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1.
Phys Chem Chem Phys ; 25(27): 18030-18037, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37378512

RESUMO

Improved dielectric constant and breakdown strength facilitates excellent energy storage density of polymer dielectrics, which is positive to miniaturize dielectric capacitors in electronic and electrical systems. Although coating polar substances on nanoparticles enhances the dielectric constants of polymer nanocomposites, it usually causes local electric field concentration, leading to poor breakdown strength. Here, fluoropolymers with tailorable fluorine content (PF0, PF30 and PF60) are coated on BaTiO3 (BT) nanoparticles to construct typical core-shell structures that are further blended with poly(vinylidenefluoride-co-hexafluoropropylene) (P(VDF-HFP)) to obtain BT@PF/P(VDF-HFP) nanocomposites. Uniform dispersion of nanoparticles and excellent compatibility of interfaces are observed for the samples. In addition, the dielectric constant gradually increases from 8.03 to 8.26 to 9.12 for the nanocomposites filled with 3 wt% BT@PF0, BT@PF30 and BT@PF60, respectively. However, 3 wt% BT@PF30/P(VDF-HFP) has the highest breakdown strength (455 kV mm-1) among the nanocomposites, which is as good as neat P(VDF-HFP). More importantly, BT@PF30 rather than BT@PF60 possesses the maximum discharged energy density (11.56 J cm-3 at 485 kV mm-1), which is about 1.65 times that of neat P(VDF-HFP). This work proposes a facile experimental route to optimize the dielectric constants of the shell layer to couple the dielectric constants between the nanoparticles, shell layer and polymer matrix, which contributes to alleviating the local electric field concentration for excellent breakdown strength and electrical energy storage of polymer nanocomposites.

2.
Environ Toxicol ; 38(10): 2332-2343, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37357614

RESUMO

Environmental pollution is complex, and co-exposure can accurately reflect the true environmental conditions that are important for assessment of human health. Cadmium (Cd) is a widespread toxicant that can cause acute kidney injury (AKI), while its combined effect with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is not fully understood. Thus, we used an in vivo model where C57BL/6J mice were treated with low dietary intake of Cd (5 mg/kg/day) and/or BDE-47 (1 mg/kg/day) for 28 days to examine AKI, and in vitro experiments to investigate the possible mechanism. Results showed that Cd or BDE-47 caused pathological kidney damage, accompanied by elevated urea nitrogen (BUN) and urinary creatinine, as well as increased interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and reduced IL-10 in kidney tissues. In vitro Cd or BDE-47 exposure decreased cell viability and induced cell swelling and blebbing of human embryonic kidney 293 (HEK-293) and renal tubular epithelial cell lines (HKCs), and changes in co-exposure was larger than that in Cd and BDE-47 treatment. Oxidative stress indicators of the reactive oxygen species (ROS) and malondialdehyde (MDA) were elevated, while the antioxidant superoxide dismutase (SOD) was decreased. Necrosis occurred with increased lactate dehydrogenase (LDH) release and propidium iodide (PI) staining, which was attenuated by the ROS scavenger N-acetyl-L-cysteine (NAC). Furthermore, necroptotic genes of receptor-interacting protein kinase-3 (RIPK3), classical mixed lineage kinase domain-like protein-dependent (MLKL), IL-1ß and TNF-α were up-regulated, whereas RIPK1 was down-regulated, which was attenuated by the RIPK3 inhibitor GSK872. These findings demonstrate that Cd or BDE-47 alone produces kidney toxicities, and co-exposure poses an additive effect, resulting in AKI via inducing oxidative stress and regulating RIPK3-dependent necroptosis, which offers a further mechanistic understanding for kidney damage, and the combined effect of environmental pollutants should be noticed.


