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1.
J Colloid Interface Sci ; 673: 997-1006, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39002361

RESUMEN

The highly dispersed ultrasmall palladium nanoparticles (Pd NPs) (1.7 nm) were successfully immobilized on a N-containing metal-organic framework (MOF, DUT-67-PZDC) using a co-reduction method, and it is used as an excellent catalyst for formic acid dehydrogenation (FAD). The optimized catalyst Pd/DUT-67-PZDC(10, 10 wt% Pd loading) shows 100% hydrogen (H2) selectivity and formic acid (FA) conversion at 60 °C, and the commendable initial turnover frequency (TOF) values of 2572 h-1 with the sodium formate (SF) as an additive and 1059 h-1 even without SF, which is better than most reported MOF supported Pd monometallic heterogeneous catalysts. The activation energy (Ea) of FAD is 43.2 KJ/mol, which is lower than most heterogeneous catalysts. In addition, the optimized catalyst Pd/DUT-67-PZDC(10) maintained good stability over five consecutive runs, demonstrating only minimal decline in catalytic activity. The outstanding catalytic performance could be ascribed to the synergistic corporations of the unique structure of DUT-67-PZDC carrier with hierarchical pore characteristic, the metal-support interaction (MSI) between the active Pd NPs and DUT-67-PZDC, the highly dispersed Pd NPs with ultrafine size serve as the catalytic active site, as well as the N sites on the support could act as the proton buffers. This work provides a new paradigm for the efficient H2 production of FAD by constructing highly active heterogeneous Pd-based catalysts using MOF supports.

2.
Front Immunol ; 15: 1371379, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38881888

RESUMEN

SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) is a devastating subtype of thoracic tumor with SMARCA4 inactivation and is characterized by rapid progression, poor prognosis, and high risk of postoperative recurrence. However, effective treatments for SMARCA4-dUT are lacking. Herein, we describe a patient with SMARCA4-dUT who exhibited an impressive response to the anti-programmed cell death protein-1 (PD-1) antibody (tislelizumab) in combination with conventional chemotherapy (etoposide and cisplatin). To the best of our knowledge, this is the first case of SMARCA4-dUT treated with chemotherapy, comprising etoposide and cisplatin, combined with anti-PD-1 inhibitors. Immunotherapy combined with etoposide and cisplatin may be a promising strategy to treat SMARCA4-dUT.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , ADN Helicasas , Factores de Transcripción , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , ADN Helicasas/genética , ADN Helicasas/deficiencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factores de Transcripción/genética , Proteínas Nucleares/genética , Proteínas Nucleares/deficiencia , Etopósido/uso terapéutico , Etopósido/administración & dosificación , Masculino , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Resultado del Tratamiento , Femenino
3.
Lung Cancer ; 192: 107818, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38763102

RESUMEN

INTRODUCTIONS: The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS: From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy. RESULTS: SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028). CONCLUSIONS: SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.


Asunto(s)
ADN Helicasas , Neoplasias Pulmonares , Proteínas Nucleares , Neoplasias Torácicas , Factores de Transcripción , Humanos , ADN Helicasas/genética , ADN Helicasas/deficiencia , Factores de Transcripción/genética , Masculino , Femenino , Neoplasias Torácicas/genética , Neoplasias Torácicas/patología , Neoplasias Torácicas/tratamiento farmacológico , Neoplasias Torácicas/terapia , Persona de Mediana Edad , Proteínas Nucleares/genética , Proteínas Nucleares/deficiencia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Anciano , Mutación , Pronóstico , Adulto , Biomarcadores de Tumor/genética
4.
Chemosphere ; 357: 141981, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626813

