased placental MDA, proteinuria, TNF-α, and IL-1ß levels in the placental tissues compared with the L group (all p < 0.05). Additionally, hydrogen-rich saline (LH group) treatment significantly decreased the p38 MAPK mRNA expression and p-p38 MAPK protein levels compared with the L group (p < 0.05). The p38 MAPK inhibitor SB203580 (LHS group) further decreased the p38 MAPK mRNA expression and p-p38 MAPK protein levels compared with the LH group (p < 0.05). CONCLUSIONS: Hydrogen can decrease the reactive oxygen species (ROS) content and inhibit the MAPK pathway. The protective effect of hydrogen may be associated with the inhibition of the p38 MAPK signaling pathway.


Assuntos
Pré-Eclâmpsia , Proteínas Quinases p38 Ativadas por Mitógeno , Ratos , Humanos , Animais , Feminino , Gravidez , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , NG-Nitroarginina Metil Éster/efeitos adversos , NG-Nitroarginina Metil Éster/metabolismo , Hidrogênio/efeitos adversos , Hidrogênio/metabolismo , Placenta , Transdução de Sinais , Estresse Oxidativo , Sistema de Sinalização das MAP Quinases , Inibidores de Proteínas Quinases/farmacologia , Proteinúria/metabolismo , RNA Mensageiro/metabolismo
7.
Front Nutr ; 9: 1035788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36424929

RESUMO

This study aimed to establish a bidirectional fermentation system using Tremella fuciformis and Acanthopanax trifoliatus to promote the transformation and utilization of the synthesized antioxidant metabolites from fermentation supernatant. The effect of fermentation conditions on the total phenolic content was investigated using response surface methodology in terms of three factors, including temperature (22-28°C), pH (6-8), and inoculum size (2-8%, v/v). The optimized fermentation parameters were: 28°C, pH 8, and an inoculum size of 2%, which led to a maximum total phenolic content of 314.79 ± 6.89 µg/mL in the fermentation supernatant after 24 h culture. The content of total flavonoids and polysaccharides reached 78.65 ± 0.82 µg/mL and 9358.08 ± 122.96 µg/mL, respectively. In addition, ABTS+, DPPH⋅, and ⋅OH clearance rates reached 95.09, 88.85, and 85.36% at 24 h under optimized conditions, respectively. The content of total phenolics, flavonoids and polysaccharides in the optimized fermentation supernatant of T. fuciformis-Acanthopanax trifoliatus increased by 0.88 ± 0.04, 0.09 ± 0.02, and 33.84 ± 1.85 times that of aqueous extracts from A. trifoliatus, respectively. Simultaneously, 0.30 ± 0.00, 0.26 ± 0.01, and 1.19 ± 0.12 times increase of antioxidant activity against ABTS+, DPPH⋅, and ⋅OH clearance rates were observed, respectively. Additionally, the metabolite composition changes caused by fermentation were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on untargeted metabolomics and the phytochemical profile of fermentation supernatant differentiated significantly based on unsupervised principal component analysis (PCA) during fermentation from 24 to 96 h. Furthermore, a significant increase in antioxidant phenolic and flavonoid compounds, such as ellagic acid, vanillin, luteolin, kaempferol, myricetin, isorhamnetin, and (+)-gallocatechin, was observed after fermentation. Thus, these results indicated that the fermentation broth of T. fuciformis and A. trifoliatus had significant antioxidant activity, and may have potential application for health products such as functional beverages, cosmetics, and pharmaceutical raw materials.

8.
Inorg Chem ; 61(49): 20133-20143, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36426769

RESUMO

Effective capture of radioactive iodine is highly desirable for decontamination purposes in spent fuel reprocessing. Cu-based adsorbents with a low cost and high chemical affinity for I2 molecules act as a decent candidate for iodine elimination, but the low utilization and stability remain a significant challenge. Herein, a facile in situ confined synthesis strategy is developed to design and synthesize a copper-encapsulated flaky silicalite-1 (Cu@FSL-1) zeolite with a thickness of ≤300 nm. The maximum iodine uptake capacity of Cu@FSL-1 can reach 625 mg g-1 within 45 min, which is 2 times higher than that of a commercial silver-exchanged zeolite even after nitric acid and NOX treatment. The Cu nanoparticles (NPs) confined within the zeolite exert superior iodine adsorption and immobilization properties as well as high stability and fast adsorption kinetics endowed by the all-silica zeolite matrix. This study provides new insight into the design and controlled synthesis of zeolite-confined metal adsorbents for efficient iodine capture from gaseous radioactive streams.


