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1.
J Am Chem Soc ; 146(17): 12087-12099, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647488

RESUMO

Electron transfer during solid-liquid contact electrification has been demonstrated to produce reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and superoxide anion radicals (•O2-). Here, we show that such a process also occurs in liquid-liquid contact electrification. By preparing perfluorocarbon nanoemulsions to construct a perfluorocarbon-water "liquid-liquid" interface, we confirmed that electrons were transferred from water to perfluorocarbon in ultrasonication-induced high-frequency liquid-liquid contact to produce •OH and •O2-. The produced ROS could be applied to ablate tumors by triggering large-scale immunogenic cell death in tumor cells, promoting dendritic cell maturation and macrophage polarization, ultimately activating T cell-mediated antitumor immune response. Importantly, the raw material for producing •OH is water, so the tumor therapy is not limited by the endogenous substances (O2, H2O2, etc.) in the tumor microenvironment. This work provides new perspectives for elucidating the mechanism of generation of free radicals in liquid-liquid contact and provides an excellent tumor therapeutic modality.


Assuntos
Fluorocarbonos , Água , Fluorocarbonos/química , Água/química , Camundongos , Animais , Neoplasias/tratamento farmacológico , Radicais Livres/química , Humanos , Radical Hidroxila/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia
2.
J Hepatol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759889

RESUMO

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

3.
Biochem Biophys Res Commun ; 710: 149884, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38598901

RESUMO

In the clinical setting, chemotherapy is the most widely used antitumor treatment, however, chemotherapy resistance significantly limits its efficacy. Reduced drug influx is a key mechanism of chemoresistance, and inhibition of the complexity of the tumor microenvironment (TME) may improve chemotherapy drug influx and therapeutic efficiency. In the current study, we identified that the major extracellular matrix protein collagen I is more highly expressed in lung cancer tissues than adjacent tissues in patients with lung cancer. Furthermore, Kaplan-Meier analysis suggested that COL1A1 expression was negatively correlated with the survival time of patients with lung cancer. Our previous study demonstrated that miR-29a inhibited collagen I expression in lung fibroblasts. Here, we investigated the effect of miR-29a on collagen I expression and the cellular behavior of lung cancer cells. Our results suggest that transfection with miR-29a could prevent Lewis lung carcinoma (LLC) migration by downregulating collagen I expression, but did not affect the proliferation, apoptosis, and cell cycle of LLC cells. In a 3D tumoroid model, we demonstrated that miR-29a transfection significantly increased cisplatin (CDDP) permeation and CDDP-induced cell death. Furthermore, neutral lipid emulsion-based miR-29a delivery improved the therapeutic effect of cisplatin in an LLC spontaneous tumor model in vivo. In summary, this study shows that targeting collagen I expression in the TME contributes to chemotherapy drug influx and improves therapeutic efficacy in lung cancer.


Assuntos
Neoplasias Pulmonares , MicroRNAs , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , MicroRNAs/farmacologia , Permeabilidade , Microambiente Tumoral
4.
Small ; : e2312141, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801318

