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1.
Aging (Albany NY) ; 13(18): 22375-22389, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34547719

RESUMO

Sevoflurane (Sev) is a commonly used anesthetic in hospitals that can cause neurotoxicity. Postoperative cognitive dysfunction (POCD) is a common clinical problem induced by some anesthetics. However, the exact mechanism of neurotoxicity induced by Sev is unclear. Here we studied a new mechanism of POCD induced by Sev. We treated 15-month-old mice with 2% Sev for 6 hours, and we had found that Sev causes POCD. Using isobaric tags for relative and absolute quantitation (iTRAQ), we found that the transporter and the metabolism of carbohydrates and inorganic ions were involved in the cognitive impairment induced by Sev. Using synchrotron radiation micro-X-ray fluorescence (µ-XRF), we showed that Sev caused the iron overload in the brain of 15-month-old mice. Subsequently, excessive iron led to oxidative stress and impaired mitochondrial function that further led to glucose metabolism disorder and reduced ATP production by regulating the expression of key enzyme genes or proteins including G6Pase, Pck1, and Cs. Meanwhile, Sev also inhibited the oxygen consumption rate and glucose absorption by downregulating the expression of glucose transporter 1 in cerebral vascular endothelial cells. The cross-dysfunction of iron and glucose metabolism caused the apoptosis in the cortex and hippocampus through Bcl2/Bax pathway. In conclusion, the data here showed a new mechanism that Sev caused apoptosis by cross-dysregulation of iron and glucose metabolism and induced energy stress in mice. Maintaining iron and glucose metabolism homeostasis may play an important role in cognitive impairment induced by Sev.

2.
Sci Total Environ ; 799: 149472, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426303

RESUMO

The systematic and scientific assessments on heavy metal pollutions and water quality characteristics are greatly important to protecting the river and coastal eco-environment. In this paper, sediment size, organic matter, total nitrogen, total phosphorus, and heavy metal contents were analyzed by collecting surface sediments and surface water in the reservoir control reach of the middle Han River. Besides, sediment enrichment factor and sediment pollution index were used to evaluate the heavy metal pollution, and enrichment analysis and redundancy analysis were applied to analyze the sources of heavy metals in sediments. The results show a low heavy metal content in the surface water, and the water quality is graded as a Good level. The average enrichment factor of Cd in surface sediments reached 4.63. Zn and Cu also showed significant enrichment in the tributary sediments, whose content far exceeded the background value of soil elements. Thus, the potential ecological risk of heavy metals was at a medium level. Statistical analysis and enrichment factors showed that the accumulation of heavy metals in sediments was affected by pollutant input and reservoir regulation, and it was urgent to conduct an integrated regulation of the heavy metals in river sediment. This study provided an insight into the understanding of feasible assessment for heavy metal contaminated sediment.


Assuntos
Metais Pesados , Poluentes Químicos da Água , China , Monitoramento Ambiental , Sedimentos Geológicos , Metais Pesados/análise , Medição de Risco , Rios , Poluentes Químicos da Água/análise , Qualidade da Água
3.
Oxid Med Cell Longev ; 2021: 9961628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394837

RESUMO

Parkinson's disease (PD) is a progressive nervous system disorder. Until now, the molecular mechanism of its occurrence is not fully understood. Paraquat (PQ) was identified as a neurotoxicant and is linked to increased PD risk and PD-like neuropathology. Ferroptosis is recognized as a new form of regulated cell death. Here, we revealed a new underlying mechanism by which ferritinophagy-mediated ferroptosis is involved in PD induced by PQ. The effect of PQ on movement injury in mice was investigated by the bar fatigue and pole-climbing test. SH-SY5Y human neuroblastoma cells were used to evaluate the mechanism of ferroptosis. Our results showed that PQ induced movement injury by causing the decrease in tyrosine hydroxylase in mice. In vitro, PQ significantly caused the iron accumulation in cytoplasm and mitochondria through ferritinophagy pathway induced by NCOA4. Iron overload initiated lipid peroxidation through 12Lox, further inducing ferroptosis by producing lipid ROS. PQ downregulated SLC7A11 and GPX4 expression and upregulated Cox2 expression significantly, which were important markers in ferroptosis. Fer-1, an inhibitor of ferroptosis, could significantly ameliorate the ferroptosis induced by PQ. Meanwhile, Bcl2, Bax, and p-38 were involved in apoptosis induced by PQ. In conclusion, ferritinophagy-mediated ferroptosis pathway played an important role in PD occurrence. Bcl2/Bax and P-p38/p38 pathways mediated the cross-talk between ferroptosis and apoptosis induced by PQ. These data further demonstrated the complexity of PD occurrence. The inhibition of the ferroptosis and apoptosis together may be a new strategy for the prevention of neurotoxicity or PD in the future.