Assuntos
Iodo , Neoplasias da Glândula Tireoide , Zeolitas , Humanos , Zeolitas/química , Cobre/química , Radioisótopos do Iodo , Prata
9.
Front Oncol ; 12: 987609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338674

RESUMO

In recent years, the miRNA is considered as a potential high-value therapeutic target because of its complex and delicate mechanism of gene regulation. The abnormal expression of miRNA can cause drug resistance, affecting the therapeutic effect of the disease. Revealing the associations between miRNAs-drug resistance can help in the design of effective drugs or possible drug combinations. However, current conventional experiments for identification of miRNAs-drug resistance are time-consuming and high-cost. Therefore, it's of pretty realistic value to develop an accurate and efficient computational method to predicting miRNAs-drug resistance. In this paper, a method based on the Support Vector Machines (SVM) to predict the association between MiRNA and Drug Resistance (SVMMDR) is proposed. The SVMMDR integrates miRNAs-drug resistance association, miRNAs sequence similarity, drug chemical structure similarity and other similarities, extracts path-based Hetesim features, and obtains inclined diffusion feature through restart random walk. By combining the multiple feature, the prediction score between miRNAs and drug resistance is obtained based on the SVM. The innovation of the SVMMDR is that the inclined diffusion feature is obtained by inclined restart random walk, the node information and path information in heterogeneous network are integrated, and the SVM is used to predict potential miRNAs-drug resistance associations. The average AUC of SVMMDR obtained is 0.978 in 10-fold cross-validation.

10.
Clin Lung Cancer ; 23(7): e415-e427, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35729005

RESUMO

BACKGROUND: Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing Phase I, multi-center, open-label, 2-part (dose escalation and cohort expansion) GARNET study (NCT02715284). MATERIALS AND METHODS: Here, we report an interim analysis of patients with recurrent/advanced NSCLC who progressed following platinum-based chemotherapy. Patients received dostarlimab (500 mg IV every 3 weeks [Q3W] for Cycles 1-4, then 1000 mg Q6W) until disease progression or unacceptable toxicity for > 2 years. The primary endpoints were immune-related objective response rate (irORR) per investigator-assessed irRECIST and safety. RESULTS: As of 8, July 2019, 67 patients with recurrent/advanced NSCLC were enrolled and treated with dostarlimab; the majority had programmed death ligand 1 (PD-L1) tumor proportion score (TPS) < 1% (35.8% of patients) or PD-L1 TPS 1%-49% (29.9% of patients); 7.5% had PD-L1 TPS ≥ 50%, and 26.9% had unknown PD-L1 TPS status. Median follow-up was 13.8 months (range: 0.0-22.6). irORR was 26.9%, including 2 complete and 16 partial responses. The median duration of response of 11.6 months (range: 2.8-19.4). Responses were observed in 2 of 24 (16.7%) patients with PD-L1 TPS < 1%, 4 of 20 (20.0%) patients with PD-L1 TPS 1%-49% and 2 of 5 (40.0%) patients with PD-L1 TPS ≥ 50%. Fatigue (4.5%) was the most common Grade ≥ 3 treatment-related treatment-emergent adverse event (TRAE). Immune-related TRAEs (any grade) were observed in 28.4% of patients. CONCLUSION: Dostarlimab demonstrated promising antitumor activity in advanced/recurrent NSCLC that progressed following platinum-based chemotherapy, including across all PD-L1 subgroups, and has an acceptable safety profile.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Recidiva Local de Neoplasia , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Ensaios Clínicos Fase I como Assunto
11.
Animals (Basel) ; 12(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35565527