RESUMEN

Metal-Organic Frameworks (MOFs) are extensively used as electrode material in various sensing applications due to their efficacious porous nature and tunable properties. However, pristine MOFs lack conductive attributes that hinder their wide usage in electrochemical applications. Electropolymerization of several aromatic monomers has been a widely used strategy for preparing conducting electrode materials for various sensing applications in the past decades. Herein, we report a similar approach by employing the electropolymerization method to create a functional polymer layer to enhance the sensitivity of an Aluminium Organic Framework (DUT-4) for the selective detection of Chloramphenicol (CAP) antibiotic in aqueous environment. The combined strategy using the conducting polymer layer with the porous Al MOF provides surpassing electrochemical performance for sensing CAP with regard to the very low detection limit (LOD = 39 nM) and exceptionally high sensitivity (11943 µA mM-1 cm-2). In addition, the fabricated sensor exhibited good selectivity, reproducibility and stability. The developed method was successfully evaluated in various real samples including lake water and river water for CAP detection with good recovery percentages even at lower concentrations.


Asunto(s)
Aluminio , Cloranfenicol , Técnicas Electroquímicas , Límite de Detección , Estructuras Metalorgánicas , Polímeros , Contaminantes Químicos del Agua , Cloranfenicol/análisis , Estructuras Metalorgánicas/química , Contaminantes Químicos del Agua/análisis , Aluminio/análisis , Aluminio/química , Polímeros/química , Técnicas Electroquímicas/métodos , Reproducibilidad de los Resultados , Antibacterianos/análisis , Electrodos , Ríos/química , Lagos/química , Lagos/análisis
5.
ACS Appl Mater Interfaces ; 16(7): 9068-9077, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38345827

RESUMEN

Metal-organic frameworks (MOFs), a sort of crystalline porous coordination polymers composed of metal ions and organic linkers, have been intensively studied for their ability to take up nonpolar gas-phase molecules such as ethane and ethylene. In this context, interpenetrated MOFs, where multiple framework nets are entwined, have been considered promising materials for capturing nonpolar molecules due to their relatively higher stability and smaller micropores. This study explores a solvent-assisted reversible strategy to interpenetrate and deinterpenetrate a Cu(II)-based MOF, namely, MOF-143 (noninterpenetrated form) and MOF-14 (doubly interpenetrated forms). Interpenetration was achieved using protic solvents with small molecular sizes such as water, methanol, and ethanol, while deinterpenetration was accomplished with a Lewis-basic solvent, pyridine. Additionally, this study investigates the adsorptive separation of ethane and ethylene, which is a significant application in the chemical industry. The results showed that interpenetrated MOF-14 exhibited higher ethane and ethylene uptakes compared to the noninterpenetrated MOF-143 due to narrower micropores. Furthermore, we demonstrate that pristine MOF-14 displayed higher ethane selectivity than transformed MOF-14 from MOF-143 by identifying the "fraction of micropore volume" as a key factor influencing ethane uptake. These findings highlight the potential of controlled transformations between interpenetrated and noninterpenetrated MOFs, anticipating that larger MOF crystals with narrower micropores and higher crystallinity will be more suitable for selective gas capture and separation applications.

6.
Gels ; 9(11)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37998999

RESUMEN

This research explores the integration of DUT-67 metal organic frameworks into polyethyleneimine-based hydrogels to assemble a composite system with enough mechanical strength, pore structure and chemical affinity to work as a sorbent for water remediation. By varying the solvent-to-modulator ratio in a water-based synthesis path, the particle size of DUT-67 was successfully modulated from 1 µm to 200 nm. Once DUT-67 particles were integrated into the polymeric hydrogel, the composite hydrogel exhibited enhanced mechanical properties after the incorporation of the MOF filler. XPS, NMR, TGA, FTIR, and FT Raman studies confirmed the presence and interaction of the DUT-67 particles with the polymeric chains within the hydrogel network. Adsorption studies of methyl orange, copper(II) ions, and penicillin V on the composite hydrogel revealed a rapid adsorption kinetics and monolayer adsorption according to the Langmuir's model. The composite hydrogel demonstrated higher adsorption capacities, as compared to the pristine hydrogel, showcasing a synergistic effect, with maximum adsorption capacities of 473 ± 21 mg L-1, 86 ± 6 mg L-1, and 127 ± 4 mg L-1, for methyl orange, copper(II) ions, and penicillin V, respectively. This study highlights the potential of MOF-based composite hydrogels as efficient adsorbents for environmental pollutants and pharmaceuticals.

