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1.
Carbohydr Polym ; 339: 122283, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823934

RESUMO

Efficient removal of uranium from radioactive wastewater is crucial for both environmental protection and sustainable development of nuclear energy. However, selectively extracting uranium from acidic wastewater remains a significant challenge. Here we present a phytic acid-functionalized polyamidoxime/alginate hydrogel (PAG) via a facile one-step hydrothermal reaction. The PAG, leveraging the robust binding affinity of phytic acid and the selective coordination of amidoxime for U(VI), exhibited high efficiency and selectivity in adsorbing U(VI) from acidic uranium-containing wastewater. At pH 2.50, U(VI) adsorption equilibrium was achieved within 60 min, showcasing a maximum theoretical adsorption capacity of 218.34 mg/g. Additionally, the PAG demonstrated excellent reusability, maintaining a uranium removal rate exceeding 90 % over five adsorption-desorption cycles. Remarkably, the as-synthesized PAG removed 94.1 % of U(VI) from actual acidic uranium-contaminated groundwater with excellent anti-interference performance, reducing U(VI) concentration from 272.0 µg/L to 16.1 µg/L and making it meet the WHO drinking water standards (30 µg/L). The adsorption mechanism was elucidated through XPS and DFT calculation, revealing that the uranyl ion primarily coordinated with phosphate and amidoxime groups on phytic acid and polyamidoxime, respectively. These findings underscore the promising potential of PAG hydrogel for addressing acidic uranium-containing wastewater from uranium mining and metallurgy.

2.
Phys Rev Lett ; 128(17): 170501, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35570417

RESUMO

Long-distance quantum state transfer (QST), which can be achieved with the help of quantum teleportation, is a core element of important quantum protocols. A typical situation for QST based on teleportation is one in which two remote communication partners (Alice and Bob) are far from the entanglement source (Charlie). Because of the atmospheric turbulence, it is challenging to implement the Bell-state measurement after photons propagate in atmospheric channels. In previous long-distance free-space experiments, Alice and Charlie always perform local Bell-state measurement before the entanglement distribution process is completed. Here, by developing a highly stable interferometer to project the photon into a hybrid path-polarization dimension and utilizing the satellite-borne entangled photon source, we demonstrate proof-of-principle QST at the distance of over 1200 km assisted by prior quantum entanglement shared between two distant ground stations with the satellite Micius. The average fidelity of transferred six distinct quantum states is 0.82±0.01, exceeding the classical limit of 2/3 on a single copy of a qubit.

3.
Eur J Med Chem ; 236: 114307, 2022 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-35436669

RESUMO

Aiming to track the potential antitumor effect of novel allosteric autotaxin (ATX) inhibitors, a hybrid strategy was utilized by merging ATX inhibitors PF-8380 and GLPG1690, while the piperazinyl group in GLPG1690 was replaced with benzene ring to furnish imidazo[1,2-a]pyridine derivatives 10ã10k. Based on ATX enzymatic assay, we further changed the substituents within benzyl carbamate moiety and tuned the carbamate linker to urea group. Delightfully, compound 10c bearing a N-hydroxyethyl piperazinyl group was identified as the optimal ATX inhibitor with an IC50 value of 3.4 nM 10c exerted the most impressive antitumor effects, especially on Hep3B (0.58 µM) and RAW264.7 (0.63 µM) cell lines highly expressing ATX mRNA. Moreover, 10c could dose-dependently suppress the RAW264.7 cell migration rate in wound healing assay and significantly inhibit RAW264.7 cell colony formation. Meanwhile, 10c was capable of inducing weak to moderate apoptosis and achieved notable G2 phase arrest on RAW264.7 cells. Taken together, 10c may serve as a novel lead to probe possible role of ATX allosteric inhibitors in tumor diseases.