Assuntos
Injúria Renal Aguda , Cádmio , Humanos , Camundongos , Animais , Cádmio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Éter/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Necroptose , Células HEK293 , Camundongos Endogâmicos C57BL , Injúria Renal Aguda/metabolismo , Estresse Oxidativo , Etil-Éteres/farmacologia , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/farmacologia
3.
Anal Bioanal Chem ; 414(5): 1891-1898, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35001192

RESUMO

Telomerase is considered a valuable diagnostic and prognostic cancer biomarker. Accurate and reliable detection of telomerase activity is of great value in clinical diagnosis, screening of inhibitors, and therapeutics. Here, we developed a novel amplified fluorescence resonance energy transfer (FRET) nanoprobe for highly sensitive and reliable monitoring of intracellular telomerase activity. The nanoprobe (QDSA@DNA) was composed of a streptavidin-modified quantum dot (QDSA) which was functionalized with a telomerase primer sequence (TP) and Cy5-tagged signal switching sequence (SS) through biotin-streptavidin interaction. When the nanoprobe was assembled, the Cy5 was in close proximity to the QDSA, resulting in high FRET efficiency from the QDSA to Cy5. In the presence of telomerase, the TP could be extended to produce telomeric repeat units, which was complementary to the loop of SS. Thus, the SS could hybridize with elongated sequences to form a rigid double-stranded structure, which forced the Cy5 away from the surface of the QDSA, causing low FRET efficiency. Furthermore, due to the production of multiple repeat units by telomerase, multiple hairpin structures could be opened, yielding significant fluorescence ratio (FQDsa/FCy5) enhancement for sensing of telomerase activity. In this way, the combination of a FRET and target-assisted strategy in a nanoprobe improved the detection accuracy and amplified the detection signal, respectively. The QDSA@DNA nanoprobe also showed high selectivity, excellent nuclease stability, and good biocompatibility. More importantly, this nanoprobe was found to be an excellent platform for efficient monitoring of intracellular telomerase activity, providing a potential platform in tumor diagnosis and screening of telomerase-related inhibitors.


Assuntos
Corantes Fluorescentes/química , Nanoestruturas/química , Telomerase/metabolismo , Transferência Ressonante de Energia de Fluorescência/métodos , Células HeLa , Humanos , Pontos Quânticos
4.
J Environ Manage ; 307: 114583, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35085962

RESUMO

It is currently thought that the incineration approach is an effective method to minimize the volume of radioactive wastes. In this paper, we used an incinerator to burn uranium-containing strippable coating waste. The migration behavior of radioactive uranium during the incineration process were investigated based on hierarchical sampling and mass spectrometry. Results shows that the radioactive uranium is more easily to adhere to the particles with smaller size. The leaching abilities of radioactive uranium in the bottom ash and the fly ash were analyzed. The leaching rate of the uranium from the fly ash and bottom ash were 1% and 6%, respectively, indicating that most of the radioactive uranium was fixed in the ash and the same storage/disposal methods can be used for both the fly ash and bottom ash. According to x-ray spectrometry and SEM-EDS, mineral compositions of the original uranium ore and the bottom ash were mostly the same. Calcium plays an important role in uranium fixation during incineration. The potential mechanism of the uranium special transformation during uranium-containing strippable coating waste combustion was revealed. Our research results can provide technical support for nuclear emergency waste treatment and disposal.


Assuntos
Metais Pesados , Resíduos Radioativos , Eliminação de Resíduos , Urânio , Cinza de Carvão/análise , Incineração , Metais Pesados/análise , Resíduos Sólidos/análise
5.
Phys Chem Chem Phys ; 23(46): 26219-26226, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34787124

RESUMO

Integrating high-loading dielectric nanoparticles into polar polymer matrices potentially can profit the intrinsic polarization of each phase and allow for greatly enhanced dielectric properties in polymer nanocomposites. It is however challenging to achieve desirable highly filled polar polymer composites because of the lack of efficient approaches to disperse nanoparticles and maintain interfacial compatibility. Here, we report a versatile route to fabricate highly filled barium titanate/fluorinated silicone rubber (BT/FSR) nanocomposites by "thiol-ene click" and isostatic pressing techniques. The loaded BT nanoparticles (from 82 wt% to 90 wt%) are chemically bonded with FSR in the nanocomposites. The existence of the polar group (-CH2CF3) of the polymer matrix does not affect the uniform dispersion of the nanoparticles or the good interfacial compatibility. The 90 wt% BT/FSR nanocomposite shows the highest dielectric constant of 57.8 at 103 Hz, while the loss tangent can be kept below 0.03. Besides, BT/FSR nanocomposites display higher breakdown strength than BT/SR nanocomposites. This work offers a facile strategy towards superior dielectric properties of polymer nanocomposites.