RESUMO

The study evaluated the effects of dry and wet solid-state fermented wheat bran (FWB) on growth performance, immune function, intestinal morphology and microflora in lipopolysaccharide (LPS)-challenged broiler chickens. The experiment was designed as a 2 × 3 factorial arrangement. A total of 252 one-day-old Arbor Acres male broiler chickens were randomly allocated to 1 of 6 treatments: basal diet + sterile saline (negative control, NC), basal diet + LPS (positive control, PC), 7% dry FWB + sterile saline (FWB-I), 7% dry FWB + LPS (FWB-II), 7% wet FWB + sterile saline (FWB-III) and 7% wet FWB + LPS (FWB-IV), with containing 6 replicate cages/treatment and 7 broiler chickens/cage, and the experimental period lasted for 42 days. Broilers were intraperitoneally injected with either 0.5 mg LPS or sterile saline solution per kg body weight at 16, 18 and 20 d of age. Growth performance, serum immunological parameters and indicators related to intestinal health were analyzed on days 21 and 42. Compared with NC, dry and wet FWB significantly increased (p < 0.05) average daily feed intake of days 21 to 42, and increased (p < 0.05) the villus height and villus height to crypt depth ratio of ileum on day 21, decreased (p = 0.101) the jejunum crypt depth and decreased (p < 0.05) the Lactobacillus and Bifidobacterium counts of the cecum digesta on day 42. Compared with NC, FWB-II and FWB-IV significantly increased (p < 0.05) the levels of serum total protein and globulin on day 21; compared with the basal diet groups, dry and wet FWB groups significantly increased (p < 0.05) glucose levels on day 21, and wet FWB significantly decreased (p < 0.05) alanine aminotransferase levels on day 42. Compared with PC and FWB-II, FWB-IV significantly increased (p < 0.05) the level of serum immunoglobulin G on day 21. Compared with PC and FWB-II, FWB-IV significantly decreased (p < 0.05) the levels of serum pro-inflammatory cytokines interleukin (IL)-6, IL-8, IL-1ß and acute C reactive protein (CRP) on day 21; compared with FWB-III, FWB-IV significantly decreased (p < 0.05) the levels of IL-6, IL-8, CRP and tumor necrosis factor alpha on day 42, but the levels of IL-4 and IL-10 were significantly increased (p < 0.05) on days 21 and 42. These results indicated that supplementing 7% dry or wet FWB can improve growth performance and serum immune functions of broilers, which effectively alleviate the LPS-challenged damage, and wet FWB had a better effect than dry FWB.

12.
Science ; 376(6596): 968-973, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35511947

RESUMO

N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Cromatina , Regulação da Expressão Gênica no Desenvolvimento , Elementos Nucleotídeos Longos e Dispersos , Células-Tronco Embrionárias Murinas , Oócitos , RNA Mensageiro , Adenosina/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Animais , Cromatina/metabolismo , Desmetilação , Elementos Nucleotídeos Longos e Dispersos/genética , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Oócitos/crescimento & desenvolvimento , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Inorg Chem ; 61(12): 4818-4824, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35289614

RESUMO

Iodine radioisotope, as one of the most important fission products of uranium, may cause severe damage to human health when it is accidentally discharged into the environment. Hence, efficient removal of radioactive iodine is one of the most critical issues for both used nuclear fuel (UNF) reprocessing and environmental remediation. In this work, three metal-organic gels (MOGs) were introduced for iodine removal. The presented zirconium-based MOGs, namely, CWNU, CWNU-NH2, and CWNU-2NH2, were prepared via moderate solvothermal reactions. These MOGs all exhibit excellent chemical stability and reusability, marked iodine sorption capability, and favorable machinability, which can even rival commercial ones. The sorption capacities are determined to be 3.36, 4.10, and 4.20 g/g, respectively. The increased amount of amino group is considered to be responsible for the elevated iodine sorption capacity and kinetics, as confirmed by combined sorption studies and XPS analysis. The presented work sheds light on the utilization of MOGs for radioiodine capture.


Assuntos
Neoplasias da Glândula Tireoide , Urânio , Géis , Humanos , Radioisótopos do Iodo , Zircônio
14.
J Immunother Cancer ; 10(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35064011

RESUMO

BACKGROUND: Dostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab. METHODS: GARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review. RESULTS: Screening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5-22.1) for cohort A1 and 11.5 months (IQR 11.0-25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1-2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab. CONCLUSION: Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile. TRIAL REGISTRATION NUMBER: NCT02715284.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores Tumorais/metabolismo , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Instabilidade de Microssatélites/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade
15.
J Hazard Mater ; 424(Pt C): 127678, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34775310