4.
Mol Cancer ; 20(1): 98, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325714

RESUMO

BACKGROUND: Breast cancer (BC) has a marked tendency to spread to the bone, resulting in significant skeletal complications and mortality. Recently, circular RNAs (circRNAs) have been reported to contribute to cancer initiation and progression. However, the function and mechanism of circRNAs in BC bone metastasis (BC-BM) remain largely unknown. METHODS: Bone-metastatic circRNAs were screened using circRNAs deep sequencing and validated using in situ hybridization in BC tissues with or without bone metastasis. The role of circIKBKB in inducing bone pre-metastatic niche formation and bone metastasis was determined using osteoclastogenesis, immunofluorescence and bone resorption pit assays. The mechanism underlying circIKBKB-mediated activation of NF-κB/bone remodeling factors signaling and EIF4A3-induced circIKBKB were investigated using RNA pull-down, luciferase reporter, chromatin isolation by RNA purification and enzyme-linked immunosorbent assays. RESULTS: We identified that a novel circRNA, circIKBKB, was upregulated significantly in bone-metastatic BC tissues. Overexpressing circIKBKB enhanced the capability of BC cells to induce formation of bone pre-metastatic niche dramatically by promoting osteoclastogenesis in vivo and in vitro. Mechanically, circIKBKB activated NF-κB pathway via promoting IKKß-mediated IκBα phosphorylation, inhibiting IκBα feedback loop and facilitating NF-κB to the promoters of multiple bone remodeling factors. Moreover, EIF4A3, acted acting as a pre-mRNA splicing factor, promoted cyclization of circIKBKB by directly binding to the circIKBKB flanking region. Importantly, treatment with inhibitor eIF4A3-IN-2 reduced circIKBKB expression and inhibited breast cancer bone metastasis effectively. CONCLUSION: We revealed a plausible mechanism for circIKBKB-mediated NF-κB hyperactivation in bone-metastatic BC, which might represent a potential strategy to treat breast cancer bone metastasis.

5.
Comput Intell Neurosci ; 2021: 5546758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211547

RESUMO

An important challenge facing cloud computing is how to correctly and effectively handle and serve millions of users' requests. Efficient task scheduling in cloud computing can intuitively affect the resource configuration and operating cost of the entire system. However, task and resource scheduling in a cloud computing environment is an NP-hard problem. In this paper, we propose a three-layer scheduling model based on whale-Gaussian cloud. In the second layer of the model, a whale optimization strategy based on the Gaussian cloud model (GCWOAS2) is used for multiobjective task scheduling in a cloud computing which is to minimize the completion time of the task via effectively utilizing the virtual machine resources and to keep the load balancing of each virtual machine, reducing the operating cost of the system. In the GCWOAS2 strategy, an opposition-based learning mechanism is first used to initialize the scheduling strategy to generate the optimal scheduling scheme. Then, an adaptive mobility factor is proposed to dynamically expand the search range. The whale optimization algorithm based on the Gaussian cloud model is proposed to enhance the randomness of search. Finally, a multiobjective task scheduling algorithm based on Gaussian whale-cloud optimization (GCWOA) is presented, so that the entire scheduling strategy can not only expand the search range but also jump out of the local maximum and obtain the global optimal scheduling strategy. Experimental results show that compared with other existing metaheuristic algorithms, our strategy can not only shorten the task completion time but also balance the load of virtual machine resources, and at the same time, it also has a better performance in resource utilization.


