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1.
Small ; : e2402925, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874069

RESUMO

Aqueous Zn metal batteries are attracting tremendous interest as promising energy storage systems due to their intrinsic safety and cost-effectiveness. Nevertheless, the reversibility of Zn metal anodes (ZMAs) is hindered by water-induced parasitic reactions and dendrite growth. Herein, a novel hydrated eutectic electrolyte (HEE) consisting of Zn(BF4)2·xH2O and sulfolane (SL) is developed to prevent the side reactions and achieve the outstanding cyclability of ZMAs. The strong coordination between Zn2+ and SL triggers the eutectic feature, enabling the low-temperature availability of HEEs. The restriction of BF4 - hydrolysis in the eutectic system can realize favorable compatibility between Zn(BF4)2-based electrolyte and ZMAs. Besides, the newly-established solvation structure with the participation of SL, H2O, and BF4 -, can induce in situ formation of desirable SEI with gradient structure consisting of B,O-rich species, ZnS, and ZnF2, to offer satisfactory protection toward ZMAs. Consequently, the HEE allows the Zn||Zn symmetric cell to cycle over 1650 h at 2 mA cm-2 and 1 mA h cm-2. Moreover, the Zn||NH4V4O10 full batteries can deliver a prolonged lifespan for 1000 cycles with a high capacity retention of 83.4%. This work represents a feasible approach toward the elaborate design of advanced electrolyte systems for next-generation batteries.

2.
Bioorg Med Chem Lett ; 104: 129727, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38582132

RESUMO

ß-galactosidase (ß-gal) has high activity in various malignancies, which is suitable for targeted positron emission tomography (PET) imaging. Meanwhile, ß-gal can successfully guide the formation of nanofibers, which enhances the intensity of imaging and extends the imaging time. Herein, we designed a ß-galactosidase-guided self-assembled PET imaging probe [68Ga]Nap-NOTA-1Gal. We envisage that ß-gal could recognize and cleave the target site, bringing about self-assembling to form nanofibers, thereby enhancing the PET imaging effect. The targeting specificity of [68Ga]Nap-NOTA-1Gal for detecting ß-gal activity was examined using the control probe [68Ga]Nap-NOTA-1. Micro-PET imaging showed that tumor regions of [68Ga]Nap-NOTA-1Gal were visible after injection. And the tumor uptake of [68Ga]Nap-NOTA-1Gal was higher than [68Ga]Nap-NOTA-1 at all-time points. Our results demonstrated that the [68Ga]Nap-NOTA-1Gal can be used for the purpose of a new promising PET probe for helping diagnose cancer with high levels of ß-gal activity.


Assuntos
Sondas Moleculares , Nanofibras , Neoplasias , beta-Galactosidase , Humanos , beta-Galactosidase/análise , Linhagem Celular Tumoral , Radioisótopos de Gálio , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos
3.
Biochem Genet ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594571

RESUMO

Thyroid cancer (THCA) is the most prevalent endocrine tumor, and its incidence continues to increase every year. However, the processes underlying the aggressive progression of thyroid cancer are unknown. We concentrated on the prognostic and biological importance of thyroid cancer cuproptosis-related genes in this investigation. Genomic and clinical data were obtained from the UCSC XENA website, and cuproptosis-related genes were obtained from the FerrDb website. We performed differential expression analysis and Cox regression analysis to identify possible predictive targets associated with thyroid cancer prognosis. To assess the role of CDKN2A in thyroid cancer and the ability to predict prognosis on the basis of the CDKN2A expression level, we performed immunohistochemical staining, survival analysis, immunological analysis, functional analysis, and clinical analysis with respect to CDKN2A gene expression. CDKN2A expression levels were found to be inversely correlated with thyroid cancer prognosis. Higher levels of CDKN2A expression were associated with higher T, N, and clinicopathological stage and more residual tumor cells. Through univariate and multivariate Cox regression analyses, the CDKN2A expression level was shown to be linked with thyroid cancer patients' overall survival (OS). Moreover, we discovered that CDKN2A expression was linked to a dysfunctional tumor immune microenvironment. The study shows that CDKN2A, a cuproptosis-related gene, can be used as a prognostic marker for thyroid cancer.

4.
Mol Med ; 29(1): 164, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38049750

RESUMO

BACKGROUND: Lung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-ß-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear. METHODS: To assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells. RESULTS: We found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice. CONCLUSIONS: Our study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.