6.
Angew Chem Int Ed Engl ; 60(34): 18815-18820, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34129262

RESUMO

Self-assembly of host molecules in aqueous media via metal-ligand coordination is well developed. However, the preparation of purely covalent counterparts in water has remained a formidable task. An anionic tetrahedron cage was successfully self-assembled in a [4+4] manner by condensing a trisamine and a trisformyl in water. Even although each individual imine bond is rather labile and apt to hydrolyze in water, the tetrahedron is remarkably stable or inert due to multivalence. The tetrahedral cages, as well as its neutral counterparts dissolved in organic solvent, have homochirality, namely that their four propeller-shaped trisformyl residues adopt the same rotational conformation. The cage is able to take advantage of hydrophobic effect to accommodate a variety of guest molecules in water. When a chiral guest was recognized, the formation of one enantiomer of the cage became more favored relative to the other. As a consequence, the cage could be produced in an enantioselective manner. The tetrahedron is able to maintain its chirality after removal of the chiral guest-probably on account of the cooperative occurrence of intramolecular forces that restrict the intramolecular flipping of phenyl units in the cage framework.

7.
Ecotoxicol Environ Saf ; 195: 110408, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32179236

RESUMO

Microcystin-LR (MC-LR) is a widely known hepatotoxin which could induce the occurrence and metastasis of hepatocellular carcinoma. In recent years, with the frequent outbreak of cyanobacteria, the harm of MC-LR has gradually attracted more attention. Hence, this study focused on the effect of MC-LR on DNA damage in HepG2 cells, identifying the types and sources of free radicals that make an important function on this issue. Our data suggested that MC-LR induced concentration- and time-dependent increasement of DNA double-strand breaks (DSBs). After exposure to 1 µM MC-LR for 3 days, the protein expression and immunofluorescence staining of γ-H2AX was significantly increased. Using a scavenger of mitochondrial O2.- (4-hydroxy-tempo), a inhibitor of mitochondrial NOS (7-nitroindazole), and a scavenger of ONOO- (uric acid), it was revealed that ONOO- originated from mitochondria made a significant contribution to the genotoxicity of MC-LR. Moreover, a significant decreasement of mitochondrial membrane potential (MMP) was observed. These findings suggested that peroxynitrite targeting mitochondria plays a vital role in the MC-LR-induced genotoxic response in mammalian cells.


Assuntos
Quebras de DNA de Cadeia Dupla , Microcistinas/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Ácido Peroxinitroso/metabolismo , Animais , Carcinoma Hepatocelular/genética , Cianobactérias/crescimento & desenvolvimento , Células Hep G2 , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/genética , Toxinas Marinhas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo
8.
BMC Palliat Care ; 18(1): 47, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167668

RESUMO

BACKGROUND: Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. METHODS: A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. RESULTS: The median survival time was 48.0 (95% CI: 38.1-57.9) days for the training cohort and 52.0 (95% CI: 34.6-69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73-0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. CONCLUSIONS: A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually.


Assuntos
Neoplasias/mortalidade , Nomogramas , Cuidados Paliativos/normas , Idoso , Distribuição de Qui-Quadrado , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Cuidados Paliativos/métodos , Cuidados Paliativos/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo
9.
Cell Physiol Biochem ; 50(5): 2004-2016, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30404076

RESUMO

BACKGROUND/AIMS: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis. METHODS: RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo. RESULTS: In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS). CONCLUSION: Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Moléculas de Adesão Celular/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Nucleares/metabolismo , Fator de Transcrição STAT3/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Fenantrenos/farmacologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Proteína 1 Relacionada a Twist/antagonistas & inibidores , Proteína 1 Relacionada a Twist/genética
10.
Cardiovasc Diabetol ; 15(1): 140, 2016 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-27716206