7.
ACS Appl Mater Interfaces ; 15(41): 48264-48276, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37796977

RESUMEN

Atmospheric water harvesting with metal-organic frameworks (MOFs) is a new technology providing a clean, long-term water supply in arid areas. In-situ positron annihilation lifetime spectroscopy (PALS) is proposed as a valid methodology for the mechanistic understanding of water sorption in MOFs and the selection of prospective candidates for desired applications. DUT-67-Zr and DUT-67-Hf frameworks are used as model systems for method validation because of their hierarchical pore structure, high adsorption capacity, and chemical stability. Both frameworks are characterized using complementary techniques, such as nitrogen (77 K) and water vapor (298 K) physisorption, SEM, and PXRD. DUT-67-Zr and DUT-67-Hf are investigated by PALS upon exposure to humidity for the first time, demonstrating the stepwise pore filling mechanism by water molecules for both MOFs. In addition to exploring the potential of PALS as a tool for probing MOFs during in situ water loading, this work offers perspectives on the design and use of MOFs for water harvesting.

8.
J Investig Med High Impact Case Rep ; 11: 23247096231176220, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37269109

RESUMEN

SMARCA4-deficient undifferentiated tumors (SMARCA4-dUT) are infrequently occurring aggressive neoplasms found predominantly in young male smokers. These tumors are distinguished by the loss of expression of Brahma-related gene 1 (BRG1) due to a deactivating mutation of SMARCA4. Immunophenotype can be variable but characteristically lack the expression of BRG1. SMARCA4-dUT has a poor prognosis and generally progresses or recurs. The median survival is around 6 months. Here, we report a case of a 36-year-old male smoker who presents with multiple right-sided lung masses. The patient was found to have a loss of SMARAC4 and SMARCA2 along with the absence of markers of vascular, melanocytic, lymphoid, keratin, or myogenic origin. Tumor size was reduced significantly after 3 cycles of carboplatin and 1 cycle of pembrolizumab. From reviewing the literature and the clinical course in our case, we suggest combination chemotherapy plus immune checkpoint inhibitor (ICI) therapy to be the first choice of therapy for treating SMARCA4-dUT of lungs. Further research and studies are needed to evaluate the response to ICI therapy alone or combination therapy (chemotherapy plus ICI).


Asunto(s)
ADN Helicasas , Inhibidores de Puntos de Control Inmunológico , Humanos , Masculino , Adulto , Terapia Combinada , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética
9.
Front Chem ; 11: 1148073, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36926381

RESUMEN

Robust DUT-67 was synthesized by the hydrothermal method and characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). To systematically study the removal of Cr(VI) ion by DUT-67, single-factor, competition ion, material regeneration, kinetic, and thermodynamic experiments were designed. The experimental results show that DUT-67 had a maximum removal rate of 96.1% and a maximum adsorption capacity of 105.42 mg g-1 with material regeneration and outstanding selective adsorption. In addition, the process of removal of the Cr(VI) ion from an aqueous solution by DUT-67, which accorded with the pseudo-second-order kinetics model and Langmuir model, was studied, and its adsorption mechanism was reasonably explained by the theoretical calculation.