Assuntos
Computação em Nuvem , Baleias , Algoritmos , Animais , Distribuição Normal
6.
Chemistry ; 27(30): 8040-8047, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33904607

RESUMO

6-Cyano-7-aminoquinoline (6CN-7AQ) and 3-cyano-7-aminoquinoline (3CN-7AQ) were synthesized and found to exhibit intense emission with quantum yield as high as 63 % and 85 %, respectively, in water. Conversely, their derivatives 6-cyano-7-azidoquinoline (6CN-7N3 Q) and 3-cyano-7-azidoquinoline (3CN-7N3 Q) show virtually no emission, which makes them suitable to be used as recognition agents in azide reactions based on fluorescence recovery. Moreover, conjugation of 6CN-7AQ with a hydrophobic biomembrane-penetration peptide PFVYLI renders a nearly non-emissive 6CN-7AQ-PFVYLI composite, which can be digested by proteinase K, recovering the highly emissive 6CN-7AQ with ∼200-fold enhancement. The result provides an effective early confirmation for RT-qPCR in viral detection.

7.
Brain Res ; 1757: 147328, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33539795

RESUMO

Sevoflurane (Sev), a commonly used volatile anesthetic, could induce nerve damage and cognitive deficiency. Oxidative stress induced by iron overload promotes nerve damage and cell apoptosis in the brain. This study revealed a new toxic mechanism of Sev to the brain occurred through the dysfunction of iron metabolism. Twelve-month-old C57BL/6 mice were randomly assigned to the following three groups: control group; 2% Sev (6 h) group; and Sev plus iron deficiency group. Iron levels and iron metabolism-related proteins and apoptosis-related factors in hippocampus and cortex tissues were detected by using synchrotron radiation micro-X-ray fluorescence (µ-XRF) and western blotting. Our results showed that a decline in cognitive function was observed in mice treated with Sev. Sev significantly induced iron accumulation through upregulating ferritin and downregulating transferrin receptor 1 which involved in ferroportin1 (Fpn1)/hepcidin pathway and increasing reactive oxygen species (ROS) and malondialdehyde (MDA) content of hippocampus and cortex. Sev aggravated BACE1 expression and Aß accumulation. Changes in the ratio of Bcl2/Bax and Tau/p-Tau intensified the cell apoptosis in hippocampus and cortex tissues. Interestingly, the cognitive deficiency and neurotoxicity induced by Sev could be ameliorated significantly by feeding a low-iron diet to mice prior to anesthesia. The data uncovered a new lesion mechanism of Sev from the role of iron metabolism. This study also suggested that the reduction in iron levels could protect the brain against neurological damage induced by Sev.

8.
Microb Drug Resist ; 27(8): 1105-1116, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33439767

RESUMO

Aim: To evaluate the antimicrobial and antibiofilm effects of chelerythrine (CHE) against carbapenem-resistant Serratia marcescens (CRSM). Materials and Methods: The minimum inhibitory concentration (MIC) of CHE against CRSM was determined using the agar dilution method. Changes in intracellular adenosine triphosphate (ATP) concentration, intracellular pH, cell membrane potential, and cell membrane integrity were investigated to assess the influence of CHE on the cell membrane. The effects of CHE on cell morphology were observed by field emission scanning electron microscopy (FESEM) and transmission electron microscopy. The antibiofilm formation of CHE was measured by crystal violet staining and visualized with confocal laser scanning microscopy (CLSM) and FESEM. The influence of CHE on biofilm components was further investigated using CLSM specific combined with double-dyeing methods. Results: Our results showed that CHE had an MIC at 125 µg/mL against CRSM was capable of inhibiting the growth of CRSM and destroying its cell membrane integrity, as well as obviously changing the cell morphology. Sub-MIC CHE displayed robust inhibitory effects against CRSM biofilm formation by mediating the production of biofilm components. In addition, CLSM- and FESEM-mediated evaluation of the damage of biofilm cells and biofilm persistence revealed that at high concentrations, CHE could compromise the cells within biofilms and remove preformed biofilms. Conclusion: CHE shows promise as a natural antimicrobial substance against biofilm-positive CRSM, with the potential to serve as an alternative therapeutic agent.

9.
Epidemiol Infect ; 148: e211, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900409

RESUMO

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56-71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911-1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563-0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.