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a recognized trigger factor for heart failure with preserved ejection fraction (HFpEF). Recent studies show that higher serum calcium level is associated with greater risk of both T2DM and heart failure. We speculate that increased serum calcium is related to HFpEF prevalence in patients with T2DM. METHODS: In this cross-sectional echocardiographic study, 807 normocalcemia and normophosphatemia patients with T2DM participated, of whom 106 had HFpEF. Multinomial logistic regression was carried out to determine the variables associated with HFpEF. The associations between serum calcium and metabolic parameters, as well as the rate of HFpEF were examined using bivariate linear correlation and binary logistic regression, respectively. The predictive performance of serum calcium for HFpEF was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Patients with HFpEF have significantly higher serum calcium than those without HFpEF. Serum calcium was positively associated with total cholesterol, triglycerides, low-density lipoprotein cholesterol, serum uric acid, HOMA-IR and fasting plasma glucose. Compared with patients in the lowest serum calcium quartile, the odds ratio (OR) for HFpEF in patients in the highest quartile was 2.331 (95 % CI 1.088-4.994, p = 0.029). When calcium was analyzed as a continuous variable, per 1 mg/dL increase, the OR (95 % CI) for HFpEF was [2.712 (1.471-5.002), p = 0.001]. Serum calcium can predict HFpEF [AUC = 0.673, 95 % CI (0.620-0.726), p < 0.001]. CONCLUSIONS: An increase in serum calcium level is associated with an increased risk of HFpEF in patients with T2DM.


Assuntos
Cálcio/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Glicemia/análise , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Ecocardiografia Doppler , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Resistência à Insulina , Modelos Lineares , Lipídeos/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Valor Preditivo dos Testes , Prevalência , Curva ROC , Fatores de Risco , Regulação para Cima , Ácido Úrico/sangue
11.
Cardiovasc Diabetol ; 14: 43, 2015 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-25924883

RESUMO

BACKGROUND: Left ventricular hypertrophy (LVH) is prevalent in patients with type 2 diabetes mellitus (T2DM). Recent studies show that an increase in albumin-adjusted serum calcium level is associated with an elevated risk of T2DM. We speculate that increased serum calcium levels in T2DM patients are related to LVH prevalence. METHODS: In this echocardiographic study, 833 normocalcemia and normophosphatemia patients with T2DM were enrolled. The associations between serum calcium and metabolic parameters, left ventricular mass index (LVMI), as well as the rate of LVH were examined using bivariate linear correlation, multivariate linear regression and logistic regression, respectively. The predictive performance of serum calcium for LVH was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Patients with LVH have significantly higher serum calcium than those without LVH. Serum calcium was positively associated with total cholesterol, triglycerides, low-density lipoprotein cholesterol, serum uric acid, HOMA-IR and fasting plasma glucose. Multivariate linear regression analysis demonstrated that serum calcium was independently associated with LVMI (p < 0.001). In comparison with patients in the lowest serum calcium quartile, the odds ratio (OR) for LVH in patients in the highest quartile was 2.909 (95% CI 1.792-4.720; p < 0.001). When serum calcium was analyzed as a continuous variable, per 1 mg/dl increase, the OR (95% CI) for LVH was [2.400 (1.552-3.713); p < 0.001]. Serum calcium can predict LVH (AUC = 0.617; 95% CI (0.577-0.656); p < 0.001). CONCLUSIONS: Albumin-adjusted serum calcium is associated with an increased risk of LVH in patients with T2DM.


Assuntos
Cálcio/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Pessoa de Meia-Idade
12.
Lipids Health Dis ; 13: 37, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24555711