RESUMO

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

5.
Respir Res ; 25(1): 93, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378600

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and represents the third leading cause of death worldwide. This study aimed to investigate miRNA regulation of Receptor for Advanced Glycation End-products (RAGE), a causal receptor in the pathogenesis of cigarette smoke (CS)-related COPD, to guide development of therapeutic strategies. METHODS: RAGE expression was quantified in lung tissue of COPD patients and healthy controls, and in mice with CS-induced COPD. RNA-sequencing of peripheral blood from COPD patients with binding site prediction was used to screen differentially expressed miRNAs that may interact with RAGE. Investigation of miR-23a-5p as a potential regulator of COPD progression was conducted with miR-23a-5p agomir in COPD mice in vivo using histology and SCIREQ functional assays, while miR-23a-5p mimics or RAGE inhibitor were applied in 16-HBE human bronchial epithelial cells in vitro. RNA-sequencing, ELISA, and standard molecular techniques were used to characterize downstream signaling pathways in COPD mice and 16-HBE cells treated with cigarette smoke extract (CSE). RESULTS: RAGE expression is significantly increased in lung tissue of COPD patients, COPD model mice, and CSE-treated 16-HBE cells, while inhibiting RAGE expression significantly reduces COPD severity in mice. RNA-seq analysis of peripheral blood from COPD patients identified miR-23a-5p as the most significant candidate miRNA interaction partner of RAGE, and miR-23a-5p is significantly downregulated in mice and cells treated with CS or CSE, respectively. Injection of miR-23a-5p agomir leads to significantly reduced airway inflammation and alleviation of symptoms in COPD mice, while overexpressing miR-23a-5p leads to improved lung function. RNA-seq with validation confirmed that reactive oxygen species (ROS) signaling is increased under CSE-induced aberrant upregulation of RAGE, and suppressed in CSE-stimulated cells treated with miR-23a-5p mimics or overexpression. ERK phosphorylation and subsequent cytokine production was also increased under RAGE activation, but inhibited by increasing miR-23a-5p levels, implying that the miR-23a-5p/RAGE/ROS axis mediates COPD pathogenesis via ERK activation. CONCLUSIONS: This study identifies a miR-23a-5p/RAGE/ROS signaling axis required for pathogenesis of COPD. MiR-23a-5p functions as a negative regulator of RAGE and downstream activation of ROS signaling, and can inhibit COPD progression in vitro and in vivo, suggesting therapeutic targets to improve COPD treatment.


Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Camundongos , Pulmão/metabolismo , MicroRNAs/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo
6.
Rapid Commun Mass Spectrom ; 38(2): e9668, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38124171

RESUMO

RATIONALE: Lithium isotope geochemistry is an important tool in the studies of Earth and planetary materials. In situ Li isotope analyses are typically performed using secondary ion mass spectrometry (SIMS) or laser ablation multicollector inductively coupled plasma mass spectrometry (LA-MC-ICPMS), but these instruments are not widely accessible. Here, the capability of laser ablation quadrupole ICPMS for conducting Li isotopic analyses is evaluated. METHODS: An array of MPI-DING and USGS silicate glass reference materials was analyzed repeatedly over the course of 6 months. These materials range from komatiite to rhyolite in terms of silica content (45.5-75.6 wt%) with 9-45 ppm Li. Their Li isotope compositions have been previously characterized so that matrix effects could be tested with these reference materials. Analyses were conducted using an NWR193 laser ablation system coupled to an Agilent 7900 ICPMS system. RESULTS: Analytical precision is primarily limited by Li concentration in the samples. For samples with ~9 ppm Li, the internal precision is 6‰ (2 SD, 150 µm spot diameter), whereas that for a sample with ~45 ppm Li is 4‰ (2 SD, 120 µm spot diameter). The technique is somewhat sensitive to sample matrix: samples with SiO2 content that deviates from the bracketing standard display fractionated δ7 Li, necessitating correction using a session-specific matrix correction curve. CONCLUSION: Lithium isotope analysis by ns-LA-QICPMS is worthwhile for samples with high Li concentrations and when a matrix-matched standard can be obtained. Although the precision of this method is not as high as those achievable with SIMS and LA-MC-ICPMS, it remains adequate for resolving large isotope fractionations found in natural and laboratory settings.

7.
J Acoust Soc Am ; 155(5): 2959-2972, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717203

RESUMO

Frequency hopping (FH) signals have been widely used to improve performance against frequency selective fading phenomenon of underwater channels. However, the channel is slowly varying in regard to changes in weather conditions, and thus the conventional FH detection transmitting signals with fixed frequency cannot guarantee good detection performance in the dynamic underwater environment. To overcome the performance degradation in slowly-varying fading dispersive channels, this paper proposes an adaptive frequency-hopping (AFH) target detection method. Compared with conventional FH detection methods, the AFH can adaptively select the optimal detection frequency based on premeasured background noise and channel frequency response measured from previous experiments. Numerical simulations and lake trials are conducted to verify the effectiveness of the AFH. The simulation results show that the AFH has better detection performance than the conventional FH. The lake trial results have also verified the validity and feasibility of AFH. Importantly, AFH also achieves a better output signal-to-noise ratio under actual noise interference.