10.
Microbiol Spectr ; 11(1): e0323222, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36622213

RESUMEN

Stl, the master repressor of the Staphylococcus aureus pathogenicity islands (SaPIs), targets phage-encoded proteins to derepress and synchronize the SaPI and the helper phage life cycles. To activate their cycle, some SaPI Stls target both phage dimeric and phage trimeric dUTPases (Duts) as antirepressors, which are structurally unrelated proteins that perform identical functions for the phage. This intimate link between the SaPI's repressor and the phage inducer has imposed an evolutionary optimization of Stl that allows the interaction with Duts from unrelated organisms. In this work, we structurally characterize this sophisticated mechanism of specialization by solving the structure of the prototypical SaPIbov1 Stl in complex with a prokaryotic and a eukaryotic trimeric Dut. The heterocomplexes with Mycobacterium tuberculosis and Homo sapiens Duts show the molecular strategy of Stl to target trimeric Duts from different kingdoms. Our structural results confirm the participation of the five catalytic motifs of trimeric Duts in Stl binding, including the C-terminal flexible motif V that increases the affinity by embracing Stl. In silico and in vitro analyses with a monomeric Dut support the capacity of Stl to recognize this third family of Duts, confirming this protein as a universal Dut inhibitor in the different kingdoms of life. IMPORTANCE Stl, the Staphylococcus aureus pathogenicity island (SaPI) master repressor, targets phage-encoded proteins to derepress and synchronize the SaPI and the helper phage life cycles. This fascinating phage-SaPI arms race is exemplified by the Stl from SaPIbov1 which targets phage dimeric and trimeric dUTPases (Duts), structurally unrelated proteins with identical functions in the phages. By solving the structure of the Stl in complex with a prokaryotic (M. tuberculosis) and a eukaryotic (human) trimeric Dut, we showed that Stl has developed a sophisticated substrate mimicry strategy to target trimeric Duts. Since all these Duts present identical catalytic mechanisms, Stl is able to interact with Duts from different kingdoms. In addition, in silico modeling with monomeric Dut supports the capacity of Stl to recognize this third family of Duts, confirming this protein as a universal Dut inhibitor.


Asunto(s)
Bacteriófagos , Humanos , Bacteriófagos/genética , Bacteriófagos/metabolismo , Pirofosfatasas/genética , Islas Genómicas , Proteínas Represoras/genética , Proteínas Represoras/metabolismo
11.
J Colloid Interface Sci ; 631(Pt B): 154-163, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36401923

RESUMEN

Designing efficient metal organic frameworks (MOF)-based photocatalysts has recently attracted wide attention. In this work, Au nanoparticles(NPs)-decorated defective DUT-67(Zr) (Au@DUT-67(Zr)) with enlarged channels was successfully fabricated and achieved 7.5 times higher conversion than Au NPs-decorated UiO-66(Zr) (Au@UiO-66(Zr)) for photocatalytic selective oxidation of amines to imines driven by visible light. Au NPs are more effectively fixed on DUT-67(Zr) due to its partially hollow structure. Au@DUT-67(Zr) possesses more active sites including unsaturated Zr atoms and oxygen vacancies (VO) than Au@UiO-66(Zr). In situ Fourier transform infrared (FTIR) spectrum reveals that benzylamine is activated on unsaturated Zr sites via HN…Zr species, facilitating deprotonation of -CH2 in benzylamine. VO can not only adsorb and activate oxygen (O2) but also capture plasmonic hot electrons, enhancing the forming of superoxide radical (O2-). Plasmonic hot holes assisted with O2- effectively achieve the selective oxidation of benzylamine. Finally, a possible synergetic mechanism combining the plasmon with the molecular activation is presented to illustrate the photocatalytic pathway at the molecular level.

12.
J Cancer Res Clin Oncol ; 149(8): 4455-4463, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36121510

RESUMEN

PURPOSE: SMARCA4-deficient thoracic tumors are rapid aggressive malignancies, often diagnosed at an advanced and inoperable stage. The value of pulmonary resection for resectable SMARCA4-deficient thoracic tumors is largely unknown. METHODS: In this observational study, we included 45 patients who received surgery for stage I-III SMARCA4-deficient tumors. We compared the molecular, clinicopathological characteristics and survival between SMARCA4-dNSCLC and SMARCA4-deficient undifferentiated tumor (SMARCA4-dUT) patients. RESULTS: Thirty-four SMARCA4-dNSCLC and 11 SMARCA4-dUT patients were included in this study. Molecular profiles were available in 33 out of 45 patients. The most common mutated gene was TP53 (21, 64%), and followed by STK11 (9, 27%), KRAS (5, 15%), FGFR1 (4, 12%) and ROS1 (4, 12%). There were 3 patients that harbored ALK mutation including 1 EML4-ALK rearrangement. There were 2 patients that harbored EGFR rare site missense mutation. SMARCA4-dUT patients had significance worse TTP (HR = 4.35 95% CI 1.77-10.71, p = 0.001) and OS (HR = 4.27, 95% CI 1.12-16.35, p = 0.022) compared to SMARCA4-dNSCLC patients. SMARCA4-dUT histologic type, stage II/III, R1/2 resection and lymphovascular invasion were independent poor prognostic predictors for both TTP and OS. There were 8 patients who received immunotherapy, the objective response rate was 50%. The SMARCA4-dNSCLC patient with ALK rearrangement was treated with crizotinib as second-line therapy, and achieved stable disease for 9.7 months. CONCLUSION: Patients with SMARCA4-deficient tumors have a high probability of early recurrence after surgery, except for stage I patients. Immunotherapy seems to be a valuable strategy to treat recurrence.