RESUMO

BACKGROUND: Serum lipids and the ratios are known to be associated with the cardiovascular diseases (CVD). However, the associations of serum lipids and the ratios related to arterial stiffness are unclear. We sought to compare the strength of these serum lipids and the ratios with arterial stiffness assessing by brachial-ankle pulse wave velocity (baPWV) in the middle-aged and elderly Chinese subjects. METHODS: A total number of 1133 Chinese aged from 50 to 90 years old were recruited from Shanghai downtown district. The serum lipids, baPWV and major cardiovascular risk factors of the participants were measured. RESULTS: Participants with high baPWV exhibited higher levels of non-HDL-c, TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, and non-HDL-c/HDL-c, while HDL-c worked in the opposite direction (all P<0.05). In addition, TC, TG, LDL-c, non-HDL-c, TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, and non-HDL-c/HDL-c had a positive relationship with the baPWV value, while HDL-c was on the contrary (all P <0.05). Finally, individuals with high non-HDL-c/HDL-c (OR 1.71, 95% CI 1.06-2.55, P = 0.013) and low HDL-c (OR 0.57, 95% CI 0.35-0.96, P = 0.024) were seem to be at high risk of arterial stiffness. CONCLUSIONS: As a risk indicator, non-HDL-c/HDL-c, which could be readily obtained from routine serum lipids, was significantly associated with baPWV. Non-HDL-c/HDL-c was superior to traditional lipid variables for estimating arterial stiffness in the middle-aged and elderly Chinese population.


Assuntos
Artérias/patologia , Lipídeos/sangue , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , China , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Nat Commun ; 15(1): 5041, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871694

RESUMO

Microspherical structures find broad application in chemistry and materials science, including in separations and purifications, energy storage and conversion, organic and biocatalysis, and as artificial and bioactive scaffolds. Despite this utility, the systematic diversification of their morphology and function remains hindered by the limited range of their molecular building blocks. Drawing upon the design principles of reticular synthesis, where diverse organic molecules generate varied porous frameworks, we show herein how analogous microspherical structures can be generated under mild conditions. The assembly of simple organic molecules into microspherical structures with advanced morphologies represents a grand challenge. Beginning with a partially condensed Schiff base which self-assembles into a hierarchical organic microsphere, we systematically synthesized sixteen microspheres from diverse molecular building blocks. We subsequently explicate the mechanism of hierarchical assembly through which these hierarchical organic microspheres are produced, isolating the initial monomer, intermediate substructures, and eventual microspheres. Furthermore, the open cavities present on the surfaces of these constructs provided distinctive adsorptive properties, which we harnessed for the immobilization of enzymes and bacteriophages. Holistically, these hierarchical organic microspheres provide an approach for designing multi-functional superstructures with advanced morphologies derived from simple organic molecules, revealing an extended length scale for reticular synthesis.

14.
Cancer Pathog Ther ; 2(3): 164-172, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027145

RESUMO

Immune checkpoint inhibitors (ICIs), a novel anti-tumor therapeutic modality, are monoclonal antibodies targeting certain immune checkpoints (ICs) that reactivate T cells to achieve anti-tumor immunity by targeting, binding, and blocking ICs. Targeted inhibitory antibodies against the ICs cytotoxic T-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with cancer. ICs may prevent autoimmune reactions. However, ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular, pulmonary, gastrointestinal, renal, musculoskeletal, dermal, and endocrine systems. Approximately 10% of patients with damage to target organs such as the thyroid, pituitary, pancreas, and adrenal glands develop endocrine system immune-related adverse events (irAEs) such as thyroid dysfunction, pituitary gland inflammation, diabetes mellitus, and primary adrenal insufficiency. However, the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions, and failure to recognize them early may lead to death. Timely detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy, prognosis, and the quality of life of patients. This study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management protocols. Here, we discuss (1) the biological mechanisms of ICs in tumorigenesis and progression, focusing on cytotoxic T-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1; and (2) the epidemiology, clinical symptoms, diagnosis, and treatment of four immunotherapy-related endocrine complications.