Assuntos
Neoplasias , Inibidores de Fosfodiesterase , Diester Fosfórico Hidrolases , Piridinas , Animais , Carbamatos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Piridinas/farmacologia , Células RAW 264.7 , Relação Estrutura-Atividade
4.
Bioorg Chem ; 120: 105590, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34998121

RESUMO

Aiming to develop novel allosteric autotaxin (ATX) inhibitors, hybrid strategy was utilized by assembling the benzyl carbamate fragment in PF-8380 onto the imidazo[1,2-a]pyridine skeleton of GLPG-1690. The piperazine moiety in GLPG-1690 was replaced with phenyl ring to enhance the π-π interactions with adjacent residues. In the light of FS-3 based ATX enzymatic assay, further structure-guided optimizations were implemented by exploring the substituents within the carbamate aromatic moiety and examining the effect of the 2-ethyl. Eventually, 13c bearing 1,3-benzodioxole and 2-hydroxyethyl piperazine group was identified as a powerful ATX inhibitor with an IC50 value of 2.7 nM. Subsequently, 13c was forwarded into an in vivo bleomycin-induced mice lung fibrosis model. In histopathological and immunohistochemical assays, 13c could typically alleviate the severity of fibrosis tissues and effectively reduce the deposition of fibrotic biomarker α-SMA. At a dose of 60 mg/kg, 13c was observed equivalent or even better potency than GLPG-1690 with a significant inhibition of the in vivo ATX activity. Except for the fundamental H-bond and π-π interactions, an extra H-bond between the 1,3-benzodioxole (O atom) and Phe306 offered great rationale in constraining the binding conformation of 13c. Finally, binding free energy calculation was conducted to assist in the efficient identification of allosteric ATX inhibitors.


Assuntos
Diester Fosfórico Hidrolases , Piridinas , Animais , Carbamatos , Modelos Animais de Doenças , Fibrose , Pulmão , Camundongos , Diester Fosfórico Hidrolases/metabolismo , Piperazinas , Piridinas/química , Piridinas/farmacologia , Piridinas/uso terapêutico , Relação Estrutura-Atividade
5.
Eur J Med Chem ; 227: 113951, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34742015

RESUMO

In recent decades, pharmacological targeting of the autotaxin (ATX)/lysophosphatidic acid (LPA) axis accounted for excellent disease management benefits. Herein, to extend the scope of structure-activity relationships (SARs), fifteen indole-based carbamate derivatives (1-15) were prepared to evaluate the ATX inhibitory potency. Among them, compound 4 bearing morpholine moiety was identified as the optimal ATX inhibitor (0.41 nM), superior to the positive control GLPG1690 (2.90 nM). To resolve the intractable issue of poor pharmacokinetic (PK) property, urea moiety was introduced as a surrogate of carbamate which furnished compounds 16-30. The dedicated modification identified the diethanolamine entity 30 with satisfactory water solubility and PK profiles with a minimum sacrifice of ATX inhibition (2.17 nM). The most promising candidate 30 was evaluated for anti-fibrosis effect in a bleomycin challenged mice lung fibrosis model. Upon treatment with 30, the in vivo ATX activity in both lung homogenate and broncheoalveolar fluid (BALF) sample was significantly down-regulated. Furthermore, the gene expression of pro-fibrotic cytokines transforming growth factor-ß (TGF-ß), interleukin- 6 (IL-6) and tumor necrosis factor-α (TNF-α) in lung tissue was reduced to normal level. Collectively, the promising biological effects may advocate potential application of 30 in fibrosis relevant diseases.


Assuntos
Modelos Animais de Doenças , Indóis/farmacocinética , Diester Fosfórico Hidrolases/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Humanos , Indóis/síntese química , Indóis/química , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Fibrose Pulmonar/metabolismo , Relação Estrutura-Atividade
6.
Bioorg Med Chem ; 46: 116362, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34428714