8.
Neuroimage ; 284: 120451, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37949259

RESUMO

BACKGROUND: Neuroimaging techniques provide insights into the brain abnormalities secondary to degenerative cervical myelopathy (DCM) and their association with neurological deficits. However, the neural correlates underlying the discrepancy between symptom severity and the degree of spinal cord compression, as well as the transcriptional correlates of these cortical abnormalities, remain unknown in DCM patients. METHODS: In this cross-sectional study, which collected resting-state functional MRI (rs-fMRI) images and the Japanese Orthopedic Association (JOA) score, enrolled 104 participants (54 patients and 50 healthy controls). The frequency-dependent amplitude of low-frequency fluctuation (ALFF) was obtained for all participants. We investigated the ALFF differences between mild-symptom DCM patients and severe-symptom DCM patients while carefully matching the degree of compression between these two groups via both univariate comparison and searchlight classification for three frequency bands (e.g., Slow-4, Slow-5, and Full-band). Additionally, we identified genes associated with symptom severity in DCM patients by linking the spatial patterns of gene expression of Allen Human Brain Atlas and brain functional differences between mild symptom and severe symptom groups. RESULTS: (1) We found that the frequency-specific brain activities within the sensorimotor network (SMN), visual network (VN), and default mode network (DMN) were associated with the varying degrees of functional impairment in DCM patients; (2) the frequency-specific brain activity within the SMN correlated with the functional recovery in patients with DCM; (3) a spatial correlation between the brain-wide expression of genes involved in neuronal migration and the brain functional activities associated with symptom severity was identified in DCM patients. CONCLUSION: In conclusion, our study bridges gaps between genes, cell classes, biological processes, and brain functional correlates of DCM. While our findings are correlational in nature, they suggest that the neural activities of sensorimotor cortices in DCM are associated with the severity of symptoms and might be associated with neuronal migration within the brain.


Assuntos
Córtex Sensório-Motor , Doenças da Medula Espinal , Humanos , Estudos Transversais , Neuroimagem , Vértebras Cervicais/diagnóstico por imagem
9.
J Cell Biochem ; 124(4): 557-572, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36842167

RESUMO

Gastric cancer (GC) with pulmonary metastasis is one of the deadliest diseases in the world; however, the underlying pathological mechanisms and potential therapeutic targets remain to be elucidated. As exosomes play indispensable roles in the formation of premetastatic niches (PMN) and cancer metastasis. Therefore, investigating the underlying mechanisms of exosome-mediated pulmonary metastasis of GC may shed new light on identifying novel therapeutic targets for GC treatment. GC-derived exosomes were isolated from the conditioned medium of mouse forestomach carcinoma (MFC) cell line. The effects of MFC-derived exosomes on pulmonary macrophage polarization were analyzed by reverse- transcription polymerase chain reaction and flow cytometry. Expression of PD-L1 and other proteins was evaluated by Western blot. Exosomal microRNAs (miRNAs) were analyzed by microarray. GC-derived exosomes (GC-exo) accumulated in high numbers in the lungs and were ingested by macrophages. The extracellular-signal-regulated kinase (ERK) signaling pathway was activated by GC-exo, inducing macrophage immunosuppressive-phenotype differentiation and increased PD-L1 expression. miRNA-sequencing identified 130 enriched miRNAs in GC-exo. Among the enriched miRNAs, miR-92a-3p plays a major role in activating ERK signaling via inhibition of PTEN expression. In addition, inhibiting ERK signaling with PD98059 significantly reduced the expression of PD-L1 in macrophages and, therefore, reversed the immunosuppressive PMN and inhibited the colonization of GC cells in the lungs. This study identified a novel mechanism of GC-exo mediated PD-L1 expression in lung macrophages that facilitates lung PMN formation and GC pulmonary metastasis, which also provided a potential therapeutic target for GC with pulmonary metastasis treatment.