Assuntos
Betacoronavirus , Plaquetas , Infecções por Coronavirus/mortalidade , Linfócitos , Neutrófilos , Pneumonia Viral/mortalidade , Adolescente , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Causas de Morte , Criança , Pré-Escolar , Infecções por Coronavirus/sangue , Infecções por Coronavirus/etiologia , Humanos , Lactente , Recém-Nascido , Pacientes Internados , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Adulto Jovem
10.
Org Biomol Chem ; 15(16): 3413-3417, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28383597

RESUMO

Oxadiazolones are first employed as the three-atom coupling partners in the Tf2NH-catalyzed cycloaddition with ynamides. This formal [3 + 2] cycloaddition allows a rapid synthesis of aminoimidazoles with a broad substrate scope. The approach also features a metal-free catalytic cycloaddition process, which may find applications in the synthesis of bioactive molecules. Besides, the resulting N-methyl products can further be readily converted to free N-H aminoimidazoles.

11.
J Org Chem ; 82(7): 3935-3942, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28276692

RESUMO

An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

12.
J Org Chem ; 81(23): 12031-12037, 2016 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-27934471

RESUMO

A ruthenium-catalyzed intermolecular [3 + 2] cycloaddition of 2H-azirines and activated alkynes is reported, which provides polysubstituted pyrroles in moderate to good yields. This approach features a C-N bond cleavage of 2H-azirines by a ruthenium catalyst. The results of this study would provide a complementary method to synthesize polysubstituted pyrroles from the known 2H-azirine approaches and advance 2H-azirine chemistry.

13.
J Org Chem ; 81(10): 4412-20, 2016 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-27128790

RESUMO

A strategy for achieving diastereodivergent azidations of enynes has been developed, employing azide transfer from the M-N3 complex to alkyl radicals. Following this concept, the diastereoselectivity has been switched by modulating the transition metals and the ligands. The Mn(III)-mediated radical cyclization/azidation cascade of 1,7-enynes afforded trans-fused pyrrolo[3,4-c]quinolinones, whereas the Cu(II)/bipyridine system gave cis-products.

14.
Angew Chem Int Ed Engl ; 55(8): 2861-5, 2016 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-26800151

RESUMO

2H-azirines can serve as three-atom synthons by C-C bond cleavage, however, it involves a high energy barrier under thermal conditions (>50.0 kcal mol(-1) ). Reported is a ruthenium-catalyzed [3+2+2] cycloaddition reaction of 2H-azirines with diynes, thus leading to the formation of fused azepine skeletons. This approach features an unprecedented metal-catalyzed C-C bond cleavage of 2H-azirines at room temperature, and the challenging construction of aza-seven-membered rings from diynes. The results of this study provide a new reaction pattern for constructing nitrogen-containing seven-membered rings and may find applications in the synthesis of other complex heterocycles.

15.
ACS Omega ; 1(5): 930-938, 2016 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31457173

RESUMO

Mesoporous structured catalysts featuring interfacial activity are the most promising candidates for biphasic interface catalysis because their nanopores can concurrently accommodate catalytic active components and provide countless permeable channels for mass transfer between the interior and the exterior of Pickering droplets. However, to date, a convenient and effective strategy for the preparation of an anchor site-containing interfacial active mesoporous catalyst is still lacking. In the present work, we report a novel and efficient interfacial active mesoporous silica (MS) catalyst, which is prepared by a facile cocondensation of two types of organosilanes and subsequent anchoring of Pd NPs onto its surface through the confinement and coordination interactions. The as-prepared catalyst is then applied as emulsifier to stabilize the water-in-oil (W/O) Pickering emulsion and investigated as an interfacial catalyst for the hydrogenation of nitroarenes. An obviously enhanced rate toward the nitrobenzene hydrogenation is observed for the 0.8 mol% Pd/PAP-functionalized mesoporous silica-20 catalyst in the emulsion system (both conversion and selectivity are >99% within 30 min) in comparison to a single aqueous solution. Moreover, the emulsion catalytic system can be easily recycled six times without the separation of the catalyst from the water phase during the recycling process. This finding demonstrates that the incorporation of phenylaminopropyl trimethoxysilane amphiphilic groups during the hydrolysis of tetramethyl orthosilicate not only endows MS with interfacial activity but also improves the catalytic activity and stability.

16.
Org Biomol Chem ; 14(2): 526-541, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26501367

RESUMO

2-Trifluoromethyl-5-(arylsulfonyl)methyl pyrroles and 2-trifluoromethyl-4-(arylsulfonyl)methyl pyrroles were selectively synthesized from trifluoromethyl-substituted 3-aza-1,5-enynes via a cyclization/sulfonyl group migration cascade catalyzed by AgOOCCF3 and CsOPiv, respectively. Alkylvinyl-substituted pyrroles were generated from seven-atom skeleton 3-aza-1,5-enynes via aryl sulfinic acid elimination in the presence of Cs2CO3. Two ion-pair intermediates were proposed and a key intermediate, aza-diene-yne, was successfully isolated in the mechanistic studies.