RESUMO

A series of imidazo[1,2-a]pyridine compounds bearing urea moiety (8-27) were designed, synthesized and evaluated for their ATX inhibitory activities in vitro by FS-3 based enzymatic assay. Delightfully, benzylamine derivatives (14-27) exhibited higher ATX inhibitory potency with IC50 value ranging from 1.72 to 497 nM superior to benzamide analogues (8-13). Remarkably, benzylamine derivative 20 bearing 4-hydroxypiperidine exerted an amazing inhibitory activity (IC50 = 1.72 nM) which exceeded the positive control GLPG1690 (IC50 = 2.90 nM). Simultaneously, the binding model of 20 with ATX was established which rationalized the well performance of 20 in enzymatic assay. Accordingly, further in vivo studies were carried out to evaluate direct anti-fibrotic effects of 20 through Masson staining. Notably, 20 effectively alleviated lung structural damage with fewer fibrotic lesions at an oral dose of 60 mg/kg, qualifying 20 as a promising ATX inhibitor for IPF treatment.


Assuntos
Antifibróticos/farmacologia , Desenho de Fármacos , Fibrose/tratamento farmacológico , Diester Fosfórico Hidrolases/metabolismo , Piridinas/farmacologia , Ureia/farmacologia , Animais , Antifibróticos/síntese química , Antifibróticos/química , Relação Dose-Resposta a Droga , Fibrose/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade , Ureia/química
7.
Science ; 366(6461): 132-135, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31604316

RESUMO

Quantum mechanics and the general theory of relativity are two pillars of modern physics. However, a coherent unified framework of the two theories remains an open problem. Attempts to quantize general relativity have led to many rival models of quantum gravity, which, however, generally lack experimental foundations. We report a quantum optical experimental test of event formalism of quantum fields, a theory that attempts to present a coherent description of quantum fields in exotic spacetimes containing closed timelike curves and ordinary spacetime. We experimentally test a prediction of the theory with the quantum satellite Micius that a pair of time-energy-entangled particles probabilistically decorrelate passing through different regions of the gravitational potential of Earth. Our measurement results are consistent with the standard quantum theory and hence do not support the prediction of event formalism.

8.
Zhonghua Yi Xue Za Zhi ; 95(46): 3770-4, 2015 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-26850020

RESUMO

OBJECTIVE: To investigate the association of thyroid autoimmunity (TAI) with pregnancy outcomes in euthyroid women undergoing in vitro fertilization (IVF). METHODS: The meta-analysis was a systematic review of cohort studies published before May 10th, 2014. Data were retrieved from Medline, Embase and Cochrane library, and the keywords were "thyroid autoimmunity" and "pregnancy outcome", with restriction to artificial reproductive technique. RevMan 5.2 software was used for data analysis. RESULTS: In all, 11 cohort studies met the inclusion criteria and were included in the meta-analysis. The results showed that TAI was not associated with clinical pregnancy rate (RR=0.99, 95%CI: 0.89-1.11, P=0.92), but significantly associated with miscarriage risk (RR=1.54, 95%CI: 1.24-1.92, P<0.001). Live birth/ongoing pregnancy rate decreased in the TAI group compared with the control group, but there was no statistically significant difference (RR=0.89, 95%CI: 0.79-1.00, P=0.06). CONCLUSION: As for euthyroid women who are receiving IVF, TAI contributes to increased risk of miscarriage. Therefore, we recommend universal screening for thyroid disease among women undergoing IVF.


Assuntos
Autoimunidade , Glândula Tireoide , Aborto Espontâneo , Feminino , Fertilização in vitro , Humanos , Gravidez , Resultado da Gravidez , Taxa de Gravidez
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 31(2): 192-5, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24711030

RESUMO

OBJECTIVE: To investigate the origin of a rare supernumerary chromosome in a patient with premature ovarian failure (POF), and to explore the relationship between this abnormal karyotype and pathogenesis of POF. METHODS: GTG banding karyotyping, Q-banding and fluorescence in situ hybridization (FISH) were employed for the investigation. RESULTS: The extra chromosome was identified as i(Y)(q10) by FISH with a panel of sex chromosome probes. The patient's karyotype was described as: 47,XX,+ ish mar i(Y)(q10) (DXZ1-, SRY-, DYZ3+, DYZ1++, wcpY+). CONCLUSION: Co-occurrence of the supernumerary i(Y)(q10) with a female kryotype is extremely rare. This supernumerary chromosome may cause failure of X chromosomes synapsis during pachytene of meiosis I, which may trigger apoptosis of many oocytes and result in POF of the patient. Q-banding, FISH and multiple probes have been critical for accurate diagnosis of the unknown chromosome.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 10 , Cromossomos Humanos Y , Insuficiência Ovariana Primária/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariótipo
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 30(4): 415-9, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23926007