L-BAIBA upregulates the expression of GPX4 and SLC7A11 by activating the AMPK/Nrf-2/GPX4/SLC7A11 signaling pathway, thereby protecting against I/R-induced increase in ROS and ferroptosis in the lung.


Assuntos
Ferroptose , Traumatismo por Reperfusão , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
5.
Bioorg Med Chem Lett ; 96: 129496, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37797805

RESUMO

In recent years, PD-1/PD-L1 checkpoint blockade immunotherapy with remarkable efficacy has set off a heat wave. The expression level of PD-L1, which plays a predictive role in anti-PD-1/PD-L1 therapy, could be quantified by noninvasive imaging with radiotracers. Herein, we introduced the synthesis and preliminary biological evaluation of a novel 99mTc-labeled small molecule radiotracer [99mTc]G3C-CBM for PD-L1 imaging. [99mTc]G3C-CBM was achieved with high radiochemical purity (>96 %) and remained good stability in PBS and FBS. In competitive combination experiment, [99mTc]G3C-CBM was displaced by increasing concentrations of unlabeled G3C-CBM, resulting in an IC50 value of 41.25±2.23 nM for G3C-CBM. The uptake of [99mTc]G3C-CBM in A375-hPD-L1 cells (17.51±2.08 %) was approximately 6.47 folds of that in A375 cells (2.71±0.36 %) after co-incubation for 2 h. The biodistribution results showed that the radioactivity uptake in A375-hPD-L1 tumor reached the maximum (0.35±0.01 %ID/g) at 2 h post injection, and the optimum tumor/muscle ratio of 2.94±0.29 occurred at the same time. In addition, [99mTc]G3C-CBM was quickly cleared from the blood with a clearance half-life of just 119.25 min. These results indicate that [99mTc]G3C-CBM is a potential SPECT PD-L1 imaging agent and is worthy of further study.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Antígeno B7-H1/metabolismo , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Transporte Biológico
6.
Clin Exp Hypertens ; 45(1): 2202367, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37144334

RESUMO

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of hypertension. However, the underlying mechanisms for lowering blood pressure (BP) by suppressing ER stress remain unclear. Here, we hypothesized that inhibition of ER stress could restore the balance between RAS components and lower BP in spontaneously hypertensive rats (SHRs). METHODS: Wistar-Kyoto (WKY) rats and SHRs received vehicle or 4-PBA, an ER stress inhibitor, in the drinking water for 4 weeks. BP was measured by tail-cuff plethysmography, and the expression of RAS components was examined by Western blot. RESULTS: Compared with vehicle-treated WKY rats, vehicle-treated SHRs exhibited higher blood pressure and increased renal ER stress and oxidative stress, accompanied by impaired diuresis and natriuresis. Moreover, SHRs had higher ACE and AT1R and lower AT2R, ACE2, and MasR expressions in the kidney. Interestingly, 4-PBA treatment improved impaired diuresis and natriuresis and lowered blood pressure in SHRs, accompanied by reducing ACE and AT1R protein expression and increasing AT2R, ACE2, and MasR expression in the kidneys of SHRs. In addition, these changes were associated with the reduction of ER stress and oxidative stress. CONCLUSIONS: These results suggest that the imbalance of renal RAS components was associated with increased ER stress in SHRs. Inhibition of ER stress with 4-PBA reversed the imbalance of renal RAS components and restored the impaired diuresis and natriuresis, which, at least in part, explains the blood pressure-lowering effects of 4-PBA in hypertension.


Assuntos
Enzima de Conversão de Angiotensina 2 , Hipertensão , Ratos , Animais , Pressão Sanguínea , Ratos Endogâmicos SHR , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/farmacologia , Ratos Endogâmicos WKY , Rim/metabolismo , Estresse do Retículo Endoplasmático
7.
Int Wound J ; 20(2): 516-528, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36008920

RESUMO

Radiodermatitis is an inevitable side effect of radiotherapy in cancer treatment and there is currently no consensus on effective drugs for treating the condition. Vitamin B12 is known to be effective for repairing and regenerating damaged skin. However, there are few studies on the use of Vitamin B12 for treating radiodermatitis. This study explored the therapeutic efficacy and mechanism of action of Vitamin B12 ointment on radiodermatitis. A porcine model of grade IV radiodermatitis was established. The ointment was applied for 12 weeks after which histological staining, transmission electron microscopy, RT-qPCR, western blotting, and gene sequencing were performed for the evaluation of specific indicators in skin samples. After 12 weeks of observation, the Vitamin B12 treatment was found to have significantly alleviated radiodermatitis. The treatment also significantly reduced the expression levels of NF-κB, COX-2, IL-6, and TGF-ß in the skin samples. The pathways involved in the effects of the treatment were identified by analysing gene expression. In conclusion, Vitamin B12 ointment was found to be highly effective for treating radiodermatitis, with strong anti-radiation, anti-inflammatory, and anti-fibrosis effects. It is thus a promising drug candidate for the treatment of severe radiodermatitis.