15.
Cancer Med ; 13(3): e7030, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38400663

RESUMO

BACKGROUND: The usefulness of postoperative adjuvant chemotherapy (ACT) for patients with stage I lung adenocarcinoma with micropapillary (MIP) components remains unclear. We analyzed whether postoperative ACT could reduce recurrence in patients with stage I lung adenocarcinoma with MIP components, thereby improving their overall survival (OS) and disease-free survival (DFS). METHODS: Data for patients with pathologically confirmed stage I lung adenocarcinoma with MIP components from January 2012 to December 2018 were retrospectively analyzed. OS and DFS were analyzed in groups and subgroups. RESULTS: Overall, 259 patients were enrolled. Patients who received ACT in stage IA showed significantly better survival than did those with no-adjuvant chemotherapy (NACT); (5-year OS 89.4% vs. 73.6%, p < 0.001; 5-year DFS 87.2% vs. 66.0%, p = 0.008). A difference was also observed for in-stage IB patients (5-year OS 82.0% vs. 51.8%, p = 0.001; 5-year DFS 76.0% vs. 41.11 %, p = 0.004). In subgroup analysis based on the proportion of MIP components, patients with 1%-5% MIP components had a significantly better prognosis in the ACT group than in the NACT group (5-year OS 82.4% vs. 66.0%, p = 0.005; 5-year DFS 76.5% vs. 49.1%, p = 0.032). A similar difference was observed for patients with MIP ≥5% (5-year OS 80.7% vs. 47.8%, p = 0.009; 5-year DFS 73.11% vs. 43.5%, p = 0.007). CONCLUSION: Among patients with stage I lung adenocarcinoma with MIP components, those who received ACT showed significant survival benefits compared to those without ACT. Patients with lung adenocarcinoma with MIP components could benefit from ACT when the MIP was ≥1%.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Quimioterapia Adjuvante
16.
J Environ Radioact ; 270: 107289, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37683596

RESUMO

In this study, grafted polymers (PAM-g-PAA/PHEA) with different grafting rates are prepared by solution method grafting polymer with polyacrylamide as the main chain, acrylic acid (AA) and 2-hydroxyethyl acrylate (HEA) as the modified monomers. Evidence of graft polymerization of AA and HEA on polyacrylamide side chains is obtained by FT-IR and 1HNMR. Scanning electron microscopy and thermogravimetric characterization further confirm the synthesis of grafted polymers. The properties of the grafting polymer are evaluated using grafting rate, viscosity, and surface tension measurements. The performance of polymer aqueous solution as an aerosol fixative for capturing and removing tellurium aerosol as a simulated polonium aerosol is examined. According to the results, grafting two monomers, acrylic acid, and 2-hydroxyethyl acrylate, effectively improve the cross-sectional structure of the polymer, increase the thermal stability of the polymer, and reduced the surface tension of the aqueous polymer solution to 42.47 mN/m. In addition, aerosol settling and fixation experiments showed that PAM-g-PAA/PHEA had a trapping and scavenging effect on tellurium aerosols with an immobilization rate of 94.86%, which revealed the immobilization mechanism of the immobilizer with tellurium aerosols.


Assuntos
Monitoramento de Radiação , Telúrio , Espectroscopia de Infravermelho com Transformada de Fourier , Estudos Transversais , Polímeros/química , Aerossóis
17.
Biochem Biophys Res Commun ; 423(4): 775-80, 2012 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-22713451

RESUMO

Cholesterol 7α-hydroxylase (CYP7A1) is the initial and rate-limiting enzyme for bile acid synthesis. Transcription of the CYP7A1 gene is regulated by bile acids, nuclear receptors and cytokines. Fibroblast growth factor 7 (FGF7) secreted from activated hepatic stellate cells (HSC) during chronic liver fibrosis regulates hepatocyte survival and liver regeneration. In the carbon tetrachloride (CCl(4))-induced fibrotic mouse liver, we demonstrated that the expression of CYP7A1 was largely decreased while the expression of FGF7 was significantly increased. We further demonstrated that FGF7 inhibited CYP7A1 gene expression in hepatocytes. Knockdown study by short interfering RNA, kinase inhibition and phosphorylation assays revealed that the suppression of CYP7A1 expression by FGF7 was mediated by FGFR2 and its downstream JNK signaling cascade. The FGF7 neutralizing antibody restored CYP7A1 expression in Hep3B cells treated with conditioned medium from HSC. In summary, the data suggest that FGF7 is a novel regulator of CYP7A1 expression in hepatocytes and may prevent hepatocytes from accumulating toxic bile acids during liver injury and fibrosis.