Asunto(s)
Proteínas Tirosina Quinasas , Neoplasias Torácicas , Humanos , Proteínas Proto-Oncogénicas , Neoplasias Torácicas/genética , Neoplasias Torácicas/cirugía , Neoplasias Torácicas/patología , Pronóstico , Proteínas Tirosina Quinasas Receptoras , Biomarcadores de Tumor/genética , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética
13.
Cureus ; 14(10): e30708, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36439610

RESUMEN

Switch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4-deficient undifferentiated tumor (SMARCA4-dUT) is a rare malignancy due to inactivating mutations in the SMARCA4 gene of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex. These are aggressive malignancies presenting predominantly in male smokers in their fifth and sixth decades of life with nonspecific respiratory symptoms. Most patients have metastatic disease on presentation. The pattern of metastasis is similar to carcinomas, and the most common metastatic sites are lymph nodes, bones, and adrenal glands. Histologically, these tumors can be either entirely sarcomatoid or with mixed features of sarcoma and carcinoma, with extensive necrosis and high mitotic activity. Immunohistochemistry demonstrates negative expression of keratin and claudin-4, and tumor cell nuclei characteristically lack expression of Brahma-related gene-1 (BRG1). No standard treatment guidelines have been established due to the relative rarity of these tumors, and systemic chemoimmunotherapy has demonstrated benefit in some cases. We report two cases of SMARCA4-dUT with their clinical course and management to provide a perspective on the behavior of these tumors in a Western population cohort.

14.
J Chiropr Med ; 21(4): 305-315, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36420365

RESUMEN

Objective: The purpose of this study was to compare Functional and Kinetic Treatment with Rehabilitation (FAKTR) combined with cryotherapy to cryotherapy alone in the treatment of acute grade I or II inversion ankle sprains. Methods: This prospective, randomized clinical trial of adult (18-40 years of age) participants (n = 40) with acute grade I or II inversion ankle sprain of less than 3 weeks, who were randomly allocated into a FAKTR and cryotherapy group (n = 20) or a cryotherapy only group (n = 20). The participants had 3 treatments (inclusive of the initial consultation), with a fourth as a measurement follow-up (2 weeks after the third treatment). Measurement procedures were completed at the outset of the first to third consultations and the fourth measurement only consultation. Clinical measures taken by a blinded research assistant included the Numerical Pain Rating Scale, Foot function index, algometer, digital inclinometer for ankle dorsiflexion range of motion measures, the figure-of-8 maneuver measured swelling, and the Stork-Balance-Stand Test. Results: Significant intergroup differences were observed for pain rating (P ≤ .01; 95% confidence interval [CI] -4.74 to 0.86), pain pressure threshold (P ≤ .05; 95% CI -1.06 to 1.52), balance and proprioception (P ≤ .01; 95% CI -5.28 to -1.39), and foot function index (P ≤ .01; 95% CI -30.12 to 4.83). No significant intergroup differences were observed in ankle dorsiflexion range of motion (P = .242; 95% CI -3.17 to 1.20) and edema measurements (P = .602; 95% CI 0.41-1.46). Conclusion: The FAKTR instrument assisted soft tissue mobilization treatment combined with cryotherapy indicated a trend toward greater clinical effectiveness than cryotherapy for measures of pain, pain pressure threshold, balance and proprioception, and foot function index; however, these outcomes were not reflected for ankle dorsiflexion range of motion and edema measurements.