Assuntos
Radiodermite , Animais , Suínos , Radiodermite/tratamento farmacológico , Pomadas/uso terapêutico , Vitamina B 12/uso terapêutico , Administração Tópica , Anti-Inflamatórios/uso terapêutico , Vitaminas/uso terapêutico
8.
Anal Chem ; 93(16): 6329-6334, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33848118

RESUMO

Positron-emission tomography (PET) imaging enables cancer diagnosis at an early stage and to determine its pathological degree. However, tumor uptake efficiency of traditional PET radiotracers is usually low. Herein, we rationally designed a precursor CBT-NODA, the cold analogue CBT-NODA-Ga, and its corresponding radiotracer CBT-NODA-68Ga. Using these three compounds, we verified that coinjection of CBT-NODA-68Ga with CBT-NODA or CBT-NODA-Ga could lead to the synthesis of hybrid gallium-68 nanoparticles in furin-overexpressing cancer cells and enhance microPET tumor imaging in mice. In vivo experiments showed that coinjection of CBT-NODA-68Ga with CBT-NODA-Ga had the most prolonged retention of the radiotracer in blood, the highest radioactivity in tumor regions, and the most enhanced microPET tumor imaging in mice. We anticipate that, by combining the coinjection strategy with our CBT-Cys click condensation reaction, more radiotracers are developed for microPET imaging of more tumors in clinical settings in the future.


Assuntos
Radioisótopos de Gálio , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Camundongos , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
9.
Pharmacol Res ; 165: 105457, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33515706

RESUMO

Microglia-mediated neuroinflammatory response and neuron damage are considered as a self-propelling progressive cycle, being strongly implicated in the progression of neurodegeneration in amyotrophic lateral sclerosis (ALS). Diphenyl diselenide (DPDS), a simple organoselenium compound, has been known to possess multiple pharmacological properties. The purpose of this study was to explore the neuroprotective effects of DPDS against microglia-mediated neuroinflammatory injury in ALS models. We found that DPDS pretreatment inhibited LPS-induced activation of IκB/NF-κB pathway and subsequent release of proinflammatory factors from activated primary hSOD1G93A microglia. Moreover, DPDS suppressed NLRP3 inflammasome activation by decreasing protein nitration via reduction in NO and ROS levels, whose low levels are related to NF-κB inhibition responsible for iNOS and NOX2 down-regulations, respectively. Notably, DPDS-mediated ROS attenuation was not linked to Nrf2 activation in this cellular model. Furthermore, in the absence of activated microglia, DPDS has no significant effect on the individual hSOD1G93A-NSC34 cells; however, in in vitro neuron-microglia conditional culture and co-culture experiments, DPDS protected motor neurons from neurotoxic damage caused by LPS or BzATP-stimulated microglia activation. Above observations suggest that DPDS-afforded neuroprotection is linked to inhibition of microglia-mediated neuroinflammation in ALS, which was further verified in vivo as shown by improvements of motor deficits, prolonged survival, and reduction of motor neuron loss and reactive microgliosis in hSOD1G93A transgenic mouse. Altogether, our results show that DPDS elicited neuroprotection in ALS models through inactivation of microglia by inhibiting IκB/NF-κB pathway and NLRP3 inflammasome activation, suggesting that DPDS may be a promising candidate for potential therapy for ALS.