Assuntos
Ácidos e Sais Biliares/biossíntese , Colesterol 7-alfa-Hidroxilase/genética , Fator 7 de Crescimento de Fibroblastos/fisiologia , Regulação Enzimológica da Expressão Gênica , Hepatócitos/enzimologia , Cirrose Hepática/enzimologia , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular Tumoral , Colesterol 7-alfa-Hidroxilase/antagonistas & inibidores , Modelos Animais de Doenças , Fator 7 de Crescimento de Fibroblastos/farmacologia , Hepatócitos/efeitos dos fármacos , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Interferente Pequeno/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo
18.
Cancer Res ; 82(11): 2185-2195, 2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35385574

RESUMO

Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor protein of the cullin 3 (CUL3) ubiquitin E3 ligase complex, protecting PD-L1 from CUL3-mediated proteasomal degradation. Inhibition of CK2 decreased PD-L1 protein levels by promoting its degradation and resulted in the release of CD80 from DC to reactivate T-cell function. In a syngeneic mouse model, combined treatment with a CK2 inhibitor and an antibody against T-cell immunoglobulin mucin-3 (Tim-3) suppressed tumor growth and prolonged survival. These findings uncover a mechanism by which PD-L1 is regulated and suggest a potential antitumor treatment option to activate DC function by blocking the CK2-PD-L1 pathway and inhibiting Tim-3. SIGNIFICANCE: This work identifies a role for CK2 in immunosuppression by phosphorylation and stabilization of PD-L1, identifying CK2 inhibition as an immunotherapeutic approach for treating cancer.


Assuntos
Antígeno B7-H1 , Caseína Quinase II , Neoplasias , Animais , Caseína Quinase II/metabolismo , Células Dendríticas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Camundongos , Fosforilação , Receptor de Morte Celular Programada 1/metabolismo
19.
Food Chem ; 356: 129632, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33831833

RESUMO

Direct electrochemical detection in real food samples remains challenging due to the fouling and interference by abundant interference components. Herein, we report an electrochemical sensing platform based on binary assembly of silica nanochannels and polydimethylsiloxane that is able to detect Pb2+ and Cd2+ in real food samples without complex pretreatments. Using differential pulse anodic stripping voltammetry, the electrochemical detection consists of electro-deposition of metal species and subsequent anodic stripping in the modified silica-nanochannels. Under the optimized conditions, the linear ranges were obtained from 4 to 1500 µg L-1 for Pb2+ and 30 to 900 µg L-1 for Cd2+. The relative standard deviations were 2.9% and 3.6% for Pb2+ and Cd2+ of 300 µg L-1. Without tedious pretreatments, the quantitative detection of Pb2+ and Cd2+ in real juice and beverage samples was successfully performed, revealing that the developed sensor possesses excellent anti-interference and practicability properties for unprocessed food.


Assuntos
Bebidas/análise , Cádmio/análise , Chumbo/análise , Cádmio/química , Cátions Bivalentes/química , Dimetilpolisiloxanos/química , Eletrodos , Fermentação , Chumbo/química , Malus/química , Nanoestruturas/química , Dióxido de Silício/química , Vitis/química
20.
ACS Sens ; 6(4): 1604-1612, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752324

RESUMO

In the present study, a novel electrochemical sensor for the direct detection of caffeine in the crude sample has been prepared by plasma-triggered polydimethylsiloxane (PDMS) deposition on the indium tin oxide electrodes supported with silica nanochannels. The deposited PDMS contains both the original hydrophobic and oxidized hydrophilic PDMS oligomers. Nanochannels modified with these two kinds of PDMS with opposite wettability only allow the passage of small amphiphilic molecules such as caffeine, while other molecules including hydrophilic, hydrophobic, and large ones were all rejected. With the excellent shielding properties, the modified nanochannel electrode exhibits excellent anti-interference and antifouling capability, which could be directly used for the detection of caffeine in real crude food such as tea, milk, coffee, and coke without sample pretreatments. Moreover, the modified electrode has good repeatability and stability. In contrast, severe interference was observed when conventional electrodes were used directly in these unprocessed samples. The linear ranges of caffeine were determined to be between 50 nmol/L and 700 µmol/L, with a limit of detection of 20 nmol/L. The developed sensor provides a very simple, rapid, and cost-effective way for the interference-free and fouling-free analysis of specific amphiphilic compounds and can be extended to a wide range of applications.


Assuntos
Cafeína , Técnicas Eletroquímicas , Dimetilpolisiloxanos , Eletrodos , Dióxido de Silício
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