15.
Cancer Lett ; 548: 215898, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-36075487

RESUMEN

Uracil misincorporation during DNA replication is a major cell toxic event, of which cancer cells overcome by activating the dUTPase enzyme. The DUT gene is the only known dUTPase in human. Despite reports on common upregulations in cancers, the role of DUT in human hepatocellular carcinoma (HCC) remains largely undetermined. In this study, we investigated the mechanism underlying DUT biology in HCC and tumor susceptibility to drug targeting dUTPase. Overexpression of DUT was found in 42% of HCC tumors and correlated with advanced stage HCC. Knockout of DUT in HCC cell lines showed suppressed proliferation through cell cycle arrest and a spontaneous induction of DNA damage. A protective effect from oxidative stress was also demonstrated in both knockout and overexpression DUT assays. Transcriptome analysis highlighted the NF-κB survival signaling as the downstream effector pathway of DUT in overriding oxidative stress-induced cell death. Interestingly, stably expressed DUT in liver progenitor organoids conferred drug resistance to TKI Sorafenib. Targeting dUTPase activity by TAS-114, could potentiate suppression of HCC growth that synergized with Sorafenib for better treatment sensitivity. In conclusion, upregulated DUT represents a nucleotide metabolic weakness and therapeutic opportunity in HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , FN-kappa B , Nucleótidos , Pirofosfatasas , Sorafenib/farmacología , Uracilo/metabolismo
16.
Am J Med Genet A ; 188(8): 2406-2412, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35611808

RESUMEN

In 2017, a homozygous DUT mutation was reported to cause a syndrome of diabetes and bone marrow failure. However, no further patient with this combination has been reported and the phenotype of heterozygous DUT mutation is unknown. We describe the genotype, phenotype, and post bone marrow transplantation (BMT) data of two unrelated families with this rare syndrome. Whole-exome and/or direct sequencing of the DUT gene were performed in all family members. Each family has two children presented within the first 10 years of life with thrombocytopenia, macrocytosis, with or without anemia, followed by non-autoimmune diabetes. The same homozygous missense DUT mutation, reported in 2017 (c.425A>G p.(Tyr142Cys), was detected in all affected children. The heterozygous carriers have no BM failure, one developed type 2 diabetes, and the rest have normal fasting glucose, insulin, HbA1c, and c-peptide. Multiple nevi were detected in homozygous and heterozygous mutation carriers. Allogenic BMT normalized BM aplasia without impact on diabetes. Post BMT follow-up revealed normal puberty and school performance; but three have height <2.5 SDS. We add two families with this syndrome supporting a role of DUT in bone marrow and ß-cell function. The heterozygous carriers of this DUT mutation appear to be healthy.


Asunto(s)
Diabetes Mellitus Tipo 2 , Trastornos de Fallo de la Médula Ósea , Trasplante de Médula Ósea , Heterocigoto , Homocigoto , Humanos , Síndrome
17.
Polymers (Basel) ; 13(23)2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34883580

RESUMEN

Zirconium-based metal-organic frameworks (Zr-MOFs) have great structural stability and offer great promise in the application of gas capture. However, the powder nature of MOF microcrystallines hinders their further industrial-scale applications in fluid-phase separations. Here, Zr-based DUT-68 was structured into nontoxic and eco-friendly alginate beads, and the gas capture properties were evaluated by CO2 and volatile iodine. DUT-68 beads were synthesized via a facile and versatile cross-linked polymerization of sodium alginate with calcium ions. The composite beads keep the structural integrity and most of the pore accessibility of DUT-68. The resulting DUT-68@Alginate (2:1) porous bead processes a surface area of 541 m2/g and compressive strength as high as 1.2 MPa, and the DUT-68 crystals were well-dispersed in the alginate networks without agglomeration. The DUT-68@Alginate bead with a 60% weight ratio of MOFs exhibits a high carbon dioxide capacity (1.25 mmol/g at 273 K), as well as an excellent high adsorption capacity for iodine, reaching up to 0.65 g/g at 353 K. This work provides a method to construct thiophene-contained composite beads with millimeter sizes for the capture of gases in potential industrial applications.