Assuntos
Esclerose Lateral Amiotrófica/prevenção & controle , Derivados de Benzeno/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Microglia/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Compostos Organosselênicos/uso terapêutico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Animais , Derivados de Benzeno/farmacologia , Linhagem Celular , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Microglia/metabolismo , Neurônios Motores/metabolismo , Fármacos Neuroprotetores/farmacologia , Compostos Organosselênicos/farmacologia , Superóxido Dismutase-1/genética
10.
Acta Pharmacol Sin ; 41(11): 1457-1464, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32424239

RESUMO

Mitsugumin 53 (MG53) is a tripartite motif family protein that has been reported to attenuate injury via membrane repair in different organs. Contrast-induced acute kidney injury (CI-AKI) is a common complication caused by the administration of iodinated contrast media (CM). While the cytotoxicity induced by CM leading to tubular cell death may be initiated by cell membrane damage, we wondered whether MG53 alleviates CI-AKI. This study was designed to investigate the effect of MG53 on CI-AKI and the underlying mechanism. A rat model of CI-AKI was established, and CI-AKI induced the translocation of MG53 from serum to injury sites on the renal proximal tubular (RPT) epithelia, as illustrated by immunoblot analysis and immunohistochemical staining. Moreover, pretreatment of rats with recombinant human MG53 protein (rhMG53, 2 mg/mL) alleviated iopromide-induced injury in the kidney, which was determined by measuring serum creatinine, blood urea nitrogen and renal histological changes. In vitro studies demonstrated that exposure of RPT cells to iopromide (20, 40, and 80 mg/mL) caused cell membrane injury and cell death, which were attenuated by rhMG53 (10 and 50 µg/mL). Mechanistically, MG53 translocated to the injury site on RPT cells and bound to phosphatidylserine to protect RPT cells from iopromide-induced injury. In conclusion, MG53 protects against CI-AKI through cell membrane repair and reducing cell apoptosis; therefore, rhMG53 might be a potential effective means to treat or prevent CI-AKI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Proteínas com Motivo Tripartido/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Animais , Membrana Celular/metabolismo , Células Epiteliais , Feminino , Humanos , Iohexol/análogos & derivados , Rim/patologia , Túbulos Renais Proximais/citologia , Masculino , Fosfatidilserinas/metabolismo , Substâncias Protetoras/metabolismo , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Proteínas com Motivo Tripartido/metabolismo
11.
Anal Chem ; 91(23): 14842-14845, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31718142

RESUMO

Positron-emission tomography (PET) is routinely used in the clinic for tumor imaging with ultrahigh sensitivity, but tumor-targeted PET imaging probes are quite few. In this work, we rationally designed a furin-responsive radiotracer Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Lys(DOTA-68Ga)-CBT (CBT-68Ga) and demonstrated that coinjection of the radiotracer with its cold analogue CBT-Ga instructed the formation of 68Ga nanoparticles in furin-overexpressing MDA-MB-468 cancer cells, which significantly enhanced microPET imaging of the tumor in vivo. In vitro results showed that CBT-Ga subjected to furin-initiated CBT-Cys condensation reaction and self-assembly to form the nanoparticles CBT-Ga-NPs with an average diameter of 258.3 nm. In vivo microPET imaging results indicate that the mice coinjected with CBT-68Ga and CBT-Ga, which warrants 68Ga nanoparticle formation in their MDA-MB-468 tumors, had a tumor/liver ratio 9.1-fold of that of the mice only injected with CBT-68Ga. We envisioned that, by replacing the RVRR substrate of CBT-68Ga with other enzyme-specific ones and using the strategy of intracellular nanoparticle formation, a series of radioactive probes could be developed for more sensitive and precise tumor microPET imaging in the near future.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico por imagem , Furina/genética , Radioisótopos de Gálio/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Furina/metabolismo , Radioisótopos de Gálio/química , Expressão Gênica , Xenoenxertos , Humanos , Fígado/metabolismo , Camundongos , Camundongos Nus , Nanopartículas/metabolismo , Compostos Radiofarmacêuticos/síntese química
12.
Mikrochim Acta ; 186(11): 715, 2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31654142

RESUMO

A highly sensitive fluorometric method is described for the determination of microRNA-141. It is based on the use of arched probe-mediated isothermal exponential amplification reaction (EXPAR) and of DNA-templated silver nanoclusters (DNA-AgNCs). The EXPAR utilizes microRNA-141 as the trigger, polymerases and endonucleases as amplification activators, and two arched probes as exponential amplification templates. This enables the conversion of microRNA to a large number of reporter sequences under isothermal conditions within minutes. The generated reporter sequences act as scaffolds for the synthesis of fluorescent DNA-AgNCs by reduction of Ag (I) with NaBH4. The DNA-AgNCs function as signalling fluorophores with excitation/emission maxima at 540/610 nm. The method exhibits high sensitivity for microRNA-141 with a detection limit as low as 0.87 fM and a dynamic range from 1 fM to 500 fM. The method can distinguish nucleotides in the microRNA-200 family. Graphical abstract Schematic representation of a fluorometric method for sensitive detection of microRNA based on arched probe-mediated isothermal exponential amplification combined with DNA-templated silver nanoclusters.