Assuntos
Exossomos , Neoplasias Pulmonares , MicroRNAs , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Exossomos/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Macrófagos/metabolismo , Neoplasias Pulmonares/metabolismo
10.
Pestic Biochem Physiol ; 194: 105495, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532354

RESUMO

Overcoming the innate immunity of insects is a key process to improve the efficiency of biological control. Antimicrobial peptides (AMPs) are important effectors in insect innate immunity, usually mediating resistance to pathogenic microorganisms through Toll and IMD signaling pathways. This study investigated the effect of key genes on upstream immune recognition receptor (GNBP3) and downstream effectors (AMPs) by RNAi technology. The transcriptome KEGG enrichment analysis and differential gene annotation results showed that the immune response genes MaltSpz and MaltRelish are important regulators of Toll and IMD signaling pathways, respectively. Both dsSpz and dsRelish could affect AMP gene expression and increase the expression of the immune recognition receptor MaltGNBP3. Moreover, they significantly reduce the survival rate of Monochamus alternatus and promote hyphal growth after Beauveria bassiana infection. This helps to improve the biological control effect of B. bassiana, control the population of vector insects and cut off the transmission route of pine wood nematode. The combined MaltSpz and MaltRelish knockdown increased the infection rate of M. alternatus larvae from 20.69% to 83.93%, achieving the best efficiency in synergistic B. bassiana infection. Our results showed important roles of MaltRelish- and MaltSpz-mediated regulation of AMP genes function in insect entomopathogenic fungi tolerance and induced significant mortality in larvae. Based on this study, MaltSpz and MaltRelish could represent candidate gene targets for the biological control of M. alternatus by RNAi.


Assuntos
Beauveria , Besouros , Animais , Besouros/genética , Larva , Controle de Pragas , Perfilação da Expressão Gênica
11.
Pestic Biochem Physiol ; 194: 105511, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532327

RESUMO

Pine wilt disease is a devastating disease of pine caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus. Long-term use of chemical nematicides leads to the development of resistance in nematodes and harms the environment. Evaluations for green environmental protection agents, identified the antibacterial peptide, MaltDef1, from Monochamus alternatus which had nematicidal effect. We studied its nematicidal activity and action against PWN. In this study, the antibacterial peptide S-defensin was synthesized from M. alternatus. The results showed that S-defensin caused mortality to the PWN, causing shrinkage, pore, cell membrane dissolution and muscle atrophy. In addition, PWN reproduction was also affected by S-defensin; it decreased in a concentration dependent manner with increasing treatment concentration. By contrast, reactive oxygen species (ROS) in vivo increased in a concentration-dependent manner. We applied transcriptome to analyze the changes in gene expressions in S-defensin treated PWN, and found that the most significantly enriched pathway was the ERK/MAPK signaling pathway. RNAi was used to validate the functions of four differential genes (Let-23, Let-60, Mek-2 and Lin-1) in this pathway. The results showed that knockdown of these genes significantly decreased the survival rate and reproductive yield of, and also increased ROS in PWN. The antibacterial peptide S-defensin had a significant inhibitory effect on the survival and reproduction of PWN, shown by cell membrane damage and intracellular biological oxidative stress via regulating the ERK/MAPK signaling pathway. This indicates that S-defensin has a target in B. xylophilus, against which new green target pesticides can be developed.


Assuntos
Besouros , Nematoides , Pinus , Tylenchida , Animais , Espécies Reativas de Oxigênio , Doenças das Plantas , Estresse Oxidativo , Antinematódeos/farmacologia , Transdução de Sinais , Reprodução , Tylenchida/genética , Defensinas
12.
Int J Mol Sci ; 24(6)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36982491

RESUMO

Insects have evolved to form a variety of complex natural compounds to prevent pathogen infection in the process of a long-term attack and defense game with various pathogens in nature. Antimicrobial Peptides (AMPs) are important effector molecules of the insect immune response to the pathogen invasion involved in bacteria, fungi, viruses and nematodes. The discovery and creation of new nematicides from these natural compounds is a key path to pest control. A total of 11 AMPs from Monochamus alternatus were classified into 3 categories, including Attacin, Cecropin and Defensin. Four AMP genes were successfully expressed by Komagataella phaffii KM71. The bioassay results showed that the exogenous expressed AMPs represented antimicrobial activity against Serratia (G-), Bacillus thuringiensis (G+) and Beauveria bassiana and high nematicide activity against Bursaphelenchus xylophilus. All four purified AMPs' protein against B. xylophilus reached LC50 at 3 h (LC50 = 0.19 mg·mL-1 of MaltAtt-1, LC50 = 0.20 mg·mL-1 of MaltAtt-2 and MaltCec-2, LC50 = 0.25 mg·mL-1 of MaltDef-1). Furthermore, the AMPs could cause significant reduction of the thrashing frequency and egg hatching rate, and the deformation or fracture of the body wall of B. xylophilus. Therefore, this study is a foundation for further study of insect biological control and provides a theoretical basis for the research and development of new insecticidal pesticides.