RESUMO

OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) and bacterial artificial chromosome FISH (BAC-FISH) for the diagnosis for patients with marker chromosomes. METHODS: Sixteen patients with marker chromosomes were analyzed with technologies including GTG-banding, Q-banding, multiplex FISH and BAC-FISH. RESULTS: The marker chromosomes in the 16 patients were verified as der(Y) (2 cases), psu dic(Y) (1 case), psu dic(15) (1 case), dic(15) (1 case), del(Y) (1 case), r(X) (5 cases), i(14 or 22) (2 cases), i(18) (1 case). CONCLUSION: FISH and BAC-FISH can both verify the origin of marker chromosomes and provide accurate information for the diagnosis and treatment of patients.


Assuntos
Aberrações Cromossômicas , Doenças Genéticas Inatas/genética , Marcadores Genéticos/genética , Hibridização in Situ Fluorescente/métodos , Adolescente , Adulto , Criança , Feminino , Doenças Genéticas Inatas/diagnóstico , Humanos , Masculino , Adulto Jovem
11.
Clin Biochem ; 45(3): 219-22, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22178106

RESUMO

OBJECTIVES: We analyzed the correlation between osteoporosis and carotid atherosclerosis (CA) by exploring the effects of ApoE gene polymorphisms on bone mineral density (BMD) of the lumbar spine and CA. DESIGN AND METHODS: We selected 221 elderly Han male patients and divided them into four groups: control, CA, BMD↓, and CA+BMD↓ according to their carotid ultrasonography and lumbar BMD results. ApoE gene polymorphisms were examined in each group. RESULTS: The CA group had a higher incidence of ApoE4 isoforms compared to normal controls (P<0.05). The ApoE4 isoform incidence in the BMD↓ and BMD↓/CA groups showed no significant difference from control. ApoE4 genotype incidences in the CA group, BMD ↓ group, and CA/BMD ↓ group were not significantly different. CONCLUSION: The ApoE4 genotype may be a risk factor for carotid atherosclerosis, but is not correlated with bone mineral density (BMD) in the lumbar spine in elderly Han males.


Assuntos
Apolipoproteínas E/genética , Densidade Óssea/genética , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/fisiopatologia , Predisposição Genética para Doença , Vértebras Lombares/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética , Idoso , Alelos , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , Masculino , Razão de Chances
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 26(5): 529-32, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-19806574

RESUMO

OBJECTIVE: To investigate the application of fluorescence in situ hybridization (FISH) technique in prenatal diagnosis of complex chromosomal abnormalities. METHODS: Eleven prenatal diagnosis cases (8 from amniocentesis and 3 from cord blood) with complex chromosomal abnormalities detected by routine G-banding, were further analyzed by FISH. RESULTS: The FISH technique confirmed the results of balanced chromosome rearrangements detected by G-banding, and clarified the structure of the derivative chromosomes in the 3 amniocentesis samples and the origin of the mark chromosomes in the 2 cord blood samples. CONCLUSION: FISH can be used to diagnose the complex chromosomal abnormalities accurately in prenatal diagnosis, and can provide very useful genetic information for clinical diagnosis and treatment.