Assuntos
DNA/química , Corantes Fluorescentes/química , Fluorometria/métodos , Nanopartículas Metálicas/química , MicroRNAs/sangue , Sondas de DNA/química , Humanos , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Prata/química
13.
Mikrochim Acta ; 186(10): 669, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489499

RESUMO

A highly sensitive fluorometric method is described for the determination of let-7a microRNA. It is based on the use of target-triggered cascade signal amplification that involves the use of (a) catalytic hairpin assembly (CHA), (b) exonuclease-assisted signal amplification (EASA), and (c) DNA-templated fluorescent silver nanoclusters (DNA-AgNCs) having excitation/emission maxima at 535/616 nm. The CHA reaction is initiated by the hybridization of the microRNA with hairpin probe HP1. The opening of HP1 results in the assembly of HP1 and another hairpin probe (HP2) to form a duplex. This releases the microRNA that which initiates another CHA reaction. The HP1-HP2 duplex binds to hairpin probe HP3 to form a stable Y-shaped junction structure HP2-HP1-HP3. The Y-shaped junction structure is cleaved by λ exonuclease to recycle the HP1-HP2 duplex to initiate the EASA reaction. This generates a large number of single-stranded reporter sequences. These act as scaffolds for the synthesis of fluorescent AgNCs by reduction of Ag (I) ions. A remarkably amplified fluorescent signal is observed whose intensity increases linearly in the 1 fM to 10 nM let-7a microRNA concentration range. The detection limit is 0.89 fM. The method can well discriminate let-7a microRNA from other microRNAs of the same family. Graphical Abstract Schematic representation of a fluorometric method based on target-triggered cascade signal amplification and DNA-templated silver nanoclusters (DNA-AgNCs) for sensitive detection of microRNA (miRNA).


Assuntos
DNA/química , Nanopartículas Metálicas/química , MicroRNAs/sangue , Sondas Moleculares/química , Técnicas de Amplificação de Ácido Nucleico , Prata/química , Técnicas Biossensoriais , Humanos , MicroRNAs/análise , Espectrometria de Fluorescência
14.
Arch Environ Contam Toxicol ; 77(1): 115-126, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31134307

RESUMO

In this study, the occurrence and distribution patterns of eight organophosphate esters (OPEs) were investigated in urban and rural surface water in a typical cosmopolitan city: Shanghai, China. In addition, concentration levels and removal efficiencies of seven sewage treatment plants were analyzed. The OPEs concentrations detected in urban rivers were significantly higher than those detected in rural rivers. Total OPEs ranged from 185.4 to 321 ng L-1 in rural surface water and from 340 to 1688.7 ng L-1 in urban, with an average of 221.8 ng L-1 and 850.2 ng L-1, respectively. Compared with other studies published in the world, the OPEs contamination in surface river water in Shanghai was at a moderate level. Furthermore, the potential sources of OPEs in urban surface water were investigated, and the results indicated that OPEs in urban surface water mainly came from three potential sources. In rural surface water, the OPE concentrations were uniformly distributed, so OPEs in rural surface water may came from nonpoint source pollution. Last, a preliminary environmental risk assessment and health risk assessment were conducted. The results showed low environmental risks at all sampling sites (except for sampling point R7: medium risk for algae) for the three aquatic organisms (algae, daphnia, and fish). Health risk assessment indicated a noncarcinogenic risk for diverse human groups for Æ©OPEs.