Assuntos
Besouros , Rabditídios , Animais , Besouros/genética , Insetos , Antinematódeos/farmacologia , Peptídeos
13.
J Mater Cycles Waste Manag ; 25(3): 1333-1343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36785749

RESUMO

Waste treatment is a problem faced by cities all over the world. In recent years, China, as a developing country, regards the municipal solid waste (MSW) classification as one of the important strategies to deal with the MSW problem. The previous MSW classification policies in China were all only advocacy in nature. It was not until January 2019 that the "Regulations on the Management of MSW in Shanghai" was officially promulgated as China's first compulsory MSW classification policy, marking the beginning of an era of compulsory MSW classification in China. How effective is the implementation of Shanghai's compulsory MSW classification policy 18 months after its implementation and can developing countries continuously and effectively implement compulsory MSW classification policies? These are important issues of concern to the government, academia, and the public. This paper establishes a three-stage DEA model to evaluate the implementation effect of the compulsory MSW classification policies in Shanghai during the period of February 2019 and July 2020. The study found that the average efficiency of the compulsory MSW classification policy in Shanghai reached 0.906 during the study period, indicating that the policy was executed reasonably well. However, there are only 5 months in 18 months that the policy was fully effective (reaching efficiency level 1), suggesting that there is still room for improvement. The main reason for not being able to achieve full effectiveness in some months is attributed to scale efficiency. At the same time, the general public budget revenue and expenditure of environmental variables have positive and negative impacts on the policy implementation effect in Shanghai. The research results can provide experience for China to comprehensively implement the compulsory MSW classification policy in the future and can also provide valuable case study information for cities in other developing countries to implement the compulsory MSW classification policy.

14.
Clin Neuropathol ; 41(6): 245-252, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35770518

RESUMO

BACKGROUND AND AIMS: The early growth response 2 gene (EGR2) mutations are associated with a group of hereditary neuropathy, including axonal neuropathy and hypomyelinating neuropathy or Charcot-Marie-Tooth disease (CMT) type 1D. We aim to perform an electrodiagnostic, nerve imaging, and histological study of EGR2-associated neuropathy. MATERIALS AND METHODS: We performed a retrospective analysis of two patients with EGR2-related neurology at our hospital. The neuropathy was confirmed by the nerve conduction study. Nerve imaging and sural biopsies were performed in two patients. RESULTS: Two unrelated boys exhibited early-onset length-dependent neuropathy. Next generation sequencing identified EGR2 gene with previously described E412K mutation in the third zine finger domain in patient 1 and a previously undescribed variant D355N mutation in the first zinc finger domain in patient 2. The magnetic resonance imaging of the lumbosacral plexus showed no abnormalities in patient 1 and thickened lumbosacral plexuses in patient 2. Electrophysiology and nerve biopsies showed a prominent axonal neuropathy, accompanied with demyelinating involvement. CONCLUSION: Therefore, it seemed that the EGR2 mutations could cause not only the known demyelinating type and axonal type but also mixed-type CMT. Our findings expanded the phenotypic heterogeneities of EGR2-associated neuropathy.


Assuntos
Doença de Charcot-Marie-Tooth , Masculino , Humanos , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Estudos Retrospectivos , Fenótipo , Axônios/patologia , Mutação , Nervo Sural/patologia , Proteína 2 de Resposta de Crescimento Precoce/genética
15.
Waste Manag Res ; 39(1): 83-92, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32787673