RESUMO

Development of high efficient adsorbents to capture iodine is of great significance for the active development of nuclear power. Herein, Bi0-SBA-15 was firstly synthesized and applied for capture of iodine gas. Bi0-SBA-15 materials were prepared by an improved impregnation reduction method. The benefit of this method was that the Bi0 nanoparticles with flocculent and spherical morphologies were loaded on the surface of SBA-15, which provide abundant active sites for iodine and improve the utilization rate of active sites, so as to attain a record high capture capacity (up to 925 mg/g within 60 min) and high stablitiy (91.2%) at 200 °C. The results demonstrated that the loading of Bi0 on the surface showed a significant impact on the structure of Bi0-SBA-15 and did greatly enhance the iodine capture. Furthermore, the high iodine capture capacity mainly derived from the chemical adsorption in the stable form of BiI3. The obtained Bi0-SBA-15 materials exhibited excellent aqueous and irradiation stability. Thus, the results indicated that the new and highly efficient Bi0-SBA-15 was a potential radioactive iodine gas capture material.

16.
Colloids Surf B Biointerfaces ; 210: 112216, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34838421

RESUMO

Efficient capture of radioactive iodine (129I, 131I) is of great significance in spent fuel treatment. In this paper, a new adsorbent named Catechin@ACF was successfully prepared through interface assembly of specific recognition gripper with plant polyphenols (catechin) on activated collagen fiber (ACF), and the catechin membrane with specific grip on iodine was successfully constructed on the surface of ACF. The results showed that the adsorbent assembled catechin membrane was rich in aromatic rings, hydroxyl groups and imine adsorption sites, and possessed specific recognition and capture characteristics of iodine. Moreover, the as-prepared Catechin@ACF showed excellent capture capacity for iodine vapor and iodine in organic solution with the maximum capture capacity of 2122.68 mg/g and 258.29 mg/g, respectively. In iodine-cyclohexane solution, the adsorption process was in according with the Pseudo first order kinetic and Langmuir isothermal model. In addition, the specific recognition and capture mechanism analysis indicated that the aromatic rings, phenolic hydroxyl groups and imine groups in the catechin membrane were the specific and effective grippers for iodine, and finally iodine formed a stable conjugated system with the adsorbent in the form of I- and I3-. Therefore, the as-prepared specific iodine capturer Catechin@ACF was expected to play a vital role in the capture of radioactive iodine in spent fuel off-gas because of its specific recognition, high capture capacity, large-scale preparation, and environment-friendly.


Assuntos
Iodo , Neoplasias da Glândula Tireoide , Adsorção , Colágeno , Humanos , Radioisótopos do Iodo
17.
J Hazard Mater ; 417: 125978, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34015715

RESUMO

Developing an efficient and cheap iodine sorbent is of great practical significance in the modern nuclear industry. In this work, novel bismuth and silver functionalized Ni foam composites as iodine sorption materials (Bi-Ni foam and Ag-Ni foam) were successfully prepared via a simple solvothermal method. Through a series of iodine sorption experiments and characterization methods, iodine capture properties and corresponding sorption mechanism were comprehensively compared and thoroughly revealed. The results show that the core-sheath structure formed by the solvothermal reaction can supply more active sites (Bi0 or Ag0 particles) for the contact of radioactive iodine gas, thereby improving the sorption capacity of sorbents. Compared with Ag-Ni foam (456 mg/g), Bi-Ni foam exhibits a higher iodine capture capacity (658 mg/g), whereas silver-based material has a faster sorption kinetics. Such excellent sorption performances were attributed to the chemical reaction between Bi0/Ag0 particles and iodine gas, generating stable BiI3/AgI. In addition, this type of sorbents inherits the external structure of the Ni foam skeleton, decreasing the physically sorbed iodine, and can be prepared in different shapes and sizes, which is of great practical significance.