Assuntos
Aberrações Cromossômicas , Hibridização in Situ Fluorescente/métodos , Gravidez/genética , Diagnóstico Pré-Natal/métodos , Líquido Amniótico/química , Feminino , Sangue Fetal/química , Humanos
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 25(5): 570-2, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18841574

RESUMO

OBJECTIVE: To explore the applications of fluorescence in situ hybridization (FISH) in the diagnosis for the patients with gonadal dysgenesis. METHODS: After routine gynecologic examination, ultrasonography and endocrine examination, 5 cases of gonadal dysgenesis and hypogonadism were analyzed by using chromosomal diagnoses including G-banding, Q-banding, multiplex FISH and BAC-FISH analyses. RESULTS: Among the 5 cases of gonad agenesis patients, 2 were pure gonadal dysgenesis with 46, XY karyotype, 3 were mixed gonadal dysgenesis with mos 45, X/47, XXX; 45, X/46, XY or 46, X, der(Y) karyotype. CONCLUSION: Sex chromosomal abnormalities resulted in gonadal dysgenesis symptoms. Applications of FISH and BAC-FISH analyses can correctly diagnose the sex chromosomal abnormalities for patients with gonad agenesis and provide accurate medical genetic data for clinical diagnosis and therapy.


Assuntos
Cromossomos Artificiais Bacterianos/genética , Disgenesia Gonadal/genética , Hibridização in Situ Fluorescente/métodos , Adolescente , Disgenesia Gonadal/diagnóstico , Disgenesia Gonadal/patologia , Disgenesia Gonadal/terapia , Humanos , Cariotipagem , Masculino , Aberrações dos Cromossomos Sexuais
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 25(2): 190-4, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18393244

RESUMO

OBJECTIVE: To investigate the clinical correlation of chromosome abnormalities and microdeletion in azoospermic factor (AZF) region on Y chromosome in 25 patients with azoospermia. METHODS: Chromosome analyses were performed by using chromosome GTG-banding, Q-banding, fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) for AZF region on chromosome Yq. RESULTS: Seven cases showed abnormal chromosome karyotype (28%). In 8 azoospermic patients tested, 2 showed microdeletions of AZFb (SY127, SY134)+ AZFc (SY254, SY255) and AZFc(SY243, SY158) on chromosome Yq, respectively. CONCLUSION: Chromosome abnormalities and AZF microdeletion are major cause of azoospermia leading to male infertility; male with azoospermia and infertility should be referred to cytogenetic diagnosis by using chromosome GTG-banding, Q-banding after ruling out clinical factors including testopathy, obstructive azoospermia, and abnormalities in incretion and immune system. FISH or PCR analysis for AZF region on chromosome Yq should be done for the patient with azoospermia if Q-banding indicates the deletion above Yq12 region. It is of essential importance to provide precise diagnosis in genetic counseling for further clinical treatment.


Assuntos
Azoospermia/genética , Cromossomos Humanos Y/genética , Adulto , Deleção Cromossômica , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 24(3): 256-60, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17557232

RESUMO

OBJECTIVE: To explore the use of fluorescence in situ hybridization (FISH) and high resolution-comparative genomic hybridization (HR-CGH) techniques in amenorrhea study. METHODS: After routine gynecologic examination, ultrasonography and endocrine examination, 17 cases of primary amenorrhea and 1 case of secondary amenorrhea were analysed by using chromosomal diagnoses including multiplex FISH and HR-CGH analyses. RESULTS: Among 17 cases of primary amenorrhea, 7 revealed a 46,XX karyotype; 10 cases (58.8%) had abnormal karyotype, including 3 cases of 46,XY females, 2 cases of Turner's syndrome with 45,X and 45,X/46,XX, and other 5 cases with abnormal structure of X chromosome (including partial monosomy of X,X isochromosome and X/Y mosaic). The karyotype of the patient with secondary amenorrhea was translocation between X chromosome and euchromosome. CONCLUSION: The using of FISH and HR-CGH can correctly diagnose the patients' karyotypes, and provide absolutely necessarily medical genetic data for clinical diagnosis and therapy.


Assuntos
Amenorreia/genética , Amenorreia/patologia , Aberrações Cromossômicas , Adolescente , Adulto , Amenorreia/diagnóstico , Cromossomos Humanos/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem
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