17.
Org Lett ; 17(16): 3944-7, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26251020

RESUMO

A base-catalyzed selective cycloisomerization of 3-aza-1,5-enynes is developed. This transformation provides a facile access to highly functionalized 2-azabicyclo[3.2.0]hept-2-enes and sulfonyl vinyl-substituted pyrroles. The chemoselectivity was controlled by the substituent pattern of the substrates.

18.
Angew Chem Int Ed Engl ; 54(36): 10613-7, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26177605

RESUMO

The direct C-H annulation of anilines or related compounds with internal alkynes provides straightforward access to 2,3-disubstituted indole products. However, this transformation proceeds with poor regioselectivity in the synthesis of unsymmetrically 2,3-diaryl substituted indoles. Herein, we report the rhodium(III)-catalyzed C-H annulation of nitrones with symmetrical diaryl alkynes as an alternative method to prepare 2,3-diaryl-substituted N-unprotected indoles with two different aryl groups. One of the aryl substituents is derived from N=C-aryl ring of the nitrone and the other from the alkyne substrate, thus providing the indole products with exclusive regioselectivity.

19.
Tree Physiol ; 35(6): 621-31, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25813701

RESUMO

During the development of woody twigs, the growth in leaf may or may not be proportional to the growth in stem. The presence or absence of a synchronicity between these two phenologies may reflect differences in life history adaptive strategies concerning carbon gain. We hypothesized that sun-adapted species are more likely to be less synchronous between growths in total leaf area (TLA) and stem length compared with shade-adapted species, with a bias in growth in stem length, and that shade-adapted species are more likely to be more synchronous between increases in individual leaf area (ILA) (leaf size) and leaf number (LN) during twig development compared with sun-adapted species, giving priority to growth of leaf size. We tested these two hypotheses by recording the phenologies of leaf emergence, leaf expansion and stem elongation during twig development for 19 evergreen woody species (including five shade-adapted understory species, six sun-adapted understory species and eight sun-adapted canopy species) in a subtropical evergreen broad-leaved forest in eastern China. We constructed indices to characterize the synchronicity between TLA and stem length (αLS) and between leaf size and leaf number (αSN) and we derived the α values from logistic functions taking the general form of A = A(max)/[1 + exp(ß - αB)] (where A is the TLA or average ILA, B is the corresponding stem length or LN at a specific time, and A(max) is the maximum TLA or the maximum ILA of a twig; the higher the numerical value of α, the less synchronous the corresponding phenologies). Consistent with our hypotheses, sun-adapted species were higher both in α(LS) and α(SN), showing less synchronous patterns in the growths of TLA vs stem length and leaf size vs LN during twig development. Moreover, α(LS) and α(SN) were significantly positively correlated with relative growth rates of LN and leaf size across species, as indicated by both analyses of ordinary regression and phylogenetic generalized least squares. The across-species synchronies during twig development show that the temporal dynamics of the leaf size-twig size spectrum is of adaptive significance in plants. We suggest that temporal dynamics of plant functional traits should be extensively studied to characterize plant life history.


Assuntos
Folhas de Planta/crescimento & desenvolvimento , Caules de Planta/crescimento & desenvolvimento , Floresta Úmida , Árvores/crescimento & desenvolvimento , Clima Tropical , Madeira/crescimento & desenvolvimento , China , Análise dos Mínimos Quadrados , Tamanho do Órgão , Filogenia , Folhas de Planta/anatomia & histologia , Análise de Regressão , Especificidade da Espécie
20.
Org Lett ; 16(18): 4806-9, 2014 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-25184304

RESUMO

A highly efficient Cu-catalyzed ring expansion reaction of 2H-azirines with terminal alkynes has been developed. This transformation provides a powerful method for the synthesis of 3-alkynyl polysubstituted pyrroles under mild conditions in good yields. The direct transformation process, specific selectivity, and good tolerance to a variety of substituents make it an alternative approach to the reported protocols.

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