18.
ACS Appl Mater Interfaces ; 13(10): 11968-11976, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33683098

RESUMO

The photocatalysts for hexavalent uranium (U(VI)) reduction suffered from the low uranium uptake capacity and weak long-wavelength light absorption. Herein, we synthesized the CdSxTe1-x nanobelts capped by ethylenediamine (EDA), which provided amino groups as the adsorption sites. With the increase of the Te content, the amino groups on the CdSxTe1-x nanobelts decreased because of the variation of the electron density of Cd2+, whereas the light adsorption was enhanced due to the narrowed bandgap. In photocatalytic reduction of U(VI), the CdS0.95Te0.05-EDA nanobelts exhibited a considerable U(VI) removal ratio of 97.4% with a remarkable equilibrium U(VI) extraction amount on per weight unit of the adsorbent (qe) of 836 mg/g. The bandgap structure and Fourier transform infrared spectroscopy (FT-IR) spectra analysis revealed that the optimum photocatalytic activity of CdSxTe1-x nanobelts was achieved at a 5% of Te2- doping, which balanced the factors of amino groups and bandgap. This adsorption-photoreduction process offers an ultrahigh uranium extraction capacity over wide uranium concentrations.

19.
Acta Obstet Gynecol Scand ; 99(10): 1346-1353, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32356359

RESUMO

INTRODUCTION: Preeclampsia affects about 10% of twin pregnancies and significantly increases the risk of adverse pregnancy outcomes. However, screening models for preeclampsia in twin pregnancies remain elusive. The present study aimed to evaluate the performance of a multi-marker first trimester preeclampsia screening model in low-risk twin pregnancies. MATERIAL AND METHODS: Between 2014 and 2017, we prospectively assessed first trimester biomarkers for preeclampsia in a 'low-risk' twin pregnancy cohort at a single center. Multiple logistic regression was used to determine significant predictors for early preeclampsia (occurring prior to 34 weeks) and late preeclampsia (occurring after 34 weeks). The performance of the screening models fitted using the significant predictors was calculated using receiver operating characteristics curves, and internal validation was performed using bootstrapping. RESULTS: A total of 769 twin pregnancies were included in the study. Early preeclampsia and late preeclampsia developed in 27 (3.5%) and 59 (7.7%) cases, respectively. Logistic regression analyses showed that maternal age, body mass index, mean artery pressure and placental growth factor were significant predictors for early preeclampsia. Maternal age, body mass index, mean artery pressure and pregnancy-associated plasma protein A were significant for late preeclampsia. Uterine artery pulsatility index was not predictive of either early or late preeclampsia. For the fitted screening model of early and late preeclampsia, the areas under receiver operating characteristics curves were 0.82 (95% confidence interval [CI] 0.76-0.88) and 0.66 (95% CI 0.59-0.73), which were expected to decrease to 0.77 and 0.60, respectively, based on bootstrapping; the positive predictive values were 10.2% and 12.5%; and the estimated detection rates were 40.7% and 22.0%, respectively, at a false-positive rate of 10%. CONCLUSIONS: A multi-marker screening model for preeclampsia in low-risk twin pregnancies, using a modified version of Fetal Medicine Foundation predictors in singletons, does not perform well. Uterine artery pulsatility index is of little value in screening for preeclampsia in low-risk twin pregnancies.


Assuntos
Pré-Eclâmpsia/diagnóstico , Primeiro Trimestre da Gravidez , Gravidez de Gêmeos , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Índice de Massa Corporal , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Idade Materna , Pré-Eclâmpsia/sangue , Valor Preditivo dos Testes , Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Estudos Prospectivos , Fluxo Pulsátil , Ultrassonografia Doppler , Artéria Uterina/diagnóstico por imagem , alfa-Fetoproteínas/análise
20.
Angew Chem Int Ed Engl ; 59(31): 12756-12761, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32343868

RESUMO

Cancer possesses normoxic and hypoxia microenvironments with different levels of oxygen, needing different efficacies of photothermal and photodynamic therapies. It is important to precisely tune the photothermal and photodynamic effects of phototherapy nano-agents for efficient cancer treatment. Now, a series of copolymeric nanoparticles (PPy-Te NPs) were synthesized in situ by controlled oxidative copolymerization with different ratios of pyrrole to tellurophene by FeCl3 . The photothermal and photodynamic effects of semiconducting nano-agents under the first near-infrared (NIR) irradiation were precisely and systematically tuned upon simply varying the molar ratio of the pyrrole to tellurophene. The PPy-Te NPs were used for cancer treatment in mice, exhibiting excellent biocompatibility and therapeutic effect. This work presents a simple method to tune photothermal and photodynamic therapies effect in semiconducting nano-agents for cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Pirróis/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Raios Infravermelhos , Camundongos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Polimerização , Polímeros/síntese química , Polímeros/efeitos da radiação , Pirróis/síntese química , Pirróis/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
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