Assuntos
Organofosfatos/análise , Rios/química , Poluentes Químicos da Água/análise , Organismos Aquáticos/efeitos dos fármacos , China , Monitoramento Ambiental/métodos , Ésteres/análise , Água Doce/análise , Organofosfatos/toxicidade , Medição de Risco , Poluentes Químicos da Água/toxicidade
15.
Anal Chem ; 90(15): 8732-8735, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30027744

RESUMO

Legumain is one of the cysteine proteases which can serve as an essential indicator for cancer diagnosis. Near-infrared (NIR) nanoprobes with fluorescence "Turn On" property are advantageous in cancer diagnosis. However, to the best of our knowledge, using a completely organic NIR nanoprobe to image legumain activity either in vitro or in vivo has not been reported. Herein, employing a CBT-Cys click condensation reaction, we used a rationally designed NIR probe Cys(StBu)-Ala-Ala-Asn-Lys(Cy5.5)-CBT (1) to synthesize its nanoprobes 1-NPs with self-quenched fluorescence. Cell and animal experiments indicated that our nanoprobes were able to specifically image legumain activity in living cells and tumors with a NIR fluorescence "Turn On" manner. We envision that the nanoprobes could be applied for the diagnosis of legumain-related diseases in the near future.


Assuntos
Carbocianinas/química , Neoplasias do Colo/diagnóstico por imagem , Cisteína Endopeptidases/análise , Corantes Fluorescentes/química , Oligopeptídeos/química , Imagem Óptica/métodos , Animais , Carbocianinas/síntese química , Química Click , Neoplasias do Colo/enzimologia , Corantes Fluorescentes/síntese química , Células HCT116 , Humanos , Raios Infravermelhos , Camundongos , Microscopia de Fluorescência/métodos , Oligopeptídeos/síntese química
16.
J Thromb Thrombolysis ; 45(1): 142-150, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29019045

RESUMO

The characteristics of coronary stenosis vary among the different countries or areas. 11,267 patients who have undergone coronary angiography (CAG) from three Southwest China hospitals were investigated. Patient characteristics, coronary stenosis and stent-implant information were recorded and analyzed according to two criteria: "visible stenosis" and "≥ 50% stenosis". The patients who have undergone CAG increased year by year, with patients from 60 to 69 years-old taking the highest ratio (34.69%). Based on the "≥ 50% stenosis" criteria, the stenotic frequency was 40.54% for Southwest China patients getting CAG. Only 8.14% patients suffered ≥ 3 stenotic vessels, while 11.58 and 20.82% patients had 2 or 1 stenotic vessel, respectively. However, when using the "visible stenosis" criteria, the stenotic frequency increased to 64.68%. The prevalence of stenosis increased with age based on the "visible stenosis" criteria. There were more male patients with stenosis than female except patients over 80 years old. The stenosis affected almost all main coronary arteries and their branches, with the most affected artery being the left anterior descending artery. There were 3246 cases (28.8%) implanted with 5423 stents with a concurrent age-dependent increasing tendency for stent-implant frequency and average implanted stent number. The numbers of patients who have undergone CAG and suffered from CVD increased rapidly. In these patients, positive rate of CAG was 64.67%, which increased to 72.2% in patients over 60-years old. The incidence of ≥ 75% stenosis and multiple stenosis increased with age, however it should be noticed there were 18.93% for ≥ 75% stenosis and 19.52% for multiple stenosis in patients under 40 years old.


Assuntos
Estenose Coronária/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/patologia , Estenose Coronária/cirurgia , Vasos Coronários/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents
17.
Anal Chem ; 89(18): 9625-9628, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28874046

RESUMO

The design of tumor-targeting, intracellular protease-activatable near-infrared fluorescence (NIRF) nanoprobes is broadly interesting but remains challenging. In this work, we report the rational design of a NIR probe Cys(StBu)-Lys(Biotin)-Lys-Lys(Cy5.5)-CBT (1) to facilely prepare the self-quenched nanoparticles 1-NPs for tumor-targeted imaging in vitro and in vivo. The biotinylated 1-NPs could be actively uptaken by biotin receptor-overexpressing tumor cells via receptor-mediated endocytosis. Upon intracellular proteolytic cleavage, 1-NPs were disassembled to yield the small molecular probe Lys(Cy5.5)-Luciferin-Lys(Biotin)-Lys-OH (1-D-cleaved), accompanied by fluorescence "Turn-On". With this NIRF "Turn-On" property, 1-NPs were successfully applied for tumor-targeted imaging. We envision that our nanoparticles could be applied for fluorescence-guided tumor surgery in the near future.