RESUMO

China is experiencing an enormous increase in municipal household solid waste (MHSW) generation and is facing multiple problems associated with the treatment of MHSW. This paper analyses factors affecting residents' satisfaction with MHSW treatment performance. Six factors were identified by the Delphi method: (a) pick-up frequency by waste collection vehicles, (b) fund supply situation, (c) charging standard for waste treatment, (d) waste bin arrangement, (e) laws and regulations, (f) publicity and education. We examine the significance of these six influencing factors, estimating binary logistic regression models. Data for this study are derived from the survey responses of 469 households in Harbin, one of the largest cities in northeast China. The results indicate that 'pick-up frequency by waste collection vehicles' is ranked the first and most important determinant of Harbin residents' satisfaction with MHSW treatment; this is closely followed by 'publicity and education'. The third and fourth significant influencing factors, respectively, are 'fund supply situation' and 'charging standard for waste treatment'. The last two factors are 'laws and regulations' and 'waste bin arrangement'. By understanding the influence of various factors on residents' satisfaction, this study aims to help in designing an effective waste management system to reduce the cost of MHSW management, and to raise the residents' satisfaction with municipal solid waste treatment. Based on the research findings, we advocate that establishing a reasonable waste transport (pick-up) system as well as strengthening publicity and education of waste management are key to improving residents' satisfaction with the MHSW treatment performance.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , China , Cidades , Satisfação Pessoal , Resíduos Sólidos
16.
Angew Chem Int Ed Engl ; 60(40): 21905-21910, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34322970

RESUMO

In solid tumors, tumor invasion and metastasis account for 90 % of cancer-related deaths. Cell migration is steered by the lamellipodia formed at the leading edge. These lamellipodia can drive the cell body forward by its mechanical deformation regulated by cofilin. Inhibiting cofilin activity can cause significant defects in directional lamellipodia formation and the locomotory capacity of cell invasion, thus contributing to antimetastatic treatment. Herein, a near infrared light (NIR)-controlled nanoscale proton supplier was designed with upconversion nanoparticles (UCNPs) as a core coated in MIL-88B for interior photoacids loading; this photoacids loading can boost H+ transients in cells, which converts the cofilin to an inactive form. Strikingly, inactive cofilin loses the ability to mediate lamellipodia deformation for cell migration. Additionally, the iron, which serves as a catalyticaly active center in MIL-88B, initiates an enhanced Fenton reaction due to the increased H+ in the tumor, ultimately achieving intensive chemodynamic therapy (CDT). This work provides new insight into H+ transients in cells, which not only regulates cofilin protonation for antimetastatic treatment but also improves chemodynamic therapy.


Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Pseudópodes/efeitos dos fármacos , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Raios Infravermelhos , Estruturas Metalorgânicas/química , Camundongos , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Tamanho da Partícula , Propriedades de Superfície
18.
Mikrochim Acta ; 187(12): 659, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201322

RESUMO

A one-pot hydrothermal synthesis of manganese-doped carbon dots (Mn-CDs) is reported for fluorescent "on-off-on" determination of Mn(VII) and L-ascorbic acid (L-AA) in aqueous solution and living cells. Mn-CDs were prepared by using sulfanilic acid, tetrakis(hydroxymethyl)phosphonium chloride, and Mn(II) chloride as precursors. Mn-CDs were characterized by several spectroscopic methods and microscopic techniques. Mn-CDs show distinctly long fluorescence lifetime (12.39 ± 0.07 ns) and high absolute fluorescence quantum yield (around 37%) with excitation and emission wavelengths of 362 and 500 nm, respectively. Mn-CDs exhibit no significant cytotoxicity to human cervical carcinoma HeLa cells and human embryonic kidney HEK-293T cells at 200 µg mL-1 level after 48 h incubation. The fluorescence of Mn-CDs at 500 nm (excited at 362 nm) is quenched efficiently by Mn(VII) and can be further recovered after the addition of L-AA, resulting in a fluorescent "on-off-on" assay for the determination of Mn(VII) and L-AA. Under optimal experimental conditions, the linear response covers the 3 to 150 µM Mn(VII) concentration range and the 3 to 140 µM L-AA concentration range. This method offers relatively low detection limits of 0.66 µM for Mn(VII) and 0.90 µM for L-AA. This strategy was applied to visual determination of Mn(VII) and L-AA in living HeLa cells with satisfying results. Graphical abstract Schematic presentation of bright Mn-CD-based fluorescence "on-off-on" assay for both Mn(VII) and L-AA. This fluorescent assay possessed low detection limit of 0.66 µM for Mn(VII) and 0.90 µM for L-AA. This strategy was applied for visual determination of Mn(VII) and L-AA in living HeLa cells with satisfying results.