18.
J Geod ; 95(7): 75, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34720450

RESUMEN

One of the main tasks of Very Long Baseline Interferometry (VLBI) is the rapid determination of the highly variable Earth's rotation expressed through the difference between Universal Time UT1 and Coordinated Universal Time UTC (dUT1). For this reason, dedicated one hour, single baseline sessions, called "Intensives", are observed on a daily basis. Thus far, the optimal geometry of Intensive sessions was understood to include a long east-west extension of the baseline to ensure a dUT1 estimation with highest accuracy. In this publication, we prove that long east-west baselines are the best choice only for certain lengths and orientations. In this respect, optimal orientations may even require significant inclination of the baseline with respect to the equatorial plane. The basis of these findings is a simulation study with subsequent investigations in the partial derivatives of the observed group delays τ with respect to dUT1 ∂ τ / ∂ d U T 1 . Almost 3000 baselines between artificial stations located on a regular 10 × 10 degree grid are investigated to derive a global and generally valid picture about the best length and orientation of Intensive baselines. Our results reveal that especially equatorial baselines or baselines with a center close to the equatorial plane are not suited for Intensives although they provide a good east-west extension. This is explained by the narrow right ascension band of visible sources and the resulting lack of variety in the partial derivatives. Moreover, it is shown that north-south baselines are also capable of determining dUT1 with reasonable accuracy, given that the baseline orientation is significantly different from the Earth rotation axis. However, great care must be taken to provide accurate polar motion a priori information for these baselines. Finally, we provide a better metric to assess the suitability of Intensive baselines based on the effective spread of ∂ τ / ∂ d U T 1 .

19.
Chemphyschem ; 22(22): 2336-2341, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34487609

RESUMEN

The dynamics of carbon dioxide in third generation (i. e., flexible) Metal-Organic Frameworks (MOFs) can be experimentally observed by 13 C NMR spectroscopy. The obtained line shapes directly correlate with the motion of the adsorbed CO2 , which in turn are readily available from classical molecular dynamics (MD) simulations. In this article, we present our publicly available implementation of an algorithm to calculate NMR line shapes from MD trajectories in a matter of minutes on any current personal computer. We apply the methodology to study an effect observed experimentally when adsorbing CO2 in different samples of the pillared layer MOF Ni2 (ndc)2 (dabco) (ndc=2,6-naphthalene-dicarboxylate, dabco=1,4-diazabicyclo-[2.2.2]-octane), also known as DUT-8(Ni). In 13 C NMR experiments of adsorbed CO2 in this MOF, small (rigid) crystals result in narrower NMR line shapes than larger (flexible) crystals. The reasons for the higher mobility of CO2 inside the smaller crystals is unknown. Our ligand field molecular mechanics simulations provide atomistic insight into the effects visible in NMR experiments with limited computational effort.

20.
Angew Chem Int Ed Engl ; 60(40): 21778-21783, 2021 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-34273230

RESUMEN

We present a toolbox for the rapid characterisation of powdered samples of paramagnetic metal-organic frameworks at natural abundance by 1 H-detected solid-state NMR. Very fast MAS rates at room and cryogenic temperatures and a set of tailored radiofrequency irradiation schemes help overcome the sensitivity and resolution limits often associated with the characterisation of MOF materials. We demonstrate the approach on DUT-8(Ni), a framework containing Ni2+ paddle-wheel units which can exist in two markedly different architectures. Resolved 1 H and 13 C resonances of organic linkers are detected and assigned in few hours with only 1-2 mg of sample at natural isotopic abundance, and used to rapidly extract information on structure and local internal dynamics of the assemblies, as well as to elucidate the metal electronic properties over an extended temperature range. The experiments disclose new possibilities for describing local and global structural changes and correlating them to electronic and magnetic properties of the assemblies.

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