Assuntos
Fluorescência , Corantes Fluorescentes/química , Nanopartículas/química , Imagem Óptica , Neoplasias do Colo do Útero/diagnóstico por imagem , Animais , Feminino , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Raios Infravermelhos , Camundongos , Camundongos Nus , Neoplasias Experimentais/diagnóstico por imagem , Proteólise , Espectrometria de Fluorescência
18.
Int J Gynecol Cancer ; 27(4): 768-775, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28267131

RESUMO

OBJECTIVE: We present a new technique of 3-dimensional computed tomography-guided interstitial (IS) brachytherapy (BT) for locally advanced cervical cancer, offering a more advantageous clinical treatment approach. MATERIALS/METHODS: Interstitial BT was performed using an applicator combining uterine tandem and metal needles; needles were inserted freehand under real-time 3-dimensional computed tomography guidance. Twenty-eight patients with bulky tumors and/or parametrial extension (tumor size > 5 cm) after external beam radiotherapy received IS BT. Dosimetric outcomes of the IS BT including the total dose (external beam radiotherapy and high dose-rate BT) D90 for the high-risk clinical target volume (HR-CTV) and D2cc for the organs at risk (OARs) were investigated and compared with a former patient group consisting of 30 individuals who received the conventional intracavitary (IC) BT. RESULTS: The mean D90 values for HR-CTV in the IC BT and IS BT groups were 76.9 ± 5.7 and 88.1 ± 3.3 Gy, respectively. Moreover, 85.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IS BT group, and only 6.7% of the patients received D90 for HR-CTV of 87 Gy or greater in the IC BT group. The D2cc for the bladder, rectum, and sigmoid were 84.7 ± 6.8, 69.2 ± 4.2, and 67.8 ± 4.5 Gy in the IC BT group and 81.8 ± 6.5, 66.8 ± 4.0, and 64.8 ± 4.1 Gy in the IS BT group. The mean number of needles was 6.9 ± 1.4, with a mean depth of 2.9 ± 0.9 mm for each IS BT. Interstitial BT was associated with only minor complications. CONCLUSIONS: The IS BT technique resulted in better dose-volume histogram parameters for large volume tumors (>5 cm) compared with the conventional IC BT and acceptable risk of acute complications in locally advanced cervical cancer and is clinically feasible.


Assuntos
Braquiterapia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/instrumentação , Feminino , Humanos , Imageamento Tridimensional/instrumentação , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Planejamento da Radioterapia Assistida por Computador/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodos
19.
Opt Lett ; 41(1): 139-42, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26696178

RESUMO

In this Letter, we investigate the feasibility of focusing relativistic laser pulses toward diffraction limit by near-critical density plasma lenses. A theoretical model is developed to estimate the focal length of the plasma lens. Particle-in-cell simulations with various pulse parameters, such as pulse duration, beam waist, and intensity, are performed to show the robustness of plasma lenses. The results prove that the near-critical density plasma lenses can be deployed to obtain higher laser peak intensities with sub-wavelength focal spots in experiments.

20.
Clin Exp Hypertens ; 38(6): 495-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27398731

RESUMO

BACKGROUND: YaAn, a city in Sichuan province, China, was struck by a major earthquake measuring 7.0 on the Richter scale on April 20, 2013. This study sought to investigate the impact of YaAn earthquake on the blood pressure (BP) among hospitalized patients in the department of cardiology. METHODS: We enrolled 52 hospitalized patients who were admitted to our hospital at least three days before the day of earthquake in 2013 (disaster group) as compared with 52 patients during April 20, 2014 (nondisaster group). BP was measured three times per day and the prescription of antihypertensive medicine was recorded. RESULTS: The earthquake induced a 3.3 mm Hg significant increase in the mean postdisaster systolic blood pressure (SBP) in the disaster group as compared with the nondisaster group. SBP at admission was positively associated with the elevated SBP in the logistic regression model (odds ratio (OR) = 1.09, 95% confidence interval (CI):1.016-1.168, p = 0.015), but not other potential influencing factors, including antihypertensive medicine, sex, age, and body weight, excluding ß-blockers. Patients with ß-blockers prescription at the time of earthquake showed a blunt response to earthquake-induced SBP elevation than those who were taking other antihypertensive drugs (OR = 0.128, 95% CI: 0.019-0.876, p = 0.036). CONCLUSION: The YaAn earthquake induced significant increase in SBP even at a distance from the epicenter among hospitalized patients. The findings demonstrate that pure psychological components seem to be a cause of the pressor response and ß-blockers might be better in controlling disaster-induced hypertension.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Pressão Sanguínea , Terremotos/estatística & dados numéricos , Hipertensão , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Serviço Hospitalar de Cardiologia/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Hipertensão/psicologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances
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