Assuntos
Ácido Ascórbico/análise , Carbono/química , Compostos de Manganês/análise , Manganês/química , Óxidos/análise , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Células HEK293 , Células HeLa , Humanos , Limite de Detecção , Magnetismo , Reprodutibilidade dos Testes , Espectrofotometria Ultravioleta
19.
Mikrochim Acta ; 187(5): 271, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32291528

RESUMO

A ratiometric fluorescent assay is fabricated for the evaluation of alkaline phosphatase (ALP) activity. This assay is composed of ionic liquid-functionalized carbon dots (IL-CDs) with blue fluorescence signal at 470 nm and 2,3-diaminophenazine (DAP) with yellow fluorescence signal at 570 nm. IL-CDs were synthesized via electrochemical method by using ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate) and ultrapure water as precursors. DAP is produced by the oxidation reaction between o-phenylenediamine and H2O2 under the catalysis of horseradish peroxidase. H2O2 is reduced by ascorbic acid which is the hydrolysis product of ascorbic acid 2-phosphate under the catalysis of ALP, finally reducing the amount of DAP. The activity of ALP is evaluated through the ratiometric fluorescent signal between IL-CDs and DAP via Förster resonance energy transfer. Under optimal experimental conditions, this ratiometric fluorescent assay has a response that covers the 0.04 to 3.2 U L-1 (12 to 960 pM) ALP activity. This assay possesses ultralow detection limit of 0.012 U L-1 (3.6 pM) for ALP and high selectivity for ALP among several enzymes. The method was used to measure ALP activity in human serum samples with satisfying results. Graphical abstract Schematic presentation of IL-CDs-based ratiometric fluorescent assay for ALP activity evaluation via FRET strategy between IL-CDs and DAP. This ratiometric fluorescent assay possessed low detection limit of ALP activity (0.012 U L-1) and high selectivity among several enzymes.


Assuntos
Fosfatase Alcalina/sangue , Corantes Fluorescentes/química , Líquidos Iônicos/química , Pontos Quânticos/química , Espectrometria de Fluorescência/métodos , Armoracia/enzimologia , Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/análise , Ácido Ascórbico/química , Carbono/química , Peroxidase do Rábano Silvestre/química , Humanos , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Imidazóis/química , Limite de Detecção , Fenilenodiaminas/química
20.
Mikrochim Acta ; 186(12): 851, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776683

RESUMO

A rapid, sensitive, and selective fluorometric assay is described for the determination of chromium(VI) in real waters and living cells. The method is making use of nitrogen, phosphorus, and sulfur tri-doped carbon dots (NPS-CDs) which have absorption/emission maxima at 360/505 nm/nm. Cr(VI) has an absorption maximum at 350 nm and causes an inner filter effect (IFE) on the blue fluorescence of the NPS-CDs. The NPS-CDs were hydrothermally synthesized using p-aminobenzenesulfonic acid and tetrakis(hydroxymethyl)phosphonium chloride as precursors. The NPS-CDs were characterized by transmission electron microscopy, X-ray diffraction, and several spectroscopic methods. They are biocompatible and negligibly cytotoxic when tested with HeLa cells and MCF-7 cells even after 48 h of incubation. The NPS-CDs were used as fluorescent probes for Cr(VI). The detection limit is 0.23 µM (three times standard deviation versus slope), and the linear response covers the 1 to 500 µM chromate concentration range. The NPS-CDs were applied to the determination of Cr(VI) in real waters and living cells (HeLa and MCF-7) and gave satisfying results. Graphical abstractSchematic representation of hydrothermal synthesis of nitrogen, phosphorus, and sulfur tri-doped carbon dots (NPS-CDs) for Cr(VI) detection via inner filter effect (IFE). NPS-CDs were applied to the determination of Cr(VI) in living cells (HeLa and MCF-7) with satisfying results.


Assuntos
Cromo/análise , Corantes Fluorescentes/química , Pontos Quânticos/química , Poluentes Químicos da Água/análise , Carbono/química , Carbono/toxicidade , Linhagem Celular Tumoral , Água Potável/análise , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Lagos/análise , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nitrogênio/química , Nitrogênio/toxicidade , Fósforo/química , Fósforo/toxicidade , Pontos Quânticos/toxicidade , Chuva/química , Rios/química , Espectrometria de Fluorescência/métodos , Enxofre/química , Enxofre/toxicidade , Águas Residuárias/análise
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